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New class of antibiotics discovered

WASHINGTON: In a breakthrough, scientists have discovered a new class of antibiotics to fight deadly bacteria such as methicillin-resistant Staphylococcus aureus and other drug-resistant bacteria that threaten public health.

The new class, called oxadiazoles, was discovered by University of Notre Dame researchers led by Mayland Chang and Shahriar Mobashery in silico (by computer) screening and has shown promise in the treatment of MRSA in mouse models of infection.

Researchers who screened 1.2 million compounds found that the oxadiazole inhibits a penicillin-binding protein, PBP2a, and the biosynthesis of the cell wall that enables MRSA to resist other drugs.

The oxadiazoles are also effective when taken orally. This is an important feature as there is only one marketed antibiotic for MRSA that can be taken orally, researchers said.

MRSA has become a global public-health problem since the 1960s because of its resistance to antibiotics.

In the US alone, 278,000 people are hospitalised and 19,000 die each year from infections caused by MRSA, said researchers.

Only three drugs currently are effective treatments, and resistance to each of those drugs already exists.

The researchers have been seeking a solution to MRSA for years.

“Professor Mobashery has been working on the mechanisms of resistance in MRSA for a very long time,” Chang said.

“As we understand what the mechanisms are, we can devise strategies to develop compounds against MRSA,” said Chang.

“Mayland Chang and Shahriar Mobashery’s discovery of a class of compounds that combat drug resistant bacteria such as MRSA could save thousands of lives around the world. We are grateful for their leadership and persistence in fighting drug resistance,” said Greg Crawford, dean of the College of Science at the University of Notre Dame.

The research is published in the Journal of the American Chemical Society.

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Scientists urge caution on antibiotic alternatives

The new treatments are intended to enable the patient to tolerate disease, and buy the immune system valuable time to get rid of the infection naturally

New types of drugs intended for use in place of antibiotics have been given a cautious welcome by scientists at the Universities of Liverpool and Edinburgh.

Researchers have been probing the long-term effectiveness of drugs being developed by the pharmaceutical industry. These work by limiting the symptoms caused by a bug or virus in the body, rather than killing it outright.

Becoming resistant

These treatments are designed to avoid the problem of infections becoming resistant to treatment, which has become widespread with antibiotics.

This approach is intended to enable the patient to tolerate disease, and buy the immune system valuable time to get rid of the infection naturally.

“Antibiotic resistance is a serious issue and these alternatives offer hope in solving the problem”

Researchers at the Universities of Liverpool and Edinburgh created a mathematical model to discover how drugs that limit the damage caused by disease could affect how infections spread and evolve.

They found that for infections where the symptoms are not linked to the spread of disease, these drugs may prevent disease from evolving too quickly. They will be useful over longer periods of time.

However, parasitologist, Dr Andy Fenton, from Liverpool’s Institute of Integrative Biology cautions that people given damage limitation treatments may appear healthy, but carry high levels of infection and so may be more likely to pass on disease. In addition, people with lesser symptoms could remain undiagnosed and add to the spread of disease.

Cautious

“Antibiotic resistance is a serious issue and these alternatives offer hope in solving the problem,” he said.

“However we should be cautious as it’s possible that in some cases these drugs may cause disease to spread.”

The study, ‘Limiting Damage during Infection: Lessons from Infection Tolerance for Novel Therapeutics’, was published in PLoS Biology. Read it here

Stop ‘abuse’ of antibiotics: Nobel laureate

HYDERABAD: “Antibiotics are not like the latest and the most powerful cars that you want to buy over the counter. Antibiotics should not be sold over the counter in India and should be sold only on the prescription of a doctor,” said Nobel laureaute Prof Venkatraman Ramakrishnan of the MRC Laboratory of Molecular Biology, Cambridge, England.

While delivering a lecture on “Antibiotics and the cell’s protein factory,” the first in the distinguished lecture series at the Centre for Cellular and Molecular Biology (CCMB-CSIR) at the IICT auditorium here on Friday, Prof Ramakrishnan held the jam-packed auditorium literally to ransom. Prof Ramakrishnan had won the Nobel prize for chemistry along with Thomas Steitz and Ada Yonath in 2009 for ‘studies of the structure and function of the ribosome’.

Prof Ramakrishnan said the ‘perfect magic bullet’ for fighting bacteria was yet to be developed as they become resistant to antibiotics over a period of time. While scientists the world over are working to find a way out to make antibiotics without side-effects, the Nobel laureate said that governments, social organisations and individuals should ensure that there is no abuse of antibiotics.

“If you need antibiotics, it means it is a sign of desperation. Antibiotics kill the protein synthesis,” he said. However, he exuded confidence that with the available technology, scientists can come out with new compounds as a solution to the problem of antibiotics causing side-effects. “Ideally, it should be the responsibility of the government and NGOs to fund programmes and not leave it to private companies to do the research and come up with drugs. Obviously, private companies have profit motive in mind,” he said.

Prof Ramakrishnan said the overuse of antibiotics has become a social problem. He said there should be enough surveillance to detect infections and treatment should be started immediately.

“In India, it is easy to buy a third generation antibiotic from a chemist without a prescription. This should stop,” he said.

In an interaction with the media, Prof Ramakrishnan said funds alone won’t suffice for India to produce better scientists. “Funds are important even to bring the best brains back to the country. What is even more important is providing the right kind of atmosphere, liberty and guidance. There should be no hierarchy, cronyism,” he said.

Asked if there was a possibility that he could collaborate with CCMB or any Indian institution, he replied in the negative explaining that his work keeps himself busy in the UK and for the kind of work he does, he can only collaborate with one who can contribute his part to the research.

“But there are scientists who are willing to collaborate with Indian scientists on problems relating to Indian conditions,” he said.

Drug at Srinagar children hospital not fake: govt

The state government on Sunday ruled out that the cause of infant deaths at Srinagar’s GB Panth hospital was due to “fake” drug.

“Pentavalent vaccine is not fake. It may not be the sole reason for infant deaths,” said minister for medical education Taj Mohi-u-Din.

There were protests over recent deaths of kids at the hospital. It was alleged that the drug was fake. “Those who attribute deaths to this vaccine should know it is supplied by the Government of India and is used all over country,” said the minister.

“There may be other reasons for infant deaths which need to be investigated,” he added.

A five-member union health ministry team is assisting investigations into the death of infants at the hospital. “We are waiting for their report,” said the minister.

Director family welfare, Dr Baldev Sharma said the department has collected samples from the children hospital. The five-member team has also visited Shopian, Baramulla and Budgam on Sunday.

“So far we have not found Pentavalent the cause of infant deaths. After thorough investigations we would make the facts public,” Sharma said.

Pentavalent vaccine, also known as Easy-Five, is given to protect infants from hepatitis-B, diphtheria, tetanus, pertussis and Hib (haemophilus influenzae type-b).

One pill for all heart problems

HeartCHANDIGARH: How often do you forget to pop that pill to control your shooting blood pressure? Or skip the aspirin tablet that could have prevented a stroke at night? Not anymore.

For the first time, doctors and researchers have come up with a single pill for all cardiovascular diseases (CVD), including high blood pressure and vulnerability to stroke, doing away with the pain of popping multiple pills to keep your heart healthy. Trials for this new pill – called the polypill – across Europe and India have proved successful, according to a study published on Wednesday in the Journal of the American Medical Association.

As many as 28 Indian institutes, including AIIMS, PGIChandigarh and George Institute for Global Health-India worked together as part of the study, planned by London’s Imperial College. The formulation for the drug was done by Dr Reddy’s Laboratories.

“Most patients with high BP require multiple drugs to keep it under control. This raises the problem of compliance over a prolonged period as patients often forget to take some of the pills. In India, compliance to multiple pills for CVD is as low as 10%. Polypill will take care of it,” said Dr Vivekanand Jha, executive director of George Institute for Global Health-India.

While studies have shown that patients with CVD do not take recommended medications in the long-term, the use of fixed-dose combinations (FDCs) like a polypill improves adherence to a large extent. The study showed adherence rate increasing by 20% with use of the polypill, a combination of aspirin, statin (cholesterol lowering drugs), and two blood pressure-lowering agents.

Funded by the European Commission’s Seventh Framework Program, the study has shown evidence, for the first time, about the risks and benefits of the single pill.

As many as 2,004 people, in the mean age of 62 and with high risk of CVD, initially participated in the study in India and across Europe between July 2010 and July 2011.

he trial follow-up concluded in July 2012. Previous trials have assessed short-term effects. At the end of the study on 1921 of the participants, conducted for an average 15 months, it was found that 829 (86.3%) of the 961 participants who were administered the polypill continued with it. In comparison, only 621 (64.7%) of the 960 participants continued with multiple pills as prescribed. But the study showed one limitation: If any of its components led to some adverse effect, the polypill had to be discontinued.

The study involved the Imperial College, London’s International Centre for Circulatory Health, The George Institute for Global Health-India, Centre for Chronic Disease Control, New Delhi, Royal College of Surgeons in Ireland, Dublin; Julius Center for Health Sciences and Primary Care, Utrech; Public Health Foundation of India, New Delhi and The George Institute for Global Health, Sydney.

“These new findings dispel several myths about the polypill. Despite the use of older medications and fixed doses, the polypill group improved blood pressure and cholesterol levels simply because those surevyed took recommended medications more regularly,” said Prof D Prabhakaran, executive director of the Centre for Chronic Disease Control.

Parliamentary panel on clinical trials seeks action against PATH

New Delhi: A Parliamentary standing committee says the government should act against a US-based non-profit for allegedly violating Indian laws while conducting clinical trials on hundreds of women and children in Gujarat and Andhra Pradesh—an allegation that is rejected by the American group.
The committee also made grave allegations of impropriety against the Indian Council of Medical Research (ICMR), the nation’s apex body for the formulation, coordination and promotion of biomedical research, and the drugs controller general of India (DCGI).
PATH carried out phase IV trials of human papilloma virus (HPV) vaccine for cervical cancer as part of a study in 2009. Phase IV safety surveillance is designed to detect any rare or long-term adverse effects over a larger patient population and longer time period than was possible during earlier phases of clinical trials.
During the trials, PATH administered Merck Ltd’s Gardasil vaccine on 108 girls aged 9-15, and GlaxoSmithKline Plc.’s Cervarix vaccine on 162 women aged 18-35. The study was suspended and an inquiry committee formed in April 2010 following the deaths of seven of those who were administered the vaccines.
However, after analysing the seven deaths—five from the Gardasil group and two from the Cervarix group—no common pattern to the deaths was found to suggest these were caused by the vaccines.
In its report presented to the Rajya Sabha on Friday, the committee urged the government to look into the roles of DCGI and ICMR for allegedly turning a blind eye to “irregularities” in the conduct of the trials.
PATH made a strong defence of its actions.
“We believe that by following the guidance provided by ICMR, as well as two state governments and three ethical review committees, we designed a project that met or exceeded the country’s existing regulatory standards for demonstration projects while providing the greatest health benefit to Indian women,” said Amy MacIver, director of media relations at PATH, in a statement issued on Friday.
But the parliamentary committee was scathing about ICMR, saying: “In their over-enthusiasm to act as a willing facilitator to the machinations of PATH, they have transgressed into the domain of other agencies which deserves the strongest condemnation and strictest action against them.”
It also questioned ICMR’s decision to promote the vaccines for inclusion in the Universal Immunization Programme even before an independent study on their utility and rationale was undertaken.
ICMR dismissed the committee’s criticism. “We have already conducted an inquiry on the deaths of the girls and no link was found between the deaths and the vaccine. The report was submitted to the ministry of health in 2010,” said Dr. Tanvir Kaur at the non-communicable diseases division of ICMR.
“The studies carried out by PATH were definitely not clinical trials,” she added.
The parliamentary panel also took on DCGI, saying it played a “questionable role”. Although DCGI initially maintained that clinical trial rules must be enforced, it stayed silent while the rules and regulations were violated, the panel said.
DCGI chief G.N. Singh responded, “Clinical trial regulations in India were not strict four years ago, but now we have a highly regulated regime.”
“We are taking the recommendations of the standing committee report in the right stride and will work on the suggestions. Such problems should not arise in the future,” said Singh, who heads the Central Drugs Standard Control Organization (CDSCO) as the DCGI.
The panel alleged that many of the consent forms for the tests had thumb impressions for signatures, or had been signed by hostel wardens. Obtaining informed consent from people participating in such drug studies is essential for clinical trials. In case of minors, forms are to be signed by parents or guardians.
The panel also raised the issue of including vulnerable and tribal populations in the trials, and the lack of preparedness to deal with adverse events.
The PATH statement said, “At the time of its review, ICMR determined the project was a post-licensure observational study and not a clinical trial.”
“The demonstration projects in India, Peru, Uganda and Vietnam generated important new evidence on the best ways to introduce HPV vaccines and are informing the work of governments across Africa, Asia, and Latin America to help prevent cervical cancer deaths,” PATH said.
The panel asked the ministry of health and family welfare to promptly report PATH’s alleged violations to the World Health Organization and UNICEF (the UN agency for children), and suggested that the National Human Rights Commission also look into the reported violations.
“It is shocking to see how an American organization used surreptitious methods to establish itself in India, performed trials on hundreds of women and children in our country with so many violations, and two of our government agencies rushed to help this organization,” said Dr. Chandra M. Gulhati, editor of Monthly Index of Medical Specialities.
India approved 475 clinical trials for “new chemical entities” not used as drugs elsewhere in the world between January 2005 and June 2012, according to documents submitted by DCGI in the Supreme Court.
The documents said 11,972 adverse effects, excluding deaths, were reported in the period, with 506 of these being directly attributable to the trials. They put deaths from trials at 2,644 in the past five years.
In a 3 January ruling, the apex court revoked the powers of the Indian drug regulator to approve trials for new chemical entities, placing the responsibility on the health secretary, who was asked to personally vet all approvals.
On 26 July, the Supreme Court directed the Union government to come up with a new regulatory regime for clinical trials that reflects the concerns of all stakeholders.
The National Institutes of Health (NIH), part of the US department of health and human services, cancelled about 40 ongoing clinical trials in India after the health ministry tightened regulatory norms for trials, Mint reported in July.
The health ministry amended the Drugs and Cosmetics Act with new provisions for regulation and ethical supervision of trials; compensation of trial subjects, and mandatory accreditation of all stakeholders, including institutional review boards, research institutions, sponsors and contract research organizations.

‘Female sperm’ and ‘male eggs’ may be possible

Researchers have suggested that it may be possible in the future to create sperm from women and eggs from men – a feat, that if achieved, could revolutionise infertility treatments.

Katsuhiko Hayashi of Kyoto University in Japan and his senior professor Mitinori Saitou used skin cells from mice to create primordial germ cells or PGCs. PGCs are the common precursor of both male and female sex cells.

These cells were then developed into both sperm and eggs. Scientists used these to create live-births via in vitro fertilisation.

The technique offers numerous possibilities for reproductive medicine. It may allow infertile women to have babies by creating eggs from their skin cells, and also make it possible for sperm and eggs cells to be created from either males or females, ‘The Independent’ reported.

In the technique, pluripotent stem cells were extracted from early-stage embryos and somatic cells, and were then converted into PGCs using signalling molecules.

These germ cells were transplanted into the ovaries and testes of living mice to develop. Once these cells were mature they were extracted and used to fertilise one another in vitro.

The initial research took place in October last year, with researchers claiming that the live-births were merely a ‘side effect’ of the research to demonstrate that the creation of PGCs had been successful.

Other researchers have replicated the production of PGCs but could not succeed in producing live births. The scientists involved also have many other hurdles to overcome including the production of ‘fragile’ and ‘misshapen’ eggs, wrote David Cyranoski in ‘Scientific American’.

The Japanese team is now working on monkey embryos and believe they could repeat the mouse work in monkeys within 5-10 years, with the creation of human PGCs following shortly after.

While making PGCs for infertility treatment will be a huge jump, many scientists are urging caution as embryonic stem cells frequently pick up chromosomal abnormalities, genetic mutations and epigenetic irregularities during culture.

Hayashi has also said that a viable infertility treatment could be 10 or even 50 years in the future.

“My impression is that it is very far away. I don’t want to give people unfeasible hope,” he said.

Antipsychotic drug use in kids ups risk of type 2 diabetes

Prescribing antipsychotic drugs to kids and young adults having behavioural problems or mood disorders could put them at a risk for acquiring type 2 diabetes, a study has showed.

The Vanderbilt University Medical Center study shows that young people using medications like risperidone, quetiapine, aripiprazol and olanzapine led to a threefold increased risk of developing type 2 diabetes within the first year of taking the drug.

Senior author Wayne A. Ray, Ph.D., professor of Preventive Medicine, said that while other studies have shown an increased risk for type 2 diabetes associated with the use atypical antipsychotic medications, this is the first large, well-designed study to look at the risk in children.

The authors noted that the use of these drugs for non-psychosis-related mood, attention or behavioral disorders in youth/children now accounts for the majority of prescriptions.

Ray said that as they wanted to address this question of risk for indications for which there were therapeutic alternatives, they deliberately excluded those taking antipsychotics for schizophrenia and other psychoses; thus, our entire sample consisted of patients for whom there were alternatives to antipsychotics.

State-provided, de-identified medical records were examined for TennCare youths ages 6-24 from 1996 through 2007.

During that time children and youth who were prescribed treatment with atypical antipsychotics for attention, behavioral or mood disorders, were compared with similar youth prescribed approved medications for those disorders.

Even with the further elimination of certain disorders that are commonly associated with diabetes, like polycystic ovarian syndrome, those taking antipsychotics had triple the risk of developing type 2 diabetes in the following year, with the risk increasing further as cumulative dosages increased. The increased risk persisted for at least a year after the medications were stopped.

Ray and his colleagues point out developing type 2 diabetes is still rare in this age group. Of the nearly 29,000 children and youth in the antipsychotic medication group and 14,400 children in the control group, 106 were ultimately diagnosed and treated for type 2 diabetes.

The study has been published in the journal JAMA Psychiatry.

Scientists discover genetic causes of pancreatitis

PancreatitisHYDERABAD: A team comprising doctors from Asian Institute of Gastroenterolgy (AIG) and scientists from Centre for Cellular anda Moleculr Biology (CCMB) along with international researchers have discovered hitherto unknown genetic causes for Chronic Pancreatitis in Indian populations. These findings will be published in the prestigious international journal Nature Genetics.

Addressing the media here on Sunday, CCMB director C H Mohan Rao said the study showed genetic mutations found in western populations need not necessarily be found in Indian populations. Pancreatitis is an inflammatory disorder of the pancreas, the organs which produce essential digestive enzymes in addition to producing insulin for sugar metabolism in the body.

The decade long research by Dr G R Chandak of CCMB, Dr D Nageshwar Reddy and Dr G V Rao of AIG representing India, involved genetic analysis of 300 patients, from Europe and Asia, afflicted with Tropical Calcific Pancreatitis which is one type of pancreatitis found largely in populations in south India. The research team’s recent discovery was identification of a mutation in an essential enzyme producing Carboxypeptidase A1 gene (CPA1) in the Indian patients which caused functional loss of the enzyme.

Dr Chandak said, “The study has found a novel mutation in CPA 1 gene that was not found in non-Indian patients. This condition has an early onset in the patients that is many of them were young people.

The study could pave the way for improved diagnosis in India populations later.”

The team’s previous discoveries have included identification of mutations in two other genes corroborating the idea that pancreatitis has strong genetic factors and not just environmental or nutritional factors as was previously thought.

New malaria vaccine shows promise in clinical trials

VaccineA new malaria vaccine, which is being developed in the US, has shown promising results in early stage clinical trials, scientists say. Researchers found that high doses of the vaccine protected 12 out of 15 patients from the disease. The vaccine involves injecting live but weakened malaria-causing parasites directly into patients to trigger immunity.

“We were excited and thrilled by the result, but it is important that we repeat it, extend it and do it in larger numbers,” said lead author Dr Robert Seder, from the Vaccine Research Center at the National Institutes of Health, in Maryland. Previous research has found that exposure to mosquitoes treated with radiation can protect against malaria. But studies have shown that it takes more than 1,000 bites from the insects over time to build up a high level of immunity.

A US biotech company called Sanaria took lab-grown mosquitoes, irradiated them and then extracted the malaria-causing parasite (Plasmodium falciparum), all under the sterile conditions. These living but weakened parasites are then counted and placed in vials, where they can then be injected directly into a patient’s bloodstream. This vaccine candidate is called PfSPZ.

To carry out the Phase-1 clinical trial, the researchers looked at a group of 57 volunteers, none of whom had had malaria before. Of these, 40 received different doses of the vaccine, while 17 did not. They were then all exposed to the malaria-carrying mosquitoes, ‘BBC News’ reported. The researchers found that for the participants not given any vaccine, and those given low doses, almost all became infected with malaria.

However, for the small group given the highest dosage, only three of the 15 patients became infected after exposure to malaria. “Based on the history, we knew dose was important because you needed 1,000 mosquito bites to get protection – this validates that,” Seder said. “It allows us in future studies to increase the dose and alter the schedule of the vaccine to further optimise it. The next critical questions will be whether the vaccine is durable over a long period of time and can the vaccine protect against other strains of malaria,” he said. The results were published in the journal Science.

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