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by sale0303 at 04-11-2013, 06:48 AM
3 comments
Freezing of human embryos (cryopreservation) became an important part of the program of medical procedures in the treatment of the infertile couples. Recent research shows that the freezing of embryos is associated with significantly higher IVF success and reduced risk of birth defects, especially in relation to Intracytoplasmic sperm injection ICSI.
Cryopreservation
In the course of an IVF treatment cycle, more viable embryos may be produced than it is desired for embryo transfer in that same cycle. If so, these "excess" embryos can be preserved by freezing and stored for future use. In some cases, all of the embryos can be frozen without fresh transfer.
Cryopreservation is a series of procedures of freezing cells and tissues. It is a controlled process of freezing to very low temperatures and storage in order to keep cells and tissues for theoretically unlimited period of time and subsequently successfully dissolve the same. At these low temperatures, any biological activity, including the biochemical reactions that would lead to cell death, has been stopped. Specific features of each type of cells undergoing cryopreservation require precise and biologically safe freezing protocol and, subsequently, thawing.
First successful embryo cryopreservation mammal was done in 1972, and the first baby conceived by embryo that was frozen was born in 1984.
Cell survival during cryopreservation depends on the reaction of cellular and extracellular water. At temperatures below zero, when the water is frozen and all metabolic processes are stopped, the cells are able to stand in a state of 'suspended vitality' or they may succumb to fatal damage. Human embryos are kept frozen in liquid nitrogen at -196 ° C.
During the freezing, all chemical reactions within the cell must be stopped. Damage embryos occur during the process of cooling and thawing, and as a result of the creation of ice crystals within the cells, or a change in osmotic pressure as a result of dehydration of the cells.
Cryoprotectant molecules are widely applied in modern cryotechnology, as protective substances that facilitate cell survival and the process of equilibration during phase transition from a liquid to a solid state and vice versa. Cryoprotectant substances have a lower freezing point and prevent making ices crystals that would at such low temperatures damage the cell. Different types of cryoprotectants are used for different stages of embryonic development. Embryos can be frozen on the stage of pronuclear to the blastocyst stage (5-7 days after fertilization). The most commonly used cryoprotectants are propanediol, dimethyl-sulfoxide or glycerol.
Two techniques used to freeze eggs are slow freezing and vitrification. As technology progresses, today is increasingly considered that vitrification is preferable to slow freezing in terms of higher pregnancy rates.
Frozen embryos are kept in special lab dishes, placed in liquid nitrogen. For each individual embryo, its origin, division phase, and the exact time and date of freezing were recorded.
The embryos will be stored in the frozen condition until the patient and spouse request their use (longest 5 years, as current law allows), and the physician responsible for your care determines that appropriate conditions exist in the patient for transfer of the embryos into the patient's uterus. At that time, some or all of the embryos will be thawed. Each embryo will be examined to determine whether it is potentially viable, and if so, the transfer into the patient's uterus will occur.
Risks and Limitations
The primary concern with the use of cryopreservation techniques is the possible loss of embryos, meaning some healthy embryos may not survive the stress of freezing and thawing. The exact number of embryos lost to cryoinjury varies, but it is very likely that freezing will cause loss of some embryos, perhaps 25-50%. However, it could have many good points, because in this way, the selection is made for more viable embryos.
Sometimes, not all embryos obtain adequate quality to be frozen, which is why this option cannot be offered to all couples.
Another concern with cryopreservation is the potential risk of birth defects in children produced from frozen/thawed embryos. But numerous studies have not shown any significant increase in abnormalities when compared to pregnancy outcomes in the rest of the population.
Advantages
Advantages of embryo freezing procedure:
This procedure reduces the number of preparatory procedures, and reduces the complications that carry the processes of stimulation and aspiration of oocytes. Freezing embryos is important to avoid ovarian hyperstimulation syndrome, since all embryos can be frozen until the transfer to the uterus in the next cycle, and used for later transfer in a non-stimulated natural cycle. Ovarian hyperstimulation has shown negative effects on the endometrial receptivity. Presently, the highest success rates in reproductive medicine are seen in the women who have not had ovarian stimulation - their endometrial tissue has not been exposed to high hormone levels, and they are not at risk of ovarian hyperstimulation syndrome. Freezing embryos for later transfer might therefore improve implantation and pregnancy rates and increase the safety of IVF.
In this way, it also increases the possibility of pregnancy in each cycle of in vitro fertilization.
This way avoids the medical and social problems associated with multiple pregnancies, providing that the appropriate cycle transmits only a small number of embryos.
Studies show that cryopreservation is associated with significantly reduced risk of birth defects, especially in relation to ICSI. This may be due to developmentally vulnerable embryos who fail to survive the process of freezing and thawing.
Embryo freezing procedure allows control of complications of in vitro fertilization process, so when due to certain circumstances the process has to be determinated, the obtained material can be saved.
This method also provides significant financial savings (costs stimulation and intervention).
Assisted reproduction is significantly improved in recent years, while the cryopreservation of ovarian and testicular tissue is significantly more complex than in the case of embryos and gametes. However, technology is constantly improving and it will be offered in many IVF centers.
Cryopreservation
In the course of an IVF treatment cycle, more viable embryos may be produced than it is desired for embryo transfer in that same cycle. If so, these "excess" embryos can be preserved by freezing and stored for future use. In some cases, all of the embryos can be frozen without fresh transfer.
Cryopreservation is a series of procedures of freezing cells and tissues. It is a controlled process of freezing to very low temperatures and storage in order to keep cells and tissues for theoretically unlimited period of time and subsequently successfully dissolve the same. At these low temperatures, any biological activity, including the biochemical reactions that would lead to cell death, has been stopped. Specific features of each type of cells undergoing cryopreservation require precise and biologically safe freezing protocol and, subsequently, thawing.
First successful embryo cryopreservation mammal was done in 1972, and the first baby conceived by embryo that was frozen was born in 1984.
Cell survival during cryopreservation depends on the reaction of cellular and extracellular water. At temperatures below zero, when the water is frozen and all metabolic processes are stopped, the cells are able to stand in a state of 'suspended vitality' or they may succumb to fatal damage. Human embryos are kept frozen in liquid nitrogen at -196 ° C.
During the freezing, all chemical reactions within the cell must be stopped. Damage embryos occur during the process of cooling and thawing, and as a result of the creation of ice crystals within the cells, or a change in osmotic pressure as a result of dehydration of the cells.
Cryoprotectant molecules are widely applied in modern cryotechnology, as protective substances that facilitate cell survival and the process of equilibration during phase transition from a liquid to a solid state and vice versa. Cryoprotectant substances have a lower freezing point and prevent making ices crystals that would at such low temperatures damage the cell. Different types of cryoprotectants are used for different stages of embryonic development. Embryos can be frozen on the stage of pronuclear to the blastocyst stage (5-7 days after fertilization). The most commonly used cryoprotectants are propanediol, dimethyl-sulfoxide or glycerol.
Two techniques used to freeze eggs are slow freezing and vitrification. As technology progresses, today is increasingly considered that vitrification is preferable to slow freezing in terms of higher pregnancy rates.
Frozen embryos are kept in special lab dishes, placed in liquid nitrogen. For each individual embryo, its origin, division phase, and the exact time and date of freezing were recorded.
The embryos will be stored in the frozen condition until the patient and spouse request their use (longest 5 years, as current law allows), and the physician responsible for your care determines that appropriate conditions exist in the patient for transfer of the embryos into the patient's uterus. At that time, some or all of the embryos will be thawed. Each embryo will be examined to determine whether it is potentially viable, and if so, the transfer into the patient's uterus will occur.
Risks and Limitations
The primary concern with the use of cryopreservation techniques is the possible loss of embryos, meaning some healthy embryos may not survive the stress of freezing and thawing. The exact number of embryos lost to cryoinjury varies, but it is very likely that freezing will cause loss of some embryos, perhaps 25-50%. However, it could have many good points, because in this way, the selection is made for more viable embryos.
Sometimes, not all embryos obtain adequate quality to be frozen, which is why this option cannot be offered to all couples.
Another concern with cryopreservation is the potential risk of birth defects in children produced from frozen/thawed embryos. But numerous studies have not shown any significant increase in abnormalities when compared to pregnancy outcomes in the rest of the population.
Advantages
Advantages of embryo freezing procedure:
This procedure reduces the number of preparatory procedures, and reduces the complications that carry the processes of stimulation and aspiration of oocytes. Freezing embryos is important to avoid ovarian hyperstimulation syndrome, since all embryos can be frozen until the transfer to the uterus in the next cycle, and used for later transfer in a non-stimulated natural cycle. Ovarian hyperstimulation has shown negative effects on the endometrial receptivity. Presently, the highest success rates in reproductive medicine are seen in the women who have not had ovarian stimulation - their endometrial tissue has not been exposed to high hormone levels, and they are not at risk of ovarian hyperstimulation syndrome. Freezing embryos for later transfer might therefore improve implantation and pregnancy rates and increase the safety of IVF.
In this way, it also increases the possibility of pregnancy in each cycle of in vitro fertilization.
This way avoids the medical and social problems associated with multiple pregnancies, providing that the appropriate cycle transmits only a small number of embryos.
Studies show that cryopreservation is associated with significantly reduced risk of birth defects, especially in relation to ICSI. This may be due to developmentally vulnerable embryos who fail to survive the process of freezing and thawing.
Embryo freezing procedure allows control of complications of in vitro fertilization process, so when due to certain circumstances the process has to be determinated, the obtained material can be saved.
This method also provides significant financial savings (costs stimulation and intervention).
Assisted reproduction is significantly improved in recent years, while the cryopreservation of ovarian and testicular tissue is significantly more complex than in the case of embryos and gametes. However, technology is constantly improving and it will be offered in many IVF centers.
by Nikolas at 04-11-2013, 02:32 AM
2 comments
New molecular technologies lead to new findings and possible treatment concerning Autism.
Autism is a neurological development disorder causing impaired social interaction and communication and restricted repetitive behavior. Its origins and causes have long been debated, but only recently has there been any real data to suggest a possible underlying pathology on the cellular level. The cause of autism still remains uncertain, showing a strong genetic component, but the genetics of autism have proven to be very complex and difficult to tackle. In some cases, autism has been attributed to agents that cause birth defects, such as heavy metals, pesticides and certain mutagens. Some have even proposed vaccination as a possible cause for autism, although this has yet to be proven or show any real scientific basis. Whatever the cause, autism remains a big scientific and medical challenge. The diagnostic spectrum of Autism has three distinct branches, with symptoms usually surfacing before the age of three. The array of symptoms is highly diverse, and as some research suggests, the causes themselves could be. An autism related culture has developed, with some individuals striving to find a cure or treatment for such individuals, and others stating that it is not a disease to be cured and people suffering from autism should be embraced an integrated into social systems.
Recent research done by the Mitochondrial and Metabolic Disease Center at the University of California, San Diego School of Medicine might shed some light on the mechanism of this disease and give hope for a future treatment or even a cure. Testing a new theory, the researchers have found that a century old drug, used to combat African sleeping disease, might just be the substance to cure autism.
Tens of UC San Diego scientist and skilled researchers from diverse areas have banded together to work on, and discover, a unifying mechanism to explain and possibly cure autism. Compiling a completely new theory using antipurinergic therapy Dr. Naviaux and colleagues have purposed a unifying mechanism explaining how the different causes, both genetic and environmental, affect the onset of autism by causing a sustained cell danger response, an innate metabolic cellular mechanism responsible for cellular immunity and inflammation.
“Our cell danger theory suggests that autism happens because cells get stuck in a defensive metabolic mode and fail to talk to each other normally, which can interfere with brain development and function. We used a class of drugs that has been around for almost a century to treat other diseases to block the ‘danger’ signal in a mouse model, allowing cells to return to normal metabolism and restore cell communication.” - says Robert Naviaux, M.D. “When cells are exposed to classical forms of dangers, such as a virus, infection, or toxic environmental substance, a defense mechanism is activated. This results in changes to metabolism and gene expression, and reduces the communication between neighboring cells. Simply put, when cells stop talking to each other, children stop talking.”
Considering mitochondria are the key players in cellular signaling and infectious and noninfectious cellular stress, innate immunity, and inflammation, the researchers first searched for a common cellular marker that was critical for immunity responses and linked to mitochondria. They found several, including adenosine triphosphate, a molecule with a very diverse metabolic role, and many other mitokines, molecules produced by mitochondria in distress. These mitokines have a high range of metabolic functions inside the cell, but a very different one outside of them. Up to fifteen different purinergic receptors on the surface of several classes of cells can be affected by these mytokines, which in turn controls a broad range of biological functions, up to 15 different functions, relating to autism.
The researchers tested many substances, among them suramine, which has been used for nearly a century to treat African sleeping disease, and found that the signal inhibitory function of suramine corrected autism-like symptoms in model organisms, mice with a form of autism. The drug restored 16 types of multiple abnormalities including normalizing brain synapse structure, cell-to-cell signaling, social behavior, motor coordination, and normalizing mitochondrial metabolism. Moreover, the drug prevented cerebellar Purkinje cell loss, correction of the ultrastructural synaptic dysmorphology, and correction of the hypothermia, metabolic, mitochondrial, P2Y2 and P2X7 purinergic receptor expression, and ERK1/2 and CAMKII signal transduction abnormalities.
Doctor Naviaux said: “The striking effectiveness shown in this study using APT to ‘reprogram’ the cell danger response and reduce inflammation showcases an opportunity to develop a completely new class of anti-inflammatory drugs to treat autism and several other disorders. Of course, correcting abnormalities in a mouse is a long way from a cure for humans, but we are encouraged enough to test this approach in a small clinical trial of children with autism spectrum disorder in the coming year. This trial is still in the early stages of development. We think this approach offers a fresh and exciting new path that could lead to development of a new class of drugs to treat autism.”
Findings published in the March 13 issue of PLOS ONE in an article titled “Antipurinergic Therapy Corrects the Autism-Like Features in the Poly(IC) Mouse Model.”
Autism is a neurological development disorder causing impaired social interaction and communication and restricted repetitive behavior. Its origins and causes have long been debated, but only recently has there been any real data to suggest a possible underlying pathology on the cellular level. The cause of autism still remains uncertain, showing a strong genetic component, but the genetics of autism have proven to be very complex and difficult to tackle. In some cases, autism has been attributed to agents that cause birth defects, such as heavy metals, pesticides and certain mutagens. Some have even proposed vaccination as a possible cause for autism, although this has yet to be proven or show any real scientific basis. Whatever the cause, autism remains a big scientific and medical challenge. The diagnostic spectrum of Autism has three distinct branches, with symptoms usually surfacing before the age of three. The array of symptoms is highly diverse, and as some research suggests, the causes themselves could be. An autism related culture has developed, with some individuals striving to find a cure or treatment for such individuals, and others stating that it is not a disease to be cured and people suffering from autism should be embraced an integrated into social systems.
Recent research done by the Mitochondrial and Metabolic Disease Center at the University of California, San Diego School of Medicine might shed some light on the mechanism of this disease and give hope for a future treatment or even a cure. Testing a new theory, the researchers have found that a century old drug, used to combat African sleeping disease, might just be the substance to cure autism.
Tens of UC San Diego scientist and skilled researchers from diverse areas have banded together to work on, and discover, a unifying mechanism to explain and possibly cure autism. Compiling a completely new theory using antipurinergic therapy Dr. Naviaux and colleagues have purposed a unifying mechanism explaining how the different causes, both genetic and environmental, affect the onset of autism by causing a sustained cell danger response, an innate metabolic cellular mechanism responsible for cellular immunity and inflammation.
“Our cell danger theory suggests that autism happens because cells get stuck in a defensive metabolic mode and fail to talk to each other normally, which can interfere with brain development and function. We used a class of drugs that has been around for almost a century to treat other diseases to block the ‘danger’ signal in a mouse model, allowing cells to return to normal metabolism and restore cell communication.” - says Robert Naviaux, M.D. “When cells are exposed to classical forms of dangers, such as a virus, infection, or toxic environmental substance, a defense mechanism is activated. This results in changes to metabolism and gene expression, and reduces the communication between neighboring cells. Simply put, when cells stop talking to each other, children stop talking.”
Considering mitochondria are the key players in cellular signaling and infectious and noninfectious cellular stress, innate immunity, and inflammation, the researchers first searched for a common cellular marker that was critical for immunity responses and linked to mitochondria. They found several, including adenosine triphosphate, a molecule with a very diverse metabolic role, and many other mitokines, molecules produced by mitochondria in distress. These mitokines have a high range of metabolic functions inside the cell, but a very different one outside of them. Up to fifteen different purinergic receptors on the surface of several classes of cells can be affected by these mytokines, which in turn controls a broad range of biological functions, up to 15 different functions, relating to autism.
The researchers tested many substances, among them suramine, which has been used for nearly a century to treat African sleeping disease, and found that the signal inhibitory function of suramine corrected autism-like symptoms in model organisms, mice with a form of autism. The drug restored 16 types of multiple abnormalities including normalizing brain synapse structure, cell-to-cell signaling, social behavior, motor coordination, and normalizing mitochondrial metabolism. Moreover, the drug prevented cerebellar Purkinje cell loss, correction of the ultrastructural synaptic dysmorphology, and correction of the hypothermia, metabolic, mitochondrial, P2Y2 and P2X7 purinergic receptor expression, and ERK1/2 and CAMKII signal transduction abnormalities.
Doctor Naviaux said: “The striking effectiveness shown in this study using APT to ‘reprogram’ the cell danger response and reduce inflammation showcases an opportunity to develop a completely new class of anti-inflammatory drugs to treat autism and several other disorders. Of course, correcting abnormalities in a mouse is a long way from a cure for humans, but we are encouraged enough to test this approach in a small clinical trial of children with autism spectrum disorder in the coming year. This trial is still in the early stages of development. We think this approach offers a fresh and exciting new path that could lead to development of a new class of drugs to treat autism.”
Findings published in the March 13 issue of PLOS ONE in an article titled “Antipurinergic Therapy Corrects the Autism-Like Features in the Poly(IC) Mouse Model.”
by bridgettpayseur at 04-11-2013, 01:55 AM
0 comments
Pet owners can be willing to go to great lengths to care for their companions. Thanks to rapidly improving medical advancements, along with more reasonable pricing, animals are able to receive benefits from many different medications and therapies. Doting pet owners can spend large amounts of money on diagnostics and treatments for their pets. As more and more people begin to view their pets as family or children, rather than “just pets” the amount of money spent on animal health care will continue to increase.
Stem cell therapies offer a great deal of promise for treating many diseases and injuries with no current acceptable therapies. However, research in the use of stem cell therapy is still very new, and very few treatments have received approval from the Food and Drug Administration (FDA). Most stem cells considered for therapeutic use are called mesenchymal stem cells (MSCs), which can mature into a many different types of specialized cells. In humans, the FDA has clearly stated that MSC are considered a drug, and therefore cannot be used therapeutically until they are approved by the government, except under specific conditions.
One reason why stem cell therapies are not widely available in humans, and why their use is controversial in animals, is the potential for serious adverse side effects. These adverse effects can even include the development of tumors in the patient, which can certainly be considered more severe than, say, a torn ligament. Stem cell therapy has not yet been well-studied, and adverse reactions are not fully understood. This means that practitioners do not have effective protocols to successfully prevent adverse reactions available.
The most common MSC therapies used in veterinary medicine involve treatment of injuries in horses and arthritis in dogs and cats. Injuries to the legs, including the bone, joints, tendons, and ligaments, are very serious concerns to horses. If a horse is not able to properly support its weight on all four legs, this can cause permanent damage. Often times, the recommended course of action for a badly injured horse is euthanasia. MSC therapy, even though it is still experimental, is a much more pleasant option for loving horse owners, as well as for potentially valuable thoroughbred racers. Pet cats and dogs that develop arthritis as they advance in age can also benefit from stem cell therapy. Increased mobility and decreased pain have been reported after MSC therapy. As many pet owners see their pets as children, being able to reduce pain through stem cell therapy is very tempting.
In animals, however, there are no clear guidelines regarding the use of stem cell therapies. This gives pet owners and veterinarians an opportunity to try experimental therapies on animals, such as horses, dogs, and cats. Previous studies have backed up the benefits of stem cell therapy in animals. In 2007, a study showed improvement of osteoarthritis symptoms in dogs that received treatment with MSCs. Two separate studies also showed healing in bones, ligaments, and tendons, as well as a reduced likelihood of re-injury, in horses after MSC therapy.
One problem with the studies conducted in veterinary settings is that very few are properly controlled. Animal owners go to clinics in hopes of getting treatment for their companions, and are not always willing to have their pet potentially be given a placebo. Veterinarians must be willing to treat the animal as requested. Properly controlled studies are important, though, as the results are more easily interpreted, and could potentially even be translated to human therapeutic use. Veterinary specialists are beginning to conduct properly controlled studies, and are working to ensure that the data obtained is usable both in animal therapeutics as well as human therapeutics.
While the use of stem cell therapies in veterinary medicine has shown promising results, and proper trials are beginning, there is some concern in the community about the future of MSC therapy in animals. The FDA is planning to issue new guidelines regarding the use of stem cell-based therapeutics in animals. If animal MSCs are labeled as drugs, clinical trials would have to be conducted and approval granted before MSCs could be used in animals legally. Changes in the FDA’s guidelines regarding MSC therapy in animals could hamper research currently being conducted, in addition to leaving many pets, and their owners, with fewer options available for treating injuries and other health problems.
References:
http://www.nature.com/news/stem-cells-bo...cs-1.12765
http://www.vet-stem.com/owners.php
http://actcells.com/
Stem cell therapies offer a great deal of promise for treating many diseases and injuries with no current acceptable therapies. However, research in the use of stem cell therapy is still very new, and very few treatments have received approval from the Food and Drug Administration (FDA). Most stem cells considered for therapeutic use are called mesenchymal stem cells (MSCs), which can mature into a many different types of specialized cells. In humans, the FDA has clearly stated that MSC are considered a drug, and therefore cannot be used therapeutically until they are approved by the government, except under specific conditions.
One reason why stem cell therapies are not widely available in humans, and why their use is controversial in animals, is the potential for serious adverse side effects. These adverse effects can even include the development of tumors in the patient, which can certainly be considered more severe than, say, a torn ligament. Stem cell therapy has not yet been well-studied, and adverse reactions are not fully understood. This means that practitioners do not have effective protocols to successfully prevent adverse reactions available.
The most common MSC therapies used in veterinary medicine involve treatment of injuries in horses and arthritis in dogs and cats. Injuries to the legs, including the bone, joints, tendons, and ligaments, are very serious concerns to horses. If a horse is not able to properly support its weight on all four legs, this can cause permanent damage. Often times, the recommended course of action for a badly injured horse is euthanasia. MSC therapy, even though it is still experimental, is a much more pleasant option for loving horse owners, as well as for potentially valuable thoroughbred racers. Pet cats and dogs that develop arthritis as they advance in age can also benefit from stem cell therapy. Increased mobility and decreased pain have been reported after MSC therapy. As many pet owners see their pets as children, being able to reduce pain through stem cell therapy is very tempting.
In animals, however, there are no clear guidelines regarding the use of stem cell therapies. This gives pet owners and veterinarians an opportunity to try experimental therapies on animals, such as horses, dogs, and cats. Previous studies have backed up the benefits of stem cell therapy in animals. In 2007, a study showed improvement of osteoarthritis symptoms in dogs that received treatment with MSCs. Two separate studies also showed healing in bones, ligaments, and tendons, as well as a reduced likelihood of re-injury, in horses after MSC therapy.
One problem with the studies conducted in veterinary settings is that very few are properly controlled. Animal owners go to clinics in hopes of getting treatment for their companions, and are not always willing to have their pet potentially be given a placebo. Veterinarians must be willing to treat the animal as requested. Properly controlled studies are important, though, as the results are more easily interpreted, and could potentially even be translated to human therapeutic use. Veterinary specialists are beginning to conduct properly controlled studies, and are working to ensure that the data obtained is usable both in animal therapeutics as well as human therapeutics.
While the use of stem cell therapies in veterinary medicine has shown promising results, and proper trials are beginning, there is some concern in the community about the future of MSC therapy in animals. The FDA is planning to issue new guidelines regarding the use of stem cell-based therapeutics in animals. If animal MSCs are labeled as drugs, clinical trials would have to be conducted and approval granted before MSCs could be used in animals legally. Changes in the FDA’s guidelines regarding MSC therapy in animals could hamper research currently being conducted, in addition to leaving many pets, and their owners, with fewer options available for treating injuries and other health problems.
References:
http://www.nature.com/news/stem-cells-bo...cs-1.12765
http://www.vet-stem.com/owners.php
http://actcells.com/
by Nikolas at 04-11-2013, 12:48 AM
0 comments
Personalized health-care is becoming more and more apparent as the future of medicine. The benefits are apparent, and the scientific and health-related impacts have been discussed many times over. However, there is an aspect of personalized medicine poorly discussed in the media, and in a sense left to “We’ll just see what happens” attitudes; the sociological, and underlying ethical, questions and complications raised by personalized medicine.
The integration of personalized medicine into the health-care system is inevitably going to change the patient-doctor relationship, the doctor’s education and approach, and most of all, the patients themselves.
With the emergence of personal genetic sequencing, a person is now able to, for a stunningly low price reaching as low as 9000$ in some companies this year, get their full genome sequenced. The price continues dropping at an increasing rate, as commercial genetic sequencing appears to follow a kind of Moore’s law, even surpassing it. A multitude of companies now offer a detailed analysis of the genomic data, providing an individual with a complete profile of genetic risks, markers and inheritable diseases and states, along with specific receptor types. This means that a genomic profile can not only tell you which disease you inherited, if any, but also which diseases and states you have a statistically significant risk for, what risk factors and susceptibility you have to which disease, the individual specifications of your immune system, and even your susceptibility to being overweight or obese.
First off, personalized medicine requires a great deal of medical literacy on part of the patient. With the increasing availability of home tests, lasting analyses and private laboratories (some of them operating with a mail-a-sample system) giving the patients personalized risk assessments and status analysis, half of the responsibility for a correct diagnosis and right treatment will fall to the patients themselves. Individual characteristics, such as age, weight, body type, race, gender, and ultimately the genetic profile, individual immune systems, reactions to certain types of treatment and medication, effectiveness of diverse substances and risk factors will all contribute greatly, if not completely determine, the course of treatment and diagnosis. The patients are expected to contribute a multitude of information, and consider the implications of each available option before making an informed decision in concert with the doctor. This can not incur with the present state, as it is. Most patients feel some symptoms, and immediately go to the doctor, expecting them to immediately determine exactly what it is and fix it. Some do the effort to goggle their symptoms and usually culminating in a worse state then before, considering the confusing multitude of information (often completely inaccurate or wrongly interpreted) on the public forums and supposed health magazines available on the net. Most of the patients have very little medical literacy or none at all, and leave everything up to the doctor. To change that, an enable the new, innovative and beneficial aspects of scientific progress concerning personalized medicine to have any effect, much will have to be invested in increasing the medical literacy and general knowledge of the population. Educational programs, coupled with a media coverage and year, perhaps decade long projects will have to be put in place before such an innovation can be successfully implemented into the medical system.
Secondly, doctors have to be re-educated to be able to grasp, understand and implement the variety of new technologies and ideas into their practice. Much attention will have to be given to patient-doctor relations and the “people approach” aspect of medical practice. The institution of medicine will have to be drastically altered, with doctors having a more limited amount of patients, and given much more attention to details of each, then before. Doctors will have to consider the individual information about every aspect of the patient’s body, not only those related to the current disease. Therapies will have to be chosen and implemented in accordance to the medical preferences of each patient individually, and the doctor will have to help the patient integrate that therapy into their daily lives.
Finally, the ethical decisions facing both the patients and the doctor will require a general consensus by the medical community. With the ability to predict the individual risks to certain diseases and susceptibility to different states doctors will have an ethical obligation to consider and advise patients on making certain, sometimes even drastic, changes considering lifestyle and choices, which will require a lot of deliberation on the doctors part. The ability to know the individual responsiveness to therapies and medicine will enable the doctor to predict the course of treatment and effectiveness thereof, but what if a person shows to be at risk to severe side-effects to a certain therapy, and other methods prove to be ineffective? Will the doctor recommend the therapy, although it has a small chance of success and a greater chance of causing undesired side-effects, if it is the only available course of action? Will that be left to the patient to decide, or will there be a legal consensus as to what degree of risk is acceptable? How will the doctors respond to questions raised by the patients considering their options for treatment in cases treatment shows chance of being ineffective or causing severe discomfort? Another, wholly different question arises; diagnostic tools, being pivotal in personalized medicine, will require biological samples, a great deal of them, from every person. These samples will be analysed by third party companies and the results provided to the patient or doctor, or perhaps insurance companies. Who will retain those results and samples, and who will have access to them? Will it be possible to identify an individual by their results? How will insurance companies react to being able to predict with great certainty the future health of an individual? Will it become mandatory to have your whole genome sequenced and provide the data to the insurance companies or even make the data public? How will the privacy of patients be insured, considering the availability of their personal genetic data to several parties before it even reaches them?
This is only a fraction of questions with no or uncertain answers, which will require a great deal of dialogue between science, industry, law and government. Each of those questions will have to be thoroughly thought over and all its implications analyzed before a standard can be set, and integration of individualized medicine can begin in existing health-care systems.
Resources:
Kickbusch I and Maag D Health Literacy. In: Kris Heggenhougen and Stella Quah, editors International Encyclopedia of Public Health, Vol 3. San Diego: Academic Press; 2008. pp. 204-211. Academic Press; 2008. pp. 204-211.
Mardis E. A decade's perspective on DNA sequencing technology. Nature, 470: 198-203. 2011.
Human genome at ten: the sequence explosion. Nature, 464: 670-671. 2010.
Wetterstrand KA. DNA Sequencing Costs: Data from the NHGRI Genome Sequencing Program (GSP)
The integration of personalized medicine into the health-care system is inevitably going to change the patient-doctor relationship, the doctor’s education and approach, and most of all, the patients themselves.
With the emergence of personal genetic sequencing, a person is now able to, for a stunningly low price reaching as low as 9000$ in some companies this year, get their full genome sequenced. The price continues dropping at an increasing rate, as commercial genetic sequencing appears to follow a kind of Moore’s law, even surpassing it. A multitude of companies now offer a detailed analysis of the genomic data, providing an individual with a complete profile of genetic risks, markers and inheritable diseases and states, along with specific receptor types. This means that a genomic profile can not only tell you which disease you inherited, if any, but also which diseases and states you have a statistically significant risk for, what risk factors and susceptibility you have to which disease, the individual specifications of your immune system, and even your susceptibility to being overweight or obese.
First off, personalized medicine requires a great deal of medical literacy on part of the patient. With the increasing availability of home tests, lasting analyses and private laboratories (some of them operating with a mail-a-sample system) giving the patients personalized risk assessments and status analysis, half of the responsibility for a correct diagnosis and right treatment will fall to the patients themselves. Individual characteristics, such as age, weight, body type, race, gender, and ultimately the genetic profile, individual immune systems, reactions to certain types of treatment and medication, effectiveness of diverse substances and risk factors will all contribute greatly, if not completely determine, the course of treatment and diagnosis. The patients are expected to contribute a multitude of information, and consider the implications of each available option before making an informed decision in concert with the doctor. This can not incur with the present state, as it is. Most patients feel some symptoms, and immediately go to the doctor, expecting them to immediately determine exactly what it is and fix it. Some do the effort to goggle their symptoms and usually culminating in a worse state then before, considering the confusing multitude of information (often completely inaccurate or wrongly interpreted) on the public forums and supposed health magazines available on the net. Most of the patients have very little medical literacy or none at all, and leave everything up to the doctor. To change that, an enable the new, innovative and beneficial aspects of scientific progress concerning personalized medicine to have any effect, much will have to be invested in increasing the medical literacy and general knowledge of the population. Educational programs, coupled with a media coverage and year, perhaps decade long projects will have to be put in place before such an innovation can be successfully implemented into the medical system.
Secondly, doctors have to be re-educated to be able to grasp, understand and implement the variety of new technologies and ideas into their practice. Much attention will have to be given to patient-doctor relations and the “people approach” aspect of medical practice. The institution of medicine will have to be drastically altered, with doctors having a more limited amount of patients, and given much more attention to details of each, then before. Doctors will have to consider the individual information about every aspect of the patient’s body, not only those related to the current disease. Therapies will have to be chosen and implemented in accordance to the medical preferences of each patient individually, and the doctor will have to help the patient integrate that therapy into their daily lives.
Finally, the ethical decisions facing both the patients and the doctor will require a general consensus by the medical community. With the ability to predict the individual risks to certain diseases and susceptibility to different states doctors will have an ethical obligation to consider and advise patients on making certain, sometimes even drastic, changes considering lifestyle and choices, which will require a lot of deliberation on the doctors part. The ability to know the individual responsiveness to therapies and medicine will enable the doctor to predict the course of treatment and effectiveness thereof, but what if a person shows to be at risk to severe side-effects to a certain therapy, and other methods prove to be ineffective? Will the doctor recommend the therapy, although it has a small chance of success and a greater chance of causing undesired side-effects, if it is the only available course of action? Will that be left to the patient to decide, or will there be a legal consensus as to what degree of risk is acceptable? How will the doctors respond to questions raised by the patients considering their options for treatment in cases treatment shows chance of being ineffective or causing severe discomfort? Another, wholly different question arises; diagnostic tools, being pivotal in personalized medicine, will require biological samples, a great deal of them, from every person. These samples will be analysed by third party companies and the results provided to the patient or doctor, or perhaps insurance companies. Who will retain those results and samples, and who will have access to them? Will it be possible to identify an individual by their results? How will insurance companies react to being able to predict with great certainty the future health of an individual? Will it become mandatory to have your whole genome sequenced and provide the data to the insurance companies or even make the data public? How will the privacy of patients be insured, considering the availability of their personal genetic data to several parties before it even reaches them?
This is only a fraction of questions with no or uncertain answers, which will require a great deal of dialogue between science, industry, law and government. Each of those questions will have to be thoroughly thought over and all its implications analyzed before a standard can be set, and integration of individualized medicine can begin in existing health-care systems.
Resources:
Kickbusch I and Maag D Health Literacy. In: Kris Heggenhougen and Stella Quah, editors International Encyclopedia of Public Health, Vol 3. San Diego: Academic Press; 2008. pp. 204-211. Academic Press; 2008. pp. 204-211.
Mardis E. A decade's perspective on DNA sequencing technology. Nature, 470: 198-203. 2011.
Human genome at ten: the sequence explosion. Nature, 464: 670-671. 2010.
Wetterstrand KA. DNA Sequencing Costs: Data from the NHGRI Genome Sequencing Program (GSP)
by bridgettpayseur at 04-10-2013, 08:44 AM
2 comments
Promising Ovarian Cancer Vaccine Shows Efficacy in Early Clinical Trials.
Currently, most cancer treatments involve chemotherapy and radiation. Both of these therapies target rapidly-replicating cells in the body, and result in the death of these cells. Cancer cells are targeted by these therapies; unfortunately, many healthy cells are also targeted. This results in side effects ranging from nausea, to hair loss, skin problems, anemia, and a compromised immune system. In addition, the current therapies are may have low efficacy rates in certain types of cancers or late stage cancers, and even after a patient enters remission, he or she may eventually relapse.
One new therapy recently put through clinical trials actually helps train a patient’s immune system to fight ovarian cancer tumors. The vaccine therapy uses tumor cells from the patient to train immune cells from the patient to fight the cancer, thus creating a personalized vaccine for each individual patient. The process involved removing tumor cells and a type of white blood cell from patients. The white blood cells, called monocytes, are innate immune cells. The monocytes will mature into cells called Dendritic Cells, which will help to prime the adaptive immune system by ingesting foreign invaders and altered host cells (called altered self). After the Dendritic Cell ingests a problematic cell, it presents antigen to the adaptive immune system. This activates adaptive immune cells, called T cells. The T cells are able to specifically recognize the problematic cell (either foreign or altered self) and will work to remove other infectious or cancerous cells.
The clinical trial involved the use of Dendritic Cell therapy. The procedure involved isolating monocytes from the patient’s blood. Once monocytes have been isolated from the patient’s blood, they are matured into Dendritic cells, and are expanded in a cell culture system. This increases the number of Dendritic Cells available to function in the patient’s immune system. After the Dendritic Cells have been expanded, they are incubated with tumor cells. The Dendritic Cells will ingest the tumor cells, and display the tumor antigen on the cell surface. The Dendritic Cells are next injected back into the patient, where they will activate T cells to fight the ovarian cancer tumor. This is a typical procedure used in Dendritic Cell therapy.
For the clinical trial studying ovarian cancer treatment, 25 of 31 patients who developed anti-tumor responses but still were affected by disease, were additionally treated with adoptive T cell therapy. T cells from the patient were expanded and primed in cell culture, then injected back into the patient, similar to the Dendritic Cell therapy. The T cells, which are the adaptive part of the immune system, are able to recognize and kill ovarian cancer cells in the patient. The T adoptive T cell therapy was supplemented with a cancer drug called Avastin, which helps prevent growth of blood vessels to feed the tumor.
A major advantage to using Dendritic Cell therapy and adoptive T cell transfer is that both of these therapies are personalized to the patient. All cells used in the therapy, including the cancer cells that prime the immune cells, originate from the patient. This means that the Dendritic Cells and T cells will be specifically designed to fight the patient’s own cancer, as opposed to cancer cells obtained from other sources. In addition, this prevents any potential adverse immune reaction that can occur when patients receive transplants from other donors, such as bone marrow or stem cell transfers.
This early clinical trial studied 35 patients with stage 3 and stage 4 ovarian cancer. Of the patients treated with only the Dendritic Cell vaccination, 61% had a noticeable clinical response. Of the patients treated with both the Dendritic Cell vaccination and the adoptive T cell transfer, 75% showed a clinical benefit. Eight patients had no signs of disease at the end of the study, and continued to receive maintenance vaccinations to prevent relapse of the cancer. One of the 31 patients even went into complete remission, meaning the cancer was completely undetectable even 42 months after the end of the study. This was the first such clinical study in which two immunotherapies were combined to treat cancer. The results provide exciting evidence that by combining two powerful anti-cancer therapies, patients’ immune systems can have a better chance to fight cancer.
References:
http://www.medicalnewstoday.com/articles/258769.php
http://www.foxnews.com/health/2013/04/08...-in-trial/
http://dendritic.info/
http://www.jci.org/articles/view/31446
Currently, most cancer treatments involve chemotherapy and radiation. Both of these therapies target rapidly-replicating cells in the body, and result in the death of these cells. Cancer cells are targeted by these therapies; unfortunately, many healthy cells are also targeted. This results in side effects ranging from nausea, to hair loss, skin problems, anemia, and a compromised immune system. In addition, the current therapies are may have low efficacy rates in certain types of cancers or late stage cancers, and even after a patient enters remission, he or she may eventually relapse.
One new therapy recently put through clinical trials actually helps train a patient’s immune system to fight ovarian cancer tumors. The vaccine therapy uses tumor cells from the patient to train immune cells from the patient to fight the cancer, thus creating a personalized vaccine for each individual patient. The process involved removing tumor cells and a type of white blood cell from patients. The white blood cells, called monocytes, are innate immune cells. The monocytes will mature into cells called Dendritic Cells, which will help to prime the adaptive immune system by ingesting foreign invaders and altered host cells (called altered self). After the Dendritic Cell ingests a problematic cell, it presents antigen to the adaptive immune system. This activates adaptive immune cells, called T cells. The T cells are able to specifically recognize the problematic cell (either foreign or altered self) and will work to remove other infectious or cancerous cells.
The clinical trial involved the use of Dendritic Cell therapy. The procedure involved isolating monocytes from the patient’s blood. Once monocytes have been isolated from the patient’s blood, they are matured into Dendritic cells, and are expanded in a cell culture system. This increases the number of Dendritic Cells available to function in the patient’s immune system. After the Dendritic Cells have been expanded, they are incubated with tumor cells. The Dendritic Cells will ingest the tumor cells, and display the tumor antigen on the cell surface. The Dendritic Cells are next injected back into the patient, where they will activate T cells to fight the ovarian cancer tumor. This is a typical procedure used in Dendritic Cell therapy.
For the clinical trial studying ovarian cancer treatment, 25 of 31 patients who developed anti-tumor responses but still were affected by disease, were additionally treated with adoptive T cell therapy. T cells from the patient were expanded and primed in cell culture, then injected back into the patient, similar to the Dendritic Cell therapy. The T cells, which are the adaptive part of the immune system, are able to recognize and kill ovarian cancer cells in the patient. The T adoptive T cell therapy was supplemented with a cancer drug called Avastin, which helps prevent growth of blood vessels to feed the tumor.
A major advantage to using Dendritic Cell therapy and adoptive T cell transfer is that both of these therapies are personalized to the patient. All cells used in the therapy, including the cancer cells that prime the immune cells, originate from the patient. This means that the Dendritic Cells and T cells will be specifically designed to fight the patient’s own cancer, as opposed to cancer cells obtained from other sources. In addition, this prevents any potential adverse immune reaction that can occur when patients receive transplants from other donors, such as bone marrow or stem cell transfers.
This early clinical trial studied 35 patients with stage 3 and stage 4 ovarian cancer. Of the patients treated with only the Dendritic Cell vaccination, 61% had a noticeable clinical response. Of the patients treated with both the Dendritic Cell vaccination and the adoptive T cell transfer, 75% showed a clinical benefit. Eight patients had no signs of disease at the end of the study, and continued to receive maintenance vaccinations to prevent relapse of the cancer. One of the 31 patients even went into complete remission, meaning the cancer was completely undetectable even 42 months after the end of the study. This was the first such clinical study in which two immunotherapies were combined to treat cancer. The results provide exciting evidence that by combining two powerful anti-cancer therapies, patients’ immune systems can have a better chance to fight cancer.
References:
http://www.medicalnewstoday.com/articles/258769.php
http://www.foxnews.com/health/2013/04/08...-in-trial/
http://dendritic.info/
http://www.jci.org/articles/view/31446
by Nikolas at 04-10-2013, 04:34 AM
0 comments
Huntington’s disease is an inherited genetic disorder affecting the brain that leads to progressive loss of both mental and physical faculty, motor control and psychiatric problems. It is an autosomal dominant mutation of either of the copies of the gene called huntingtin, with heritability of 50%, meaning that a child with a parent suffering from Huntington’s disease has a 50% chance to develop it. It usually presents symptoms between the ages of 35 and 50, but can present itself in any point in life, ranging from childhood to old age. Once diagnosed, it continues to progress leading to a steady decline in the individuals health, ultimately resulting in death of the weekend organism usually due to pneumonia, emphysema or similar condition. So far, there have been only a few ways to ease the symptoms and none to combat the disease itself.
April, 2013, two pharmaceutical giants, Isis Pharmaceuticals and Roche Pharmaceuticals have pooled their recourses in an alliance to attempt and cure Huntington’s disease combining Isis’ antisense oligonucleotide technology and Roches expertise in developing neurodegenerative medicine. The collaboration will include a combination of Isis’ antisense oligonucleotide technology and Roshe’s new “brain shuttle” program, to attempt and increase the antisense oligonucletoide penetration into the brain by adding systematic administration to Isis’ technology.
At first, the research will focus on Isis’ drug candidate for the blockage of all forms of the huntingtin protein (the main product of the huntingtin gene, a malfunctioning protein which is the main causative of the disease) production, hoping it will show effective in halting the degeneration caused by Huntington’s, or even prevent it altogether. Isis is also conducting research into experimental treatments that specifically block the production of the disease-causing forms of the huntingtin protein, which has the potential to treat subsets of Huntington’s patients. In a parallel research, Roche’s scientists will combine their brain shuttle technology to allow the systematic administration of the antisense oligonucleotide drug directly into the brain of asymptomatic patients.
Under the terms of the agreement, Roche will make a payment of $30 million to Isis, with total payments related to license fee and pre- and post-licensing milestone payments reaching potentially $362 million, including a further $80 million in potential commercial milestone payments. In addition, Isis will receive royalties on the sales of the drugs. Roche has the option to license the drugs from Isis through the completion of the first Phase I trial and additional unstated payments.
By this agreement, Isis is responsible for the development and testing of the antisense drug, and Roche will provide it’s brain shuttle technology to collaborate on the developmental stages of the drug. Roche will be responsible for the marketing, logistics, production and distribution of the drug.
“Huntington's is a severely debilitating neurodegenerative disease and a large unmet medical need. Patients experience gradually worsening motor function and psychological disturbances, with a significant shortening of life expectancy after the disease is diagnosed. Treatments are urgently needed, and we believe that the Isis approach in combination with Roche's brain shuttle represent one of the most advanced programs targeting the cause of HD with the aim of slowing down or halting the progression of this disease.” said Luca Santarelli, head of neuroscience and small molecules research at Roche.
B. Lynne Parshall, COO of Isis said: “We believe that Roche's expertise in developing CNS drugs, along with their clinical development experience, will greatly enhance our development efforts for this program and allow us to move forward more rapidly. In addition, by utilizing Roche's brain shuttle technology with our antisense drug discovery capabilities, we have the potential to significantly improve the therapeutic potential for this program,”
“By partnering our more complex and nuanced research and development programs earlier in development, like our Huntington's disease CNS program, we add value and resources with partners that bring unique benefits.”
April, 2013, two pharmaceutical giants, Isis Pharmaceuticals and Roche Pharmaceuticals have pooled their recourses in an alliance to attempt and cure Huntington’s disease combining Isis’ antisense oligonucleotide technology and Roches expertise in developing neurodegenerative medicine. The collaboration will include a combination of Isis’ antisense oligonucleotide technology and Roshe’s new “brain shuttle” program, to attempt and increase the antisense oligonucletoide penetration into the brain by adding systematic administration to Isis’ technology.
At first, the research will focus on Isis’ drug candidate for the blockage of all forms of the huntingtin protein (the main product of the huntingtin gene, a malfunctioning protein which is the main causative of the disease) production, hoping it will show effective in halting the degeneration caused by Huntington’s, or even prevent it altogether. Isis is also conducting research into experimental treatments that specifically block the production of the disease-causing forms of the huntingtin protein, which has the potential to treat subsets of Huntington’s patients. In a parallel research, Roche’s scientists will combine their brain shuttle technology to allow the systematic administration of the antisense oligonucleotide drug directly into the brain of asymptomatic patients.
Under the terms of the agreement, Roche will make a payment of $30 million to Isis, with total payments related to license fee and pre- and post-licensing milestone payments reaching potentially $362 million, including a further $80 million in potential commercial milestone payments. In addition, Isis will receive royalties on the sales of the drugs. Roche has the option to license the drugs from Isis through the completion of the first Phase I trial and additional unstated payments.
By this agreement, Isis is responsible for the development and testing of the antisense drug, and Roche will provide it’s brain shuttle technology to collaborate on the developmental stages of the drug. Roche will be responsible for the marketing, logistics, production and distribution of the drug.
“Huntington's is a severely debilitating neurodegenerative disease and a large unmet medical need. Patients experience gradually worsening motor function and psychological disturbances, with a significant shortening of life expectancy after the disease is diagnosed. Treatments are urgently needed, and we believe that the Isis approach in combination with Roche's brain shuttle represent one of the most advanced programs targeting the cause of HD with the aim of slowing down or halting the progression of this disease.” said Luca Santarelli, head of neuroscience and small molecules research at Roche.
B. Lynne Parshall, COO of Isis said: “We believe that Roche's expertise in developing CNS drugs, along with their clinical development experience, will greatly enhance our development efforts for this program and allow us to move forward more rapidly. In addition, by utilizing Roche's brain shuttle technology with our antisense drug discovery capabilities, we have the potential to significantly improve the therapeutic potential for this program,”
“By partnering our more complex and nuanced research and development programs earlier in development, like our Huntington's disease CNS program, we add value and resources with partners that bring unique benefits.”
by Nikolas at 04-09-2013, 11:46 PM
0 comments
Obesity has presented itself as the modern world disease, with stunning calculations; nearly 30% of all non-violent deaths are caused or closely tied to obesity and associated health risks. Childhood obesity and the increasing presence of Type II Diabetes in children presents a major concern for the World Health Organization, with millions of dollars invested each year in obesity research and potential treatment.
Since the 1960 there has been a prevailing thought that obesity is not merely a consequence of life choices and diet, but that there is an overlaying genetic mechanism behind it. Only in the 1980 were scientists able to prove it, with the discovery of the leptin gene in mice, by dr. Jeffrey Freidman, who was studying obese and diabetic mice. He studied a genetic variant of the laboratory mouse which was inherently obese, and one that was diabetic. After several years of studies, research and experimentation, the scientists got a glimpse of a mechanism which was present in both strains, although in different ways. They discovered that the obese mice lacked the gene that produces leptin, a hormone secreted from the bodies fat cells, which is the body’s natural “stop eating” signal. These mice, literally did not know when to stop eating. The diabetic mice, on the other hand, had the gene and the hormone, but their brains showed less sensitivity to it, lacking the crucial receptor for leptin in parts of the brain.
The biology of leptin proved to be extremely complex and is still being worked on.
"If the fat mass falls," Friedman says, "the level of leptin falls, and the urge to eat goes up. After an eating binge, the level of leptin rises, which is a signal to eat less. In addition to modulating food intake and energy expenditure, leptin has an effect on fertility, temperature maintenance, and fat and glucose metabolism."
On the other hand, since this ground braking research, there has been a boom in obesity genetics research and studies, and there has been much progress; many new genetic components contributing to obesity and being overweight have been found and cross-linked to get a better understanding of the underlying mechanism.
Recently, a new study has been published by an international team of researchers, pinpointing a large number of genes linked to obesity, involving over 260 000 people worldwide. This new study shows that the genes contributing to obesity are in fact the same genes responsible for milder forms of being overweight; pointing out that the same basic mechanism is behind weight gain in any form.
"We know from experience that genetic factors are important for the emergence of both milder and more extreme forms of obesity, but how much overlap there is between genes that are involved in extreme obesity and normal or slightly elevated BMI [a measure of body fat] has not been examined systematically previously," study coordinator Erik Ingelsson, a professor at Uppsala University in Sweden, stated.
According to this study, obesity and overweight are the results of a greater number of genetic variants and interactions, rather than completely new genes being involved. Professor Ingelsson added that the results "suggest that extremely obese individuals have a greater number of gene variants that increase the risk of obesity, rather than completely different genes being involved. In the long term, our findings may lead to new ways of preventing and treating obesity, which is one of the greatest global public health problems of our age."
Other studies have pointed that obesity largely runs in the family, with twin studies showing up to 50% heritability. Many ongoing studies are concerned with childhood obesity, and have so far shown that it has in fact several components different from adult obesity, although they are severely linked. Childhood obesity, more than others, shows a strong genetic component, and is a good way to study the “obesity genes” as the children are less likely to be obese duo to environmental factors, such as diet and life-style.
Yet other studies have shown that obesity has a DNA regulatory effect, with the BMI (body-mass-index, the rough measurement of a body’s percentage of fat) and other obesity linked environmental factors have an impact on how genes are expressed.
Since the 1960 there has been a prevailing thought that obesity is not merely a consequence of life choices and diet, but that there is an overlaying genetic mechanism behind it. Only in the 1980 were scientists able to prove it, with the discovery of the leptin gene in mice, by dr. Jeffrey Freidman, who was studying obese and diabetic mice. He studied a genetic variant of the laboratory mouse which was inherently obese, and one that was diabetic. After several years of studies, research and experimentation, the scientists got a glimpse of a mechanism which was present in both strains, although in different ways. They discovered that the obese mice lacked the gene that produces leptin, a hormone secreted from the bodies fat cells, which is the body’s natural “stop eating” signal. These mice, literally did not know when to stop eating. The diabetic mice, on the other hand, had the gene and the hormone, but their brains showed less sensitivity to it, lacking the crucial receptor for leptin in parts of the brain.
The biology of leptin proved to be extremely complex and is still being worked on.
"If the fat mass falls," Friedman says, "the level of leptin falls, and the urge to eat goes up. After an eating binge, the level of leptin rises, which is a signal to eat less. In addition to modulating food intake and energy expenditure, leptin has an effect on fertility, temperature maintenance, and fat and glucose metabolism."
On the other hand, since this ground braking research, there has been a boom in obesity genetics research and studies, and there has been much progress; many new genetic components contributing to obesity and being overweight have been found and cross-linked to get a better understanding of the underlying mechanism.
Recently, a new study has been published by an international team of researchers, pinpointing a large number of genes linked to obesity, involving over 260 000 people worldwide. This new study shows that the genes contributing to obesity are in fact the same genes responsible for milder forms of being overweight; pointing out that the same basic mechanism is behind weight gain in any form.
"We know from experience that genetic factors are important for the emergence of both milder and more extreme forms of obesity, but how much overlap there is between genes that are involved in extreme obesity and normal or slightly elevated BMI [a measure of body fat] has not been examined systematically previously," study coordinator Erik Ingelsson, a professor at Uppsala University in Sweden, stated.
According to this study, obesity and overweight are the results of a greater number of genetic variants and interactions, rather than completely new genes being involved. Professor Ingelsson added that the results "suggest that extremely obese individuals have a greater number of gene variants that increase the risk of obesity, rather than completely different genes being involved. In the long term, our findings may lead to new ways of preventing and treating obesity, which is one of the greatest global public health problems of our age."
Other studies have pointed that obesity largely runs in the family, with twin studies showing up to 50% heritability. Many ongoing studies are concerned with childhood obesity, and have so far shown that it has in fact several components different from adult obesity, although they are severely linked. Childhood obesity, more than others, shows a strong genetic component, and is a good way to study the “obesity genes” as the children are less likely to be obese duo to environmental factors, such as diet and life-style.
Yet other studies have shown that obesity has a DNA regulatory effect, with the BMI (body-mass-index, the rough measurement of a body’s percentage of fat) and other obesity linked environmental factors have an impact on how genes are expressed.
by Nikolas at 04-09-2013, 11:45 PM
0 comments
A new study has shown that the reason some people can eat apparently what they want, get no exercise and still not gain weight, might be neurological. The study shows that people with a high-fat diet and low amounts of exercise who still somehow remain slim, might have a slightly different neurological circuitry then people with a high tendency towards gaining weight.
The study, led by the Australian Monash University, showed that a high-fat diet in some people can cause a group of cells in the brain to become insulated, effectively preventing and dampening the bodies signals. These signal, the hormone leptin among them, are responsible for telling the brain that the body is full and ready to burn energy. When the signal is dampened or completely absent, the brain has no way of telling when the body’s energy reserves have been replenished, and is in a state of constant appetite.
Professor Cowly, of the Monash University stated that there are two clear results from this findings.
“We discovered that a high-fat diet caused brain cells to become insulated from the body, rendering the cells unable to detect signals of fullness to stop eating," Professor Cowley said. "Secondly, the insulation also created a further complication in that the body was unable to detect signals to increase energy use and burn off calories/kilojoules."
The research has shown that a group of supporting brain cells, the tanycytes, becomes insulated with fat as a result of a high-fat diet, thus preventing an important system in the brain, the melanocortin system, from receiving signals from the body and connecting with other neural circuitry. The melanocortin system determines the level of appetite and body’s energy expenditure levels.
According to Cowly, this research presents a critical link in obesity research, and can provide with new approaches to treating obesity and weight related problems.
"These neuronal circuits regulate eating behaviors and energy expenditure and are a naturally occurring process in the brain. The circuits begin to form early in life so that people may have a tendency towards obesity even before they eat their first meal," Professor Cowley said.
Additionally, when the cells are insulated with fat and start dampening or preventing signals from the body, it becomes increasingly difficult for the person to start losing weight, as the body tries to prevent any unnecessary loss of energy.
A subsequent study, done in the UK, lead by researcher Dr Mohammad Hajihosseini, may provide a glimmer of hope for chronically obese people. After a study done in East Anglia, it has become increasingly clear that the fat insulation of tanycytes, although under genetic and prenatal influence, can be altered and significantly contributed to by environmental factors. This study showed that tanycytes can, in most cases, be altered throughout childhood and well into adulthood.
"This study has shown that the neural circuitry that controls appetite is not fixed in number and could possibly be manipulated numerically to tackle eating disorders," Hajihosseini said.
Unfortunately, they say it would be another 10-15 years before they can be ready to design and test a therapy aimed at obese human patients.
"The next step is to define the group of genes and cellular processes that regulate the behavior and activity of tanycytes," he said. "This information will further our understanding of brain stem cells and could be exploited to develop drugs that can modulate the number or functioning of appetite-regulating neurons."
The study is published in the Journal of Neuroscience.
T. L. Horvath, B. Sarman, C. Garcia-Caceres, P. J. Enriori, P. Sotonyi, M. Shanabrough, E. Borok, J. Argente, J. A. Chowen, D. Perez-Tilve, P. T. Pfluger, H. S. Bronneke, B. E. Levin, S. Diano, M. A. Cowley, M. H. Tschop. Synaptic input organization of the melanocortin system predicts diet-induced hypothalamic reactive gliosis and obesity. Proceedings of the National Academy of Sciences, 2010; 107 (33): 14875 DOI:10.1073/pnas.1004282107
The study, led by the Australian Monash University, showed that a high-fat diet in some people can cause a group of cells in the brain to become insulated, effectively preventing and dampening the bodies signals. These signal, the hormone leptin among them, are responsible for telling the brain that the body is full and ready to burn energy. When the signal is dampened or completely absent, the brain has no way of telling when the body’s energy reserves have been replenished, and is in a state of constant appetite.
Professor Cowly, of the Monash University stated that there are two clear results from this findings.
“We discovered that a high-fat diet caused brain cells to become insulated from the body, rendering the cells unable to detect signals of fullness to stop eating," Professor Cowley said. "Secondly, the insulation also created a further complication in that the body was unable to detect signals to increase energy use and burn off calories/kilojoules."
The research has shown that a group of supporting brain cells, the tanycytes, becomes insulated with fat as a result of a high-fat diet, thus preventing an important system in the brain, the melanocortin system, from receiving signals from the body and connecting with other neural circuitry. The melanocortin system determines the level of appetite and body’s energy expenditure levels.
According to Cowly, this research presents a critical link in obesity research, and can provide with new approaches to treating obesity and weight related problems.
"These neuronal circuits regulate eating behaviors and energy expenditure and are a naturally occurring process in the brain. The circuits begin to form early in life so that people may have a tendency towards obesity even before they eat their first meal," Professor Cowley said.
Additionally, when the cells are insulated with fat and start dampening or preventing signals from the body, it becomes increasingly difficult for the person to start losing weight, as the body tries to prevent any unnecessary loss of energy.
A subsequent study, done in the UK, lead by researcher Dr Mohammad Hajihosseini, may provide a glimmer of hope for chronically obese people. After a study done in East Anglia, it has become increasingly clear that the fat insulation of tanycytes, although under genetic and prenatal influence, can be altered and significantly contributed to by environmental factors. This study showed that tanycytes can, in most cases, be altered throughout childhood and well into adulthood.
"This study has shown that the neural circuitry that controls appetite is not fixed in number and could possibly be manipulated numerically to tackle eating disorders," Hajihosseini said.
Unfortunately, they say it would be another 10-15 years before they can be ready to design and test a therapy aimed at obese human patients.
"The next step is to define the group of genes and cellular processes that regulate the behavior and activity of tanycytes," he said. "This information will further our understanding of brain stem cells and could be exploited to develop drugs that can modulate the number or functioning of appetite-regulating neurons."
The study is published in the Journal of Neuroscience.
T. L. Horvath, B. Sarman, C. Garcia-Caceres, P. J. Enriori, P. Sotonyi, M. Shanabrough, E. Borok, J. Argente, J. A. Chowen, D. Perez-Tilve, P. T. Pfluger, H. S. Bronneke, B. E. Levin, S. Diano, M. A. Cowley, M. H. Tschop. Synaptic input organization of the melanocortin system predicts diet-induced hypothalamic reactive gliosis and obesity. Proceedings of the National Academy of Sciences, 2010; 107 (33): 14875 DOI:10.1073/pnas.1004282107
by sale0303 at 04-09-2013, 09:17 PM
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Organ and tissue transplantation in developed countries is in steady increase. There are whole networks in some parts of the world, and these methods have significantly prolonged lives of many people. However, there are some difficulties in simple organ and tissue transplantations. The main difficulty is shortage of matched organs for people who are waiting for transplantation. Next disadvantage is constant immunosuppressive therapy which can damage health of the patients. Impossibility of nerve transplantation and limited life of transplanted organs are also big disadvantages of this technique.
Most of these problems can be solved in future by constructing whole organs and tissues in laboratories. Tissue engineering has a lot of hard but not impossible tasks. Tissue engineering's objectives are repairing and replacing the malfunctioned organ or preserving and improving of the function in vital organs. Unfortunately, in presence, only repairing of a lost function is possible, other objectives are about to be achieved.
Tissue engineering is based on creating tissues of cells and scaffold (extracellular matrices that provide support to cells)and suitable conditions under which cells are kept.
Cells in Artificial Tissue
Every organ and tissue in human organism is consisted of cells and scaffold. For laboratory cell growing, the ideal cell would be easily accessible, huge proliferation ability and property to differentiate into desired cell type. Many types of cells are available today, and we can divide them in many ways, but the simplest way is to divide them in 1. Autologous cells (cells from the same person) 2. Allogenic cells (cells from same species) 3. Xenogenic cells (cells from another species individuals). Some authors are using stem cells separately in this classification, and some include them in first or second category. Another, maybe better classification is in five types of cells are available for tissue engineering.
First type of cells are adult cells taken from the same person. This way of tissue production is very good, because the donor is the recipient. Thus infection with viruses if avoided. Also good side of this method is complementary tissue, because immune response is not activated after this way of transplantation. Second type of cells are adult stem cells (ASC). ASC of the different tissues are responsible for reparation of that tissue by modifying themselves into type of cells which are lacking. Also mesenchymal stem cells are good way of replacing adult stem cells. Third type of cells are embryonic stem cells. There are opinions that embryonic stem cells are not that reliable because of their potential tumorigenic properties. Fourth type are induced pluripotent stem cells (iPSC). Scientists have managed to build these cells by reprogramming adult cells with retroviral activity. This is excellent concept providing us plenty of autologous stem cells. However, these cells are potentially oncogenic because this type of stem cells relies on retroviral vector that integrates in hosts genom. Fifth type are cells from placental tissue, umbilical cord and amniotic fluid. This type can be considered as part of the third type or embryonic stem cells, but it has no tumorigenic properties.
Scaffold in Artificial Tissue
Scaffold is artificial three-dimensional structure for cell implantation. It is made of glycoproteins and proteoglycans. It presents simulation of extracellular matrix in human tissue. Scaffold structures should be made of bioresorbable materials like collagen and some polyesters. Commonly used material is polylactic acid.
Cells are carried out in two dimensions and if scientists want to have third dimension they use scaffold structure. Scaffold must have micro pores for diffusion of nutrients, growth factors and diffusion of the waste. Tiny pores suitable for blood vessels are also expected from scaffolds.
Today, new technologies give possibility of organ-printing. Organ-printing is process of making scaffold from small fragments with complete control of making structure. This way of making scaffold is more complex, but it can provide space for future vascular tree. Providing space for vascular elements is crucial and limiting factor in making various kinds of tissues.
Instead of making scaffolds, there are some alternatives in tissue bioengineering. The important sources for cell implantation are native decellularized tissue and organs. This kind of scaffold is better than artificial scaffolds because they already have developed structure of blood vessels. This technique has provided production of whole organs such as heart and liver. This scaffolds are most likely the future of laboratory organ-making process.
Tissue Engineering Problems
Beside cells and scaffolds, external conditions are very important factors. There are some basic conditions that have to be provided for tissue growth. Temperature of 37 °C with 5%-10%, isolation and growth and differentiation factors are required. In many cell cultures these basic factors are not sufficient. Physical and chemical factors, hormones, specific metabolites are necessary for some tissues. Thus chondrocytes should be used to hypoxia, shear stress is involved in normal differentiation of endothelial cells and others. All these additional factor are obligatory for functional development of tissues.
Bioreactors
Our organs are receiving constant stimulations from electrical, biochemical, mechanical and other stimuli. These stimuli help our organs to work properly. Also tissue engineered tissues should receive these stimuli. This can be obtained with bioreactors. Bioreactor is device that provides mechanical and biological stimuli. There are many bioreactors for various tissues. Every bioreactor provides different stimuli for specific tissue.
Angiogenesis in TE Tissues
The limitations in production of more complex tissues and organs for sure is nutrition of tissues. Tissues thicker than few millimeters are vulnerable because diffusion is not effective for supplying central parts of the tissue. This is the biggest limitation in TE and scientists are struggling with this obstacle.
Tissue Bioengineering is for sure the future of transplantation. It has many advantages in comparison with traditional organ transplantation. However, there are some limitations and challenges for scientists. Major challenges for TE is the need for more complex functionality, providing additional factors for tissue and organ development and development of ideal scaffolds.
Most of these problems can be solved in future by constructing whole organs and tissues in laboratories. Tissue engineering has a lot of hard but not impossible tasks. Tissue engineering's objectives are repairing and replacing the malfunctioned organ or preserving and improving of the function in vital organs. Unfortunately, in presence, only repairing of a lost function is possible, other objectives are about to be achieved.
Tissue engineering is based on creating tissues of cells and scaffold (extracellular matrices that provide support to cells)and suitable conditions under which cells are kept.
Cells in Artificial Tissue
Every organ and tissue in human organism is consisted of cells and scaffold. For laboratory cell growing, the ideal cell would be easily accessible, huge proliferation ability and property to differentiate into desired cell type. Many types of cells are available today, and we can divide them in many ways, but the simplest way is to divide them in 1. Autologous cells (cells from the same person) 2. Allogenic cells (cells from same species) 3. Xenogenic cells (cells from another species individuals). Some authors are using stem cells separately in this classification, and some include them in first or second category. Another, maybe better classification is in five types of cells are available for tissue engineering.
First type of cells are adult cells taken from the same person. This way of tissue production is very good, because the donor is the recipient. Thus infection with viruses if avoided. Also good side of this method is complementary tissue, because immune response is not activated after this way of transplantation. Second type of cells are adult stem cells (ASC). ASC of the different tissues are responsible for reparation of that tissue by modifying themselves into type of cells which are lacking. Also mesenchymal stem cells are good way of replacing adult stem cells. Third type of cells are embryonic stem cells. There are opinions that embryonic stem cells are not that reliable because of their potential tumorigenic properties. Fourth type are induced pluripotent stem cells (iPSC). Scientists have managed to build these cells by reprogramming adult cells with retroviral activity. This is excellent concept providing us plenty of autologous stem cells. However, these cells are potentially oncogenic because this type of stem cells relies on retroviral vector that integrates in hosts genom. Fifth type are cells from placental tissue, umbilical cord and amniotic fluid. This type can be considered as part of the third type or embryonic stem cells, but it has no tumorigenic properties.
Scaffold in Artificial Tissue
Scaffold is artificial three-dimensional structure for cell implantation. It is made of glycoproteins and proteoglycans. It presents simulation of extracellular matrix in human tissue. Scaffold structures should be made of bioresorbable materials like collagen and some polyesters. Commonly used material is polylactic acid.
Cells are carried out in two dimensions and if scientists want to have third dimension they use scaffold structure. Scaffold must have micro pores for diffusion of nutrients, growth factors and diffusion of the waste. Tiny pores suitable for blood vessels are also expected from scaffolds.
Today, new technologies give possibility of organ-printing. Organ-printing is process of making scaffold from small fragments with complete control of making structure. This way of making scaffold is more complex, but it can provide space for future vascular tree. Providing space for vascular elements is crucial and limiting factor in making various kinds of tissues.
Instead of making scaffolds, there are some alternatives in tissue bioengineering. The important sources for cell implantation are native decellularized tissue and organs. This kind of scaffold is better than artificial scaffolds because they already have developed structure of blood vessels. This technique has provided production of whole organs such as heart and liver. This scaffolds are most likely the future of laboratory organ-making process.
Tissue Engineering Problems
Beside cells and scaffolds, external conditions are very important factors. There are some basic conditions that have to be provided for tissue growth. Temperature of 37 °C with 5%-10%, isolation and growth and differentiation factors are required. In many cell cultures these basic factors are not sufficient. Physical and chemical factors, hormones, specific metabolites are necessary for some tissues. Thus chondrocytes should be used to hypoxia, shear stress is involved in normal differentiation of endothelial cells and others. All these additional factor are obligatory for functional development of tissues.
Bioreactors
Our organs are receiving constant stimulations from electrical, biochemical, mechanical and other stimuli. These stimuli help our organs to work properly. Also tissue engineered tissues should receive these stimuli. This can be obtained with bioreactors. Bioreactor is device that provides mechanical and biological stimuli. There are many bioreactors for various tissues. Every bioreactor provides different stimuli for specific tissue.
Angiogenesis in TE Tissues
The limitations in production of more complex tissues and organs for sure is nutrition of tissues. Tissues thicker than few millimeters are vulnerable because diffusion is not effective for supplying central parts of the tissue. This is the biggest limitation in TE and scientists are struggling with this obstacle.
Tissue Bioengineering is for sure the future of transplantation. It has many advantages in comparison with traditional organ transplantation. However, there are some limitations and challenges for scientists. Major challenges for TE is the need for more complex functionality, providing additional factors for tissue and organ development and development of ideal scaffolds.
by Nikolas at 04-09-2013, 03:01 AM
0 comments
Intestinal diseases have presented a big problem in medicine up until now. Cellular death in the intestine caused by several diseases such as celiac disease, radiation and chemo therapy has proven to be hard to ameliorate and almost impossible to cure. The human intestine, being a specifically layered organ, provides several challenges in research, let alone therapy. Recently, as with many similar conditions, stem cell therapy was considered, but proven to be impossible due to the apparent hardships involved in extracting and cultivating human intestine stem cells. Namely, only rat intestine stem cells have been successfully extracted and cultivated by now. Although scientists have been able to learn a great deal about the basic mechanisms of stems cells from rat derived cultures, it has been impossible to conceive with a therapy or treatment for human patients due to the lack of any viable human derived cells.
That might have changed recently, as the laboratory that first derived the rat intestine stem cells has published a new paper, stating that they have successfully extracted and cultivated the first human intestine adult stem cells.
Researchers at the University of North Carolina report that for the first time, the much sought after human intestine stem cells have been isolated. This findings provide scientists worldwide with the much needed recourses to start considering stem cell treatments aimed at human intestine diseases. This is a significant step forward for scientists looking to uncover the true human stem cell mechanisms, as much as it is a hope for those suffering from any form of intestine degeneration, either from disease or cancer therapy.
“Not having these cells to study has been a significant roadblock to research,” stated senior study author Scott T. Magness, Ph.D., assistant professor in the departments of medicine, biomedical engineering, and cell and molecular physiology at UNC, the leader of this laboratory. “Until now, we have not had the technology to isolate and study these stem cells. Now we have to tools to start solving many of these problems.”
“While the information we get from mice is good foundational mechanistic data to explain how this tissue works, there are some opportunities that we might not be able to pursue until we do similar experiments with human tissue,” noted lead study co-author Adam D. Gracz, a graduate student in Dr. Magness’ lab.
As Magnesses lab was the first to isolate and cultivate rat intestine stem cells, they had the startup required to do the same for human tissue. That has proven hard until now, due to the lack of intestinal material with human origins required as the source for the cells. Recently, they were able to get their hands on some uniquely qualified material to start their work, originating from gastric bypass surgery. With this material on their hands, they used the exact same technique used on the rat tissue. They tested the cells for specific cellular markers; proteins named CD24 and CD44, and surprisingly found out that rat intestine and human intestine exhibit these same markers. They then proceeded to tag the cells using fluorescent molecules. So tagged, the cells could then be inserted into a machine, the fluorescence activated cell sorter, to sort and isolate the cells from the tissue. They found that not only can they isolate the stem cells from the gut tissue samples, but they can also separate different types of stem cells from one another. This two types, active and reserve stem cells, are a hot topic in stem cell research currently, as scientist try to uncover the exact mechanism allowing for the transformation from reserve to active in case of injury or cell damage. This new findings provide room for much speculation concerning future uses and research into regenerative stem cell medicine concerning not only intestinal tissue, but stem cell research altogether. In an interview, Dr. Magness states the optimistic possibilities opened with this breakthrough.
"Now that we have been able to do this, the next step is to carefully characterize these populations to assess their potential," said Dr. Magness. "Can we expand these cells outside of the body to potentially provide a cell source for therapy? Can we use these for tissue engineering? Or to take it to the extreme, can we genetically modify these cells to cure inborn genetic disorders or inflammatory bowel disease? Those are some questions that we are going to explore in the future.”
Study results published in the journal Stem Cells
That might have changed recently, as the laboratory that first derived the rat intestine stem cells has published a new paper, stating that they have successfully extracted and cultivated the first human intestine adult stem cells.
Researchers at the University of North Carolina report that for the first time, the much sought after human intestine stem cells have been isolated. This findings provide scientists worldwide with the much needed recourses to start considering stem cell treatments aimed at human intestine diseases. This is a significant step forward for scientists looking to uncover the true human stem cell mechanisms, as much as it is a hope for those suffering from any form of intestine degeneration, either from disease or cancer therapy.
“Not having these cells to study has been a significant roadblock to research,” stated senior study author Scott T. Magness, Ph.D., assistant professor in the departments of medicine, biomedical engineering, and cell and molecular physiology at UNC, the leader of this laboratory. “Until now, we have not had the technology to isolate and study these stem cells. Now we have to tools to start solving many of these problems.”
“While the information we get from mice is good foundational mechanistic data to explain how this tissue works, there are some opportunities that we might not be able to pursue until we do similar experiments with human tissue,” noted lead study co-author Adam D. Gracz, a graduate student in Dr. Magness’ lab.
As Magnesses lab was the first to isolate and cultivate rat intestine stem cells, they had the startup required to do the same for human tissue. That has proven hard until now, due to the lack of intestinal material with human origins required as the source for the cells. Recently, they were able to get their hands on some uniquely qualified material to start their work, originating from gastric bypass surgery. With this material on their hands, they used the exact same technique used on the rat tissue. They tested the cells for specific cellular markers; proteins named CD24 and CD44, and surprisingly found out that rat intestine and human intestine exhibit these same markers. They then proceeded to tag the cells using fluorescent molecules. So tagged, the cells could then be inserted into a machine, the fluorescence activated cell sorter, to sort and isolate the cells from the tissue. They found that not only can they isolate the stem cells from the gut tissue samples, but they can also separate different types of stem cells from one another. This two types, active and reserve stem cells, are a hot topic in stem cell research currently, as scientist try to uncover the exact mechanism allowing for the transformation from reserve to active in case of injury or cell damage. This new findings provide room for much speculation concerning future uses and research into regenerative stem cell medicine concerning not only intestinal tissue, but stem cell research altogether. In an interview, Dr. Magness states the optimistic possibilities opened with this breakthrough.
"Now that we have been able to do this, the next step is to carefully characterize these populations to assess their potential," said Dr. Magness. "Can we expand these cells outside of the body to potentially provide a cell source for therapy? Can we use these for tissue engineering? Or to take it to the extreme, can we genetically modify these cells to cure inborn genetic disorders or inflammatory bowel disease? Those are some questions that we are going to explore in the future.”
Study results published in the journal Stem Cells
by Nikolas at 04-09-2013, 12:00 AM
0 comments
Biomimicry is a field of biotechnology long present in the scientific world. Copying existing mechanisms present in organisms has been around since technology first evolved, thus in some sense it predates even the notion of biotechnology itself. Technological solutions based on the elegant solutions present in nature range from mimicking hooks of certain plants to produce adhering textiles to mimicking the structure and function of living tissues to produce synthetic copies. One such research has spawned an interesting breakthrough recently. Scientists at Oxford University have come up with a novel approach to building synthetic copies of tissue using another relatively novel technique, the 3-D printer.
A three-dimensional material could, in theory, one day mimic the function and structure of living tissues and cells. The tissue-like material was developed in an Oxford laboratory by Hygan Bayley and associates, using a 3-D printer to “print” thousands of tiny water droplets into a layer of lipids, inciting the lipids to array around the water droplets, creating a cell-like structure. Further, they have figured out how to inject different biochemical solutions into those droplets, and insert proteins into the lipid layers, furthering the mimicking potential. These inserted proteins can form pores, and connect the water droplets within the layer, thus establishing a kind of “cellular” communication. Then, they printed several different types of droplets, colored differently and with different biochemical solutions and concentrations, establishing a “realistic” copy of a tissue. As a finishing touch, they made the tissue move and contract, forming a closing and opening flower-like structure.
These same authors, in an earlier publication, described a similar network of water droplets encapsulated within a layer of oil, forming lipid droplets which adhere to one-another and assemble to form a lipid bilayer reminiscent of a cellular membrane on the surface of the solution. They named them “multisomes”. These droplets could then form semi-permanent pores to allow cellular communication. This theory was now proven, and improved upon by actually printing the fake tissue and forming communicating, functioning “tissues”.
This new approach can be used in drug delivery systems, as scaffolding for cellular regrowth or even to interface and replace damaged tissues, the scientist propose.
The scientist custom built a 3-D printer for this job, as no commercially available printer had the precision required for this job. Then they mixed batches of biochemicals and injected them into the lipid layer. The lipid droplets, or multisomes, can be released by changing the Ph, temperature or chemical content of the surrounding solution. The printed network of droplets, after printing, is moved on to a mobile tray, and adhering droplets are separated by a single thin membrane, inserting pores that connect the content of each droplet. So formed structures have shown several interesting traits, for example the ability to contract and move by changing the volume of a part of the cells, or the ability to transfer and conduct an impulse, just like nerve cells.
By now, the team has created tissues containing up to 35000 individual droplets, but as Bayley states: “The amount of integrated cells is limited only by time and money”. In their experiments they used only two different kinds of droplets, but up to fifty can be used without affecting the integrity of the created tissue.
In an interesting setup, the researchers used two kinds of droplets, differently colored, and injected different concentrations of salt in the two different groups. Then the two different types of droplets were integrated into two separate layers, who were then combined to form a bilayer, with one type of cells comprising the upper layer and the other the bottom one. The droplets formed petal like structures, resembling a flower. By opening and closing pored between then, they were able to use the concentration gradient to mimic osmotic pressure in cells and made the bilayer contract. The petals of the lipid droplet flower closed and opened, mimicking the closing and opening of a flower.
Gabriel Villar of Oxford University's department of chemistry, the inventor of the 3D printer used in the research stated, “We have created a scalable way of producing a new type of soft material. The printed structures could in principle employ much of the biological machinery that enables the sophisticated behavior of living cells and tissues.”
Resources:
G. Villar, A. D. Graham and H. Bayley. A tissue-like printed material. Science. Vol. 340, April 5, 2013, p.48. doi: 10.1126/science.1229495
A three-dimensional material could, in theory, one day mimic the function and structure of living tissues and cells. The tissue-like material was developed in an Oxford laboratory by Hygan Bayley and associates, using a 3-D printer to “print” thousands of tiny water droplets into a layer of lipids, inciting the lipids to array around the water droplets, creating a cell-like structure. Further, they have figured out how to inject different biochemical solutions into those droplets, and insert proteins into the lipid layers, furthering the mimicking potential. These inserted proteins can form pores, and connect the water droplets within the layer, thus establishing a kind of “cellular” communication. Then, they printed several different types of droplets, colored differently and with different biochemical solutions and concentrations, establishing a “realistic” copy of a tissue. As a finishing touch, they made the tissue move and contract, forming a closing and opening flower-like structure.
These same authors, in an earlier publication, described a similar network of water droplets encapsulated within a layer of oil, forming lipid droplets which adhere to one-another and assemble to form a lipid bilayer reminiscent of a cellular membrane on the surface of the solution. They named them “multisomes”. These droplets could then form semi-permanent pores to allow cellular communication. This theory was now proven, and improved upon by actually printing the fake tissue and forming communicating, functioning “tissues”.
This new approach can be used in drug delivery systems, as scaffolding for cellular regrowth or even to interface and replace damaged tissues, the scientist propose.
The scientist custom built a 3-D printer for this job, as no commercially available printer had the precision required for this job. Then they mixed batches of biochemicals and injected them into the lipid layer. The lipid droplets, or multisomes, can be released by changing the Ph, temperature or chemical content of the surrounding solution. The printed network of droplets, after printing, is moved on to a mobile tray, and adhering droplets are separated by a single thin membrane, inserting pores that connect the content of each droplet. So formed structures have shown several interesting traits, for example the ability to contract and move by changing the volume of a part of the cells, or the ability to transfer and conduct an impulse, just like nerve cells.
By now, the team has created tissues containing up to 35000 individual droplets, but as Bayley states: “The amount of integrated cells is limited only by time and money”. In their experiments they used only two different kinds of droplets, but up to fifty can be used without affecting the integrity of the created tissue.
In an interesting setup, the researchers used two kinds of droplets, differently colored, and injected different concentrations of salt in the two different groups. Then the two different types of droplets were integrated into two separate layers, who were then combined to form a bilayer, with one type of cells comprising the upper layer and the other the bottom one. The droplets formed petal like structures, resembling a flower. By opening and closing pored between then, they were able to use the concentration gradient to mimic osmotic pressure in cells and made the bilayer contract. The petals of the lipid droplet flower closed and opened, mimicking the closing and opening of a flower.
Gabriel Villar of Oxford University's department of chemistry, the inventor of the 3D printer used in the research stated, “We have created a scalable way of producing a new type of soft material. The printed structures could in principle employ much of the biological machinery that enables the sophisticated behavior of living cells and tissues.”
Resources:
G. Villar, A. D. Graham and H. Bayley. A tissue-like printed material. Science. Vol. 340, April 5, 2013, p.48. doi: 10.1126/science.1229495
by Nikolas at 04-08-2013, 10:37 PM
0 comments
Drug abuse is one of the prevailing social problems of this age, and has proven difficult for scientists to tackle over the years. From behavioral therapies to lobotomy and substitute substances, the drug-abuse mechanism in the brain has yet to be conquered with significant success. Recent research has pointed to manipulation of neural circuitry as a potentially viable way of affecting and possibly treating the drug abuse tendency of certain individuals.
Lab-animal drug self administration has been a major tool in most drug related research for a few decades now. The experimental setup is intended to show the addictive degree of drugs, and the ability of the animals to resist self administering drugs after certain treatments, or in face of “punishment”. Several such experiments were performed over the years, successfully proving many theories, but it has yet to provide with a successful way of treating severe addictions and preventing drug abuse.
A new research provides helpful insights concerning the cocaine addiction mechanism in rats, scientists report in an article in Nature magazine, April 4th.
These scientists successfully located a region in the brain, an area known as the prelimbic cortex, which serves as the relay point for drug addiction mechanisms, especially in cocaine addiction, and serves as the impulse-control and reward driven behavior center. The neurons in this area of the brain appear to be sluggish, showing a decrease in activity and impulse firing speed, as a consequence of desensitization caused by ingesting cocaine.
The rats in this experiment were divided into two groups, one control group, and one that had access to a mechanism by which they would activate a lever and receive a dose of cocaine. After roughly two months, the scientists started administering shocks every third time the rats would pull the lever, which caused about 70 percent of the rats to stop using the lever and administering themselves with cocaine, but 30% continued this behavior regardless of the ensuing shock. After being tested with electric current, the brains of these rats showed significantly less responsiveness in their prelimbic cortex region, effectively showing that the neurons were slower and less responsive. They were, in fact, the compulsive cocaine addicts of the group. It has earlier been shown that a decrease in prelimbic cortex neuron sensitivity causes the organisms to lose self control and peruse pleasure-giving action in spite of evident punishment and danger.
Further, the scientists wanted to prove that it is in fact this region and the subsequent loss of sensitivity that caused addiction driven behavior, so they turned to an area called optogenetics. Optogenetics uses light emissions to manipulate the firing and action of neurons in a brain, effectively turning them off or on. The rats were injected with a virus, which infected their brains and inserted a genetically engineered strain which in turn caused the neurons of those rats to exhibit a light sensitive receptor on their surface, allowing for external stimulation by light. Then, they used a laser to stimulate the neurons in the prelimbic cortex, doubling their firing speed. This caused a remarkable drop in addiction-driven behavior; roughly one third of the compulsive cocaine user rats stopped their addiction based behavior. The same experiment performed on the control group had no effect. The scientist then revised the experiment, this time doing the opposite. The non-compulsive group of rats was injected with the same virus, but this time the laser was used to turn the neurons of the prelimbic cortex off, decreasing their firing speed by half. Almost all of these rats exhibited a cocaine addiction after this experiment.
Although remarkable, this study does not show why some rats exhibit a cocaine addiction and some not. The scientists hope to use this findings to come up with an addiction treatment for humans, involving a transcranial magnetic stimulator that would be inserted into the prelimbic cortex of addicts, and hope to move to clinical trials with this.
Although the study was well done, it addresses only one component of addiction, says neuroscientist Peter Kalivas of the Medical University of South Carolina. Other experiments earlier have found that in some cases, silencing the same neurons can have a reducing effect on addiction-driven behavior.
Resources:
B.T. Chen et al. Rescuing cocaine-induced prefrontal cortex hypoactivity prevents compulsive cocaine seeking. Nature. Vol. 496, April 4, 2013. doi: 10.1038/nature12024.
Lab-animal drug self administration has been a major tool in most drug related research for a few decades now. The experimental setup is intended to show the addictive degree of drugs, and the ability of the animals to resist self administering drugs after certain treatments, or in face of “punishment”. Several such experiments were performed over the years, successfully proving many theories, but it has yet to provide with a successful way of treating severe addictions and preventing drug abuse.
A new research provides helpful insights concerning the cocaine addiction mechanism in rats, scientists report in an article in Nature magazine, April 4th.
These scientists successfully located a region in the brain, an area known as the prelimbic cortex, which serves as the relay point for drug addiction mechanisms, especially in cocaine addiction, and serves as the impulse-control and reward driven behavior center. The neurons in this area of the brain appear to be sluggish, showing a decrease in activity and impulse firing speed, as a consequence of desensitization caused by ingesting cocaine.
The rats in this experiment were divided into two groups, one control group, and one that had access to a mechanism by which they would activate a lever and receive a dose of cocaine. After roughly two months, the scientists started administering shocks every third time the rats would pull the lever, which caused about 70 percent of the rats to stop using the lever and administering themselves with cocaine, but 30% continued this behavior regardless of the ensuing shock. After being tested with electric current, the brains of these rats showed significantly less responsiveness in their prelimbic cortex region, effectively showing that the neurons were slower and less responsive. They were, in fact, the compulsive cocaine addicts of the group. It has earlier been shown that a decrease in prelimbic cortex neuron sensitivity causes the organisms to lose self control and peruse pleasure-giving action in spite of evident punishment and danger.
Further, the scientists wanted to prove that it is in fact this region and the subsequent loss of sensitivity that caused addiction driven behavior, so they turned to an area called optogenetics. Optogenetics uses light emissions to manipulate the firing and action of neurons in a brain, effectively turning them off or on. The rats were injected with a virus, which infected their brains and inserted a genetically engineered strain which in turn caused the neurons of those rats to exhibit a light sensitive receptor on their surface, allowing for external stimulation by light. Then, they used a laser to stimulate the neurons in the prelimbic cortex, doubling their firing speed. This caused a remarkable drop in addiction-driven behavior; roughly one third of the compulsive cocaine user rats stopped their addiction based behavior. The same experiment performed on the control group had no effect. The scientist then revised the experiment, this time doing the opposite. The non-compulsive group of rats was injected with the same virus, but this time the laser was used to turn the neurons of the prelimbic cortex off, decreasing their firing speed by half. Almost all of these rats exhibited a cocaine addiction after this experiment.
Although remarkable, this study does not show why some rats exhibit a cocaine addiction and some not. The scientists hope to use this findings to come up with an addiction treatment for humans, involving a transcranial magnetic stimulator that would be inserted into the prelimbic cortex of addicts, and hope to move to clinical trials with this.
Although the study was well done, it addresses only one component of addiction, says neuroscientist Peter Kalivas of the Medical University of South Carolina. Other experiments earlier have found that in some cases, silencing the same neurons can have a reducing effect on addiction-driven behavior.
Resources:
B.T. Chen et al. Rescuing cocaine-induced prefrontal cortex hypoactivity prevents compulsive cocaine seeking. Nature. Vol. 496, April 4, 2013. doi: 10.1038/nature12024.
by Nikolas at 04-08-2013, 08:53 AM
0 comments
Nanotechnology has excited the public’s eye ever since Eric Drexler detailed its possibilities in his 1986 book “Engines of Creation”. Much research had been done in the past 20 years regarding this topic, and many a million was invested in the development of the first nano-scale machines. However, molecular nanotechnology is a very tricky field and, although the past 20 years have yielded much insight and useful experiments, manipulation of matter on the atomic and molecular scale remains far from having widespread industrial use. However, new research regarding synthetic biology may present us with the opportunity to control living matter at the molecular scale, a possibility of building, inserting and using cell and molecule sized computing machines regarding not only our own bodies, but any living system. Synthetic biology is a new, promising area of biological research that evolved in past few years. It deals with the building blocks of life, DNA and proteins, and manipulating them to create, control and use mechanisms within living systems. Recently, a new, interesting boom has arisen from research in synthetic biology. Dubbed “biological computing”, this new strain of thought may provide scientist with the means of creating biologically based computers, utilizing living cells and their mechanisms as the computer parts.
March this year, a paper was published, unveiling the discovery of biological transistors, the basic building blocks of logical circuitry by Stanford University’s bioengineering laboratory. This same laboratory, last year, has published another paper regarding biological computing, proving that DNA can be used as a rewritable mass data storage medium. These two papers combined give the basic building blocks of electronic circuitry, and the ability to program living systems for a variety of uses.
“We can write and erase DNA in a living cell, now we can bring logic and computation inside a cell itself.” – Says Jerome Bonett, a scientist at Stanford’s bioengineering department.
In their paper from April 2012, they first presented their results from experiments with DNA. The researchers at Stanford choose to use DNA as a memory medium, as it already is, as they say “the stuff of memory”. They used enzymes called recombinases to flip segments of DNA on or off. The enzymes came from bacteriophages, viruses that use it to flip bacterial DNA and insert their own instead. In their experiment, they used the enzyme to flip a certain segment of DNA, so it reads backwards. With another signal, they were able to flip it back again, thus representing the basic computing language of 1s and 0s. They then “programmed” DNA of an Escherichia Coli bacterium to glow a certain color depending on the way the segment of DNA is oriented, green for one direction, red for the other. They could then observe as the bacterium changed color red to green, and back again, every time the segment of DNA was flipped over. This represents only one bit of memory, but is the first, most important step. In the next few years, the researchers are confident to be able to scale up to several bytes, and speed up the process. However, the most important thing these experiments have yielded is the ability to preserve the flips, or bytes of memory, through 100 generations of bacteria.
A year later, March 2013, the same laboratory published another paper, this time about biological transistors, dubbed “transcriptors”. This time, the laboratory was able to manipulate strands of DNA, and DNA snipping enzymes to create a basic building block of logical circuitry, a “yes/no” switch. Different from electronic chips, which direct the flow of electrons to flip switches on and off, this “biological chips” manipulate the flow of a protein along a strand of DNA (or RNA), sending information along its way, telling the cell to synthesize or not synthesize a specific molecule. The same “flipping technology” was used as with the DNA memory storage experiments, only this time the orientation of the strand, coupled with the protein traveling along it, sent out certain information to the cell itself. Although now only at a level of several different responses, or logical switches, this technology can be very useful for some basic cellular computing. For example, a cell can be programmed to release a certain cue in case it detects a cancer marker, coloring your stool or urine green or blue, as an early warning mechanism. Bacteria can also be altered to glow a certain color in case it detects a contaminant in water or the ground, thus warning us of pollution or contamination.
Although this technology is not very likely to replace electrical computing, it nonetheless provides great possibilities and opens many interesting doors for further research and experimentation.
Resources:
J. Bonnet et al. Amplifying genetic logic gates. Science. Published online March 28, 2013. doi: 10.1126/science.1232758.
J. Bonnet, P. Subsoontorn, and D. Endy. Rewritable digital data storage in live cells via engineered control of recombination directionality. Proceedings of the National Academy of Sciences. Published online May 21, 2012. doi:10.1073/pnas.1202344109.
March this year, a paper was published, unveiling the discovery of biological transistors, the basic building blocks of logical circuitry by Stanford University’s bioengineering laboratory. This same laboratory, last year, has published another paper regarding biological computing, proving that DNA can be used as a rewritable mass data storage medium. These two papers combined give the basic building blocks of electronic circuitry, and the ability to program living systems for a variety of uses.
“We can write and erase DNA in a living cell, now we can bring logic and computation inside a cell itself.” – Says Jerome Bonett, a scientist at Stanford’s bioengineering department.
In their paper from April 2012, they first presented their results from experiments with DNA. The researchers at Stanford choose to use DNA as a memory medium, as it already is, as they say “the stuff of memory”. They used enzymes called recombinases to flip segments of DNA on or off. The enzymes came from bacteriophages, viruses that use it to flip bacterial DNA and insert their own instead. In their experiment, they used the enzyme to flip a certain segment of DNA, so it reads backwards. With another signal, they were able to flip it back again, thus representing the basic computing language of 1s and 0s. They then “programmed” DNA of an Escherichia Coli bacterium to glow a certain color depending on the way the segment of DNA is oriented, green for one direction, red for the other. They could then observe as the bacterium changed color red to green, and back again, every time the segment of DNA was flipped over. This represents only one bit of memory, but is the first, most important step. In the next few years, the researchers are confident to be able to scale up to several bytes, and speed up the process. However, the most important thing these experiments have yielded is the ability to preserve the flips, or bytes of memory, through 100 generations of bacteria.
A year later, March 2013, the same laboratory published another paper, this time about biological transistors, dubbed “transcriptors”. This time, the laboratory was able to manipulate strands of DNA, and DNA snipping enzymes to create a basic building block of logical circuitry, a “yes/no” switch. Different from electronic chips, which direct the flow of electrons to flip switches on and off, this “biological chips” manipulate the flow of a protein along a strand of DNA (or RNA), sending information along its way, telling the cell to synthesize or not synthesize a specific molecule. The same “flipping technology” was used as with the DNA memory storage experiments, only this time the orientation of the strand, coupled with the protein traveling along it, sent out certain information to the cell itself. Although now only at a level of several different responses, or logical switches, this technology can be very useful for some basic cellular computing. For example, a cell can be programmed to release a certain cue in case it detects a cancer marker, coloring your stool or urine green or blue, as an early warning mechanism. Bacteria can also be altered to glow a certain color in case it detects a contaminant in water or the ground, thus warning us of pollution or contamination.
Although this technology is not very likely to replace electrical computing, it nonetheless provides great possibilities and opens many interesting doors for further research and experimentation.
Resources:
J. Bonnet et al. Amplifying genetic logic gates. Science. Published online March 28, 2013. doi: 10.1126/science.1232758.
J. Bonnet, P. Subsoontorn, and D. Endy. Rewritable digital data storage in live cells via engineered control of recombination directionality. Proceedings of the National Academy of Sciences. Published online May 21, 2012. doi:10.1073/pnas.1202344109.
by Nikolas at 04-08-2013, 08:49 AM
0 comments
Italian research foundation like 'Stamina' have raised ethical questions, even legal ramifications and protests to a certain level.
Stem cell research has become quite popular in the last few years. The potential of stem cells is invaluable in regenerative medicine research. Many papers have been written, many different therapies proposed and just some approved for clinical testing, but for now, medicine based on stem cells remains experimental and very costly. Most countries possessing stem cell research hold it under strict regulation, and require sound evidence and theory to allow testing of such therapies, most notably human trials.
Stem cell approaches used in medicine are most often based on their ability to maintain and repair tissue by replacing senescent cells in adult organisms. The prevailing part of stem cell and regenerative medicine research is conducted by utilizing embryonic stem cells, which is controversial by itself, because it involves the destruction of embryos. In contrast to that, adult stem cells are also available and being worked upon. Adult stem cells by comparison have a lesser degree of multipotence then embryonic stem cells, being able to assume the role of a smaller number of adult cells and tissues.
May last year, an Italian research foundation named “Stamina” had its research halted by the Italian government due to several issues concerning the effectiveness and viability of their adult stem cell research. As stated by the health inspectors, the conditions in Stamina’s laboratory were “unsanitary, with terrible maintenance and a critical lack of cleanliness, resulting in highly inadequate conditions”. But, March this year; the Italian government overruled the decision to halt the Stamina research by allowing the company to continue their experimental therapies on 32 terminally ill patients, some of them children. Many scientists across Europe have sent letters to the Italian health minister regarding this decision, stating their concerns about this untested, unproven and theoretically unsound research. Such blatant disregard of protocol and established rulings may cause harm to other, viable stem cell research being conducted in appropriate conditions, with sound theories behind them – say the scientists. They continue to say that Stamina’s therapies may prove harmful to the patients and cause unforeseen collateral damage.
"There is no rationale for this and no evidence that these procedures are not dangerous for patients," said Professor Michele De Luca of the University of Modena. One of the main concerns of the scientists remains the disregard of established European licensing criteria, which were put in place to prevent the exploitation and harming of patients.
The patients families have filled class action motions via their lawyers, with the judges preceding over these cases stating that a modification of the law is necessary, to allow to terminally ill patients to undergo experimental treatment which might potentially save their lives, however small the chance.
The judges and supporters of the ruling have stated that it would be cruel to deny the therapies to the patients, considering it has not shown any “grave collateral effects”.
"These unproven and ill-prepared stem cell therapies, for which there is no scientific basis, will do nothing for patients and their families except make them poorer," said Charles French-Constant from the University of Edinburgh's Center for Regenerative Medicine.
This decision by the Italian Health minister was made as a result of receiving several emotional pleas from the parents of terminally ill children, and an increasing media pressure to “give them a chance”. Protest were held in the Roman square, with one notable protester, an almost naked woman, having the words “Yes to Life, yes to Stamina” written on her body. The scientists fear that the decision was based solely on emotional and political pressure and serves no good either to the patients or the scientific community. The minister himself has stated that this ruling was mainly brought about by “compassion”, and that the experimental treatment will continue only in public hospitals and under strict monitoring.
"The decision of the government to authorize the continuation of therapies ordered by judges was necessary to prevent discrimination, based on autonomous decisions by judges, between patients who had begun treatment with the Stamina Method," Balduzzi, the Italian minister of Health stated.
Several British scientists have stated that this ruling by the Italian government presents a dangerous precedent, and may encourage patients to look for experimental treatments abroad, disregarding the validity or safety of such therapies.
Stem cell research has become quite popular in the last few years. The potential of stem cells is invaluable in regenerative medicine research. Many papers have been written, many different therapies proposed and just some approved for clinical testing, but for now, medicine based on stem cells remains experimental and very costly. Most countries possessing stem cell research hold it under strict regulation, and require sound evidence and theory to allow testing of such therapies, most notably human trials.
Stem cell approaches used in medicine are most often based on their ability to maintain and repair tissue by replacing senescent cells in adult organisms. The prevailing part of stem cell and regenerative medicine research is conducted by utilizing embryonic stem cells, which is controversial by itself, because it involves the destruction of embryos. In contrast to that, adult stem cells are also available and being worked upon. Adult stem cells by comparison have a lesser degree of multipotence then embryonic stem cells, being able to assume the role of a smaller number of adult cells and tissues.
May last year, an Italian research foundation named “Stamina” had its research halted by the Italian government due to several issues concerning the effectiveness and viability of their adult stem cell research. As stated by the health inspectors, the conditions in Stamina’s laboratory were “unsanitary, with terrible maintenance and a critical lack of cleanliness, resulting in highly inadequate conditions”. But, March this year; the Italian government overruled the decision to halt the Stamina research by allowing the company to continue their experimental therapies on 32 terminally ill patients, some of them children. Many scientists across Europe have sent letters to the Italian health minister regarding this decision, stating their concerns about this untested, unproven and theoretically unsound research. Such blatant disregard of protocol and established rulings may cause harm to other, viable stem cell research being conducted in appropriate conditions, with sound theories behind them – say the scientists. They continue to say that Stamina’s therapies may prove harmful to the patients and cause unforeseen collateral damage.
"There is no rationale for this and no evidence that these procedures are not dangerous for patients," said Professor Michele De Luca of the University of Modena. One of the main concerns of the scientists remains the disregard of established European licensing criteria, which were put in place to prevent the exploitation and harming of patients.
The patients families have filled class action motions via their lawyers, with the judges preceding over these cases stating that a modification of the law is necessary, to allow to terminally ill patients to undergo experimental treatment which might potentially save their lives, however small the chance.
The judges and supporters of the ruling have stated that it would be cruel to deny the therapies to the patients, considering it has not shown any “grave collateral effects”.
"These unproven and ill-prepared stem cell therapies, for which there is no scientific basis, will do nothing for patients and their families except make them poorer," said Charles French-Constant from the University of Edinburgh's Center for Regenerative Medicine.
This decision by the Italian Health minister was made as a result of receiving several emotional pleas from the parents of terminally ill children, and an increasing media pressure to “give them a chance”. Protest were held in the Roman square, with one notable protester, an almost naked woman, having the words “Yes to Life, yes to Stamina” written on her body. The scientists fear that the decision was based solely on emotional and political pressure and serves no good either to the patients or the scientific community. The minister himself has stated that this ruling was mainly brought about by “compassion”, and that the experimental treatment will continue only in public hospitals and under strict monitoring.
"The decision of the government to authorize the continuation of therapies ordered by judges was necessary to prevent discrimination, based on autonomous decisions by judges, between patients who had begun treatment with the Stamina Method," Balduzzi, the Italian minister of Health stated.
Several British scientists have stated that this ruling by the Italian government presents a dangerous precedent, and may encourage patients to look for experimental treatments abroad, disregarding the validity or safety of such therapies.
by bridgettpayseur at 04-08-2013, 06:12 AM
0 comments
Human immunodeficiency virus (HIV) causes a chronic infection of a type of immune cell, called CD4+ T cells. Vaccines against HIV have so far been elusive, due mainly to the fact that HIV is a retrovirus. A retrovirus is a type of virus that contains a ribonucleic acid (RNA genome). The RNA is reverse-transcribed into deoxyribonucleic acid (DNA), which is then inserted into the host cell’s genome. In most organisms, DNA is the molecule of choice for storage of genetic information. DNA is then converted to RNA, which then directs the cell to produce protein.
Retroviral infections are difficult to prevent and treat for several reasons. First, the reverse-transcriptase, the enzyme that converts RNA to DNA, is very error-prone. It constantly makes mistakes, which causes a large number of mutations in the virus. These mutations can change viral proteins enough to make them unrecognizable by the immune system. The high mutation rate is also responsible for the large number of different strains of HIV-1 that are found in patients. Also, because the viral genome integrates into the host genome, the virus is difficult to remove completely from the host. As the host cell replicates, the viral genome is also replicated. Even if all HIV particles are removed from the bloodstream, some may remain quietly integrated in a host cell genome, waiting to be reactivated.
The high mutation rate of HIV has made vaccine development very difficult. The biggest hope for a successful vaccine lies in the development of broadly neutralizing antibodies. An antibody is a protein produced by the immune system that helps target a cell or virus for destruction to prevent and control infections. Broadly neutralizing antibodies recognize HIV viral proteins, such as the HIV envelope protein, that are involved in binding to the CD4+ T cell. These proteins are less likely to mutate significantly, and tend to be similar even in different strains of virus, as they are necessary for the infection process. A small percentage of HIV-infected patients, termed elite controllers, are able to produce these broadly-neutralizing antibodies. Because of these antibodies, elite controllers maintain low-to-undetectable levels of virus in their blood for extended periods, without the use of anti-retroviral therapy.
This week, researchers published information in the journal Nature following the development of broadly neutralizing antibodies in an HIV-infected patient. Generally, early on during an infection, a host is primarily infected with a founder strain that eventually evolves many changes due to the high mutability of the virus. The researchers followed the evolution of both the virus as it collected mutations, and the antibodies produced in response to the virus. By learning how broadly neutralizing antibodies are naturally developed within the host, scientists can rationally design vaccines to mimic the natural production of these antibodies. Studying the evolution of the virus within the host can also aid in vaccine design, by showing researchers which proteins mutate the most rapidly, and which the most slowly. Amazingly, the antibodies produced were able to neutralize over half of the HIV-1 strains tested by the researchers. This is also an important concept for vaccine design, as one vaccine could protect against multiple strains of HIV, and even provide protection as the virus mutates within the host.
The production of an effective, highly versatile anti-HIV vaccine is of the utmost importance to defeating the virus and stopping the world-wide pandemic. As mentioned above, because HIV integrates into the host cell genome, it may never completely be removed from the host, even by the most advanced retroviral therapies. Even when viral proteins are undetectable in the plasma of a host, it is still possible that virus is lurking in the genome of CD4+ T cells. The most likely way to stop transmission of the virus is to prevent infection in the first place, by the use of a vaccine. A vaccine that elicits broadly neutralizing antibodies would be able to prevent the virus from getting a strong hold in the host. Even patients who have already been infected with HIV could benefit from vaccination. If the immune response has not yet been severely impacted by the virus, the host could potentially develop broadly neutralizing antibodies that prevent further reproduction and growth of the virus.
References:
http://www.the-scientist.com/?articles.v...V-Vaccine/
http://www.medindia.net/news/new-effecti...6972-1.htm
http://www.nature.com/nature/journal/vao...12053.html
http://www.hivcontrollers.org/
Retroviral infections are difficult to prevent and treat for several reasons. First, the reverse-transcriptase, the enzyme that converts RNA to DNA, is very error-prone. It constantly makes mistakes, which causes a large number of mutations in the virus. These mutations can change viral proteins enough to make them unrecognizable by the immune system. The high mutation rate is also responsible for the large number of different strains of HIV-1 that are found in patients. Also, because the viral genome integrates into the host genome, the virus is difficult to remove completely from the host. As the host cell replicates, the viral genome is also replicated. Even if all HIV particles are removed from the bloodstream, some may remain quietly integrated in a host cell genome, waiting to be reactivated.
The high mutation rate of HIV has made vaccine development very difficult. The biggest hope for a successful vaccine lies in the development of broadly neutralizing antibodies. An antibody is a protein produced by the immune system that helps target a cell or virus for destruction to prevent and control infections. Broadly neutralizing antibodies recognize HIV viral proteins, such as the HIV envelope protein, that are involved in binding to the CD4+ T cell. These proteins are less likely to mutate significantly, and tend to be similar even in different strains of virus, as they are necessary for the infection process. A small percentage of HIV-infected patients, termed elite controllers, are able to produce these broadly-neutralizing antibodies. Because of these antibodies, elite controllers maintain low-to-undetectable levels of virus in their blood for extended periods, without the use of anti-retroviral therapy.
This week, researchers published information in the journal Nature following the development of broadly neutralizing antibodies in an HIV-infected patient. Generally, early on during an infection, a host is primarily infected with a founder strain that eventually evolves many changes due to the high mutability of the virus. The researchers followed the evolution of both the virus as it collected mutations, and the antibodies produced in response to the virus. By learning how broadly neutralizing antibodies are naturally developed within the host, scientists can rationally design vaccines to mimic the natural production of these antibodies. Studying the evolution of the virus within the host can also aid in vaccine design, by showing researchers which proteins mutate the most rapidly, and which the most slowly. Amazingly, the antibodies produced were able to neutralize over half of the HIV-1 strains tested by the researchers. This is also an important concept for vaccine design, as one vaccine could protect against multiple strains of HIV, and even provide protection as the virus mutates within the host.
The production of an effective, highly versatile anti-HIV vaccine is of the utmost importance to defeating the virus and stopping the world-wide pandemic. As mentioned above, because HIV integrates into the host cell genome, it may never completely be removed from the host, even by the most advanced retroviral therapies. Even when viral proteins are undetectable in the plasma of a host, it is still possible that virus is lurking in the genome of CD4+ T cells. The most likely way to stop transmission of the virus is to prevent infection in the first place, by the use of a vaccine. A vaccine that elicits broadly neutralizing antibodies would be able to prevent the virus from getting a strong hold in the host. Even patients who have already been infected with HIV could benefit from vaccination. If the immune response has not yet been severely impacted by the virus, the host could potentially develop broadly neutralizing antibodies that prevent further reproduction and growth of the virus.
References:
http://www.the-scientist.com/?articles.v...V-Vaccine/
http://www.medindia.net/news/new-effecti...6972-1.htm
http://www.nature.com/nature/journal/vao...12053.html
http://www.hivcontrollers.org/
by bridgettpayseur at 04-08-2013, 06:10 AM
3 comments
Few statements in medical science are met with as much skepticism as the words, “We found a cure for cancer.” Cancer is a description given to more than 100 distinct diseases, affecting almost every part of the body. Cancer is caused when normal cells accumulate various mutations, or changes to the DNA that remove normal barriers to cellular replication. Thus, the mutated cancerous cell can replicate more frequently than normal cells, causing a tumor. If enough mutations accumulate, the cancerous cells can begin to leave the original site, and spread, or metastasize, to other parts of the body. Different types of cancers result from different combinations of mutations to factors that regulate cell growth and replication. To find one cure for all cancers seems like an impossible goal, given the various causes, locations, and types of cancers.
One great hope for cancer treatments comes from the host immune system. Normally, when either a foreign cell or a defective host cell is present in the body, the immune system will attempt to kill the cell. This prevents disease, such as infection or cancer. However, many cancer cells are able to evade the host’s immune system, by producing and displaying proteins that tell the host they are normal.
One such protein that is found on normal human cells is CD47. In normal cells, CD47 is expressed at a low level that is still sufficient to protect them from the immune system. Cancer cells, on the other hand, express very high levels of CD47. In 2012, researchers found that anti-CD47 antibody was able to target human-origin tumor cells in mice. The antibody, which binds to CD47 and makes it ‘invisible’ to immune cells, allowed macrophages and other phagocytes to destroy the tumor cells. This prevented tumor growth, and in some cases even decreased the size of the tumors. Shrinking tumors and preventing growth can help prevent the spread of cancer to other parts of the body.
The anti-CD47 antibody was effective at reducing the size and growth of a variety of human tumors, including breast cancer, bladder cancer, glioblastoma, lung cancer, and ovarian cancer. In many mice, the tumor was completely destroyed, and the mice remained cancer free several months after the study was completed. Additionally, the antibody did not show severe toxic reactions in the mice; only short-term anemia was noted. This is because cancer cells have a much higher number of CD47 molecules on their surface than normal cells, so they are targeted much more efficiently by the CD47 antibody. This lack of toxicity is a drastic change from conventional cancer therapies, such as chemotherapy and radiation, which work by targeting and killing all rapidly-multiplying cells.
Now, clinical trials are being prepared to test the efficacy of anti-CD47 antibody in human patients, and hopefully will begin in 2014. It is a difficult process to move from animal-based studies into clinical trials for many reasons. The antibody used in the clinical trials must be ‘humanized’ so that it interacts with the correct cells. In addition, the antibody must be produced in large quantities under very exacting conditions to ensure safety. The setup of the clinical trial must also be carefully planned, so that any data obtained can be properly interpreted. Investigators must determine how much antibody to give, which patients will be eligible, how to compare study results to placebo results, and more.
While this news is exciting, given the variety of cancers the anti-CD47 antibody was able to recognize, it must be met with cautious optimism. The natural tumors found in human patients may have key differences from the transplanted tumors in the mice. For example, these tumor cells may have other defense mechanisms in place to protect against the immune system. In addition, not all tumors may be good targets for the anti-CD47 immunotherapy. Solid tumors might be the best candidates for this immunotherapy, as the antibody could easily be injected directly into the tumor. However, if the tumor is too large, the antibody might not be able to reach and bind to all the cancer cells, necessitating multiple treatments. Blood cancers, such as lymphoma and leukemia, may not be suitable targets for the antibody. Because they do not consist of solid tumors, it might be difficult to localize the antibody to the cancerous cells. Also, since normal blood cells also express small amounts of CD47, intravenous injection of anti-CD47 antibody might cause more pronounced and long-lasting anemia that what was demonstrated in the mouse models. Despite these concerns, the promises of anti-CD47 immunotherapy could revolutionize future cancer treatments.
References:
http://www.pnas.org/content/109/17/6662.full.pdf+html
http://news.sciencemag.org/sciencenow/20...umors.html
http://www.webmd.com/cancer/default.htm
http://www.huffingtonpost.com/2013/03/28...72708.html
http://stemcell.stanford.edu/CD47/
http://clinicaltrials.gov/ct2/about-studies/learn
One great hope for cancer treatments comes from the host immune system. Normally, when either a foreign cell or a defective host cell is present in the body, the immune system will attempt to kill the cell. This prevents disease, such as infection or cancer. However, many cancer cells are able to evade the host’s immune system, by producing and displaying proteins that tell the host they are normal.
One such protein that is found on normal human cells is CD47. In normal cells, CD47 is expressed at a low level that is still sufficient to protect them from the immune system. Cancer cells, on the other hand, express very high levels of CD47. In 2012, researchers found that anti-CD47 antibody was able to target human-origin tumor cells in mice. The antibody, which binds to CD47 and makes it ‘invisible’ to immune cells, allowed macrophages and other phagocytes to destroy the tumor cells. This prevented tumor growth, and in some cases even decreased the size of the tumors. Shrinking tumors and preventing growth can help prevent the spread of cancer to other parts of the body.
The anti-CD47 antibody was effective at reducing the size and growth of a variety of human tumors, including breast cancer, bladder cancer, glioblastoma, lung cancer, and ovarian cancer. In many mice, the tumor was completely destroyed, and the mice remained cancer free several months after the study was completed. Additionally, the antibody did not show severe toxic reactions in the mice; only short-term anemia was noted. This is because cancer cells have a much higher number of CD47 molecules on their surface than normal cells, so they are targeted much more efficiently by the CD47 antibody. This lack of toxicity is a drastic change from conventional cancer therapies, such as chemotherapy and radiation, which work by targeting and killing all rapidly-multiplying cells.
Now, clinical trials are being prepared to test the efficacy of anti-CD47 antibody in human patients, and hopefully will begin in 2014. It is a difficult process to move from animal-based studies into clinical trials for many reasons. The antibody used in the clinical trials must be ‘humanized’ so that it interacts with the correct cells. In addition, the antibody must be produced in large quantities under very exacting conditions to ensure safety. The setup of the clinical trial must also be carefully planned, so that any data obtained can be properly interpreted. Investigators must determine how much antibody to give, which patients will be eligible, how to compare study results to placebo results, and more.
While this news is exciting, given the variety of cancers the anti-CD47 antibody was able to recognize, it must be met with cautious optimism. The natural tumors found in human patients may have key differences from the transplanted tumors in the mice. For example, these tumor cells may have other defense mechanisms in place to protect against the immune system. In addition, not all tumors may be good targets for the anti-CD47 immunotherapy. Solid tumors might be the best candidates for this immunotherapy, as the antibody could easily be injected directly into the tumor. However, if the tumor is too large, the antibody might not be able to reach and bind to all the cancer cells, necessitating multiple treatments. Blood cancers, such as lymphoma and leukemia, may not be suitable targets for the antibody. Because they do not consist of solid tumors, it might be difficult to localize the antibody to the cancerous cells. Also, since normal blood cells also express small amounts of CD47, intravenous injection of anti-CD47 antibody might cause more pronounced and long-lasting anemia that what was demonstrated in the mouse models. Despite these concerns, the promises of anti-CD47 immunotherapy could revolutionize future cancer treatments.
References:
http://www.pnas.org/content/109/17/6662.full.pdf+html
http://news.sciencemag.org/sciencenow/20...umors.html
http://www.webmd.com/cancer/default.htm
http://www.huffingtonpost.com/2013/03/28...72708.html
http://stemcell.stanford.edu/CD47/
http://clinicaltrials.gov/ct2/about-studies/learn
by ExpertScie at 04-08-2013, 12:46 AM
0 comments
Dreams are to fulfill them in real life. Many times our dreams are secret and we don’t like to share them. But it is interesting fact that, they will not remain secret in future and can be scanned! Don’t worry, scientist had just begun first step into understanding in details what dreams are and this scanning of dreams is not successful in real time, but rather they can be scanned latter. This will not open every secret but positive side is that it will remind things that you want to achieve in real life through scientific ways, and to make them come true.
This research will not disclose anyone secret dreams but scientifically speaking, the scanning will help to understand and to further improve the mental state of patients. The Advanced Telecommunications Research Institute International in Kyoto, Japan is the place where a team of scientist is working to decode dreams by brain scans.
As we all know that dreams are one of the most fascinating aspects of the human experience, understanding them can open a new way for the well being of mankind and even every life that dreams.
In its first phase of study, neuroscientist Yukiyasu Kamitani and colleagues examined, three young men as they tried to get some sleep inside an fMRI scanner. During this, the attached machine monitored their brain activity and evaluated neurological concepts of dreams. The volunteer’s brains activity was monitored with EEG electrodes. What is interesting is that they saw an EEG signature which is indication of dreaming. After this, they woke him up and as a part of study, ask what did they dreamed. After which the logic of it was studied with the signals on EEG.
Scientifically speaking, this is what Neuroscientist call hypnagogic imagery, the state of dream that occurs as people fall asleep. The data base was generated in several days time and the reason was to have a significant data to arrive at any conclusion. The repeatability was ensured and results were collected in detail. During this testing, Kamitani and colleagues, focused more on type of imagery rather than the dream itself, which is scientific evidence of understanding it.
After collection of significant data, the researcher developed a visual imagery decoder which was purely based on machine learning algorithms. As a part of development of decoder, they trained it to distinguish patterns of brain activity of men while they were awake and watching a video montage. This was from hundreds of images which were selected from many online databases. After this training to decoder, the researcher successfully could input a pattern of activity of brain and have the decoder evaluate or predict which image was most likely have developed that pattern of activity of brain. In this way researcher, co-related it scientifically.
But if we see at earlier research in this field, this was not any new addition. What they did after this was beyond previous work. The team was feeding the decoder pattern of brain activity, while the subject was dreaming. This enabled them to correctly identify objects the men had seen in their dream! Or rather, they could identify the broader part of object the men had seen in their dreams. For example, the man had dreamt about a car, and researcher could have identified it as some vehicle or something related to driving or moving etc. Obviously not in a moving picture like he might have dreamt.
In this case, the drawback is that this should have been feed in decoder earlier to trace similarities in the two. Adding to this, researcher said that this is just a primitive study and we are positive on the further research for understanding dreams neurologically as far as possible.
Adding to it, Kamitani said, that today’s technology is still beyond the scope to decode color, emotions or actions in every details. At present, it works for imagery that had occurred just about 15 second before waking up. Another limitation of this research is that every time the same decoder cannot be used for different person. In such case, the decoder has to be trained again with person viewing hundreds of images.
It is remarkable achievements, to study the nature and functions of dreams in spite of such limitation. Kamitani is correlating between the frequency and memory performance with respect to dreams.
This is based on one of the theory which states that dreaming is for strengthening memory, while at the same time, another theory states dreaming is for forgetting. The understanding of co-relation between the two will conclude which theory is correct or none.
I hope science will make this entire dream come true!
This research will not disclose anyone secret dreams but scientifically speaking, the scanning will help to understand and to further improve the mental state of patients. The Advanced Telecommunications Research Institute International in Kyoto, Japan is the place where a team of scientist is working to decode dreams by brain scans.
As we all know that dreams are one of the most fascinating aspects of the human experience, understanding them can open a new way for the well being of mankind and even every life that dreams.
In its first phase of study, neuroscientist Yukiyasu Kamitani and colleagues examined, three young men as they tried to get some sleep inside an fMRI scanner. During this, the attached machine monitored their brain activity and evaluated neurological concepts of dreams. The volunteer’s brains activity was monitored with EEG electrodes. What is interesting is that they saw an EEG signature which is indication of dreaming. After this, they woke him up and as a part of study, ask what did they dreamed. After which the logic of it was studied with the signals on EEG.
Scientifically speaking, this is what Neuroscientist call hypnagogic imagery, the state of dream that occurs as people fall asleep. The data base was generated in several days time and the reason was to have a significant data to arrive at any conclusion. The repeatability was ensured and results were collected in detail. During this testing, Kamitani and colleagues, focused more on type of imagery rather than the dream itself, which is scientific evidence of understanding it.
After collection of significant data, the researcher developed a visual imagery decoder which was purely based on machine learning algorithms. As a part of development of decoder, they trained it to distinguish patterns of brain activity of men while they were awake and watching a video montage. This was from hundreds of images which were selected from many online databases. After this training to decoder, the researcher successfully could input a pattern of activity of brain and have the decoder evaluate or predict which image was most likely have developed that pattern of activity of brain. In this way researcher, co-related it scientifically.
But if we see at earlier research in this field, this was not any new addition. What they did after this was beyond previous work. The team was feeding the decoder pattern of brain activity, while the subject was dreaming. This enabled them to correctly identify objects the men had seen in their dream! Or rather, they could identify the broader part of object the men had seen in their dreams. For example, the man had dreamt about a car, and researcher could have identified it as some vehicle or something related to driving or moving etc. Obviously not in a moving picture like he might have dreamt.
In this case, the drawback is that this should have been feed in decoder earlier to trace similarities in the two. Adding to this, researcher said that this is just a primitive study and we are positive on the further research for understanding dreams neurologically as far as possible.
Adding to it, Kamitani said, that today’s technology is still beyond the scope to decode color, emotions or actions in every details. At present, it works for imagery that had occurred just about 15 second before waking up. Another limitation of this research is that every time the same decoder cannot be used for different person. In such case, the decoder has to be trained again with person viewing hundreds of images.
It is remarkable achievements, to study the nature and functions of dreams in spite of such limitation. Kamitani is correlating between the frequency and memory performance with respect to dreams.
This is based on one of the theory which states that dreaming is for strengthening memory, while at the same time, another theory states dreaming is for forgetting. The understanding of co-relation between the two will conclude which theory is correct or none.
I hope science will make this entire dream come true!
by sale0303 at 04-07-2013, 09:02 AM
1 comments
The most common cause of unsuccessful implanting embryo in the uterus and abortions in the first trimester of pregnancy are genetic anomalies. Genetic information is contained in the chromosomes.
Genomic DNA analysis includes preimplantation genetic diagnosis - PGD and preimplantation genetic screening - PGS. Basis of PGD and PGS involves genetic analysis of embryos before implantation and transferring certain "normal" embryos. The first successful application of PGD for hereditary diseases is published in 1990. For the application of PGD / PGS patients must use IVF to create embryos for in vitro analysis. For diagnosis are described three distinct developmental stages: polar corpuscles removed from the oocyte / zygote (polar body biopsy); blastomers 6-8-cell embryos, day three (cleavage stage biopsy); or biopsy blastocysts cell, 5 or 6 days develops (blastocyst biopsy).
Biopsy samples are analyzed by PCR (polymerase chain reaction) or FISH (fluorescence in situ hybridization) of relevant techniques. PCR techniques are applied for the diagnosis of specific genetic diseases, whereas the FISH technique to analyze the number of chromosomes in patients with chromosomal anomalies or for sex selection of embryos for diseases transmitted on the X-chromosome.
PGD
PGD is an important scientific advance for patients who are carriers of genetic diseases, and who are at risk for transmission of inherited diseases (haemophilia, cystic fibrosis, Fragile X, Duchenne muscular dystrophy, etc.).
Statistic shows that PGD procedures are increasing each year as a result of new and successful methods of detection of abnormal gene on one level blastomers and completing the human genome sequence. One of the techniques that have been developed recently is amplification genome. This method allows the collection of DNA from one microgram blastomers, analysis and application of whole-genome microarrays.
It is very important for the detection of chromosomal abnormalities, mutations, and aneuploidies. The indications for PGD biopsy is done on the third day of embryonic development, in one or two blastomers, and transferred to a "normal" embryo of the fifth or sixth day.
PGS
PGS, unlike PGD was developed to improve the success of IVF, especially in elderly women. Indications for PGS are: elderly patients, multiple miscarriages, repeated IVF failure and male infertility.
Concerns with PGD/PGS
The embryos could be traumatized by the biopsy procedure - particularly during cleavage stage biopsy. There is some evidence that carefully performed trophoectoderm biopsies blastocysts might not weaken the embryo at all.
As with any new technique and technology, there is a "learning curve". There could be large differences between centers performing these techniques, and even between technicians within the same IVF center.
Mosaicism can complicate matters. An embryo is a mosaic if there are 2 (or more) different chromosomal patterns in cells of that embryo. There is evidence that mosaic embryos sometimes "self-repair", or possibly designate abnormal cells preferentially to the placenta instead of the fetus. More research on mosaicism is needed.
Many people believe that because life begins at conception and that the destruction of an embryo is the destruction of a person. In some cases, a genetically defective fertilized egg will mature without the presence of disorder or disease.
Sampling of Embryonic DNA Without Biopsy
On the fifth day of developmental processes in the embryo begins to absorb liquid (endometrial gland secretions), which initially accumulates in the form of vacuoles in blastomers and soon extracellularly. In this way, it creates a cavity within the embryo - blastocists cavity and structure of the embryo at this stage is called a blastocyst developmental processes.
In a recent study published in Reproductive Biomedicine Online, a group of researchers sought to achieve diagnose of genetic disease in embryonic DNA without the use of a biopsy. They found that extracting fluid from human embryos at the blastocyst stage contains DNA from embryo. Blastocysts are embryos, which are 5 or 6 days old, and they are the last free-living stage that can be studied in the laboratory prior to transfer into the uterus. They contain between 50 and 300 cells that surround a fluid-filled cavity called the blastocoels. The scientists got the idea to the blastocyst stage liquid removed, leaving the cells intact. The analysis of this fluid have proven that it contained cell-free DNA in a sufficiently good state, enough to determine several known genes of the sex chromosomes by polymerase chain reaction (PCR).
This method removes some ethical issues that arise using PGD methods. The study above is a good start. However, it is important to consider that regardless of the outcome of these studies, we need a large number of studies.
These methods cannot identify all the genetic and chromosomal disorders. These methods are not determined at the level of gene disorders or other developmental malformations and congenital anomalies. Performing these methods in any case does not reimburse prenatal screening for congenital anomalies of development during pregnancy.
Conclusion
These procedures are used for determining the presence of a particular genetic condition in the embryo prior to implantation. In this way it is possible to determine whether it is in the process of artificial insemination to damage genetic material, a disturbance in the number of chromosomes, etc. These procedures are used to mother spared spontaneous abortions, reduce the chances of multiple birth, as well as to select out an embryo that is in the best condition, which gives a greater chance of success interventions. In addition, it is possible to test for the presence of gene alleles inherited disorders, as well as a wide range of other information.
These methods are used to determine the different genetic abnormalities, and predisposition to a variety of serious diseases, and the number of genes associated with pathological conditions that can be examined is increasing. Same as with any new technology, here is also the main problem - the problem of borders. Like everything else, these technologies should be used within the limits of the moral.
Genomic DNA analysis includes preimplantation genetic diagnosis - PGD and preimplantation genetic screening - PGS. Basis of PGD and PGS involves genetic analysis of embryos before implantation and transferring certain "normal" embryos. The first successful application of PGD for hereditary diseases is published in 1990. For the application of PGD / PGS patients must use IVF to create embryos for in vitro analysis. For diagnosis are described three distinct developmental stages: polar corpuscles removed from the oocyte / zygote (polar body biopsy); blastomers 6-8-cell embryos, day three (cleavage stage biopsy); or biopsy blastocysts cell, 5 or 6 days develops (blastocyst biopsy).
Biopsy samples are analyzed by PCR (polymerase chain reaction) or FISH (fluorescence in situ hybridization) of relevant techniques. PCR techniques are applied for the diagnosis of specific genetic diseases, whereas the FISH technique to analyze the number of chromosomes in patients with chromosomal anomalies or for sex selection of embryos for diseases transmitted on the X-chromosome.
PGD
PGD is an important scientific advance for patients who are carriers of genetic diseases, and who are at risk for transmission of inherited diseases (haemophilia, cystic fibrosis, Fragile X, Duchenne muscular dystrophy, etc.).
Statistic shows that PGD procedures are increasing each year as a result of new and successful methods of detection of abnormal gene on one level blastomers and completing the human genome sequence. One of the techniques that have been developed recently is amplification genome. This method allows the collection of DNA from one microgram blastomers, analysis and application of whole-genome microarrays.
It is very important for the detection of chromosomal abnormalities, mutations, and aneuploidies. The indications for PGD biopsy is done on the third day of embryonic development, in one or two blastomers, and transferred to a "normal" embryo of the fifth or sixth day.
PGS
PGS, unlike PGD was developed to improve the success of IVF, especially in elderly women. Indications for PGS are: elderly patients, multiple miscarriages, repeated IVF failure and male infertility.
Concerns with PGD/PGS
The embryos could be traumatized by the biopsy procedure - particularly during cleavage stage biopsy. There is some evidence that carefully performed trophoectoderm biopsies blastocysts might not weaken the embryo at all.
As with any new technique and technology, there is a "learning curve". There could be large differences between centers performing these techniques, and even between technicians within the same IVF center.
Mosaicism can complicate matters. An embryo is a mosaic if there are 2 (or more) different chromosomal patterns in cells of that embryo. There is evidence that mosaic embryos sometimes "self-repair", or possibly designate abnormal cells preferentially to the placenta instead of the fetus. More research on mosaicism is needed.
Many people believe that because life begins at conception and that the destruction of an embryo is the destruction of a person. In some cases, a genetically defective fertilized egg will mature without the presence of disorder or disease.
Sampling of Embryonic DNA Without Biopsy
On the fifth day of developmental processes in the embryo begins to absorb liquid (endometrial gland secretions), which initially accumulates in the form of vacuoles in blastomers and soon extracellularly. In this way, it creates a cavity within the embryo - blastocists cavity and structure of the embryo at this stage is called a blastocyst developmental processes.
In a recent study published in Reproductive Biomedicine Online, a group of researchers sought to achieve diagnose of genetic disease in embryonic DNA without the use of a biopsy. They found that extracting fluid from human embryos at the blastocyst stage contains DNA from embryo. Blastocysts are embryos, which are 5 or 6 days old, and they are the last free-living stage that can be studied in the laboratory prior to transfer into the uterus. They contain between 50 and 300 cells that surround a fluid-filled cavity called the blastocoels. The scientists got the idea to the blastocyst stage liquid removed, leaving the cells intact. The analysis of this fluid have proven that it contained cell-free DNA in a sufficiently good state, enough to determine several known genes of the sex chromosomes by polymerase chain reaction (PCR).
This method removes some ethical issues that arise using PGD methods. The study above is a good start. However, it is important to consider that regardless of the outcome of these studies, we need a large number of studies.
These methods cannot identify all the genetic and chromosomal disorders. These methods are not determined at the level of gene disorders or other developmental malformations and congenital anomalies. Performing these methods in any case does not reimburse prenatal screening for congenital anomalies of development during pregnancy.
Conclusion
These procedures are used for determining the presence of a particular genetic condition in the embryo prior to implantation. In this way it is possible to determine whether it is in the process of artificial insemination to damage genetic material, a disturbance in the number of chromosomes, etc. These procedures are used to mother spared spontaneous abortions, reduce the chances of multiple birth, as well as to select out an embryo that is in the best condition, which gives a greater chance of success interventions. In addition, it is possible to test for the presence of gene alleles inherited disorders, as well as a wide range of other information.
These methods are used to determine the different genetic abnormalities, and predisposition to a variety of serious diseases, and the number of genes associated with pathological conditions that can be examined is increasing. Same as with any new technology, here is also the main problem - the problem of borders. Like everything else, these technologies should be used within the limits of the moral.
by sale0303 at 04-06-2013, 11:22 PM
0 comments
Syringes and needles have been used for immunization since 1853. This way of application is very old and very good, but it has a lot of disadvantages like high expenses in preservation of vaccines, complications with needle application, discomfort at 10% of the patients and phobia caused by needles etc. A revolution in human vaccines is currently under development. This revolution is called Nanopatch vaccines. This Nanopatch approach is made of an array of thousands of vaccine- coated microprojections which perforate skin but only its outer layers. This is maybe one of the greatest achievements, because this way of application is absolutely painless. This way of application is made not to reach the deeper layers of the skin where nerve endings are located. Major doubt about this way of application was the question- will there be enough material which will activate immune system, because there is used only a tiny fraction of the dose. The answer is- YES. Yes, there is sufficient amount of immune material because there is a huge difference between conservative way and the Nanopatch way of presentation.
Conservative way with syringes and needles is oriented on muscle cells, but the Nanopatch technology is oriented on skin cells. It has been proven in past 30 years that skin, unlike muscle, is rammed full of immune cells. Those immune cells are dendritic cells (DC) which are potent antigen presenting cells. Whereas the biological characteristics and immunological functions of epidermal DC known as Langernahs cells (LC) have been the focus of intense research in the past, less is known regarding their dermal counterparts named dermal dendritic cells (DDC). Because of the lack in immune cells in muscle cell, skin is preferable place for vaccines.
Benefits of Nanopatch vaccines
The outer layer of skin is different from person to person. It varies in thickness, humidity, age, gender and other factors. This is one of the potential problems for Nanopatch vaccine application, but Nanopatch application achieves delivery of vaccine by choosing the coated Nanopatch arrays with an adequate applicator. This is the way of skipping possible problems related to dose.
Another important advantage of Nanopatch vaccines is the way of preserving. This vaccines are not like conventional vaccines because they don’t need cold chain for transport. Professor Mark Kendall from University of Queensland's Institute for Biotechnology and Nanotechnology and his team have tested these vaccines in extreme conditions. They traveled to Papua New Guinea, which is one of the leading countries in infection with HPV virus. They were in extreme conditions with nearly 100% humidity and they have not noticed loss in vaccines activity. This was a huge achievement for this team, because they cut out expenses, and there was no danger that vaccines will be ineffective or possibly harmful.
Next benefit of these Nanopatch vaccines is expenses cost effectiveness. This is so far the main benefit for most of the countries in development. These vaccines could be made for fifty times less cost than many current vaccines. This price could cure the people from the countries which cannot afford many current vaccines. Also cost effectiveness can be increased with cost savings due to using less vaccine to reach an effective immunization, reduction of cold chains and, for sure, reduction in the costs which are connected with needle injuries. There are some opinions that these vaccines could be sent by mail in remote parts of the countries or even remote parts of the world! Those mailed vaccines could be applied by people themselves even by people who have fobia of needles, because it is absolutely not painful and there are no complications which we have in conventional way of application.
Needles and syringes have also risk of blood-transmitted diseases like Hepatitis B, Hepatitis C, Human Immunodeficiency Virus and other viruses. With this way of vaccine application there is no risk of infection with similar viruses.
This benefits from above are strong and unique in world of vaccines. Therefore this way of application may be suitable for a vast majority of vaccines.
History of Development
This way of application is still under development. Professor Mark Kendall from University of Queensland's Institute for Biotechnology and Nanotechnology and his team have only tested this type of immunization on mice using various inoculations. In animals treated with influenza vaccines, Nanopatch induced immune response with a tiny dose which was ten times better than any other way of application.
Beside this influenza vaccine there were good results with Human Papiloma Virus vaccine, Human Simplex Virus, Chikungunya Virus and West Nile Virus. Although this type of vaccination has shown great results, it has a long, long way to go to bring what is still an experimental device to market, but Professor Mark Kendall from University of Queensland's Institute for Biotechnology and Nanotechnology and his team are sure that this way of immunization will be the future of vaccines.
There were attempts of creation similar with this Nanopatch system but all of them were failures. The Austrian biotech firm Intercell tried to create experimental VEP (vaccine enhancement patch) system against pandemic flu. This project was a complete failure. However this system had completely different way of action which was applied after a needle vaccination and it was designed to boost vaccines effect. But this Nanopatch vaccine applies directly, in outer layers of the skin. Than it is presented to immune skin cells without adjuvant.
This way of application is definitely utopia of all vaccine applications as it is, according to recent studies, more effective than any other way of application and costs about fifty times less than then many current vaccines. If it shows good results in human trials, it will definitely bring bright future to human vaccination.
Conservative way with syringes and needles is oriented on muscle cells, but the Nanopatch technology is oriented on skin cells. It has been proven in past 30 years that skin, unlike muscle, is rammed full of immune cells. Those immune cells are dendritic cells (DC) which are potent antigen presenting cells. Whereas the biological characteristics and immunological functions of epidermal DC known as Langernahs cells (LC) have been the focus of intense research in the past, less is known regarding their dermal counterparts named dermal dendritic cells (DDC). Because of the lack in immune cells in muscle cell, skin is preferable place for vaccines.
Benefits of Nanopatch vaccines
The outer layer of skin is different from person to person. It varies in thickness, humidity, age, gender and other factors. This is one of the potential problems for Nanopatch vaccine application, but Nanopatch application achieves delivery of vaccine by choosing the coated Nanopatch arrays with an adequate applicator. This is the way of skipping possible problems related to dose.
Another important advantage of Nanopatch vaccines is the way of preserving. This vaccines are not like conventional vaccines because they don’t need cold chain for transport. Professor Mark Kendall from University of Queensland's Institute for Biotechnology and Nanotechnology and his team have tested these vaccines in extreme conditions. They traveled to Papua New Guinea, which is one of the leading countries in infection with HPV virus. They were in extreme conditions with nearly 100% humidity and they have not noticed loss in vaccines activity. This was a huge achievement for this team, because they cut out expenses, and there was no danger that vaccines will be ineffective or possibly harmful.
Next benefit of these Nanopatch vaccines is expenses cost effectiveness. This is so far the main benefit for most of the countries in development. These vaccines could be made for fifty times less cost than many current vaccines. This price could cure the people from the countries which cannot afford many current vaccines. Also cost effectiveness can be increased with cost savings due to using less vaccine to reach an effective immunization, reduction of cold chains and, for sure, reduction in the costs which are connected with needle injuries. There are some opinions that these vaccines could be sent by mail in remote parts of the countries or even remote parts of the world! Those mailed vaccines could be applied by people themselves even by people who have fobia of needles, because it is absolutely not painful and there are no complications which we have in conventional way of application.
Needles and syringes have also risk of blood-transmitted diseases like Hepatitis B, Hepatitis C, Human Immunodeficiency Virus and other viruses. With this way of vaccine application there is no risk of infection with similar viruses.
This benefits from above are strong and unique in world of vaccines. Therefore this way of application may be suitable for a vast majority of vaccines.
History of Development
This way of application is still under development. Professor Mark Kendall from University of Queensland's Institute for Biotechnology and Nanotechnology and his team have only tested this type of immunization on mice using various inoculations. In animals treated with influenza vaccines, Nanopatch induced immune response with a tiny dose which was ten times better than any other way of application.
Beside this influenza vaccine there were good results with Human Papiloma Virus vaccine, Human Simplex Virus, Chikungunya Virus and West Nile Virus. Although this type of vaccination has shown great results, it has a long, long way to go to bring what is still an experimental device to market, but Professor Mark Kendall from University of Queensland's Institute for Biotechnology and Nanotechnology and his team are sure that this way of immunization will be the future of vaccines.
There were attempts of creation similar with this Nanopatch system but all of them were failures. The Austrian biotech firm Intercell tried to create experimental VEP (vaccine enhancement patch) system against pandemic flu. This project was a complete failure. However this system had completely different way of action which was applied after a needle vaccination and it was designed to boost vaccines effect. But this Nanopatch vaccine applies directly, in outer layers of the skin. Than it is presented to immune skin cells without adjuvant.
This way of application is definitely utopia of all vaccine applications as it is, according to recent studies, more effective than any other way of application and costs about fifty times less than then many current vaccines. If it shows good results in human trials, it will definitely bring bright future to human vaccination.
by Abida Sara at 04-06-2013, 02:56 AM
0 comments
INTRODUCTION:
After years of research on liposome it has been possible to create a new class of drug delivery vehicles called COCHLEATES. They are stable, protects drug from harsh environmental condition and also prevent drying of drug. Cochleate are calcium-phospholipids structures that engulf the drug to be introduced to body within itself.
DISCOVERY:
Cochleate were discovered by Dr. D. Papahadjoupoulos and co-workers, in 1975 and have been used in late 80s and early 90s for delivery of antigens. Nanocochleates were introduced in 1999 to develop smaller particles for encapsulation of hydrophobic drugs of small size. They are cigar like micro structure composed of multiple series of lipid bi layer. They are elongated structures unlike liposome which are circular in shape.
COMPOSITION:
Nanocochleates consists of a purified soy based phospholipids that contains at least about 75% by weight of lipid which can be phosphotidyl serine (PS), dioleoylphosphatidylserine (DOPS), phosphatidic acid (PA), phosphatidylinositol (PI), phosphatidyl glycerol (PG) and /or a mixture of one or more of these lipids with other lipids. A multivalent cation, which can be Zn+2 or Ca+2 or Mg+2 or Ba+2 and a drug.
Drug can be protein, peptide, polynucleotide, antiviral agent, anesthetic, anticancer agent, immunosuppressant, steroidal anti inflammatory agent, non steroidal anti inflammatory agents, tranquilizer, nutritional supplement, herbal product, vitamin and/or vasodilator agent .
PREPRATION:
Cochleates are generally prepared by four major methods:
a) Hydrogel method:
b) Trapping method
c) Dialysis method
d) Direct calcium dialysis method
STABILITY OF COCHLEATES:
Even though the outer layer of the cochleate is exposed to harsh conditions or enzyme the component within the multilayer remains intact. The interior of cochleates is essentially free of water and resistant to penetration of foreign components. Even after drying cochleates to powder and storing at freezing temperature they can be reconstructed and the process of drying have no adverse effect on the working of them.
ADVANTAGES:
• They are easily observed under microscope and are produced with ease and safety.
• Due to limited oxygen permeability, drugs are prevented from oxidation.
• Provide ease of shipping and storage of drugs before administration.
• Hydrophobic molecules and tissues impermeable drugs can be transferred into body via cochleates.
• Specificity of target part of the body can be maintained using them.
• They are made unique by their structure that enables them to be a great delivery vehicle.
• With administration of live vaccine they are many life threatening risk associated like allergies , inversion of vaccine effect to wild infection etc. these can be neglected by use of Nanocochleates
• Multiple administrations of high doses of cochleate formulations to the same animal show no toxicity and do not result in either the development of an immune response to the cochleat.
APPLICATION:
• Production of ApoA1 (i.e. Apo lipoprotein) in treatment of Atherosclerosis and other heart diseases.
ApoA1 is a High Density Lipoprotein (HDL) which carries out esterification of cholesterol and transfers it to lever thus protecting it from arthrosclerosis. As ApoA1 is a protein it degrades gastrointestinal enzymes hence are not used as in tact molecule. So Nanocochlaetes provide a good platform for ApoA1 delivery.
• Used in delivering Amphotericin B, an anti fungal agent orally with least harm, good safety and also reduced cost of treatment.
• They can also deliver omega 3 in cakes, soups and cookies without harming products taste appearance or odor
• They are also used to deliver protein, DNA for vaccine and gene therapy.
CONCLUSION:
Nanocochleates could be a major breakthrough in scientifically made drugs suitable for large level of drug delivery with up most care and accuracy of treatment.
REFERENCES:
1. V. Ravi Shankar, Y. Dastagiri Reddy ; NANOCOCHLEATE –A NEW APPROCH INLIPID DRUG DELIVERY
2. Dr. David Deimarre, Dr. Susan Gould Fogerite, Dr. Rapheal J. Mannino ; FORMULATION OF HYDROPHOBIC DRUGS INTO COCHLEATES DELIVERY VEHICLE
After years of research on liposome it has been possible to create a new class of drug delivery vehicles called COCHLEATES. They are stable, protects drug from harsh environmental condition and also prevent drying of drug. Cochleate are calcium-phospholipids structures that engulf the drug to be introduced to body within itself.
DISCOVERY:
Cochleate were discovered by Dr. D. Papahadjoupoulos and co-workers, in 1975 and have been used in late 80s and early 90s for delivery of antigens. Nanocochleates were introduced in 1999 to develop smaller particles for encapsulation of hydrophobic drugs of small size. They are cigar like micro structure composed of multiple series of lipid bi layer. They are elongated structures unlike liposome which are circular in shape.
COMPOSITION:
Nanocochleates consists of a purified soy based phospholipids that contains at least about 75% by weight of lipid which can be phosphotidyl serine (PS), dioleoylphosphatidylserine (DOPS), phosphatidic acid (PA), phosphatidylinositol (PI), phosphatidyl glycerol (PG) and /or a mixture of one or more of these lipids with other lipids. A multivalent cation, which can be Zn+2 or Ca+2 or Mg+2 or Ba+2 and a drug.
Drug can be protein, peptide, polynucleotide, antiviral agent, anesthetic, anticancer agent, immunosuppressant, steroidal anti inflammatory agent, non steroidal anti inflammatory agents, tranquilizer, nutritional supplement, herbal product, vitamin and/or vasodilator agent .
PREPRATION:
Cochleates are generally prepared by four major methods:
a) Hydrogel method:
b) Trapping method
c) Dialysis method
d) Direct calcium dialysis method
STABILITY OF COCHLEATES:
Even though the outer layer of the cochleate is exposed to harsh conditions or enzyme the component within the multilayer remains intact. The interior of cochleates is essentially free of water and resistant to penetration of foreign components. Even after drying cochleates to powder and storing at freezing temperature they can be reconstructed and the process of drying have no adverse effect on the working of them.
ADVANTAGES:
• They are easily observed under microscope and are produced with ease and safety.
• Due to limited oxygen permeability, drugs are prevented from oxidation.
• Provide ease of shipping and storage of drugs before administration.
• Hydrophobic molecules and tissues impermeable drugs can be transferred into body via cochleates.
• Specificity of target part of the body can be maintained using them.
• They are made unique by their structure that enables them to be a great delivery vehicle.
• With administration of live vaccine they are many life threatening risk associated like allergies , inversion of vaccine effect to wild infection etc. these can be neglected by use of Nanocochleates
• Multiple administrations of high doses of cochleate formulations to the same animal show no toxicity and do not result in either the development of an immune response to the cochleat.
APPLICATION:
• Production of ApoA1 (i.e. Apo lipoprotein) in treatment of Atherosclerosis and other heart diseases.
ApoA1 is a High Density Lipoprotein (HDL) which carries out esterification of cholesterol and transfers it to lever thus protecting it from arthrosclerosis. As ApoA1 is a protein it degrades gastrointestinal enzymes hence are not used as in tact molecule. So Nanocochlaetes provide a good platform for ApoA1 delivery.
• Used in delivering Amphotericin B, an anti fungal agent orally with least harm, good safety and also reduced cost of treatment.
• They can also deliver omega 3 in cakes, soups and cookies without harming products taste appearance or odor
• They are also used to deliver protein, DNA for vaccine and gene therapy.
CONCLUSION:
Nanocochleates could be a major breakthrough in scientifically made drugs suitable for large level of drug delivery with up most care and accuracy of treatment.
REFERENCES:
1. V. Ravi Shankar, Y. Dastagiri Reddy ; NANOCOCHLEATE –A NEW APPROCH INLIPID DRUG DELIVERY
2. Dr. David Deimarre, Dr. Susan Gould Fogerite, Dr. Rapheal J. Mannino ; FORMULATION OF HYDROPHOBIC DRUGS INTO COCHLEATES DELIVERY VEHICLE