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Natural compounds derived from plants could yield hundreds of new drugs

NYBG scientist says the plant world has “great potential” as a source of new medicines

There are probably at least 500 medically useful chemicals awaiting discovery in plant species whose chemical constituents have not yet been evaluated for their potential to cure or treat disease, according to a new analysis by a New York Botanical Garden scientist who has more than 15 years of experience in collecting plants for natural-products discovery programs.

Currently, 135 drugs on the market are derived directly from plants; the analysis indicates that at least three times as many disease-fighting substances have yet to be found that could be developed into drugs or used as the basis for further drug research.

“Clearly, plant diversity has not been exhausted, and there is still great potential in the plant world,” said James S. Miller, Ph.D., Dean and Vice President for Science at the Botanical Garden.

Dr. Miller’s analysis, “The Discovery of Medicines from Plants: A Current Biological Perspective,” is published in the December issue of the peer-reviewed journal Economic Botany.

To arrive at his estimate, Dr. Miller used a formula based on the ratio of the number of drugs that have been developed from plants to the number of plants that were screened to find those drugs. He then applied that ratio to the number of plant species that have not yet been screened.

Because of uncertainties in some of those numbers, the formula yields a range of potential drug discoveries. While there is no general agreement among botanists about the number of plant species that are likely to exist, Dr. Miller concluded that there are 300,000 to 350,000 species of plants. Of those, he determined that the chemistry of only 2,000 species has been thoroughly studied, and perhaps only 60,000 species have been evaluated even partially for medicinally useful chemicals.

Working with those numbers, Dr. Miller calculated that there are likely to be a minimum of 540 to 653 new drugs waiting to be discovered from plants; the actual number could be much greater.

“These calculations indicate that there is significant value in continuing to screen plants for the discovery of novel bioactive medicinally useful compounds,” concludes Dr. Miller, who has run natural-products discovery programs that have collected specimens in North America, Central and Southeast Asia, and Africa for government agencies, pharmaceutical companies, and academic programs.

As part of his Economic Botany paper, Dr. Miller reviews the disappointing history of past plant-screening efforts and evaluates the potential for future programs.

Technological advances in the 1970s and 1980s gave medical researchers the capacity to evaluate large numbers of plant samples. That prompted the federal government and large pharmaceutical companies to institute aggressive plant collecting and screening programs. Those programs led to the development of several important drugs such as Taxol from Taxus brevifolia (used in cancer treatment) and Camptothecin from Camptotheca acuminata (derivatives of which are used to treat cancer). Other drugs indirectly trace their discovery to natural-products research, including the anti-viral Oseltamivir, which derives from Illicium anisatum and is marketed in the United States as Tamiflu.

The number of drug discoveries, however, was substantially less than anticipated. By the early 2000s, many of the large pharmaceutical companies had abandoned their efforts.

Dr. Miller argues that one possible explanation for the low yield is the relatively crude way in which plant extracts were tested for their pharmaceutical potential. Plants may contain as many as 500 to 800 different chemical compounds, but the screening programs of the late 20th century used extracts made from a whole plant or at best extracts that contained many hundreds of compounds.

Under those circumstances, one compound may interfere with the action of another, or the amount of one compound may be too small to register in a mix of hundreds of chemicals.

To correct this problem, new technologies now allow researchers to separate complex mixtures of natural products into a “library” of relatively pure compounds that can be tested individually. A 2002 study demonstrated that testing such libraries dramatically improves discovery rates.

Bringing these advances together with refinements in collecting strategies could lead to what Dr. Miller calls a “second renaissance” of natural-products discovery.

Miller undertook his analysis to highlight the fact that despite past collecting programs, the plant world represents a poorly explored source of potentially lifesaving drugs. That adds urgency, he said, to efforts to conserve natural habitats so that species are not driven to extinction before they can be studied.

“The natural world has a great and diverse array of interesting chemicals that have been only minimally studied and still hold considerable potential,” he writes.

Contact: Stevenson Swanson
718-817-8512
The New York Botanical Garden

Source: http://www.eurekalert.org/pub_releases/2011-12/tnyb-nmc121211.php

Links related to natural compounds and plant extracts:

Natural Compounds

Plant Extracts

Natural and Natural Derivatives Libraries

Nigeria: FG and Cost of Cancer Screening

THE Federal Government’s recent directive to its hospitals to reduce the cost of cancer screening, though very commendable, is long overdue, considering that late diagnosis of the disease has resulted in the high rate of cancer related deaths in the country.

Cancer is one of the leading causes of deaths in the world, especially in developing countries, which carry about 80 per cent of the burden, globally. Unfortunately, in Nigeria with over 160 million people, going by the latest global report on population, detection of the killer non-communicable disease (NCD) is usually late.

Minister of Health, Prof. Onyebuchi Chukwu, who announced the reduction in the cost of screening for breast, cervical, prostate and colon cancers during the recent 17th Annual Conference of the Nigerian Association of Urological Surgeons (NAUS) in Abuja, said the directive to provide screening services at affordable prices is to ensure that the disease is detected early.

Other measures being taken by government to tackle the cancer scourge, he said, include equipping fully the University of Port Harcourt Teaching Hospital, the Federal Medical Centre, Gusau, Zamfara State and the Vesico Virginal Fistula (VVF) Centre, Abakaliki, Ebonyi State with mammography machines, cryoprobes, video culposcopes, ultrasound, loop electrosurgical excision procedure and enzyme-linked immunosorbent assay machines, so that these institutions can serve as referral centres for those who screen positive for pre-malignant lesions.

With the World Health Organisation (WHO) projecting that about 84 million people may die of cancer by 2015 if urgent steps are not taken to arrest the scourge, there is, indeed, need to facilitate a national policy on cancer management, starting with free or significantly reduced cost of cancer screening.

These moves by the Federal Government are steps in the right direction, considering that cancer is one disease that is no respecter of social status and one that has continued to deal devastating blows on the productive segments of the nation’s economy.

Among notable Nigerians whose lives were cut short by cancer are human rights activist and lawyer, Chief Gani Fawehinmi, who died in 2009 after a prolonged battle with lung cancer, Dr. Bekolari Ransome-Kuti, a medical doctor and human rights activist and Yemi Tella, coach of the Nigerian 2007 FIFA U-17 World Cup winning team.

Maryam, wife of former military president, Gen. Ibrahim Babangida, died of ovarian cancer on December 27, 2009 at California’s City Hope Hospital in the United States, aged 61, while the wife of Edo State Governor, Adams Oshiomhole, was swept away by cancer of the breast.

Presently, about two million cancer cases are said to be recorded in Nigeria with an estimated 350,000 new cases being diagnosed annually. Of the two million, only 10 per cent or about 200,000, have access to hospitals with radiotherapy facilities, while out of the number, only five per cent, about 10,000, have the resources to go abroad where they pay between $10,000 and $15,000 per patient for a three to five-weeks course of radiotherapy.

While about 27 per cent of the two million cases are suffering from breast cancer, about 25 per cent are cancer of the cervix cases. And of these two cancers that are devastating women in Nigeria, one has good prognosis, if detected early, while the other can be prevented. Yet they continue to cause untold hardships and deaths simply because of the dearth, and high cost, of facilities, especially for early detection, among other constraints.

Nigeria’s mortality and morbidity statistics for cancer are said to be high due to the late presentation syndrome involving 83-87 per cent of cancer patients, simply because the awareness level of Nigerians, especially women, is very low, even as this is dogged by superstition and cultural restraints.

As a matter of fact, some medical experts have argued that even the estimated 350,000 new cases of cancer diagnosed annually in Nigeria is far from the true figure of the cancer crisis in the country, insisting that a large number of cancers are not detected as majority of Nigerians are poor and live in rural areas, far removed from health facilities.

Lack of, or inadequate, research into this debilitating disease is also a major challenge. Nigeria, for instance, is said to contribute little or nothing to the global body of literature on cancers and most of these contributions are hospital based, perhaps representing the tip of the iceberg as majority of Nigerians live in rural areas, unable to access any health facilities.

As such, the cancer awareness efforts and screening methods to enhance early detection do not seem to have had much impact on the nation.

No doubt, the problems of lack of access to quality health care, ignorance, poverty and poor co-ordination of issues of health education complicate issues. For instance, facilities such as computerised tomography (CT) and Magnetic Resonance Imaging (MRI) are difficult to come by, and when available, the cost of accessing such facilities put them out of reach of the average citizen.

Of more concern is the fact that clinical services for cancer are grossly inadequate and poorly distributed. Only a few centers have functioning radiotherapy equipment, and though radiologic services are said to be generally available, access is seriously limited by high cost.

So, while the Federal Government’s move to reduce the cost of cancer screening in federal hospitals is commended, we call on the authorities to ensure that the screening equipment are available and more easily accessible, especially in the rural areas, while a more vigorous and better co-ordinated effort into cancer research must be encouraged in institutions across the country.

Source: http://allafrica.com/stories/201111241060.html

NMR Fine-Tuned for High-Content Metabolomics Screening

Scientists report on the development of a nuclear magnetic resonance (NMR)-based method forscreening the metabolomic response of drug-treated mammalian cells to drug therapy. TheSanford-Burnham Medical Research Institute, and Rady Children’s Hospital investigators, say the highly sensitive, fast, and simple method is carried out in 96-well format, and could have particular utility as a method for high-throughput primary screens. The preparation technique takes just five minutes to metabolically inactivate and lyse hundreds of drug-treated samples, and a metabolomic screening of around 100 samples can be carried out in 24 hours.

Giovanni Paternostro, M.D., and colleagues describe their approach, analyze the results of validation studies on drug-treated cancer cell lines, and evaluate the technique for screening a kinase inhibitor library. Their work is described in Nature Communications in a paper titled “Metabolomic high-content nuclear magnetic resonance-based drug screening of a kinase inhibitor library.”

High-throughput screening (HTS) is widely used as a tool in drug discovery, but most screens monitor a single variable, which is often related to activity on a single target, the researchers explain. Although high-content screening (HCS) approaches that provide multivariate readouts are gaining ground, these techniques generally rely on automated digital microscopy.

The technique developed by the Sanford-Burnham researchers involves seeding cells into a 96-well plate and treating them with several drugs. The cells’ metabolism is then quenched using sodium dodecyl sulphate (SDS), and the cells lysed using ultrasonication, in an overall process that takes just five minutes. The entire content of the well, including endo- and exo-metabolome, is then transferred into an NMR tube for analysis.

The team needed to address the relative contribution of the intracellular metabolome to the NMR spectrum acquired on the well content, including both medium and the lysed cell metabolomes. To answer this they generated NMR spectra on the entire content of the well (i.e., both endo- and exo-metabolomes), and also on the exometabolome, the endometabolome, and the medium. They found that major NMR signals arose from the extracellular metabolites, but several signals arising from the intracellular metabolites were also detected, for example glutamate, choline, and phosphocholine. Importantly, they found that spectra acquired on samples containing both endo- and extracellular metabolomes included signals resulting exclusively from the endometabolome—such as phosphocholine and glycerophosphocholine—which didn’t overlap with other extracellular resonances.

The researchers evaluated the sensitivity of the approach for monitoring metabolic changes induced by 24 hours of drug treatment, on both suspension (CCRF-CEM human leukemia cells) and adherent mammalian carcinoma cell lines (human SKOV-3 ovarian cancer cells). The cell lines were treated using either dexamethasone (Dex), rapamycin (Rap) dichloroacetate (DCA), vincristine (Vin), and different doses of L-asparaginase. The resulting spectra, generated using three different 1H NMR pulse sequences, showed that, as expected, the response to drug treatment by the more resistant SKOV-3 cells was far less pronounced compared with the CCRF-CEM cells. Encouragingly, the NMR screening approach could also be applied to detecting metabolic changes in response to forms of intervention, such as the transfection of HeLa cells the microRNAs mir-121 and mir-16. These results indicated that mir-16 induced a greater degree of metabolomic change than mir-121.

Because the developed technique requires just a small amount of cells, the investigators suggest in might have utility in studying drug response directly in primary cells, and so avoid phenotypic changes that can be induced by growth in culture. They evaluated metabolomic changes in cells isolated from bone marrow specimens of an untreated AML patient, in response to treatment with Rap and L-asparaginase, at different doses. In order to specifically highlight metabolic changes in the cells themselves, the NRM spectra acquired on unconditioned medium were compared to those acquired on AML primary cells with and without drug administraton. The resulting spectra clearly showed distinct changes in the metabolome of the primary cells as a result of drug treatment. Further analyses indicated these changes were more pronounced in response to L-asparaginase than for Rap therapy.

The team then moved on to use the approach for carrying out screening of metabolomic response to a kinase inhibitor (KI) library. Multiple rounds of screening on KIs with well-characterized and less well-characterized effects on the metabolome confirmed the utility of the technique for identifying metabolic alterations resulting from inhibitor treatment. More specifically, four hits were validated from their action on the well-characterized lactate to pyruvate ratio parameter.

“We believe that this NMR-based assay might find an immedi­ate relevant application for screening a large number of individual or combinatorial drug interventions, reducing the number of pos­sible drugs to be studied in more detail,” the authors state. “In addition, it might find an immediate relevant application into clinical studies.”

They admit that the main drawback of NMR is the relatively limited number of compounds that can be detected. However, they stress, “although not comprehensive of all metabolites, the wealth of information obtained from the multivariate metabolic readout is of great advantage for drug screening purposes.” The method could therefore represent a valuable high-throughput primary screen, which could then be followed by secondary assays to analyze the exo- and endo-metabolomes of selected hits using combinations of different anaytical platforms.

“There are many other possible applications of this method, for example lactate production and substrate utilization in cancer versus noncancer cells, or gluconeogenesis from different sub­strates in hepatocytes, relevant to diabetes. Importantly, because the measurements are performed within a global metabolic profile, they can also provide a series of compounds with partially different mechanisms of actions, which can be explored for potential syner­gies.”

Source: http://www.genengnews.com/gen-news-highlights/nmr-fine-tuned-for-high-content-metabolomics-screening/81245988/

Ancient Chinese cures translate into modern Western medicines

The Chem-TCM is the most comprehensive database of its kind and translates more than 12,000 chemicals from more than 300 Chinese herbs used in traditional Chinese medicine (TCM) into Western terminology.

“Future researchers will now be able to better understand the chemical basis of remedies that have been in use for thousands of years,” says David Barlow of King’s College London (KCL), who has helped to develop the database.

TCM chemicals are rarely used as raw materials to develop Western drugs because their complex nature makes the registration process difficult.

The database may also answer one of TCM’s regulatory challenges in the United Kingdom. An EU directive came into effect in the UK this May that makes it illegal for individual practitioners to sell TCM over the counter, except for varieties registered with the UK drug safety watchdog, the Medicines and Healthcare Products Agency.

read more…

XXI Century Database of Traditional Chinese Medicine Released

October 18, 2011

A comprehensive database developed by King’s College London researchers that features the chemical components found in traditional Chinese medicines has been released to market this month, allowing researchers to explore age-old remedies in the search for tomorrow’s new drugs.

Provided under licence to Tim Tec LLC, a US-based life science supplier company, the ‘Chem-TCM’ database is the most comprehensive of its kind. Featuring over 12,000 chemicals found in plants used in Chinese medicine, the database provides a valuable research tool for the pharmaceutical and biotechnology industries, academic researchers, and the medical profession (including the complementary health sector).

Part-funded by Innovation China UK (ICUK), the database has been developed through collaboration between researchers in the Institute of Pharmaceutical Science at King’s, Dr David Barlow, Dr Thomas Ehrman and Professor Peter Hylands, and the Shanghai Institute of Materia Medica (SIMM).

To create the Chem-TCM database, the King’s researchers analysed patterns in the known and predicted biological activities of 12,000 chemicals from over 300 Chinese herbs in relation to their usage in traditional Chinese medicine. Their results reveal that many categories in Chinese medicine are translatable into Western terminology. Dr David Barlow said: ‘Traditional Chinese medicine has undergone a remarkable renaissance in recent years. However, the unique language used to describe categories of medicines has hindered effective understanding of one of the most developed and mature systems of alternative medicine in existence.

‘With the Chem-TCM database, future researchers will now be better able to understand the chemical basis of remedies that have been in use for thousands of years. This is likely to be of benefit both in the search for new drugs and, equally significantly, in understanding how Chinese medicine works.’

Chem-TCM features four major parts: chemical identification, botanical information, predicted activity against Western therapeutic targets, and estimated molecular activity according to traditional Chinese medicine categories.

Dr. Marat Niazoff, CEO of TimTec LLC, said: ‘This database is a comprehensive attempt to link Chinese and Western medicine on the molecular level. It is a great contribution to the further study of natural products and their pharmacological potential. The database gathers diverse structural material and a wealth of phytochemical information, opening new possibilities for virtual screening in particular.’ With over 15 years of experience in serving life-science R&D and established global customer base TimTec is well positioned to assume product development and distribution role. Chem-TCM commercial license is the protected adaptation of ChemDBsoft, TimTec chemical records and database managements software. TimTec welcomes this unique database product to its offerings.

Manyi Cristofoli, Director of ICUK, said: ‘I am pleased another ICUK-funded proof-of-concept project has now been commercialised in the pharmaceutical industry – this is a very good example of how academia and industry can successfully collaborate for innovation at a truly international level. The partnership with TimTec opens up a new global channel to jointly realise the wide potential in traditional Chinese medicine.’

King’s College London

King’s College London is one of the top 30 universities in the world (2011/12 QS international world rankings), and was The Sunday Times ‘University of the Year 2010/11′, and the fourth oldest in England. A research-led university based in the heart of London, King’s has nearly 23,500 students (of whom more than 9,000 are graduate students) from nearly 140 countries, and some 6,000 employees. King’s is in the second phase of a £1 billion redevelopment programme which is transforming its estate.

King’s has an outstanding reputation for providing world-class teaching and cutting-edge research. In the 2008 Research Assessment Exercise for British universities, 23 departments were ranked in the top quartile of British universities; over half of our academic staff work in departments that are in the top 10 per cent in the UK in their field and can thus be classed as world leading. The College is in the top seven UK universities for research earnings and has an overall annual income of nearly £450 million.

King’s has a particularly distinguished reputation in the humanities, law, the sciences (including a wide range of health areas such as psychiatry, medicine, nursing and dentistry) and social sciences including international affairs. It has played a major role in many of the advances that have shaped modern life, such as the discovery of the structure of DNA and research that led to the development of radio, television, mobile phones and radar. It is the largest centre for the education of healthcare professionals in Europe; no university has more Medical Research Council Centres.

King’s College London and Guy’s and St Thomas’, King’s College Hospital and South London and Maudsley NHS Foundation Trusts are part of King’s Health Partners. King’s Health Partners Academic Health Sciences Centre (AHSC) is a pioneering global collaboration between one of the world’s leading research-led universities and three of London’s most successful NHS Foundation Trusts, including leading teaching hospitals and comprehensive mental health services. For more information, visit: www.kingshealthpartners.org.

The College is in the midst of a five-year, £500 million fundraising campaign – World questions|King’s answers – created to address some of the most pressing challenges facing humanity as quickly as feasible. The campaign’s three priority areas are neuroscience and mental health, leadership and society, and cancer. For more information, please visit www.kcl.ac.uk

TimTec

TimTec LLC is a privately held company located in Newark, Delaware, USA. It was founded in 1995 to begin its work in the areas of acquisition and distribution of synthetic organic and natural compounds, custom synthesis, scientific software and laboratory equipment to become a full service partner for drug discovery.

TimTec has developed strong in-house expertise in the design of screening products to offer a full line of libraries and compound sets of various specialisation for different assays. In addition, the company provides compound management, custom formatting and computational services.

www.chemtcm.com , www.timtec.net, or info@timtec.net


Innovation China UK

Funded by HEIF3 and BIS Global Partnership Fund, the Innovation China UK (ICUK) is a collaboration programme supporting joint innovation and knowledge transfer between the UK and China. Based at Queen Mary Innovation Limited – a wholly-owned subsidiary company of Queen Mary University of London, ICUK provides a full range of services to UK companies and HEIs seeking to develop and commercialise their research and technology in the Chinese market. www.icukonline.org

Body & Mind – HEALTH U.S. Doctor Cautious About HIV Vaccine

A New York City-based infectious disease specialist said a new vaccine developed by Spanish scientists, which could turn HIV into minor infection status, is reason to be cautiously optimistic.

Dr. Joseph Rahimian said Thursday news of an HIV vaccine is certainly exciting, but questions remain.

“An HIV vaccine has been the holy grail for infectious disease doctors for a very long time,” Rahimian said. “ There are a lot of people interested in creating one and obviously a lot of demand for it, so there would be a lot of excitement if this research is accurate.”

The vaccine, developed by scientists at the Spanish Superior Scientific Research Council (CSIC) in Madrid, works by training the immune system to detect HIV and learn how to combat the virus.

In a trial involving 30 healthy volunteers, scientists found that 90 percent of those who were given the MVA-B vaccine developed an immunity against the virus and 85 percent maintained this for a year.

Professor Mariano Esteban, from CSIC, said, “MVA-B vaccine has proven to be as powerful as any other vaccine currently being studied, or even more.”

He said the vaccine was like showing the body a picture of the HIV, “so that it is able to recognize it if it sees it again in the future.”

“If the virus enters the body and tries to develop in a cell, the immune system is ready to inactivate the virus and destroy the infected cell,” he added. Scientists hope that if bigger trials are successful, HIV would no longer cause AIDS and would be much less contagious.

‘”If this genetic cocktail passes Phase II and Phase III future clinic trials, and makes it into production, in the future HIV could be compared to herpes virus nowadays,” according to the study.

However, Rahimian said this study needs much more room to grow.

“The population that they used is very small, and they followed them out to one year. So one important question is how long does this last for? A vaccine that has to be given repeatedly every year is less exciting than a vaccine that can give long-term immunity,” he said.

On the other hand, Rahimian pointed out there are some vaccines given every year, which are successful, like the flu shot.

“I would say many people have tried to create vaccines, and it is a very difficult task, so any enthusiasm for a successful vaccine is guarded,” he said.

Source: http://www.foxnews.com/health/2011/09/29/new-vaccine-could-turn-hiv-into-minor-infection/

Insulin May Help Treat Alzheimer’s

Researchers are investigating insulin as a possible treatment for Alzheimer’s disease, and in a preliminary study, the results look promising.A study in the journal Archives of Neurology suggests that intranasal insulin – that is, delivered through the nose – may help with cognition and functioning in patients who have both mild and more severe dementia.It’s premature to think of this as a treatment; the study only looked at 104 people, and needs to be repeated in much larger groups before it can be deemed effective. But it sets the stage for broader clinical trials.Recent research has suggested that insulin plays an important role in a number of brain functions, in addition to regulating blood sugar. Insulin promotes cell repair and cell genesis, so the thinking is that it could actually modify the course of Alzheimer’s disease, says lead study author Suzanne Craft, professor of psychiatry at VA Puget Sound and University of Washington.It also appears to protect against the toxic effects of beta-amyloid, the protein involved in the brain plaques associated with dementia. Insulin also prevents the formation of the toxic form of tau, a biomarker found in the cerebrospinal fluid of Alzheimers’ patients, Craft said.”What we saw was that for the insulin-treated patients, the ones who had improvement in memory and function had improvement in spinal fluid biomarkers,” she said.The goal of this study was to supplement and normalize the insulin levels in the brain without affecting levels in the rest of the body. This was done with a device that was designed to deliver insulin through the nose to the brain without getting too much into the blood.Researchers tested patients who had either early Alzheimer’s or mild cognitive impairment, a team for the early stages of dementia.Patients treated with insulin were able to remember information over a period of time better than those who got placebo; in fact, performance improved 20%. They also showed an enhancement in brain glucose metabolism in some areas; those who received placebo tended to show a decline.Alzheimer’s patients in the insulin group benefited more in terms of daily function than those with mild cognitive impairment, but by definition mild cognitive impairment does not greatly impair daily functioning.The treatment had the mild side effects of occasional mild headache and runny nose, but had a good safety profile generally, Craft said.In patients with mild cognitive impairment, researchers observed improvement in daily function and general cognitive abilities.But researchers don’t know what would be the optimal dosing and schedule of intranasal insulin for treating dementia; that is still an open question.So what does this mean for diabetics who already give themselves daily injections of insulin to manage their condition? Researchers don’t yet understand how much of that insulin is actually getting into the brain, Craft said; and if you’re not diabetic, having high levels of insulin in the blood is probably not good in the long run, so no one should experiment with this at home. Diabetes is a known risk factor for Alzheimer’s, but there are a lot of unanswered questions about that connection.

Source: http://www.kxly.com/health/29172695/detail.html

7TH DUESSELDORF SYMPOSIUM ON IMMUNOTOXICOLOGY Biology of the Arylhydrocarbon Receptor

Heinrich Heine University Duesseldorf
September 21 – 24, 2011

AhR research has taken great momentum recently, with a number of seminal discoveries, especially regarding its role in physiological events. This has opened new arenas, attracted new groups into the field, and led to a steep interest in the potential of AhR as a therapeutic target for the immune system, cancer and other diseases.

We invite you to join us for this exciting meeting on the biology of AhR.

Presentations by international renowned speakers.

Sessions will cover

  • AhR and Signaling
  • AhR and Skin biology
  • AhR and Immunology
  • AhR and Neurobiology
  • AhR and Translational Medicine

We invite you to register, submit an abstract and join us for three days of exciting presentations. Opportunities for oral presentations from selected abstracts will be scheduled as well. We look forward to lively scientific exchange.

The meeting will take place from September 21-24, 2011 at the University of Düsseldorf, Germany, Lecture Hall 13B.

Browse Aryl Hydrocarbon Receptor (AhR) Ligands

Canadian-made virus shows promise as cancer treatment

An Ottawa-based research team has developed a virus that is showing promise as a new way of attacking and shrinking cancer tumours while leaving healthy tissue alone.

It’s early days in the still-experimental field of therapeutic cancer viruses, called oncolytic viruses. But this new study from researchers from the Ottawa Hospital Research Institute (OHRI) and the University of Ottawa advances the field a little further by showing that the virus is safe in most patients.

For the study, researchers recruited 23 advanced cancer patients whose cancer had spread to multiple organs. All had failed to respond to the usual treatments and all were in the final stages of the disease.

The patients agreed to receive a single infusion of an experimental virus into their blood, called JX-594.

JX-594 is a form of vaccinia virus that’s been used as a live vaccine against smallpox. The JX-594 virus has been genetically engineered to enhance its natural anti-cancer properties.

The doctors tried out five doses of the virus, and then took biopsies of the tumours eight to 10 days later.

The researchers found that seven of the eight patients in the highest dose groups had evidence that the virus was in place and replicating in their tumours — and not in normal tissues.

What’s more, six of eight patients in the two highest dose groups experienced a shrinking or stabilization of their tumours, while those in lower dose groups saw less of this effect.

None of the 23 patients experienced significant side effects from the virus injection, with the most common side effect being mild to moderate flu-like symptoms that lasted less than one day.

The study, which is published in the journal Nature, was designed primarily to test the safety of the virus, not to cure the patients. In fact, some of the patients later died of their disease.

But the observation that some patients saw their tumours shrink was a welcome discovery.

Dr. John Bell, one of the study’s co-authors and a researcher at OHRI says it’s exciting that the virus led to results after just one dose.

“Of course, we will need to do more trials to know if this virus can truly make a difference for patients,” he said in a statement.

Bell says the advantage of therapeutic viruses is that they can be sent through the blood, infect the cancer tumours and leave the healthy tissue alone. It’s possible that oncolytic viruses could one day offer an alternative to conventional chemotherapy and radiation treatment, which tend to destroy healthy cells as well as cancer cells.

“Oncolytic viruses are unique because they can attack tumours in multiple ways, they have very mild side effects compared to other treatments, and they can be easily customized for different kinds of cancer,” Bell said.

“We’re still in the early stages of testing these viruses in patients, but I believe that someday, viruses and other biological therapies could truly transform our approach for treating cancer.”

JX-594 was developed with Jennerex Inc., a biotherapeutics company co-founded by Dr. Bell in Ottawa and Dr. David Kirn in San Francisco.

The study was funded in part by Jennerex, as well as the Terry Fox Foundation, the Canadian Institutes of Health Research and the Ontario Institute for Cancer Research, and others.

Bell and his research team plan to do further tests on many more patients to show the treatment actually works and that the body doesn’t learn to resist the virus over time.

A Phase 2 trial is to start soon aimed at patients with end-stage liver cancer or colon cancer.

Dr. Don Morris, a professor of Medicine and Oncology at the University of Calgary says even if this treatment is shown to be effective in cancer patients, it would be years before it would be widely available.

“Truly, this is not a treatment that could be applied to community cancer patients out of a trial. We may be three, five or seven years away before this is mainstream. The caution is that this is new hope, but tempered hope,” he told CTV News.

Source: http://calgary.ctv.ca/servlet/an/local/CTVNews/20110831/cancer-tumour-virus-ottawa-110831/20110831/?hub=CalgaryHome

Genetic Link Predisposes to Mesothelioma

An investigation led by scientists at the University of Hawaii Cancer Center, Honolulu, and Fox Chase Cancer Center, Philadelphia has identified germline mutations in the BAP1 gene that predispose individuals to malignant mesothelioma. The research, published online yesterday in Nature Genetics, describes two U.S. families with a high incidence of mesothelioma, as well as other cancers, associated with mutations of the gene BAP1 [1].

Scientists have discovered that individuals who carry a mutation in a gene called BRCA1-associated protein 1 (BAP1) are susceptible to developing two forms of cancer — mesothelioma and melanoma of the eye. When these individuals are exposed to asbestos or similar mineral fibers, their risk of developing mesothelioma, an aggressive cancer of the lining of the chest and abdomen, may be markedly increased.

Mesothelioma tumors are typically associated with asbestos and erionite exposure. Erionite is a naturally occurring mineral fiber similar to asbestos that is found in rock formations and volcanic ash. Deposits have been located in at least 12 states. However, unlike asbestos, erionite is not currently regulated by the U.S. Environmental Protection Agency as one of the six asbestos fibers [2]. Only a small percentage of people exposed to asbestos or erionite actually develop mesothelioma.

Mesothelioma is one of the deadliest forms of cancer, killing approximately 3,000 people each year in the United States, with half of those diagnosed dying within one year. Moreover, rates of new cases of mesothelioma in parts of the world, including Europe and China, have risen steadily over the past decade.

Michele Carbone, M.D., Ph.D., study co-leader and director of the University of Hawaii Cancer Center, said [3]:

This discovery is a first step in understanding the role of the BAP1 gene and its potential utility when screening for mutations in those at high risk. Identifying people at greatest risk for developing mesothelioma, especially those exposed to dangerous levels of asbestos and erionite worldwide, is a task made easier by virtue of this discovery.

Joseph R. Testa, Ph.D., study co-leader and Carol and Kenneth E. Weg chair in Human Genetics at Fox Chase Cancer Center, added [3]:

This is the first study to demonstrate that individual genetic makeup can greatly influence susceptibility to mesothelioma. People exposed to dangerous levels of asbestos or erionite, those with a strong family history of mesothelioma, or those who have been previously diagnosed with a rare tumor of the eye known as uveal melanoma, may benefit from this new discovery.

The researchers focused on two US mesothelioma families — one in Wisconsin and one in Louisiana — in which members were not exposed to asbestos or erionite. Family members developed a number of malignancies, including breast, ovarian, pancreatic and renal cancers, although mesothelioma predominated.

The scientists suspected that mutations in the BAP1 gene might underlie mesothelioma in people with a strong family history of the disease after noticing genetic changes in or near other stretches of DNA where the BAP1 gene is located. Looking more closely at two families with unusually high rates of mesothelioma, they saw that every person who had provided a sample and had developed mesothelioma or melanoma of the eye also carried mutations in the BAP1 gene. Further study led to sequencing the gene in 26 individuals who had developed mesothelioma but did not have a family history of the disease. Tumors from about 25 percent of this group carried mutations in the BAP1 gene, and in two cases the mutations were inherited. Both of the individuals with inherited mutations had previously developed melanoma of the eye.

The researchers hypothesize that when individuals with BAP1 mutations are exposed to asbestos, mesothelioma predominates over melanoma of the eye. Alternatively, the BAP1 mutation alone may be sufficient to cause mesothelioma, providing a cause for tumors that arise spontaneously without previous environmental exposure.

Source: http://www.highlighthealth.com/research/genetic-link-predisposes-to-mesothelioma/

Critical Protein Discovery Could Help Prevent Lethal Ebola Virus

An international team of scientists has discovered a biochemical route used by the deadly Ebola virus to infect human cells.   Scientists say the discovery points the way to new drugs that could prevent or treat one of the world’s most lethal viral diseases.

The Ebola hemorrhagic virus, which got its name from the central African river near where the disease first emerged in 1976, kills an estimated 90 percent of the people and non-human primates it infects.

The disease causes very high fever, both internal and external bleeding, and has led to thousands of deaths in many sub-Saharan African countries, including Gabon, Sudan, the Ivory Coast and Uganda, since the first reported outbreak 35 years ago.

Although considered a rare disease, Ebola causes panic whenever there is an outbreak, in part because little is known about where the illness comes from or how it spreads.

Experts believe infected bats may be one source of these sporadic occurrences of Ebola, and the disease is then spread from person to person through tainted body fluids or blood.

To better understand the biology of Ebola, a team of researchers at Albert Einstein College of Medicine, Harvard Medical School, the Whitehead Institute at MIT and the U.S. Army Medical Research Institute of Infectious Diseases studied how the virus actually infects cells.

Kartik Chandran, a professor of microbiology and immunology at Albert Einstein, is a senior author of the study.

“The critical step that we were studying is what we call viral entry,” Chandran explained.  “And it’s basically the step that results in the virus getting into the cytoplasm where the [genetic] goodies are for making copies of itself.”

Researchers looked at normal cell proteins that the Ebola virus might be hijacking, in effect, to get inside and infect mammalian cells.  Investigators focused on one protein in particular – called Neimann-Pick C1  or NPC1.

Chandran says that in experiments with both human cells and in mice, the Ebola virus was unable to gain a toehold in cells that were missing the NPC1 protein.

“You couldn’t infect the cells with Ebola.  And there are also mice that, like the human[s], don’t have the protein and develop Neimann-Pick disease,” Chandran said.

The Neimann-Pick protein, which is embedded naturally in cell membranes, helps transport cholesterol throughout cells.  People who are born with a rare genetic defect and don’t make the protein eventually die of Neimann-Pick disease, in which fatty substances called lipids collect and clog various internal organs.

Chandran says the disease progresses over time. But to prevent or treat an Ebola infection, he thinks it might be possible to design a small molecule that interferes with production of the Neimann-Pick protein in cells temporarily — too briefly to cause problems with elevated cholesterol.

Chandran says such a compound would not have to totally block production of the NPC1 protein.

“You know the [Ebola] virus, it’s like ‘shock and awe.’  It’s like over within a week,” noted Chandran.   “I mean the virus grows very quickly and it kills off the very cells you need to mount your immune response.  If we could stop that from happening or slow it down enough, we might give the person a chance.”

Chandran says scientists have developed a candidate drug that could be used to treat or prevent an Ebola outbreak.  He says another hemorrhagic virus called Marburg uses a similar mechanism to infect cells and should also respond to a drug that blocks the Neimann-Pick protein.

Two articles by Chandran and colleagues on the biochemical keys involved in Ebola virus infections are published in the journal Nature.

Source: http://www.voanews.com/english/news/science-technology/Critical-Protein-Discovery-Could-Help-Prevent-Lethal-Ebola-Virus-128374013.html

Adding caffeine to sunscreen could guard against skin cancer

Scientists have worked out how caffeine might protect against certain skin cancers – a finding that could lead to better sunscreens.

The research, conducted in mice, suggests that caffeine changes the activity of a gene involved in the destruction of cells that have DNA damage and are therefore more likely to become cancerous. The scientists said this may lead to new ways of preventing skin cancer, though other experts cautioned that it did not mean coffee lovers were better protected against the disease.

Skin cancer is a common disease. According to Cancer Research UK, around 100,000 cases of non-melanoma were registered in the UK in 2008, and just under 12,000 cases of the more dangerous malignant melanoma. These cancers can be caused by over-exposure to ultraviolet light from the sun, which can damage the DNA of skin cells, leading to errors when the cells divide.

The overall protective role of caffeine against cancers has been noted in previous studies, but Allan Conney of the department of chemical biology at Rutgers University in New Jersey wanted to find the specific molecular mechanisms behind it. He suspected that the response might involve a gene called ATR, which is suppressed when caffeine molecules are around. This suppression encourages the death of DNA-damaged cells.

Conney tested the idea by creating genetically modified mice whose ATR genes were deficient and exposing them to ultraviolet light until they developed skin cancer. After 19 weeks of UV exposure, he found that these mice developed 69% fewer tumours than those that had fully functioning ATR genes. In addition, tumours in the GM mice developed three weeks later than in standard mice.

After 34 weeks of UV exposure, all the mice had developed tumours, mainly a type of non-melanoma cancer called squamous cell carcinoma (SCC). The results were published on Monday in the Proceedings of the National Academy of Sciences.

“All of this suggests the possibility that caffeine, possibly [applied to the skin], would have an inhibitory effect on sunlight-induced skin cancer,” said Conney. “In addition to the effects on the ATR pathway, caffeine also has sunscreening properties.”

SCCs are less common than the other type of non-melanoma cancer, called basal cell carcinomas, but it’s the former that are more dangerous. “People rarely die from basal cell carcinomas, but you need more invasive cutting to get it out,” said Conney. “There’s more disfiguration with basal cell than squamous cell. It’s the squamous cell cancers that can metastasise and are more dangerous.”

Jessica Harris, a health information manager at Cancer Research UK, pointed out that Conney’s study examined how caffeine affected genes when it was directly applied to the skin, rather than ingested. “It didn’t look at the effects of drinking coffee, so doesn’t tell us whether or not this could reduce the risk of skin cancer,” she said.

Studies looking at coffee consumption and cancer in large groups of people have provided mixed results, she added. “Some have found that coffee drinking may slightly reduce the risk of certain types of cancer, but the evidence is not yet strong enough to be certain, and these effects tend to be seen among people who drink very large amounts.”

The best way to reduce the risk of skin cancer, said Harris, “is to enjoy the sun safely, taking care not to burn by using a combination of shade, clothing and sunscreen.”

Dot Bennett, a professor of cell biology at St George’s, University of London, said that any move to add caffeine or related molecules to sunscreens should be undertaken with care. “First one might want to check there is no adverse effect of caffeine on the incidence of other cancers, especially melanoma (pigmented skin cancer), which kills over four times as many people as [squamous cell carcinoma]. But caffeine lotion might promote tanning a little, since this family of molecules stimulates pigment cells to make more pigment.”

Source: http://www.guardian.co.uk/science/2011/aug/15/adding-caffeine-sunscreen-skin-cancer

Five Genes May Be Tied to Lethal Prostate Cancer

TUESDAY, Aug. 16 (HealthDay News) — In what may be a diagnostic advance, U.S. and Swedish researchers have linked five inherited genetic mutations to the development of a particularly aggressive and deadly form of prostate cancer.

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The findings could someday lead to development of an easy-to-administer blood test to screen for such mutations to help physicians assess the long-term risk faced by newly diagnosed prostate cancer patients, the researchers suggested.

“The ability to distinguish patients at elevated risk for having aggressive, life-threatening prostate cancer at the time of diagnosis could improve care for the subset of cases most likely to benefit from aggressive therapy and help avoid over-treatment of patients whose tumors are likely to remain indolent,” the study team, led by Janet L. Stanford, co-director of the Fred Hutchinson Cancer Research Center’s program in prostate cancer research, reported in the Aug. 16 online edition of Cancer Epidemiology, Biomarkers and Prevention.

At issue are longstanding concerns about unnecessary over-treatment of many prostate cancer patients who actually face a relatively low risk for fast disease progression and death. Because treatment can bring about undesirable side effects, such as sexual impotence and urinary incontinence, an effort has been under way to achieve a more personalized assessment of a patient’s particular prognosis after diagnosis.

“Biomarkers that could distinguish between patients with indolent vs. more aggressive tumors are urgently needed,” Stanford said in a journal news release. “The panel of markers we’ve identified provides the first validated evidence that inherited genetic variants play a role in prostate cancer progression and mortality. Ultimately these markers could be used in the clinic, along with other known predictors that are used to assess tumor aggressiveness, such as a high Gleason score, to identify men with a high-risk profile.”

The authors, looking for genetic differences that could highlight risk differences, gathered blood samples from more than 1,300 prostate cancer patients living in the Seattle region. All were between the ages of 35 and 74 when diagnosed.

DNA analyses of the samples were compiled with those of nearly 2,900 Swedish prostate cancer patients.

The result: Five single-letter mutations (or SNPs) were isolated among the patients’ “DNA alphabet” as having a significant bearing on prostate cancer progression in terms of affecting cell death, tumor growth, inflammation, androgen hormone levels, blood-vessel development and bone density.

Patients found to have at least four out of the five cited SNP mutations appeared to face a 50 percent higher risk for dying from their disease compared with those who carried two or fewer of the mutations.

William Phelps, program director of translational and preclinical cancer research at the American Cancer Society, said the push to develop more revealing diagnostic tools is driven by an acknowledgement that current treatment options can debilitate patients.

“If the treatments we had for prostate cancer were very tolerable or very safe you would probably treat everybody,” he explained. “But the treatments we have available today are less than ideal.”

“So certainly we can try to improve treatment,” Phelps noted. “But at the same time we can also try to improve ways to identify patients who are more likely to progress rapidly from those likely to be very slow going, so we can reserve treatment for only those instances when it’s really necessary.”

If there are markers that better define the men whose cancer is most likely to progress, “that would certainly prove very useful in the current climate,” he said.

Source: http://health.usnews.com/health-news/family-health/cancer/articles/2011/08/16/five-genes-may-be-tied-to-lethal-prostate-cancer

Suicide-Bombing Bacteria Could Fight Infections

Like any good military unit, infectious bacteria have access to numerous weapons and efficient communication systems. But like soldiers in the field, they’re also susceptible to suicide bombers. Researchers have used the tools of synthetic biology to create an Escherichia coli cell that can infiltrate foreign bacteria and explode, killing off the pathogens along with itself.

The project, says bioengineer Chueh Loo Poh of Nanyang Technological University in Singapore, was “inspired by nature,” particularly by quorum sensing, the ability of some bacteria to detect the number of microorganisms—either of their own species or others—in their environment. When pathogenic Pseudomonas aeruginosa sense other species impeding on their space and nutrients, they communicate with members of their own species using chemical signals and collectively start releasing a bacterial toxin called pyocin that kills off the competition. Together, these communication and defense capabilities allow P. aeruginosa to form tightly packed layers called biofilms, which can cause respiratory tract infections in humans and are particularly dangerous to cystic fibrosis patients.

Poh and chemical engineer Matthew Wook Chang, also at Nanyang Technological University, decided to turn P. aeruginosa‘s weapon system against itself, using E. coli as the carrier. The researchers tweaked the genes that allow P. aeruginosa to detect other members of its species and put this synthetic genetic code into E. coli‘s genome. They also gave E. coli a gene for making a modified pyocin that is toxic to P. aeruginosa. By linking the pyocin gene to the sensing genes, the researchers ensured that when the E. coli detected P. aeruginosa in the vicinity, it would fill itself with large amounts of pyocin and become a biological time bomb.

The researchers gave E. coli one last synthetic component: a “suicide gene” that is activated once the pyocin has had some time to build up, causing the cells to burst open and release their toxin. When Chang and Poh grew these synthetic E. coli in a dish with P. aeruginosa, the suicide bomber was able to kill 99% of the P. aeruginosa cells, the researchers report today in Molecular Systems Biology.

Justin Gallivan, a synthetic biologist at Emory University in Atlanta, says in an e-mail that the study “nicely illustrates” how synthetic bacteria can perform complex tasks. But he worries they may not be able to finish the job, because 1% of the infectious bacteria remained after the treatment—even when the researchers put four times as many E. coli as P. aeruginosa into the mix.

The system would also have to undergo a lot of work before it can be considered for use in humans—including, perhaps, replacing E. coli with another delivery system, says Richard Kitney, a synthetic biologist at Imperial College London. “Exposing people to E. coli is not a good thing,” Kitney says, as the bacteria are toxic outside the gut. He adds that the team would also have to show that pyocin is effective at killing P. aeruginosa that have already formed a biofilm.

For their part, Chang and Poh say that they plan to test the suicidal bacteria in mice infected with P. aeruginosa. It’s not clear, they say, whether pyocin is harmful to mammals, although some other natural bacterial toxins are currently approved for use as food preservatives. They also hope to tweak the synthetic system so that it can sense and respond to signaling molecules released by other species of pathogenic bacteria, such as those responsible for cholera.

Source: http://news.sciencemag.org/sciencenow/2011/08/suicide-bombing-bacteria-could-f.html

MS genetic discovery casts doubt on vein theory

Scientists have discovered 29 new genetic variations linked to multiple sclerosis, with many involving genes relevant to the immune system – a finding that they say bolsters the theory that MS is a primarily an autoimmune disease.

The new study, published Wednesday in the journal Nature, is the largest-ever study on the genetics of multiple sclerosis. More than 250 scientists collaborated on the work, and close to 10,000 MS patients were involved.

Many of the gene variations the team discovered are involved in the development of the immune system’s T-cells, which are the immune cells that protect against infections. When T-cells become “confused,” they trigger autoimmune diseases that mistake healthy body tissues as foreign and attack them.

The study authors say the findings reaffirm the long-held assertion that MS is primarily an autoimmune disorder and that changes in the immune system set off the disease.

“Our research settles a longstanding debate on what happens first in the complex sequence of events that leads to disability in multiple sclerosis,” Dr. Alastair Compston, a University of Cambridge neurology professor who was one of the leaders of the study, said in a statement.

“It is now clear that multiple sclerosis is primarily an immunological disease. This has important implications for future treatment strategies.”

The findings also cast doubt on the recent theory proposed by Italian vascular surgeon Dr. Paolo Zamboni that MS is related to blocked neck veins.

For this new study, researchers in Britain, Canada and a dozen other countries performed genome-wide scans on the DNA of 9,772 people with MS. They looked for genetic anomalies that didn’t appear in the DNA of 17,376 healthy people without MS.

They discovered the MS patients had 29 genetic variations that other patients didn’t have. They also confirmed 23 other genetic variations that had already been associated with MS. As well, the team identified five more associations that might be significant and that require further study.

One third of the genes identified have previously been implicated in playing a role in other autoimmune diseases such as Crohn’s Disease and Type 1 diabetes, indicating that the same processes occur in more than one type of autoimmune disease.

The findings cast doubt on the theory put forward by Dr. Zamboni. He suggests that blocked neck and chest veins stop blood from draining properly from the brain – a condition he calls CCSVI – which leads the blood to deposit iron in the brain. It’s the iron deposits that lead to the brain changes that mark MS, he contends.

To treat this, he proposes a vascular procedure to open blocked and twisted neck veins. Hundreds of Canadian patients have flown to overseas clinics for the so-called “libertion treatment,” spending upwards of $20,000 or more.

They’ve returned with various results. Some have reported the procedure helped relieve their fatigue; others said it allowed them to walk again, while still others say it offered no relief at all.

At least two patients have died after having the procedure, though it’s unclear what role it played in the deaths.

Zamboni has conducted studies that suggest that the majority of MS patients have CCSVI while few healthy patients so. But further studies have been unable to replicate his findings.

One study published this week in the Archives of Neurology found no significant difference in venous abnormalities between MS patients and healthy controls. But CCSVI proponents argue the studies were performed improperly.

The vein theory has not been embraced by many neurologists who specialize in MS. Many contend that patients have a genetic predisposition for MS and that one or more environmental factors trigger the condition.

Multiple sclerosis is marked by damage to nerve fibres in the brain and spinal cord and their protective insulation, called the myelin sheath. When the myelin is destroyed, it causes patients to struggle with everyday activities such as walking, feeling, thinking and controlling the bowel and bladder.

Even among those who believe MS is an autoimmune disease, it’s been unclear what sparks the immune changes. Previous research has suggested a vitamin D deficiency might be the trigger. Populations in northern hemispheres have higher rates of MS than populations with more year-round sunlight.

In this latest genetics study, researchers did identify two genetic variations that are involved in the metabolism of vitamin D.

Source: http://ottawa.ctv.ca/servlet/an/local/CTVNews/20110811/ms-gene-study-immune-system-110811/20110811/?hub=OttawaHome

Genetic mutations cause schizophrenia

More than 50 per cent of sporadic cases of schizophrenia are caused by new, or “de novo,” protein-altering mutations-genetic errors that are present in patients but not in their parents, a new research has shown.

A group led by Maria Karayiorgou, MD, and Joseph A. Gogos, MD, PhD, examined the genomes of patients with schizophrenia and their families, as well as healthy control groups. All were from the genetically isolated, European-descent Afrikaner population of South Africa.

They found 40 mutations, all from different genes and most of them protein-altering.

The results point the way to finding more, perhaps even hundreds, of mutations that contribute to the genetics of schizophrenia-a necessary step toward understanding how the disease develops, the researchers said.

“Identification of these damaging de novo mutations has fundamentally transformed our understanding of the genetic basis of schizophrenia,” says Bin Xu, PhD, assistant professor of clinical neurobiology at Columbia University Medical Center and first author of the study.

“The fact that the mutations are all from different genes,” says Karayiorgou, “is particularly fascinating. It suggests that many more mutations than we suspected may contribute to schizophrenia. This is probably because of the complexity of the neural circuits that are affected by the disease; many genes are needed for their development and function,” she added.

The study was recently published online in Nature Genetics.

Source: http://timesofindia.indiatimes.com/life-style/health-fitness/health/Genetic-mutations-cause-schizophrenia/articleshow/9527010.cms

Proteus Syndrom Gene Variant Identified

Researchers have discovered the gene mutation that leads to Proteus syndrome, a condition that causes different parts of the body to grow faster and larger than others, HealthDay reports.

With only about 500 cases known in the developed world, Proteus syndrome is rare. The condition is marked by a partial enlargement of the hands or feet, an enlarged head and overgrowth of one side of the face, body or limbs. It is thought to be the cause of the disabilities of 19th century Englishman Joseph Merrick, popularly known as the “Elephant Man.”

According to HealthDay, Proteus syndrome is a mosaic disorder, one in which some cells in the body have the genetic mutation and some don’t. Working on identifying the specific gene variant since 1996, researchers at the U.S. National Human Genome Research Institute were finally able to compare tissue samples from affected areas of the body to unaffected areas in 29 Proteus syndrome patients. They were able to identify the same mutation in 26 patients.

The mutation occurred in the AKT1 gene, they said. HealthDay explains the mutation as “a single ‘misspelling’ in the billions of letters that make up the human genome.”

HealthDay noted that the gene mutation in Proteus syndrome creates an oncogene, which drives the uncontrolled cell division. Oncogenes are usually associated with cancer, the website reported.

Researchers hope that finding the gene will be able to lead to better treatment for people with Proteus syndrome.

“It may become possible to treat those with Proteus syndrome with a drug originally developed for cancer,” said the study’s senior author Leslie Biesecker. “This allows us to leapfrog a number of steps. But, Proteus syndrome is not an overgrowth syndrome so we would have to adapt cancer treatments.”

Source: http://www.thirdage.com/news/proteus-syndrom-gene-variant-identified_07-28-2011

Daily pill can prevent HIV infection

The partners of people who have HIV can protect themselves from infection by taking a once-daily pill, two groundbreaking studies in Botswana, Kenya and Uganda have shown.

The discovery could bring work to combat Aids close to a “tipping point”, experts say. Attempts to promote condom use to protect against HIV in the hardest-hit parts of the world, and particularly Africa, have hit cultural barriers and had limited success.

But now it appears that men or women who know – or suspect – their partner has HIV could protect themselves, secretly if necessary. The larger study, involving 4,758 “discordant” couples (where one has HIV but the other has not) in Kenya and Uganda, led by the University of Washington’s International Clinical Research Centre, shows that those taking a single daily tablet of the Aids drug tenofovir had 62% fewer infections and those who took a pill combining tenofovir and emtricitabine had 73% fewer infections than those who took a placebo pill.

The drugs have few side-effects, which is important if they are to be given to healthy individuals. Both are made by Gilead, which has licensed their manufacture to generic companies in the developing world, allowing them to produce cheap copies – so this is a relatively inexpensive intervention.

“This study demonstrates that antiretrovirals are a highly potent and fundamental cornerstone for HIV prevention and should become an integral part of global efforts for HIV prevention,” said Dr Connie Celum, professor of global health and medicine at the university and principal investigator of the study, known as the Partners PrEP Study, which was funded by the Bill and Melinda Gates Foundation.

The second study in Botswana was conducted by the United States Centres for Disease Control. It followed 1,200 heterosexual men and women without HIV who received either a once-daily tenofovir/emtricitabine tablet or a placebo pill. The antiretroviral tablet reduced the risk of acquiring HIV infection by roughly 63% overall.

“This is a major scientific breakthrough which re-confirms the essential role that antiretroviral medicine has to play in the Aids response,” said Michel Sidibé, Executive Director of the Joint United Nations Programme on HIV/Aids (UNAids). “These studies could help us to reach the tipping point in the HIV epidemic.”

The news follows hard on the heels of another very significant finding – that people with HIV who are taking combinations of antiretroviral drugs not only stay healthy themselves but are unlikely to infect their partner.

The two pieces of research give a massive boost to the cause of rolling out more Aids drugs and treating people at the earliest stage of their illness.

“Effective new HIV prevention tools are urgently needed, and these studies could have enormous impact in preventing heterosexual transmission,” said Dr Margaret Chan, WHO’s director general. “WHO will be working with countries to use the new findings to protect more men and women from HIV infection.”

Source: http://www.guardian.co.uk/world/2011/jul/14/hiv-daily-pill-breakthrough

Scientists Discover Gonorrhea Resistant to Antibiotics

(EndPlay Staff Reports) – A new untreatable strain of gonorrhea has been discovered in Japan and is causing concern in the United States.

Scientists reported that the strain, which is named H041, is resistant to all known forms of antibiotics. The researchers discussed the findings at a Monday meeting in Canada about three days after the CDC warned on July 8 that gonorrhea samples in the U.S. are also showing signs of drug resistance.

The concern is that the new strain of Neisseria gonorrhoeae is resistant to the cephalosporin family of antibiotics such as ceftriaxone, cefixime and cefpodoxime, which are widely used to treat the sexually transmitted disease in the United States. The CDC warned that this is a concern because it only leaves a few antibiotic options that are “simple, well-studied, and highly effective.”

The resistance to antibiotics, according to the CDC , was first documented in Asia before emerging in Hawaii and other western states then spreading elsewhere.

“This is a large public health problem and the era of untreatable gonorrhea may now have been initiated,” the team of researchers said at the Quebec City meeting of the International Society for Sexually Transmitted Disease Research, The Los Angeles Times reported.

The US Gonococcal Isolate Surveillance Project launched in 1986 has not discovered any U.S. cases in which treatment with cephalosporin antibiotics was a complete failure. The Times, though, reported there have been more cases that required unusually high doses of the antibiotic to cure them.

The majority of samples showing this trend were obtained from men having sex with men, the newspaper stated. The largest growth in cases noticed between 2000 and 2010 have been in Hawaii and California.

As a precaution, the CDC is suggesting dual treatment with another antibiotic such as azithromycin or doxycycline.

Gonorrhea, ABC News reported, is one of the most common STDs with about 700,000 new cases each year in the United States. It is spread through direct contact with the penis, vagina, mouth or anus and can also be transmitted from mother to baby during birth.

Only about half of infected women and less than five percent of infected men develop symptoms including a burning sensation and discharge. ABC News said it can spread to the skin, blood and other organs and cause pain, infertility and death if not treated.

Scientists are concerned that such a strain could spread quickly if new ways are not found to stop it. Dr. William Schaffner, chair of preventive medicine at Vanderbilt University Medical Center in Nashville, Tenn., told ABC News that this coincides with cutbacks in research as pharmaceutical companies invest less in the search for new antibiotics.

While the strain that did not respond at all to antibiotics was discovered in Kyoto, Japan, he warned, such bacteria “don’t need a passport” to spread.

Source: http://www.myfoxboston.com/dpps/health/scientists-discover-gonorrhea-resistant-to-antibiotics-dpgoha-20110712-fc_14088790

A deadly new reason to avoid deer ticks

Move over, Lyme disease: Another tick-borne illness is on the rise in various parts of the country, and this one can kill.

Known as babesiosis, the disease is caused by a microscopic parasite that attacks blood cells, causing flu-like symptoms that can make it difficult to accurately diagnose. Like Lyme disease, which is caused by bacteria, babesia microti parasites are carried by deer ticks.

First documented in Massachusetts in 1969, the once-obscure babesiosis has surfaced as a significant public health threat in parts of the Northeast and Upper Midwest over the last several years. A recent study in the journal Emerging Infectious Diseases, published by the U.S. Centers for Disease Control and Prevention, revealed that between 2001 and 2008 cases climbed from six to 119 in New York’s Lower Hudson Valley — a 20-fold regional increase.

And many cases may be escaping detection, experts say.

“I think it’s underreported. One of the reasons we’re seeing more about it is because people are becoming more aware,” said Dr. Peter Krause, a babesiosis researcher and senior research scientist at the Yale University School of Public Health. “The theory is that it’s spreading from east to west, as if you were dropping a pebble in a pond and it spread outward geographically.”

About 1,000 cases are reported annually in affected locales, Krause said, but many people with babesiosis have no symptoms and never know they’re harboring the parasite. For others, symptoms can include high fever, severe headache, fatigue, chills, and muscle aches and pains. It is treated with antimicrobial drugs, such as antibiotics.

People with compromised immune systems — including the elderly and those with cancer, HIV or no spleens — are especially at risk of potentially deadly complications such as organ failure. Between 10 percent and 20 percent of patients in those populations die as a result, Krause said.

The more prolific Lyme disease causes similar symptoms in early stage cases but is easier to diagnose by its telltale bullseye rash, said Dr. Barbara Herwaldt, a medical epidemiologist at the CDC who specializes in parasitic conditions.

Deer are pivotal to the life cycle of ticks carrying the babesia microti parasite by serving as a blood meal, shelter and a place to mate, Krause said. Ticks also feed on birds, who serve as carriers for Lyme disease, which affects the entire continental United States. Fortunately for humans, birds don’t carry babesia microti.

Krause noted that ticks need a moist climate to thrive, so dry states such as Arizona are not likely to see babesiosis cases caused by tick bites. But the disease can potentially spread to all states in an even sneakier way — through the blood supply.

Although a blood screening test is in trials, Krause said, donors are currently only asked if they have had babesiosis, and those who harbored it but never showed symptoms can pass it through their donated blood. And because most blood recipients are already physically compromised, babesiosis has about a 30 percent mortality rate in that group, he said.

“Getting babesiosis through the blood supply is a rare event and people shouldn’t panic,” he said. “I don’t think it will reach a crisis level, but it’s still a concern.”

To help prevent babesiosis, the CDC advises people with compromised immune systems or other vulnerabilities to avoid tick-infested wooded areas, particularly during warm months. The agency also recommends that everyone walk in the middle of trails and avoid bushy areas with lots of leaves or tall grasses and to use the repellent DEET and pre-treat clothes with an insect repellent containing permethrin before going outdoors.

The CDC also recommends doing full-body checks and showering within a few hours of being in the woods, as well as tossing used clothes in the dryer to kill any ticks that might be hiding there.

The authors of the study also advised clinicians to consider babesiosis in patients who have been exposed to ticks or received blood products and who show up for treatment with a fever and anemia resulting from the destruction of red blood cells.

Source: http://yourlife.usatoday.com/health/story/2011/07/A-deadly-new-reason-to-avoid-deer-ticks/49212700/1