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“The more we study watermelons, the more we realize just how amazing a fruit it is in providing natural enhancers to the human body,” said Dr. Bhimu Patil, director of Texas A&M’s Fruit and Vegetable Improvement Center in College Station.

“We’ve always known that watermelon is good for you, but the list of its very important healthful benefits grows longer with each study.”

Beneficial ingredients in watermelon and other fruits and vegetables are known as phyto-nutrients, naturally occurring compounds that are bioactive, or able to react with the human body to trigger healthy reactions, Patil said.

In watermelons, these include lycopene, beta carotene and the rising star among its phyto-nutrients – citrulline – whose beneficial functions are now being unraveled. Among them is the ability to relax blood vessels, much like Viagra does.

Scientists know that when watermelon is consumed, citrulline is converted to arginine through certain enzymes. Arginine is an amino acid that works wonders on the heart and circulation system and maintains a good immune system, Patil said.

“The citrulline-arginine relationship helps heart health, the immune system and may prove to be very helpful for those who suffer from obesity and type 2 diabetes,” said Patil. “Arginine boosts nitric oxide, which relaxes blood vessels, the same basic effect that Viagra has, to treat erectile dysfunction and maybe even prevent it.”

While there are many psychological and physiological problems that can cause impotence, extra nitric oxide could help those who need increased blood flow, which would also help treat angina, high blood pressure and other cardiovascular problems.

“Watermelon may not be as organ specific as Viagra,” Patil said, “but it’s a great way to relax blood vessels without any drug side-effects.”

The benefits of watermelon don’t end there, he said. Arginine also helps the urea cycle by removing ammonia and other toxic compounds from our bodies.

Citrulline, the precursor to arginine, is found in higher concentrations in the rind of watermelons than the flesh. As the rind is not commonly eaten, two of Patil’s fellow scientists, drs. Steve King and Hae Jeen Bang, are working to breed new varieties with higher concentrations in the flesh.

In addition to the research by Texas A&M, watermelon’s phyto-nutrients are being studied by the U.S. Department of Agriculture’s Agricultural Research Service in Lane, Oklahoma.

As an added bonus, these studies have also shown that deep red varieties of watermelon have displaced the tomato as the lycopene king, Patil said. Almost 92 percent of watermelon is water, but the remaining 8 percent is loaded with lycopene, an anti-oxidant that protects the human heart, prostate and skin health.

“Lycopene, which is also found in red grapefruit, was historically thought to exist only in tomatoes,” he said. “But now we know that it’s found in higher concentrations in red watermelon varieties.”

Lycopene, however, is fat-soluble, meaning that it needs certain fats in the blood for better absorption by the body, Patil said.

“Previous tests have shown that lycopene is much better absorbed from tomatoes when mixed in a salad with oily vegetables like avocado or spinach,” Patil said. “That would also apply to the lycopene from watermelon, but I realize mixing watermelon with spinach or avocadoes is a very hard sell.”

No studies have been conducted to determine the timing of the consumption of oily vegetables to improve lycopene absorption, he said.

“One final bit of advice for those Fourth of July watermelons you buy,” Patil said. “They store much better uncut if you leave them at room temperature. Lycopene levels can be maintained even as it sits on your kitchen floor. But once you cut it, refrigerate. And enjoy.”

Led by professor of Pharmacology and Toxicology Donald Maurice, the study focuses on the effects of Viagra – the popular erectile dysfunction drug, which is also used to treat pulmonary hypertension.

“As scientists, we’re excited about this discovery because it’s a fundamentally new approach to regulating what enzymes do in cells,” says Dr. Maurice, a Career Scientist with the Ontario Heart and Stroke Foundation. “The fact that it also offers a potentially novel use of a drug already widely in use for other applications is an unexpected bonus.”

The enzyme targeted by the Queen’s researchers is known to regulate the activity of platelets: small blood cells needed for normal blood clotting. Problems can arise when people have stents permanently implanted in their arteries to maintain blood flow. Their platelets sometimes bind to the stent and, if enough platelets accumulate to form a blockage, this may cause a sudden, massive heart attack or stroke to occur.

Drugs like Viagra have been shown to inhibit PDE5, explains Lindsay Wilson, a PhD student in Pathology and Molecular Medicine and first author on the study. Until now, however, it hasn’t been possible to isolate the small “pool” of activity within the cell where this is occurring.

The Queen’s study shows that within each cell there are two different pools of the PDE5 enzyme, but that only one of them regulates platelet activation. “Understanding how the cell works should allow us to affect the activity of enzymes in one neighborhood – and leave alone their ‘identical twins’ in a different neighborhood in that cell,” says Ms Wilson.

“The idea is to use a PDE5 inhibitor such as Viagra selectively to inhibit platelet function,” she continues. We now know that not all the enzymes in the cell are doing the same job. Just like in real estate, it’s all about the location!”

The team’s findings were recently published online in the international journal Proceedings of the National Academy of Sciences. Other members of the Queen’s research team are Hisham Elbatarny and Brian Bennett (Pharmacology and Toxicology), and Scott Crawley (Biochemistry). Funding came from the Ontario Heart and Stroke Foundation and the Canadian Institutes of Health Research (CIHR).

The experiments were conducted at Cedars-Sinai Medical Center’s Maxine Dunitz Neurosurgical Institute.

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.

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 vardenafil was found to be more effective than sildenafil in increasing blood-brain tumor barrier permeability and transport, vardenafil 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 vardenafil alone survived about 35 days and those treated with adriamycin alone survived about 42 days. When vardenafil was combined with adriamycin, rats survived an average 53 days.

Although the researchers exposed the laboratory animals to doses of sildenafil and vardenafil 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.

Funding for the studies was provided by the National Institute of Neurological Disorders and Stroke (the Javits Award), the Maxine Dunitz Neurosurgical Institute and the Ruth and Lawrence Harvey Chair in Neuroscience, held by Black.

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.

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 sildenafil (Viagra), 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. “[T]his 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 tadalafil 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.

A cold slice of watermelon has long been a Fourth of July holiday staple. But according to recent studies, the juicy fruit may be better suited for Valentine’s Day.

That’s because scientists say watermelon has ingredients that deliver Viagra-like effects to the body’s blood vessels and may even increase libido.

“The more we study watermelons, the more we realize just how amazing a fruit it is in providing natural enhancers to the human body,” said Dr. Bhimu Patil, director of Texas A&M’s Fruit and Vegetable Improvement Center in College Station.

“We’ve always known that watermelon is good for you, but the list of its very important healthful benefits grows longer with each study.”

Beneficial ingredients in watermelon and other fruits and vegetables are known as phyto-nutrients, naturally occurring compounds that are bioactive, or able to react with the human body to trigger healthy reactions, Patil said.

In watermelons, these include lycopene, beta carotene and the rising star among its phyto-nutrients - citrulline - whose beneficial functions are now being unraveled. Among them is the ability to relax blood vessels, much like Viagra does.

Scientists know that when watermelon is consumed, citrulline is converted to arginine through certain enzymes. Arginine is an amino acid that works wonders on the heart and circulation system and maintains a good immune system, Patil said.

“The citrulline-arginine relationship helps heart health, the immune system and may prove to be very helpful for those who suffer from obesity and type 2 diabetes,” said Patil. “Arginine boosts nitric oxide, which relaxes blood vessels, the same basic effect that Viagra has, to treat erectile dysfunction and maybe even prevent it.”

While there are many psychological and physiological problems that can cause impotence, extra nitric oxide could help those who need increased blood flow, which would also help treat angina, high blood pressure and other cardiovascular problems.

“Watermelon may not be as organ specific as Viagra,” Patil said, “but it’s a great way to relax blood vessels without any drug side-effects.”

The benefits of watermelon don’t end there, he said. Arginine also helps the urea cycle by removing ammonia and other toxic compounds from our bodies.

Citrulline, the precursor to arginine, is found in higher concentrations in the rind of watermelons than the flesh. As the rind is not commonly eaten, two of Patil’s fellow scientists, drs. Steve King and Hae Jeen Bang, are working to breed new varieties with higher concentrations in the flesh.

In addition to the research by Texas A&M, watermelon’s phyto-nutrients are being studied by the U.S. Department of Agriculture’s Agricultural Research Service in Lane, Oklahoma.

As an added bonus, these studies have also shown that deep red varieties of watermelon have displaced the tomato as the lycopene king, Patil said. Almost 92 percent of watermelon is water, but the remaining 8 percent is loaded with lycopene, an anti-oxidant that protects the human heart, prostate and skin health.

“Lycopene, which is also found in red grapefruit, was historically thought to exist only in tomatoes,” he said. “But now we know that it’s found in higher concentrations in red watermelon varieties.”

Lycopene, however, is fat-soluble, meaning that it needs certain fats in the blood for better absorption by the body, Patil said.

“Previous tests have shown that lycopene is much better absorbed from tomatoes when mixed in a salad with oily vegetables like avocado or spinach,” Patil said. “That would also apply to the lycopene from watermelon, but I realize mixing watermelon with spinach or avocadoes is a very hard sell.”

No studies have been conducted to determine the timing of the consumption of oily vegetables to improve lycopene absorption, he said.

“One final bit of advice for those Fourth of July watermelons you buy,” Patil said. “They store much better uncut if you leave them at room temperature. Lycopene levels can be maintained even as it sits on your kitchen floor. But once you cut it, refrigerate. And enjoy.”