New Jersey Cosmetic Laser Surgery & Dermatology

Johns Hopkins scientists have found that a safe and inexpensive antibiotic in use since the 1970s for treating acne effectively targets infected immune cells in which HIV, the virus that causes AIDS, lies dormant and prevents them from reactivating and replicating.

The drug, minocycline, likely will improve on the current treatment regimens of HIV-infected patients if used in combination with a standard drug cocktail known as HAART (Highly Active Antiretroviral Therapy), according to research published now online and appearing in print April 15 in The Journal of Infectious Diseases. “The powerful advantage to using minocycline is that the virus appears less able to develop drug resistance because minocycline targets cellular pathways not viral proteins,” says Janice Clements, Ph.D., Mary Wallace Stanton Professor of Faculty Affairs, vice dean for faculty, and professor of molecular and comparative pathobiology at the Johns Hopkins University School of Medicine.

“The big challenge clinicians deal with now in this country when treating HIV patients is keeping the virus locked in a dormant state,” Clements adds. “While HAART is really effective in keeping down active replication, minocycline is another arm of defense against the virus.”

Unlike the drugs used in HAART which target the virus, minocycline homes in on, and adjusts T cells, major immune system agents and targets of HIV infection. According to Clements, minocycline reduces the ability of T cells to activate and proliferate, both steps crucial to HIV production and progression toward full blown AIDS.

If taken daily for life, HAART usually can protect people from becoming ill, but it’s not a cure. The HIV virus is kept at a low level but isn’t ever entirely purged; it stays quietly hidden in some immune cells. If a person stops HAART or misses a dose, the virus can reactivate out of those immune cells and begin to spread.

The idea for using minocycline as an adjunct to HAART resulted when the Hopkins team learned of research by others on rheumatoid arthritis patients showing the anti-inflammatory effects of minocycline on T cells. The Hopkins group connected the dots between that study with previous research of their own showing that minocycline treatment had multiple beneficial effects in monkeys infected with SIV, the primate version of HIV. In monkeys treated with minocycline, the virus load in the cerebrospinal fluid, the viral RNA in the brain and the severity of central nervous system disease were significantly decreased. The drug was also shown to affect T cell activation and proliferation.

“Since minocycline reduced T cell activation, you might think it would have impaired the immune systems in the macaques, which are very similar to humans, but we didn’t see any deleterious effect,” says Gregory Szeto, a graduate student in the Department of Cellular and Molecular Medicine working in the Retrovirus Laboratory at Hopkins.

“This drug strikes a good balance and is ideal for HIV because it targets very specific aspects of immune activation.”

The success with the animal model prompted the team to study in test tubes whether minocycline treatment affected latency in human T cells infected with HIV. Using cells from HIV-infected humans on HAART, the team isolated the “resting” immune cells and treated half of them with minocycline. Then they counted how many virus particles were reactivated, finding completely undetectable levels in the treated cells versus detectable levels in the untreated cells.

“Minocycline reduces the capability of the virus to emerge from resting infected T cells,” Szeto explains. “It prevents the virus from escaping in the one in a million cells in which it lays dormant in a person on HAART, and since it prevents virus activation it should maintain the level of viral latency or even lower it. That’s the goal: Sustaining a latent non-infectious state.”

The team used molecular markers to discover that minocycline very selectively interrupts certain specific signaling pathways critical for T cell activation. However, the antibiotic doesn’t completely obliterate T cells or diminish their ability to respond to other infections or diseases, which is crucial for individuals with HIV.

“HIV requires T cell activation for efficient replication and reactivation of latent virus,” Clement says, “so our new understanding about minocyline’s effects on a T cell could help us to find even more drugs that target its signaling pathways.”

The research was supported by grants from the National Institutes of Health. Authors of the paper, in addition to Clements and Szeto, are Angela K. Brice, Sheila A. Barber and Robert F. Siliciano, all of Johns Hopkins. Also, Hung-Chih Yang of National Taiwan University Hospital.

To Schedule an acne treatment contact Dr. Milgraum at his New Jersey Dermatology office at 1800-laser-18

Source
Johns Hopkins Medicine

For the approximately 7.5 million Americans affected by psoriasis, the thick, red, scaly, itchy plaques it causes only scratch the surface when it comes to the overall implications of this disease. Now, ongoing research linking psoriasis to other serious medical conditions and the incredible toll it can take on a person’s overall quality of life are shifting the way psoriasis is viewed from a common skin disease to a complex systemic condition.

Speaking today at the 68th Annual Meeting of the American Academy of Dermatology (Academy), dermatologist Alan Menter, MD, FAAD, chair of the Psoriasis Research Unit at Baylor Research Institute in Dallas, addressed the need for psoriasis to be viewed as a serious disease affecting the whole body with significant quality of life issues.

“In the past, psoriasis was viewed primarily as a cosmetic nuisance that was not thought to extend beyond the obvious plaques apparent on the skin,” said Dr. Menter. “With the discovery of multiple genes related to psoriasis, a better understanding of the immune system responses involved in this disease, and the frequent associations with other serious diseases, we know that psoriasis is a much more complex disease that demands continual monitoring and evaluation by a dermatologist and, if necessary, other medical professionals to address related health issues.”

The Link between Psoriasis and Other Serious Medical Conditions

Over the years, multiple studies have found that psoriasis is associated with a number of potentially serious medical conditions, including cardiovascular disease, cancer and lymphoma, obesity and metabolic syndrome (also known as “Syndrome X”), autoimmune diseases (Crohn’s disease and diabetes mellitus I and II, for example), psychiatric diseases (such as depression and sexual dysfunction), psoriatic arthritis, sleep apnea, personal behavior issues, chronic obstructive pulmonary disease (COPD) and even increased mortality. Dr. Menter explained that the majority of these diseases can have a significant impact on a patient’s overall health and affect psoriasis patients in different degrees of severity.

“It is important to note that while we are unsure whether psoriasis causes other diseases or that these other diseases cause psoriasis, the fact that an association exists at all is critically important in treating psoriasis patients,” said Dr. Menter.

One recent observational study of 3,236 patients with psoriasis and 2,500 patients without psoriasis who served as the controls concluded that patients with psoriasis experienced an increased incidence of ischemic heart disease (where the blood vessels are blocked leading to the heart), cerebrovascular disease (where the blood vessels are blocked leading to the brain), and peripheral vascular disease (the obstruction of arteries in the arms and legs), and mortality.1

Another study examining the increased risk of mortality in psoriasis patients suggests that patients with severe psoriasis may have shorter life expectancies by an average of three to five years than individuals who are not affected by psoriasis. 2

In addition, other studies have shown that psoriasis patients are more likely to consume excessive amounts of alcohol and cigarettes, both of which can negatively impact a psoriasis patient’s health. These detrimental behaviors can further aggravate other conditions associated with psoriasis, such as heart disease and COPD.

Impact on Quality of Life from Psoriasis Cannot be Underestimated

Since psoriasis is a chronic lifelong disease that needs to be controlled with a customized treatment regimen, the constant presence of psoriatic lesions or unexpected flare-ups at times when patients least expect it can cause a considerable amount of stress and anxiety. In fact, psoriasis has long been known to cause considerable emotional stress for patients, including low self-esteem and feelings of rejection, introspection, weight gain, increased use of alcohol and tobacco, and depression (which in some cases can be severe).

Another study conducted by the National Psoriasis Foundation examining attitudes and beliefs about contagious diseases among the general population of young adults found that approximately one-third (36 percent) of those surveyed were unsure whether psoriasis was contagious. In addition, when asked their attitudes about dating and skin conditions, more than half (62 percent) of the respondents reported that they take the condition of a person’s skin into consideration when first asking someone out on a date.

Dr. Menter added that the findings of this survey lend credence to the belief held by many psoriasis patients that their disease can have a negative impact on their personal lives and affect their interpersonal relationships.

“We cannot underestimate the complexity of psoriasis, particularly the psychological impact the disease can have on young people,” said Dr. Menter. “Even at a young age, psoriasis can affect a person’s relationships at home, work or school, and the disease can contribute to an overall poor body image that can be hard to reverse throughout life.”

Dr. Menter added that studies conducted regarding the effect of newer biologic medications, such as adalimumab, etanercept and infliximab, on psychiatric symptoms have shown that psoriasis patients may experience significant improvement in fatigue and other symptoms of depression. The newest biologic agent recently approved by the Food and Drug Administration (FDA), ustekinumab, also has been shown to improve sexual dysfunction in patients with moderate to severe psoriasis up to 10 fold.

“Although psoriasis is an incurable disease, it is controllable in the majority of cases with proper treatment,” said Dr. Menter. “Over the past several years, there have been a number of newer therapies introduced that are effective in managing psoriasis, and a patient’s dermatologist can determine which therapy would work best to control each patient’s disease.”

Headquartered in Schaumburg, Ill., the American Academy of Dermatology (Academy), founded in 1938, is the largest, most influential, and most representative of all dermatologic associations. With a membership of more than 16,000 physicians worldwide, the Academy is committed to: advancing the diagnosis and medical, surgical and cosmetic treatment of the skin, hair and nails; advocating high standards in clinical practice, education, and research in dermatology; and supporting and enhancing patient care for a lifetime of healthier skin, hair and nails.

If you have Psoriasis contact Dr. Milgraum at his New Jersey Dermatology office at 1800-laser-18
References

(1) Archives of Dermatology: Vol 145 (NO. 6), June 2009, Pages 700-703

(2) Archives of Dermatology: Vol 147 (NO. 12), December 2007, Pages 1,493-1,499.

Source: American Academy of Dermatology (AAD)