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Serotoninergic receptor activation by dextrofenfluramine enhances the blunted pituitary-adrenal responsiveness to corticotropin-releasing hormone in obese subjects
No full textTo explore the interrelationships between the serotoninergic system and the hypothalamic-pituitary-adrenal (HPA) axis in human obesity, we evaluated cortisol and adrenocorticotropic hormone (ACTH) response to synthetic human corticotropin-releasing hormone (hCRH, 1 μg/kg intravenously [IV]) before and after stimulation of the serotoninergic system by dextrofenfluramine (d- FF, 30 mg/d for 3 months) in nine obese women. These responses were compared with a CRH test (1 μg/kg) carried out in nine age-matched normal-weight women. Plasma cortisol of obese subjects did not significantly increase after CRH (peak value 127.1 ± 11.2 ng/mL v 104.1 ± 9.5 ng/mL). This response was lower (P < .005) than in the controls, in whom the basal cortisol value of 120.6 ± 11.8 ng/mL reached a peak value of 221.2 ± 13.4 ng/mL. However, after administration of d-FF, CRH significantly increased (P < .0001) plasma cortisol (peak value 170.6 ± 18.0 ng/mL v 111.5 ± 10.8 ng/mL) and the response was enhanced (P < .05) as compared with that obtained before d-FF. The ACTH levels of our patients showed a small increment after CRH injection (peak value 13.5 ± 1.7 pg/mL v 9.6 ± 1.1 pg/mL), but the hormonal response was lower (P < .005) than in controls (peak value 38.1 ± 5.5 pg/mL v 13.8 ± 0.8 pg/mL). However, after d-FF, CRH induced a significant increment (P < .05) in plasma ACTH at 30 minutes (20.4 ± 3.7 pg/mL v 10.9 ± 0.9 pg/mL) and 45 minutes (18.0 ± 2.6 pg/mL), even though this response was not significantly different from that observed before d-FF administration. In conclusion, we found a blunted pituitary response to CRH in obese subjects, which was improved by serotoninergic stimulation. This finding indicates a reduced serotonin activity in these subjects and shows that the serotoninergic system is also involved in the regulation of the HPA axis function
Blunted growth hormone (GH) responsiveness to GH-releasing hormone (GHRH) in obese patients: influence of prolonged administration of the serotoninergic drug fenfluramine
No full textThe aim of the present study was to ascertain if reduced central serotoninergic activity might contribute to the well-known blunted growth hormone (GH) response to GH-releasing hormone (GHRH) in obese patients. Thus, we studied the effect of prolonged stimulation of the serotoninergic system by fenfluramine (FF; 60 mg twice daily for 7 days) on GHRH-induced GH release in nine obese and seven normal subjects. In controls, GHRH (100 μg intravenously [IV]) injection increased GH levels from 2.3 ± 1.8 (±SE) to 18.5 ± 2.8 mU/L, P < .002. FF administration enhanced both basal and GHRH-stimulated GH levels (peak, 38.4 ± 8.3 v 6.9 ± 2.6 mU/L, P < .002). This response was significantly higher (P < .02) than in pretreatment. In obese patients, GH responsiveness to GHRH was slight (peak, 7.1 ± 2.0 v 0.6 ± 0.18 mU/L, P < .01) and lower (P < .01) than in controls. FF administration did not affect this response. In controls, the enhanced FF-induced GH release after a maximal dose of GHRH indicates that serotoninergic activation influences GH secretion and that the mechanism involved is independent of endogenous GHRH. In obese patients, we found a blunted GH responsiveness to GHRH that was not affected by FF, thus supporting the hypothesis that the serotoninergic control on GH release is impaired
Effects of fenfluramine and ritanserin on prolactin response to insulin-induced hypoglycaemia in obese patients: evidence for failure of the serotoninergic system
No full textIn order to study the hypothesized impairment of the serotoninergic system in human obesity, an insulin tolerance test (ITT) was carried out on 12 obese normoprolactinemic women and on 6 normal-weight women before (A) and after (B) the administration of a serotoninergic drug, fenfluramine (60 mg twice a day per os for 7 days). After a washout period, a new ITT (C) followed the administration of fenfluramine at the same dose, associated with a specific S2 blocker receptor agent, ritanserin (30 mg/day for the first 2 days and 20 mg/day for a further 5 days). In obese subjects, the prolactin (PRL) response to ITT A was reduced as compared to the controls: in 6 patients ('nonresponders') the PRL levels did not change, while in the other 6 ('responders') they increased (p < 0.003) but less than in the controls (p < 0.02). In normal-weight subjects, the administration of fenfluramine alone or with ritanserin did not modify the PRL response to ITT. In the responders, the serotoninergic drug normalized the PRL response to ITT while significantly improving it in the nonresponders; these effects were not antagonized by ritanserin. In conclusion, our data suggest that the serotoninergic system of obese patients is impaired and that the different secretory pattern observed in the two groups before and after fenfluramine may reflect differing degrees of this impairment
Effetti della fenfluramina sulla risposta della prolattina alla ipoglicemia insulinica nei soggetti obesi
No full textNaloxone does not antagonize the antihypertensive effect of chronic captopril therapy in hypertensive patients
No full textIt has been reported that naloxone, an opiate receptor antagonist, blunts the hypotensive effect of captopril in normotensives. However, our previous data did not show any interaction between captopril given acutely and naloxone (0.1 mg/kg) in hypertensives. To test whether a greater naloxone dose could interfere with the hemodynamic effect of chronically administered captopril, 12 male hypertensives were studied: Six of them had been under captopril treatment (50 mg tid) for at least 1 month, whereas the others had been drug free for the same time. Both groups randomly received a saline or naloxone (0.2 mg/kg) infusion for 1 hour, and blood pressure, heart rate, PRA, plasma aldosterone, adrenaline, and noradrenaline were measured at regular intervals before, during, and after naloxone infusion. In drug-free hypertensives, naloxone tended to reduce blood pressure slightly and did not modify heart rate, PRA, plasma aldosterone, adrenaline, or noradrenaline. In captopril-treated hypertensives, naloxone did not blunt the hypotensive effect of captopril, but rather enhanced it, without changing the heart rate, adrenaline, and noradrenaline. Moreover, naloxone increased the renin-stimulating action and did not modify the aldosterone-inhibiting effect of captopril. Our results show that the hemodynamic action of captopril given chronically is not influenced by opioid receptor blockade and therefore that the antihypertensive effect of this drug seems to be unrelated to the activation of the opioidergic system
Impaired growth hormone response to insulin-induced hypoglycaemia in obese patients: restoration blocked by ritanserin after fenfluramine administration
No full textThe aim of the present study was to test whether the serotoninergic system may be involved in the well known reduced growth hormone (GH) response to insulin-induced hypoglycaemia (IIH) in obese patients. Ten obese women and 10 normal-weight control women underwent three IIH tests, at 14-day intervals: the first in basal conditions, the other two after randomized administration of a serotoninergic drug, fenfluramine (FF, 120 mg/day for 7 days) and FF plus ritanserin (RIT, 30 mg/day for the first 2 days and 20 mg/day on the following days). Ritanserin is a new selective 5-HT2 blocker receptor agent. Both controls and obese patients showed similar normal basal GH levels before each test and insulin administration always effectively reduced glucose levels to values lower than 2.2 mmol/l. In the controls, the expected GH increase to IIH (peak value 56 ± 13.4 mU/l, AUC 234.4 ± 55 mU/min/ml) was unaffected by FF administration (peak value 43 ± 11.4; AUC 216.8 ± 34.8). In response to the first IIH, the obese patients showed a significantly lower GH increase than in the case of the controls (peak value 21.4 ± 4.6 mU/l, P < 0.02; AUC 93.2 ± 18.6, P < 0.02). However, in comparison with the basal test, FF administration significantly (P < 0.001) enhanced GH response to insulin hypoglycaemia (peak value 33.4 ± 4; AUC 150 ± 14.6), reaching values not significantly different from those of the controls. This effect was completely antagonized by RIT administration (peak value 18 ± 5; AUC 85.6 ± 21). In conclusion, the reduced GH response to insulin hypoglycaemia in obese women has been confirmed in the present study. However, the restoration of the hormonal response obtained after FF administration in obese patients only, which is effectively antagonized by RIT, strongly suggests the involvement of the serotoninergic system in this impaired secretory pattern and provides indirect evidence of the failure of this system in human obesity
Naloxone does not modify fenfluramine-induced prolactin increase in obese patients.
No full textObjective. To evaluate whether the supposed physiological interaction between serotoninergic and opioidergic pathways in the modulation of PRL release is preserved in human obesity, a pathological condition in which these two systems are greatly impaired. Design. According to a single-blind randomized procedure, three tests were performed: test A (oral placebo + saline infusion over 5 hours), test B (fenfluramine, a well known serotoninergic drug, 60 mg orally + saline infusion over 5 hours) and test C (fenfluramine at the same dose + naloxone, an opiate receptor antagonist, infusion over 5 hours at a dose of 3 mg/h). Patients. Ten obese women (body mass index 34.4 ± 2.3 kg/m 2, mean ± SE) and ten normal-weight sex and age-matched subjects (body mass index 22.3 ± 2.4 kg/m 2) volunteered for the study. Measurements. At each test, blood samples for PRL determination were collected in basal conditions (time 0) and every hour for 5 hours. Plasma PRL was determined by radioimmunoassay. Results. In controls, naloxone significantly reduced the clear-cut PRL increase induced by fenfluramine. In obese patients, serotoninergic stimulation caused an increment in PRL levels similar to that in the controls, but opioid receptor blockade by naloxone did not affect this response. Conclusions. These findings confirm that there is a physiological relationship between the serotoninergic and the opioidergic systems in the control of PRL secretion and show that this interaction is not present in obese subjects. Our data provide indirect proof of the functional impairment of these two systems in human obesity
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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