Androgens, cardiovascular disease and osteoporosis.

Epidemiological studies correlated the age-related decline of serum testosterone levels to the concomitant increase of cardiovascular diseases, osteoporosis and bone fractures. For this reason, testosterone replacement therapy (TRT) in older men with late-onset hypogonadism has been advocated. Testosterone has an anti-resorptive effect that may increase bone density at lumbar spine. Androgens may also have cardio-protective effects by improving endothelial function and reducing the risk factors for atherosclerosis. It has been proposed that atherosclerosis and osteoporosis share common pathophysiological mechanisms. The role of inflammatory cells, citokynes and calcium deposition into the vascular walls has been reviewed to explore the causal nexus between these frequently associated diseases. Experimental studies indicate that a deregulation in the commitment of pluripotent mesenchimal stem cells toward specialized phenotypes might participate in the development of these conditions. The crossed-over beneficial effect of bisphosphonate on the cardiovascular system and statins on bone metabolism supports the research for a unitary pharmacological approach to both conditions. The findings that androgens regulate mesenchimal cell differentiation, as well as body composition, lipid profile and bone metabolism, have claimed a role for TRT in aging men with late onset-hypogonadism.

Thyroid C-cell hyperplasia in an adolescent with neurofibromatosis type 1.

BACKGROUND: Subjects with neurofibromatosis type 1 (NF1) show an increased risk of endocrine tumors, especially pheochromocytoma, whereas thyroid C-cell hyperplasia (CCH) and medullary thyroid carcinoma (MTC) are very rare events described only in adult patients. METHOD: A case of CCH diagnosed in a 14-year-old girl affected with NF1 is reported. Calcitonin serum level after pentagastin was elevated (286 pg/ml). Genetic testing was performed in order to rule out mutations in the RET proto-oncogene. RESULT: No germline mutation previously reported in MEN2 was detected. Multifocal and bilateral CCH was demonstrated by immunohistochemistry. CONCLUSION: It is suggested that in such a genetic background of high risk for malignancy, CCH could be considered as an extremely rare condition likely preceding MTC.

Re-dosing of prostaglandin-E1 versus prostaglandin-E1 plus phentolamine in male erectile dysfunction: a dynamic color power Doppler study.

During penile pharmacotesting, anxiety may overcome complete smooth muscle relaxation and lead to false positive diagnosis of organic male erectile dysfunction (ED). We tested the efficacy and safety of re-dosing of PGE1 alone versus combination of PGE, and the alpha1,2-blocker phentolamine (PHE) to improve an incomplete pharmaco-induced erection during color-power-Doppler (CPD) sonography. 116 consecutive impotent patients were submitted to CPD and injected with 10 microg PGE, plus audiovisual sexual stimulation. Clinical evaluation of rigidity and CPD parameters were normal in 26 patients while in the remaining they were upgraded in 15% and 35% after redosing of 10 microg PGE1 alone and 10 microg PGE1 plus 1 mg PHE, respectively (P < 0.05); furthermore, in these latter patients CPD studies showed increased visualisation of distal ramifications of helicine arterioles. The final diagnosis was changed in those patients who responded to re-dosing with no differences in the occurrence of prolonged erections between the two treatments. We conclude that re-dosing of PGE1/PHE mixture is a safe and effective procedure to maximize erectile response during dynamic CPD sonography and has a better diagnostic sensitivity than re-dosing of PGE1 alone.

[The use of dynamic Doppler color ultrasonography of the penis in the study of erectile dysfunction]. / Utilizzazione dell'eco color Doppler dinamico del pene nello studio delle disfunzioni erettili.

INTRODUCTION: We investigated the diagnostic accuracy of dynamic color Doppler sonography (D-CDS) in men with erectile dysfunctions (ED). Terminal microcirculation alterations and their correlation with erectile response after drug testing were investigated with power Doppler energy. MATERIAL AND METHODS: 134 impotent patients were submitted to CDS during flaccidity: 8 of them (6%) had sparse hyperechoic spots inside the corpora. A standardized intracavernous injection of 10 micrograms alprostadil (PGE1) was followed by audiovisual sexual stimulation. If rigid erection was not achieved after 20 minutes, patients were randomized to redosing of either 10 micrograms PGE1 (phase 2a) or 10 micrograms PGE1 plus 1 mg phentolamine (phase 2b), with reassessment of power Doppler recordings after 20 minutes (peak systolic velocities and the resistive index, RI). RESULTS: A rigid erection (RI > .90) was achieved in 26% of patients after the first injection. As for the remaining patients, the RI was improved in 12% after phase 2a and in 34% after phase 2b (p < .05), with no differences in mean peak systolic velocities. Power Doppler showed two/three orders of distal branches of helicine arterioles with regular morphology, in most of the latter subjects. A negative correlation (r = .68, p < .001) was found between penile fibrosis and the degree of rigidity achieved after the first injection. CONCLUSIONS: Penile sonography in the flaccid state can show calcificic plaques and/or fibrosis of the corpora. Redosing of PGE1 plus phentolamine during D-CDS is a safe procedure and improves diagnostic accuracy in erectile dysfunctions, with significantly fewer non-responders than redosing of PGE1 alone. Power Doppler energy shows altered morphology of helicine arterioles otherwise missed at color Doppler and is thus recommended to make an accurate diagnosis in some men with erectile dysfunctions.

[Pharmacology of male sexual dysfunction]. / Farmacologia delle disfunzioni sessuali maschili.

The understanding of pharmacology of impotence has shown a steady improvement over the last 15 years which has resulted in a better appreciation of the neurovascular mechanisms of the erectile process especially at the level of the corpora cavernosa; however, central mechanisms which control libido and erection are not yet completely elucidated. Frequent diseases most commonly encountered in elderly patients--i.e. diabetes, hypertension, atherosclerosis, depression, etc--represent a frequent cause of erectile dysfunction (ED) and are treated with medications that can interfere with sexual functioning at the central and/or peripheral level. Antidepressants, including the tricyclics and the monoamine oxidase inhibitors, have been implicated in ED, decreased libido, and impaired ejaculation. Most antihypertensives have been associated with some erectile impairment, but diuretics seem to have little effect on erectile function. The calcium channel blockers and ACE inhibitors are associated with a low incidence of ED. Sympatholytic antihypertensives seldom cause importence but can cause retrograde ejaculation because of the relaxation of the smooth muscles in the prostatic urethra and bladder neck. The most commonly prescription drugs that can affect sexual function are briefly discussed and an integrated pharmacological approach to the patient with drug-induced ED is proposed.

[Adrenal adenoma or hyperplasia? Problems of differential diagnosis in an unusual case of primary hyperaldosteronism]. / Adenoma surrenalico o iperplasia? Problemi di diagnostica differenziale in un caso inusuale di iperaldosteronismo primitivo.

Although primary hyperaldosteronism is an uncommon cause of hypertension, it is the most common form of renin-independent hypermineralocorticoidism. The plasma aldosterone concentration and PRA with orthostatic test and saline infusion test are very useful aids to make a diagnosis. In this case the inconsistency between hormonal data and morphologic images (TC and NMR) led us to a dilemma: it was a question of adrenal adenoma or hyperplasia? Because it was impossible to dose the 18-OH-corticosterone, we had to perform a iodocholesterol scintigraphy NP 59. To distinguish an hyperplasia as cause of this kind of hyperaldosteronism made us able to define a therapeutic program useful to hypertension control.

Recombinant-growth hormone (rec-hGH) therapy in infertile men with idiopathic oligozoospermia.

The study was designed to be an open test for short-term efficacy of rec hGH-therapy on spermatogenesis of ten infertile men with idiopathic severe oligozoospermia (1-5 x 10(6)) and normogonadotropinemia or moderate ipergonadotropinemia (FSH: range 1.90-9.60 IU/L, mean +/- SD 5.78 +/- 2.84; LH: 2.70-12.70 IU/L, mean +/- SD 6.60 +/- 3.61). FSH, LH, Testosterone, GH, and IGF-I were evaluated. Seminal parameters: sperm concentration, sperm motility and morphology were studied before and after therapy. Five responder patients showed an increase of seminal parameters both in sperm concentration and total number of motile spermatozoa. The short-term rec-hGH therapy significantly increased sperm concentration and total motile spermatozoa in five out of ten infertile patients who didn't show any modification in seminal parameters to other preavious treatment.

[Blood levels of somatotropic hormone in patients with various degrees of heart failure]. / Livelli ematici dell'ormone somatotropo in pazienti con diverso grado di scompenso cardiaco.

BACKGROUND: The hypothesis that in normal pituitary patients (pts) with heart failure the heart is a target-organ of the hypophysis has not be held in due consideration. Aim of the study was: 1) to determine Growth Hormone (GH) plasma levels in pts with various degree of heart failure; 2) to evaluate the relationship between GH, left ventricular mass and some haemodynamic and endocrine parameters of ventricular dysfunction. MATERIALS AND METHODS: Blood samples for determination of GH and Atrial Natriuretic Factor (ANF) were collected 24 hours before haemodynamic study. Plasma concentrations of GH and ANF were determined by radio-immuno-assay in 20 normotensive pts (age ranging 31 to 54) without mellitus diabetes in IV (10 pts) and III (10 pts) NYHA FC: Echocardiographic determination of left atrial diameter, end-diastolic and end-systolic left ventricular diameters, index of left ventricular mass (ILVM), were performed. All pts underwent right and left cardiac catheterization and coronary angiography. RESULTS: The pts in IV NYHA FC, Group A, had lower cardiac index (IC) (1.8 +/- 0.4 vs 2.9 +/- 0.1, p < 0.0001) and higher GH and ANF plasma levels than those in III NYHA FC, Group B (4.9 +/- 4.5 vs 0.12 +/- 0.04, p < 0.01; 157.9 +/- 43.9 vs 65.6 +/- 14.6, p < 0.0001). No significant difference was found by comparing in both groups ILVM (212.6 +/- 64.7 vs 192.9 +/- 71.9, NS). GH and ANF plasma levels were 4.1 +/- 5.0 and 113.8 +/- 59.6 in pts with ILVM > or = 200 g/mq and 0.9 +/- 2.7 and 109.7 +/- 57.3 in pts with ILVM < 200 g/mq (no significant statistical difference). We found an high correlation by comparing GH and ANF in group with ILVM > or = 200 g/mq (r = 0.82, p < 0.005) and in group with ILVM < 200 g/mq (r = 0.68, p < 0.05). CONCLUSIONS: Our study demonstrated: 1) increased GH plasma levels in pts with severe heart failure; 2) an high correlation between GH and ANF plasma levels in pts with ILVM > or = 200 g/mq.

[Medullary carcinoma of the thyroid: a case of multiple endocrine neoplasia type 2A]. / Carcinoma midollare della tiroide: un caso di neoplasia endocrina multipla tipo 2 A.

Medullary thyroid carcinoma (MTC) is a neoplasm derived from thyroid C-cells. It can appear under different variants; in the 20-30% of the cases, it's a familial variant. Nevertheless, the MTC appearing in MEN 2-A has a better prognosis compared to MEN 2-B. Usually, the diagnosis of MEN 2-A is done at the age of 20, and frequently (in the 50% of the cases) these patients develop, in a second time, adrenal hyperplasia and/or pheochromocytoma. The case we are talking about, concerns a patient of 49 years old, who came to our observation with a history of bilateral adrenalectomy for pheochromocytoma. What attracted our attention was the presence, in his family, of a brother, who died from pheochromocytoma, and the mother, died for a MTC. During the admit in our section, the patient has undergone a screening for the thyroid function, also if there wasn't a sign or symptom of interest of the gland. It has been possible to single out some nodular formations that, together with the high value of the calcitonin found, allowed the diagnosis of MTC. It has been very important to make diagnosis of MEN 2-A because we can introduce the patient and his family to a program of screening to precociously single out the presence of the typical signs of this pathology. In MEN 2-A a precocious diagnosis allows to sensibly improve the prognosis.

Piroxicam-induced analgesia: evidence for a central component which is not opioid mediated.

Piroxicam is a nonsteroidal anti-inflammatory drug with a potent analgesic effect. In order to establish whether the analgesic action of Piroxicam has a central component, we studied the effect of the drug on the nociceptive orbicularis oculi reflexes evoked by electrical stimulation of the cornea and supraorbital nerve in healthy subjects. Piroxicam significantly suppressed the corneal reflex and R3 component of the blink reflex by 28% (p < 0.05) and 50% (p < 0.01), respectively. This effect was not reversed by the i.v. injection of naloxone. Beta-endorphin levels did not change. Piroxicam administration induces distinct inhibitory changes in nociceptive reflexes, which suggests that the analgesic action of the drug has a central component. The ineffectiveness of naloxone, and the lack of beta-endorphin changes, indicate that this central action is independent of the opioid system; other pain regulatory systems are probably involved.

Immunohistochemical localization of growth hormone-releasing hormone in human gonads.

Human gonads were examined for the presence of ir growth hormone-releasing-hormone. We demonstrated the presence of immunostainable cells both in ovarian and in testicular tissue using a non-crossreactive anti-GRH antiserum and the immunoperoxidase detection technique. In ovaries from ovulating women, GRH immunoreactivity was localized in the corpora lutea; granulosa cells, theca cells and cells of primary follicles did not stain. In premenopausal ovaries, staining was detectable in scattered luteinized stromal cells. In testes from post-puberal men GRH immunoreactivity was localized in the Leydig cells; cells of the germinal epithelium did not stain. These results demonstrate the presence of GRH in human gonads and suggest that this peptide may exert regulatory function at the testicular and ovarian levels.

Gastrin-releasing peptide-like immunoreactivity in porcine follicular fluid and ovary.

Porcine follicular fluid was found to contain gastrin-releasing peptide (GRP) by radioimmunoassay. High pressure liquid chromatography of the extracted material showed two peaks of GRP immunoreactivity that closely resembled the C-terminal fragments of GRP, GRP18-27 and GRP14-27. Immunohistochemical studies revealed specific staining for GRP in the granulosa cells of adult porcine ovary. These results demonstrate the presence of substances which behave like authentic GRP-like peptides in porcine ovary and follicular fluid and suggest that these peptides may play a paracrine and/or autocrine role in the regulation of the ovarian function.

Isolation of a human seminal plasma peptide with bombesin-like activity.

Bombesin (BN) and BN-like peptides such as gastrin-releasing peptide (GRP) belong to the growing group of regulatory peptides. Bombesin and GRP share the same carboxyl-terminal heptapeptide sequence that is essential for receptor recognition and biologic activity. Immunohistochemical findings have indicated the presence of a BN-like peptide in the neuroendocrine cells of the human prostate. These findings, together with the high concentrations of different regulatory peptides recently found in seminal plasma, prompted us to characterize a BN-like peptide in human semen by gel-filtration chromatography, reverse-phase high-pressure liquid chromatography, and in vitro bioassay. Here we demonstrate that human semen contains high levels (mean +/- standard deviation, 288.9 +/- 114.39 pg/ml) of a substance that closely resembles the 14-27 carboxyl-terminal fragment of GRP (GRP 14-27). The partially purified peptide obtained from this source, examined on an in vitro bioassay that is especially useful for testing BN-like activities, elicits a contractile response of the rat uterus that is indistinguishable from that stimulated by standard BN and GRP 14-27. The GRP 14-27 present in human seminal plasma may be involved in some aspect of the process of fertilization.

Naloxone increases bioactive LH in man: evidence for selective release of early LH pool.

Opioid peptides inhibit LH secretion and the opiate antagonist naloxone provokes increases in plasma LH levels by release of endogenous GnRH from the hypothalamus. To explore the effect of endogenously released GnRH on the mobilization of bioactive LH pools, the bioactive LH response to a single iv bolus dose of 20 mg naloxone has been evaluated and compared to the immunoactive pattern of the hormone in eight young normal male volunteers. Blood samples were withdrawn at 15, 30, 45, 60, 90, 120 min after naloxone injection and LH levels were measured by RIA and rat interstitial cell testosterone (RICT) bioassay. A significant increase in both bio and immuno active LH was observed in all subjects after 15-30 min (p less than 0.05 to p less than 0.001), reaching maximal levels at 30-60 min for both forms of the hormone. The time course of the bioactive LH response magnified the immunoactive LH pattern, and the maximum fold increases were 1.4 and 1.3 fold (62.4 +/- 5.5 SE and 25.0 +/- 3.7 SE mIU/ml) from basal bio and immuno LH levels of 25.9 +/- 4.3 SE and 11.1 +/- 2.0 SE mIU/ml respectively. An early single peak response of bio and immunoactive LH was observed in six subjects while a biphasic pattern was observed in two subjects with a clearly defined and prominent early pool followed by a second pool of higher magnitude. Both bio and immunoactive LH levels began to decline at 45-60 min, but in most subjects remained significantly elevated by about 30% above the basal values at 120 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Salmon calcitonin inhibits human sperm motility in vitro.

We have evaluated by a stroboscopic technique the in vitro effect of salmon calcitonin and human calcitonin on the motility of human migrated spermatozoa. We report here that human calcitonin is uneffective while salmon calcitonin is a potent inhibitor of the sperm motility. This salmon calcitonin action is abolished by the preincubation of the peptide with an anti-salmon calcitonin antiserum, demonstrating the specificity of the effect. In addition, we provide evidence that the release of intracellular calcium represents a necessary step for the action of the peptide. In fact, the salmon calcitonin effect is prevented in a dose-dependent way by dantrolene sodium which inhibits the release of calcium from intracellular stores while the calcium channel blocker verapamil is unefficacious. These results suggest a potential role for calcitonin in regulating human sperm motility.

Effects of a new glucocorticoid, deflazacort, on pituitary-adrenal function in man: a comparison with prednisone.

The influence on plasma ACTH and cortisol and on blood sugar have been evaluated in seven volunteers after single oral doses of prednisone 4 mg and 8 mg and deflazacort 5 mg and 10 mg. Drugs were administered at midnight to achieve a maximum inhibitory effect on the hypothalamic-pituitary-adrenal axis. No difference was detected in the majority of cases between the high and the low dose of each drug. In particular, the results obtained with the higher doses show a significant effect of both drugs on ACTH (at hour 4 after drug administration) and on cortisol (at hours 4, 8, 12 and 16). As for blood sugar, the hyperglycemic activity of deflazacort appears to be lower than prednisone at hours 12 and 16. On the whole, the potency of deflazacort appears similar to that of prednisone.