‘Rectal-Friendly’ Version Of Tenofovir Gel

A new clinical trial conducted by the U.S. National Institutes of Health categorizes tenofovir (marketed in the United States under the name of Viread) as acceptable and safe to prescribe. Tenofovir is an antiretroviral drug prescribed, based on previous studies, to reduce the number of HIV infections. The study was funded by the Microbicide Trials Network and was presented on the 6th of March at the 19th Conference on Retroviruses and Opportunistic Infections, held in Seattle. Scientists suggest that the new results will be an important step towards developing new rectal microbicide drugs that could prevent HIV infections transmitted through anal sex.

Rectal Tenofovir Gel

Microbicide drugs are chemical substances that have the ability to destroy specific microorganisms. Microbicides can be found as gels, creams, tables or even films. Most of them are gels and creams and are applied on the inside of either the rectum or the vagina. Until now, the use of microbicides was to prevent the infection with HIV through unprotected vaginal sex but future studies will focus on developing new products that would prevent HIV infections caused by unprotected anal sex, as studies show that unprotected anal sex is 20 times riskier than unprotected vaginal sex.

The current study was based on tests conducted on 65 men and women from three different locations. These locations were the University of Pittsburgh, the University of Alabama and Fenway Health in Boston. This study represents a follow-up trial which assessed the impact of rectally using a vaginal formulation of tenofovir. Results showed a present antiviral effect but arguable side effects.

Scientists randomly separated the patients into four study groups. Patients in the first group received a new rectal formulation of tenofovir gel. The patients in the second group received a gel containing spermicide. The patients in the third group  were given a placebo gel. Patients in the last group did not receive any gel but participated in all of the procedures and tests that were conducted on the other patients.

The evaluation of the results of the study shows that there are no important differences between the side effects of the three types of gel. Insignificant side effects were reported by almost 80 percent of the participants whilst bearable side effects were reported by 18 percent of the participants. More than 90 percent of tested patients used the products accordingly, following the instruction given prior to the start of the trial. Almost 90 percent of the test subjects who were asked whether or not they would use the tenofovir gel in the future responded affirmative. In comparison, 93 percent of patients using the placebo gel responded affirmative to the same question while only 63 percent of the patients using the spermicide had the same answer.

Besides safety and tolerability of the new rectal formulation of the tenofovir gel, scientists also conducted gene expression tests, whilst noting down every change that appeared and was believed to be an effect of the drug.

“These findings tell us that the ‘rectal-friendly’ version of tenofovir gel was much better tolerated than the vaginal formulation of the gel when used in the rectum,” said professor Ian McGowan, M.D., Ph.D., while also adding that “We are very encouraged that the rectal gel was quite safe, and that most people who used it said they would be willing to use it in the future”.

A future follow-up for the current study is already being planned. The follow-up study will be a trial on 186 patients from countries such as South Africa, Thailand, the United States and even Peru. This new study will have patients divided into two groups that will analyze the effects and side effects of the tenofovir rectal gel applied daily, before and after anal sex and a third group of patients that will receive an antiretroviral tablet called Truvada.

Baby’s Eczema Risk Linked To Smoking During Late Pregnancy

Eczema is an allergic skin condition characterized by red, itchy skin and according to a new study it has a greater risk of incidence during infancy in case of mother exposure to tobacco smoke while in the last three months of pregnancy.

It is already known that mother exposure to tobacco smoke during pregnancy increases the child’s risk of developing a disease of the respiratory system like asthma or infections. Earlier studies that have been conducted in order to link exposure to smoke with eczema, until now revealev only inconclusive results. The connection was exposed by a new study that was conducted on more than 1,400 infants aged between 2 months and 18 months. Researchers noted all cases of eczema and collected information about allergic diseases and the level of exposure to tobacco smoke during pregnancy and after, from the families of all the children participating in the study.

The result was very clear – the incidence rate of eczema increased among children exposed to tobacco smoke during their mother’s third trimester of pregnancy, but there was no notable difference between the incindece rate of eczema among the other groups of children: those that have not been exposed to tobacco smoke, those exposed to tobacco smoke during their mother’s first trimester and those exposed to tobacco smoke during the first six months after birth.

Dr. Kenji Matsumoto, the study’s senior editor explains that a contributing factor to developing eczema after birth might be explained by the fact the immune system’s development is affected by tobacco smoke exposure during the third trimester. The study did not focus on tobacco smoke exposure during infancy as a determinant eczema factor. Its purpose was only to show that an association between the two was found. “This also raises questions of whether or not tobacco smoke exposure may affect the innate immune responses of the skin,” he adds in a news release from the American Academy of Allergy, Asthma & Immunology.

The results of this study are to be presented by Matsumoto and colleague Dr. Miwa Shinohara on Saturday during a meeting of the American Academy of Allergy, Asthma & Immunology in Orlando, Fla. Data and conclusions presented at medical meetings should be considered preliminary until published in a peer-reviewed medical journal.

Study Reveals How Blood Stem Cells Differentiate

A new study conducted by scientists at University of California, Los Angeles (UCLA) finds a new stem cell niche along with a signaling tract, both having an important role in providing a good blood supply during life, whilst preventing any premature differentiation. The study has been published in the journal Developmental Cell. This newfound stem cell niche is responsible for the production and multiplication of stem cells without them differentiating into mature blood cells. This allows the development of a blood cell precursor pool, thus providing the necessary blood cells later in life, whenever needed.

Associate professor Dr. Hanna Mikkola reports that her team of researchers have found a link between trophoblasts and premature differentiation of blood stem cells. Platelet-derived growth factor subunit B (PDGFB) favors the exchange of nutrients and oxygen between the mother and fetus, thus being a vital factor in limiting the premature differentiation of blood precursors. This differentiation could lead to the appearance of red blood cells in the placenta. Researchers used laboratory rats for their studies.

Blood Stem Cells

Scientists previously discovered that the placenta is the place where numerous blood stem cells reside in an undifferentiated state until needed. Dr. Mikolla says that her team has discovered that the inhibition of the PDGFB causes the differentiation of the stem cells into normal red blood cells, thus providing the information that trophoblasts are a very important factor in this particular process. The inhibition of the PDFGB signals allows the production of Erythropoietin (EPO), which is in direct control of the differentiation of red blood cells process.

In order to verify the connection between every factor that was involved (cells and signaling paths), Dr. Mikolla and her team used laboratory rats with a discontinued placenta.

 “The idea was, if we mess up the home where the blood stem cells live, how do these cells respond to the altered environment”, said Akanksha Chhabra, post-doctoral fellow of Dr. Mikolla and first author of the current paper. “We found that it was important to suppress EPO where blood stem cell expansion is desired and to restrict its expression to areas where red blood cell differentiation should occur”.

Dr. Mikolla suggests that the growth and differentiation of the blood stem cells into the placenta could be hazardous for the stem cell niche. She adds that progress has been made in the past years regarding the presence of niche cells in adult bone marrow, but only now have they discovered the importance of these niches in fetal growth.

“All hematopoietic niches in the embryo are unique in their own way, the stem cells are made in one location, expand in another and differentiate somewhere else”, says Dr. Mikolla.

The study shows a new discovery in the development of blood stem cells whilst offering new findings that could lead to further development of artificial hepatopoietic niches that could help researchers understand the defects that originate from the placenta.

Researchers received funds from the National Institutes of Health, the California Institute of Regenerative Medicine and UCLA.

Alzheimer’s Disease Symptoms Reversed By Researchers

Researchers found that the enzyme HDAC2 can represent a new target for Alzheimer’s disease treatment. The study, recently published in Nature, shows that Alzheimer symptoms can be reversed by inhibiting HDAC2, an enzyme associated with memory function. More exactly, HDAC2 is an  overproduced enzyme that prevents storage of new memories in the brain of patients suffering from Alzheimer.

Alzheimer is a degenerative brain disease which primarily affects the elderly.  This disease, also called dementia, is manifested by loss of intellectual abilities, behavioral disorders and speech impairment. Hallmarks of the disease are the senile plaques and neurofibrillary degenerescence. In other words, the brains shrink due to cortex atrophy. In the United States of America, Alzheimer’s affects over 5 million people and is expected that number will double in the next 20 years. Discovery of new therapeutic targets might develop new strategys of treating Alzheimer’s disease. However, Li-Huei Tsai, leader of the research team says it will take at least 10 years to begin to market the new drugs.

Alzheimer

The discovered enzyme actually belongs to deacetylase enzymes family, a group of 11 enzymes that modify histones. By deacetylation, chromatin becomes compacted, and this hampers the process of transcription. By inhibiting this enzyme, chromatin would be less compacted, in other words, the genes in that region would be more likely to be transcribed. Previous studies showed that HDAC2 plays a key role in memory and learning processes. In the new experiment, conducted on mice, it was found that inhibition of this gene makes Alzheimer’s symptoms reversible.

The study showed that HDAC2 is very abundant in the hippocampus, the region of the brain responsible for memory. It was also found that HDAC2 is associated with genes involved in neuronal plasticity, which has an important role in learning and memory. Also, it was found that in affected mice, these genes were much less acetylated and expressed. By using the Short Hairpin RNA molecules Called, the scientists were able to block the HDAC2 in the affected rats. Thus, the acetylation was resumed, and genes with a role in neuronal plasticity could be expressed. Therefore, synaptic activity and cognition function improved significantly.

Furthermore, the study also showed that beta amyloid, one of the markers of Alzheimer’s, increases the production of HDAC2. This explains why drugs that act at the level of beta amyloid plaques had only modest results.

Researchers One Step Closer Towards Xenotransplantation Of Pig Cells

According to a study conducted at Bellvitage Biomedical Institute, natural killer cells are the culprit behind porcine chondrocytes rejection. The study was published in The Journal Of Immunology and pointed out that natural killer cells activate the innate immune system, thus having a major role in xenotransplantation (organs or cells that are transplanted from another species) rejection mechanism.

Natural killer cells represent the first line of defence of the immune system, having a very important role in the not-acquired immune response, along with macrophages and neutrophils. NK cells are part of the innate response of the response of immune system. The main roles of natural killer cells are to identify and to destroy by toxic action specific aggressive factors like cancer cells, infectious germs or cells that are foreign to the body.

Microscopic Image of Natural Killer Cells

Normally, the human body has a small number of natural killer cells, but they play a major role in transplantation because acquired immunity (also regulating by NK cells) is the main factor that favorizes organ rejection.

With this study, scientists wanted to create porcine cartilage cells for human transplantation that cold repare injured cartilage without initiating an immune response that is responsible for rejection. To achieve this goal, researchers studied the action of natural killer cells in the presence of porcine chondrocytes. They observed that after transplantation, levels of antibodies and cytokines that have the property to activate natural killer cells are increased. Activated natural killer cells will destroy non-self cells by direct cytotoxic action.

“In this work we have characterized several molecules involved in the processes of adhesion and cytotoxicity of natural killer cells,” explained scientists. They believe that this study is the first step in investigating the reject action mediated by natural killer cells because “on one hand we have to fight the deposition of antibodies that is a critical factor in increasing the toxicity and on the other we must work to reduce cell adhesion by modifying any of the molecules we have involved.”

In conclusion, in order to achieve a cartilage xenotransplantation without rejection response, researchers must to modify the genetic conformation of porcine cartilage cells, so that the immune system and especially natural killer cells don not recognize this type of cells as non-self, thus avoiding rejection.

Transplantation of cartilage tissue does not represent a technique that is often encountered in medical practice, but was realized successfully in cartilage traumatic injuries. An autologous transplant represents harvesting cells from the same person and transplanting them back. Allogenic transplantation is defined as transplantating cells or tissues harvested from another person. Either way the major setback is represented by the limited amount of cells available. If patients could benefit from cartilage xenotransplantation, it would drastically increase the amount and quality of cells.

In the not so distant future, researchers hope to be able to help patients with osteoarthritis or even rheumatoid arthritis by xenotransplantation of pig condrocytes.

Immune Cells Can Promote Ovarian Cancer Progression, According To New Study

Scientists from Wistar Institute demonstrated that aggressive forms of ovarian cancer have their origin in malignant cells under-controlled by the immune system until one point when they develop metastases. Researchers also found that ovarian cancers do not necessarily overcome the immune system’s ability to suppress them but their uncontrolled proliferation is supported by the activity of dendritic cells. The research evidentiated that it may be possible to restore the suppressing activity of the immune system by depleting the patient’s own dendritic cells.

“Our model shows where the cancer is kept in check for relatively long periods, but once they become noticeable, tumors grow exponentially. More importantly, we show that by depleting these dendritic cells of the immune system, we can reverse the effect, once again allowing our immune system to recognize the ovarian tumors.”, said the leader of the study.

This study will be presented in the March issue of the Journal of Experimental Medicine. With this research, scientist were able to induce ovarian tumors to mice that are respecting the patterns of human forms of ovarian cancers. These patterns were represented by the inflammatory reactions of the surrounding tissues  that ovarian cancer produces in humans.

“Our system uses oncogene-driven tumors that are spontaneously antigenic, thus avoiding the use of artificial foreign antigens that do not accurately replicate what drives anti-tumor immune responses in humans”, said the researchers.

Ovarian cancer represents one of the most fatal form of cancer in woman with no early stages specific symptoms, many women being diagnosed in the advanced stages of the disease. Over the last 40 years an increase in the survival rates for most cancers was observed but for ovarian cancer, the survival rate only improved slightly since 1970’s.

For this study, researchers created their own ovarian cancer model, hoping to better understand how this type of tumor overcomes the immune system and becomes very aggressive.

A tumor that is developing on one ovary is unrecognizable until one moment when the cancerous cells are growing exponentially. This stage according to the study, is equivalent with some phenotypic changes that take place in the dendritic cells of the immune system.

Dendritic Cells

Normally, dendritic cells are part of a worning system of the immune system for potential threats. They are known as antigen-presenting cells, having a very important role in presenting antigens to leukocytes, cells that can respond and combat an infection, or in this particular case, can inhibit tumor developing. This process takes place until dendritic cells switch sides and favor tumor growing.

Scientist observed that when this phenomenon appears, dendritic cells suffer changes that allows ovarian cancer to develop quickly and to metastasize. It was also observed that tumors are still immunogenetic and they can trigger an immune response. Dendritic cells are those that are constantly suppressing anti-tumor cells of the immune system, especially T cells.

The results question the cancer immunoeditting theory according to which the immune system can actively eliminate cancerous cells that are recognized as antigens, thus producing tumor stagnation, until one moment when it becomes symptomatic. In conclusion all tumors that are presenting symptoms are secondary to a failure of the immune system, where tumors lose the capacity to trigger an immune response and to be recognized by the immune system.

The study brings a valuable information that shows that dendritic cells that are depleted in the early stages of ovarian cancer, are favoring tumor expansion, while depleted dendritic cells later in tumor progression stops cancer development. Results suggest that rapid cancer progression is not caused by a loss of tumor immunogenicity, but due to a change in the dendrtic cells which are a part of the immune system.

Nano-Enabled Intranasal Formulation Of Teriparatide Announced

The University of Nottingham and Critical Pharmaceuticals announced a partnership for developing a nasal spray based on teriparatide for treating osteoporosis using nanotechnology. Osteoporosis is a bone disorder that leads to an increased risk of fracture and is considered an important worldwide health issue as it affects over 75 million people in Europe, US and Japan each year. It is said that one in two Caucasian women suffer from a fractured bone due to osteoporosis in her lifetime.

Osteoporosis is a disease that has no specific symptoms, it is actually an asymptomatic disease. People become aware of this disorder only  after they fracture a bone. Low bone density leads to debilitating acute and chronic pain in elderly people, affecting the vertebral column, the rib, hips and wrists. Risk factors for osteoporosis are the female gender, menopause, family history of osteoporosis, a diet low in calcium, lack of exercise, low circulating levels of estrogens. The treatment includes on the one side antiresorptive agents, and on the other side, bone anabolic agents. Antiresorptive agents, such as hormone replacement therapy, biphosphates, selective estrogen receptor modulators calcitonin, reduce bone resorption, while bone anabolic agents, teriparatide, calcium salts, stimulates new bone formation.

Teriparatide acts as the parathyroid hormone and stimulates osteoblats and therefore increases bone density. It is actually the main drug that determines new bone formation. It’s main inconvenience is that it needs to be injected every day. New findings in nanotechnology enabled scientist to start designing a nasal spray formulation of teriparatide.

Nasal Sprays

CEO, Dr. Gareth King expressed his excitement about working with internationally recognized scientists at the University of Nottingham. He added that this new formulation of teriparatide is very useful for older people suffering from osteoporosis as it is easier to administer.

Some of the members of the interdisciplinary research team include Dr. Richard Pearson (Division of Orthopaedic & Accident Surgery), Professor Alan Perkins (Division of Radiological and Imaging Sciences) and Professor Tahir Masud (Geriatric Medicine). The project will be supported by the Technology Strategy Board and the Engineering and Physical Sciences Research Council (EPSRC) with grant funding as part of investment in nano scale technology.

The University of Nottingham is well-known worldwide for its proficiency in the filed of bone disorders research, geriatric care, osteoporosis and medical imaging.

Type 1 Diabetes

Type 1 diabetes is a form of disease that is recorded in about ten percent of people suffering from diabetes. The body produces T cells that attack its own insulin secreting pancreatic islet beta cells. The disease is characterized by a lack of insulin secretion, with a relatively sudden onset, obvious symptoms (frequent urination, thirst, increased appetite, weight loss) and a tendency to ketoacidosis (ketones in the presence of high blood sugar + blood + acidosis). This form of disease can be seen in all ages, but particularly characterizes patients whose disease begins before 30 years. Below this age almost all patients are insulin dependent. Therefore patients require daily insulin injections to maintain an adequate insulin level and proper glucose levels.

Insulin Injection

A new method published in BioMed Central’s open access journal BMC Medicine , uses stem cells from cord blood in order to re-educate the patient’s faulty T cells and therefore regain the lost pancreatic function leading to a reduced need of insulin injections.

Stem Cell Educator therapy is a technique that uses immobilized cord blood stem cells (harvested from healthy patients) over which, lymphocytes  separated from a patient suffering from diabetes are passed. After this procedure, which generally lasts about three hours, the re-educated lymphocytes are injected back to the patient. Evolution of patients was then monitored and checked at four, twelve, twenty-four and forty weeks after therapy.

C peptide is produced by the pancreas as a result of proteolytic cleavage of proinsulin into insulin. This peptide is important because it is secreted in equal amounts as insulin. Unlike insulin, C peptide is not degraded in the liver. For this reason C peptide can indicate more precisely the insulin secretion of the pancreas.

By twelve weeks after the initial treatment all patients presented improved levels of C peptide. This encouraging result was also noted after twenty-four weeks and was maintained until the end of the study. This result translates into a reduced need of insulin injections of the patients included in the study. Simultaneously glycosylated hemoglobin value also decreased for study participants but not for patients in the control group.

Dr Yong Zhao, from University of Illinois at Chicago, who led the multi-centre research, explained, “We also saw an improved autoimmune control in these patients. Using this technique, the percentage of regulatory T lymphocytes raises in the patient’s blood, other immune function markers are improved like TGF-beta1, and pancreatic islet beta cells are able to recover “.

Weekly Fish Consumption May Reduce The Risk For Alzheimer’s Disease

According to a new study, people who consume fish once a week have an improved brain metabolism, thus reducing the risk of developing Alzheimer’s disease and mild cognitive impairment. This study was presented at the annual meeting of the Radiological Society of North America.

Study leader, Cyrus Raji, M.D., Ph.D. stated that this is the first time when, a link was established between fish consumption, brain structures and Alzheimer’s disease and the results are very promising.  People who consume fish, especially baked or broiled, once a week, show a better preservation of the grey matter of the brain areas with risk for Alzheimer’s disease. Eating fried fish, on the other hand, was not proven to increase brain volume or exercit any protection against cognitive decline.

Alzheimer’s disease is a progressive and incurable pathological entity that is irreversibly affecting memory and cognitive skills. In mild cognitive impairment memory loss occurs, but not as sever as in Alzheimer’s disease. Patients with mild cognitive impairment have a higher risk to develop Alzheimer’s disease in the near future.

From 260 people with normal cognitive function that were included in the study, 163 people consumed baked or broiled fish at least once a week, for 10 years. The average consumption of fish dishes was between one and four times per week. Each subject underwent a MRI examination of the brain and then a brain mapping examination which has the capacity to measure the volume of grey matter.  The results of this two examinations where then analyzed by scientists to see if there is any corelation between weekly fish consumption and impoved brain activity. Only people who did not present the expression of apolipoprotein E4 ( ApoE4), a gene that is increasing the risk of developing Alzheimer’s disease were included in the study.

Broiled Fish

It is very important to have a higher volume of gray matter, as this reflects a good brain health. If during a routine imaging examination of the brain a decrease in gray matter volume is detected, that means that neurons are shrinking. The results of this study showed that consumption of broiled or baked fish, at least once a week, was associated with a higher volume of grey matter in certain areas of the brain (hippocampal, posterior cingulate and orbital cortex)

“Consuming baked or broiled fish promotes stronger neurons in the brain’s gray matter by making them larger and healthier. This simple lifestyle choice increases the brain’s resistance to Alzheimer’s disease and lowers risk for the disorder.”, said Dr. Raji.

Another observation was that people who consume bake or broiled fish, at least once a week, also present increased levels of cognition.

The researchers discovered that these subjects have higher levels of working memory, even when other factors such as education, age, gender, physical activity were analyzed. Working memory is one of the most important component of cognitive function as it allows people to focus in tasks and to use their short-term memory. In Alzheimer’s disease, the working memory is greatly diminished.

Hyperglycemia Linked To Increased Colorectal Cancer Risk In Older Woman

Researchers from Albert Einstein College of Medicine of Yeshiva University linked hyperglycemia to an increased risk of developing colon cancer, after they conducted a study on nearly five thousand postmenopausal woman. The study was published yesterday in the online edition of British Journal of Cancer.

Cancers of the colon and rectum, called colorectal carcinomas account for 15% of the total number of diagnosed cancers. Their frequency is increasing in Western, high living standard countries being the third leading cause of cancer death in the U.S. In the European Union, the incidence of colon cancer is  about 58 / 100 000 inhabitants / year with a mortality rate of about 50%.

For 2007, the US Centers for Disease Control and Prevention announced that there were 142,672 Americans newly diagnosed with colorectal carcinomas. From the total number of diagnosed patients 69,917 were women. The number of deaths caused by colon cancer that was reported in 2007 ,was 53,219.

The fasting blood sugar and insulin levels of the women included in the study were measured at the start of the study (at baseline) then the tests were repeated several times over the next year.  After one year, a number of 81 woman were diagnosed with colorectal cancer. Researchers from Albert Einstein College correlated the elevated baseline blood sugar levels with an increased risk of developing colon cancer. No link was found between insulin levels and an increased risk for colon carcinomas.

High Glucose Levels

A well-known risk factor for colon cancer is obesity, and researchers then turned their attention to findind the exact mechanism. Obesity is often associated with hyperinsulinism. A very curious finding, was that obesity’s influence on colon cancer risk  (thought to be caused by hyperinsulinism – elevated levels of insulin in the blood of a person) may be actually due to elevated glucose levels.

The next challenge for researchers is to find and describe the exact mechanism by which high glucose levels raise the risk of colorectal cancer according to leading author of the paper Geoffrey Kabat, PhD.

One theory is that elevated glucose levels are correlated to increased circulatory levels of growth and inflammatory factors that could encourage the development of intestinal polyps, some of which, could later turn malignant.