Supra-physiological rhGH administration induces gender-related differences in the hypothalamus-pituitary-thyroid (HPT) axis in healthy individuals.

PURPOSE: The use of recombinant human growth hormone (rhGH) is a common habit among athletes. While the effects of rhGH administration have been described with contrasting results in males, no data exist in females to date. The aim of the present study was to evaluate the effects of rhGH administration on TSH, FT4 and FT3 levels and the time requested to return to baseline values after treatment withdrawal. METHODS: Twenty-one healthy trained male and female athletes were treated with 0.03 mg rhGH/kg body mass 6 days/week for 3 weeks. We collected blood samples immediately before the first daily rhGH administration, at 3, 4, 8, 15 and 21 days of treatment and at 3 and 9 days after rhGH withdrawal. RESULTS: In males, rhGH administration induced a significant (p < 0.01) early and stable TSH decrease and IGF-I increase, and a delayed FT4 reduction without FT3 modification, suggesting a central regulatory mechanism. In females, rhGH administration induced a significant (p < 0.01) early and transient TSH decrease and IGF-I increase, and a transient reduction in FT4 without any changes in FT3 concentrations. rhGH withdrawal was associated with a prompt normalization of TSH and FT4 levels in males, while in females the effects of rhGH treatment had already disappeared during the last period of treatment. CONCLUSION: We suggest that rhGH inhibits TSH at central level both in males and females. The pattern of normalization was different in the two genders probably due to gonadal steroids modulation on GH-IGF-I axis.

Effects of chronic Rhodiola Rosea supplementation on sport performance and antioxidant capacity in trained male: preliminary results.

AIM: Rhodiola Rosea, is an adaptogen plant which has been reported to promote fatty acids utilisation, to ameliorate antioxidant function, and to improve body resistance to physical strenuous efforts. The purpose of the present study was to investigate the effects on physical performance as well as on the redox status of a chronic Rhodiola Rosea supplementation in a group of competitive athletes during endurance exercise. METHODS: Following a chronic supplementation with Rhodiola Rosea for 4 weeks, 14 trained male athletes underwent a cardio-pulmonary exhaustion test and blood samples to evaluate their antioxidant status and other biochemical parameters. These data were compared with those coming from the same athletes after an intake of placebo. RESULTS: The evaluation of physical performance parameters showed that HR Max, Borg Scale level, VO(2) max and duration of the test were essentially unaffected by Rhodiola Rosea assumption. On the contrary, Rhodiola Rosea intake reduced, in a statistically significative manner, plasma free fatty acids levels. No effect on blood glucose was found. Blood antioxidant status and inflammatory parameters resulted unaffected by Rhodiola Rosea supplementation. Blood lactate and plasma creatine kinase levels were found significantly lower (P<0.05) in Rhodiola Rosea treated subjects when compared to the placebo treated group. CONCLUSION: Chronic Rhodiola Rosea supplementation is able to reduce both lactate levels and parameters of skeletal muscle damage after an exhaustive exercise session. Moreover this supplementation seems to ameliorate fatty acid consumption. Taken together those observation confirm that Rhodiola Rosea may increase the adaptogen ability to physical exercise.

Do aspartate and asparagine acute supplementation influence the onset of fatigue in intense exercise?

AIM: Oxaloacetic acid represents a fundamental intermediary in the metabolism of energy substrate. Asparagine and aspartate constitute precursor compounds of this substance. Therefore, they could affect tricarbossilic acids cycle. Besides, it was suggested that supplementation with aspartate and asparagine determines a muscular glycogen sparing during strenuous physical exercise, even if the real effectiveness remain controversial. The aim of the present pilot study was to evaluate the hypothesis that a supplementation with oxaloacetate precursors, precisely aspartate and asparagine, could improve sport performance during high intensity endurance exercise. METHODS: We recruited 15 male trained athletes, aged from 20 to 30 years (mean age: 24.13+/-3.87 years), practicing triathlon. We administered them placebo or aspartate (7 g) and asparagine (7 g) mixture, using a double blind technique, before performing an exhaustion stress test on cycloergometer carried out to 90% of each athlete's maximum oxygen consumption, previously determined. RESULTS: We evaluated lactatemia through earlobe punctures at the end of warming up, at the maximum effort and at recovery time (3 min, 5 min, 10 min, 15 min, 30 min). Furthermore, subjects were submitted to three blood samples from brachial artery in order to assess the glycemia (before the exercise, at the end of the exercise, and 30 min after the end of the exercise). CONCLUSION: The analysis of these parameters and the results of the ergometric tests after amino acids assumption indicate that acute supplementation with aspartate and asparagine do not significantly affect physical performance in athletes practicing high intensity exercises, and that acute administration of aspartate does not cause a sparing of muscle glycogen concentration.

Complex ventricular arrhythmia induced by overuse of potassium supplementation in a young male football player. Case report.

People practising regular physical activity usually drink hydrosaline beverages. In this study is reported the case of a young football player suffering from premature ventricular beats. He used to take regularly an hydrosaline supplementation which gave him a daily intake of potassium of about 5 g. A stress test on a cycle ergometer showed many monomorphus premature ventricular beats which disappeared when the heart rate was higher than 110 beats/min. Moreover, 3629 polimorphus premature ventricular beats were recorded during a 24 hr ECG monitoring. At the time of the first examination, the plasma potassium concentration was 7,8 mEq x l(-1). The football player was then suspended from practicing sport and he was asked to stop his intake of potassium. The clinical examination was repeated after 3 and 6 months and no ventricular arrhythmias were observed during the stress test as well as during the 24 hours ECG monitoring. The plasma potassium concentration was normal again. The present case report is an example of how the misuse of saline supplementations could result in hyperkalemia and how this condition may lead to ventricular arrhythmias.

Interleukin-6 involvement in antidepressant action of Hypericum perforatum.

Hypericum, a plant widely used as antidepressant has been shown to interact with the immune system. We studied the effects of the administration of the Hypericum perforatum extract Ph-50, a Hypericum extract, standardized to flavonoids (50%) and containing 0.3% of hypericin and 4.5% of hyperforin in a forced swimming test and tryptophan, serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) diencephalic content using a high performance liquid chromatography method in male interleukin-6 (IL-6) knock-out (IL-6(-/-)) and wild type (IL-6(+/+)) mice. Hypericum extract (Ph-50; 500 mg/kg) oral acute administration reduced the immobility time of wild type, but not of knockout mice. Tryptophan content was not modified by Hypericum in all the animal groups. Serotonin and 5-HIAA diencephalic content was increased by Hypericum in both wild type and knockout mice. However, the increase observed in the wild type was greater than in knockout mice. These data indicate that IL-6 could be necessary to the antidepressant action of Hypericum, and that this cytokine (probably) mediates the effects of Hypericum through activation of the serotonin system.

Serotonin, norepinephrine and dopamine involvement in the antidepressant action of hypericum perforatum.

Hypericum perforatum is considered an effective alternative to the synthetic antidepressants in the treatment of mild-to-moderate depression. Recently, we showed that the effects on neurotransmitter contents in different brain regions of laboratory animals are more evident after administration of hypericum extracts containing a higher concentration of flavonoids, thus suggesting that these compounds are important in the antidepressant action of hypericum perforatum. We studied the effects of Ph-50, a hypericum extract standardized to flavonoids (50%) and containing 0.3% hypericin and 4.5% hyperforin on brain serotonin content, norepinephrine and dopamine by a high-performance liquid chromatography method in discrete brain areas (cortex, diencephalon and brainstem) in male Sprague-Dawley rats. Moreover, we evaluated the effects of Ph-50 alone or in association with sulpiride (a dopamine receptor antagonist), metergoline (a serotonin receptor antagonist) and 6-hydroxydopamine (6-OH-DA, destroying norepinephrine-containing neurons) using a forced-swimming test in the rat. Hypericum extract (Ph-50; 250-500 mg/kg) with acute oral administration enhanced serotonin, norepinephrine and dopamine content in the brain and reduced the immobility time of rats in the forced-swimming test. Sulpiride, metergoline and 6-OH-DA significantly increased the period of immobility in the forced-swimming test for the rats receiving hypericum extract (Ph-50). The results indicate that the neurotransmitters studied could be involved in the anti-immobility effects of hypericum, and suggest that its antidepressant action is probably mediated by serotonergic, noradrenergic and dopaminergic system activation.

Neuroprotective effects of Ginkgo biloba extract in brain ischemia are mediated by inhibition of nitric oxide synthesis.

We studied the effects of pre-treatment (15 days) with oral administration of Ginkgo biloba extract (Ph-Gb 37.5-150 mg/kg) on brain malonildialdehyde (MDA), brain edema, brain nitrite and nitrate and delayed neuronal death following transient cerebral ischemia in the Mongolian gerbil. Survival was not modified, however, pre-treatment with Ginkgo biloba significantly and in a dose-dependent way reduced post-ischemic brain MDA levels and post-ischemic brain edema. Delayed neuronal death in the CA1 of the hippocampus was attenuated by the highest dose of the extract. Increase of nitrite and nitrate was observed after cerebral ischemia in the hippocampus and it was dose-dependently reduced in animals pretreated with Ph-Gb, thus suggesting that neuroprotective effects of Ginkgo biloba may be due to an inhibitory action on nitric oxide formation.

The efficacy of exercise as an aid for smoking cessation in women: a randomized controlled trial.

BACKGROUND: Smoking prevalence rates among women are declining at a slower rate than among men. OBJECTIVE: To determine if exercise, a healthful alternative to smoking, enhances the achievement and maintenance of smoking cessation. METHODS: Two hundred eighty-one healthy, sedentary female smokers were randomly assigned to either a cognitive-behavioral smoking cessation program with vigorous exercise (exercise) or to the same program with equal staff contact time (control). Subjects participated in a 12-session, group-based smoking cessation program. Additionally, exercise subjects were required to attend 3 supervised exercise sessions per week and control subjects were required to participate in 3 supervised health education lectures per week. Abstinence from smoking was based on self-report, was verified by saliva cotinine level, and was measured at 1 week after quit day (week 5), end of treatment (week 12), and 3 and 12 months later (20 and 60 weeks after quit day, respectively). RESULTS: Compared with control subjects (n = 147), exercise subjects (n = 134) achieved significantly higher levels of continuous abstinence at the end of treatment (19.4% vs 10.2%, P = .03) and 3 months (16.4% vs 8.2%, P=.03) and 12 months (11.9% vs 5.4%, P=.05) following treatment. Exercise subjects had significantly increased functional capacity (estimated VO2 peak, 25+/-6 to 28+/-6, P<.01) and had gained less weight by the end of treatment (3.05 vs 5.40 kg, P = .03). CONCLUSIONS: Vigorous exercise facilitates short- and longer-term smoking cessation in women when combined with a cognitive-behavioral smoking cessation program. Vigorous exercise improves exercise capacity and delays weight gain following smoking cessation.

Penetration of solar erythemal UV radiation in the shade of two common Australian trees.

The penetration of solar erythemal ultraviolet radiation has been measured in the shade of a gum (Eucalyptus sp.) and a she oak (Casaurina) tree, both on a horizontal plane and with polysulphone dosimeters to human anatomical sites. This has provided new data useful for protection strategies against harmful ultraviolet radiation. For larger solar zenith angles, the relative penetration of solar erythemal ultraviolet in the shade of the trees is higher. On a horizontal plane, at noon, in winter, the shade erythemal ultraviolet ranged from 44 to 55% of that in the sun whereas in spring it ranged from 29 to 37% of the irradiances in the sun. Similarly, at 9:00 EST and 15:00 EST, the shade erythemal ultraviolet in winter ranged from 51 to 81% of the irradiances in the sun whereas in spring and summer they ranged from 35 to 51% of the unshaded irradiances. The shade ratios for specific body sites provided by the shade of the two trees were 0.05 to 0.45 for the solar zenith angles in this research. The shade ratios ranged from 0.14 to 0.45 for the gum tree and from 0.05 to 0.28 for the she oak. The denser foliage of the she oak provided higher ultraviolet protection compared to that of the gum tree.

Percutaneous transluminal coronary angioplasty versus medical therapy for stable angina pectoris: outcomes for patients with double-vessel versus single-vessel coronary artery disease in a Veterans Affairs Cooperative randomized trial. Veterans Affairs ACME InvestigatorS.

OBJECTIVES: This study sought to assess outcomes of men with double-vessel coronary artery disease randomly assigned to treatment by percutaneous transluminal coronary angioplasty (PTCA) or medical therapy, compared with previously reported outcomes for men with single-vessel disease. BACKGROUND: We previously reported that PTCA provides better symptom relief and treadmill performance than medical therapy for men with stable angina pectoris due to single-vessel disease. Whether this advantage applies to patients with double-vessel disease is unknown. METHODS: Male patients (n = 328) with stable angina pectoris and ischemia on treadmill testing were randomly assigned to PTCA or medical therapy; 101 patients had double-vessel disease, and 227 had single-vessel disease. Symptoms, treadmill performance, quality of life score, coronary stenosis and myocardial perfusion were compared at baseline and at 6 months. Patients were followed up for up to 6 years and underwent additional treadmill testing 2 to 3 years after randomization. RESULTS: PTCA-treated and medically treated patients with double-vessel disease experienced comparable improvement in exercise duration (+1.2 vs. +1.3 min, respectively, p = 0.89), freedom from angina (53% and 36%, respectively, p = 0.09) and improvement of overall quality of life score (+1.3 vs. +4.4, respectively, p = 0.32) at 6 months compared with baseline. This contrasts with greater advantages favoring PTCA by these criteria in patients with single-vessel disease (p = 0.0001 to 0.02). Trends present at 6 months persisted at late follow-up. Patients undergoing double-vessel dilation had less complete initial revascularization (45% vs. 83%) and greater average stenosis of worst lesions at 6 months (74% vs. 56%). Likewise, patients with double-vessel disease showed less improved myocardial perfusion imaging (59% vs. 75%). CONCLUSIONS: PTCA is beneficial in male patients with double-vessel disease; however, we cannot demonstrate the same advantage over medical therapy seen in similar patients with single-vessel disease. Less complete revascularization and greater restenosis for patients having multiple dilations would account for these findings. Alternatively, a type 2 error might be operative. Technical advances since completion of this trial might improve these outcomes. These findings warrant further investigation in a larger trial.

Can loss and grief activate latent neoplasia? A clinical case of possible interaction between genetic risk and stress in breast cancer.

BACKGROUND: Nineteenth-century physicians working with cancer patients frequently reported that severe emotional losses and grief occurred in some cases before cancer. Research on psychoneuroimmunology seems to reactivate this interest and could give a possible convincing background. METHOD: We recently observed the case of a 45-year-old woman who developed symptoms of breast cancer (ductal infiltrating carcinoma, T1, N1, M0) 3 years after the loss of her only child. The affection for the child compensated inadequacies of her marriage, which became increasingly unstable. The child died in a dramatic accident at home, while his mother was near him but unable to help. RESULTS: The patient had a moderate genetic-familial risk of mammary cancer. Animal studies strongly suggest that stress, through neuroimmunomodulatory mediatory mechanisms, can significantly affect appearance and progression of mammary cancer. The patient developed long-lasting intense grief, despair and hopelessness. DISCUSSION: We discuss the case from three main standpoints: genetic and risk factors for breast cancer; findings which demonstrated a relationship between stress, neuroimmunomodulation and cancer in animals; data from autopsy studies which found foci of latent breast cancer in 20% of healthy women in the same age range. Stress does not create cancer. However we hypothesize that in this case it could have contributed by the activation of a latent neoplasia and/or by impairing immunosurveillance during a critical life phase.

Combined use of calcium-channel and beta-adrenergic blockers for the treatment of chronic stable angina. Rationale, efficacy, and adverse effects.

During the past decade, the therapy for stable angina pectoris has greatly expanded with the introduction of the calcium-channel blockers. Initially studied as monotherapy, these agents have been regularly used in combination with other antianginal medications, most notably the beta-adrenergic blockers. Although there are pharmacologic rationales for combining these agents, in daily practice, the major impetus for combination therapy is continuing angina during monotherapy. At least one well-conducted double-blind study was done to confirm that diltiazem, verapamil, and nifedipine each can markedly improve both subjective and objective measures of efficacy when used in combination with a beta-blocker. However, individual patient responses are of chief importance. Many persons do better with monotherapy than with combination treatment. The offsetting hemodynamic effects of nifedipine and a beta-blocker generally work well together; however, minor side effects are not infrequent. In the patient with underlying conduction system disease, this combination is clearly preferable. Diltiazem with a beta-blocker is usually well-tolerated, with a low incidence of adverse effects, similar to the experience with diltiazem monotherapy. Verapamil in conjunction with a beta-blocker warrants the greatest concern; approximately 10% to 15% of patients will have significant bradycardia, heart block, hypotension, or congestive failure. When these agents are used concurrently, reduced dosages, especially of the beta-blocker, will likely result in a lower incidence of adverse effects with maintained efficacy.

The efficacy of the addition of nifedipine in patients with mixed angina compared to patients with classic exertional angina: a multicenter, randomized, double-blind, placebo-controlled clinical trial.

Episodes of myocardial ischemia in patients with coronary artery disease may be due to transient increases in coronary vasomotor tone superimposed on a fixed atherosclerotic obstruction. The purpose of this study was to determine whether identification of the clinical pattern of angina could predict the therapeutic response to the addition of nifedipine to a regimen of beta blockers and/or long-acting nitrates. Seventy-two patients with stable exertional angina were divided into two groups: "classic exertional angina" (17 patients), defined as exertional angina with a stable threshold; and "mixed angina" (55 patients), defined as exertional angina provoked by a variable threshold and/or at least two episodes of rest angina within the 3 months prior to screening. Patients were studied with nifedipine and placebo in a 6-week, double-blind, crossover design that used serial anginal diaries, exercise treadmill tests, and 24-hour ambulatory ECG monitoring. In patients with mixed angina, nifedipine reduced the frequency of angina compared to that during placebo treatment (13.1 vs 9.9 episodes/3 weeks, p less than 0.01) and reduced nitroglycerin consumption (11.7 vs 7.5 tablets/3 weeks, p less than 0.05); while in patients with classic exertional angina, nifedipine had no symptomatic effect (7.9 vs 6.8 anginal episodes/3 weeks, NS; 6.4 vs 5.8 nitroglycerin tablets/3 weeks, NS). Patients in both groups experienced a significant decrease in the manifestations of ischemia during exercise testing. Patients with mixed angina experienced a reduction in the daily frequency of painful episodes of ST segment depression during nifedipine treatment compared to placebo (0.6 vs 0.2 episodes, p less than 0.05), but there was no effect on the frequency of episodes of silent ischemia (4.2 vs 3.4 episodes, NS). In patients with classic exertional angina, the addition of nifedipine had no effect on any measure of ambulatory ischemia. We conclude that patients with mixed angina are more likely to benefit symptomatically from the addition of nifedipine therapy than patients with classic exertional angina. The lack of a consistently preferential response to nifedipine in patients with mixed angina, however, suggests that episodic coronary vasoconstriction may not be the only mechanism responsible for ischemia in these patients, and/or that nifedipine may not necessarily provide additional therapeutic benefit beyond that conferred by a regimen of beta blockers and/or nitrates.

Considerations in evaluating new antianginal drugs.

Diseases that cause symptoms incompletely relieved by available modes of treatment stimulate search for new therapies. Chronic disease processes, in which interventions are palliative rather than curative provide a particular challenge in determining the value of therapeutic intervention. Management of patients with angina pectoris is an example of this challenge.