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Background: Maternal smoking is linked with several neonatal metabolic disorders. Adiponectin is an adipose-specific hormone with anti-inflammatory and antiatherogenic properties., Aim: The aim of this study was to evaluate the effect of maternal smoking on cord blood adiponectin concentrations., Methods: We evaluate the effect of maternal smoking on cord blood adiponectin concentrations comparing 14 full-term and seven preterm newborns born to mothers who smoked during pregnancy with 77 full-term and 10 preterm neonates born to non-smokers mothers., Results: Maternal smoking during pregnancy was significantly associated with decreased adiponectin levels of preterm newborns (p < 0.05)., Conclusions: Our findings also reveal a significant relationship between the reported number of cigarettes smoked during pregnancy and cord blood adiponectin concentrations (p = 0.01), suggesting that this association could have a causal relationship.

Objective: To determine cord blood leptin levels in newborns appropriate for gestational age, according to gender, birth weight, birth height and ponderal index., Methods: A cross-sectional study was carried out with 132 term newborns appropriate for gestational age (68 females, 64 males), gestational age between 35-42 weeks. Data were collected through interviews with the mothers at the maternity, anthropometrycal study of the newborns, and cord blood estradiol, testosterone and leptin assays obtained immediately after birth., Results: The levels of leptin were significantly higher in females than in males (8.34+/-0.65 ng/ml versus 6.06+/-0.71 ng/ml; p = 0.000). The concentrations of estradiol and testosterone did not differ between males and females. Leptin levels were positively correlated with gestational age (r = 0.394, p < 0.01), birth weight (r = 0.466, p < 0.01), birth length (r = 0.335, p < 0.01) and ponderal index (r = 0.326, p < 0.01)., Conclusions: Leptin concentration in the umbilical cord is positively correlated with gestational age, birth weight, birth height, and ponderal index, suggesting its participation in the neonatal growth process. In addition, a gender difference with higher levels of leptin in females neonates was observed, suggesting that the sexual dimorphism in relation to body composition already exists in newborns.

Autoimmune chronic lymphocytic thyroiditis appears in two forms, goitrous and atrophic. The evidence available is not enough to prove that the goitrous precedes the atrophic form, but immunogenetic analysis suggests that they may be distinct entities. The distribution of HLA class II alleles DRB1* and DQB1* was verified in patients from the region of Campinas, São Paulo, Brazil with both forms of thyroiditis. Ninety-one patients with primary hypothyroidism through autoimmune thyroiditis were classified as goitrous - 54 patients, 42.27 +/- 11.72 years old, having had hypothyroidism for 8.57 +/- 6.63 years - or atrophic - 37 patients, 42.72 +/- 12.01 years old, hypothyroidism for 6.73 +/- 4.07 years. The distribution of class II alleles was determined, DRB1* and DQB1* were genotyped after purifying DNA blood samples using the DNAzol technique, and the low-resolution PCR-SSP system was utilized for determination of generic alleles. Chi-square and Fisher's exact test were utilized to compare the distribution frequency of HLA alleles and the significant p-values were subjected to Bonferroni correction. We have demonstrated that the DRB1*04 allele is associated with autoimmune thyroiditis, and that there are genotypic differences regarding the presentation forms with a strong association between DRB1*04 and DQB1*03 and the atrophic form only.

This review reports the etiological aspects of insulin resistance as well as the participation of zinc in this process. Zinc participates in the metabolic pathways involving protein synthesis, and the metabolism of carbohydrate, lipid and nucleic acid. This element has been associated with the interaction between hormones and their receptors and to the improvement in the post-receptor stimulus. In vitro studies show that insulin may form a complex with zinc improving the solubility of this hormone in the pancreatic beta cells and also increasing the binding ability of insulin to its receptor. Regarding obesity and insulin resistance, alterations in zinc concentration and distribution in tissues, as well as improvement in sensitivity to insulin after supplementation with this element, have been detected. Thus, the metabolic role of zinc in the insulin resistance syndrome should be further investigated having in mind that this element may contribute to the control of the usual metabolic alterations present in obese patients.

Objective: Adiponectin is the only adipose-specific hormone that, despite its exclusive production by adipose tissue, is reduced in obesity and is inversely correlated with leptin levels in adults. The aim of this study was to evaluate the adiponectin concentration in umbilical cord blood at different gestational ages and to investigate its possible associations with leptin levels and birth weight., Research Methods and Procedures: Umbilical cord blood was obtained from 132 newborns (male = 65, female = 67, gestational age: 35 to 42 weeks). The anthropometric variables of the newborns studied were birth weight, birth length, body weight/body length, and ponderal index. Adiponectin, insulin, and leptin levels were measured by radioimmunoassay methods., Results: Adiponectin levels in males were not different from those in females (24.10 +/- 0.81 vs. 25.62 +/- 0.84 micro g/mL, p = 0.280). Adiponectin concentrations were positively correlated with birth weight (p < 0.05), birth length (p < 0.05), body weight/body length (p < 0.05), gestational age (p < 0.01), and leptin levels (p < 0.01)., Discussion: These findings indicate that adiponectin is present in umbilical cord blood after 35 to 42 weeks of gestation, with higher levels than those usually found in adults, no gender differences, and a positive correlation with birth weight and leptin. These results suggest that not only could neonatal hyperadiponectinemia be associated with the increase of adiponectin production by fetal adipose tissue but also with a possible reduction in an unknown mechanism related to the suppression of adiponectin observed in adults.

Aim: To assess the effect of sibutramine-assisted weight reduction program on insulin sensitivity and metabolic parameters in obese normal glucose tolerant individuals over a period of 24 weeks., Research Design and Methods: A double-blind, placebo-controlled, parallel, prospective clinical trial was carried out at our medical centre. Forty female normal glucose tolerant patients, body mass index: 34.3 +/- 2.9 kg/m2 and age: 41.1 +/- 9.9 (range: 19-58 years), were randomized to placebo or sibutramine, 10 mg once daily., Results: Seventeen patients from sibutramine group and 14 placebo had completed the study protocol. Significant weight change was seen in sibutramine (p < 0.01) (-5.6 kg or -6.1% vs. +0.9 kg or +1.1% in placebo). Insulin sensitivity enhanced in sibutramine group (Kitt: from 4.03 +/- 1.97 to 5.09 +/- 2.48%/min; p < 0.05). Homeostasis model assessment-IR (HOMA-IR) decreased from 7.8 +/- 6.9 to 5.6 +/- 4.5 (p < 0.05). HOMA-beta also decreased from 508 +/- 381 to 374 +/- 256 (p < 0.05). No changes were observed in the placebo control group regarding insulin sensitivity or secretion. Concomitant reductions were observed in the sibutramine group in lipid parameters (triglycerides and high-density lipoprotein-cholesterol), uric acid and gamma-glutamyl transferase (p < 0.05)., Conclusions: Sibutramine has demonstrated efficacy in reducing weight in non-diabetic women along with amelioration in insulin sensitivity and additional improvement in metabolic parameters.

Background: Ghrelin is a newly recognized gastric hormone with orexigenic and adipogenic properties, produced primarily by the stomach. Ghrelin is reduced in obesity. Weight loss is associated with an increase in fasting plasma ghrelin. We assessed the effect of massive weight loss on plasma ghrelin concentrations and its correlation with serum leptin levels and the presence of type 2 diabetes mellitus (DM) in severely obese patients., Methods: A prospective study was conducted on 28 morbidly obese women (BMI 56.3 +/- 10.2 kg/m2) who underwent gastric bypass, divided into 2 groups: 14 non-diabetics (NGT) and 14 type 2 diabetics (DM2). Ghrelin and leptin were evaluated before silastic ring transected vertical gastric bypass, and again 12 months postoperatively., Results: Fasting plasma ghrelin concentrations were 56% lower in NGT and 59% lower in DM2 compared with a lean control group (P < 0.001). There was no difference in ghrelin levels between NGT and DM2 groups before and after surgery (P > 0.05). Ghrelin was negatively correlated with leptin before gastric bypass surgery (r = 0.51, P < 0.01). The mean plasma ghrelin concentration decreased significantly after surgery in both groups (P < 0.001)., Conclusion: Ghrelin was inversely related to leptin concentrations. Presence of diabetes did not affect the ghrelin pattern. Reduced production of ghrelin after gastric bypass could be partly responsible for the lack of hyperphagia and thus for the weight loss.

Context: Thyroid uptake and scintigraphy using 99mTc-pertechnetate has proven to be more advantageous than with 131I-iodide, since the images have better quality, the procedure is faster and the patient is submitted to a lower radiation dose., Objective: The purpose of this study was to standardize a simple and fast methodology for performing thyroid uptake and scintigraphy and to determine the normal values for 99mTc- pertechnetate uptake., Type of Study: Prospective, non-randomized., Setting: Division of Nuclear Medicine, Department of Radiology, School of Medical Sciences, Campinas State University., Participants: The study consisted of 47 normal individuals, 30 women and 17 men, with ages ranging from 19 to 61 years (mean of 33 years)., Procedures: The laboratory assessment of thyroid function consisted of serum dosages of ultra-sensitive thyroxin and thyrotrophin. Twenty minutes after an intravenous injection of 10 mCi (370 MBq) of 99mTc-pertechnetate, the images were obtained on a computerized scintillation camera equipped with a low-energy high-resolution parallel hole collimator., Results: All the individuals were euthyroid both on clinical and laboratory evaluation. The baseline thyroid 99mTc-pertechnetate uptake ranged from 0.4 to 1.7%. The uptake values obtained in these normal individuals showed that 95% presented a thyroid uptake that ranged from 0.4 to 1.5% of the injected dose., Conclusion: The assessment of thyroid structure and function using 99mTc-pertechnetate is a simple, fast and efficient method, which could easily become a part of the routine studies in nuclear medicine laboratories.

Background: A longitudinal, clinical intervention study with bariatric surgery was done to investigate the relationship between leptin levels, BMI, and insulin during weight loss across a range of glucose tolerance from normal to diabetes., Methods: 43 morbidly obese patients (BMI: 42-75 kg/m2) undergoing vertical banded gastroplasty Roux-en-Y gastric bypass (VBG-RGB), were divided into 3 groups: 21 normal (NGT), 12 impaired glucose tolerance (IGT) and 10 type 2 diabetes (DM). Leptin, insulin, glucose, lipids and uric acid were measured at baseline and 2, 4, 6, and 12 months following surgery., Results: BMI fell from 54.1 +/- 9.1 to 34.6 +/- 6.3 kg/m2, similarly in all groups. Leptin decreased from 73.9 +/- 8.7 to 16.9 +/- 10.2 ng/ml and was strongly correlated with BMI during 1-year follow-up (r = 0.78; p < 0.001). Linear univariate analysis for repeated evaluation showed a positive correlation between leptin and glucose, triglycerides, uric acid, and insulin. Multivariate regression analysis indicated that BMI was independently correlated with the decrease in leptin (p < 0.001), accounting for 66% of the variance in leptin levels during weight loss. These results were found in the NGT and IGT groups. In the DM group, a small additional influence in leptin levels was attributed to glucose decrease., Conclusions: A strong link between leptin and BMI was found after surgery. BMI was the main determinant of the decrease of leptin. In these patients submitted to bariatric surgery, ranging from normal glucose tolerance to diabetes, changes in insulin levels and metabolic parameters, except for glucose in the DM group, did not appear to be correlated with changes in leptin levels.

Objective: To assess the effect of massive weight loss in relation to insulin resistance and its correlation to changes in glycemic homeostasis and lipid profile in severely obese patients., Research Methods and Procedures: A prospective clinical intervention study was carried out with 31 morbidly obese women (body mass index: 54.2 +/- 8.8 kg/m(2)) divided into three groups according to their glucose tolerance test: 14 normal, 8 impaired glucose tolerance, and 9 type 2 diabetes. All subjects underwent an insulin tolerance test with intravenous bolus of 0.1 U insulin/kg body weight before silastic ring vertical gastroplasty Roux-en-Y gastric bypass surgery, and again at 2, 4, 6, and 12 months postoperatively. Fasting plasma glucose, hemoglobin A1c, and lipid profile were also evaluated., Results: A reduction of 68 +/- 15% in initial excess body weight was evident within 1 year. Along with weight loss, the following statistically significant changes were found: an increase in the insulin-sensitivity index (Kitt) and a decrease in fasting plasma glucose and hemoglobin A1c, most notably in the type 2 diabetes group. An overall improvement in lipid profile was observed in all three groups., Discussion: Bariatric surgery was an effective therapeutic approach for these obese patients because it reduced both weight and insulin resistance, along with improving metabolic parameters. Significant correlations were found between insulin resistance and metabolic improvements. Weight loss after bariatric surgery induced an improvement in metabolic fitness, related to the reduction in insulin resistance over a range of glucose tolerance statuses from normal to diabetic.

Antithyroid drugs have been reported to reduce the expression of HLA-DR in thyrocytes in Graves' disease, but only circumstantial evidence has been provided about their in vivo immunologic effects. This present study was designed to examine the in vivo immunologic effect of antithyroid drugs on thyroid follicular cells. The study was conducted on 25 patients who had Graves' disease in remission or in activity and who were or were not receiving treatment (7 in overt thyrotoxicosis, 6 patients in remission, and 12 patients under medication). HLA-DR expression in thyroid biopsies was verified by immunohistochemistry. The follicular cells of all patients in overt thyrotoxicosis expressed HLA-DR whereas those of patients in remission were negative for HLA-DR. HLA-DR was also not expressed in all patients under medication, but this did not correlate with the clinical evolution after thyroid drug withdrawal. In conclusion, antithyroid drugs inhibit follicular cell HLA-DR expression in Graves' disease, when thyrotoxicosis is controlled. This suggests that additional mechanisms not involving HLA-DR play a role in thyroid autoimmune disease.

Objective: The thyroid suppression test is still used in some centres as an adjunt in the diagnosis of autonomous functioning thyroid nodules. With the purpose of minimizing the disadvantages of the original T3 suppression test, we have evaluated the efficacy of a method using L-thyroxine as TSH suppression agent and [99 mTc] pertechnetate as radiopharmaceutical., Design: Open nonrandomized prospective study, Materials and Methods: A control group of 15 normal volunteers (11 males, 4 females; 21-35 years, mean 26.4 years) and a patient group of 20 patients (18 females, 2 males; 27-83 years, mean 53.6 years) divided into 4 subgroups, were studied: 7 patients with autonomous functioning nontoxic nodules, 3 with autonomous functioning toxic nodules, 7 with Graves disease and 3 with nonautoimmune diffuse toxic goitre. Baseline thyroid uptake and imaging were begun 20 minutes after an intravenous injection of 370 MBq (10 mCi) of [99 mTc] pertechnetate. This was followed by a single daily intake of 2 microg/kg of L-thyroxine, for 10 days. Thyroid imaging and uptake were then repeated., Results: In the control group [99 mTc] pertechnetate uptake after L-thyroxine suppression had a mean reduction of 75.8 +/- 7.69% (58-87%) in comparison to the baseline level. All subjects were euthyroid by clinical and laboratory criteria and none complained of side-effects, despite significant suppression of TSH levels. In the patient group, thyroid uptake after suppression decreased in 10 patients (maximum reduction 39%), was unchanged in 2 patients and increased in the remaining 8 patients., Conclusion: The method described was efficient for demonstration of autonomous thyroid tissue, since none of the patients showed significant reduction of thyroid uptake after L-thyroxine suppression compared with the control group. This test was as effective as the original T3 suppression test, but more convenient to the patient: no side-effects, ease of hormonal intake, low dosimetry and short stay in the nuclear medicine laboratory.

Graves' disease (GD) is an autoimmune thyroid disorder which is associated with the human leucocyte antigens HLA-DR3 and DQA1* O501 in Caucasians. We have explored the possibility that some patients with certain HLA specificities develop anti-HLA antibodies which are correlated with environmental factors that may contribute to the development of GD. We studied 40 GD patients and 157 healthy individuals (controls). Serology was used to type HLA-A, -B, -Cw, and -DR antigens. The frequencies of these antigens in relation to lymphocytotoxic anti-HLA-A-B-Cw-DR antibodies and two environmental factors (Yersinia enterocolitica and Coxsackie B virus) were determined. The frequencies of HLA-B15, -B21 and DR3 antigens were increased, whereas HLA-DR5 antigen was decreased in GD patients. A significant association between HLA-DR3 antigen and lymphocytotoxic antibodies was observed, i.e., IgGs from GD patients were cytotoxic to HLA-DR3+ normal B cells. Following absorption with Yersinia enterocolitica or Coxsackie-B-virus, only Coxsackie-B virus completely inhibited the lymphocytotoxic reactions against HLA-DR3+ B cells. Besides confirming the association of HLA-DR3 with GD, this study also suggests the role of Coxsackie-reactive HLA-DR3 antibodies as contributing factors to the pathogenesis of the disease.

Modulation of free plasma zinc levels has been implicated in the increase in plasma prolactin levels seen in patients with chronic renal insufficiency (CRI). The relative importance of this mechanism in comparison to others, however, has not been elucidated. Zinc equilibrium between plasma and red blood cells is partly dependent upon red blood cell carbonic anhydrase (CA). In the present paper, we have investigated the interrelationships among total plasma zinc, leukocyte zinc, prolactin, and erythrocyte CA in patients with CRI. Uremic patients were shown to have significantly increased levels of plasma prolactin and erythrocyte CA activity when compared to normal controls. Moreover, red blood cell CA total concentration and isoenzyme-I and-II levels, as well as plasma zinc were found to be significantly decreased in uremic patients in comparison to normal controls. In patients with CRI, a negative correlation was demonstrated between erythrocyte CA catalytic activity and plasma zinc, as well as between plasma zinc and plasma prolactin levels. Moreover, leukocyte zinc content, which is a reliable indicator of total body zinc stores, was found to be significantly decreased in uremic patients when compared to normal controls. A strong negative correlation between leukocyte zinc content and plasma prolactin levels was documented in CRI patients. Our results suggest that alterations in erythrocyte CA levels, enzymatic activity or isoenzyme profile are most probably mechanistically and etiologically unrelated to the high plasma prolactin levels in CRI patients. Contrariwise, depletion of total body zinc stores, rather than redistribution of this trace metal among extracellular compartments, may represent one of the major contributing mechanisms leading to uremic hyperprolactinemia.

A patient with Cushing's disease due to a chromophobe adenoma was studied for 243 days before pituitary surgery and evidence for periodicity in cortisol steroid production was found with cycles occurring every 85.8 days (peak-to-peak length), associated with laboratory remissions and paradoxical response to dexamethasone. The autonomy of ACTH secretion was suggested by the nonresponsiveness to repeated lysine-vasopressin stimulation tests and lack of increase in urinary 170HCS following metyrapone. A distinct response of the hyperplastic glands (as demonstrated by percutaneous adrenal venography) was obtained on several B1-24 corticotropin stimulation. The patient's hypercortisolism disappeared following removal of the chromophobe adenoma through transphenoidal hypophysectomy.