 |
|
New lab test offers better prediction of HIV microbicide safety
July 10, 2009Scientists at Albert Einstein College of Medicine of Yeshiva University have devised a laboratory test for predicting whether microbicides against HIV are safe for human use. The researchers have also discovered why several supposedly "safe" microbicides made women more susceptible to HIV infection. The study appears today in the online version of the Journal of Infectious Diseases.
For years, scientists have been trying to develop a topical vaginal microbicide for preventing transmission of HIV, the virus that causes AIDS. A safe and effective microbicide would help protect women in settings where male condoms are not used - a common situation in many cultures. The need for an HIV microbicide is especially urgent in Africa, where AIDS is the leading cause of death and where women account for six out of ten of those living with HIV.
Several microbicide gels have been assessed in clinical trials after passing laboratory and animal safety tests. But with just one exception, all the microbicides were found to be ineffective against HIV; and two of the gels - nonoxynol-9 and cellulose sulfate - actually increased the risk of HIV infection in women.
"Our goal was to develop assays that are predictive of safety before proceeding to clinical trials that typically cost millions of dollars, involve thousands of women, and take many years," says study leader Betsy C. Herold, M.D., professor of pediatrics, of microbiology & immunology, and of obstetrics & gynecology and women's health at Einstein.
In evaluating a microbicide's safety, researchers look primarily for signs that the chemical inflames cells of the vaginal lining, or epithelium. That could cause more harm than good: When the epithelium becomes inflamed, T cells flock to the damaged area - which might actually encourage HIV infection, since T cells are the main targets of HIV.
Dr. Herold theorized that another mechanism may also compromise a microbicide's safety. The cells of the vaginal epithelium normally are tightly packed together, forming an impermeable barrier to HIV. If a microbicide disrupts the barrier's structural integrity, HIV would be able to slip through the gaps and infect circulating T cells.
To test this theory, Pedro Mesquita, a postdoctoral fellow in Dr. Herold's lab, developed a model that mimicked the genital tract environment. It was composed of two chambers separated by a barrier of cultured human cells that form tight junctions. After treating the epithelial cells with different microbicides, the researchers tested the barrier's permeability to HIV by placing HIV in the upper chamber, T cells in the lower chamber, and then monitoring the infection of the T cells over time.
When the epithelial barrier was treated with placebo, HIV was unable to pass through to the lower chamber, leaving the T cells uninfected. "But when we applied nonoxynol-9, the virus went right through the barrier and infected the T cells," says Dr. Herold. This result was no surprise, since nonoxynol-9 is a detergent, a class of chemicals known to be disruptive to cells. What was surprising, she says, was to observe the same result with cellulose sulfate ─ a sulfated polymer that is not a detergent and was shown to be safe in all of the other bioassays and in early clinical trials. These findings may explain the unanticipated clinical trial results in which use of cellulose sulfate was associated with an increase in HIV transmission.
The researchers later tested their model on two other microbicide candidates now being evaluated in large-scale clinical efficacy trials. Both drugs - tenofovir and PRO 2000 -performed well by not disrupting the epithelial barrier.
"Our findings strongly suggest that microbicides can increase the risk of HIV infection through a mechanism other that inflammation - namely, by disrupting the protective epithelial cell barrier," says Dr. Herold. "If confirmed by further study, this assay should be used early on to screen for microbicide safety before advancing a product to clinical trials involving thousands of women," she adds.
Dr. Herold is also developing animal models for evaluating microbicides. Since these models use actual epithelial tissue, they could offer even better predictions of microbicide safety.
Dr. Herold's paper, "Disruption of tight junctions by cellulose sulfate facilitates HIV infection: Model of microbicide safety," was published July 8, 2009 in the online version of the Journal of Infectious Diseases. All research was conducted at Einstein. Pedro M. M. Mesquita, Ph.D., was the lead author. Other Einstein co-authors were Natalia Cheshenko, Sarah S. Wilson, Mohak Mhatre, Esmeralda Guzman, Esra Fakioglu, and Marla J. Keller.
Albert Einstein College of Medicine
"Our goal was to develop assays that are predictive of safety before proceeding to clinical trials that typically cost millions of dollars, involve thousands of women, and take many years," says study leader Betsy C. Herold, M.D., professor of pediatrics, of microbiology & immunology, and of obstetrics & gynecology and women's health at Einstein.
In evaluating a microbicide's safety, researchers look primarily for signs that the chemical inflames cells of the vaginal lining, or epithelium. That could cause more harm than good: When the epithelium becomes inflamed, T cells flock to the damaged area - which might actually encourage HIV infection, since T cells are the main targets of HIV.
Dr. Herold theorized that another mechanism may also compromise a microbicide's safety. The cells of the vaginal epithelium normally are tightly packed together, forming an impermeable barrier to HIV. If a microbicide disrupts the barrier's structural integrity, HIV would be able to slip through the gaps and infect circulating T cells.
To test this theory, Pedro Mesquita, a postdoctoral fellow in Dr. Herold's lab, developed a model that mimicked the genital tract environment. It was composed of two chambers separated by a barrier of cultured human cells that form tight junctions. After treating the epithelial cells with different microbicides, the researchers tested the barrier's permeability to HIV by placing HIV in the upper chamber, T cells in the lower chamber, and then monitoring the infection of the T cells over time.
When the epithelial barrier was treated with placebo, HIV was unable to pass through to the lower chamber, leaving the T cells uninfected. "But when we applied nonoxynol-9, the virus went right through the barrier and infected the T cells," says Dr. Herold. This result was no surprise, since nonoxynol-9 is a detergent, a class of chemicals known to be disruptive to cells. What was surprising, she says, was to observe the same result with cellulose sulfate ─ a sulfated polymer that is not a detergent and was shown to be safe in all of the other bioassays and in early clinical trials. These findings may explain the unanticipated clinical trial results in which use of cellulose sulfate was associated with an increase in HIV transmission.
The researchers later tested their model on two other microbicide candidates now being evaluated in large-scale clinical efficacy trials. Both drugs - tenofovir and PRO 2000 -performed well by not disrupting the epithelial barrier.
"Our findings strongly suggest that microbicides can increase the risk of HIV infection through a mechanism other that inflammation - namely, by disrupting the protective epithelial cell barrier," says Dr. Herold. "If confirmed by further study, this assay should be used early on to screen for microbicide safety before advancing a product to clinical trials involving thousands of women," she adds.
Dr. Herold is also developing animal models for evaluating microbicides. Since these models use actual epithelial tissue, they could offer even better predictions of microbicide safety.
Dr. Herold's paper, "Disruption of tight junctions by cellulose sulfate facilitates HIV infection: Model of microbicide safety," was published July 8, 2009 in the online version of the Journal of Infectious Diseases. All research was conducted at Einstein. Pedro M. M. Mesquita, Ph.D., was the lead author. Other Einstein co-authors were Natalia Cheshenko, Sarah S. Wilson, Mohak Mhatre, Esmeralda Guzman, Esra Fakioglu, and Marla J. Keller.
Albert Einstein College of Medicine
Microbicide Current Events and Microbicide News RSSScientists develop a new HIV microbicide -- and a way to mass produce it in plants
In what could be a major pharmaceutical breakthrough, research published online in The FASEB Journal describes how scientists from St George's, University of London have devised a one-two punch to stop HIV.
Clinical trial finds microbicide promising as HIV prevention method for women
A clinical trial involving more than 3,000 women in the U.S. and southern Africa demonstrates for the first time the promise of a vaginal microbicide gel for preventing HIV infection in women.
Anti-HIV gel shows promise in large-scale study in women
An investigational vaginal gel intended to prevent HIV infection in women has demonstrated encouraging signs of success in a clinical trial conducted in Africa and the United States.
UT Pathologists Believe They Have Pinpointed Achilles Heel of HIV
Human Immunodeficiency Virus (HIV) researchers at The University of Texas Medical School at Houston believe they have uncovered the Achilles heel in the armor of the virus that continues to kill millions.
HIV prevention researchers to compare common ARV as a pill and vaginal gel in unique study
In battle with an epidemic that has outpaced nearly all efforts to contain it, researchers are turning to strategies centered on the same antiretroviral (ARV) drugs that have been used successfully to treat HIV in hopes they will be as effective a stronghold for preventing the virus.
Anti-HIV gel proven safe, tolerable for women
An experimental anti-HIV gel is safe for women to use on a daily basis, according to researchers at the University of Alabama at Birmingham (UAB) and the University of Pittsburgh School of Medicine.
Safety of new microbicide for HIV prevention to be tested in young women in US trial
Nearly half of all people infected with HIV/AIDS are now women, the majority of whom contracted the disease through sexual intercourse with male partners.
Phase III trials of cellulose sulfate microbicide for HIV prevention closed
CONRAD, a reproductive health research organization, announced today that it has halted a Phase III clinical trial of cellulose sulfate — a topical microbicide gel being tested for HIV prevention in women — because preliminary results indicated that cellulose sulfate could lead to an increased risk of HIV infection in women who use the compound.
Study defines effective microbicide design for HIV/AIDS prevention
Duke University biomedical engineers have developed a computer tool they say could lead to improvements in topical microbicides being developed for women to use to prevent infection by the virus that causes AIDS.
Anti-HIV drug has potential to prevent transmission in women
A new study from infectious disease researchers at The Miriam Hospital and Brown Medical School finds that a drug already given orally to treat HIV is also safe when applied as a vaginal microbicide gel.
More Microbicide Current Events and Microbicide News Articles
 |
Directory of Microbicides for the Protection of Materials and Processes by Wilfried Paulus (Editor) The book presents a comprehensive discussion of the most common microbicides (approx. 300) used for the protection of materials and processes against biodeterioration. The characteristics of each microbicide, e.g. chemical and physical properties, effectiveness and spectrum of efficacy, the knowledge of which is a prerequisite for the effective use of microbicides, are discussed. It is also informed about the toxicity and ecotoxocity of the microbicides. The corresponding depth of knowledge and experience makes uses of microbicides possible without damage to human health and environment. The corresponding legislative aspects are regarded in a special chapter. This new book is not a simple revised new edition (second) of the Handbook Microbicides for the Protection of... |
 |
Care Tech Techni Care Surgical Scrub 8 Oz Bottle Broad Spectrum Topical Microbicide - Model c222-8z by Care Tech Care Tech Techni Care Surgical Scrub 8Oz Bottle Broad Spectrum Topical Microbicide - Model c222-8z |
 |
Diesel Fuel Microbicide 16Oz Multi Fuel Microbiocide 960Ga by PRI Add PRI-OCIDE to your diesel fuel to instantly kill any bacteria, algae, or fungi that has grown in the fuel, and to prevent any further growth. PRI-OCIDE is a synergistic combination of two microbiocides designed to provide a broad spectrum of microbicidal activity, especially where the control of such growth has historically been difficult. PRI-OCIDE contains two active ingredients that work together synergistically to kill growth in both the water and emulsified oil phases. PRI-OCIDE penetrates the emulsified oil phase, killing growth therein, and quickly disperses into the water phase, where the bulk of mirco-organisms grow. As PRI-OCIDE kills these microorganisms, the emulsified oil separates and this valuable fuel is returned to a usable form. The creation of sludge is... |
 |
Microbicides for the Protection of Materials: A Handbook by W. Paulus (Author) This handbook presents the first discussion of approximately 250 of the commonest microbicides and their related production processes. They are arranged in substance classes such as alcohols and oxidizing agents, and information about the physical and chemical properties of each microbicide, its toxicity and ecotoxicity, anitimicrobial effectiveness, mode of action and its uses is provided. |
|
Business Wire : NIH Initiates International Microbicide Trial Including Pro 2000. by Business Wire (Publisher) | |
|
|
Diesel Fuel Microbicide 16Oz Multi Fuel Microbiocide 960Ga by PRI Add PRI-OCIDE to your diesel fuel to instantly kill any bacteria, algae, or fungi that has grown in the fuel, and to prevent any further growth. PRI-OCIDE is a synergistic combination of two microbiocides designed to provide a broad spectrum of microbicidal activity, especially where the control of such growth has historically been difficult. PRI-OCIDE contains two active ingredients that work together synergistically to kill growth in both the water and emulsified oil phases. PRI-OCIDE penetrates the emulsified oil phase, killing growth therein, and quickly disperses into the water phase, where the bulk of mirco-organisms grow. As PRI-OCIDE kills these microorganisms, the emulsified oil separates and this valuable fuel is returned to a usable form. The creation of sludge is... |
 |
SILVER SOFT 7.1 oz by LaSalle Laboraties Silversoft Special Naturally formulated Silver Soft for Skin soothes, softens, and sanitizes your skin. Use it on all external body parts from head to toe to relieve dry, cracked skin, burns, acne, cold sores, abrasions, sunburn, rashes, bites, and cuts. Silver Soft is uniquely effective in killing germs, bacteria, viruses, and fungus on contact-without the use of harsh, skin-drying chemicals like alcohol, iodine, or chlorine. Silver Softs active germ-killing ingredient is Chelated Silver-microscopic particles of silver evenly dispersed throughout a healthful, skin-loving solution of deonized water, glycerine, and fruit polypectate. The silver ions in Silver Soft are chemically bonded to nonmetallic ions in solution (not merely in suspension, as in colloidal silver). This in-solution... |
|
Vaginal microbicide provides 24-hour protection in study.(INFECTIOUS DISEASES): An article from: Skin & Allergy News by Kate Johnson (Author) This digital document is an article from Skin & Allergy News, published by International Medical News Group on September 1, 2009. The length of the article is 558 words. The page length shown above is based on a typical 300-word page. The article is delivered in HTML format and is available immediately after purchase. You can view it with any web browser. Citation Details Title: Vaginal microbicide provides 24-hour protection in study.(INFECTIOUS DISEASES) Author: Kate Johnson Publication: Skin & Allergy News (Magazine/Journal) Date: September 1, 2009 Publisher: International Medical News Group Volume: 40 Issue: 9 Page: 31(1) Distributed by Gale, a part of Cengage... | |
|
Setbacks and steps forward in the search for safe and effective microbicides.: An article from: Women's Health Activist by Bindiya Gillenwater Patel (Author) This digital document is an article from Women's Health Activist, published by Thomson Gale on May 1, 2007. The length of the article is 2283 words. The page length shown above is based on a typical 300-word page. The article is delivered in HTML format and is available in your Amazon.com Digital Locker immediately after purchase. You can view it with any web browser. Citation Details Title: Setbacks and steps forward in the search for safe and effective microbicides. Author: Bindiya Gillenwater Patel Publication: Women's Health Activist (Magazine/Journal) Date: May 1, 2007 Publisher: Thomson Gale Volume: 32 Issue: 3 Page: 1(3) Distributed by Thomson... | |
|
Spermicidal microbicide joins contraceptive armamentarium.: An article from: Skin & Allergy News by Gale Reference Team (Author) This digital document is an article from Skin & Allergy News, published by Thomson Gale on December 1, 2006. The length of the article is 472 words. The page length shown above is based on a typical 300-word page. The article is delivered in HTML format and is available in your Amazon.com Digital Locker immediately after purchase. You can view it with any web browser. Citation Details Title: Spermicidal microbicide joins contraceptive armamentarium. Author: Gale Reference Team Publication: Skin & Allergy News (Magazine/Journal) Date: December 1, 2006 Publisher: Thomson Gale Volume: 37 Issue: 12 Page: 39(1) Distributed by Thomson... |
| © 2009 BrightSurf.com |