Boldebolin by Alpha-Pharma Healthcare

Boldebolin by Alpha-Pharma Healthcare is an injectable steroid which contains the hormone Boldenone Undeclynate.

Boldenone is a very popular steroid. Boldebolin is a highly anabolic, moderately androgenic steroid. For this very reason, Boldebolin is typically taken in a stack with other steroids like Testosterone if you are on a mass cycle or perhaps with Winstrol if you are on a cutting cycle. The main benefit of taking Boldebolin is that Boldenone increases protein synthesis in the muscle cells. This effect of Boldebolin is very similar to what you would experience while taking Anavar. Boldebolin gives you slower but much more high quality gains in muscle as opposed to the normal "quick" muscle gains that you would expect from a testosterone. Boldebolin is not a rapid mass builder, instead it provides a slow but steady gain of strength and quality of muscle mass. The most positive effects of Boldebolin are seen when it is used for longer cycles, usually lasting more than 8-10 weeks in duration. You can expect around 3 weeks before you start seeing results and they are not going to be staggering, but will be "more permanent" than any gains you would get from any of the multiple testosterones that are available. Boldenone stays active in the system longer than most of the testosterones as well. This makes Boldebolin a poor choice if you run the possibility of being drug tested.

Boldebolin is very common in the precontest arena for two main reasons. First off, there is a low amount of aromitization and secondly there is very little water retention while taking Boldebolin. This makes Boldebolin a good precontest steroid. Boldebolin is well known to give a good increase in the pumps you get while working out. This is caused from the increase in red blood cells that you will experience while taking Boldebolin. It is also well known to help cause a dramatic increase in appetite. Boldebolin is a very versatile compound.

We can create a number of drug combinations with it depending on the desired result. For mass (bulking cycle), one may want to stack it with Anadrol or Sustanon (any injectable testosterone). The result should be an incredible gain of muscle size and strength, without the same intensity of side effects if using the androgen (at a higher dose) alone. When used in a cutting cycle, muscle hardness and density can be greatly improved when combining Boldebolin with a non-aromatizable steroid such as Trenbolone Acetate or Winstrol. For some however, even the low buildup of estrogen associated with Boldebolin is enough to relegate its use to bulking cycles only.



GP Clen (clenbuterol) by Geneza Pharmaceuticals

GP Clen is an weight loss drug, its active substance is Clenbuterol. This drug is manufactured by Geneza Pharmaceuticals.

Clenbuterol belongs to the class of drugs classified as sympathomimetics. Sympathomimetic drugs are compounds that mimic or imitate the effects of the hormone epinephrine (adrenaline) and the hormone/neurotransmitter norepinephrine (noradrenaline). Clenbuterol is a popular drug prescribed as a decongestant and bronchodilator and commonly used by sufferers of asthma. However, it is now becoming popular as a dietary supplement endorsed as an effective slimming pill.

GP Clen (clenbuterol) by Geneza Pharmaceuticals is on of the most popular and potent cutting agents available. GP Clen (clenbuterol) by Geneza Pharmaceuticals is known to burn fat with thermogenic properties and also build lean muscle mass. Clenbuterol is a potent, long-lasting bronchodilator that is used in some European countries to treat asthma and related lung disorders. However, the drug is also a potent thermogenic agent and can selectively decrease fat and increase lean muscle mass. This property of GP Clen (clenbuterol) by Geneza Pharmaceuticals has made it a widely abused drug among many individuals. Because of this selective partitioning effect, the drug is widely abused by both amateur and professional athletes around the world.

Many bodybuilders, as well as other athletes, find GP Clen (clenbuterol) by Geneza Pharmaceuticals beneficial because of its thermogenic abilities. As a thermogenic it increases blood pressure, stimulating the heart muscles. This stimulation, in turn, leads to an increase in body temperature. In addition, GP Clen (clenbuterol) by Geneza Pharmaceuticals boosts glycogenolysis, or the breakdown of glycogen. This process results to release of glycogen into the bloodstream (in the form of glucose) and renders the body incapable of storing or using more glycogen. This hikes the rate at which fat and protein are used up in the body for these three essential purposes – energy production, for recycling of their molecular components, or for their excretion. This is how GP Clen (clenbuterol) by Geneza Pharmaceuticals users lose adipose (fat) tissues.

GP Clen (clenbuterol) by Geneza Pharmaceuticals is also particularly appealing to bodybuilders and other athletes because it heightens aerobic capacity. Aerobic means "with oxygen", and refers to the use of oxygen in the body's metabolic or energy-generating process. In simple terms, GP Clen (clenbuterol) by Geneza Pharmaceuticals improves oxygen transportation via increased blood pressure. This makes Clenbuterol a staple of many endurance athletes’ drug protocol.

This drug is also used as an anabolic agent although its anabolism effect remains a contentious issue. In several animal studies, it has exhibited anabolism resulting to muscle gains. However, this has not been observed on human subjects.

The recommended regimen with this drug is to gradually ramp up its dosage. Slowly build up the intake each day until an effective and comfortable range is established. This way, most of the drug’s effects can be avoided, specifically its negative effect on blood pressure. Males typically take 2-8 tablets a day while females take 2 - 4 tablets a day.

The length of time this drug is to be cycled is dependent on the goal of the user. If your objective is to lose fat, GP Clen (clenbuterol) by Geneza Pharmaceuticals highest efficacy is observed when taken in a period of 4 - 6 weeks. During this phase, it is important to monitor temperature increase or decrease.

Remember that as a thermogenic this drug works by elevating the temperature, and thus a decrease or a drop in temperature means its losing its potency. This also signals that you need to break for at least several weeks. Increasing the dosage or prolonging the intake will prove to be ineffective and a total waste of money since the decreased efficacy may mean that the body is growing immune or resistant to its effects.

To heighten its fat-burning ability, many stack GP Clen (clenbuterol) by Geneza Pharmaceuticals with other drugs such as the thyroid hormone Cytomel. This stack is great during contest preparation or cutting cycle when bodybuilders need to get rid of undesirable fat without sacrificing caloric intake.

GP Clen (clenbuterol) by Geneza Pharmaceuticals is also typically stacked with non-aromatizing anabolic steroids, those that do not cause water retention. This stack regimen induces the so-called synergistic effect of drugs.

GP Clen (clenbuterol) by Geneza Pharmaceuticals dosage is dependent on body weight and can be optimized by measuring the body temperature. Athletes usually take 5 - 7 tablets, 100 - 140 mcg per day. For women 80 - 100 mcg/day is usually sufficient. It is advisable to begin GP Clen (clenbuterol) by Geneza Pharmaceuticals by taking only one tablet on the first day and then increasing the dosage by one tablet each of the following days until the desired maximum dosage is reached. The compound is usually taken over a period of 8 - 10 weeks.

Possible side effects of GP Clen (clenbuterol) by Geneza Pharmaceuticals include restlessness, palpitations, tremor (involuntary trembling of fingers), headache, increased perspiration, insomnia, muscle spasms, increased blood pressure, and nausea. Individuals who have been diagnosed of cardio-vascular problems should not take GP Clen (clenbuterol) by Geneza Pharmaceuticals. 

GP Andromix by Geneza Pharmaceuticals

GP Andromix is a product brought to you by Geneza Pharmaceuticals. It is a professionally manufactured blend of 3 different hormones in equal quantities, which are all known for their effects in building and enhancing musculature in the body. The product is a liquid blend of these chemicals which is injected directly into the intra-muscular spaces in order to have a direct and significant effect on muscle mass. GP Andromix is appropriately named as it has a very high androgen content. Androgen is known for the effect it has on increasing muscle mass and leading to greater definition in muscle shape. Users of GP Andromix from Geneza Pharmaceuticals will usually inject 1cc per day or 2ccs every other day as part of their steroid cycle.

GP Andromix contains 3 different hormones and these are Testosterone, Trenbolone Acetate (a form of trenbolone) and Masteron. Each 10 millilitre vial contains equal quantities of the 3 hormones, working out at 150 milligrams per millilitre. All 3 of these hormones have the effect of increasing the level of muscle in the body and in combination with each other these effects are compounded. It is popular with athletes and body-building enthusiasts who use it in cycles to remain lean whilst “bulking up” their muscles.

Taking each of these hormones in turn, what are the desirable effects of the testosterone included in this blend? Well, testosterone is the male sex hormone and is present in male bodies in greater quantities than in females. This is why male bodies generally comprise significantly higher muscle levels and significantly lower fat levels than women. The testosterone contained in GP Andromix is a particularly fast acting preparation of the hormone and allows users to gain leaner muscle through its use. Negative side-effects of excess testosterone in the system are well-documented and include hair loss and increased secretion of oil thorough the skin.

The second active substance included in GP Andromix is the hormone trenbolone acetate, often referred to in its abbreviated form, Trenbolone Acetate or tren. This hormone brings many advantages in terms of bodybuilding and developing muscles artificially. Trenbolone Acetate strength and potency as a hormone is the first of these advantages. Trenbolone Acetate is generally considered 3 times as strong in anabolic terms as testosterone. Trenbolone Acetate popularity as a muscle-enhancing substance is largely due to the fact that it results in a hard-looking, “ripped” appearance for its users. Trenbolone Acetate has this effect more noticeably than other similar chemicals because other hormones are broken down by the body into oestrogen, the female hormone, which can reverse some of the impact. Trenbolone acetate dos not break down in this well.

The third and final compound in this hormone mixture is Masteron. Its side-effects include an increase in general strength, but also in feelings of aggression, seen by some to be positive and by others to be negative. Masteron is popular amongst bodybuilders for the same reason as the other hormones already described. Masteron finds particular favour because of its dramatic effects. Many competition body-builders use Masteron directly before competing because it gives their physiques an impressively toned appearance.

Cell-associated HIV mucosal transmission: The neglected pathway

Dr. Deborah Anderson from Boston University School of Medicine (BUSM) and her colleagues are challenging dogma about the transmission of the human immunodeficiency virus type 1 (HIV-1). Most research has focused on infection by free viral particles, while this group proposes that HIV is also transmitted by infected cells. While inside cells, HIV is protected from antibodies and other antiviral factors, and cell-to-cell virus transmission occurs very efficiently through intercellular synapses. The Journal of Infectious Diseases (JID) has devoted their December supplement to this important and understudied topic.

The 10 articles, four from researchers at BUSM, present the case for cell-associated HIV transmission as an important element contributing to the HIV epidemic. Anderson chides fellow researchers for not using cell-associated HIV in their transmission models: "The failure of several recent vaccine and microbicide clinical trials to prevent HIV transmission may be due in part to this oversight."

Approximately 75 million people in the world have been infected with HIV-1 since the epidemic started over 30 years ago, mostly through sexual contact and maternal-to-child transmission. A series of vaccine and microbicide clinical trials to prevent HIV transmission have been unsuccessful, and scientists are returning to the drawing board to devise new approaches. The JID supplement advocates for new strategies that target HIV-infected cells in mucosal secretions.

The publication presents evidence that HIV-infected cells populate genital secretions from HIV-infected men and women as well as breast milk, and genetic evidence suggesting that cell-associated HIV transmission occurs in people. Various models for studying cell-associated HIV transmission and molecular targets for intervention are also presented. Finally, the efficacy of current HIV prevention strategies against cell-associated HIV transmission and opportunities for further development are described.

Bone metastases in prostate cancer blocked by HIV drug

The receptor CCR5, targeted by HIV drugs, is also key in driving prostate cancer metastases, suggesting that blocking this molecule could slow prostate cancer spread

Although prostate cancer can be successfully treated in many men, when the disease metastasizes to the bone, it is eventually lethal. In a study researchers show that the receptor CCR5 best known for its role in HIV therapy, may also be involved in driving the spread of prostate cancer to the bone.

"Because this work shows we can dramatically reduce metastasis in pre-clinical models, and because the drug is already FDA approved for HIV treatment- we may be able to test soon whether this drug can block metastasis in patients with prostate cancer," says Richard Pestell, M.D., Ph.D., MBA, Director of the Sidney Kimmel Cancer Center at Thomas Jefferson University and senior author on the study.

The work builds on previous research from Dr. Pestell's lab that showed in 2012 that CCR5 signaling was key in the spread of aggressive forms of breast cancer to the lungs. Their prior paper demonstrated that breast cancer cells that carried the CCR5 receptor on their surface were drawn to the lung. Given that prostate cancer cells were attracted to the bone and brain, Pestell's team investigated whether CCR5 could play a role in prostate cancer metastases as well.

The research was complicated by the fact that there was no immune competent mouse model of prostate cancer that reliably developed bone and brain metastases. So the researchers developed a prostate cancer cell line, driven by an upregulated Src gene, that regularly caused bone metastases in immune-competent mouse models. Because the immune system is so important in human prostate cancer it was important to develop a model that reflected human disease.

The researchers analyzed the genes of the metastasized bone and brain tumors and found genes driving the cancer were also involved in the CCR5 signaling pathway. To investigate further, the researchers administered the CCR5-blocking drug maraviroc to the new prostate cancer mouse model. In comparison to control animals, maraviroc dramatically reduced the overall metastatic load by 60 percent in the bone, brain and other organs.

Finally, in order to determine whether a similar mechanism might be at play in human prostate cancer, the researchers mined the genomic data of patients with prostate cancer and found that CCR5 was more highly expressed in prostate cancer tissue compared with normal tissue, and even more highly expressed in metastases compared with primary tumors. "In fact, we noticed that patients who had a lower expression of the CCR5-pathway genes had a longer survival times, whereas high expression of these CCR5 genes was associated with a shorter overall survival," said co-first author Xuanmao Jiao, Ph.D., and an instructor in the department of Cancer Biology at Jefferson.

Hepatitis C ruled out as cause of mental impairment in HIV patients

To stop these changes, scientists have to learn what is causing them. One possibility researchers are considering is that long-term infections with other pathogens, common in HIV-positive patients, are affecting the brain. But a new study has eliminated one of their prime suspects: the hepatitis C virus, which infects about one in every three HIV-positive patients in the United States.

The research, conducted by a team that includes scientists at Washington University School of Medicine in St. Louis, appeared Dec. 10 in Neurology.
"Hepatitis C infection has serious long-term side effects, such as damage to the liver, but our research indicates that it does not affect the brain," said lead author David Clifford, MD, of Washington University.

The research was conducted as part of the CNS HIV Anti-retroviral Therapy Effects (CHARTER) study, a multicenter collaborative that is examining the long-term neurological effects of HIV infection.

Hepatitis C most commonly infects illicit-drug users who share needles used to inject the drugs. Drug abuse can harm the brain, making it difficult to determine whether hepatitis C or problems caused by drug use contribute to brain impairment in patients with both HIV and hepatitis C.

To answer this question, Clifford and his colleagues studied 1,582 HIV patients, 408 of whom were also infected with hepatitis C. Each patient received a detailed neuropsychological exam devised by Clifford and other CHARTER researchers to detect signs of HIV-associated mental deficits.

The exam takes two to 2 1/2 hours, and includes written examinations taken by the patient and physical exams given by medical professionals. Patients are tested for their ability to express themselves, to make decisions, to learn and retain new information using multiple types of memory, and to move the body and control muscles.

"In all, we looked at seven domains of mental function," said Clifford, who is the Melba and Forest Seay Professor of Clinical Neuropharmacology in Neurology. "We studied their overall performance and looked at each domain individually and found no evidence that the group with hepatitis C performed worse."

According to Clifford, this was particularly impressive because the participants in the group with hepatitis C were older, had less education and had lower scores on tests of reading, comprehension, spelling and math.

With hepatitis C eliminated, Clifford and his colleagues are turning their attention to the immune responses triggered by HIV in the brain and the bowel during the initial stages of infection. He and others believe these early responses, which include bursts of inflammation, lead to chronic inflammation that adversely affects the brain.

"If a hepatitis C infection gets to the point where it damages liver function, the resulting inflammation might well contribute to mental impairment," Clifford said. "Beyond that, though, it doesn't seem to be an active collaborator in the harm HIV does to the brain."

People with mental illness more likely to be tested for HIV

People with mental illness are more likely to have been tested for HIV than those without mental illness, according to a new study. The researchers also found that the most seriously ill – those with schizophrenia and bipolar disease – had the highest rate of HIV testing

The study assessed nationally representative data from 21,785 adult respondents from the 2007 National Health Interview Survey (NHIS) and provides an update of prior research using 1999 and 2002 NHIS data. The 2007 version is the most recent cycle of the survey that included information both on mental health diagnoses and HIV testing.

The current Penn-led study adds precision to earlier research by reporting on HIV-testing rates according to specific mental health diagnoses; previous studies did not differentiate persons with, for example, depression, bipolar disorder, and schizophrenia spectrum disorder.

The researchers found that 15 percent of respondents reported a psychiatric disorder. Of these, 89 percent had symptoms of depression and/or anxiety, 8.5 percent had bipolar disorder, and 2.6 percent had schizophrenia spectrum disorder. Among persons reporting at least one mental illness, 48.5 percent had been tested for HIV. The 48.5 percent rate compares to a testing rate of 35 percent among those without mental illness. More specifically, 64 percent of persons with schizophrenia, 63 percent of persons with bipolar disorder, and 47 percent of persons with depression and/or anxiety reported ever being tested for HIV.

"Our study shows that persons with mental illness and/or their care providers recognize that they are at higher risk and should be tested," said senior author Michael B. Blank, PhD, associate professor in Psychiatry at Penn and co-director of the Penn Mental Health AIDS Research Center. "However, by no means we should be complacent since these results may in large part be due to individual vigilance. The fact is there are few formal prevention and screening efforts targeted at this at-risk population. In light of the fact that mentally ill people are more likely to engage in risky behavior, mental health providers should consider routinely offering HIV/AIDS testing, something that does not typically occur now."

HIV infection and mental illness are often co-occurring health conditions, with nearly half of persons living with HIV having a psychiatric disorder while between 5-23 percent of those with mental illness are infected with HIV.

In addition, the study found that persons aged 25-44, women, racial and ethnic minorities, individuals who are windowed/divorced/separated, those reporting excessive use of alcohol or tobacco, and persons with HIV risk factors were significantly more likely to be tested for HIV than their counterparts.
Separate research has found that mentally ill individuals are more likely than others to engage in high-risk behaviors associated with HIV transmission, including unprotected sexual intercourse, injection drug use, and sex with multiple partners.

"Our finding that persons with mental illness were tested for HIV at a higher rate than those without mental illness is encouraging and consistent with previous analyses," said lead author Baligh R. Yehia, MD, MPP, MSHP, assistant professor of Medicine at the Perelman School of Medicine at the University of Pennsylvania and director of the Penn Medicine Program for LGBT Health. "However, the large number of people with mental illness who still have not been tested necessitates increased public health prevention efforts, particularly in light of the increased HIV risk in this population."

The CDC recommends that all persons aged 13-64 be tested for HIV in healthcare settings and that persons with increased risk such as injecting drug users and their sex partners, sex workers, men who have sex with men, and heterosexuals with multiple sex partners be tested at least annually.

HIV/AIDS drugs could be repurposed to treat AMD, researchers suggest

Drugs that have been used for the past 30 years to treat HIV/AIDS, could be repurposed to treat the dry form of age-related macular degeneration (AMD), a new study suggests. Age-related macular degeneration is a progressive condition that is untreatable in up to 90 percent of patients and is a leading cause of blindness in the elderly worldwide. The two forms of age-related macular degeneration, wet and dry, are classified based on the presence or absence of blood vessels that have invaded the retina.

Age-related macular degeneration is a progressive condition that is untreatable in up to 90 percent of patients and is a leading cause of blindness in the elderly worldwide. The two forms of age-related macular degeneration, wet and dry, are classified based on the presence or absence of blood vessels that have invaded the retina. A detailed understanding of the molecular mechanisms underlying wet age-related macular degeneration has led to several robust FDA-approved therapies. In contrast, there are no approved treatments for dry age-related macular degeneration thus far.

Nucleoside reverse transcriptase inhibitors (NRTIs) are the most widely used class of anti-HIV drugs. NRTIs are thought to be therapeutic in HIV/AIDS patients because they target the enzyme reverse transcriptase, which is critical for replication of HIV. Previous work from the Ambati lab found that a type of toxic molecule called Alu RNA accumulate in the retina to cause dry age-related macular degeneration; interestingly, Alu RNA and HIV are similar in that they both require reverse transcriptase to fulfill their life cycle.

In their Science publication, Fowler et al. report that multiple FDA-approved NRTIs prevented retinal degeneration in a mouse model of dry age-related macular degeneration. Surprisingly, this effect of NRTIs in the eye was not due to the well-known function of these drugs to inhibit reverse transcriptase. Instead, NRTIs blocked an innate immune pathway called the "inflammasome," even in experimental systems in which the NRTIs were not capable of blocking reverse transcriptase. In their report, they also showed that NRTIs were effective in other disease models that share common signaling pathways with the dry age-related macular degeneration model, including the "wet" form of age-related macular degeneration -- a disease that when treated still does not lead to substantial vision improvement in two-thirds of patients -- and graft-versus-host disease which is the major obstacle preventing successful allogeneic hematopoietic stem cell transplantation.

"Repurposing of NRTIs could be advantageous, for one, because they are very inexpensive. Moreover, through decades of clinical experience, we know that some of the drugs we tested are incredibly safe. Since these NRTIs are already FDA-approved, they could be rapidly and inexpensively translated into therapies for a variety of untreatable or poorly treatable conditions," said Benjamin Fowler, the lead author and a postdoctoral fellow in the Ambati lab. Ambati added, "We are excited at the prospect of testing whether NRTIs could be effective in halting the progression of age-related macular degeneration in patients."

NRTIs were originally designed to treat cancer in the 1960s. They re-emerged in the late 1980s and became the first drugs the FDA-approved to treat HIV/AIDS.

Semen directly impairs effectiveness of microbicides that target HIV

Researchers have discovered why microbicides developed to prevent HIV succeed in the lab but fail in clinical trials: Semen. Semen enhances the infectiousness of HIV by causing the virus to cluster together, increasing its ability to attach to and infect cells. This effect is then sufficient to override the antiviral properties of the microbicides.

In the fight against HIV, microbicides -- chemical compounds that can be applied topically to the female genital tract to protect against sexually transmitted infections -- have been touted as an effective alternative to condoms. However, while these compounds are successful at preventing transmission of the virus in a petri dish, clinical trials using microbicides have largely failed. A new study from the Gladstone Institutes and the University of Ulm now reveals that this discrepancy may be due to the primary mode of transportation of the virus during sexual transmission, semen.

"We think this may be one of the factors explaining why so many drugs that efficiently blocked HIV infection in laboratory experiments did not work in a real world setting," explains co-first author Nadia Roan, PhD, a visiting scientist at Gladstone and an assistant professor-in-residence in the Department of Urology at the University of California, San Francisco. "We've shown previously that semen enhances HIV infection, but this is the first time we've shown that this activity markedly reduces the antiviral efficacy of microbicides."

Semen markedly enhances the infectiousness of HIV through the presence of protein aggregates called amyloid fibrils. HIV binds to these fibrils, causing the virus to cluster together and increasing its ability to attach to and infect cells in the host -- in this case the sexual partner of the infected individual. This effect is then sufficient to increase the infectiousness of the HIV virus, thereby diminishing the antiviral properties of the microbicides.

In the study researchers tested the effectiveness of several different types of microbicides targeting the HIV virus on cells that had been exposed to HIV alone compared with cells that were treated with both HIV and semen. Across the board, they saw that not only did the cells with semen have rates of HIV infection approximately ten-fold higher than normal, these microbicides were up to twenty times less effective at blocking the virus in these cells than in those not exposed to semen.

Senior author Jan Munch, PhD, from the University of Ulm says, "Our findings suggest that targeting amyloids in semen is an alternative strategy to improve drug efficacy. The next step is to create a compound or cocktail of drugs that targets both the HIV virus and these amyloid fragments and to test its effectiveness. Also, given that semen is the main means of transmission of HIV, future testing of microbicides in the lab should be performed in the presence of semen to better predict antiretroviral efficacy in real life."

To test that it was the HIV-enhancing ability of semen that was having this effect on the microbicides and not some other substance, the researchers repeated the experiments using semen from men whose semen does not enhance HIV infection due to a disorder called ejaculatory duct obstruction. In the presence of these samples, there was no decrease in effectiveness of the anti-viral microbicides, confirming the importance of the HIV-promoting effects of semen in counteracting the effectiveness of these drugs.

Most microbicides work by targeting the virus itself, attempting to break it down or blocking its ability to infect a cell. However, the heightened infectiousness of HIV in the presence of semen appears to over-power any anti-viral effects the microbicides possess. The one exception to this finding is a different type of microbicide that acts on the host cells' receptors, stopping the virus from latching on from within. In the current study, this microbicide, called Maraviroc, was equally effective in preventing infection both with and without the presence of semen.

"There are important potential clinical implications for this study," says Warner Greene, MD, PhD, director of the Gladstone Institute of Virology and Immunology and a senior author on the paper. "Microbicides were originally developed as a way to empower and protect women in sub-Saharan Africa who often don't have a way to negotiate safe sex or condom use. However, the first generation of microbicides were largely ineffective or worse, some even leading to increased transmission of the virus. This study sheds light on why these microbicides did not work, and it provides us with a way to fix this problem by creating a new compound drug combining antivirals and amyloid inhibitors."

Altered milk protein can deliver aids drug to infants

A novel method of altering a protein in milk to bind with an antiretroviral drug promises to greatly improve treatment for infants and young children suffering from HIV/AIDS, according to a researcher.

That's critical because an estimated 3.4 million children are living with HIV/AIDS, the World Health Organization reports, and nine out of 10 of them live in resource-limited countries in sub-Saharan Africa, where effective antiretroviral treatments still are not widely accessible or available. International medical experts believe less than a third of affected children worldwide receive an antiretroviral drug.

Complicating treatment is that most antiretroviral drugs are not well tolerated by very young children. One of the most commonly prescribed antiretroviral drugs for treating and preventing HIV infection, Ritonavir, has undesirable side effects and important oral-delivery problems. Its physicochemical properties challenge its administration to infants, explained Federico Harte, associate professor of food science.

"Ritonavir has a high hydrophobicity and low solubility in water, which lead to a low dissolution rate in the gastrointestinal fluid and, hence, to insufficient bioavailability. The liquid formulation used to treat infants over one month of age contains 43 percent ethanol and has an awful flavor that has been described as bitter-metallic, medicinal, astringent, sour and burning," he said.

"Moreover, when coming into contact with the stomach mucosa, Ritonavir causes nausea, vomiting and diarrhea. Therefore, we need to develop alternative pediatric formulations of Ritonavir and overcome its poor water solubility to improve its oral administration to infants and children."

To solve that problem, Harte looked to a group of proteins in cow's milk celled caseins. Casein proteins form spherical aggregates called casein micelles, which are responsible, incidentally, for the white color of milk. The casein micelles in mammals' milk are natural delivery systems for amino acids and calcium from mother to young, and Harte reasoned, might deliver Ritonavir molecules as well.

"I have been working with bovine casein micelles for a few years now, and we have investigated the structure and functionality of these proteins," he said. "What we found is these micelles are able to carry molecules that have very little solubility in water, that have low molecular weight and that are very hydrophobic -- such as Ritonavir."

Significantly, Harte discovered in his research that subjecting milk to ultrahigh-pressure homogenization enhances the binding properties of the casein micelles. In previous studies, he learned that casein micelles could be bound to triclosan -- an antimicrobial used in deodorants -- and vitamin D, which is added regularly to skim milk.

Normal milk is homogenized at 10 to 15 megapascals, he pointed out. Milk in this research was homogenized at between 400 and 500 megapascals, disassociating the casein micelles and improving the protein's binding qualities to attach to drug molecules.

"As a result of this enhanced binding of molecules, we believe a milk powder containing Ritonavir can be used as baby formula, providing a transport system for a drug that is not very soluble in water. Right now we are running tests, and we are in the final stages of an experiment in which we gave three different formulations to piglets," Harte said.

"We are taking blood serum samples every three hours to study the kinetics of the drug in the piglets," he said. "The hope is that -- and we don't have the data yet -- we find that the Ritonavir is being adequately delivered by the protein in milk. So if that works, I think we are pretty close to having a formulation that can be used with hydrophobic drugs."

Harte noted that with his proposal for research funding he included a letter from a pediatrician at St. Jude Children's Research Hospital describing the challenge of orally administering Ritonavir to infants and young children.

"She has been treating patients with AIDS, and the awful flavor and ethanol content of Ritonavir were big issues for her," he said. "I am hopeful that this may lead to an application that works against AIDS. We have not done any clinical trials yet, so we will need to get data from those trials to say for sure."