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

Atorvastatin drug plus zoledronic acid may help treat toxoplasmosis

In continuation of my update on Atorvastatin and Zoledronic acid

Researchers at the University of Georgia have discovered that a combination of two commonly prescribed drugs used to treat high cholesterol and osteoporosis may serve as the foundation of a new treatment for toxoplasmosis, a parasitic infection caused by the protozoan Toxoplasma gondii. They published their findings recently in PLOS Pathogens.

Toxoplasma gondii is a parasite capable of infecting nearly all warm-blooded animals. While healthy human adults usually suffer no lasting ill effects from infection, it can be harmful or fatal to unborn fetuses or those with weakened immune systems.

"For many years, therapies for toxoplasmosis have focused on drugs that target only the parasite," said Silvia Moreno, senior author of the article and professor of cellular biology in UGA's Franklin College of Arts and Sciences. "But in this paper, we show how we can hit the parasite with two drugs simultaneously, one that affects body chemistry in the host and one that affects the parasite."

The UGA researchers discovered that a combination of the cholesterol lowering drugatorvastatin and osteoporosis medication zoledronic acid, both more commonly known by their respective trade names, Lipitor and Zometa, produce changes in the mammalian host and in the parasite that ultimately block parasite replication and spread of the infection.

"These two drugs have a strong synergy," said Moreno, who is also a member of UG

A's Center for Tropical and Emerging Global Diseases. "The mice we treated were cured from a lethal infection using this combination approach."

Moreno and her colleagues began working on this drug combination following a series of experiments with unexpected results. They created a genetically modified version of the parasite in the laboratory that lacked a specific enzyme essential for one of the organism's most basic functions.

Atorvastatin drug plus zoledronic acid may help treat toxoplasmosis

New clinical trial shows increased asthma control with FeNO-guided anti-inflammatory treatment

A new randomised clinical trial shows lower incidence of asthma exacerbations and increased asthma control with Fractional exhaled Nitric Oxide (FeNO)-guided anti-inflammatory treatment. The study has been published on the website of Journal ofAllergy and Clinical Immunology.

A total of 187 non-smoking asthma patients (18-64 years) with perennial allergy and on regular inhaled corticosteroid (ICS) treatment were recruited at 17 primary health care centres in Sweden, randomly assigned to two groups and followed for one year. One group was treated with standard of care whereas treatment of the patients in the other group were guided by FeNO. Aerocrine's patented FeNO test, with the NIOX® MINO® device was used in the study. In the standard of care group FeNO was blinded for both patient and physician.

"FeNO-guided anti-inflammatory treatment enabled the physicians to optimize the treatment with for example inhaled corticosteroids so that both over- and undertreatment can be avoided. This may be a useful tool in long-term management of patients with asthma", says Dr Jörgen Syk, General Practitioner at Runby primary care clinic, Stockholm, Sweden and being the principal investigator in the study.

Overall, FeNO-guided management resulted in improved asthma symptom control and reduced exacerbation frequency in adults with asthma. The FeNO-guided group reported almost 50% fewer asthma exacerbations without an increase in the used average dose of corticosteroids.

Although there was no difference in perceived quality of life (which was the primary endpoint of the study) between the groups, the FeNO-guided group reported fewer symptoms than the group following standard of care treatment.

Ref : http://www.jaci-inpractice.org/article/S2213-2198(13)00352-8/abstract

New clinical trial shows increased asthma control with FeNO-guided anti-inflammatory treatment