The study, published online in the Journal of the American Chemical Society, ran a large number of simulations to predict how strongly the drug saquinavir would bind to three resistant mutants of HIV-1 protease, a protein produced by the virus to propagate itself. These protease mutations are associated with the disease’s resistance to saquinavir, an HIV-inhibitor drug.

The study, by Professor Peter Coveney and colleagues at the UCL Department of Chemistry, involved a sequence of simulation steps, performed across several supercomputers on the UK’s National Grid Service and the US TeraGrid, which took two weeks and used computational power roughly equivalent to that needed to perform a long-range weather forecast.

The idea behind the Virtual Physiological Human (VPH) is to link networks of computers across the world to simulate the internal workings of the human body. The VPH – mainly a research initiative at present – allows scientists to simulate the effects of a drug and see what is happening at the organ, tissue, cell and molecular level.

Although nine drugs are currently available to inhibit HIV-1 protease, doctors have no way of matching a drug to the unique profile of the virus as it mutates in each patient. Instead, they prescribe a course of drugs and then test whether these are working by analysing the patient’s immune response. One of the goals of VPH is for such ‘trial and error’ methods to eventually be replaced by patient-specific treatments tailored to a person’s unique genotype.

Professor Peter Coveney says: “This study represents a first step towards the ultimate goal of ‘on-demand’ medical computing, where doctors could one day ‘borrow’ supercomputing time from the national grid to make critical decisions on life-saving treatments.

“For example, for an HIV patient, a doctor could perform an assay to establish the patient’s genotype and then rank the available drugs’ efficacy against that patient’s profile based on a rapid set of large-scale simulations, enabling the doctor to tailor the treatment accordingly.

“We have some difficult questions ahead of us, such as how much of our computing resources could be devoted to helping patients and at what price. At present, such simulations – requiring a substantial amount of computing power – might prove costly for the National Health Service, but technological advances and those in the economics of computing would bring costs down.”

For the moment, Professor Coveney’s group is continuing to look at all the protease inhibitors in a similar way. The VPH initiative, now underway with 72 million euros of initial funding from the EU, will boost collaboration between clinicians and scientists to explore the scope for patient-specific medical treatments based on modern modelling and simulation methods.

About UCL

Founded in 1826, UCL was the first English university established after Oxford and Cambridge, the first to admit students regardless of race, class, religion or gender, and the first to provide systematic teaching of law, architecture and medicine. In the government’s most recent Research Assessment Exercise, 59 UCL departments achieved top ratings of 5* and 5, indicating research quality of international excellence.

UCL is in the top ten world universities in the 2007 THES-QS World University Rankings, and the fourth-ranked UK university in the 2007 league table of the top 500 world universities produced by the Shanghai Jiao Tong University. UCL alumni include Marie Stopes, Jonathan Dimbleby, Lord Woolf, Alexander Graham Bell, and members of the band Coldplay.

University College London

“Reprinted with permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

Discriminatory and punitive laws will be the focus for an audience of senior lawyers and diplomats at the first World AIDS Day Commonwealth lecture, chaired by Cherie Booth QC, in London on 30 November. The lecture will be given by Justice AP Shah who created shockwaves across the continent when he decriminalised homosexuality in Delhi, India.

“We see the problem that punitive laws and enforcement practices can cause for people who need quick and easy access to HIV treatment, care and prevention. Governments and the legal profession need to work more closely with the affected communities to address these laws and access legal services,” said Alvaro Bermejo, Executive Director of International HIV/AIDS Alliance.

Women and girls, men who have sex with men, sex workers and injecting drug users as well as people who are living with HIV struggle to access the services they need because of environments where they feel judged or punished.

The World AIDS Day lecture is organised by the International HIV/AIDS Alliance and the Commonwealth HIV & AIDS Action Group and hosted by the Commonwealth Foundation.

Cherie Booth, QC commented, “The legal profession has an important role to play in providing an environment where people can come forward and be tested for HIV and cared for.”

Justice AP Shah who is giving the lecture made history in India when he overturned Section 377 that criminalised consenting homosexual relationships in the capital Delhi.

“Indian society is very conservative but from the evidence presented I could see that without changing the legal framework to help men who have sex with men access good healthcare and HIV prevention services we would not successfully be able to deal with the epidemic in our country,” said Justice Shah today.

HIV and AIDS is a major issue in many Commonwealth countries which have inherited outdated British laws. Over 60 per cent of people living with HIV live in Commonwealth countries.

“The Commonwealth Foundation is committed to doing all it can to help people access HIV prevention, treatment and care. This Commonwealth lecture on World AIDS Day will help more countries become familiar with the example of India, which has identified the benefits of starting to decriminalise homosexuality and abolish laws that drive HIV and AIDS underground,” said Mark Collins, Director of the Commonwealth Foundation.

Notes:

– World AIDS Day is an annual event and is on Wednesday 1 December 2010.

– 2.6 million people worldwide are infected with HIV every year.

– At least 20 African countries have introduced HIV specific offences since 2000.

– People living with HIV have been prosecuted for biting, spitting or scratching although the risk of HIV transmission is minimal.

Justice AP Shah

Born in Solapur, Western India, Justice Shah was formerly Chief Justice of the Delhi High Court, he has been described as ‘one of the finest judges in the country’ by his peers. He retired in February but during his distinguished career in the High Courts of Bombay, Madras and Delhi he ushered in reforms that mean he is hero-worshipped by the poor and disposed of India.

It is his ruling that overturned Section 377, a 150-year old British law banning gay sex between consenting adults that will be most remembered. His decision made news around the world.

He admits he hadn’t expected to be the person that would legalise homosexual sex. “I didn’t switch on TV channels till late in the evening because I was not sure about the reactions from various quarters. When I attended a workshop with some gay rights activists in 1997 I had categorically said to them that it would be very difficult for an Indian court to legalise homosexual sex. I didn’t realise then that I would be deciding the issues one day.”

Cherie Booth, QC

Booth is Cherie Blair’s professional name. Called to the Bar in 1976, she became a Queens Counsel in 1995 and is a founder member of Matrix Chambers. She sits as a part-time judge and is also an accredited mediator.

As well as fighting for human rights in her professional career, Cherie Blair is an active campaigner on equality and human rights issues. She has spoken across the world on both issues and also on the need for improved work/life balance for both women and men.

Source:

International HIV/AIDS Alliance

Commonwealth HIV & AIDS Action Group

Commonwealth Foundation

“Reprinted with permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

Or, imagine diabetics with hard-to-heal wounds finding a source of relief from the battle against infections and limb amputation.

Those scenarios are the hope of the developers of a revolutionary borate glass nanofiber material, which appears to have helped the final healing long-term wounds in eight out of 12 venous stasis wound sufferers in a recent clinical trial held at a medical center in Rolla, Mo.

Details about the trials and the glass fiber material were published in the May issue of the American Ceramic Society’s Bulletin magazine.

The story reports on the discovery of the fibers and on an empirical study that began late in the fall of 2010 supervised by the internal review board of the Phelps County Regional Medical Center. The trial groups originally had 13 volunteer members, but one dropped out during the early stages.

According to Peggy Taylor, the PCRMC registered nurse who administered the treatments, all of the volunteers in the trial are enthusiastic about the use of the glass fiber product, which she says “looks like cotton candy.”

“All of the participants had diabetes and several of them had wounds that had been unhealed for more than a year,” says Taylor, a specialist in wound care. “One patient had the same wound for three years. After using the glass fiber product for a few months, we were able to repair the skin in eight of the patients. Remarkably, the other four have made a lot of progress and all of their wounds should be healed soon, too.”

All of the patients suffered from problems associated with venous stasis, a condition where blood circulation in extremities is poor. As the blood pools, typically in lower legs, fluids accumulate causing unusual pressure on skin tissues. Sores and wounds can then develop when the fluid “weeps” from skin cracks, cuts or abrasions.

Because of an enzyme in the weeping fluid, the skin surrounding small venous stasis injuries can quickly erode and turn into large and deep wounds. Even small bruises can eventually develop into bone-deep openings.

The goal of the PCRMC trial was to provide an initial evaluation of the effects of the novel fibrous glass material produced by the Mo-Sci Corporation, a Rolla company already known for creating glass-based materials for medical applications.

“Bioglass” materials aren’t particularly new to the medical field, but thus far all bioglass has been formed from a silica-based glass composition, and these primarily have been used in hard-tissue regeneration, such as bone repair.

Glass scientist Steve Jung, who helped develop the new material, says he and co-developer Delbert Day had wondered whether a different type of bioactive glass material could be used for soft-tissue regeneration. “We felt from our in-vitro studies that bioactive glasses containing boron would react to body fluids much faster than silicate glasses,” says Jung, who obtained his Ph.D from Missouri University of Science and Technology, where he conducted his research with Day, a professor at the university. “We also knew that an in-vitro study of lithium borate glasses had showed it to have beneficial effects against bacteria, such as E. coli, salmonella and staphylococcus microbes.”

Lastly, Jung and Day recall they were interested in a composition that was rich in calcium. “Previously, investigators have reported that calcium is important for wound healing. It appears to assist the migration of epidermal cells and help the body regulate the healing process of open wounds,” says Jung.

Besides composition, Jung and Day thought the structure of the material may be important to consider, too, and suspected that providing a healing “scaffold” might be beneficial. “We thought it might be advantageous to have a material that could mimic the microstructure of fibrin that forms the basis of a blood clot. We reasoned that if the structure could imitate fibrin, it might trap blood platelets and allow the formation of a wound cover that could support the healing process.”

Jung and Day finally settled on a particular borate glass composition – called 13-93B3 glass – one that Mo-Sci, a company founded by Day, already knew how to form into cottony glass fibers, 300 nanometers to 5 micrometers in diameter.

After animal tests showed no adverse effects, Mo-Sci obtained a license for the material from Missouri S&T, named the borate glass material “DermaFuse,” and approached PCRMC about starting the small-scale human test.

PCRMC approved the trial in July 2010, and nurse Taylor saw her first patient one month later. Once the study was underway, the company provided Taylor with individual, foil-sealed packets containing pads made of the glass fibers. She says the material is easy to apply. “It gets kind of squished in the packs, but you can form it, pick it, make it into any kind of shape you need out of it. I used tweezers to pack the material up into all of the recesses before filling the rest of the wound. I didn’t pack it hard, but enough to fill all the crevices. Once it was in place, I covered it with a secondary covering or compression wrap.”
One thing that surprised Taylor was that the glass fibers seem to disappear over time, a phenomenon that has been observed with other bioglasses. “Does it dissolve? Does it become part of the tissue? We don’t quite know, but it is just such a neat thing to watch that process.”

Taylor acknowledges that under her care, the wounds would have probably healed without the glass material, but they would have required expensive vacuum-assisted healing systems that must be carried by patient at all times.

Besides low cost and ease of use, Taylor says the glass fibers seem to offer another stunning benefit: low scarring. “All but one of the patients in the trial were elderly and had a lot of skin discoloration, but we healed wounds that show nothing or negligible scarring,” she says.

Jung, who now works as a senior researcher for Mo-Sci, says that the next step is expanded human trials, which will be conducted in partnership with the Center for Wound Healing and Tissue Regeneration at the University of Illinois at Chicago. He says the center has agreed to begin testing the material this summer.
In the meantime, Jung says he and Day are optimistic about a new era in wound treatment. “We are really hoping the properties of these fibers can help with more extensive wounds, such as burns, and we easily foresee the day when soldiers or EMT workers carry packets of these glass fibers to provide healing protective covers that don’t have to be removed.”

The story, “Cotton candy that heals? Borate glass fibers look promising”

Source:
Peter Wray
The American Ceramic Society

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Simultaneously, Family Health International (FHI) has halted a second Phase III cellulose sulfate trial in Nigeria. Although the FHI trial did not detect an increased HIV risk associated with cellulose sulfate, the decision was made as a precautionary measure, given the preliminary results in the CONRAD trial. Cellulose sulfate (CS) was one of four microbicides currently in effectiveness trials for prevention of HIV and other sexually transmitted infections.

At this point, it is not clear why use of cellulose sulfate was associated with an increased risk of HIV infection in the CONRAD trial. The Independent Data Monitoring Committee (IDMC), an independent advisory group of experts overseeing the trial, will conduct a detailed review of the data to better understand the findings, and help determine any implications for other microbicide studies.

Dr. Lut Van Damme, principal investigator of the CONRAD trial, stated: “It was our hope that this product would have helped women in protecting themselves from HIV. While the findings are unexpected and disappointing, we will learn scientifically important information from this trial that will inform future HIV prevention research.”

The microbicide, also known as Ushercell, is a cotton-based compound developed by Polydex Pharmaceuticals, based in Toronto, Canada. Prior to beginning the Phase III efficacy trials, there were 11 earlier safety and contraceptive trials on cellulose sulfate involving more than 500 participants in Africa, India, and the U.S. — none of which identified safety concerns.

Recruitment for the CONRAD Phase III study began in July 2005. The study was conducted in areas of the world where HIV risk is greatest, and where infection occurs primarily through heterosexual intercourse. Half of the participating women were given cellulose sulfate, and half a placebo gel, in a double-blinded randomized trial design. All participants received intensive HIV prevention counseling at each monthly visit and all women were given high-quality condoms free of charge. Participants received regular testing and treatment for sexually transmitted infections. Pregnant women were not included in the study.

Participants were admitted into the study only after receiving detailed information about the purpose of the study and the possible health benefits and risks. During this process, their understanding of the study was assessed prior to their signing a consent form. Each trial site is linked to local organizations that provide care for women who become HIV-infected during the trial. As part of the trial preparation, CONRAD set aside funding for women who become HIV-positive during the trial to ensure adequate health care, including HIV antiretroviral treatment when needed.

Jeff Spieler, Chief of USAID’s Research, Technology and Utilization Division, Office of Population and Reproductive Health said, “I am surprised and disappointed by these findings given the pre-clinical effectiveness and safety profile of CS, and its safety profile demonstrated in Phase I trials. I believe strongly that the field learns a great deal from every study, even those with disappointing results. The effort and resources that have been expended in terms of site and infrastructure development, training of clinical and laboratory staff, and community involvement activities will help move the field forward and pave the way to future studies.” He continued, “I am also hopeful that one or more of the other microbicide candidates now in Phase III trials, and the next generation of products under development, will be shown to be safe and effective in helping to prevent HIV infection along with other behavioral interventions.”

“Developing new tools to prevent HIV — particularly for women — is an urgent priority,” said Dr. Henry Gabelnick, Executive Director of CONRAD. “We are committed to learning as much as possible from the trials of cellulose sulfate, and will use that knowledge to continue searching for compounds and collecting evidence to find a successful microbicide. Continued support for microbicide research is critical to our eventual success.”

Cellulose Sulfate: Clinical Trial History (Safety and Efficacy)

Overview:

Prior to initiating two HIV prevention trials, CONRAD sponsored 11 clinical trials of cellulose sulfate (CS) involving 518 women and 48 men in the CS arms. These studies fall into four categories as follows:

* Safety studies in women — 5

* Safety studies in men — 2

* Other (safety of CS when used with a diaphragm and MRI imaging)- 2

* Contraceptive effectiveness studies – 2

Most of the trials were undertaken in the United States (7), one was done in Europe, and three in countries where the HIV prevention trials were expected to be carried out. The contraceptive effectiveness trials were carried out in the United States in mutually monogamous populations at low risk for STIs in which condom counseling was not required.

The safety studies in women and men varied in terms of control group (inactive sexual lubricant such as K-Y? Jelly or active spermicidal gel such as Conceptrol®), frequency of use (once, twice, or four times daily), duration of use (6-14 days), sexual activity (abstinent or active), and HIV status of participants (infected or uninfected). Endpoints included signs and symptoms of genital irritation, colposcopic findings, changes in vaginal microflora and, in some cases, vaginal inflammatory markers, and responses on acceptability questionnaires. The contraceptive studies used the prevention of pregnancy as the primary endpoint. The results of these studies have indicated that CS was as safe, acceptable, and effective as marketed spermicides and sexual lubricants.

The initial safety study was begun in 1999 and the contraceptive effectiveness trial was completed in July, 2006. The results of all eleven clinical studies to date have indicated that CS was as safe, acceptable, and effective as marketed spermicides and sexual lubricants.

###

CONRAD is a cooperating agency of USAID committed to improving reproductive health by expanding the contraceptive choices of women and men and by helping to prevent the transmission of HIV/AIDS and other sexually transmitted diseases. CONRAD is administered through the Department of Obstetrics and Gynecology at Eastern Virginia Medical School (EVMS) in Norfolk, VA and headquartered in Arlington, VA.

Contact: Annette Larkin

CONRAD

These grants, allocated between July 2007 and January 2008, fund more than 80 cutting-edge research projects in fields as diverse as arthritis, Alzheimer’s disease, multiple forms of cancer, nutrition, epilepsy, medical imaging, health care delivery, infertility, heart disease, cell biology and pharmacology, to name but a few.

“Funding from CIHR, in the hands of our researchers, leads to knowledge-creation, improved quality of life, and even cures for many of the diseases and conditions that affect Canadians and people the world over,” said Denis Th?©rien, McGill’s Vice-Principal (Research and International Relations). “McGill, in partnership with CIHR, will continue to provide our researchers with the support they need to pursue their important investigations.”

The Canadian Institutes of Health Research (CIHR) is the Government of Canada’s agency for health research. CIHR’s mission is to create new scientific knowledge and to catalyze its translation into improved health, more effective health services and products, and a strengthened Canadian health care system. Composed of 13 Institutes, CIHR provides leadership and support to more than 11,000 health researchers and trainees across Canada.

“We are immensely proud of the researchers at the MNI,” said Dr. David Colman, Director of the Montreal Neurological Institute. “Our extraordinary success in securing CIHR funding is a testament to the outstanding and innovative new projects under development here at the MNI and McGill, and to the commitment of the CIHR to advance the best biomedical research, which is the ultimate key to improving the health of all Canadians.”

“The Jewish General Hospital’s Lady Davis Institute for Medical Research (LDI) has become a world leader thanks to the work of our dedicated researchers,” said Dr. Hartley Stern, Executive Director of the JGH. “With the assistance of the CIHR we will be able to continue the excellent work that has improved the lives of patients at the JGH and the province of Quebec.”

“The results from the most recent competition amount to just over $7.3 million in operating and seed grants for Douglas researchers. We are proud of those results, which testifies to the high quality of scientific research at the Douglas,” stated R?©mi Quirion, OC, PhD, FRSC, CQ, MS, Scientific Director of the Douglas Research Centre and Scientific Director of the Institute of Neurosciences, Mental Health and Addiction (INMHA).

“One of the primary objectives of the Research Institute of the MUHC is to ensure that the MUHC continues its role as a leader in patient-centered, innovative medicine to provide the best care for life to our patients,” said Dr. Vassilios Papadopoulos, Director of the Research Institute of the MUHC. “Continued funding from the CIHR helps ensure these goals are supported.”

“The Government of Canada is committed to investing in knowledge, science and innovation,” said Minister Clement. “In Budget 2008, we increased CIHR’s budget by $34 million and we made a number of other strategic investments designed to further strengthen Canada’s research capacity. The research being supported with the funding announced today will help us address important health issues affecting Canadians, such as cancer, heart disease and HIV/AIDS.”

###

This release is available in French.

Source: Mark Shainblum

McGill University

“Reprinted with permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

Reprinted with kind permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation© 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.