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Exploring large virtual environments, such as cities, is a central task in several domains, such as gaming and urban planning. VR systems can greatly help this task by providing an immersive experience; however, a common issue with viewing and navigating a city in the traditional sense is that users can either obtain a local or a global view, but not both at the same time, requiring them to continuously switch between perspectives, losing context and distracting them from their analysis. In this article, our goal is to allow users to navigate to points of interest without changing perspectives. To accomplish this, we design an intuitive navigation interface that takes advantage of the strong sense of spatial presence provided by VR. We supplement this interface with a perspective that warps the environment, called UrbanRama, based on a cylindrical projection, providing a mix of local and global views. The design of this interface was performed as an iterative process in collaboration with architects and urban planners. We conducted a qualitative and a quantitative pilot user study to evaluate UrbanRama and the results indicate the effectiveness of our system in reducing perspective changes, while ensuring that the warping doesn't affect distance and orientation perception.

Large scale shadows from buildings in a city play an important role in determining the environmental quality of public spaces. They can be both beneficial, such as for pedestrians during summer, and detrimental, by impacting vegetation and by blocking direct sunlight. Determining the effects of shadows requires the accumulation of shadows over time across different periods in a year. In this paper, we propose a simple yet efficient class of approach that uses the properties of sun movement to track the changing position of shadows within a fixed time interval. We use this approach to extend two commonly used shadow techniques, shadow maps and ray tracing, and demonstrate the efficiency of our approach. Our technique is used to develop an interactive visual analysis system, Shadow Profiler, targeted at city planners and architects that allows them to test the impact of shadows for different development scenarios. We validate the usefulness of this system through case studies set in Manhattan, a dense borough of New York City.

Visual analytics systems can greatly help in the analysis of urban data allowing domain experts from academia and city governments to better understand cities, and thus enable better operations, informed planning and policies. Effectively designing these systems is challenging and requires bringing together methods from different domains. In this paper, we discuss the challenges involved in designing a visual analytics system to interactively explore large spatio-temporal data sets and give an overview of our research that combines visualization and data management to tackle these challenges.

Saffron may be spoiled by a variety of microorganisms during cultivation, harvesting, and post harvesting. As saffron can be dried and stored in different ways, this preliminary study explored the natural microbiota present in Moroccan saffron when subjected to different drying techniques. An analysis of the carotenoid-derived volatiles present in the saffron was also carried out. The culturable microbiota of the saffron samples dried using different methods, namely in the shade (also called natural), in the sun, or in the oven, were studied using classical and molecular approaches. The effect of the drying methods on head-space chemical volatiles was also determined. Eighty-two isolates grown in the different culture media were chosen from the colonies, and genotype analysis grouped the microorganisms into 58 clusters, revealing a wide diversity. Out of the 82 isolates, 75 belonged to the Bacillaceae family. The other isolates were distributed within the Dietziaceae, Paenibacillaceae and Carnobacteriaceae families. The dominant species was Bacillus simplex, which was detected in all samples, regardless of the drying method used. Lysinibacillus macroides was dominant in the sun-dried saffron. No pathogens were isolated, but an isolate belonging to Dietzia maris, a potential human pathogenic species, was detected. The biodiversity indexes were linked to the drying method and generally decreased as the intensity of the treatment increased. The results of this preliminary work show that the different drying methods strongly influenced the microbiota and affect the saffron volatile profile. Further analysis will be needed to determine possible effects of selected microbiota on saffron volatiles., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Black garlic is an elaborated product obtained from fresh garlic (Allium sativum L.) at a controlled high humidity and temperature, which leads to modifications in color, taste, and texture. To clarify the physicochemical changes that occur during the thermal process, this work aimed to evaluate and contrast the antioxidant capacity and that of other compounds between purple garlic ecotype "Purple from Las Pedroñeras" and its black garlic derivative. Our results showed numerous differences between both, because black garlic presented a significant divergence in its volatile profile, a decreased amount of ascorbic acid, an increment in sugar and polyphenol contents, a greater antioxidant capacity, and a different composition of phenolic acids and flavonoids.

Cities are inherently dynamic. Interesting patterns of behavior typically manifest at several key areas of a city over multiple temporal resolutions. Studying these patterns can greatly help a variety of experts ranging from city planners and architects to human behavioral experts. Recent technological innovations have enabled the collection of enormous amounts of data that can help in these studies. However, techniques using these data sets typically focus on understanding the data in the context of the city, thus failing to capture the dynamic aspects of the city. The goal of this work is to instead understand the city in the context of multiple urban data sets. To do so, we define the concept of an "urban pulse" which captures the spatio-temporal activity in a city across multiple temporal resolutions. The prominent pulses in a city are obtained using the topology of the data sets, and are characterized as a set of beats. The beats are then used to analyze and compare different pulses. We also design a visual exploration framework that allows users to explore the pulses within and across multiple cities under different conditions. Finally, we present three case studies carried out by experts from two different domains that demonstrate the utility of our framework.

Major League Baseball (MLB) has a long history of providing detailed, high-quality data, leading to a tremendous surge in sports analytics research in recent years. In 2015, MLB.com released the StatCast spatiotemporal data-tracking system, which has been used in approximately 2,500 games since its inception to capture player and ball locations as well as semantically meaningful game events. This article presents a visualization and analytics infrastructure to help query and facilitate the analysis of this new tracking data. The goal is to go beyond descriptive statistics of individual plays, allowing analysts to study diverse collections of games and game events. The proposed system enables the exploration of the data using a simple querying interface and a set of flexible interactive visualization tools.

Objectives: To compare the 28-joint Disease Activity Score (DAS28) and its components in patients with rheumatoid arthritis (RA) with and without concomitant fibromyalgia (FM), and to investigate the use of biological treatment in the two groups., Method: Questionnaires developed to diagnose FM were handed out among RA patients during their planned visits. Values for DAS28 were obtained from the DANBIO registry. Demographic data and data on patients' medical treatment, disease duration, serological and radiological status were retrieved from patients' files. The χ 2 test and an unpaired t-test were applied to investigate group differences in the use of biological therapy, baseline characteristics, patient-reported outcomes, and DAS28 between groups when appropriate., Results: Questionnaires were completed by 162 out of 264 (61%) patients. Twenty-five patients (15.4%) with concomitant FM were identified. No group differences were found regarding disease duration, age, gender, and serological status. Of the RA patients with concomitant FM, 64% were treated with biological therapy vs. 32% of RA patients without concomitant FM (p = 0.002). The mean DAS28 in the FM group was 4.4 compared to 2.9 in the non-FM group (p < 0.001). Elevated DAS28 in the FM group resulted from a high tender joint count (p = 0.003) and a high visual analogue scale (VAS)-global score (p < 0.001). Erosions were more frequent in the non-FM group (p = 0.04)., Conclusions: Concomitant FM in patients with RA is associated with a higher DAS28 due to subjective parameters and with the more frequent use of biological treatments. This raises the question of whether the more frequent use of biologics in these patients is justified by inflammation, or is instead due to persistent pain and other centrally mediated symptoms.

Lipodystrophies are a group of diseases mainly characterized by a loss of adipose tissue and frequently associated with insulin resistance, hypertriglyceridemia, and hepatic steatosis. In uncommon lipodystrophies, these complications frequently are difficult to control with conventional therapeutic approaches. This retrospective study addressed the effectiveness of recombinant methionyl leptin (metreleptin) for improving glucose metabolism, lipid profile, and hepatic steatosis in patients with genetic lipodystrophic syndromes. We studied nine patients (five females and four males) with genetic lipodystrophies [seven with Berardinelli-Seip syndrome, one with atypical progeroid syndrome, and one with type 2 familial partial lipodystrophy (FPLD)]. Six patients were children under age 9 years, and all patients had baseline triglycerides levels >2.26 mmol/L and hepatic steatosis; six had poorly controlled diabetes mellitus. Metreleptin was self-administered subcutaneously daily at a final dose that ranged between 0.05 and 0.24 mg/(kg day) [median: 0.08 mg/(kg day)] according to the body weight. The duration of treatment ranged from 9 months to 5 years, 9 months (median: 3 years). Plasma glucose, hemoglobin A1c (Hb A1c), lipid profile, plasma insulin and leptin, and hepatic enzymes were evaluated at baseline and at least every 6 months. Except for the patient with FPLD, metreleptin replacement significantly improved metabolic control (Hb A1c: from 10.4 to 7.1 %, p < 0.05). Plasma triglycerides were reduced 76 % on average, and hepatic enzymes decreased more than 65 %. This study extends knowledge about metreleptin replacement in genetic lipodystrophies, bearing out its effectiveness for long periods of time.

Background and Aims: Reduction of cardiovascular risk with high consumption of fish in diet is still a matter of debate, and concerns about heavy metal contamination have limited consumption of oily fish. We aimed to evaluate the effect of regular ingestion of white fish on cardiovascular risk factors in patients with metabolic syndrome., Methods and Results: Multicenter randomized crossover clinical trial including 273 individuals with metabolic syndrome. An 8-week only-one dietary intervention: 100 g/d of white fish (Namibia hake) with advice on a healthy diet, compared with no fish or seafood with advice on a healthy diet. Outcomes were lipid profile, individual components of the metabolic syndrome, serum insulin concentrations, homeostasis model of insulin resistance, serum C-reactive protein and serum fatty acid levels. We found a significant lowering effect of the intervention with white fish on waist circumference (P < 0.001) and diastolic blood pressure (P = 0.014). A significant lowering effect was also shown after the dietary intervention with fish on serum LDL concentrations (P = 0.048), whereas no significant effects were found on serum HDL or triglyceride concentrations. A significant rise (P < 0.001) in serum EPA and DHA fatty acids was observed following white fish consumption. Overall adherence to the intervention was good and no adverse events were found., Conclusion: In individuals with metabolic syndrome, regular consumption of hake reduces LDL cholesterol concentrations, waist circumference and blood pressure components of the metabolic syndrome., Clinical Trial Registry: White Fish for Cardiovascular Risk Factors in Patients with Metabolic Syndrome Study, Registered under ClinicalTrials.gov Identifier: NCT01758601., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Introduction: Anorexia nervosa (AN) is characterised by a refusal to normal body weight accompanied by a marked restriction of food intake, frequently leading to severe malnutrition. In severe malnutrition and wasting syndromes, mucosal atrophy, altered gastrointestinal motility and pancreatic atrophy, which alter digestive function and can exacerbate malnutrition, have been described. The objective of this work was to determine intestinal absorption and pancreatic function in severely malnourished AN patients before and after recovery., Methods: Ten severely malnourished AN women were studied at hospital admittance (body mass index = 11.44-16.16 kg/m(2)) and after weight recovery with artificial nutrition (body mass index ≥ 20 kg/m(2)). A (13)C-labelled triglycerides digestion test, faecal elastase test and d-xylose absorption test were performed., Results: In nine patients, (13)C-labelled triglycerides digestion tests and the faecal elastase and d-xylose tests were normal both before and after weight recovery. In one patient, the results were abnormal, and they led to the detection of a previously undiagnosed celiac disease in addition to her AN., Conclusion: In this series, there was neither intestinal absorption nor pancreatic function disturbances in severely malnourished AN patients either before or after weight recovery. The usefulness of these tests in the differentiation of functional versus structural changes needs further studies., (Copyright © 2013 John Wiley & Sons, Ltd and Eating Disorders Association.)

Functional defects in growth hormone (GH) secretion and its efficacy as a complementary treatment have been suggested for fibromyalgia. This study investigated the efficacy and safety of low-dose GH as an add-on therapy in patients with both severe FM and low insulin-like growth factor 1 levels. A total of 120 patients were enrolled in a multicenter, placebo-controlled study for 18 months. They were randomly assigned to receive either 0.006 mg/kg/day of GH subcutaneously (group A, n=60) or placebo (group B, n=60) for 6 months (blind phase). The placebo arm was switched to GH treatment from month 6 to month 12 (open phase), and a follow-up period after GH discontinuation was performed until month 18. Standard treatment for fibromyalgia (selective serotonin re-uptake inhibitors, opioids, and amitriptyline) was maintained throughout the study. Number and intensity of tender points, Fibromyalgia Impact Questionnaire (FIQ) with its subscales, and EuroQol 5 dimensions test (EQ5D) with visual analogue scale (VAS) were assessed at different time points. At the end of the study, 53% of group A patients obtained fewer than 11 positive tender points, vs 33% of group B patients (P<.05). 39.1% vs 22.4% reached more than 50% improvement in VAS (P<.05). Group A patients showed significantly improved FIQ scores (P=.01) compared with group B. Although GH discontinuation worsened all scores in both groups during follow-up, impairment in pain perception was less pronounced in the GH-treated group (P=.05). In this largest and longest placebo-controlled trial performed in FM (NCT00933686), addition of GH to the standard treatment is effective in reducing pain, showing sustained action over time., (Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Context: Appetite-related hormones may play an important role in weight regain after obesity therapy., Objective: Our objective was to investigate the potential involvement of ghrelin, leptin, and insulin plasma levels in weight regain after a therapeutic hypocaloric diet., Design: A group of obese/overweight volunteers (49 women and 55 men; 35 ± 7 yr; 30.7 ± 2.4 kg/m(2)) followed an 8-wk hypocaloric diet (-30% energy expenditure) and were evaluated again 32 wk after treatment. Body weight as well as plasma fasting ghrelin, leptin, and insulin concentrations were measured at three points (wk 0, 8, and 32)., Results: After the 8-wk hypocaloric diet, the average weight loss was -5.0 ± 2.2% (P < 0.001). Plasma leptin and insulin concentrations decreased significantly, whereas ghrelin levels did not markedly change. In the group regaining more than 10% of the weight loss, leptin levels were higher (P < 0.01), whereas ghrelin levels were lower (P < 0.05). No differences were observed in insulin levels. Weight regain at wk 32 was negatively correlated with ghrelin and positively associated with leptin levels at baseline (wk 0) and endpoint (wk 8). These outcomes showed a gender-specific influence, being statistically significant among men for ghrelin and between women for leptin. Moreover, a decrease in ghrelin after an 8-wk hypocaloric diet was related to an increased risk for weight regain (odds ratio = 3.109; P = 0.008) whereas a greater reduction in leptin (odds ratio = 0.141; P = 0.001) was related to weight-loss maintenance., Conclusions: Subjects with higher plasma leptin and lower ghrelin levels at baseline could be more prone to regain lost weight, and hormones levels could be proposed as biomarkers for predicting obesity-treatment outcomes.

Vector fields analysis traditionally distinguishes conservative (curl-free) from mass preserving (divergence-free) components. The Helmholtz-Hodge decomposition allows separating any vector field into the sum of three uniquely defined components: curl free, divergence free and harmonic. This decomposition is usually achieved by using mesh-based methods such as finite differences or finite elements. This work presents a new meshless approach to the Helmholtz-Hodge decomposition for the analysis of 2D discrete vector fields. It embeds into the SPH particle-based framework. The proposed method is efficient and can be applied to extract features from a 2D discrete vector field and to multiphase fluid flow simulation to ensure incompressibility.

Aims: To determine the ability of a novel Bacillus subtilis AMR isolated from poultry waste to hydrolyse human hair producing peptidases including keratinases and hair keratin peptides., Methods and Results: The Bacillus subtilis AMR was identified using biochemical tests and by analysis of 16S rDNA sequence. The isolate was grown in medium containing human hair as the sole source of carbon and nitrogen. The supplementation of hair medium (HM) with 0.01% yeast extract increased the keratinolytic activity 4.2-fold. B. subtilis AMR presented high keratinase production on the 8th day of fermentation in hair medium (HM) supplemented with 0.01% yeast extract (HMY) at pH 8.0. Keratinase yield was not correlated with increase in biomass. Zymography showed keratin-degrading peptidases migrating at c. 54, 80 and 100 kDa and gelatin-degrading bands at c. 80, 70 63, 54 32 and 15 kDa. Keratinases were optimally active at 50 degrees C and pH 9.0 and was fully inhibited by the serine proteinase inhibitor (PMSF). Scanning electron microscopy showed complete degradation of the hair cuticle after exposure to B. subtilis AMR grown in HMY. MALDI-TOF analysis of culture supernatant containing peptides produced during enzymatic hydrolysis of hair by B. subtilis AMR revealed fragments in a range of 800-2600 Da., Conclusions: This study showed that B. subtilis AMR was able to hydrolyse human hair producing serine peptidases with keratinase and gelatinase activity as well as hair keratin peptides., Significance and Impact of the Study: This is the first report describing the production and partial characterization of keratinases by a B. subtilis strain grown in a medium containing human hair. These data suggest that peptides obtained from enzymatic hair hydrolysis may be useful for future applications on pharmaceutical and cosmetic formulations.

Growth hormone deficiency (GHD) in adults is a recognized syndrome which is defined biochemically within an appropriate clinical context. Clinically, patients investigated for GHD should include those with signs and symptoms of hypothalamic-pituitary disease, those who have received cranial irradiation or tumor treatment and those with traumatic brain injury or subarachnoid hemorrhage. Patients with three or more pituitary hormone deficiencies and an IGF-I below the reference range do not require provocative testing. The other patients need a provocative test of GH secretory reserve for the diagnosis of GHD. Insulin tolerance test is considered the diagnostic test of choice, however, the GH-releasing hormone (GHRH)+arginine, the GHRH+growth hormone-releasing peptide and the glucagon stimulation tests are well validated alternative tests in adults. Cutoffs differ across tests and results may be influenced by gender, age, body mass index, and the assay reference preparation., (Copyright (c) 2010 S. Karger AG, Basel.)

Objective: Abnormal ghrelin regulation may influence the development of obesity-associated conditions including polycystic ovary syndrome (PCOS). Our aim was to compare ghrelin regulation between PCOS cases and controls., Design: We compared serum ghrelin (total) levels, fasting and 30-min post-oral (75 g) glucose load, between 50 PCOS cases and 28 female controls, including 22 body mass index (BMI)/fat mass-matched pairs. All subjects were of UK British/Irish origin., Methods: Measurements included serum ghrelin (RIA technique (LINCO Research, St Charles MO, USA)), fat mass, serum testosterone, fasting serum insulin and plasma glucose levels. Insulin sensitivity was calculated as the homeostasis model assessment of insulin resistance (HOMA2 IR)., Results: Fasting serum ghrelin levels were significantly lower in PCOS cases versus BMI/fat mass-matched controls (geometric mean (s.d. range), 1104 pg/ml (764-1595) vs 1756 pg/ml (1314-2347) respectively; P=2.3 x 10(-4)). Ghrelin suppression following oral glucose load was significantly blunted in PCOS cases versus BMI/fat mass-matched controls (geometric mean ghrelin suppression (s.d. range), 160 pg/ml (88-289) vs 424 pg/ml (220-818) respectively; P=2.0 x 10(-4)). Whole-group comparisons (50 PCOS cases versus 28 controls) adjusted for fat mass and age revealed similar results. In PCOS cases, there was a significant negative correlation between fasting serum ghrelin and HOMA2 IR (r(2)=-0.40, P=5.7 x 10(-3)). Following adjustment for HOMA2 IR, fat mass and age, comparisons between the whole groups of PCOS cases and controls revealed attenuated but significant differences in fasting serum ghrelin (P=1.3 x 10(-3)) and ghrelin suppression (P=1.8 x 10(-3))., Conclusions: In women with PCOS, serum ghrelin levels are suppressed, showing a negative relationship with HOMA2 IR and a blunted response to oral glucose.

Gonadal development and function is sustained by the complex interaction of an array of regulatory signals that operate directly on the gonads and/or indirectly via modulation of gonadotropin secretion. During the last decade, different factors primarily involved in the control of food intake and energy balance have been demonstrated as putative modulators of different elements of the reproductive axis, including the gonads, thus helping to define the neuroendocrine basis for the link between body energy stores and fertility. These factors include not only the adipocyte-derived hormone leptin, which is indispensable for proper energy balance and reproduction, but also a number of neuropeptides and hormones of central and peripheral origin. In the latter, growing evidence strongly suggests the involvement of the stomach-secreted peptide ghrelin in the control of several aspects of gonadal function. Interestingly, leptin and ghrelin have been proposed as reciprocally related regulators of energy homeostasis; however, their potential interplay in the control of reproduction remains ill defined. This work will summarize the most salient findings concerning the potential roles of leptin and ghrelin in the functional control of the gonads. In addition, open issues regarding the reproductive facets of these metabolic signals will be highlighted. Overall, the authors propose that through complementary or antagonistic actions, leptin and ghrelin may jointly cooperate to modulate a wide set of reproductive functions, thereby contributing to the physiologic integration of energy balance and reproduction.

Unlabelled: As hypopituitarism is frequent in patients who have suffered a traumatic brain injury (TBI) a hormonal check-up is necessary. However, the prevalence of TBI is so large that the number of potential candidates to be tested is difficult to manage, in particular for GH deficiency diagnosis that requires cumbersome and expensive dynamic tests. GHRH plus GH-releasing hexapeptide (GHRP-6) is a safe and effective test capable of segregating normal subjects from GH deficient patients. As the GHRH+GHRP-6 test induces GH peaks consistently in the first 30 min, the working hypothesis assessed in this study was whether a single determination of GH 30 min after stimulus could provide the same biochemical classification as the whole secretory curve. A total of 83 subjects who suffered TBI at least one year before the study were administered GHRH 1 mug/kg iv plus GHRP-6 1 mug/kg iv at 0 min, and blood samples were obtained at regular intervals. GH was determined in all samples. An excellent correlation was observed between GH values at 30 min and GH peaks (r=0.972, p<0.0001). When comparing the 30-min GH values against the peaks, the biochemical classification changed only in 5 out of 83 subjects from normal GH secretion to uncertain., Conclusions: The GHRH+GHRP-6 test is convenient, safe and in patients with TBI can be reduced to a single fixed GH determination 30 min after stimulus without losing diagnostic power.

Although erectile dysfunction (ED) has been considered a complication of other medical conditions, clinicians and researchers suggest that ED may serve as a clinical marker of vascular health. This retrospective claims study examined the prevalence of predefined comorbid conditions in men with ED (N=301 994) in the 12 months before and the 6 months following ED diagnosis. Consistent with previous research, comorbid conditions were prevalent among men with ED. Comorbid conditions were most often diagnosed before an ED diagnosis, although new diagnoses in the 6 months following an ED diagnosis were common and occured more frequently than new diagnoses in a matched sample of men without ED during the same period. Differences by age, region and insurance coverage for ED medications were also examined. Findings support previous research that suggests ED may serve as a marker for previously undetected comorbid conditions.

Traumatic brain injury (TBI) was traditionally considered an infrequent cause of hypopituitarism. However recent reports strongly suggest that TBI-mediated pituitary hormones deficiency may well be more frequent than previously thought. As the prevalence of hypopituitarism is not dependent on the severity of the trauma and considering the high number of TBI events in all industrialized countries a screening procedure for detecting hormone deficiencies in all TBI patients is not possible. In the present work a suggestion for screening a subgroup of TBI patients is discussed in order to increase the effectiveness of the whole procedure.

A positive power-law relationship between the number of species in an area and the size of that area has been observed repeatedly in plant and animal communities. This species-area relationship, thought to be one of the few laws in ecology, is fundamental to our understanding of the distribution of global biodiversity. However, such a relationship has not been reported for bacteria, and little is known regarding the spatial distribution of bacteria, relative to what is known of plants and animals. Here we describe a taxa-area relationship for bacteria over a scale of centimetres to hundreds of metres in salt marsh sediments. We found that bacterial communities located close together were more similar in composition than communities located farther apart, and we used the decay of community similarity with distance to show that bacteria can exhibit a taxa-area relationship. This relationship was driven primarily by environmental heterogeneity rather than geographic distance or plant composition.

Objectives: The aim of this study was to assess whether once-daily Concerta extended-release (XR) methylphenidate (MPH) is associated with: (1) better compliance; (2) decreased likelihood of accidents/injuries; and (3) lower health-care resource use over a 1-year period than 3-times-daily immediate-release (IR) MPH in children with attention deficit hyperactivity disorder (ADHD)., Methods: Multivariate regression analyses were performed using an administrative database. Inclusion criteria were: (1) an age of 6-12 years at the date of first prescription for XR/IR MPH (index date); (2) patient-level data available for least 6 months before and 12 months after the index date; (3) no ADHD medications in the 6-month prior period; and (4) no XR MPH use by the IR MPH group., Results: IR MPH: n=344, mean age 9.55 years, 76% male; XR MPH: n=1431, mean age 9.78 years, 75% male. XR MPH patients were less likely to discontinue, less likely to switch, and more likely to persist (i.e., no gaps >14 days) with therapy (p <0.0001). Children receiving XR MPH were less likely to experience an accident or injury (OR=0.58, 95% CI 0.353-0.945). Use of XR MPH was associated with significantly fewer emergency room visits and general practitioner visits per patient, on average, over 1 year., Conclusions: These data support the use of XR MPH with its simplified dosing regimen for children with ADHD.

Grhelin is an endogenous ligand for the growth hormone secretagogue receptor from the stomach. It is a 28-aminoacid peptide of which the serine 3 residue is n-octanoylated. Ghrelin strongly stimulates GH secretion in vivo as well as in vitro. This endogenous ligand promotes the production of orexigenic neuropeptides (NPY and AgRP) in the hypothalamic arcuate nuclei and activates the neurons that produce these orexigenic peptides, resulting in an increase in feeding and body weight. Ghrelin has other significant actions, including control of acid secretion, influences on sleep and on the regulation of anxiety.

Ghrelin, the endogenous ligand for GHS-R, was isolated from rat stomach, although other tissues exist expressing ghrelin, such as pituitary, hypothalamus, placent, ovary, testes, etc. It was showed that ghrelin is implicated in GH secretion, in vivo and in vitro. There are direct evidences that proof that ghrelin administration induces GH secretion. There are in vivo data, showing ghrelin as a most potent GH secretor than GHRH. Evidences exist of ghrelin actions in the regulation of food intake and energy homeostasis. Ghrelin has a clear role in the differents pathologies such as obesity, anorexia and bulimia.

More than 40 years after the introduction of growth hormone (GH) treatment, many questions remain unanswered. Clearly, with the availability of rhGH and with current treatment protocols, treatment efficacy has improved. However, it still remains unclear whether current treatment protocols are the best possible. Before GH deficiency was recognized as a chronic disease, children only received treatment until normal adult height had been reached. However, it has recently been shown that not all GH-dependent body structures and functions normalize in parallel with height. Furthermore, in adolescents with GH deficiency, the interruption of GH substitution leads to severe hormone deficiency symptoms in adulthood. In the case of an adolescent who meets the biochemical criteria for GH deficiency in adulthood, but does not show alterations of metabolism, body structure, or emotional state, should GH treatment be started in adolescence, or only if and when the clinical syndrome becomes apparent? This is a difficult question to which there is not yet any clear answer, and we suggest that there is a need for further studies in this area. Furthermore, it will be necessary to re-evaluate the situation of patients who have completed their growth, and definitive conclusions will require controlled studies.

Background: There is experimental evidence that leptin is required for the development of T helper 1 (Th1)-mediated autoimmune diseases. However, to our knowledge, there are no studies demonstrating such a role in human autoimmune thyroid disease., Objective: In the present study we have retrospectively examined patients developing postpartum thyroiditis (PPT), as a model of autoimmune disease, for changes in serum leptin levels during the postpartum period., Materials and Methods: The study group included 61 women in the first month postpartum who were positive for thyroid peroxidase antibodies (TPOAb+ve). Twenty TPOAb-negative (-ve), age and body mass index (BMI)-matched, postpartum women were enrolled as the control group. All subjects were evaluated for BMI, serum leptin values, thyroid function [serum free-triiodiothyronine (FT3), free-thyroxine (FT4), thyrotropin (TSH)] and autoimmunity [TPOAb levels and complement activity index (C3 index)] at 4, 12, 16, 20 and 24 weeks' postpartum. During the postpartum period, 32 of 61 TPOAb+ve women (52.4%) showed one or more episodes of thyroid dysfunction (PPTD group), whereas the remaining 29 TPOAb+ve women remained euthyroid throughout the study period (PPTE group). None of the control group developed thyroid dysfunction., Results: Four weeks postpartum, TPOAb+ve women showed higher serum leptin values than TPOAb-ve women, despite comparable BMI. At this time, PPTE and PPTD patients showed no significant differences in leptin levels or leptin/BMI ratio. Throughout the postpartum period, PPTD patients maintained significantly higher leptin values and leptin/BMI ratio compared to the healthy women. In PPTE women, however, a significant reduction in leptin levels and leptin/BMI ratio was seen at 12 weeks' postpartum. This decrease was transient and correlated negatively with the variation in C3 index at the same time. No significant correlation was found between serum leptin variations and FT4 or TSH levels., Conclusions: This study has demonstrated that women developing postpartum thyroiditis have higher leptin values compared to the healthy women. The higher levels were maintained for 6 months postpartum. This result would suggest an involvement of leptin in the pathogenesis of postpartum thyroid disease, although further studies are needed to characterize the reciprocal effects of leptin, immune system and thyroid hormones during the course of this disease.

Exercise initiates a coordinated series of physiological responses, including hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system activation, that, in combination, lead to the appropriate selection and utilization of metabolic substrates. Physical activity acts as a powerful stimulus for the hypothalamic-pituitary axis, leading to the liberation of several neuroendocrine hormones. The nature of this stimulation varies according to the kind of exercise (intensity, duration, aerobic, strength) and subject characteristics (gender, previous training), as well as depending on the time of the day and meal ingestion. As a whole, the neuroendocrine responses to exercise represent an accurate regulator of fuels (glucose, free fatty acids) homeostasis in a special situation characterized by a drastic increase of the energy requirements at muscle level. In this article the current knowledge about this topic is reviewed.

Background: The diagnosis of GH deficiency in adults is based on the provocative testing of GH secretion. When testing a patient with suspected GH deficiency, clinicians assess the whole secretory curve and select the GH peak as an index of secretory capability. This procedure is time consuming and the determination of GH in several samples is necessary. The combined administration of growth hormone releasing hormone (GHRH) plus growth hormone releasing peptide-6 (GHRP-6) is an effective test of GH secretion, and it has been unambiguously demonstrated that the elicited GH peak is capable of segregating normal GH secretion subjects from GH deficient patients on an individual basis. The GHRH + GHRP-6 test biochemically classifies patients into three groups; those with a stimulated GH peak >/= 20 micro g/l are considered normal and those with peaks at

Leptin is a hormone secreted by the adipocytes that contribute to the control of energy balance, and circulating leptin levels reflect the amount of adipose tissue in the body, helping to regulate food intake and energy expenditure. Since it has been shown that human milk contains immunoreactive leptin, which is identical to intact human leptin, we decided to investigate the possible presence of immunoreactive bovine leptin in different kinds of common commercial milk. To determine the presence or absence of immunoreactive leptin in bovine milk for human consumption, 81 samples (66 commercial pasteurized milk and 15 artificial formulae for new-born babies) of the most common Spanish commercial types of milk were studied. All samples were evaluated before and after centrifugation, and leptin levels were measured by RIA. Leptin was detected in all samples and RIA standard curves were not perturbed when centrifuged and non-centrifuged milk replaced the buffer. Mean values of leptin in full-cream, semi-skimmed and skimmed samples, were: 5.7+/-0.3 ng/ml, 4.1+/-0.1 ng/ml, 3.7+/-0.1 ng/ml (significantly different). Leptin values were reduced after centrifugation. A significant correlation was observed between leptin levels and lipid content (p<0.0005, r=0.67) while no correlation was observed with respect to carbohydrate and protein levels. Interestingly, some preparations of infant formulae present very high leptin values reaching up to 18.9 ng/ml. In conclusion, leptin is present in significant and variable concentrations in edible commercial bovine milk, with higher concentrations in infant formula.

The aim of this study was to examine the independent effect of high lean mass on glucose metabolism, as well as its consequences on the classic relationship between BMI and insulin sensitivity (SI) in 3 groups: 1) 8 strength-trained males with BMI >27 kg/m2 (athletes); 2) 10 sedentary males with BMI >27 kg/m2 (obese); and 3) 12 sedentary males with BMI 22-25 kg/m2 (control). Body composition was measured with impedance analysis. Iv glucose tolerance test was performed at 09:00 h after overnight fast. Estimation of insulin sensitivity and glucose effectiveness by Minimal Model Approach. Plasma glucose and insulin determination by glucose-oxidase and RIA respectively. BMI and lean mass (LM) were greater in athletes than in controls, but there were no differences in fat mass (FM), basal glucose (Gb), basal insulin (Ib), glucose tolerance (Kg), SI, glucose effectiveness (Sg), acute insulin response to glucose (AIRG) and leptin. Obese showed greater FM, leptin, lb and AIRG than athletes, while SI was lower; BMI, LM, Gb, Kg and Sg were similar. BMI, FM, LM, Ib, AIRG and leptin were lower in controls than in obese, while SI index was greater; Gb, Sg and Kg were similar. We found that: 1) Resistance exercise does not modify glucose effectiveness, but can improve insulin sensitivity through FM reduction (LM augmentation alone has no effect on glucose metabolism); and 2) High BMI causes insulin resistance only if it depends on adipose tissue hypertrophy.

Leptin is an adipose tissue-secreted hormone that actively participates in the regulation of energy homeostasis. Besides this principal role, leptin has been implicated in a large variety of neuroendocrine, paracrine, and autocrine actions involved in the regulation of reproductive function in both experimental animals and humans. Although the participation of leptin in female reproduction is well established, any role in male reproductive function is at best tenuous. The aim of this study was to ascertain whether true leptin is present in human seminal fluid and the tissue of its production. Pooled human seminal plasma obtained from healthy donors showed by direct radioimmunoassay (RIA) the presence of radioimmunoassayable leptin. Serial dilutions of unextracted semen paralleled the RIA standard curve, also devoid of interference in the assay. To prove that this activity was true leptin, seminal plasma was subjected to size-exclusion chromatography, which showed that leptin immunoreactivity eluted with the same partition coefficient as cold leptin, 125I-leptin, and 125I-leptin preincubated with seminal plasma. The results demonstrate that true leptin was present in semen in a free form, i.e., without binding proteins. The presence of leptin charge variants in seminal plasma was assessed by anion-exchange chromatography, which showed two peaks of leptin inmunoreactivity, while 125I-leptin eluted as a single peak. Preincubation of 125I-leptin with seminal fluid converted the single peak into a double peak, indicating that components of the seminal fluid introduce a charge variation in leptin. Leptin levels in seminal plasma of 40 healthy men were 0.95+/-0.19 ng/mL while in 5 vasectomized men the levels were 0.92+/-0.25 ng/mL, suggesting that testicular tissues were not the source of seminal leptin. No correlation was observed between leptin concentrations in semen and the physical characteristics of semen samples or physical characteristics of spermatozoids, such as concentration, motility, vitality, or morphology. In conclusion it was unambiguously demonstrated that human leptin is present in seminal fluid, with at least two charge variants and no binding proteins, the most likely source being either seminal vesicles or prostate tissue. The role of seminal fluid leptin in the male reproductive function or sperm capacitation is at present unknown.

Leptin, the product of the ob gene, is secreted into the circulation by white adipose tissue; its major role being to participate in the regulation of energy homeostasis. Plasma leptin levels are mainly determined by the relative adiposity of the subject; however, the great dispersion of values for any given body mass index and the noteworthy gender-based differences indicate that other factors are operating. Steroid hormones actively participate in the regulation of leptin secretion; however, non-steroid nuclear hormones have either not been studied or have provided contradictory results. In order to understand the role of hormones of the non-steroid superfamily such as 3,5,3'-tri-iodothyronine (T(3)), vitamin D(3) and retinoic acid (RA) in the control of leptin secretion, in the present work doses of 10(-9), 10(-8) and 10(-7) M of these compounds have been studied on in vitro leptin secretion. The organ culture was performed with omental adipose tissue samples from healthy donors (n=28). T(3) was devoid of effect at any dose studied, while an inhibition of leptin secretion was observed with 9-cis-RA (slight) and all-trans-RA (potent). Interestingly, vitamin D(3) exerted a powerfully inhibitory role at the doses studied, and its action was synergistic with all-trans-RA. In conclusion, in vitro leptin secretion by human adipose tissue is negatively controlled by either RA or vitamin D(3). The clinical significance of leptin regulation by this superfamily of nuclear receptors remains to be ascertained.

Objective: Leptin is an adipocyte-secreted hormone acting as a signal to the central nervous system, where it regulates energy homeostasis and neuroendocrine processes. Leptin plasma levels are mainly regulated by the percentage of body fat, but are also controlled by several metabolic and nutritional variables. Data regarding leptin secretion suggest that it is gender regulated, and higher levels are present in women than men; however, the biological basis for this sex-related difference is unknown. To clarify those points, a systematic study with tissue cultures from human omental adipose tissue was performed., Design and Methods: Surgically obtained samples from 137 patients (68 women, 69 men) were evaluated. The assay was standardized in periods of 24 h ending at 96 h. Each adipose tissue sample from a single donor was incubated in triplicate and leptin results expressed as the mean of the integrated secretion into the medium (nanograms of leptin/g tissue per time)., Results: Tissue adipose cultures showed a steady leptin secretion throughout the 96 h studied, with the peak of secretory activity reached at 48 h; afterwards, the in vitro secretion reached a plateau state. Spontaneous leptin secretion in the 24 h and 48 h period, as well as the area under the curve analyzed in the 0-48 h period, showed a gender-based difference that was significantly (P<0. 05) higher in women than in men. When data of spontaneous leptin secretion were correlated with the body mass index (BMI) of the donors, no correlation was found. This suggests that in vivo leptin levels are dependent on the total amount of fat of the individual, but independent of the leptin secretory rate by the adipose tissue of the donor., Conclusions: Leptin secretion from omental adipose tissue in vitro is: (i) significantly higher in samples from women than in samples from men; and (ii) not correlated with the BMI, showing that in vitro leptin secretion is not related to the adiposity of the donor.

Unlabelled: Available data about the influence of exercise on leptin level are controversial, and there are no studies concerning leptin levels in trained men with low fat mass plus large increase of muscle. 65 healthy young male matched for age were separated in three groups. 1) 25 non-professional body builders; 2) 21 mild overweight sedentary subjects; 3) 19 normal weight sedentary controls. Body composition was determined by bioelectrical impedance. Serum leptin was measured in duplicate by RIA., Statistics: Student's t and Pearson's test. Athletes showed similar BMI than overweight subjects: 26.98+/-0.49 vs 27.12+/-0.41 but lower fat mass: 12.53+/-0.96 vs 16.16+/-1.01 % (p=0.0064) and lower leptin: 4.66+/-0.51 vs 7.31+/-0.76 microg/l (p=0.014). Athletes showed higher BMI than controls: 26.98+/-0.49 vs 23.08+/-0.30 (p<0.0001) but similar fat mass: 12.53+/-0.96 vs 12.48+/-0.73% and leptin: 4.66+/-0.51 vs 4.79+0.58 microg/l. Overweight subjects showed higher BMI than controls: 27.12+/-0.41 vs 23.08+/-0.30 (p<0.0001), higher fat mass: 16.16+/-1.01 vs 12.48+/-0.73% (p=0.0064) and higher leptin: 7.31+/-0.76 vs 4.79+/-0.589 microg/l (p=0.014). When leptin was calculated by fat mass no differences were observed between the three groups. There was a significant correlation between leptin and fat mass in all groups. Leptin correlated with BMI in overweight subjects (r=0.438, p=0.0463), but this correlation was not observed either in athletes or in controls. In conclusion 1) regardless of the high BMI characteristic of body builders, no correlation was observed with leptin; 2) trained state induced by resistance exercise does not influence leptin production independently of variations in body composition.

Objective: Children with diabetes mellitus are prone to develop obesity and to experience a delay in onset of the pubertal process. In order to understand the role of leptin in these abnormalities, serum leptin levels were analysed in children with type 1 diabetes mellitus., Subjects: Twenty diabetic girls, 23 diabetic boys and 66 healthy children (selected from a reference population of 706 normal children), age-, sex- and BMI-matched with diabetic patients, were studied., Measurments: Standing height, weight and BMI were determined in each child. Serum testosterone, oestradiol and leptin were measured by specific radioimmunoassays, and HBA1c by high performance liquid chromatography., Results: Both diabetic girls and boys showed higher leptin levels than the normative healthy population and a group of age-, sex- and BMI-matched normal children. In an age-related analysis, leptin levels in diabetic girls rose from 7.4 +/- 1.2 and 8.1 +/- 2.1 microg/l for the 5-7.99 and 8-10.99 year groups, to 12.6 +/- 2.4 microg/l for the 11-13.99 year group, and to 15.6 +/- 4.0 microg/l in the 14-15.99 year group in parallel with body weight. Leptin concentrations were parallel but higher (P < 0.05) than those of healthy girls. Diabetic boys had lower leptin levels than girls and, in contrast with normal boys, did not show a drop after the 10-year period. Leptin levels were 4.9 +/- 2.2, 3.9 +/- 0.2, 5.5 +/- 0.6 and 5.1 +/- 0.9 microg/l for the 5-7.99, 8-10. 99, 11-13.99 and 14-15.99 year groups, respectively. When divided by pubertal stage, leptin levels in the prepuberty stage of diabetic girls (8.6 +/- 1.0 microg/l) were higher (P < 0.05) than those in the controls (4.1 +/- 0.4 microg/l). In overt puberty girls, leptin was higher (P < 0.05) for diabetic (15.9 +/- 2.9 microg/l) than for healthy girls (9.2 +/- 1.1 microg/l). In prepubertal boys, differences were observed in leptin levels (4.9 +/- 0.5 microg/l for diabetic boys and 3.4 +/- 0.6 microg/l for healthy boys). In the overt puberty stage, diabetic boys showed higher (P < 0.05) levels of leptin (5.2 +/- 0.7 microg/l) than the healthy matched controls (2.1 +/- 0.2 microg/l). A multiple step regression analysis in the diabetic children revealed no associations between leptin and other relevant variables such as glycosylated haemoglobin, daily insulin dose, or years of suffering from the disease., Conclusion: Serum leptin levels were higher in diabetic than in healthy children. These differences were not attributable to age, adiposity or stage of pubertal development, and were probably conditioned by the metabolic perturbation intrinsic to the diabetic state, or the chronic hyperinsulinemia.

To determine the prevalence of pregnancy and postpartum thyroid dysfunction in the Spanish population, 691 women divided into six cohorts were studied. Biochemical hypothyroidism was observed in 9.4%, 4.4%, 1.9%, 4.6% and 4.8% at the first trimester of pregnancy, at delivery and at the second, fourth and sixth to twelfth postpartum months, respectively. Biochemical hyperthyroidism was observed in 6.7%, 0.8%, 1.9%, 4.6% and 2.4% in the same cohorts of subjects. Thyroiditis was observed in 4%, 0%, 0.6%, 6.2% and 7.3% in the cohorts studied. No depression or psychological alterations were detected either in pregnancy or in the postpartum period. Our data suggest that if screening for thyroid dysfunction is to be recommended in the postpartum period, this must be based on biochemical parameters.

Leptin, the product of the Ob gene, is a polypeptide hormone expressed in adipocytes which acts as a signalling factor from the adipose tissue to the central nervous system, regulating food intake and energy expenditure. It has been reported that circulating leptin levels are higher in women than in men, even after correction for body fat. This gender-based difference may be conditioned by differences in the levels of androgenic hormones. To explore this possibility, a systematic in vitro study with organ cultures from human omental adipose tissue, either stimulated or not with androgens (1 microM), was undertaken in samples obtained from surgery on 44 non-obese donors (21 women and 23 men). The assay was standardized in periods of 24 h, ending at 96 h, with no apparent tissue damage. Leptin results are expressed as the mean+/-s.e.m. of the integrated secretion into the medium, expressed as ng leptin/g tissue per 48 h. Spontaneous leptin secretion in samples from female donors (4149+/-301) was significantly higher (P<0.01) than that from male donors (2456+/-428). Testosterone did not exert any significant effect on in vitro leptin secretion in either gender (4856+/-366 in women, 3322+/-505 in men). Coincubation of adipose tissue with dihydrotestosterone (DHT) induced a significant (P<0.05) leptin decrease in samples taken from women (3119+/-322) but not in those taken from men (2042+/-430). Stanozolol, a non-aromatizable androgen, decreased (P<0.05) leptin secretion in female samples (2809+/-383) but not in male (1553+/-671). Dehydroepiandrosterone sulphate (DHEA-S) induced a significant (P<0.01) leptin decrease in female samples (2996+/-473), with no modifications in samples derived from males (1596+/-528). Exposure to androstenedione also resulted in a significant reduction (P<0.01) of leptin secretion in samples taken from women (2231+/-264), with no effect on male adipose tissue (1605+/-544). In conclusion, DHT, stanozolol, DHEA-S and androstenedione induced a significant inhibition of in vitro leptin secretion in samples from female donors, without affecting the secretion in samples from men. Testosterone was devoid of activity in either gender.

Objective: In pregnancy, important changes occur in the body weight of the mother, caused by sodium and water retention and by an increase in body fat tissue, but the mechanisms that regulate maternal and foetal changes in fat mass are poorly understood. Leptin is a hormone produced by adipocytes in order to regulate food intake and energy expenditure at the hypothalamic level in man. In order to verify whether leptin participates in the changes in body composition during pregnancy and postpartum, 630 healthy women were studied at specific time periods and leptin and auxological parameters were determined., Design: A cross-sectional study in which leptin levels were measured in women at specific time periods related to pregnancy. Each woman was assessed only once., Patients: 630 women participated in the study, and were divided into categories as follows: Group A, 29 internal controls, with no previous or current pregnancy; Group B, 73 women in the first trimester of pregnancy; Group C, 60 women in the 24 h before delivery; Group D, 212 women in the 24 h postpartum; Group E, 93 women in the eightH postpartum week (2 months group); Group F, 71 women in the sixteenth postpartum week (4 months group); Group G, 20 women in the sixth month postpartum; Group H, 23 women one year postpartum; Group I, 20 women two years postpartum; finally Group J, of 29 women who had suffered spontaneous abortion in the first trimester of pregnancy and were studied in the 24 h after the stillborn delivery., Measurements: Serum leptin levels were measured in duplicate by radioimmunoassay using commercial kits. Height and weight was measured and BMI (kg/m2) calculated., Results: Compared with serum leptin in the control group (11.7 +/- 1.0 micrograms/l), a non significant (NS) increase was observed in the first trimester of pregnancy (14.3 +/- 1.4 micrograms/l), with no parallel changes in body weight. A reduction in leptin occurred in the 24 h after delivery (9.4 +/- 1.4 micrograms/l, P = 0.02). After delivery a progressive increase in leptin concentrations was observed, 13.3 +/- 1.5 micrograms/l at two months (NS) and 17.4 +/- 2.6 micrograms/l at four months (P = 0.035 vs controls). Afterwards leptin values decreased towards normal values at 6, 12 and 24 months after delivery 14.4 +/- 1.8 micrograms/l; 12.9 +/- 1.6 micrograms/l; and 10.1 +/- 1.1 micrograms/l respectively (all NS). With the exception of the postpartum group, a significant correlation was observed between leptin concentrations and body weight or BMI in each group of women studied. In the women who suffered spontaneous abortion in the first trimester of pregnancy a reduction in leptin levels occurred (8.8 +/- 1.0 micrograms/l, P = 0.001 vs first trimester group)., Conclusion: Serum leptin concentrations rose slightly during pregnancy, fell following delivery and subsequently increased during the first six months postpartum. These variations were unrelated to changes in body composition, and may be responsible for the postpartum weight gain observed in some women. Abnormally low serum leptin levels were observed in women suffering spontaneous abortion in the first trimester of pregnancy.

Leptin is a hormone secreted by the adipocytes to serve as a signal to the central nervous system to regulate energy homeostasis. Circulating leptin mainly reflects both total fat mass and the size of constituent adipocytes, although other ancillary hormonal factors may contribute to its blood concentration. Relevant gender differences in leptin concentrations have been reported, but it is not clear whether the elevated leptin levels in women are an intrinsic property of their adipocytes or merely reflect a greater amount of fat reserves. To clarify these points, a systematic study with organ culture from human omental adipose tissue either stimulated or not with steroid hormones was undertaken in samples obtained at surgery from 67 nonobese donors (33 women and 34 men). The assay was standardized in periods of 24 h ending at 96 h, with no apparent tissue damage. Each adipose tissue sample from a single donor was incubated in triplicate, and leptin results are expressed as the mean +/- SEM of the integrated secretion to the medium (area under the curve; nanograms of leptin per g tissue/48 h). Control nonstimulated samples showed a steady leptin secretion along the 96 h studied, with the peak of secretory activity reached at 48 h; afterward, the in vitro secretion reached a plateau state. Spontaneous leptin secretion in samples from 33 women (3904 +/- 347) was significantly higher (P < 0.05) than that in samples from 34 men (2940 +/- 323). Coincubation of adipose tissue with 1 mumol/L dexamethasone induced a clear-cut leptin increase (P < 0.05) in samples from women (5848 +/- 624; n = 12), but did not change the spontaneous release of leptin in samples from men (3353 +/- 741; n = 6). Similarly, coincubation of adipose tissue with 1 mumol/L estradiol induced a notable leptin increase (P < 0.05) in samples from women (5698 +/- 688; n = 9), whereas it did not alter the secretion in the male samples (3373 +/- 444; n = 6). In samples from both sexes, coincubation with 1 mumol/L estrone or progesterone had no effect, whereas 1 mumol/L forskolin significantly (P < 0.05) reduced leptin release. In conclusion, leptin secretion from omental adipose tissue in vitro 1) is significantly higher in samples from women than in samples from men, 2) is stimulated by dexamethasone and estradiol in women but not in men, 3) is not modified by progesterone or estrone in both sexes, and 4) is inhibited by forskolin in both genders. This different response to the stimulation of adipose tissue may be the biological basis for the gender differences observed in circulating levels of human leptin.

Vitreous body extracts show a potent Ca(2+)-mobilizing activity on fibroblast cells. This Ca2+ signal is complex, and due to the presence of two different bioactive substances. The first one was identified as acid FGF. The second one was shown to be a low molecular weight substance identified as a complex lipid by a combination of chromatographic and biochemical data. This finding raises the possibility that non-classical substances with growth factor-like activity might play a role in the regulation of proliferative processes in the eye.

Sex-based differences in serum leptin concentrations have been reported in adolescence and adulthood. To discover when such differences were generated, serum leptin concentrations were measured in umbilical cord blood from 46 healthy infants and in the mother's blood at delivery. Considering the respective body weights of the mothers and infants (68.5 +/- 1.3 kg and 3.3 +/- 0.0 kg), umbilical cord concentrations of leptin were disproportionately high in the infants (9.4 +/- 1.2 micrograms/l) compared with those in the mothers (18.7 +/- 1.3 micrograms/l). There was a wide variation in the infants leptin values (1.2 +/- 56.8 micrograms/l) that did not correlate with height, weight, cephalic circumference, or any other growth-related parameter. The most striking differences emerged when results were analysed by sex: umbilical cord concentrations of leptin in the girls (12.9 +/- 2.2 micrograms/l) were significantly (P < 0.01) greater than those in the boys (6.8 +/- 0.9 micrograms/l), although no differences in leptin concentrations were observed between the mothers who gave birth to a girl (19.5 +/- 2.2 micrograms/l) and those who gave birth to a boy (18.1 +/- 1.7 micrograms/l). The sex-based differences were not attributable to any growth-related differences between the sexes, except heavier placental weights in the girls (P < 0.007) than in the boys. These differences in leptin concentrations may reflect a sex-based difference in the regulation of leptin production by the fetal adipose tissue.

It has been reported that cis-unsaturated free fatty acids (cis-FFA) block intracellular Ca2+ rise in EGFR T17 and GH3 cells by perturbing the generation of Ins(1,4,5)P3. In the present work, it was found that cis-FFA did not alter potassium-induced cell depolarization in GH3 cells, while blocking Ca2+ rise and GH secretion. Interestingly enough, saturated or trans-unsaturated FFA exert the opposite actions, i.e., they block cell depolarization without altering Ca2+ rise and hormone secretion. As depolarization activates GH3 cells via direct opening of Ca2+ channels with no generation of intracellular mediators, these results suggest that cis-FFA act by a direct perturbation of the Ca2+ channel opening.

Unlabelled: It is commonly accepted that at least in girls puberty starts when a minimum level of body mass or a certain amount of body fat are present. However the precise signal by which adipose stores inform the hypothalamus of the degree of energetic reserves is unknown. Leptin is a hormone produced by the adipocytes to regulate food intake and energy expenditure at the hypothalamic level. To understand whether leptin is the adipose tissue signal that allows puberty, 789 normal children of both sexes, age 5-15 yr, were transversally studied. Leptin levels, as well as gonadal and gonadotropins, levels, were analyzed in addition to the determination of auxological parameters. In an age-related analysis, leptin levels in girls rose from 5-15 yr (from 4.3 +/- 0.4 to 8.5 +/- 0.9 micrograms/L) in parallel with body weight. Boys always had lower leptin levels than girls (3.3 +/- 0.3 micrograms/L at 5 yr), but they rose in parallel with weight until 10 yr (5.3 +/- 0.7 micrograms/L), when a striking decrease was observed until 15 yr (3.0 +/- 0.3 micrograms/L). In girls, leptin was the first hormone to rise followed by FSH and later by LH and estradiol. A similar pattern occurred in boys, despite the fact that leptin dropped after 10 yr when testosterone rises. Divided into three pubertal stages, i.e. P1 = prepuberty, P2 = early puberty, and P3 = overt puberty, in girls the four hormones rose progressively from P1 to P3, but from P2 to P3 the present increment was greater for LH and estradiol. In boys, leptin decreased from P1 to P3, whereas FSH, LH, and testosterone rose. The age-related changes were not caused by adiposity variations, because data did not change when subtracting values of children over 97% of standard deviation score of body mass index., In Conclusion: 1) leptin appears to increase in both boys and girls before the appearance of other reproductive hormones related to puberty; 2) leptin levels in boys are always lower than in girls, although they increase with age until the age 10 yr; 3) leptin in boys declines about the time testosterone increases. Leptin may well be a permissive factor for the initiation of pubertal events.

The usually accepted effect of corticosteroids on growth hormone secretion (GH) is the reduction or blockage of secretion. Our laboratory has previously reported that corticosteroids could have an acute stimulatory effect on this secretion; we have now studied the effect of administering THR on corticosteroids induced GH secretion. Three stimulatory tests were performed to three healthy volunteers on different days. Saline administration on time 0 and time 120 minutes (control test) did not modify GH levels. On the contrary, the administration of 4 mg Dexamethasone i.v. on time 0 induced an increase in GH with a maximum peak of 10 = 3.3 micrograms/L after three hours being these differences statistically significant (p less than 0.05) when referred to the control test from 120 to 240 minutes. The corticosteroid GH stimulus presented a peculiar secretion pattern: During two hours there were no changes in basal values and afterwards the values were maintained in maximum peak values during two hours, with a great net release of GH. The administration of THR (400 micrograms iv) 120 minutes after the administration of Dexamethasone did not notify GH secretion pattern when compared with the group receiving only Dexamethasone. To conclude, the administration of corticosteroids is a new and peculiar stimulus for GH secretion. Lack of THR inhibitory function suggests that the corticosteroid stimulatory function is probably at the hypothalamus level.