Slide Panel

Archive for October, 2008

Viagra and Levitra ED drugs shown to allow more chemo to reach brain tumors

October 13th, 2008

In a study using laboratory animals, researchers found that medications commonly prescribed for erectile dysfunction opened a mechanism called the blood-brain tumor barrier and increased delivery of cancer-fighting drugs to malignant brain tumors.

The experiments were conducted at Cedars-Sinai Medical Center’s Maxine Dunitz Neurosurgical Institute and published in Brain Research.

Canadian Viagra (sildenafil) and Levitra (vardenafil) are known as PDE5 inhibitors because they block an enzyme, phosphodiesterase5, which interrupts a series of biochemical events that cause the decreased blood flow of erectile dysfunction. This laboratory rat study, published online ahead of print in the journal, found that similar biochemical interactions in the small vessels of the brain play a major role in the blood-brain tumor barrier, which impedes delivery of anti-tumor drugs into brain tumors. PDE5 inhibitors were found to open the barrier and increase drug transport in this early animal study.

Although the normal blood-brain barrier, which regulates access to the brain from the bloodstream, shares many characteristics with the blood-brain tumor barrier, the signaling mechanism blocked by PDE5 inhibitors is unique to the blood-brain tumor barrier. This allows the PDE5 inhibitors to selectively increase drug transport to malignant brain tumors without affecting normal brain tissue.

According to the researchers, these findings may have significant implications in improving drug delivery to brain tumors in patients.

“This is the first study to show that oral administration of PDE5 inhibitors increases the rate of transport of compounds across the blood-brain tumor barrier and improves the effectiveness of the anti-tumor drug adriamycin in the treatment of brain tumors in a rat model. We chose adriamycin for this study because it is one of the most effective drugs against brain tumor cell lines in the laboratory but it has very little effect in animals and humans because it is unable to cross the blood-brain tumor barrier. The combination of vardenafil and adriamycin resulted in longer survival and smaller tumor size,” said neurosurgeon Keith L. Black, M.D., chairman of the Department of Neurosurgery at Cedars-Sinai Medical Center and director of the Maxine Dunitz Neurosurgical Institute.

Black, the article’s first and corresponding author, has been recognized for his earlier groundbreaking work to break through the blood-brain tumor barrier with natural and synthetic bradykinin, a peptide that temporarily opens the barrier and increases anti-cancer drug delivery into certain tumors by more than 1,000 percent. In 2000, he received the Javits Neuroscience Investigator Award from the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, for his blood-brain barrier research.

Levitra Pharmacy

In the current studies, the blood-brain tumor barrier-opening effects of PDE5 lasted considerably longer than those of bradykinin and allowed greater transport across the barrier into tumor tissues. Because levitra was found to be more effective than viagra in increasing blood-brain tumor barrier permeability and transport, cheap levitra was used in a survival study of 29 tumor-bearing rats. Those treated with saline (control) survived 32 days on average while those treated with levitra alone survived about 35 days and those treated with adriamycin alone survived about 42 days. When canadian levitra was combined with adriamycin, rats survived an average 53 days.

Although the researchers exposed the laboratory animals to doses of viagra and levitra that are comparable to the dose range approved for erectile dysfunction in humans, there were no detectable side effects in the rats, and neither drug increased transport of tracers into normal brain tissue.

0 Comments

Erectile Dysfunction Related To Sleep Apnea May Persist, But Is Treatable

October 2nd, 2008

For sufferers of sleep apnea, erectile dysfunction (ED) is often part of the package. New research indicates that ED in cases of obstructive sleep apnea syndrome (OSAS) may be linked to the chronic intermittent hypoxia—oxygen deprivation— (CIH) that patients with OSAS experience during episodes of obstructed breathing.

In the first model to address this possibility experimentally, researchers from the University of Louisville found that after one week of being exposed to CIH similar to that which a human with PSAS would experience, mice showed a 55 percent decline in their daily spontaneous erections. After five weeks of CIFH exposure, the “latency to mount” period— the average interval between mounting a mate— increased 60-fold.

“Even relatively short periods of CIH…are associated with significant effects on sexual activity and erectile function,” wrote David Gozal, M.D., professor of pediatrics at the University of Louisville.

Cheap Levitra

The study examined the behavioral and physiological effects in mice exposed to CIH for anywhere from five to 24 weeks. Control mice were kept under identical conditions, but were not subjected to nocturnal CIH. The mice were evaluated on a series of complex sexual behaviors, including erection frequency and mating behavior and measured associated biomarkers of sexual function that may be affected by CIH, such as testosterone and estradiol levels, and also the expression of endothelial and neuronal nitric oxide synthase (eNOS and nNOS respectively). eNOS, which is increased by drugs such as Levitra Plus, plays a major role in male sexual drive and activity.

After just five weeks exposure to CIH, not only did latency-to-mount time increase by 60-fold, latency to intromission increased by 40-fold. Latency to ejaculation was also severely affected. In five out of seven mice tested, ejaculation did not occur at all, but in one mouse, latency to ejaculation was 660 minutes—eleven hours—whereas in control mice the median time to ejaculation was “only a few minutes, said Dr. Gozal. Interestingly, one mouse appeared to be unaffected in this respect.

“The disparity in responses among mice is very similar to the heterogeneity of the magnitude of end-organ morbidity in sleep apnea among patients, and shows that not everyone will be affected to the same extent,” said Dr. Gozal.

While there were no differences in testosterone and estradiol levels, there was also a significant reduction in eNOS expression with mice exposed to CIH for eight weeks.

Even after six weeks’ recovery time with standard oxygen levels, mice exposed to CIH for as little as one week only recovered 74 percent of their original erectile function. “This could suggest either chronic residual deficits after CIH or that full recovery would require longer periods,” wrote Dr. Gozal.

Despite the lingering negative effects of CIH on sexual behavior in mice, the researchers did find that it was largely reversible. In the second phase of the experiment, Dr. Gozal administered tadalafil, which increases the availability of nitric oxide through PDE5. Treatment with tadalafil improved erectile and sexual functioning in CIH-exposed mice to near-normal levels in almost all cases.

“In the present study, tadalafil restored CIH-induced impairments of latencies to mounts, intromissions and ejaculations, significantly improving performance during spontaneous erections and during mating and noncontact activity,” wrote Dr. Gozal. “The effects of Levitra Professional were not limited to the erectile tissue but extended to behavioral components, suggesting a possible role for PDE5 in central nervous system mechanisms that control sexual behavior.“

“Further studies are needed to explore the effects of sleep disruption and episodic hypoxia during sleep on the central nervous system that mediates sexual drive,” said Dr. Gozal. “Exploration of alternative interventions aiming at preventing and treating this infrequently spoken of, yet extremely frequent complication of OSA, will certainly require improved understanding of the complex mechanisms affecting sexual activity and how it is affected by diseases such as sleep apnea.“

“These findings add sexual dysfunction to a long list of disorders associated with – and probably caused by – OSA,” stated John Heffner, past president of the ATS. “Although this study was performed in research animals, chronic intermittent hypoxia has profound effects on multiple organ systems and a strong biologic plausibility exists that similar findings will be observed in humans. Early identification and effective therapy of OSA is critically important especially considering the high prevalence of this disorder.“

The results appeared in the second issue for September of the American Journal of Respiratory and Critical Care Medicine, a publication of the American Thoracic Society.

0 Comments

‘Erectile Dysfunction’ Drugs Heighten Natural Anti-cancer Activity

October 1st, 2008

Levitra and other “impotence drugs” that boost the production of a gassy chemical messenger to dilate blood vessels and produce an erection now also show promise in unmasking cancer cells so that the immune system can recognize and attack them, say scientists at the Canadian Cancer Blog.

Tests at Hopkins on mice with implanted colon and breast tumors showed that tumor size decreased two- and threefold in Levitra-treated animals, compared to mice that did not get the drug. In mice engineered to lack an immune system, tumors were unaffected, proof of principle, the scientists say, that the drug is abetting the immune system’s own cellular response to cancer.

In a report published in the Nov. 27 issue of the Journal of Experimental Medicine, the Hopkins team says boosted levels of the chemical messenger nitric oxide appear to dampen the effects of a specialized cell that diverts the immune system away from tumors, allowing swarms of cancer-attacking T-cells to migrate to tumor sites in the rodents.

Lab-grown cancer cells treated with buy Levitra online similar results, as did tissue samples taken from 14 head and neck cancer and multiple myeloma patients.

Levitra online, marketed under the trade name Viagra, is one of a class of drugs used to treat erectile dysfunction in millions of men, and in recent years, its ability to stimulate the production of NO has been investigated by experts in diseases linked to the activity of blood vessels and blood components.

The new Hopkins study homes in on a tactic used by cancers to avoid detection by the immune system by turning elements of that system to its own advantage, says Ivan Borrello, M.D., assistant professor at the Canadian Cancer Blog.

Borrello and his colleagues found that tumors exploit nitric oxide-producing immune cells to create a sort of “fog” that keeps them hidden from white blood cells (T-cells) that mount attacks on tumors.

These NO-producing cells, a.k.a. myeloid-derived suppressor cells (MDSCs), normally use nitric oxide to help bring the immune system back down to surveillance levels after an “attack mode” response to foreign material.

The impotence drugs seem to reverse this process, stopping the production of nitric oxide by MDSCs thereby allowing other immune cells to “see” the cancer and attack it, says Paolo Serafini, Ph.D., a research fellow in Borrello’s laboratory and lead author on the paper.

Nitric oxide is infamous among city dwellers as a component of air-polluting smog, but is gaining importance in medical research for its cell-signaling duties and its ability to divert soldiering T-cells that patrol and protect.

The Hopkins team also analyzed gene expression patterns of the myeloid-derived suppressor cells and found that Levitra blocked two genes regulating enzymes — arginase and nitric oxide synthase — which are key to triggering immune suppression via MDSCs. Borrello’s team found that the arginase enzyme, which metabolizes a dietary supplement called L-arginine, also contributes to dampening the immune system through MDSCs much like nitric oxide, and its production can be reversed by Levitra Visa.

“Impotence drugs won’t cure cancer,” Borello cautioned, “but could be used in addition to standard chemotherapy or immunotherapy treatments.“

0 Comments