Prostate disorder proteins found

WESTERN AUSTRALIAN INSTITUTE FOR MEDICAL RESEARCH
MONDAY, 16 APRIL 2012
Innovative new technology has been used to identify and profile a novel combination of proteins that may improve treatment for prostate disorders. The study was published in the April 13th 2012 edition of the prestigious Journal of Biological Chemistry.
Researchers from the Western Australian Institute for Medical Research (WAIMR) and The University of Western Australia, in collaboration with the Monash Institute of Pharmaceutical Sciences in Melbourne, have used the novel G Protein-Coupled Receptor Heteromer Identification Technology.
Study senior author Associate Professor Kevin Pfleger co-invented this technology to identify and study 'G protein-coupled receptors', a family of 'receptors' that enable cells to respond to hormones and neurotransmitters. They are extremely important in treating disease and are the target of up to 50 per cent of all therapeutic drugs.
The technology was developed in the Laboratory for Molecular Endocrinology at WAIMR/UWA and assigned to the UWA spin-out company Dimerix Bioscience.
Associate Professor Pfleger, winner of the 2011 Australian Museum 3M Eureka Prize for Emerging Leader in Science, said G protein-coupled receptors were very important proteins on the outside of our cells that enabled signals from hormones and neurotransmitters to be transferred into the cell.
"Scientists now realise that these receptors do not work in isolation, but in particular combinations, which they call 'heteromers'," he said. "It is suggested that a number of side effects from drugs may result from not fully understanding which combinations form and what happens when they do."
Professor Pfleger said prostate disorders such as benign prostatic hyperplasia affected nearly every man at some point in his life. Better drugs with fewer side effects were needed to reduce or eliminate the need for surgical intervention in more serious cases, he said.
"This publication is itself the culmination of over four years of research and builds upon a decade of technological development in our laboratory," Professor Pfleger said.
"We hope that the identification of this novel combination of receptors, and the novel functioning that results from their interaction, will provide opportunities to develop better treatments for debilitating prostate disorders that affect so many ageing men."

UCLA-engineered stem cells seek out and kill HIV in living organisms By Enrique Rivero April 12, 2012

HIV virus
Expanding on previous research providing proof-of-principle that human stem cells can be genetically engineered into HIV-fighting cells, a team of UCLA researchers has now demonstrated that these cells can actually attack HIV-infected cells in a living organism.
The study, published April 12 in the journal PLoS Pathogens, demonstrates for the first time that engineering stem cells to form immune cells that target HIV is effective in suppressing the virus in living tissues in an animal model, said lead investigator Scott G. Kitchen, an assistant professor of medicine in the division of hematology and oncology at the David Geffen School of Medicine at UCLA and a member of the UCLA AIDS Institute. 
"We believe that this study lays the groundwork for the potential use of this type of an approach in combating HIV infection in infected individuals, in hopes of eradicating the virus from the body," he said. 
In the previous research, the scientists took CD8 cytotoxic T lymphocytes — the "killer" T cells that help fight infection — from an HIV-infected individual and identified the molecule known as the T cell receptor, which guides the T cell in recognizing and killing HIV-infected cells. However, these T cells, while able to destroy HIV-infected cells, do not exist in great enough quantities to clear the virus from the body. So the researchers cloned the receptor and used this to genetically engineer human blood stem cells. They then placed the engineered stem cells into human thymus tissue that had been implanted in mice, allowing them to study the reaction in a living organism.
The engineered stem cells developed into a large population of mature, multi-functional HIV-specific CD8 cells that could specifically target cells containing HIV proteins. The researchers also discovered that HIV-specific T cell receptors have to be matched to an individual in much the same way an organ is matched to a transplant patient.
In this current study, the researchers similarly engineered human blood stem cells and found that they can form mature T cells that can attack HIV in tissues where the virus resides and replicates. They did so by using a surrogate model, the humanized mouse, in which HIV infection closely resembles the disease and its progression in humans.
In a series of tests on the mice's peripheral blood, plasma and organs conducted two weeks and six weeks after introducing the engineered cells, the researchers found that the number of CD4 "helper" T cells — which become depleted as a result of HIV infection — increased, while levels of HIV in the blood decreased. CD4 cells are white blood cells that are an important component of the immune system, helping to fight off infections. These results indicated that the engineered cells were capable of developing and migrating to the organs to fight infection there.
The researchers did note a potential weakness with the study: Human immune cells reconstituted at a lower level in the humanized mice than they would in humans, and as a result, the mice's immune systems were mostly, though not completely, reconstructed. Because of this, HIV may be slower to mutate in the mice than in human hosts. So the use of multiple, engineered T cell receptors may be one way to adjust for the higher potential for HIV mutation in humans.
"We believe that this is the first step in developing a more aggressive approach in correcting the defects in the human T cell responses that allow HIV to persist in infected people," Kitchen said.
The researchers will now begin making T cell receptors that target different parts of HIV and that could be used in more genetically matched individuals, he said. 
Other study authors are Bernard R. Levin, Gregory Bristol, Valerie Rezek, Sohn Kim, Christian Aguilera-Sandoval, Arumugam Balamurugan, Otto O. Yang and Jerome A. Zack, all of UCLA.
The National Institutes of Health, the California HIV/AIDS Research Program, the California Institute for Regenerative Medicine, the UC Multicampus Research Program and Initiatives from the California Center for Antiviral Drug Discovery, and the UCLA Center for AIDS Research (CFAR) funded this study.
The UCLA AIDS Institute, established in 1992, is a multidisciplinary think tank drawing on the skills of top-flight researchers in the worldwide fight against HIV and AIDS, the first cases of which were reported in 1981 by UCLA physicians. Institute members include researchers in virology and immunology, genetics, cancer, neurology, ophthalmology, epidemiology, social sciences, public health, nursing and disease prevention. Their findings have led to advances in treating HIV, as well as other diseases, such as hepatitis B and C, influenza and cancer.

Gene therapy genes need 'off' switch: WA research investigates

 Gene therapy is a relatively new strategy that attempts to help injured brain cells survive and regrow and is being used to treat brain and spinal cord injury and neuro-degeneration. Image
THE alteration of nerve cell shape has been identified as a potential side effect of gene therapy.
The study, published in PLoS One, was led by Winthrop Professor Alan Harvey from UWA’s school of Anatomy, Physiology and Human Biology, and Associate Professor Jennifer Rodger, NHMRC Research Fellow in Experimental and Regenerative Neurosciences at UWA.
Gene therapy is a relatively new strategy that attempts to help injured brain cells survive and regrow and is being used to treat brain and spinal cord injury and neuro-degeneration.
Prof Harvey says his team has carried out work using modified viral vectors to introduce growth-promoting genes into injured nerve cells (neurons).
“We have looked at ways of protecting the neurons and getting them to regrow their nerve fibers after they are injured,” he says.
“But I had the concern that, using the current generation of commonly used vectors, the introduced gene is switched on all the time.”
“Once inside the cell, it’s likely that the new gene is constantly producing messages and constantly making its protein, which is not normally what happens with genes—they are switched on and off depending on when they’re needed.”
The team set out to determine what happened over a period of months to nerve cells in the retina that contained genes introduced by gene therapy, looking especially where the gene was “switched on” all the time and the protein, a growth factor, was being made consistently.
“There were changes in the shape of the processes of these cells over time,” Prof Harvey says.
“The changes varied depending on the type of growth factor gene that was introduced, but what was interesting was that the change didn’t only occur in the cells that contained the gene—the neighbouring cells changed as well, presumably due to secreted proteins present in the extracellular space,” he says.
Prof Harvey hopes this research raises a flag to what he says is an additional aspect that the gene therapy field really should be concerned about.
“If you are using these sorts of vectors and you can’t switch the gene off, then potentially that gene—if it’s making a protein that’s secreted into the extracellular space—may have all sorts of effects on those cells and on neighbouring cells,” Prof Harvey says
At this stage, the functional consequences of these findings are unknown.
“It is important to develop vectors where the expression of the introduced gene can be controlled, can be switched on or off when appropriate,” he says.

Ringworm (Tinea)

Ringworm facts

• Ringworm is a common fungal infection of the skin and is not due to a worm.
• The medical term for ringworm is tinea. The condition is further named for the site of the body where the infection occurs.
• Ringworm causes a scaly, crusted rash that may itch.
• Ringworm can be successfully treated with antifungal medications used either topically or orally.

What causes ringworm?

Although the world is full of yeasts, molds, and fungi, only a few cause skin problems. These agents are called the dermatophytes, which means "skin fungi." An infection with these fungi is sometimes known as dermatophytosis. Skin fungi can only live on the dead layer of keratin protein on top of the skin. They rarely invade deeper into the body and cannot live on mucous membranes, such as those in the mouth or vagina.
Scientific names for the most common of the dermatophyte fungi that cause ringworm include Trichophyton rubrum, Trichophyton tonsurans,Trichophyton interdigitale, and/or Trichophyton mentagrophytes,Microsporum canis, and Epidermophyton floccosum.

What is the treatment for ringworm? Are there home remedies?

Home remedies cannot cure ringworm. To cure ringworm, it is necessary to take antifungal medications. Ringworm can be treated topically (with external applications) or systemically (for example, with oral medications):
Topical treatment: When fungus affects the skin of the body or the groin, many antifungal creams can clear the condition in around two weeks. Examples of such preparations include those that contain clotrimazole (Cruex cream, Desenex cream, Lotrimin cream, lotion, and solution), miconazole (Monistat-Derm cream), ketoconazole (Nizoral cream), econazole (Spectazole), naftifine (Naftin), and terbinafine (Lamisil cream and solution). These treatments are effective for many cases of foot fungus as well. Many of these antifungal creams are available as over-the-counter preparations. It is usually necessary to use topical medications for at least two weeks.
Systemic treatment: Some fungal infections do not respond well to external applications. Examples include scalp fungus and fungus of the nails. To penetrate these areas and in cases of particularly severe or extensive disease, oral medications can be used.
For a long time, the only effective antifungal tablet was griseofulvin (Fulvicin, Grifulvin, and Gris-PEG). Now, other agents are available that are both safer and more effective. These include terbinafine, itraconazole (Sporanox), and fluconazole (Diflucan). Oral medications are usually given for a three-month course.

HEART DISEASE

FDA Warns Statin Users of Memory Loss and Diabetes Risks

By ALICE PARK | @aliceparkny | February 29, 2012 | 25

PHOTO RESEARCHERS / GETTY IMAGES

New safety warnings on statins like Zocor, above, cite increased risks of memory loss and diabetes.

The Food and Drug Administration (FDA) added new safety warnings to cholesterol-reducing statin drugs on Wednesday, noting increased risks of Type 2 diabetes and memory loss for patients who take the medications.

The changes to the prescribing information apply to the class of statins, including many popularly prescribed drugs such as Lipitor (atorvastatin), Crestor (rosuvastatin), Zocor (simvastatin) and Vytorin (simvastatin/ezetimibe). The new warnings are based on results from the latest clinical trials and reports of adverse events from patients, physicians and drugmakers.

The FDA said that statins may increase users’ risk of brain-related effects like memory loss and confusion. The reports have generally not been serious, however, and the symptoms go away once the drug is stopped, the agency said.

Statins’ labels will now also warn patients and doctors that the drugs may cause a small increase in blood sugar levels and Type 2 diabetes — an effect that has been shown previously in studies. Type 2 diabetes can further increase the risk of heart disease.

In addition, the FDA made a label change specific to Mevacor (lovastatin). Mevacor can interact with other drugs, increasing the risk for muscle pain and weakness, another side effect that has previously been associated with high-dose statin use. Other drugs may raise such risks by increasing the amount of statins in the blood, and the FDA warned that Mevacor should not be taken with protease inhibitors, which are used to treat HIV, certain antibiotics and some anti-fungal medications.

At the same time, the statins’ labeling will no longer require the routine monitoring of patients’ liver enzymes, which was originally intended to alert doctors if the medications were becoming toxic and starting to damage the liver. The FDA concluded that such serious damage is rare, and regular testing for all users isn’t necessary. The agency now recommends that liver enzyme tests be performed before starting statin therapy, and as clinically indicated thereafter.

MORE: Who Should Take Statins? The Debate Continues

Despite the new safety warnings, the agency said patients should not be scared off statins. “The value of statins in preventing heart disease has been clearly established,” said Dr. Amy G. Egan, deputy director for safety in the FDA’s division of metabolism and endocrinology products, in an agency statement. “Their benefit is indisputable, but they need to be taken with care and knowledge of their side effects.”

But some experts worried that the labeling changes would result in unnecessarily alarming patients and causing some who may benefit to shy away. “I do not believe there is enough hard evidence to justify information and warnings about memory loss and confusion or increase in blood sugar,” Dr. Scott Grundy of the University of Texas Southwestern Medical Center told MedPage Today. “I also think that these warnings will cause some people who need statins to stop taking them. That would be unfortunate.”

In general, however, experts tended to support the FDA’s action, noting that while the potential diabetes and cognitive side effects were rare, they should still be highlighted to doctors and patients. “These are reasonable and prudent recommendations,” Dr. Steven Nissen of the Cleveland Clinic also told MedPage Today. “I am pleased that FDA did not overstate the diabetes and cognitive function risks. Both problems are uncommon and don’t diminish the importance of statins in cardiovascular protection. For the vast majority of patients, the benefits far outweigh the risks.”

Dr. Gordon Tomaselli, president of the American Heart Association noted people concerned about their cholesterol levels should always focus on prevention through lifestyle changes first, trying drug treatment only if their physicians recommend it. “As with all therapies, the decision to use statins for primary or secondary prevention must include careful consideration of the risks and benefits, side effects and cost,” Tomaselli said in a statement. “The FDA’s announcement on the label changes does not question the benefit of statins to lowering cholesterol, but it does provide patients and healthcare providers the most current information about the safe use of statins.”

Read more: http://healthland.time.com/2012/02/29/fda-warns-statin-users-of-memory-loss-and-diabetes-risks/#ixzz1rkrJrsD9

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