Folate helps keep men's sperm normal,

Wed Mar 19, 2008 7:06pm EDT

WASHINGTON (Reuters) - Vitamins known as folates that prevent birth defects when consumed by women also help to keep men's sperm normal, researchers reported on Wednesday.

Men who took folic acid supplements and who ate folate-rich foods such as leafy greens had fewer abnormal sperm, the team at the University of California, Berkeley said.

Specifically, the men had fewer abnormal sperm in which a chromosome had been lost or gained, known as aneuploidy, they reported in the journal Human Reproduction.

"We found a statistically significant association between high folate intake and lower sperm aneuploidy," said Brenda Eskenazi, who helped lead the study.

"There was increasing benefit with increasing intake, and men in the upper 25th percentile who had the highest intake of folate between 722-1150 micrograms, had 20 percent to 30 percent lower frequencies of several types of aneuploidy compared with men with a lower intake," Eskenazi added in a statement.

She said larger studies were needed to confirm the findings.

Sperm aneuploidy can cause failure to conceive, causes up to a third of miscarriages and causes children to be born with Down's syndrome and other rare chromosomal syndromes.

Chemotherapy for cancer and exposure to pesticides also can damage sperm in this way but diet had not been investigated, the researchers said.

Folic acid can prevent nerve damage in growing babies and is so important that it is added to flour, rice and other staples in many countries.

But few studies had looked its effects on fathers.

Eskenazi's team said estimates suggest that between 1 percent and 4 percent of sperm in a healthy man have some type of aneuploidy but this varies from man to man.

Her team analyzed sperm samples from 89 healthy, non-smoking men of all ages and also questioned them about their daily total intake of zinc, folate, vitamin C, vitamin E and beta-carotene in both food and supplements.

Eskenazi said her team and others had previously shown that vitamin intake may help make men more fertile by improving the quality of the sperm. "This study is the first to suggest that paternal diet may play a role after conception in the development of healthy offspring," she said.

The current U.S. recommended daily intake of folate for men aged over 19 is 400 micrograms. Men seeking to become fathers may need more, Eskenazi said.

Men who ate the most zinc and beta-carotene also had fewer instances of some sperm abnormalities, but not aneuploidy, the researchers found.

(Reporting by Maggie Fox; Editing by Will Dunham and Eric Walsh)

http://www.reuters.com/article/healthNews/idUSN1960164920080319

Children with healthier diets do better in school

A new study reveals that children with healthy diets perform better in school
Alberta, Canada – March 20, 2008 – A new study in the Journal of School Health reveals that children with healthy diets perform better in school than children with unhealthy diets.

Led by Paul J. Veugelers, MSc, PhD of the University of Alberta, researchers surveyed around 5000 Canadian fifth grade students and their parents as part of the Children's Lifestyle and School-Performance Study.

Information regarding dietary intake, height, and weight were recorded and the Diet Quality Index-International (DQI-I) was used to summarize overall diet quality. The DQI-I score ranges from 0 to 100, with higher scores indicating better diet quality. Less healthful dietary components included saturated fat and salt, while healthy foods were classified by fruits, vegetables, grains, dietary fiber, protein, calcium and moderate fat intake.

A standardized literacy assessment was administered to the children. Multilevel regression methods were used to examine the association between indicators of diet quality and academic performance.

Students with an increased fruit and vegetable intake and less caloric intake from fat were significantly less likely to fail the literacy assessment. Relative to students in the group with the lowest DQI-I scores, students in the group with the best scores were 41 % less likely to fail the literacy assessment.

"We demonstrated that above and beyond socioeconomic factors, diet quality is important to academic performance," the authors conclude. "These findings support the broader implementation and investment in effective school nutrition programs that have the potential to improve student's diet quality, academic performance, and, over the long term, their health."

Erectile dysfunction drugs tame lower urinary tract symptoms in apparent class effect

By Betsy Bates

ANAHEIM, Calif. (EGMN) - Three separate PDE-5 inhibitors approved for the treatment of erectile dysfunction showed powerful effects on lower urinary tract symptoms in trials unveiled at the annual meeting of the American Urological Association.

Effects of these drugs seen on standardized measurements were on par with or even surpassed the effects of traditional medications used in treating symptoms secondary to benign prostatic hyperplasia (BPH), including alpha-blockers and 5-alpha-reductase inhibitors, said Dr. Kevin T. McVary, professor of urology at Northwestern University, Chicago.

"These are all pilot studies, preliminary studies," he said of research from his institution, the South Florida Medical Research group in Aventura, and the Ludwig Maximilians University, Munich. "But if this is consistent, we are going to see this class of drugs used for this indication."

A potential pathophysiologic link between erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) was first proposed by a French urologist in 1996.

"Basically, at the AUA, he was laughed off the stage," Dr. McVary recalled.

"We looked at these diseases as totally separate, perhaps occurring in the same people by coincidence. We now realize from different studies that these two diseases, ED and [BPH]/LUTS ... in a sense have a common etiology. In the last couple of years, we have been attempting to link the biology by treating one disease and seeing an impact on the other."

Two of the studies enrolled men with BPH, whether or not they suffered from ED. The third enrolled patients with both conditions. All showed improvement in ED, as expected, but they also had strong, consistent reductions in LUTS.

The German study, presented by Dr. Boris Schlenker, randomized 223 men aged 45-64 years with moderate to severe BPH (based on International Prostate Symptom Score [IPSS]) to receive 10 mg of vardenafil (Levitra) twice daily. Subjects were excluded if they had prostatitis, a history of prostate cancer or certain cardiovascular diseases, acute urinary retention, or previous treatment of their BPH.

By 8 weeks, mean scores on the total IPSS (a 0-35 scale) had declined from a mean 16.8 to 11 in the vardenafil group, compared with a reduction from 16.8 to 13.2 in the placebo group, a highly significant difference (P = .0013).

Even more dramatic were reductions in obstruction and irritation subscores of the IPSS, Dr. Schlenker said at a press briefing during the meeting.

Significant improvements also were seen on a urologic quality-of-life scale, the UROLIFE, among men randomly assigned to receive the active drug.

Paralleling findings from the other two studies, no differences were seen in peak urinary flow rates or postvoid residuals, which pointed to a mechanism of action other than a nitric oxide effect on the prostate, Dr. Schlenker said.

Dr. McVary agreed and suggested a number of other theories, including PDE-5 (phosphodiesterase type 5) activation in the bladder, an impact on neural transmission of altered sensory perceptions at the spinal cord, dilation of small vessels responsible for pelvic ischemia, or a muting of autonomic hyperreactivity in systemic nervous tone.

Regardless of the mechanism, the PDE-5 inhibitors seem to have a class effect on LUTS, investigators at the press briefing agreed.

Dr. McVary, for example, conducted a post hoc analysis of 186 men with severe LUTS and 155 with moderate LUTS in a 12-week study of 369 subjects aged 45 years or older with both ED and BPH. The men were randomized to receive placebo or sildenafil 50 mg titrated to 100 mg daily if tolerated.

He found that those patients with the most severe LUTS had the greatest improvement in IPSS (–8.6, compared with –2.4 among men with severe LUTS assigned to placebo). Men with moderate LUTS saw a 3.6-point decline in IPSS scores, compared with a 1.7-point drop in those with moderate LUTS who received placebo.

In part, the study design favored a larger decline in symptoms among those with the most severe disease, Dr. McVary noted, but he said the findings were nonetheless striking.

"The magnitude of IPSS improvement is really quite comparable to all of the other drugs [for LUTS] we've come to know and love over the last 20 years," he said.

"It's very similar to what we see with alpha-blockers - in fact, better than a lot of alpha-blocker studies."

The third study was presented at the press briefing by Dr. Marc Gittelman of the South Florida Medical Research group.

He found that the impact of tadalafil (Cialis) on ED was not significantly diminished in a subset of 156 men with moderate to severe LUTS in a 12-week study of the PDE-5 inhibitor in men with any degree of LUTS severity. The men were randomly assigned to placebo or tadalafil 5 mg escalating to 20 mg daily, with those on active drug achieving significantly better scores on the International Index of Erectile Function scale, regardless of the severity of their symptoms secondary to BPH.

All three studies were sponsored or supported by pharmaceutical companies: Dr. McVary's by Pfizer Inc., for which he is a consultant and lecturer; Dr. Gittelman's by Lilly ICOS, for which he is a consultant and lecturer; and Dr. Schlenker's by Bayer Health Care Pharmaceuticals.

ED Drugs May Soon Enter Armamentarium for BPH

It may be some time before clinicians begin routinely prescribing PDE-5 inhibitors to treat symptoms of benign prostatic hypertrophy, but eventually they will, investigators predicted at a press briefing during the annual meeting of the American Urological Association.

"Some people are going to be pioneers, early adopters, investigator-minded type people, and physicians who are frustrated with nonresponse in their patients" to traditional classes of drugs used to treat benign prostatic hypertrophy (BPH), Dr. McVary said.

Although many options are available to treat the symptoms of BPH, known as lower urinary tract symptoms (LUTS), these drugs are not without problems.

Roughly 30% of men discontinue using alpha-blockers within the first 12 months because of side effects or nonresponse. One drug in the class, tamsulosin (Flomax), causes ejaculatory dysfunction in 8%-30% of men, depending on the dose.

Meanwhile, 5-alpha-reductase inhibitors can induce sexual dysfunction in a number of ways, impacting ejaculation in 3% of men, diminishing libido in 3%, and causing erectile dysfunction in 3%.

The notion of prescribing a phosphodiesterase type 5 (PDE-5) inhibitor to reduce LUTS in such patients holds a certain appeal, Dr. McVary said.

Drugs in that class are rarely discontinued due to side effects such as headache, dyspepsia, or diarrhea.

"Having a better erection is a pretty nice side effect," he added.

The practical issues involved in prescribing a PDE-5 inhibitor for daily use may pose many challenges, however, Dr. Gittelman said.

A change in indication by the Food and Drug Administration could take 4 years or longer.

"How much [prescribing of PDE-5 inhibitors for BPH] will trickle into our practices depends on how much you want to practice off-label medicine," he said.

The cost and prescription plan coverage of the drug is another concern.

"I would say that in a general sense, if you could have a medication that would do more than one thing, that's a plus from a pharmaco-economic standpoint," Dr. Gittelman said.

Dr. McVary believes PDE-5 inhibitor therapy for BPH is inevitable, but he predicted widespread prescribing is probably unlikely until labeling, packaging, dosing, and cost catch up to the science. "I'm just a doctor; I'm not an economist," he said. "But I can't see us taking, say, sildenafil off the shelf and using it every day for LUTS. I just can't see that working economically."

On the other hand, Dr. McVary said that millions of men may already be unknowingly receiving low-dose therapy for their BPH whenever they pop a pill for ED.

Study of the response of the penile corporal tissue and cavernosus muscles to micturition

by Ahmed Shafik, Ismail Shafik, Olfat El-Sibai and Ali Shafik

Background: The reaction of the corpora cavernosa (CC), the corpus spongiosum (CS), the bulbocavernosus (BCM) and ischiocavernosus (ICM) muscles to passage of urine through the urethra during micturition is not known. We investigated the hypothesis that the passage of urine through the urethra stimulates the corporal tissue and cavernosus muscles.Methods. In 30 healthy men (mean age 42.8A+/-11.7 years), the electromyographic activity (EMG) of the CC, CS, BCM, and ICM were recorded before and during micturition, and on interruption of and straining during micturition. These tests were repeated after individual anesthetization of urethra, corporal tissue, and cavernosus muscles. Results: During micturition, the slow wave variables (frequency, amplitude, conduction velocity) of the CC and CS decreased while the motor unit action potentials of the BCM and ICM increased; these EMG changes were mild and returned to the basal values on interruption or termination of micturition. Micturition after individual anesthetization of urethra, corporal tissue and cavernosal muscles did not effect significant EMG changes in these structures, while saline administration produced changes similar to those occurring before saline administration. Conclusion: The decrease of sinusoidal and increase of cavernosus muscles' EMG activity during micturition apparently denotes sinusoidal relaxation and cavernosus muscles contraction. Sinusoidal muscle relaxation and cavernosus muscles contraction upon micturition are suggested to be mediated through a 'urethro-corporocavernosal reflex'. These sinusoidal and cavernosus muscle changes appear to produce a mild degree of penile tumescence and stretch which might assist in urinary flow during micturition.

Shot in the Arm for Prostate Cancer

Even though prostatic adenocarcinoma is the second leading cause of cancer death among American men, therapeutic options for advanced disease remain limited. Consequently, there is great interest in developing novel immunotherapy approaches to attack several of the prostate cancer-associated antigenic peptides identified over the past two decades.

Prostate stem cell antigen (PSCA) has long been considered one of the most attractive targets for this disease because it is overexpressed in a large percentage of advanced prostate cancers, but is absent in the majority of normal tissues. Now, an article by Garcia-Hernandez and colleagues in Cancer Research reports that a PSCA-based vaccine provides long-term protection against prostate cancer progression in one of the best mouse models of the disease.

A 123-amino acid protein of unknown function, human PSCA is overexpressed in at least a third of primary prostate cancers and essentially all those metastatic to bone. Moreover, increasing levels of PSCA strongly correlate with higher tumor grade/stage and progression to antigen independence.

Recently, a murine homologue of PSCA was discovered and found to be highly expressed in tumor cells of the transgenic adenocarcinoma mouse prostate (TRAMP) cancer model. Genetically engineered to express a strong oncogene in the prostate from the time of birth, TRAMP mice develop prostatic intraepithelial neoplasia (PIN) by 8 weeks and universally succumb to metastatic prostate carcinoma by one year of age.

In the current study, the researchers show that TRAMP mice vaccinated against PSCA at the time of PIN development had a 90% survival rate at 12 months of age and no evidence of autoimmunity or other adverse effects from the vaccine.

These remarkable results suggest that vaccination against PSCA at the earliest signs of prostate cancer holds promise as a therapeutic strategy against this disease.

Medical Writer, MDLinx OncologyMedical Writer, MDLinx Oncology