Two Vaccines Help Cut Bacteria That Cause Meningitis, Study Finds

Two new vaccines can reduce the spread of meningitis by reducing the number of meningitis-causing bacteria that people carry, according to a new study.

Researchers tested the two vaccines -- MenACWY-CRM and 4CMenB -- on volunteers aged 18 to 24. MenACWY-CRM cut meningitis-causing bacteria populations in the nose and throat by 39 percent and 4CMenB lowered those populations by 20 to 30 percent.

Two Vaccines Help Cut Bacteria That Cause Meningitis, Study Finds 

New Drug May Fight Serious Respiratory Virus in Infants

 An experimental drug shows promise in treating respiratory syncytial virus (RSV), a leading cause of pneumonia in infants, researchers report.

"We are finally making major progress in being able to treat human RSV infections -- the world's second leading cause of serious viral pneumonia, second only to influenza virus," said study author Dr. John DeVincenzo, a professor of pediatrics at the University of Tennessee College of Medicine in Memphis.

"There is no current treatment or vaccine for RSV pneumonia, and so patients were previously forced to get over the virus by themselves," he said. RSV is the leading cause of hospitalization among infants in the United States, the researchers noted.

In this small study of 140 adults, the drug, dubbed GS-5806, reduced the amount of the virus in the systems of those who received the medication.

"For the first time, we showed that once we reduce the amount of virus in patients, they very quickly started to feel better," DeVincenzo said.

New Drug May Fight Serious Respiratory Virus in Infants  

Drug Gives 'New Hope' Against Heart Failure, Expert Says

In a head-to-head comparison, an experimental drug was more effective than standard treatment at preventing deaths and hospitalizations in heart failure patients.

According to the study authors, the trial was stopped early because of the marked benefit of the new drug, dubbed LCZ696. [LCZ696 is an investigational combination drug consisting of two antihypertensives (blood pressure lowering drugs), valsartan (left below) and AHU-377 (right below), in a 1:1 mixture. It is being developed by Novartis. The combination is often described as a dual-acting angiotensin receptor-neprilysin inhibitor (ARNi)]

In the trial, 26.5 percent of those getting the standard medication, enalapril (Vasotec), either died or were hospitalized due to heart failure, compared with 21.8 percent of those on the new drug. Enalapril belongs to a class of blood pressure-lowering medications known as ACE inhibitors.

"LCZ696 could become the new gold standard, replacing ACE inhibitors," said lead researcher Dr. John McMurray, a professor of cardiology at the British Heart Foundation Cardiovascular Research Center at the University of Glasgow, in Scotland.

LCZ696 combines two blood pressure drugs -- an angiotensin II receptor blocker (ARB) and the neprilysin inhibitor known as sacubitril.

"We found that LCZ696 was superior to the gold-standard ACE inhibitor for heart failure -- an ACE inhibitor being the absolute cornerstone of treatment for this problem," he said.

Not only did LCZ696 beat enalapril, but it did that even when added to other treatments, McMurray noted.

"The new treatment was very well tolerated, with no significant safety concerns," he added.

Drug Gives 'New Hope' Against Heart Failure, Expert Says 

Synthesis produces new fungus-derived antibiotic

A fortuitous collaboration has led to the total synthesis of a recently discovered natural antibiotic. The laboratory recreation of a fungus-derived antibiotic, viridicatumtoxin B, may someday help bolster the fight against bacteria that evolve resistance to treatments in hospitals and clinics around the world.

As part of the process, Rice organic chemist K.C. Nicolaou and structural biologist Yousif Shamoo and their colleagues created and tested a number of variants of viridicatumtoxin B that could lead to the simplified synthesis of a new generation of more effective antibiotics.

The work reported this month in the Journal of the American Chemical Society (JACS) focused on a tetracycline discovered in 2008 by scientists who isolated small amounts from penicillium fungi. The yield wasn't nearly enough for extensive testing, but it provided a basis for the discoverers to analyze its structure through magnetic resonance imaging, Nicolaou said.

"We're inspired by molecules that are biologically active and have the potential to become medicines one day," he said.

The new discovery belongs to a class of antibiotics known as tetracyclines for their distinctive molecular structure. They proved potent  in  initial tests on
Gram-positive bacteria, so named for a staining technique to mark bacteria that are more susceptible to antibiotics than their Gram-negative counterparts.

The first tetracyclines, discovered in the late 1940s, ushered in a new class of
powerful antibacterial agents to treat high-mortality diseases,    among  them
anthrax and plague as well as such bacterial infections as chlamydia, syphilis
and Lyme disease.

To find new weapons, especially  against  "superbugs" that resist nearly all antibiotics, synthetic chemists pursue the complex  process  of  mimicking the
structures of effective natural molecules as they build drug candidates atom by atom.

"Tetracyclines are widespread antibiotics today, but bacteria are building resistance to a lot of them," Nicolaou said. "This new tetracycline is not plentiful in nature, so the only way we can make it available to study by biologists for its potential in medicine is to synthesize it in the laboratory."

Ref : http://pubs.acs.org/doi/abs/10.1021/ja506472u

Synthesis produces new fungus-derived antibiotic 

Experimental Drug Would Help Fight Ebola if Supply Increases, Study Finds - NYTimes.com

A new study provides strong evidence that the experimental drug given to two American aid workers stricken with Ebola in Africa really works and could make a difference in the current outbreak — if more of it could be produced.

In the study, all 18 monkeys exposed to a lethal dose of Ebola virus survived when given the drug, known as ZMapp, even when the treatment was started five days after infection, when the animals were already sick.

Moreover, the monkeys’ symptoms, such as excessive bleeding, rashes and signs of liver toxicity, eventually disappeared. By contrast, all three monkeys in the control group died.

Experts said these were the best monkey results reported to date for any Ebola drug, raising hopes that the drug will work in people.

Experimental Drug Would Help Fight Ebola if Supply Increases, Study Finds - NYTimes.com

Chili peppers for a healthy gut: Spicy chemical may inhibit gut tumors

In continuation of my update on capsaicin

Researchers report that dietary capsaicin – the active ingredient in chili peppers – produces chronic activation of a receptor on cells lining the intestines of mice, triggering a reaction that ultimately reduces the risk of colorectal tumors....

Chili peppers for a healthy gut: Spicy chemical may inhibit gut tumors  

Pesticide DDT linked to slow metabolism, obesity and diabetes, mouse study finds -- ScienceDaily

A new study in mice is the first to show that developmental exposure to DDT increases the risk of females later developing metabolic syndrome -- a cluster of conditions that include increased body fat, blood glucose, and cholesterol.

Pesticide DDT linked to slow metabolism, obesity and diabetes, mouse study finds  

Researchers uncover how malaria parasite becomes resistant to fosmidomycin drug

Researchers have uncovered a way the malaria parasite becomes resistant to an investigational drug. The discovery, at Washington University School of Medicine in St. Louis, also is relevant for other infectious diseases including bacterial infections and tuberculosis.

The study appears July 24 in Nature Communications.

Many organisms, including the parasite that causes malaria, make a class of molecules called isoprenoids, which play multiple roles in keeping organisms healthy, whether plants, animals or bacteria. In malaria, the investigational drug fosmidomycin blocks isoprenoid synthesis, killing the parasite. But over time the drug often becomes less effective.

"In trials testing fosmidomycin, the malaria parasite returned in more than half the children by the end of the study," said senior author Audrey R. Odom, MD, PhD, assistant professor of pediatrics. "We wanted to know how the parasite is getting around the drug. How can it manage to live even though the drug is suppressing these compounds that are necessary for life?"

Fosmidomycin, an antibiotic, is being evaluated against malaria in phase 3 clinical trials in combination with other antimalarial drugs.

Using next-generation sequencing technology, the research team compared the genetics of malaria parasites that responded to the drug to the genetics of malaria parasites that were resistant to it. With this approach, Odom and her colleagues found mutations in a gene called PfHAD1. With dysfunctional PfHAD1, malaria is resistant to fosmidomycin.

"The PfHAD1 protein is completely unstudied," Odom said. "It's a member of a larger family of proteins, and there are almost no biological functions assigned to them."

In malaria parasites, Odom's team showed that the PfHAD1 protein normally slows down the synthesis of isoprenoids. In other words, when present, PfHAD1 is doing the same job as the drug, slowing isoprenoid manufacturing. Since isoprenoids are necessary for life, it's not clear why the organism would purposefully slow down isoprenoid production.

Ref : http://www.nature.com/ncomms/2014/140724/ncomms5467/full/ncomms5467.html

Researchers uncover how malaria parasite becomes resistant to fosmidomycin drug

Antifungal drug resistance evoked through RNAi-dependent epimutations

Microorganisms like bacteria and fungi can evade treatment by acquiring mutations in the genes targeted by antibiotics or antifungal drugs. These permanent mutations were once thought to be the only way for drug-resistant strains to evolve. Now a new study has shown that microorganisms can use a temporary silencing of drug targets -- known as epimutations -- to gain the benefits of drug resistance without the commitment.

Though the new mechanism was discovered in a fungus called Mucor circinelloides, it is likely to be employed by other fungi as well as bacteria, viruses and other organisms to withstand treatment with various drugs. The finding appears July 27, 2014, in Nature.

"This mechanism gives the organism more flexibility," said Joseph Heitman, M.D., Ph.D., senior study author and professor and chair of molecular genetics and microbiology at Duke University School of Medicine. "A classic, Mendelian mutation is a more permanent binding decision, like a traditional marriage. These epimutations are reversible, more akin to moving in together. If conditions change, it is easier to revert to the way things were."

The epimutations are so transient, in fact, that the researchers almost disregarded them. Cecelia Wall, a graduate student in Drs. Heitman and Maria Cardenas' labs, had been looking for mutations that would make the human fungal pathogen M. circinelloides resistant to the antifungal drug FK506 (also known as tacrolimus). This pathogen causes the rare but lethal fungal infection mucormycosis, an emerging infectious disease that predominantly affects individuals with weakened immune systems.

Ref:http://www.nature.com/nature/journal/vaop/ncurrent/full/nature13575.html

Antifungal drug resistance evoked through RNAi-dependent epimutations

Flamel Technologies Announces FDA Approval of Vazculep

 Flamel Technologies (NASDAQ: FLML) today announced that the U.S. Food and Drug Administration (FDA) has approved the company's New Drug Application (NDA) for Vazculep (phenylephrine hydrochloride). Vazculep Injection is an alpha-1 adrenergic receptor agonist indicated for the treatment of clinically important hypotension resulting primarily from vasodilation in the setting of anesthesia. Flamel expects to launch Vazculep in the next few months in 1 mL single use vials, and 5 mL and 10 mL pharmacy bulk package vials. The drug strength is the same in all vials at 10 mg/mL. Phenylephrine hydrochloride is used in operating rooms and is injected intravenously either as a bolus or in a dilute solution as a continuous infusion.

Flamel Technologies Announces FDA Approval of Vazculep