Drinking tart Montmorency cherry juice can reduce early signs of hypertension

 

The Montmorency cherry is a variety of sour cherry (Prunus cerasus) grown in the United States, Canadaand France, particularly in Michigan and in Door County, Wisconsin. Montmorency cherries are part of the lighter-red Amarelle cultivar of sour cherries, rather than the darker-red Morello cultivar. Michigan produces over 90,000 tons of Montmorency cherries each year.

Drinking tart Montmorency cherry juice significantly reduces high blood pressure at a level comparable to that achieved by medication, according to new research from Northumbria University, Newcastle.

The findings, which are published in The American Journal of Clinical Nutrition today (Wednesday 4 May), found that men with early signs of hypertension - more commonly known as high blood pressure - saw a 7% reduction in blood pressure after drinking Montmorency cherry concentrate when compared to drinking a fruit-flavoured cordial.

This reduction is comparable to the level achieved by anti-hypertensive medication.

High blood pressure affects over five million people in England and, if left untreated, increases risk of heart attack, heart failure, kidney disease, stroke or dementia. Normal blood pressure is around 120/80 mmHg.

Researchers from Northumbria University's Department of Sport, Exercise and Rehabilitation worked with fifteen participants who were displaying early hypertension with blood pressure readings of at least 130/90 mmHg, meaning they were at higher risk of experiencing cardiovascular related problems.

They were told that the study was to investigate the effect of a fruit juice on vascular function and were given either 60ml of a Montmorency cherry concentrate or the same amount of a commercially available fruit-flavoured cordial.

Blood pressure and blood samples were taken before the cherry concentrate was consumed and blood pressure was measured on an hourly basis thereafter. Blood samples and a series of other cardiovascular screening tests were taken again on a regular basis over the following eight hours.

The researchers found that the participants who were given the cherry concentrate saw a peak reduction in their blood pressure of 7 mmHg in the three hours after consuming the drink.

Past studies have shown that a reduction of between 5-6 mmHg over a sustained period has been associated with a 38% reduced risk of stroke and 23% reduced risk of coronary heart disease.

Interestingly, those participants with blood pressure levels at the higher end of the scale saw the most benefit.

The greatest improvement in systolic blood pressure occurred when the phenolic acids, protocatechuic and vanillic, within the cherry concentrate reached their peak levels in the plasma. The researchers believe that these particular compounds are, at least in part, responsible for the reduction.

Lead author and Lecturer in Sport and Exercise Nutrition, Karen Keane, explained: "The majority of cardiovascular disease is caused by risk factors that can be controlled, treated or modified, such as high blood pressure, cholesterol, obesity, tobacco use, lack of physical activity and diabetes. Raised blood pressure is the leading cause of deaths from cardiovascular disease, yet relatively small reductions in blood pressure can have a large impact on mortality rates.

"The magnitude of the blood pressure lowering effects we observed was comparable to those achieved by a single anti-hypertensive drug and highlights the potential importance that Montmorency cherries could have in the effective management of high blood pressure."

Drinking tart Montmorency cherry juice can reduce early signs of hypertension: Drinking tart Montmorency cherry juice significantly reduces high blood pressure at a level comparable to that achieved by medication, according to new research from Northumbria University, Newcastle.

The 2016 Nobel Prize in Chemistry.......

A tiny lift, artificial muscles and miniscule motors. The Nobel Prize in Chemistry 2016 is awarded to Jean-Pierre Sauvage, Sir J. Fraser Stoddart and Bernard L. Feringa for their design and production of molecular machines. They have developed molecules with controllable movements, which can perform a task when energy is added.

The development of computing demonstrates how the miniaturisation of technology can lead to a revolution. The 2016 Nobel Laureates in Chemistry have miniaturised machines and taken chemistry to a new dimension.

The first step towards a molecular machine was taken by Jean-Pierre Sauvage in 1983, when he succeeded in linking two ring-shaped molecules together to form a chain, called a catenane. Normally, molecules are joined by strong covalent bonds in which the atoms share electrons, but in the chain they were instead linked by a freer mechanical bond. For a machine to be able to perform a task it must consist of parts that can move relative to each other. The two interlocked rings fulfilled exactly this requirement.

The second step was taken by Fraser Stoddart in 1991, when he developed arotaxane. He threaded a molecular ring onto a thin molecular axle and demonstrated that the ring was able to move along the axle. Among his developments based on rotaxanes are a molecular lift, a molecular muscle and a molecule-based computer chip.

Bernard Feringa was the first person to develop a molecular motor; in 1999 he got a molecular rotor blade to spin continually in the same direction. Using molecular motors, he has rotated a glass cylinder that is 10,000 times bigger than the motor and also designed a nanocar.

2016's Nobel Laureates in Chemistry have taken molecular systems out of equilibrium's stalemate and into energy-filled states in which their movements can be controlled. In terms of development, the molecular motor is at the same stage as the electric motor was in the 1830s, when scientists displayed various spinning cranks and wheels, unaware that they would lead to electric trains, washing machines, fans and food processors. Molecular machines will most likely be used in the development of things such as new materials, sensors and energy storage systems.

Details : https://www.nobelprize.org/nobel_prizes/chemistry/laureates/2016/advanced-chemistryprize2016.pdf

  

Blueberry component PS may protect against dry eye disease

  

Pterostilbene (PS), a component of blueberries, have been found to protect against dry eye disease according to a new study. The research is being presented at the 2016 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) this week in Seattle, Wash.

When introduced to human corneal epithelial cells, PS significantly reduced the levels of oxidative damage, which in turn reduced inflammation. Inflammation can contribute to dry eye disease, a condition that becomes increasing common with age. PS is a molecule chemically related to resveratrol.

Omega-3 Fish Oil Supplements Might Boost Antidepressants' Effects

Omega-3 fish oil supplements may improve the effectiveness of antidepressants, new research suggests.

Researchers reviewed the findings of eight clinical trials worldwide, as well as other evidence, and concluded that the supplements appear to help battle depression in people already on medication.

"Omega-3 fish oil -- in combination with antidepressants -- had a statistically significant effect over a placebo," said study leader Jerome Sarris. He is head of the ARCADIA Mental Health Research Group at the University of Melbourne in Australia.

The study looked at the result of trials where patients battling depression took either a standard antidepressant plus a form of omega-3 fish oil, versus the antidepressant plus an inactive placebo.

"The difference for patients taking both antidepressants and omega-3, compared to a placebo, was highly significant," Sarris said in a university news release. "This is an exciting finding because here we have a safe, evidence-based approach that could be considered a mainstream treatment," he explained.

"Many studies have shown omega-3s are very good for general brain health and improving mood, but this is the first analysis of studies that looks at using them in combination with antidepressant medication," Sarris said.

Doctors may be reluctant to prescribe dietary supplements in combination with antidepressants due to a lack of scientific evidence and concerns about safety. But, Sarris noted, the researchers found no major safety concerns in combining the two therapies.

However, the study authors stressed that patients should always talk with their health care provider before taking dietary supplements. In addition, people need to be aware that these supplements can differ in quality.

"We're not telling people to rush out and buy buckets of supplements. Always speak to your medical professional before changing or initiating a treatment," Sarris said.

One expert in the United States believes the findings might be of use to patients.

"The general population is often looking for natural remedies to treat health problems," said Dr. Victor Fornari.

"A large number of individuals with depression do not reach remission with one or two trials of medication," added Fornari. He directs child and adolescent psychiatry at Cohen Children's Medical Center in New Hyde Park, N.Y.

"This may enhance the recovery of individuals who do not respond to antidepressants alone," he said. However, Fornari agreed with the authors that "individuals are cautioned to consult with their medical professional before proceeding."

Omega-3 Fish Oil Supplements Might Boost Antidepressants' Effects  

Coffee, Wine Good for Healthy Gut, Sodas May Be Bad

The food you eat and the medicines you take can alter your gut bacteria in ways that either help or harm your health, two new studies suggest.

Foods like fruits, vegetables, coffee, tea, wine, yogurt and buttermilk can increase the diversity of bacteria in a person's intestines. And that diversity can help ward off illness, said Dr. Jingyuan Fu, senior author of one of the studies.

"It is believed that higher diversity and richness [in gut bacteria] is beneficial," explained Fu. She is an associate professor of genetics at the University of Groningen in the Netherlands.

On the other hand, foods containing loads of simple carbohydrates appear to reduce bacterial diversity in the gut, Fu and colleagues found. These include high-fat whole milk and sugar-sweetened soda.

In addition, medications can also play a part in the makeup of your gut bacteria. Antibiotics, the diabetes drug metformin and antacids can cut down on gut bacterial diversity, the researchers found. Smoking and heart attacks also can have a negative effect, the team said.

Each person's intestines contain trillions of microorganisms, which doctors refer to as the "gut microbiome," said Dr. David Johnson. He is chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Va., and a past president of the American College of Gastroenterology.

The gut microbiome plays an essential but little-understood role in human health, said Johnson, who was not involved with the new studies.

"It's the largest immune system in the body," Johnson explained. "These bacteria have a very dramatic and prominent role in determining health and disease."

To study the effect of lifestyle on the gut microbiome, Fu and her colleagues collected stool samples from more than 1,100 people living in the northern Netherlands.

The samples were used to analyze the DNA of the bacteria and other organisms that live in the gut. In addition to stools, the study collected information on the participants' diets, medicine use and health.

In the second study, researchers with the Flemish Gut Flora Project performed a similar analysis on stool samples taken from 5,000 volunteers in Belgium.

Both studies concluded that diet has a profound effect on the diversity of gut bacteria, although, Fu said, the "underlying theories of these dietary factors remain largely unknown."

Johnson added that medicines can have the same effect, and antibiotics actually can kill off some important strains of gut bacteria. "One dose of an antibiotic may disrupt your gut bacteria for a year," he said.

Both sets of researchers emphasized that their studies only help explain a fraction of gut bacteria variation -- roughly 18 percent for the Netherlands study, and about 7 percent for the Flemish study.

However, the findings from the two groups overlapped about 80 percent of the time, indicating that they are on the right track, the researchers said.

The Belgian researchers estimated that over 40,000 human samples will be needed to capture a complete picture of gut bacteria diversity.

Johnson noted that other research has shown that poor sleep, obesity, diabetes and the use of artificial sweeteners also can interfere with gut bacteria.

"The general rule is a balanced diet with high fiber and low carbs tends to drive a better gut health overall," he said.

According to Fu, once researchers have a clearer understanding of the gut microbiome and its effects on health, doctors could be able to help prevent or heal illness by reading or influencing the bacteria within people's bodies.

"The personalized microbiome may assist in personalized nutrition, personalized medicine, disease risk stratification and treatment decision-making," she said.

Both studies were published in the April 29 issue of the journal Science.

Coffee, Wine Good for Healthy Gut, Sodas May Be Bad  

Additional Treatments Offer Little Benefit for Pancreatic Cancer: Study

In continuation of my updates on Erlotinib, gemcitabine and capecitabine

Additional treatments for locally advanced pancreatic cancer don't appear to boost survival, a new French study reports.

Researchers looked at the effects of adding a second drug -- erlotinib (Tarceva) -- to the initial round of chemotherapy. They also tested whether adding radiation to a second round of chemotherapy (chemoradiotherapy) would offer any survival benefit.

 erlotinib (Tarceva)

Unfortunately, the addition of the second drug didn't help people live longer, and those on chemoradiotherapy didn't fare any better.

"Chemoradiotherapy was not superior to chemotherapy," said the study's senior author, Dr. Pascal Hammel. Hammel is from the department of gastroenterology-pancreatology at Beaujon Hospital, in Clichy, France.

The study was funded by the pharmaceutical company Roche, the maker of Tarceva, and the French National Institute of Cancer.

More than 53,000 Americans are diagnosed with pancreatic cancer annually, the U.S. National Cancer Institute (NCI) says. About 42,000 Americans die each year from the disease, the NCI reports.

The new study focused on 449 people with pancreatic cancer. Their average age was just over 63.

All received standard four-month chemotherapy with the drug gemcitabine (Gemzar). Gemzar is currently used to treat a range of cancers, including pancreatic, ovarian, breast, and non-small cell lung cancers, the drug's labeling information says. For the study, about half the patients (219) also took Tarceva along with Gemzar.

 gemcitabine (Gemzar).

After completing initial treatment, imaging tests revealed that 269 patients appeared to have tumors that were under control. That meant their cancer was stable and didn't appear to have spread, or metastasized.

But the tumors couldn't be surgically removed because they had developed around the arteries surrounding the pancreas, study authors said.

About half this group of stable patients (136) received two additional months of the same chemotherapy regimen. The other half (133) was treated with a combination of radiation and the chemotherapy drug capecitabine (Xeloda).

 capecitabine (Xeloda)

After three years of follow-up, the researchers found that patients given Gemzar chemotherapy alone survived an average of 13.6 months. Those given the combination of Gemzar and Tarceva had an average survival of 11.9 months, the study found.

Patients treated with chemoradiotherapy lived an average of 15.2 months. Those who got chemotherapy alone lived an average of 16.5 months, the study found.

Hammel said there's still work to be done to improve the results of both chemotherapy and radiotherapy treatments.

But for now, Dr. Deborah Schrag agreed that "the French trial demonstrates that routine addition of chemo-radiation following initial chemotherapy for patients with locally advanced pancreatic cancer does not improve survival compared to continued chemotherapy." Schrag, chief of the Division of Population Sciences, Medical Oncology, at the Dana-Farber Cancer Institute in Boston, wrote an accompanying editorial in the same issue of the journal.

"[And] given the burdens of daily radiation therapy, there is no routine role for the application of this treatment strategy," added Schrag.

Schrag said it's possible there might be a certain group of pancreatic cancer patients who could get some measurable benefit from radiation. "Further evaluation of the tumor samples from the study participants might help to more precisely determine who might benefit from radiation, and such data are eagerly awaited," she said.

Additional Treatments Offer Little Benefit for Pancreatic Cancer: Study  

Eisai Announces FDA Approval of Fycompa (perampanel) Oral Suspension

In continuation of my update on Fycompa

Eisai Inc.  announced that the U.S. Food and Drug Administration (FDA) has approved Fycompa (perampanel) CIII Oral Suspension as adjunctive therapy for the treatment of partial-onset seizures (POS) with or without secondarily generalized seizures, and primary generalized tonic-clonic (PGTC) seizures in patients with epilepsy 12 years of age and older. The oral suspension formulation is a bioequivalent, interchangeable alternative to the Fycompa tablet formulation, and is expected to be available to patients in June 2016.

"We are excited about the approval of Fycompa Oral Suspension, as it gives another option to patients with epilepsy who may have difficulty swallowing tablets or prefer liquids," said Lynn Kramer, M.D., Chief Clinical Officer and Chief Medical Officer, Neurology Business Group, Eisai. "The development of this new formulation underscores Eisai's commitment to advancing epilepsy care by making contributions to help address the diversified needs of epilepsy patients and their families."

The approval of Fycompa Oral Suspension was based on a bioequivalence (BE) study that demonstrated BE between a single dose of perampanel oral suspension and a single dose of perampanel tablet, when administered under fasted conditions in healthy subjects.

About Fycompa

Fycompa (perampanel) is indicated as adjunctive therapy for the treatment of partial-onset seizures with or without secondarily generalized seizures and primary generalized tonic-clonic seizures in patients with epilepsy 12 years of age and older.

Fycompa is an oral medication and the first and only FDA-approved non-competitive AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor antagonist. The precise mechanism by which Fycompa exerts its antiepileptic effects in humans has not been fully elucidated.

Fycompa is supplied as 2 mg, 4 mg, 6 mg, 8 mg, 10 mg and 12 mg film-coated tablets, and now in an oral suspension formulation. Fycompa has been designated by the U.S. Drug Enforcement Administration as a federally-controlled substance (CIII).

Fycompa, approved in 43 countries, was discovered and developed by Eisai. Over 60,000 patients globally have been treated with Fycompa.

Eisai Announces FDA Approval of Fycompa (perampanel) Oral Suspension

Brintellix (vortioxetine) Renamed Trintellix (vortioxetine) in U.S. to Avoid Name Confusion

In continuation of my update on vortioxetine

Takeda Pharmaceuticals U.S.A., Inc., a wholly-owned subsidiary of Takeda Pharmaceutical Company Limited (TSE:4502) (collectively “Takeda”), and Lundbeck announced today that Brintellix(vortioxetine) will be marketed in the United States under the new name Trintellix(vortioxetine) starting in June of 2016. The vortioxetine product is a prescription medicine approved to treat Major Depressive Disorder (MDD) in adults. The formulation, indication and dosages of Trintellix remain the same as that of Brintellix.

This name change comes after receiving reports of name confusion in the marketplace between Brintellix and the anti-blood clotting therapy Brilinta® (ticagrelor). In response, Takeda and Lundbeck, in coordination with the U.S. Food and Drug Administration (FDA), determined that a name change would be the best way to minimize future product name confusion by patients and providers.

“Though the original name was fully screened prior to launch, after learning about name confusion issues with Brintellix and Brilinta, we quickly took action to educate healthcare professionals and pharmacies about the potential for name confusion,” said Thomas Harris, Vice President Global Regulatory Affairs at Takeda. “Takeda and Lundbeck then proactively worked with the FDA and decided to change the name of our product as we believe this action will help minimize future risk of patients inadvertently receiving the incorrect medication.”

“Even though the name of the product is changing, together with Takeda, we will work to ensure providers and patients are aware that the vortioxetine product itself has not changed. It’s still the same medication, dosing and expected outcomes,” said Gregg Pratt, Vice President, U.S. Regulatory Affairs at Lundbeck.

“Patient safety is our utmost priority at Takeda and Lundbeck,” said Ramona Sequeira, President, U.S. Business Unit at Takeda. “Together, with our partners at Lundbeck, we will initiate a robust communication campaign and actively work to ensure that patients, healthcare professionals and pharmacies have uninterrupted access to this important medication. We believe these actions speak to our goals of building our business around patients, trust and reputation.”

During the transition period this summer, healthcare providers can still prescribe, and patients will still have access to, the product under its current brand name. The newly named Trintellix will be available in June 2016. Additionally, markings on the Trintellix tablets will be identical to the markings on tablets prior to the name change. Trintellix will have new National Drug Code (NDC) numbers associated with the product. Individuals and healthcare professionals who have questions about Brintellix, Trintellix and/or the name change, should contact Takeda at 1-877-TAKEDA-7.

Errors involving Brintellix/Trintellix or any other products should be reported to the FDA MedWatch program online at www.fda.gov/medwatch.

About Brintellix (vortioxetine), now known as Trintellix (vortioxetine), in the United States

Brintellix (vortioxetine) Renamed Trintellix (vortioxetine) in U.S. to Avoid Name Confusion

New drug against nerve agents in sight

A model of how sarin and HI-6 are positioned in the protein acetylcholinesterase just before HI-6 removes sarin and restores the function of the protein. The model was developed by a combination of X-ray crystallography and quantum chemical calculations. Sarin in magenta, HI6 in green, oxygen in red, phosphorus in orange and nitrogen in blue. 

The nerve agent sarin causes a deadly overstimulation of the nervous system that can be stopped if treated with an antidote within minutes of poisoning. Today, a ground-breaking study has been published in PNAS, which in detail describes how such a drug works. Researchers at the Swedish Defence Research Agency, Umeå University and in Germany are behind the study.

Sarin is a colourless, odourless liquid fatal even at very low concentrations. Serious sarin poisoning causes visual disturbance, vomiting, breathing difficulties and, finally, death.

"Nerve agents are dreadful weapons, and our hope is for these results to lead to improved drugs against them," says Anders Allgardsson, Biochemist at the Swedish Defence Research Agency (FOI).

Nerve agents destroy the function of a very important protein in the nervous system called acetylcholinesterase. As long as the nerve agent is bound to the protein, the breakdown of an important signal substance is prevented. The antidote HI-6 removes the nerve agent and restores the function of the nervous system. Drugs against nerve agent poisoning have been used for a long time, still it has been unclear how they actually work.

After years of hard work, chemists from FOI and Umeå University are now presenting a three-dimensional structure that depicts the HI-6 moments before the bond between the nerve agent and the protein is broken. The structure gives a high-resolution image that, in detail, describes the individual positions of atoms and provides an understanding of how the bond breaks.

The scientific breakthrough was enabled by combining three-dimensional structural depictions with advanced calculations and biochemical experiments.

"With the help of X-ray crystallography, we could see weak traces of the signal we were looking for. As the signal was weak, we decided to integrate the data with quantum chemical methods. After demanding calculations on the supercomputer at the High Performance Computing Center North (HPC2N) at Umeå University, we finally succeeded," says Anna Linusson, Professor at the Department of Chemistry at Umeå University.

The calculations supported the theory that the weak signal in the X-ray crystallography data actually came from HI-6 and sarin. Important knowledge also fell into place after experiments where the system was disturbed by mutating the protein or by introducing isotopes.

"After seven years of work using many different techniques, we have finally been able to bring this to a successful close and can show a uniform picture of how HI-6 approaches sarin. It opens up for new opportunities in finding antidotes to sarin and other nerve agents by structure-based molecular design," says Anders Allgardsson.

Ref : http://www.pnas.org/content/early/2016/04/28/1523362113

New drug against nerve agents in sight 

Experimental Alzheimer's drug reverses genetic changes thought to spur the disease

After treatment with riluzole, the brains of old rats showed more of a transporter molecule that removes excess glutamate, (green fluorescence, right) as compared to untreated rats (left).

Aging takes its toll on the brain, and the cells of the hippocampus--a brain region with circuitry crucial to learning and memory--are particularly vulnerable to changes that can lead to Alzheimer's disease or cognitive decline. With the hope of counteracting the changes that can lead to these two conditions, researchers at Rockefeller University and their colleagues have begun examining the effects of a drug known to affect this circuitry.

In new research described recently in Molecular Psychiatry, a team led by Ana Pereira, Instructor in Clinical Medicine in Bruce McEwen's laboratory found that the drug, riluzole, is capable of reversing key genetic changes associated with these conditions.

 riluzole

"In aging and Alzheimer's, the chemical signal glutamate can accumulate between neurons, damaging the circuitry," Pereira says. "When we treated rats with riluzole, we saw a suite of changes. Perhaps most significantly, expression of molecules responsible for clearing excess glutamate returned to more youthful levels."

Previous work in McEwen's lab by Pereira has shown that the drug prompted structural changes in rats' neurons that prevent the memory loss often seen in old animals. Pereira is currently testing riluzole for the first time in Alzheimer's patients in a clinical trial at the Rockefeller University Hospital.

Glutamate clean up

Generally, glutamate is released to excite other neurons and doesn't linger in the spaces between them. As we age, though, the system gets a little leaky and glutamate can build up in these intercellular spaces. This happens in part when neurons make less and less of the transporter molecule responsible for removing excess glutamate. When it accumulates, this essential neurotransmitter can cause big problems, damaging or killing neurons and so contributing to Alzheimer's disease, and other disorders.

Pereira and co-first author Jason Gray, a postdoc in the lab sought to better understand the molecular vulnerabilities of an aging glutamate system and riluzole's effect on it.

"The essence is we used a drug known to modulate glutamate, and when we gave it to old rats, we saw it reversed many of the changes that begin in middle age in the hippocampus," Gray says. "We saw a similar pattern when we compared the riluzole-induced changes to data from Alzheimer's patients--in a number of key pathways in the hippocampus, the drug produced an effect opposing that of the disease."

The drug, it turns out, modifies the activity of certain genes in an aged animal to resemble that of a younger rat. For example, the researchers found that the expression of a gene called EAAT2, which has been linked to Alzheimer's and is known to play a role in removing excess glutamate from nerve fibers, declines as the animals age. However, in rats treated with riluzole this gene's activity was brought back to its youthful levels.

New targets for treatments?

In addition to its potential ability to allay memory loss and cognitive decline, riluzole is attractive as a potential treatment for Alzheimer's. The drug is already being used to treat another neurological disease, amyotrophic lateral sclerosis, and is therefore considered relatively safe. In Pereira's ongoing clinical trial, patients with Alzheimer's disease have thus far been treated with either the drug or a placebo, and have been undergoing tests to help determine whether their brain functions have been improved.

"We hope to use a medication to break the cycle of toxicity by which glutamate can damage the neurons that use it as a neurotransmitter, and our studies so far suggest that riluzole may be able to accomplish this," Pereira says. "We found that in addition to recovering the expression of EAAT2, the drug restored genes critical for neural communication and plasticity, both of which decline with aging and even more significantly in Alzheimer's disease."

The findings also help to lay the groundwork for further study of glutamate transporters as potential targets for treating both conditions.

Ref : http://newswire.rockefeller.edu/2016/05/02/an-experimental-alzheimers-drug-reverses-genetic-changes-thought-to-spur-the-disease/

Ref : http://www.nature.com/mp/journal/vaop/ncurrent/full/mp201633a.html

Experimental Alzheimer's drug reverses genetic changes thought to spur the disease  

Screening method uncovers drugs that may combat deadly antibiotic-resistant bacteria

In recent years, hospitals have reported dramatic increases in the number of cases of the highly contagious, difficult-to-treat, and often deadly antibiotic-resistant bacteria carbapenem-resistant Enterobacteriaceae (CRE). Now, investigators at Beth Israel Deaconess Medical Center (BIDMC) have developed a promising method of identifying new antimicrobials that target these organisms. The research is published in April issue of the journal ASSAY and Drug Development Technologies.

CRE are Gram-negative bacteria that frequently express a gene that codes for carbapenemase--an enzyme that breaks down carbapenem and other antibiotics--and that is located on "mobile genetic elements" called plasmids, which can jump from one bacterium to another. The two most common types of CRE are carbapenem-resistant Klebsiella species and carbapenem-resistant Escherichia coli. Patients who become infected with these bacteria have few antibiotic treatment options.

"The US Centers for Disease Control and Prevention recently classified these carbapenem-resistant organisms in their highest, most urgent antimicrobial resistance threat level," said James Kirby, MD, Director of the Clinical Microbiology Laboratory at BIDMC and an Associate Professor of Pathology at Harvard Medical School. "Unfortunately, often either no effective or only toxic antimicrobial options remain for CRE treatment. Moreover, CRE are particularly frightening as they are now increasing in prevalence across the United States and the world."

While there is a critical need for new antimicrobial agents against CRE and other emerging antibiotic-resistant bacteria, the number of new antibiotics that have been developed and approved has steadily decreased in recent decades. To identify new or existing drugs that can destroy multidrug-resistant CRE, Kirby and postdoctoral fellow Kenneth Smith, PhD examined approximately 10,000 compounds with known activity--so called known bioactive molecules--including most previously FDA-approved drugs, veterinary drugs and inhibitors of various cellular processes not currently used as therapeutics.

Through a process called high throughput screening, the investigators looked to see whether any of these compounds could either directly inhibit the growth of CRE or restore the effectiveness of carbapenem against these organisms.

From these screening experiments, 79 compounds were found to inhibit CRE. Of these, three had already been approved for human and veterinary use: azidothymidine (also known as AZT, a therapy for HIV infection), spectinomycin (a treatment for gonorrhea infection) and apramycin (a veterinary antimicrobial). When tested against a large number of CRE strains, the three compounds were broadly active against the strains.

azidothymidine, Spectinomycin

 Apramycin

"These antimicrobials currently have other intended uses and are not currently considered as treatments for CRE, however our findings suggest they could potentially be repurposed for CRE treatment," said Smith. Apramycin and spectinomycin are of particular interest because they have minimal side effects, making them potentially ideal new therapeutic options for CRE infection.

Smith added that while these drugs might be used by themselves to treat CRE infection, they could also be used as starting points for further drug development. "Specifically, these antibiotics could be structurally modified to further increase their activity and prevent resistance from developing against them," he explained.

The next step in this line of research is to examine the potency of the identified drugs in an animal model of CRE infection. "We are also using the same high throughput screening technology to investigate a collection of more than 200,000 completely novel compounds with as yet uncharacterized biological activity in the hopes of identifying new classes of compounds with potent activity against CRE and other multi-drug resistant pathogens," Kirby said.

Ref : http://online.liebertpub.com/doi/10.1089/adt.2016.701

Screening method uncovers drugs that may combat deadly antibiotic-resistant bacteria 

New drug more effective in treating atrial fibrillation

Vernakalant, a new drug for treating recent-onset atrial fibrillation, has proved to be considerably more effective than Ibutilide, an established drug in this indication. It was able to normalize patients' heart rhythm more rapidly and with fewer side-effects ocurring. This was revealed by a study conducted at the Department of Emergency Medicine at Medical University of Vienna/General Hospital that has recently been published in Europace, a journal of the European Society of Cardiology.

 Vernakalant   Ibutilide 

Atrial fibrillation, the most common cardiac arrhythmia, accounts for many medical consultations, hospitalisations and is associated with a high economical burden. Atrial fibrillation affects 2% of the population and its prevalence increases significantly with age (to more than 10% in those over 80). Typical symptoms are sensation of a rapid and irregular heartbeat, dizziness and shortness of breath. In recent onset atrial fibrillation the aim is to restore a normal, regular heartbeat (sinus rhythm) as quickly as possible. This can be achieved either by electrical therapy or by drugs, so called antiarrhythmics.

Two potent antiarrhythmic drugs, Vernakalant (Brinavess) and Ibutilide (Corvert), which is particularly suitable for treating atrial flutter, were compared in a randomized trial at the Department of Emergency Medicine at Medical University of Vienna.

Vernakalant was found to have significant advantages: it achieved conversion to a normal sinus rhythm within an average of 10 minutes, compared to Ibutilide with an average of 26 minutes. 90 minutes after treatment start, 69% of Vernakalant treated patients were in sinus rhythm, compared to 43% of patients treated with Ibutilide.

Consequently, electrical cardioversion under brief anesthesia was less often required to restore sinus rhythm in the Vernakalant group. "Furthermore, in Vernakalant pretreated patients sinus rhythm could be restored easier, necessitating a lower number of shocks," explains study author Alexander Spiel.

Therefore, Ibutilide remains first choice for treating patients with atrial flutter. However, the results of this trial show that in patients with recent onset atrial fibrillation and with no or moderate structural heart disease Vernakalant has several advantages. "In this trial, none of the patients from either group experienced any serious adverse side effects," emphasizes study author Hans Domanovits.

Ref : http://europace.oxfordjournals.org/content/early/2016/03/21/europace.euw052

 New drug more effective in treating atrial fibrillation  

Expand prescribing of buprenorphine for opioid abuse? Experts weigh pros and cons....

In continuation of my update on Buprenorphine

Buprenorphine is a critical part of treatment for the growing epidemic of opioid abuse--but also carries the potential for misuse and diversion. The debate over whether 'to expand or not to expand' prescribing of buprenorphine for opioid abuse is discussed in an expert review in the Journal of Psychiatric Practice, published by Wolters Kluwer.

Based on the strong evidence of effectiveness, "We should not limit or impede the use and expansion of buprenorphine therapy," write Drs. Xiaofan Li, Daryl Shorter, and Thomas Kosten, of the Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas. They propose specific strategies to promote buprenorphine use while ensuring quality of care and reducing the risk of diversion and abuse.

Focus on Expanding Buprenorphine Use 'Safely and Effectively'

A "partial agonist" of the μ-opioid receptor in the brain, buprenorphine has similar actions to other opioids, but with less potential for abuse and a more favorable safety profile. Because it reduces demand for opioids, buprenorphine therapy is an effective deterrence strategy to combat opioid abuse. The authors cite studies suggesting that access to buprenorphine therapy can sharply reduce heroin mortality--including reductions of more than 50 percent in France and 37 percent in Baltimore.

Compared to methadone--long the standard for treating opioid and heroin addiction--buprenorphine poses lower risks related to diversion and non-medical use. The most commonly prescribed form of buprenorphine includes the opioid antagonist (blocker) naloxone, decreasing the potential for intravenous abuse.

But there are strict controls on prescribing of buprenorphine, which is classified as a Schedule III controlled substance in the United States. To prescribe buprenorphine in office-based settings, physicians must receive a Drug Enforcement Agency (DEA) waiver, complete special training, and comply with limits on the number of treated patients.

While medical use of buprenorphine has skyrocketed over the past decade, most prescribers are located in urban areas. It is estimated that 53 percent of US counties do not have any physician with a DEA waiver to prescribe buprenorphine.

Measures to make buprenorphine treatment more accessible have been proposed, such as allowing prescribing by qualified advanced nurse practitioners and physician assistants and loosening limits on number of patients treated. But these measures have been controversial, reflecting legitimate concerns about increased potential for diversion and abuse. Data show that, as use of buprenorphine to treat opioid use disorder has increased, so have the rates of misuse and diversion.

Drs. Li, Shorter, and Kosten raise special concern about the recent emergence of intravenous buprenorphine abuse. They write, "This real-world, almost paradoxical, phenomenon demonstrates the complexity inherent in the treatment of addictive disorders--a medication intended to treat substance use disorder that has its own abuse potential, upon gaining popularity and increased availability, will inevitably be explored by drug abusers for reward and reinforcement purposes."

Earlier this year, President Obama announced an initiative to increase access to effective medications for treating opioid addiction--specifically, buprenorphine and naloxone. Drs. Li, Shorter, and Kosten outline strategies to expand effective treatment with buprenorphine while reducing the risks of diversion and abuse, including:

• Additional support for physicians with high caseloads and other measures to help prescribers comply with guidelines.
• Continuing medical education targeting improvements in office-based therapy for opioid abuse.
• Policies and regulations promoting safe practice.
• Financial incentives coupled with mandatory enforcement of essential components of safe practice.
• More active pharmacy involvement, including supervised dispensing.
• Identification of groups at high risk of intravenous buprenorphine abuse.

"The question is not whether or not to expand buprenorphine prescribing," the authors add. "It is how to expand buprenorphine prescribing safely and effectively."

Ref :1. http://journals.lww.com/practicalpsychiatry/pages/articleviewer.aspx?year=2016&issue=05000&article=00004&type=abstract

 http://dx.doi.org/10.1097/PRA.0000000000000154

Expand prescribing of buprenorphine for opioid abuse? Experts weigh pros and cons