Research brings hope of new treatment for asthma patients resistant to corticosteroids

New research from Japan brings hope of a new treatment for asthma patients resistant to corticosteroids. In a study published today in the journal Nature Communications, researchers from the RIKEN Center for Integrative Medical Sciences and Keio University in Japan report that a type of lymphocytes called natural helper (NH) cells plays a critical role in corticosteroid resistance and demonstrate that the anti-psychotic drug Pimozide can be used to overcome resistance to steroids in severe asthma patients.

Research brings hope of new treatment for asthma patients resistant to corticosteroids

Cinnamon May Help Ease Common Cause of Infertility, Study Says...

A small study by researchers from Columbia University Medical Center in New York City found that women with polycystic ovary syndrome who took inexpensive daily cinnamon supplements experienced nearly twice the menstrual cycles over a six-month period as women with the syndrome given an inactive placebo. Two of the women in the treated group reported spontaneous pregnancies during the trial.

"There is a lot of interest in homeopathic or natural remedies for this condition," said study author Dr. Daniel Kort, a postdoctoral fellow in reproductive endocrinology at the medical center. "This may be something we can do using a totally natural substance that can help a large group of patients."

The study was scheduled for presentation Wednesday at a meeting of the International Federation of Fertility Societies and American Society for Reproductive Medicine in Boston.

An estimated 5 percent to 10 percent of women of childbearing age have polycystic ovary syndrome, with up to 5 million Americans affected. Polycystic ovary syndrome, which involves many of the body's systems, is thought to be caused by insensitivity to the hormone insulin. Typical symptoms include menstrual irregularity, infertility, acne, excess hair growth on the face or body, and thinning scalp hair.

Treatment for polycystic ovary syndrome currently includes weight loss, ovulation-inducing drugs such as clomiphene (brand name Clomid) and diabetes medications such as metformin, said Dr. Avner Hershlag, chief of the Center for Human Reproduction at North Shore University Hospital in Manhasset, N.Y.

Kort said that it's not yet clear exactly why cinnamon may work to regulate menstrual cycles in those with polycystic ovary syndrome, but it may improve the body's ability to process glucose and insulin. Prior research among diabetic patients suggested the spice can reduce insulin resistance.

Of the 16 patients who completed Kort's trial, 11 were given daily 1,500-milligram cinnamon supplements and five were given placebo pills. Diet and activity levels were monitored, and patients completed monthly menstrual calendars.

After six months, women receiving cinnamon had significant improvement in menstrual cycle regularity, having an average of nearly four menstrual periods over that time compared to an average of 2.2 periods among the placebo group. Two women reported spontaneous pregnancies after three months of cinnamon treatment, meaning they became pregnant without additional help.

Polycystic ovary syndrome "is one of the most common causes why women don't have regular menstrual cycles," Kort said. "But the clinical consequences later in life are truly great from an increased risk of diabetes and glucose intolerance to endometrial cancer. Many women can go their whole lives without regular menstrual cycles, and it doesn't necessarily bother them until they want to have children."

The 1,500-milligram cinnamon dose was chosen for this trial because it was between the 1,000 to 2,000 mg daily that seemed to have metabolic effects on diabetic patients in earlier research, Kort said. But all doses in that range are cheaply obtained, costing pennies per capsule.

"Compared to most medical therapies these days, the cost is very small," he said.

Although the study suggests a link between cinnamon and improvement of polycystic ovary syndrome, it doesn't establish a direct cause-and-effect relationship.

Still, Hershlag called the study "welcome and interesting" and said he sees no reason women with polycystic ovary syndrome shouldn't use more cinnamon in their food or take cinnamon supplements.

"Any work that's something nutritional in nature and seems to affect the abnormal physiology of polycystic ovaries is welcome," Hershlag said. "If they want to spice up their life and take it, that's fine , but I think the best thing to do when you have polycystic ovaries is to be under the control of a physician."

Cinnamon May Help Ease Common Cause of Infertility, Study Says - Drugs.com MedNews

Bacteria-eating viruses 'magic bullets in the war on superbugs'

Dr Martha Clokie, from the University of Leicester's Department of Infection, Immunity and Inflammation has been investigating an alternative approach to antibiotics, which utilizes naturally occurring viruses called bacteriophages, meaning 'eaters of bacteria'.

The work has predominantly been funded by the Medical Research Council (MRC).

Dr Clokie said: "Ever since the discovery of the first antibiotic, penicillin, antibiotics have been heralded as the 'silver bullets' of medicine. They have saved countless lives and impacted on the well-being of humanity.

"But less than a century following their discovery, the future impact of antibiotics is dwindling at a pace that no one anticipated, with more and more bacteria out-smarting and 'out-evolving' these miracle drugs. This has re-energised the search for new treatments.

"One alternative to antibiotics is bacteriophages, known as phages, which unlike antibiotics, are specific in what they kill and will generally only infect one particular species, or even strain, of bacteria -- referred to as the 'host'. Following attachment to their hosts, they inject their DNA into the bacterium, which then replicates many times over, ultimately causing the bacterial cell to burst open. The phages released from the dead bacterium can then infect other host cells."

Dr. Clokie and her team have achieved the remarkable feat of isolating and characterising the largest known set of distinct C. diff phages that infect clinically relevant strains of C. diff. Of these, a specific mixture of phages have been proved, through extensive laboratory testing, to be effective against 90% of the most clinically relevant C. diff strains currently seen in the U.K.

As a testament to their therapeutic potential, these phages, that are the subject of a patent application, have been licensed by AmpliPhi Biosciences Corporation -- a US-based biopharmaceutical company and pioneers in developing phage-based therapeutics. AmpliPhi have already made progress in developing phages targeted against Pseudomonas aeruginosa, a pathogen that causes acute, life-threatening lung infections in cystic fibrosis patients. They were also the first biopharmaceutical company to demonstrate the effectiveness ofPseudomonas phages in controlled and regulated human clinical trials.

Read more

Bacteria-eating viruses 'magic bullets in the war on superbugs'

Painkillers May Worsen Headaches Following Concussion

The researchers found that daily headache, female sex, the presence of nausea, throbbing headache versus steady or stabbing pain, irritability following concussion, and a relatively longer interval between the concussive event and neurological evaluation were more common in the 54 patients with probable medication-overuse headache than in the 23 without. Within two months of stopping analgesics, 37 of the 54 in the probable group had improvement in symptoms, i.e., complete resolution or reversion to preconcussion levels of the headache. The study was presented as a poster session at the Child Neurology Society (CNS) annual meeting, held during October-November 2013 in Austin.

“Continued use of analgesics for headache despite lack of efficacy can cause chronification of a headache syndrome. Because withdrawal of painkillers alleviated these patients' headaches, a diagnosis of medication-overuse headache may be made,” concluded study authors Geoffrey Heyer, MD, and Syed Idris, MD. “Management of patients with prolonged postconcussion headache should include analgesic detoxification when medication overuse is suspected.”

Hospimedica - Painkillers May Worsen Headaches Following Concussion

MNK-795 for acute pain management: an interview with Dr Lynn Webster

MNK-795 is an investigational, extended-release, oral formulation of oxycodone  (left) and acetaminophen (right) that has been studied for the management of moderate to severe acute pain where the use of an opioid analgesic is appropriate. 

MNK-795 is a product in development that is intended to be used for acute pain. It has some unique properties. First, it is an extended release formulation, meaning that it’s going to last more than three to four hours. It was studied to be dosed once every 12 hours, and that is unique for an acute pain formulation.

Secondly, it has abuse deterrent properties which mean that the new design and technology within this formulation may prevent people who try to manipulate, alter or convert the extended release into an immediate release in order to achieve a greater high.

Research has found that when the formulation is manipulated, when it’s crushed in some way or ground up, it actually delays the onset of some of its properties, the liking properties. So rather than causing more liking, more of a high, it actually causes less of a liking and less of a high when it’s manipulated.

This is the first time I’m aware that any technology has delayed and lessened the liking once it’s manipulated. I must, however, stress that at present these are only research results and we cannot yet confirm how MNK-795 will perform in the real world.

MNK-795 for acute pain management: an interview with Dr Lynn Webster

Researchers discover new approach to tackle global threat of antibiotic drug resistance

Researchers at McMaster University are addressing the crisis in drug resistance with a novel approach to find new antibiotics.

"We have developed technology to find new antibiotics using laboratory conditions that mimic those of infection in the human body," said Eric Brown, professor in the Department of Biochemistry and Biomedical Sciences.

He is the lead author of the paper published in the online edition of Nature Chemical Biology today. Brown is also a member of the Michael G. DeGroote Institute for Infectious Disease Research (IIDR).

The findings report on the discovery of chemical compounds that block the ability of bacteria to make vitamins and amino acids, processes that are emerging as Achilles' heels for bacteria that infect the human body.

"The approach belies conventional thinking in antibiotic research and development, where researchers typically look for chemicals that block growth in the laboratory under nutrient-rich conditions, where vitamins and amino acids are plentiful," said Brown. "But in the human body these substances are in surprisingly short supply and the bacteria are forced to make these and other building blocks from scratch."

Brown's research group targeted these processes looking for chemicals that blocked the growth of bacteria under nutrient-limited conditions.

"We threw away chemicals that blocked growth in conventional nutrient-rich conditions and focused instead on those that were only active in nutrient-poor conditions," he said.

"We're taking fresh aim at bacterial vitamin and amino acid production and finding completely novel antibacterial compounds."

The approach and the new leads discovered by Brown's lab have potential to provide much-needed therapies to address the growing global threat of antibiotic drug resistance.

"When it comes to this kind of new drug discovery technology, Brown's group are fishing in a new pond," said professor Gerry Wright, director of the IIDR. "These leads have real prospects as an entirely new kind of antibacterial therapy."

Researchers discover new approach to tackle global threat of antibiotic drug resistance

Nail Fungus Drug Might Help Against HIV, Study Suggests - Drugs.com MedNews

We know that, Ciclopirox olamine (used in preparations called Batrafen, Loprox, Mycoster, Penlac and Stieprox) is a synthetic antifungal agent for topical dermatologic treatment of superficial mycoses. It is most useful against Tinea versicolor.

According to a new study this  drug used to treat nail fungus may hold promise against HIV, the virus that causes AIDS.

Read more at: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0074414

Nail Fungus Drug Might Help Against HIV, Study Suggests - Drugs.com MedNews

Copper promises cheaper, sturdier fuel cells

The copper nanowire films consist of networks of microscopic metal rods, the properties and applications of which Wiley's lab has studied for years. The nanowires provide a high surface area for catalyzing chemistry, and Wiley's team experimented with coating them in either cobalt or nickel -- metals that serve as the actual chemical catalyst. Even with a coat of cobalt or nickel, the nanowire films allow nearly seven times more sunlight to pass through than ITO. The films are also flexible, leading Wiley to imagine the completed fuel cells one day being attached to backpacks or cars.

In the meantime, engineering and chemistry challenges remain. The nanowire films carry out only one half of the water-splitting equation, a process called water oxidation. The other half of the reaction involves using the electrons obtained from water oxidation to reduce water to hydrogen. Wiley's team expects to publish their work on this process in the coming year.

"A lot of groups are working on putting together complete devices to generate fuels from sunlight," he said, but "the efficiencies and costs of these systems have to be improved for them to get to commercial [production]."

Wiley noted that solar energy production is just one application of the copper nanowire films they study. The nanowires also show promise for use in flexible touch screens, organic LED (or OLED) lights and smart glass.

Copper promises cheaper, sturdier fuel cells

Ticagrelor drug may reduce risk of dying following heart attack

In continuation of my update on ticagrelor 

Scientists from the University of Sheffield have discovered ground breaking clues as to how the pioneering heart drug ticagrelor might reduce the risk of dying following a heart attack, in comparison to previous standard treatments.

The new findings, published in Platelets, show that ticagrelor (see left structure above) may reduce the risk of dying as a result of a lung infection after suffering a heart attack compared to patients treated with the drug clopidogrel (see right structure below).

The analysis, which was led by researchers from the University of Sheffield and Uppsala University Sweden, is the latest to come from the PLATO study which originally included over 18,000 patients worldwide. 

In the initial PLATO study, the annual mortality rate for patients treated with clopidogrel was 5.9 per cent and this rate was significantly reduced to 4.5 per cent for patients treated with ticagrelor.

The extent of this reduced risk was unexpected, as previous similar trials had not been so successful in reducing mortality risk - prompting speculation as to the possible mechanisms for this benefit.

Professor Robert Storey said: "We have now shown that there were fewer deaths due to overwhelming bacterial infection (sepsis) in patients treated with ticagrelor, with lung infection accounting for the source of this sepsis in many cases.

"This is a surprising finding but does seem to provide a potential lead in explaining why ticagrelor saved so many lives in comparison to clopidogrel treatment.

"Ticagrelor not only has greater anticlotting activity compared to clopidogrel, which easily explains its greater effectiveness in preventing further heart attacks, but also has another property not possessed by clopidogrel that allows it to prevent adenosine from being cleared from the blood stream.

"Adenosine has many different effects in the body including influencing the activity of white blood cells that are involved in tackling pneumonia and other infections."

Ticagrelor drug may reduce risk of dying following heart attack

Caffeine in coffee may help small blood vessels work better

The caffeine in a cup of coffee might help your small blood vessels work better, according to research presented at the American Heart Association's Scientific Sessions 2013.

A study of 27 healthy adults showed - for the first time - that drinking a cup of caffeinated coffee significantly improved blood flow in a finger, which is a measure of how well the inner lining of the body's smaller blood vessels work. Specifically, participants who drank a cup of caffeinated coffee had a 30 percent increase in blood flow over a 75-minute period compared to those who drank decaffeinated coffee.

"This gives us a clue about how coffee may help improve cardiovascular health," said Masato Tsutsui, M.D., Ph.D., lead researcher and a cardiologist and professor in the pharmacology department at the University of the Ryukyus in Okinawa, Japan.

The study adds to a growing body of research about coffee, the most widely consumed beverage worldwide. Previous studies showed that drinking coffee is linked to lower risks of dying from heart disease and stroke, and that high doses of caffeine may improve the function of larger arteries.

Caffeine in coffee may help small blood vessels work better

New Cancer Targeting Technique to Improve Cancer Drugs

Cancer drugs work because they’re toxic, but that’s also why they afflict healthy cells, producing side effects that can compromise their efficacy. Nobuhide Ueki thinks he may have found a way to get the drugs to selectively target only the cancer cells, and his team’s patent-pending research is the subject of a paper entitled “Selective cancer targeting with prodrugs activated by histone deacetylases and a tumour-associated protease,” 

Authors demonstrate a new prodrug strategy for selective cancer therapy that utilizes increased histone deacetylase (HDAC) and tumour-associated protease activities produced in malignant cancer cells. By coupling an acetylated lysinegroup to puromycin, a masked cytotoxic agent is created, which is serially activated by HDAC and an endogenous protease cathepsin L (CTSL) that remove the acetyl group first and then the unacetylated lysine group liberating puromycin. The agent selectively kills human cancer cell lines with high HDAC and CTSL activities. In vivo studies confirm tumour growth inhibition in prodrug-treated mice bearing human cancer xenografts. This cancer-selective cleavage of the masking group is a promising strategy for the next generation of anticancer drug development that could be applied to many other cytotoxic agents.

Read : Nature Communications

New Cancer Targeting Technique to Improve Cancer Drugs

Scientists develop new drug to treat obstructive airway diseases

Scientists have developed a new drug (RPL554, see structure) that could treat obstructive airway diseases such as asthma and chronic obstructive pulmonary disease (COPD) in two ways at once, according to new research published in The Lancet Respiratory Medicine. RPL554 has the potential to both reverse the narrowing of the airways (bronchodilation) and reduce inflammation quicker and with fewer side effects than current therapies.

“Further longer term studies of RPL554 are now eagerly awaited because this could be one of the most substantial advances for some time in the management of patients with chronic airway obstruction”, writes Professor Jadwiga A Wedzicha from University College London, UK, in a linked Comment.

The unique inhaled dual inhibitor—two actions in a single molecule—works by impeding the ability of two enzymes from the phosphodiesterase family (PDE3 and PDE4) to inhibit processes that help relax airway smooth muscle and reduce inflammation.

For the past 40 years, the mainstay of treatment for asthma and COPD (eg, chronic bronchitis and emphysema) has been inhaled anti-inflammatory drugs (corticosteroids) plus bronchodilators (usually long-acting ß2 agonists). But corticosteroids can have substantial side effects, while long-acting ß2 agonists have come under scrutiny for their risk of worsening asthma symptoms. What is more, most people with severe disease and frequent flare-ups fail to achieve good control of symptoms and new treatments are needed. 

Between February, 2009 and January 3013, four small proof-of-concept clinical trials were done in the Netherlands, Italy, and the UK to assess the safety and efficacy of inhaled RPL554 in healthy participants (39 people) and people with mild-to-moderate asthma (28) and COPD (12).

In COPD patients, a single dose of nebulised RPL554 improved respiratory function, producing a 17% increase in FEV1 (forced expiratory volume at 1 second; which measures the volume of air that can be forcibly exhaled in one second after taking a deep breath)—a bronchodilator response at least as effective as the widely use ß2 agonist Salbutamol.

Ref : http://www.thelancet.com/journals/lanres/article/PIIS2213-2600(13)70187-5/fulltext

Scientists develop new drug to treat obstructive airway diseases

Nintedanib drug to treat NSCLC is submitted for approval from European Medicines Agency

In continuation of my update on NSCLC (non-small cell lung carcinoma)

We know that, Nintedanib (see structure, formerly BIBF 1120; trade name Vargatef) is a small molecule of angiokinase inhibitor class inhibiting vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR) and platelet derived growth factor receptor(PDGFR) being developed by Boehringer Ingelheim for use as an anti-vascular anti-cancer agent.

"We are proud that nintedanib, a compound out of our innovative oncology research programme, is the second compound in our portfolio to be filed with the European Medicines Agency."

Nintedanib drug to treat NSCLC is submitted for approval from European Medicines Agency

Researchers identify C. perfringens type B bacteria believed to trigger multiple sclerosis

A research team from Weill Cornell Medical College and The Rockefeller University has identified a bacterium it believes may trigger multiple sclerosis (MS), a chronic, debilitating disorder that damages myelin forming cells in the brain and spinal cord.

Their study, published in PLoS ONE, is the first to identify the bacterium, Clostridium(C.) perfringens type B, in humans. The scientists say their study is small and must be expanded before a definitive connection between the pathogen and MS can be made, but they also say their findings are so intriguing that they have already begun to work on new treatments for the disease.

"This bacterium produces a toxin that we normally think humans never encounter. That we identified this bacterium in a human is important enough, but the fact that it is present in MS patients is truly significant because the toxin targets the exact tissues damaged during the acute MS disease process," say the study's first author, K. Rashid Rumah, an MD/PhD student at Weill Cornell Medical College, and the study's senior investigator, Dr. Timothy Vartanian, professor of neurology and neuroscience at Weill Cornell Medical College and director of the Judith Jaffe Multiple Sclerosis Center at New York-Presbyterian Hospital/Weill Cornell Medical Center.

"While it is clear that new MS disease activity requires an environmental trigger, the identity of this trigger has eluded the MS scientific community for decades," Dr. Vartanian says. "Work is underway to test our hypothesis that the environmental trigger for MS lays within the microbiome, the ecosystem of bacteria that populates the gastrointestinal tract and other body habitats of MS patients."

Ref : http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0076359

Researchers identify C. perfringens type B bacteria believed to trigger multiple sclerosis

Combination of heat, doxorubicin drug and nanotech system may improve ovarian cancer treatment

The combination of heat, chemotherapeutic drugs and an innovative delivery system based on nanotechnology may significantly improve the treatment of ovarian cancerwhile reducing side effects from toxic drugs, researchers at Oregon State University report in a new study.

The findings, so far done only in a laboratory setting, show that this one-two punch of mild hyperthermia and chemotherapy can kill 95 percent of ovarian cancer cells, and scientists say they expect to improve on those results in continued research.

The work is important, they say, because ovarian cancer - one of the leading causes of cancer-related deaths in women - often develops resistance to chemotherapeutic drugs if it returns after an initial remission. It kills more than 150,000 women around the world every year.

"Ovarian cancer is rarely detected early, and because of that chemotherapy is often needed in addition to surgery," said Oleh Taratula, an assistant professor in the OSU College of Pharmacy. "It's essential for the chemotherapy to be as effective as possible the first time it's used, and we believe this new approach should help with that."

It's known that elevated temperatures can help kill cancer cells, but heating just thecancer cells is problematic. The new system incorporates the use of iron oxidenanoparticles that can be coated with a cancer-killing drug and then heated once they are imbedded in the cancer cell.

Other features have also been developed to optimize the new system, in an unusual collaboration between engineers, material science experts and pharmaceutical researchers.

A peptide is used that helps guide the nanoparticle specifically to cancer cells, and the nanoparticle is just the right size - neither too big nor too small - so the immune system will not reject it. A special polyethylene glycol coating further adds to the "stealth" effect of the nanoparticles and keeps them from clumping up. And the interaction between the cancer drug and a polymer on the nanoparticles gets weaker in the acidic environment of cancer cells, aiding release of the drug at the right place.

"The hyperthermia, or heating of cells, is done by subjecting the magnetic nanoparticles to an oscillating, or alternating magnetic field," said Pallavi Dhagat, an associate professor in the OSU School of Electrical Engineering and Computer Science, and co-author on the study. "The nanoparticles absorb energy from the oscillating field and heat up."

The result, in laboratory tests with ovarian cancer cells, was that a modest dose of the chemotherapeutic drug, combined with heating the cells to about 104 degrees, killed almost all the cells and was far more effective than either the drug or heat treatment would have been by itself.

Doxorubicin (see structure), the cancer drug, by itself at the level used in these experiments would leave about 70 percent of the cancer cells alive. With the new approach, only 5 percent were still viable.

The work was published in the International Journal of Pharmaceutics, as a collaboration of researchers in the OSU College of Pharmacy, College of Engineering, and Ocean NanoTech of Springdale, Ark. It was supported by the Medical Research Foundation of Oregon, the PhRMA Foundation and the OSU College of Pharmacy.

Combination of heat, doxorubicin drug and nanotech system may improve ovarian cancer treatment