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Biomedical subjects

R Pasquali

Publications and source records attributed to R Pasquali.

At least 19 recordsLinked to original sources
PubMed2007

Acyl ghrelin and metabolic hormones in pregnant and lactating sows.

Ghrelin, the endogenous ligand of the growth hormone (GH) secretagogue receptor, is considered a pleiotropic regulator involved in a large array of functions, including control of energy balance, regulation of food intake and, more recently, modulation of the reproductive axis. The present study was aimed at determining the changes in plasma concentrations of acyl-ghrelin in pregnant and lactating sows, with special emphasis on the relationship with the levels of GH, leptin, non-esterified fatty acids (NEFA) and insulin-like growth factor (IGF-1). Blood samples were collected via jugular venipuncture from 22 multiparous sow 30, 60 and 90 days after artificial insemination, 7 and 21 days after farrowing and at first oestrus post-weaning. Plasma concentrations of acyl-ghrelin, leptin, GH and IGF-1 were quantified by validated radioimmunoassay; NEFA were determined using a colorimetric procedure. Plasma acyl ghrelin levels were highest at 30 days of pregnancy and decreased thereafter and during lactation. At the beginning of lactation, GH, IGF-1 and NEFA concentrations significantly increased, while a significant reduction occurred in leptin. In conclusion, ghrelin concentrations in sow maternal circulation does not seem to play an important role in maintaining circulating GH levels during lactation; moreover, ghrelin is not associated with leptin, NEFA and IGF-1 levels.

Animals↗
PubMed2006

The impact of obesity on reproduction in women with polycystic ovary syndrome.

The polycystic ovary syndrome (PCOS) is one of the most common causes of infertility due to anovulation in women. The clinical features of PCOS are heterogeneous and may change throughout the lifespan, starting from adolescence to postmenopausal age. This is largely dependent on the influence of obesity and metabolic alterations, including an insulin-resistant state and the metabolic syndrome, which consistently affect most women with PCOS. Obesity does in fact have profound effects on both the pathophysiology and the clinical manifestation of PCOS, by different mechanisms leading to androgen excess and increased free androgen availability and to alterations of granulosa cell function and follicle development. Notably, simple obesity per se represents a functional hyperandrogenic state. These mechanisms involve early hormonal and metabolic factors during intrauterine life, leptin, insulin and the insulin growth factor system and, potentially, the endocannabinoid system. Compared with normal weight women with PCOS, those with obesity are characterised by a worsened hyperandrogenic and metabolic state, poorer menses and ovulatory performance and, ultimately, poorer pregnancy rates. The importance of obesity in the pathogenesis of PCOS is emphasised by the efficacy of lifestyle intervention and weight loss, not only on metabolic alterations but also on hyperandrogenism, ovulation and fertility. The increasing prevalence of obesity among adolescent and young women with PCOS may partly depend on the increasing worldwide epidemic of obesity, although this hypothesis should be supported by long-term prospective epidemiological trials. This may have great relevance in preventive medicine and offer the opportunity to expand our still limited knowledge of the genetic and environmental background favouring the development of the PCOS.

Adipose Tissue↗
PubMed2006

The potential role of increased adrenal volume in the pathophysiology of obesity-related type 2 diabetes.

The hypothalamic-pituitary-adrenal (HPA) axis seems to play an important role in obesity and Type 2 diabetes (DM). The aim of the present study was to determine the adrenal volume in obese patients with DM in comparison to obese non-diabetic patients. Eleven diabetic obese and 19 non-diabetic obese women were sequentially invited to take part in the study. Computed tomography (CT) scan of the abdomen was performed to determine adrenal volume, visceral (VF) and sc fat (SCF). Daily urinary free cortisol (UFC) was used as a measure of integrated cortisol production. In the diabetic patients, hemoglobin A1c was measured as an index of metabolic control. Compared to nondiabetic controls, patients with diabetes had a significantly higher total adrenal volume (4.29+/-1.50 vs 2.95+/-1.64; p=0.03). A highly significant correlation was detected between VF and VF/SCF ratio and total adrenal volume in the whole group (r=0.36, p=0.04 and r=0.48, p=0.008, respectively). This study, therefore, suggests an association between abdominal obesity, enlarged adrenals and Type 2 diabetes. These findings support the hypothesis that an increased activity of the HPA axis in obese subjects may be involved in the pathogenesis of Type 2 diabetes.

Adrenal Glands↗
PubMed2006

How many sites of action for endocannabinoids to control energy metabolism?

The promising results obtained by clinical trials using Rimonabant to tackle visceral obesity and related disorders recently promoted a remarkable impulse to carry out detailed investigations into the mechanisms of action of endocannabinoids in regulating food intake and energy metabolism. The endocannabinoid system has been known for many years to play an important role in the modulation of the neuronal pathways mediating the rewarding properties of food. However, in the last few years, with the advanced understanding of the crucial role of the hypothalamic neuronal network in the regulation of appetite, several studies have also directed attention to the orexigenic role of the endocannabinoid system, substantiating the well known appetite stimulating properties of derivatives of Cannabis sativa. Furthermore, the last 2 years have seen a number of relevant publications emphasizing the role of endocannabinoids as significant players in various peripheral metabolic processes. To date, the roles of the endocannabinoid system in influencing energy metabolism have proved to be more complex than was formerly believed. However, the diverse ability to modulate both central and peripheral processes highlights the pivotal involvement of the endocannabinoid system in the control of metabolic processes. This review describes the roles of endocannabinoids and the cannabinoid type 1 receptor (CB1) in the control of energy balance.

Adipose Tissue↗
PubMed2006

Endocannabinoids and energy metabolism.

Although adjustments to nutritional lifestyle and increased physical activity remain the milestones of weight loss therapy, it is evident from the exponential increase of the number of obese subjects in Western countries that these two approaches alone are no longer able to limit this progression. This alarming phenomenon occurs in spite of a great effort exerted in the last 10 yr to shed light on the pathogenetic mechanisms inducing obesity, although many inconclusive hopes have been generated in the field of pharmacotherapeutics to tackle obesity. Among the several targets exploited in recent years, the endocannabinoid system nowadays constitutes the most promising and the most intriguing proposed so far. On one hand, our aim is to provide an overview on the role of the endocannabinoid system in the physiology of energy metabolism, on the other hand a further aim is to summarize how the system also controls food intake and energy balance by acting at both cerebral and peripheral level.

Animals↗
PubMed2005

Short-term modification of sex hormones is associated with changes in ghrelin circulating levels in healthy normal-weight men.

The aim of this study was to evaluate the effect of selective and short-term sex hormone modifications on ghrelin levels in normal-weight eugonadal men undergoing hormonal contraceptive treatments. Seven men received an oral progestin [cyproterone acetate (CPA) or dienogest (DNG)] 10 mg/day for 3 weeks (CPA-DNG group), 7 CPA orally 5 mg/day in association with testosterone enanthate (TE) im 200 mg/week for 8 weeks (CPA-TE group), and 7 placebo (PLAC) for 8 weeks (PLAC group). Anthropometry and blood levels of LH, FSH, testosterone, estradiol, glucose, insulin and total ghrelin were evaluated. At baseline, no parameters differed among the three groups. After treatment, LH and FSH decreased in both CPA-DNG and CPA-TE groups, whereas they did not change in the PLAC group. Testosterone and estradiol decreased in the CPA-DNG group to the hypogonadal range, increased in the CPA-TE group to supraphysiological concentrations and, as expected, remained unchanged in the PLAC group. Total ghrelin levels increased in the CPA-DNG, decreased in the CPA-TE and did not change in the PLAC group. Ns modifications in the other parameters were observed in any group, demonstrating that the short-term changes of circulating sex hormones are able to modify ghrelin levels. These data, therefore, suggest that sex steroids are important regulators of ghrelin in normal-weight healthy men too.

Adult↗
PubMed2005

Gastric immunolocalization and plasma profiles of acyl-ghrelin in fasted and fasted-refed prepuberal gilts.

Ghrelin is a peripheral circulating hormone, mainly released from the stomach, which can stimulate food intake. We studied fed, fasted and fasted-refed prepuberal gilts in order to outline possible changes in gastric mucosal ghrelin cells and in plasma ghrelin profiles in response to food deprivation. Acyl-ghrelin-immunoreactive cells were numerous in oxyntic glands, less abundant in cardiac glands and least frequent in pyloric glands, with the addition of a minor population of labelled cells in the gastric pit mucosa. When fed and fasted animals were compared (72-h fast versus fed; n = 4 each), no clear-cut differences were revealed in labelled cell numbers, nor in their staining intensity. An RIA for plasma porcine acyl-ghrelin (n-octanoylated at Ser-3), not recognizing des-acyl-ghrelin, was validated. Plasma acyl-ghrelin progressively increased upon fasting (over 6, 12, 24 and 48 h); ghrelin levels significantly (P<0.05) higher than those prefast were reached at 72 h. After refeeding, plasma ghrelin was rapidly restored to basal values by 6 h. In the same animals, plasma insulin was significantly reduced throughout the fasting period (6-72 h), while rapidly increasing after refeeding. Non-esterified fatty acid levels increased during fasting (12-72 h) and rapidly returned to low values after refeeding. In conclusion, the present study demonstrates that starvation and refeeding influence ghrelin plasma level in prepuberal gilts. The absence of detectable changes in ghrelin cells, as seen in immunohistochemistry, could be due to a large intracellular storage of potentially releasable acylghrelin.

Animals↗
PubMed2005

Metabolic alterations and cardiovascular risk factors in the polycystic ovary syndrome.

Available literature indicates that polycystic ovary syndrome (PCOS) represents a condition with a high prevalence of the metabolic syndrome, a greater and precocious appearance of glucose intolerance states, including type 2 diabetes mellitus, and a potentially greater risk for cardiovascular diseases. With respect to metabolic disorders, however, there is also emerging evidence that they are more prevalent in PCOS rather than in the general population, and that there are regional differences in the world, depending on lifestyle and other environmental factors. This evidence should be taken into consideration in future strategies focusing on prevention of metabolic and cardiovascular disorders in PCOS, not only on treatment of infertility and signs of androgen excess.

Cardiovascular Diseases↗
PubMed2004

Response of the hypothalamic-pituitary-adrenal axis to small dose arginine-vasopressin and daily urinary free cortisol before and after alprazolam pre-treatment differs in obesity.

OBJECTIVE: Arginine vasopressin (AVP) has a central role in the response of the hypothalamic-pituitary-adrenal (HPA) axis to stress conditions. A low dose of AVP has been shown to have a modest, but significant effect on ACTH response in normal weight subjects. The aim of this study was to test the response of the HPA axis in obese subjects in order to assess eventual primary neuroendocrine alterations, previously demonstrated by using AVP combined with corticotropin releasing hormone (CRH). In addition, given its central inhibitory action on the HPA axis, we investigated whether the suppressive capacity of alprazolam (APZ) pretreatment on the hormone response to low-dose AVP challenge and daily urinary free cortisol (UFC) excretion rate may be altered in the presence of obesity. DESIGN: Fifteen overweight or obese women and eight normal-weight controls randomly underwent two low-dose AVP tests (0.3 UI iv bolus), one without (AVP test) and the other preceded by APZ administration (0.5 mg at midnight and 0.5 mg 90 min before the test in the morning at 08:30 h) (APZ/AVP test). Blood samples for ACTH and cortisol assay were obtained at baseline and throughout each test. The day before each test, 24h-UFC/ creatinine was also mea-sured. RESULTS: Basal ACTH levels were similar in the two groups, whereas cortisol concentrations were significantly lower in the overweight/obese group. Overweight/obese women had higher ACTH and cortisol responses to the AVP tests and significantly greater hormone inhibition after APZ than controls. In both groups, AVP-induced delta-peak cortisol values before and after APZ pre-treatment were significantly correlated. Body fat distribution had no effect on the HPA axis response to AVP either before or after APZ. Moreover, APZ decreased 24h-UFC/creatinine values unsignificantly in controls and by approximately 50% in the overweight/obese subjects. These changes were unrelated to the cortisol response to the AVP test before and after APZ pretreatment. On the other hand, percent changes of 24h-UFC/creatinine after APZ were negatively related to the body mass index (BMI) but positively with waist circumference values, which indicates that the abdominal obesity phenotype may counteract the 24 h-UFC/creatinine that would be expected on the basis of BMI values. CONCLUSIONS: Our data further support the concept that in women obesity may represent a condition of hyperresponsiveness or hypersensitivity of the HPA axis to neuroendocrine stimuli, which appear to be independent of feedback control. In addition, the data on the inhibiting capacity of APZ on UFC excretion confirm that the alterations of the HPA axis in obesity is particularly evident in the abdominal phenotype.

Adult↗
PubMed2004

Type 2 diabetes and the polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder, affecting women in reproductive age, characterized by chronic anovulation and hyperandrogenism. The etiology of PCOS is still unknown. However, several studies have suggested that insulin resistance plays an important role in the pathogenesis of the syndrome. As a consequence of insulin-resistance, women affected by PCOS often present abnormalities of glucose metabolism and lipid profile, and have an increased risk of type 2 diabetes and cardiovascular disease over-time. Besides insulin-resistance, it has been demonstrated that some of these women also have alterations in beta-cell-function. Both disorders (insulin-resistance and beta-cell-dysfunction) are recognized as major risk factors for the development of type 2 diabetes. Long-term studies, evaluating the glucose-insulin system in women affected by PCOS, have shown a higher incidence of glucose intolerance, including both impaired glucose tolerance and type 2 diabetes, compared to age and weight matched control populations. The risk of glucose intolerance among PCOS subjects seems to be approximately 5 to 10 fold higher than normal and appears not limited to a single ethnic group. Moreover, the onset of glucose intolerance in PCOS women has been reported to occur at an earlier age than in the normal population (approximately by the 3rd-4th decade of life). However, other risk factors such as obesity, a positive family history of type 2 diabetes and hyperandrogenism may contribute to increasing the diabetes risk in PCOS.

Adult↗
PubMed2003

Effect of small doses of dexamethasone on plasma leptin levels in normal and obese subjects: a dose-response study.

To further elucidate the role of glucocorticoids in the regulation of leptin secretion, we studied the effects of overnight small doses of dexamethasone on plasma leptin levels in normal weight controls and in obese patients and correlated the results with indexes of insulin sensitivity and body fat distribution. In 114 subjects (81 obese patients, 49 women and 32 men, BMI 37.4 +/- 0.77 kg/m2 and 33 normal-weight subjects, 17 women and 16 men, BMI 22.1 +/- 0.41 kg/m2) plasma F and leptin levels were measured at 08:00 h basally and after the administration of different doses of dexamethasone (a fixed dose of 1-mg and 0.0035, 0.007, 0.015-mg/kg bw, given po at 23:00 h the night before). Tests were performed one week apart with bw remaining stable over the study period. Basal leptin levels were significantly higher in obese than in normal subjects (31.9 +/- 2.41 vs 7.7 +/- 0.93 ng/ml, p<0.0001). In obese patients, leptin levels increased significantly by 1-mg (from 31.9 +/- 2.41 to 35.0 +/- 2.59 ng/ml, p<0.005) and the 0.015-mg/kg bw dose (from 31.5 +/- 2.34 to 33.7 +/- 2.44 ng/ml, p<0.05), while they were unaffected by each dose of dexamethasone in normal subjects. However, after splitting subjects by gender, mean leptin levels rose from 39.3 +/- 2.97 to 43.3 +/- 3.12 ng/ml after the 1-mg dose, p<0.005, from 39.1 +/- 2.87 to 43.6 +/- 2.91 ng/ml after the 0.015-mg/kg bw dose, p<0.005, from 39.3 +/- 2.90 to 42.2 +/- 2.90 ng/ml after the 0.007-mg/kg bw dose, p<0.05 and from 38.8 +/- 2.66 to 41.1 +/- 2.87 ng/ml after the 0.0035-mg/kg bw dose, p=0.055, only in obese women. Conversely, no leptin changes were seen in the other groups and no differences were observed in the leptin response between groups. After the 1-mg dose, in the whole group, the absolute leptin variation was weakly but significantly related to BMI values (r=0.231, p<0.02) while in all sessions the percent leptin changes over baseline were not significantly correlated with age, BMI, waist, WHR, insulin, HOMA index, a marker of insulin sensitivity, plasma dexamethasone concentrations and to the percent cortisol variation following dexamethasone. In conclusion, in obese women but not in obese men and in normal weight subjects, small overnight increases in plasma glucocorticoid concentrations induced gender-related plasma leptin elevations that were unrelated to body fat distribution and insulin sensitivity. A greater sensitivity of female adipose tissue to glucocorticoids probably underlies this sexually dimorphic pattern of leptin response. These findings provide an additional piece of information on the regulation of leptin secretion exerted by glucocorticoids.

Adult↗
PubMed2003

Testosterone levels in obese male patients with obstructive sleep apnea syndrome: relation to oxygen desaturation, body weight, fat distribution and the metabolic parameters.

To investigate the impact of obstructive sleep apnea syndrome (OSAS) on testosterone levels and on the main parameters of the metabolic syndrome in abdominally obese men, 15 male subjects with abdominal obesity phenotype and polysomnographic diagnosis of OSAS (OB-OSAS) and 15 controls matched for age and anthropometric parameters (OB) were investigated. Anthropometry, SHBG, sex hormones and several parameters of the metabolic syndrome were measured. Only subjects with an Epworth Sleepiness Score greater than 10 underwent a polysomnographic study with calculation of the number of desaturation rates per sleeping hour (ODI), the minimal oxygen saturation during each desaturation episode (minSaO2) and the mean minimal arterial oxygen saturation for the whole night period (MminSaO2). Both total and free testosterone levels were lower in OB-OSAS than in OB patients. A negative correlation between polysomnographic parameters (ODI, minSaO2 and MminSaO2) and testosterone levels was found. The relationship between total and free testosterone and ODI persisted after adjusting for body mass index (BMI) and waist (W) values. Triglyceride and uric acid levels were significantly higher in OB-OSAS than in OB patients. A negative correlation between testosterone and acid uric level and a positive correlation between testosterone and HDL-cholesterol level was found, regardless of BMI and W circumference, particularly in the OB-OSAS group. Our study suggests that, in patients with obesity and OSAS, the severity of hypoxia during sleeping hours may be an additional factor in reducing testosterone levels, regardless of BMI and abdominal fatness. This may contribute in worsening metabolic abnormalities which, in men with OSAS, exceed those expected on the basis of degree of obesity and pattern of fat distribution.

Adipose Tissue↗
PubMed2003

Anti-androgen treatment increases circulating ghrelin levels in obese women with polycystic ovary syndrome.

In a previous study we were the first to describe a negative correlation between circulating ghrelin concentrations and androgen levels in human plasma, suggesting an interaction between ghrelin and the endocrine regulation of reproductive physiology. We now investigated a potential direct regulatory influence of circulating androgens on plasma ghrelin levels. Fourteen obese women with polycystic ovary syndrome (PCOS) on a hypocaloric diet were randomly assigned to treatment groups (open-labeled design), receiving either placebo (no.=7) or the antiandrogen flutamide (no.=7) for 6 months. Anthropometry, visceral (VAT) and subcutaneous (SAT) adipose tissue (quantified by computerized tomography), plasma hormone levels, insulin sensitivity indexes (Quantitative Insulin-Sensitivity Check Index-QUICKI) and Homeostatic Model Assessment applied to the oral glucose tolerance test (HOMA(OGTT)) were evaluated at baseline and at the end of the study. Body weight decreased and insulin resistance indexes improved in both groups. A tendency toward a greater loss of VAT was observed in the flutamide group. Only in the flutamide group was a significant reduction of androgens levels observed. Plasma ghrelin levels significantly increased following treatment with flutamide, while ghrelin remained unchanged in the placebo group. We observed a negative correlation between changes of ghrelin levels and changes of androgen plasma concentration in the flutamide-treated group. In the same group a positive correlation was found between plasma ghrelin changes and insulin sensitivity as expressed by HOMA(OGTT). Analysis in a multiple regression model, however, showed that plasma ghrelin changes were mainly due to changes of androgen levels rather than improved insulin sensitivity. We, therefore, conclude that androgens are independent modulators of circulating ghrelin concentrations.

Adult↗
PubMed2003

Endogenous cannabinoid system as a modulator of food intake.

The ability of Cannabis sativa (marijuana) to increase hunger has been noticed for centuries, although intensive research on its molecular mode of action started only after the characterization of its main psychoactive component Delta(9)-tetrahydrocannabinol in the late 1960s. Despite the public concern related to the abuse of marijuana and its derivatives, scientific studies have pointed to the therapeutic potentials of cannabinoid compounds and have highlighted their ability to stimulate appetite, especially for sweet and palatable food. Later, the discovery of specific receptors and their endogenous ligands (endocannabinoids) suggested the existence of an endogenous cannabinoid system, providing a physiological basis for biological effects induced by marijuana and other cannabinoids. Epidemiological reports describing the appetite-stimulating properties of cannabinoids and the recent insights into the molecular mechanisms underlying cannabinoid action have proposed a central role of the cannabinoid system in obesity. The aim of this review is to provide an extensive overview on the role of this neuromodulatory system in feeding behavior by summarizing the most relevant data obtained from human and animal studies and by elucidating the interactions of the cannabinoid system with the most important neuronal networks and metabolic pathways involved in the control of food intake. Finally, a critical evaluation of future potential therapeutical applications of cannabinoid antagonists in the therapy of obesity and eating disorders will be discussed.

Animals↗
PubMed2003

Low ghrelin concentrations in nonalcoholic fatty liver disease are related to insulin resistance.

Several physiological and pathophysiological conditions, including changes in body fat, food intake, and insulin resistance, are known to be associated with variations in plasma ghrelin concentrations. We tested the hypothesis that insulin resistance exerts a primary role by measuring ghrelin in 86 patients with nonalcoholic fatty liver disease (NAFLD), a condition in which insulin resistance is relatively independent of obesity. Compared with 40 matched healthy subjects, patients with NAFLD had similar glucose levels and higher plasma insulin and insulin resistance [homeostasis model assessment (HOMA)-R index] by over 60%. Ghrelin was reduced (mean +/- SD, 226 +/- 72 pmol/liter in NAFLD vs. 303 +/- 123 in controls; P < 0.0001). In relation to quartiles of body mass index, ghrelin progressively decreased in controls (P = 0.003), but not in patients (P = 0.926). In relation to quartiles of HOMA-R, ghrelin decreased in both groups, and significantly correlated with HOMA-R. After adjustment for age and sex, HOMA-R was the sole factor significantly associated with low ghrelin in the whole group (odds ratio, 5.79; 95% confidence interval, 2.62-12.81; P < 0.0001) and specifically in NAFLD (2.96; 1.12-7.79; P = 0.028). The study suggests that insulin resistance is a major factor controlling ghrelin levels in subjects with and without NAFLD.

Adult↗
PubMed2002

Laparoscopic body--tail pancreatic resection for insulinoma.

A case of pancreatic insulinoma with a neuroglycopenic syndrome was treated with laparoscopic body--tail pancreatic resection. An en bloc splenectomy was required due to the close anatomic relation of the insulinoma with the splenic vein, as shown on intraoperative ultrasonography. The operative time was 4 h, and blood loss was minimal (<200 ml). Laparoscopic coagulating shears were used for the pancreatic mobilization, and an endoGIA was used for the section of the splenic vessels and the central pancreatic transection. The postoperative course was uneventful, and the patient was discharged in good condition on the 7th postoperative day. We concluded that laparoscopic access in patients with pancreatic disease is not only a valuable way to establish or confirm a diagnosis and assess the severity of the disease but also a safe way to perform distal pancreatic resection.

Female↗
PubMed2002

Adrenal and gonadal function in obesity.

Obesity is associated with multiple alterations of the endocrine systems, including abnormal circulating blood hormone concentrations, due to changes in their pattern of secretion and/or metabolism, altered hormone transport, and/or action at the level of target tissues. There is evidence that alterations of endocrine systems regulating sex hormones and corticosteroids may play a crucial role in the development of obesity, particularly the abdominal phenotype. Obese women are characterized by a condition of sc"functional hyperandrogenism", whereas in males, obesity is associated with reduced T levels and decreased LH secretory pattern from the pituitary. In addition, in both sexes a dysregulation of the hypothalamic-pituitary-adrenal axis has been reported, including both neuroendocrine and peripheral alterations, finally leading to inappropriately higher than normal exposure to F of peripheral tissues, particularly the visceral adipose tissue. By these mechanisms, it can be hypothesized that both visceral fat enlargement and alterations of insulin action and associated metabolic disturbances may develop, therefore predisposing abdominally obese individuals to Type 2 diabetes and cardiovascular disease.

Adipose Tissue↗