Treatment target identified for a public health risk parasite
In the developing world, Cryptosporidium parvum has long been the scourge of freshwater. A decade ago, it announced its presence in the United States, infecting over 400,000 people - the largest waterborne-disease outbreak in the county’s history. Its rapid ability to spread, combined with an incredible resilience to water decontamination techniques, such as chlorination, led the National Institutes of Health (NIH) in the United Sates to add C. parvum to its list of public bioterrorism agents. Currently, there are no reliable treatments for cryptosporidiosis, the disease caused by C. parvum, but that may be about to change with the identification of a target molecule by investigators at the Research Institute of the McGill University Health Centre (RI-MUHC). The findings of this study have been recently published in the Antimicrobial Agents and Chemotherapy (AAC) journal.
“In the young, the elderly and immunocompromised people such as people infected with HIV/Aids, C. parvum is a very dangerous pathogen. Cryptosporidiosis is potentially life-threatening and can result in diarrhea, malnutrition, dehydration and weight loss,” says first author of the study, Dr. Momar Ndao, Director of the National Reference Centre of Parasitology (NRCP) at the MUHC and an Assistant Professor of the Departments of Medicine, Immunology and Parasitology (Division of Infectious Diseases) at McGill University.
The oocysts of C. parvum, which are shed during the infectious stage, are protected from a thick wall that allows them to survive for long periods outside the body as they spread to a new host. C. parvum is a microscopic parasite that lives in the intestinal tract of humans and many other mammals. It is transmitted through the fecal-oral contact with an infected person or animal, or from the ingestion of contaminated water or food. Since the parasite is resistant to chlorine and difficult to filter, cryptosporidiosis epidemics are hard to prevent.
Early Heart Data Look Good for Obesity Drug
Interim data from a cardiovascular safety study of an investigational weight-loss agent have met FDA criteria, and drugmaker Orexigen Therapeutics will seek to resubmit the drug for U.S. approval.
A company press release reported that the combination of naltrexone and bupropion (Contrave) didn’t double the risk of major adverse cardiovascular events (MACE) compared with placebo - a requirement set by the FDA - in an interim look at data from the Light Study, a cardiovascular outcomes trial.
The drug was denied FDA approval in February 2011, even though an advisory committee had voted largely in favor of approval. The agency required that the company conduct a cardiovascular outcome trial before it would approve the drug.
It also agreed that if the study could exclude a doubling of the risk of MACE with the drug compared with placebo, the company could submit the interim analysis for consideration in a resubmitted new drug application (NDA).
New technique for testing drugs to treat cystic fibrosis and epilepsy
Researchers from the University of Southampton, in collaboration with researchers at the University of Quebec at Montreal, have developed a new microsystem for more efficient testing of pharmaceutical drugs to treat diseases such as cystic fibrosis, MG (myasthenia gravis) and epilepsy.
A large percentage of pharmaceutical drugs target ion channels, which are proteins found in a cell’s membrane, that play a pivotal role in these serious disorders and that are used to test the effectiveness of new drugs.
Ion channels create tiny openings in the membrane for specific ions (atoms that are positively or negatively charged) to pass through.
Currently researchers use electrophysiology, which measures an electric current through ion channel proteins, to evaluate the effectiveness of drugs on ion channels.
Mail order pharmacy use safe for people with diabetes
Most people with diabetes can safely get their medications though mail order pharmacies, a new study suggests.
Among some patients, getting drugs through the mail instead of in person was tied to a lower risk of ending up in the emergency department (ED), researchers found.
Mail order pharmacies are convenient, especially for people with disabilities or who can’t get to the pharmacy to pick up their regular orders, researchers said. But there have been concerns about those systems as well - for instance that people might miss out on important information by not seeing a pharmacist face-to-face.
“Mail order pharmacy use is actually fairly common in the United States and has become more and more so over the past 10 or 15 years,” Julie Schmittdiel told Reuters Health.
Maternal mood disorder and newborn neurobehavior
A great number of women experience depression or anxiety while pregnant, and exposure of the fetus to these maternal mood disorders may lead to long-term emotional and behavioral problems in the offspring. Many studies have shown that the fetal environment has a strong influence on offspring neurobehavioral outcomes by altering the developing brain, although the exact mechanisms by which this occurs are not completely understood.
Researchers from the Brown Center for the Study of Children at Risk, Women and Infants Hospital of Rhode Island, Brown University, in Providence, RI, have now tested the influence of maternal depression and/or anxiety during pregnancy on newborn neurobehavior by specifically looking at epigenetic changes (modifications on the DNA that are different from changes in DNA sequence) in two genes expressed in the placenta that have been previously implicated in perturbations of the HPA axis (a system that controls reactions to stress and regulates many body processes).
In a study published in the December 2013 issue of Epigenetics, the authors report that specific adjustments that occur in the fetus (more specifically in the regulation of gene expression) in response to cues from the intrauterine environment, in this case an increased exposure to maternal cortisol, may lead to poor neurodevelopmental outcomes.
Cubist says urinary tract infection drug succeeds in study
Cubist Pharmaceuticals Inc said its experimental treatment for a type of urinary tract infection showed it was as effective as an approved antibiotic.
The main goal of a late-stage trial was to show whether the treatment, a combination of ceftolozane and tazobactam, eradicated the infection and cured patients five to nine days after the last dose.
The most commonly reported adverse events of the treatment were headaches, constipation, hypertension, nausea and diarrhea.
Study pinpoints cell type and brain region affected by gene mutations in autism
A team led by UC San Francisco scientists has identified the disruption of a single type of cell - in a particular brain region and at a particular time in brain development - as a significant factor in the emergence of autism.
The finding, reported in the November 21, 2013 issue of Cell, was made with techniques developed only within the last few years, and marks a turning point in autism spectrum disorders (ASDs) research.
Large-scale gene sequencing projects are revealing hundreds of autism-associated genes, and scientists have begun to leverage new methods to decipher how mutations in these disparate genes might converge to exert their effects in the developing brain.
The new research focused on just nine genes, those most strongly associated with autism in recent sequencing studies, and investigated their effects using precise maps of gene expression during human brain development.
Researchers from Braunschweig describe new possibilities of the CRISPR-Cas-system
Viruses cannot only cause illnesses in humans, they also infect bacteria. Those protect themselves with a kind of ‘immune system’ which - simply put - consists of specific sequences in the genetic material of the bacteria and a suitable enzyme. It detects foreign DNA, which may originate from a virus, cuts it up and thus makes the invaders harmless. Scientists from the Helmholtz Centre for Infection Research (HZI) in Braunschweig have now shown that the dual-RNA guided enzyme Cas9 which is involved in the process has developed independently in various strains of bacteria. This enhances the potential of exploiting the bacterial immune system for genome engineering.
Even though it has only been discovered in recent years the immune system with the cryptic name ‘CRISPR-Cas’ has been attracting attention of geneticists and biotechnologists as it is a promising tool for genetic engineering. CRISPR is short for Clustered Regularly Interspaced Palindromic Repeats, whereas Cas simply stands for the CRISPR-associated protein. Throughout evolution, this molecule has developed independently in numerous strains of bacteria. This is now shown by Prof Emmanuelle Charpentier and her colleagues at the Helmholtz Centre for Infection Research (HZI) who published their finding in the international open access journal Nucleic Acids Research.
The CRISPR-Cas-system is not only valuable for bacteria but also for working in the laboratory. It detects a specific sequence of letters in the genetic code and cuts the DNA at this point. Thus, scientists can either remove or add genes at the interface. By this, for instance, plants can be cultivated which are resistant against vermins or fungi. Existing technologies doing the same thing are often expensive, time consuming or less accurate. In contrast to them the new method is faster, more precise and cheaper, as fewer components are needed and it can target longer gene sequences.
Optimal site for cell transplantation to treat spinal cord injury investigated
It is known that transplanting neural stem/progenitor cells (NS/PCs) into the spinal cord promotes functional recovery after spinal cord injury (SCI). However, which transplantation sites provide optimal benefit? This question was investigated by a Japanese research team and their findings will be published in a future issue of Cell Transplantation, but are currently freely available on-line as an unedited early e-pub at http://url.health.am/1326/.
“It is critical to determine the optimal transplantation site for NS/PCs aimed at treating SCI,” said Dr. Masaya Nakamura of the Department of Orthopedic Surgery at the Keio University School of Medicine.
Previous work by the same research team revealed that NS/PCs injected into non-injury sites such as by intravenous or intrathecal administration did not engraft to the injury site in sufficient numbers, but instead were often “trapped” in the lungs and kidneys. They concluded that intralesional application might be the most effective and reliable method for transplanting NS/PCs. This study, also using laboratory mice with SCI, sought to determine how effective intralesional injection might be. NS/PCs were obtained from mice transgenic for Venus and luciferase fusion protein, which allowed the cells to be tracked by bioluminescence imaging (BLI) after transplantation.
“Wild-type mice were given a contusive spinal cord injury at the T10 level,” explained Dr. Nakamura. “Low and high doses of NS/PCs derived from fetal transgenic mice were injected into four groups of mice at either the lesion epicenter (E) or at rostral and caudal sites (RC) with neural stem/progenitor cells derived from fetal transgenic mice while a fifth group of controls was injected with phosphate buffered saline at E.”
Fungus-fighting drug may make mild flu meaner
Mice given a drug commonly used in patients to fight systemic fungal infections more often succumb to what would otherwise be a mild case of the flu. The evidence reported in the Cell Press journal Cell Reports on November 21st shows that the drug called Amphotericin B, which has an estimated $330 million in sales around the world each year, can render a protein important for antiviral defense ineffective in both cells and mice.
The findings suggest that patients receiving the antifungal therapy may be functionally immunocompromised and more vulnerable to influenza and other viral infections, the researchers said.
“Many critically ill cancer and bone marrow transplant patients are treated with Amphotericin B-based therapies each year,” said Abraham Brass of the University of Massachusetts Medical School (UMMS). “Given these results in cells and mice, it may be worthwhile to consider that patients receiving, or who may receive, Amphotericin B-based therapies be appropriately vaccinated against influenza virus. Also, clinical consideration may be given to close monitoring of patients receiving Amphotericin B-based therapies for any symptoms suggestive of flu so that they might be considered for the early administration of an antiflu therapy.”
The researchers showed that Amphotericin-B prevents the antiviral protein in cells known as IFITM3 from fending off influenza A virus.
Stanford scientists think mysterious virus could be a signal of a weak immune system
More than 260,000 Americans are alive today thanks to transplant operations that have replaced their failing kidneys, hearts, lungs or livers with healthy organs donated by volunteers or accident victims.
But treatment doesn’t end with surgery. Transplant recipients follow strict drug regimens designed to suppress their immune systems just enough to prevent rejection of the donated organ, but not so much as to leave them prone to infection.
Until now, maintaining this delicate balance has been something of a medical guessing game. But in a study to be published Nov. 21 in Cell, Stanford University scientists report the discovery of what may be a barometer of immune system strength: a little-known virus that proliferates as the medications suppress the immune system.
The work was led by senior author Stephen Quake, PhD, the Lee Otterson Professor in the School of Engineering and professor of bioengineering and of applied physics.
Intestinal bacteria influence food transit through the gut
Food transit through the small intestine affects the body’s absorption of nutrients and, consequently, our health. The discovery that food transit time is regulated by a hormone indicates new ways to increase the intestinal absorption of nutrients, and thus potentially treat malnutrition.
One of the tasks of the gut microbiota is to break down essential nutrients from our diet to provide a usable energy source in the colon.
Researchers at the Sahlgrenska Academy, University of Gothenburg, Sweden, have now shown that lack of energy in the colon leads to increased release of a hormone primarily associated with appetite control and insulin secretion, GLP-1.
Importantly, they also showed that the released GLP-1 regulates how quickly food passes through the small intestine. These findings may open up new possibilities to treat malnutrition and malnutrition-related diseases.
Stanford research upends understanding of how humans perceive sound
A key piece of the scientific model used for the past 30 years to help explain how humans perceive sound is wrong, according to a new study by researchers at the Stanford University School of Medicine.
The long-held theory helped to explain a part of the hearing process called “adaptation,” or how humans can hear everything from the drop of a pin to a jet engine blast with high acuity, without pain or damage to the ear. Its overturning could have significant impact on future research for treating hearing loss, said Anthony Ricci, PhD, the Edward C. and Amy H. Sewall Professor of Otolaryngology and senior author of the study.
“I would argue that adaptation is probably the most important step in the hearing process, and this study shows we have no idea how it works,” Ricci said. “Hearing damage caused by noise and by aging can target this particular molecular process. We need to know how it works if we are going to be able to fix it.”
The study will be published Nov. 20 in Neuron. The lead author is postdoctoral scholar Anthony Peng, PhD.
Long-term unemployment may accelerate aging in men
Men who are unemployed for more than two years show signs of faster ageing in their DNA, a new study has found.
Researchers at Imperial College London and the University of Oulu, Finland studied DNA samples from 5,620 men and women born in Finland in 1966.
They measured structures called telomeres, which lie at the ends of chromosomes and protect the genetic code from being degraded. Telomeres become shorter over a person’s lifetime, and their length is considered a marker for biological ageing. Short telomeres are linked to higher risk of age-related diseases such as type 2 diabetes and heart disease.
The researchers looked at telomere length in blood cells from samples collected in 1997, when the participants were all 31 years old. The study, funded by the Wellcome Trust, found that men who had been unemployed for more than two of the preceding three years were more than twice as likely to have short telomeres compared to men who were continuously employed.
Reducing the salt in bread without losing saltiness, thanks to a texture trick
Want to make bread taste pleasantly salty without adding more salt? Change the bread’s texture so it is less dense, say scientists. They report in ACS’ Journal of Agricultural and Food Chemistry that simply making the pores, or holes, larger can make people perceive bread as having saltier taste. The process could become a new strategy for reducing salt intake, which is a risk factor for high blood pressure and heart disease.
Peter Koehler and colleagues explain that every day, people in industrialized countries consume, on average, twice as much salt as the World Health Organization recommends. Much of that salt - 35 percent in the United Kingdom and about 25 percent in Germany - comes from bread, which for millennia has ranked as one of the world’s most ubiquitous foods. Cutting dietary salt would reduce people’s risk for developing high blood pressure, which has been diagnosed in 40 percent of adults aged 25 and older worldwide, and heart disease, which was the cause of 30 percent of all deaths in 2008. But the big question is how to do it in a palatable way. Researchers have tried different methods, such as using salt substitutes, but only to limited effect. Studies on cheese and gels has shown that changing texture can make a product taste salty even if salt content is reduced, so Koehler’s team decided to see if this would work with bread.
To alter the texture of bread for the study, they baked bread using different proofing times. Proofing is when a baker lets the dough rise. Longer proofing times lead to softer breads with larger pores. The subjects in the study rated the fluffier bread with the longest proofing time as noticeably more salty, even though each bite actually contained less salt. “Appropriate modification of crumb texture thus leads to enhanced saltiness, suggesting a new strategy for salt reduction in bread,” say the researchers.