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Biomedical subjects

F Fraioli

Publications and source records attributed to F Fraioli.

At least 19 recordsLinked to original sources
PubMed1989

Endorphins in male impotence: evidence for naltrexone stimulation of erectile activity in patient therapy.

In the present study we evaluated whether naltrexone administration could stimulate sexual function in 30 male patients, ages 25 to 50 years, with idiopathic impotence of at least one year's duration and not of organic etiology. The patients received naltrexone (50 mg/day) or placebo, on a random basis for two weeks. Sexual performance, expressed as the number of full coitus/week, was assessed before (time 0) and during (on days 7 and 15) each treatment. The naltrexone therapy significantly increased the number of successful coitus compared to placebo after 7 and 15 days of treatment: improvement of sexual performance was evident in 11 out of the 15 treated patients. All the patients experienced a significant increase in morning and spontaneous full penile erections/week. No significant side effects were reported. Endocrine studies revealed no significant modification of plasma LH, FSH or testosterone by naltrexone, suggesting that the positive effect of the drug on sexual behavior was exerted at a central level. A two-month follow-up, at which time patients were off treatment, erectile capacity had returned to baseline in 10 patients, while five reported complete recovery of their sexual ability. We hypothesize that an alteration in central opioid tone is present in idiopathic impotence and is involved in the impairment of sexual behavior.

Adult↗
PubMed1987

Mechanism of action of ECT in major depressive disorders: a neuroendocrine interpretation.

Electroconvulsive therapy (ECT) is often efficacious in severe depression, and it is occasionally used in the treatment of schizophrenia. The mechanism of action of ECT is still poorly understood. We evaluated thyroid-stimulating hormone (TSH) and prolactin responses to thyrotropin-releasing hormone (TRH) after a first ECT and at the end of a series of seven ECTs in eight unipolar depressed patients with blunted basal TSH/TRH response, eight unipolar depressed patients with normal TSH/TRH response, and eight schizophrenic patients. The hormone patterns obtained after the first ECT showed an increase in prolactin and a decrease in TSH in all groups of patients, suggesting a nonspecific response. At the end of the therapeutic course, TSH responses increased in both groups of depressed patients, and the elevation was more relevant in depressed patients with normal TSH/TRH. Our data suggest that the mechanism of action of ECT becomes more specific when it is performed chronically and differs according to the organic substrate underlying different mental disorders. Moreover, an aminergic activation in the two groups of depressed patients seems to take place.

Adult↗
PubMed1986

Metabolic clearance of biologically active luteinizing hormone in man.

The plasma metabolic clearance of biologically active luteinizing hormone (bioactive LH) was studied using the rat interstitial cell testosterone (RICT) bioassay in six hypogonadotropic men after single bolus injection of highly purified human LH and during continuous steady-state infusions of three graded doses of LH. The LH bolus disappearance curves provided estimates of metabolic clearance rates (MCR) of 24.1 +/- 4.7 (+/- SD) ml/min for bioactive LH vs. 56.2 +/- 12 ml/min for immunoactive LH in the same men (P = 0.03). A lower MCR of bioactive LH compared with immunoactive LH was also observed during continuous infusions of physiological doses of LH; for example, the mean steady-state MCRs for bioactive and immunoactive LH were, respectively, 26.1 +/- 3.1 and 34.2 +/- 3.2 ml/min (P = 0.02). Moreover, the stepped-dose infusion regimens permitted us to demonstrate that increasing doses of pure human LH resulted in progressive and parallel decreases in the apparent MCRs of both bioactive and immunoactive LH. Based on the respective steady-state MCRs calculated at physiological plasma concentrations of immunoactive and bioactive LH, we estimate a mean endogenous production rate for bioactive hormone of 1,937 IU/24 h, and for immunoactive LH of 589 IU/24 h in normal men. These results indicate that previous estimates of LH production rates from immunoassay data alone markedly underestimate the quantity of biologically active hormone secreted in man.

Adult↗
PubMed1986

Evidence for the presence of specific receptors for N-formyl chemotactic peptides on human spermatozoa.

Synthetic N-formylated peptides are potent chemoattractants for human spermatozoa in vitro. The specific structure-activity relations for eliciting a chemotactic response and the ability of the antagonist tertbutoxycarbonyl-phenylalanyl-leucyl-phenylalanyl-leucyl- phenylalanine (Boc-Phe-Leu-Phe-Leu-Phe) to inhibit the chemotaxis induced by these peptides strongly suggest the presence of receptors on human spermatozoa. The following studies were performed to identify specific binding sites on human spermatozoa by using [35S]-N-formyl-methionyl-leucyl-phenylalanine [( 35S]f-Met-Leu-Phe), a potent chemotactic peptide. Binding of the [35S]formyl-peptide to human spermatozoa was rapid (t1/2, 8 min) and reversible. Binding isotherms of the saturation experiments revealed a single class of high affinity, low capacity binding sites (equilibrium dissociation constant, 17.7 nM; maximal binding, 109 fmol/2 X 10(6) cells) and an average number of 60,000 receptors per cells. The biological potencies of a series of formyl peptides as chemoattractants correlated closely with their relative abilities to compete with [35S]f-Met-Leu-Phe for specific binding to human spermatozoa. These data fulfill the major criteria for demonstration of specific receptors for chemotactic peptides on human spermatozoa. It is likely that these receptor sites initiate the chemotactic response of human spermatozoa to N-formyl peptides.

Adult↗
PubMed1985

Calcitonin receptors in the rat mesencephalon mediate its analgesic actions: autoradiographic and behavioral analyses.

Autoradiographic analyses of salmon calcitonin (sCT) binding in the rat mesencephalon revealed an exceptionally high concentration of receptors in the ventral and ventrolateral segments of the periaqueductal gray matter (PAG) extending along the entire rostral-caudal axis. Relatively heavy labeling was also seen along a band extending ventrolaterally through the mesencephalic reticular formation. Other receptor-rich areas include the nucleus linearis, pars compacta and lateralis of the substantia nigra, locus coeruleus, parabrachial nuclei and nucleus raphe pontis of the pontine reticular formation. Injections of sCT into the PAG induced a dose-dependent increase in hot-plate latencies. All rostral-caudal levels of these brain regions appeared to be equally responsive. Injections into the midline pontine reticular formation were also effective in increasing response latencies. Unilateral injections into the hypothalamus, medial thalamus, ventral thalamus and mesencephalic reticular formation proved to be ineffective. Human calcitonin (hCT) was considerably less potent. These biological effects are consistent with the potencies of both peptides in displacing 125I-sCT from slide-mounted sections of rat PAG. Naloxone failed to antagonize sCT-induced analgesia, suggesting an opiate independent mechanism for this peptide in eliciting analgesia.

Animals↗
PubMed1985

Calcitonin inhibits the phosphorylation of various proteins in rat brain synaptic membranes.

The present report examines the effect of different calcitonins and analogs on the in vitro phosphorylation of brain synaptic membrane proteins. The findings demonstrate that calcitonin is a potent inhibitor of several brain synaptic proteins and that salmon and eel calcitonins are considerably more potent than thyrocalcitonin in eliciting this effect. Deletion of leucine from position 16 in salmon calcitonin sequence resulted in a drastic loss of inhibitory activity, indicating the importance for a hydrophobic residue at position 16 in the intact calcitonin molecule. The mechanism of calcitonin inhibition of protein phosphorylation was likely due to the blockade of stimulation of protein kinases by calmodulin.

Animals↗
PubMed1985

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)

Adult↗
PubMed1985

Demonstration of receptor-mediated chemotaxis by human spermatozoa. A novel quantitative bioassay.

A novel in vitro technique is described for measuring the chemotactic activity of soluble substances for human spermatozoa. This new bioassay has demonstrated that the synthetic chemotactic peptide N-formyl-Met-Leu-Phe elicits a potent, specific (i.e., receptor-mediated) chemotactic effect on human spermatozoa with an EC50 of 3.2 X 10(-10) M. Quantitative chemotactic studies on human spermatozoa with nine N-formylated-peptide analogs have shown a rank order of peptide potency indistinguishable (p less than 0.001) from that obtained in binding and chemotactic studies with rabbit neutrophils. The competitive antagonist Boc (t-butoxycarbonyl)-Phe-Leu-Phe-Leu-Phe, 10(-6) M, completely inhibited the chemotaxis elicited by f-Met-Leu-Phe, 10(-9) M, and was able to shift by one order of magnitude the molar concentration required by f-Met-Leu-Phe-Phe and f-Met-Leu-Phe to elicit the maximal response. The ability of N-formylated peptides to function as sperm chemoattractants reveals a high degree of correlation with binding, chemotaxis, and lysosomal enzyme release previously employed to define the neutrophil chemotactic receptor. This first unequivocal demonstration of substances having a receptor-mediated chemotactic effect for human male gametes suggests that human spermatozoa may indeed have the ability to respond chemotactically to appropriate environmental signals.

Biological Assay↗
PubMed1985

ACTH, beta-endorphin and met-enkephalin: peripheral modifications during the stress of human labor.

We investigated the psychoneuroendocrine and emotional correlates of the natural stress situation of human labor. State anxiety, subjective pain, plasma ACTH, peripheral plasma beta-lipotropin (Beta-LPH), beta-endorphin (Beta-EP), and met-enkephalin (Met-Enk) were serially evaluated at six predetermined time points before, and after labor in a sample of 14 women with normal pregnancies. State anxiety and subjective pain showed a progressive increase during labor, with a levelling during the final stage. Plasma Beta-EP and ACTH showed a similar progressive increasing from baseline until the end of labor. Beta-LPH showed no significant modification. Met-Enk remained at nearly baseline values throughout labor, with a marked progressive rise in the postpartum stage. The findings of this study seem to confirm the role of plasma Beta-EP as a stress hormone. Possible relationship between pain and anxiety curves and plasma Beta-EP are discussed in light of psychobiological studies on stress, the opioid system and analgesia. Plasma Met-Enk, according to our findings, should probably not be regarded as a stress hormone. Its rise in the postpartum stage might be as one of the psychoneuroendocrine mechanisms maintaining elevated prolactin levels during lactation.

Adrenocorticotropic Hormone↗
PubMed1985

Opiate receptors are present in the rat testis. Identification and localization in Sertoli cells.

We have characterized opioid binding sites in the Sertoli cells of adult and 18-day-old rat testes. Maximal specific etorphine binding was attained after 30 min at 4 C. The binding was reversible, with association and dissociation rate constants of 0.98 X 10(5) M-1 min-1 and 0.33 min-1, respectively. Scatchard analyses and saturation curves revealed a single class of high-affinity, low-capacity binding sites. No opioid binding was observed in Leydig cell cultures. Exposure to opioids for 3 days caused a significant increase in [3H]etorphine specifically bound to the Sertoli cells that was completely prevented by naloxone, demonstrating opioid up-regulation of its own receptor. Chronic opioid treatment of the cultures significantly inhibited androgen-binding protein production, and this effect was prevented by naloxone. Since the circulating concentrations of endorphins (10(-12) M) are lower than the Kd of testis opiate receptors, it is conceivable that opioids of Leydig cell origin act on the specific high-affinity receptors of the Sertoli cells, and may play a role in modulating their function.

Androgen-Binding Protein↗
PubMed1985

Human semen inhibits T rosette formation through an opiate mediated mechanism.

Seminal plasma contains high levels of opioid peptides and both seminal plasma and endogenous opioids can influence the immune system. In order to investigate whether these two findings can be related, semen was collected from 7 normal subjects, and assayed for beta-endorphin content and for its in vitro ability to inhibit the total T rosette formation of human lymphocytes in the presence or in the absence of 10(-6) M naloxone, an universal opiate antagonist. The results were as follows: 1) immunoreactive beta-endorphin content in seminal plasma was 4 to 12 times higher than the peripheral plasma levels detected in the same subjects (76.1 +/- 42.1 SD vs 10.5 +/- 2.0 SD pg/ml); 2) increasing concentrations of seminal plasma (1%, 5%, and 10%) in RPMI 1640 significantly depressed the T rosette formation ability of lymphocytes; and 3) the simultaneous addition to the incubation mixture of 10(-6) M naloxone prevented the phenomenon, while naloxone per se was ineffective. The possibility that endogenous opioids may play a role in the immunomodulatory action of human semen is suggested.

Adult↗
PubMed1980

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.

Adrenocorticotropic Hormone↗