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Biomedical subjects

A Fabbri

Publications and source records attributed to A Fabbri.

At least 91 records · Page 5Linked to original sources
PubMed1999

Expression of functional leptin receptors in rodent Leydig cells.

Several studies indicate that the size of body fat stores and the circulating levels of the adipocyte-derived hormone leptin are able to influence the activity of the hypothalamic-pituitary-gonadal axis. The leptin-hypothalamic-pituitary-gonadal interactions have been mainly studied at the level of the central nervous system. In this study, we investigated the possibility that leptin may have direct effects on the rodent Leydig cell function. To probe this hypothesis, we first analyzed the expression of leptin receptors (OB-R) in rodent Leydig cells in culture. RT-PCR studies showed that rat Leydig cells express both the long (OB-Rb) and short isoform (OB-Ra) of leptin receptor, whereas MLTC-1 cells (a murine Leydig tumor cell line) express only the long isoform. Short-term (30-90 min) incubation of rat Leydig cells with increasing concentrations ofleptin (2-500 ng/ml) led to a significant and dose-dependent inhibition of human (h)CG-stimulated testosterone (T) production (approximately 60% reduction, IC50 = 20 ng/ml) but no change in basal androgen release. Also, leptin (150 ng/ml) amplified hCG-induced intracellular cAMP formation (1- to 2-fold) without modifying basal cAMP levels. Subsequent experiments showed that leptin inhibited 8Br-cAMP-stimulated T production, indicating that leptin's effect is exerted beyond cAMP. The inhibitory effect of leptin on hCG-induced T secretion was accompanied by a significant reduction of androstenedione and a concomitant rise of the precursor metabolites pregnenolone, progesterone, and 17-OH-progesterone, conceivable with a leptin-induced lesion of 17,20 lyase activity. Separate experiments performed with the MLTC-1 cells (not expressing cytochrome P450-17alpha) showed that leptin, though amplifying hCG-stimulated cAMP production, did not modify hCG-stimulated pregnenolone and progesterone release. These results further indicate that leptin action on steroidogenesis occurs downstream of progesterone synthesis. Northern Blot experiments showed no acute effect of leptin on cytochrome P450-17alpha messenger RNA accumulation in rat Leydig cells in basal and hCG-stimulated conditions, excluding that the rapid changes observed were caused by messenger RNA degradation. In conclusion, these findings, for the first time, show that leptin has direct, receptor-mediated actions on rodent Leydig cells in culture, at concentrations within the range of obese men.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1999

Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels.

Leptin circulates in plasma at concentrations that parallel the amount of fat reserves. In obese males, androgen levels decline in proportion to the degree of obesity. Recently, we have shown that in rodent Leydig cells leptin inhibits hCG-stimulated testosterone (T) production via a functional leptin receptor isoform; others have found that leptin inhibits basal and hCG-induced T secretion by testis from adult rats. In this study, we further investigated the relationship linking leptin and androgens in men. Basal and hCG-stimulated leptin and sex hormone levels were studied in a large group of men ranging from normal weight to very obese (body mass index, 21.8-55.7). Initial cross-sectional studies showed that circulating leptin and fat mass (FM) were inversely related with total and free T (r = -0.51 and r = -0.38, P < 0.01 and P < 0.05, respectively). Multiple regression analysis indicated that the correlation between leptin or FM and T was not lost after controlling for SHBG and/or LH and/or estradiol (E2) levels and that leptin was the best hormonal predictor of the lower androgen levels in obesity. Dynamic studies showed that in obese men the area under the curve of T and free T to LH/hCG stimulation (5000 IU i.m.) was 30-40% lower than in controls and inversely correlated with leptin levels (r = -0.45 and r = -0.40, P < 0.01 and P < 0.05, respectively). Also, LH/hCG-stimulation caused higher increases in 17-OH-progesterone to T ratio in obese men than in controls, whereas no differences were observed between groups either in stimulated E2 levels or in the E2/T ratio. In all subjects, the percentage increases from baseline in the 17-OH-progesterone to T ratio were directly correlated with leptin levels or FM (r = 0.40 and r = 0.45, P < 0.01), but not with E2 or other hormonal variables. In conclusion, our studies, together with previous in vitro findings, indicate that excess of circulating leptin may be an important contributor to the development of reduced androgens in male obesity.

17-alpha-Hydroxyprogesterone↗
PubMed1999

Dyspnoea, peripheral airway involvement and respiratory muscle effort in patients with type I diabetes mellitus under good metabolic control.

Dyspnoea and pulmonary dysfunction have recently been associated with Type I (insulin-dependent) diabetes mellitus. The putative role of altered pulmonary mechanics and of performance of inspiratory muscles in inducing dyspnoea has not been yet assessed in Type I diabetes. To better focus on this topic we evaluated nine patients with Type I diabetes mellitus, aged 19 to 48 years with good and stable metabolic control, without a history of smoking and microvascular complications, alongside a group of 14 healthy control subjects. In each subject, pulmonary volumes, static and dynamic compliance, pleural pressure swings (Pplsw), maximal inspiratory pressures (Pplsn), Pplsw(%Pplsn), a measure of respiratory muscle effort, and tension-time index [TTI=TI/TTOTxPplsw(%Pplsn)] were measured (TI=inspiratory time;TTOT=total time of the respiratory cycle). All subjects were studied at baseline and during hypoxic rebreathing. Patients had normal pulmonary volumes. During hypoxic rebreathing, a normal change in respiratory muscle effort [DeltaPplsw(%Pplsn)/DeltaSaO2] and DeltaTTI/DeltaSaO2, and a lower change in tidal volume versus change in oxygen saturation [DeltaVT(% vital capacity)/DeltaSaO2], resulted in a higher ratio of respiratory effort to tidal volume [Pplsw(%Pplsn)/VT(% vital capacity)], a measure of neuroventilatory dissociation of the respiratory pump. Hypoxic dyspnoea, assessed by a modified Borg scale, showed a greater rate of rise (DeltaBorg/DeltaSaO2) and a greater increase for a given level of respiratory effort in patients. Moreover, neuroventilatory dissociation related to the expression of peripheral airway involvement, as assessed in terms of low dynamic compliance, and to concurrent change in dyspnoea sensation. Patients with Type I diabetes mellitus under good metabolic control and with normal lung volumes may have abnormal peripheral airway function. The latter is thought to be responsible for the association between dyspnoea sensation and neuroventilatory dissociation.

Adult↗
PubMed1999

[The use of dynamic Doppler color ultrasonography of the penis in the study of erectile dysfunction].

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.

Erectile Dysfunction↗
PubMed1998

Toxin-induced activation of Rho GTP-binding protein increases Bcl-2 expression and influences mitochondrial homeostasis.

It is now well established that apoptosis plays a pivotal role in several physiological and pathological situations. Consequently, the mechanisms controlling the cell fate are currently the subject of intense investigation. In this work, we report that an Escherichia coli protein toxin (Cytotoxic Necrotizing Factor 1, CNF1) which activates the Rho GTP-binding protein and prevent apoptosis in epithelial cells was able to: (i) influence the mitochondrial homeostasis and (ii) modulate the expression of proteins belonging to the Bcl-2 family. In particular, the content of the antiapoptotic products Bcl-2 and Bcl-XL resulted to be increased in treated cells, whereas the expression of the proapoptotic protein Bax remained unaltered. CNF1 induces cell spreading via activation of Rho and cell spreading has been reported to promote cell survival. Cytochalasin B, which provokes most of the morphological changes typical of CNF1, including cell spreading, but without the involvement of Rho, was unable to counteract apoptosis. Altogether our results suggest a link between the Rho GTP-binding protein and the regulation of the mitochondrial homeostasis via an effect on the antiapoptotic proteins of the Bcl-2 family.

Apoptosis↗
PubMed1998

Effects of systemic prostaglandin E1 on hepatic amino acid-nitrogen metabolism in patients with cirrhosis.

Prostaglandins of the E (PGE) series have long been considered "catabolic" hormones, but recent data suggest that they may be secreted in critically ill patients to counteract stress hormones, stimulating protein synthesis. Their use is under scrutiny to improve hepatic microcirculation and as cytoprotective agents. We tested the effects of PGE1 on hepatic and whole-body nitrogen metabolism in eight patients with cirrhosis. Urea-nitrogen synthesis rate, alpha-amino-nitrogen levels, and nitrogen exchange were measured in the basal, postabsorptive state and in response to continuous alanine infusion, in paired experiments, during superinfusion of PGE1 or saline. Splanchnic and systemic hemodynamics were assessed by echo-Doppler at the beginning and at the end of each experiment. PGE1 produced a rapid fall in plasma amino acids and in urea-nitrogen synthesis rate, as well as a positive nitrogen exchange. The slope of the regression of alpha-amino-nitrogen levels on urea-nitrogen synthesis rate, a measure of liver cell metabolic activity, was not affected, but the regression line was shifted rightward, suggesting a nitrogen-sparing effect of PGE1. Mesenteric artery and portal flow were unchanged, whereas femoral artery flow increased by 30%. Insulin and glucagon levels were not systematically different. We conclude that PGE1 reduces hepatic urea synthesis rate, independent of hormones and/or hepatic flow, possibly acting at the peripheral level on amino acid transport, thus reducing amino acid supply to the liver. The resulting net nitrogen sparing might be the basis for the beneficial effect of PGE1 in clinical hepatology.

Aged↗
PubMed1998

Effects of systemic prostaglandin E1 on splanchnic and peripheral haemodynamics in control subjects and in patients with cirrhosis.

Prostaglandins of the E series showed metabolic and clinical effects in patients with liver disease; changes in splanchnic haemodynamics might be involved. Blood flow in femoral and mesenteric artery and in the portal vein was measured by echo-Doppler in 10 controls and 14 cirrhotic patients, in response to the systemic infusion of a PGE1 analogue (30 micrograms/h for 2-6 h) or saline, performed in random order. Intraparenchymal resistive and pulsatility indices in the liver, spleen and kidney were also measured. In both groups PGE1 increased femoral artery flow by 40%, irrespective of infusion time. Heart rate increased slightly, whereas mean arterial pressure decreased. There were no changes in mesenteric artery and portal vein flow, as well as in resistance indices. Saline infusion increased femoral artery flow by 4%. PGE1 infusion does not produces significant effects on Doppler-assessed splanchnic hemodynamics in controls and in cirrhotic patients, in spite of significant effects on peripheral circulation.

Aged↗
PubMed1998

Rapid decline of fertility in a case of adrenoleukodystrophy.

Adrenoleukodystrophy/adrenomyeloneuropathy (ALD/AMN) is a group of genetically determined peroxisomal disorders associated with progressive central demyelination, primary adrenal cortical insufficiency (Addison's disease) and, frequently, primary hypogonadism. Recently, testicular dysfunction was described in ALD/AMN patients but no information on sperm characteristics was provided. In this paper we studied the reproductive function of a patient with adult cerebral ALD, focusing our attention on sperm characteristics. At the time of diagnosis the patient was 22 years old, had high plasma C26 and C24 very-long-chain fatty acid (VLCFA) concentrations and adrenal insufficiency. Plasma testosterone concentration was in the normal range. The patient was prescribed a low-fat diet and 'Lorenzo's oil', which led to normalization of plasma VLCFA concentrations within 3 months of therapy. Semen analysis showed normal sperm count, gross morphological alterations and reduced motility. Electron microscopy analysis of sperm cells showed pathological changes in the head, the plasma membrane and the nucleus in 60% of the spermatozoa examined. However, isolated motile spermatozoa showed normal molecular dynamics of phospholipid bilayer surface and physiological responsiveness to progesterone. At the 12 months follow-up, the patient became azoospermic and testicular histology showed arrested maturation. To our knowledge, this is the first description of sperm alterations in a post-pubertal ALD patient, in which severe impairment of spermatogenesis and rapid progression to azoospermia occurred despite normalization of plasma VLCFA concentrations.

Adrenoleukodystrophy↗
PubMed1998

Analysis of Yq microdeletions in infertile males by PCR and DNA hybridization techniques.

Defects in spermatogenesis have been found associated with deletions of different portions of Y chromosome long arm (Yq), suggesting the presence of the azoospermia factor in the control of spermatogenesis. We studied 67 men with idiopathic azoospermia and severe oligozoospermia, cytogenetically normal, for the presence of microdeletions on Yq chromosome. By using polymerase chain reaction (PCR) and Southern blotting techniques we analysed the AZFa, AZFb and AZFc loci on Yq, where deletions have been associated with defects in spermatogenesis. Deletions of a portion of the Y chromosome were detected in five patients. Four of these patients shared deletions in distal Yq11 interval 6, including the DAZ gene, while one patient lacked loci in the proximal Yq11. Testicular histology of two patients bearing distal Yq11 deletions showed two different spermatogenic defects including Sertoli cell-only (SCO) syndrome and maturation arrest, while the patient with microdeletions in the proximal Yq11 showed a SCO phenotype.

Blotting, Southern↗
PubMed1998

Clostridium difficile toxin B induces apoptosis in intestinal cultured cells.

Toxigenic strains of the anaerobic bacterium Clostridium difficile produce at least two large, single-chain protein exotoxins involved in the pathogenesis of antibiotic-associated diarrhea and colitis. Toxin A (CdA) is a cytotoxic enterotoxin, while toxin B (CdB) is a more potent cytotoxin lacking enterotoxic activity. This study dealt with CdB, providing the first evidence that intestinal cells exposed to this toxin exhibit typical features of apoptosis in that a significant proportion of the treated cells displayed nuclear fragmentation and chromatin condensation. In keeping with ultrastructural data, CdB-treated cells showed the typical flow cytometric hallmark of apoptosis consisting of a distinct sub-G1 peak. The CdB-induced apoptotic response was dose and time dependent and not simply due to the actin-disrupting effect of the toxin or to the subsequent impairment of cell anchorage. Rather, the inhibition of proteins belonging to the Rho family due to CdB seems to play a role in the induction of apoptosis in intestinal cells. The origin of cells and the growth rate may also be cofactors relevant to such a response.

Actins↗
PubMed1998

Myths and reality concerning hypertension in peritoneal dialysis patients: results of a multicenter study.

OBJECTIVES: To evaluate the prevalence of hypertension, the average blood pressure level, the 24 h blood pressure profile, and the efficacy of antihypertensive therapy for a large population of peritoneal dialysis patients.DESIGN: A cross-sectional, observational multicenter study. METHODS: From 504 peritoneal dialysis patients (18% of the Italian peritoneal dialysis population) involved in a multicenter observational study, we selected 414 who had undergone successful ambulatory blood pressure monitoring (i.e. no hours with data absent, >/= 75% successful readings and monitoring duration >/= 24 h). Office blood pressure measurements and ambulatory blood pressure monitoring were performed for each patient on the same day with a standard mercury sphygmomanometer and a SpaceLabs 90207 device, respectively.RESULTS: According to World Health Organization/International Society of Hypertension criteria, 44 peritoneal dialysis patients (10.6%) were normotensive and 370 patients (89.4%) were hypertensive, 304 (82.1%) of whom were being administered antihypertensive therapy. Daytime systolic and diastolic blood pressures were both significantly lower than office systolic and diastolic blood pressures (140.7 +/- 19.7/72.1 +/-11.1 versus 148.3 +/- 23.6/85.6 +/- 12 mmHg; P < 0.001). The difference between office blood pressure and daytime blood pressure was significantly correlated to office blood pressure (P < 0.001 for systolic and P < 0.001 for diastolic). The diurnal blood pressure rhythm evaluated by visual inspection of hourly mean plots was not influenced by sex, age, antihypertensive treatment, and peritoneal dialysis modality. Systolic and diastolic blood pressures exhibited a day-night mean decreases of 8.6 +/- 11.7 and 7.7 +/- 6.9 mmHg, respectively, and daytime blood pressure values were significantly higher than night-time ones (P < 0.001). Two hundred and twenty patients (53.1%) were nondippers according to O'Brien's criteria, 247 patients (59.7%) were nondippers according to Verdecchia's criteria, and 269 patients (65.0%) were nondippers according to Staessen's criteria. Only 39 patients (9.4%) had a reversed circadian rhythm. The day-night differences of systolic and diastolic blood pressures were in a unimodal distribution. Among hypertensive patients not being administered antihypertensive therapy, only six patients ( five women and one man) had white-coat hypertension. Among hypertensive patients being administered antihypertensive therapy, 235 patients (77.3%) had 24 h blood pressure loads > 30%.CONCLUSION: There is a high prevalence of hypertension among peritoneal dialysis patients. White-coat hypertension is very rare in this population. Despite the extensive use of antihypertensive therapy, control of blood pressure is maintained in a large number of our peritoneal dialysis patients. Any classification of patients into dipers and nondippers must be interpreted cautiously.

Journal Article↗
PubMed1998

[Pharmacology of male sexual dysfunction].

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.

Androgens↗
PubMed1997

Hinderance of apoptosis and phagocytic behaviour induced by Escherichia coli cytotoxic necrotizing factor 1: two related activities in epithelial cells.

Several microbial factors are recognized able to modulate apoptosis. In this work, we analyze the activity of a toxin from pathogenic strains of Escherichia coli, the Cytotoxic Necrotizing Factor 1 (CNF1), which influences epithelial cell structure and function. This toxin activates the Rho GTP-binding protein leading to actin filament reorganization, membrane ruffling and multinucleation. Functionally, CNF1 induces a phagocytic activity in non-professional phagocytes. Surprisingly, we found that the increase of phagocytic activity induced by CNF1 corresponds to a decrease of apoptotic cell death. We therefore hypothesize that the two activities together might have a finalistic role in the pathogenesis of bacterial infection.

Actins↗