Plasma obestatin concentrations are negatively correlated with body mass index, insulin resistance index, and plasma leptin concentrations in obesity and anorexia nervosa

Background: Obestatin is a recently identified ghrelin gene product that was reported to inhibit appetite and gastric motility in contrast to ghrelin. We investigated fasting obestatin and ghrelin levels in patients with obesity and anorexia nervosa. Methods: Fasting plasma obestatin, acyl-ghrelin, desacyl-ghrelin, leptin, glucose serum adiponectin, and insulin were measured in 10 obese subjects, 11 restricting-type anorexics, and 11 control subjects. Results: Obese group had significantly lower levels of obestatin (p < .01), while anorexic group had significantly higher levels (p < .01). Obestatin was negatively correlated with body mass index (BMI) (r = -.74), glucose (r = -.56), insulin (r = -.55), leptin (r = -.66), and also with the homeostasis model assessment of insulin resistance (HOMA-R) (r = -.49) and was positively correlated with acyl-ghrelin (r = .65) and desacyl-ghrelin (r = .60). No correlation was seen between obestatin and adiponectin, but the latter was negatively correlated with both acyl-ghrelin and desacyl-ghrelin. Desacyl-ghrelin to acyl-ghrelin ratio was significantly different between anorexic and control groups (p < .05), while no difference was seen between obese and control groups. Conclusions: Both obestatin and ghrelin are increased in anorexic and decreased in obesity. We suggest that obestatin is a nutritional marker reflecting body adiposity and insulin resistance.

Avaliação hemodinâmica e metabólica da cetamina e cetamina S(+) após a reposição volêmica com hidroxietilamido 130/0,4 e solução salina hipertônica 7,5%

O objetivo deste estudo foi avaliar os efeitos hemodinâmicos e metabólicos, após a administração de solução salina hipertônica (NaCL) 7,5% ou em associação ao hidroxietilamido (HES), em cães com hipovolemia induzida e tratados com cetamina. Após a indução da hipovolemia, administrou-se NaCl 7,5% (4,0ml kg-1) no grupo hipertônica levógira (GHL) e grupo hipertônica racêmica (GHR) ou HES 130/0,4 na mesma proporção de sangue retirado, associado a NaCl 7,5% (4ml kg-1) no grupo hipertônica colóide levógira (GHCL) e no grupo hipertônica colóide racêmica (GHCR). Após 30 minutos, administrou-se, por via IV, cetamina levógira (CL) (5mg kg-1) no GHL e GHCL ou cetamina racêmica (CR) (10mg kg-1) no GHR e GHCR. Empregou-se a análise de variância de uma única via com repetições múltiplas (ANOVA) e o teste de Student Newman Keuls (P£0,05). A frequência cardíaca e a pressão arterial sistólica foram menores após a hipovolemia e após a CR. As pressões arteriais média e diastólica foram menores após a hipovolemia e cetamina. A pressão venosa central foi maior após a administração do colóide. Os índices cardíaco e sistólico foram menores após a hipovolemia em todos os grupos e, após a fase de expansão no GHL e GHR. A pressão média da artéria pulmonar foi menor após a hipovolemia em todos os grupos. A pressão de oclusão da artéria pulmonar foi maior após o colóide. O índice do trabalho ventricular esquerdo foi menor após a hipovolemia no GHCL e GHCR. O índice da resistência periférica total foi maior após a hipovolemia e menor após a CL. Observou-se acidose metabólica após a hipovolemia e após a cetamina. Ocorreu acidose respiratória após a cetamina no GHL e GHR. Conclui-se que a administração de NaCl 7,5% associado ao HES 130/0,4 promove o restabelecimento imediato dos parâmetros hemodinâmicos e metabólicos no paciente hipovolêmico; a administração isolada de NaCl 7,5% não é capaz de restaurar a PAM no período imediato, mas melhora os demais parâmetros hemodinâmicos e metabólicos; a administração de CR ou CL produz efeitos hemodinâmicos e metabólicos similares no paciente hipovolêmico.

CHANGES IN FETAL AND MATERNAL DOPPLER PARAMETERS OBSERVED DURING ACUTE SEVERE HYPERTENSION TREATMENT WITH HYDRALAZINE OR LABETALOL: A RANDOMIZED CONTROLLED TRIAL

We evaluated 16 pregnant women with gestational age between 20 and 32 weeks in acute severe hypertension which were randomly allocated to receive either hydralazine or labetalol. Blood pressure and Doppler ultrasound parameters from maternal uterine and fetal middle cerebral and umbilical arteries were assessed during acute severe hypertension and after treatment. A significant reduction in systolic and diastolic blood pressure was observed in both groups. A significant change in Doppler parameters was observed only in pregnant women who received hydralazine: an increase in uterine arteries resistance index. We concluded that both drugs were highly effective in reducing blood pressure in these women. Despite the observed increase in resistance index of uterine arteries associated with hydralazine, the use of hydralazine and labetalol were not related to any significant changes in fetal Doppler, which is reassuring about the safety of these drugs when treating acute severe hypertension in pregnancy. (E-mail: wpmartins@gmail.com) (C) 2011 World Federation for Ultrasound in Medicine & Biology.

The role of nutritional profile in the orexigenic neuropeptide secretion in nonalcoholic fatty liver disease obese adolescents

Background Little progress has been made to identify the central neuroendocrine pathway involved in the energy intake control in nonalcoholic fatty liver disease (NAFLD) patients. Objective To assess the influence of orexigenic neuropeptides in the nutritional aspects of NAFLD obese adolescents submitted to a long-term interdisciplinary approach. Methods Fifty adolescents aged 15-19 years, with body mass index at least 95th percentile, consisting of 25 patients without NAFLD and 25 with NAFLD. The NAFLD diagnosis was determined by ultrasonography. Blood samples were collected to analyze glycemia, hepatic transaminases, and lipid profile. Insulin resistance was estimated by Homeostasis Model Assessment Insulin Resistance Index. Neuropeptide Y (NPY) and agouti related protein concentrations were measured by enzyme-linked immunosorbent assay. Analyses of food intake were made by 3 days recordatory inquiry. Results At baseline conditions, the patients with NAFLD had significantly higher values of body mass, body mass index, visceral fat, triglycerides, VLDL-C, and hepatic transaminases. After the long-term intervention, they presented a significant reduction in these parameters. In both the groups, it was observed a significant decrease in energy intake, macronutrients and dietetic cholesterol. Only the patients with NAFLD presented a positive correlation between the saturated fatty acids intake and the orexigenic neuropeptides NPY and agouti related protein, and carbohydrate with NPY. Indeed, it was observed a positive correlation between energy intake, lipid (%) and saturated fatty acids with visceral fat accumulation. Conclusion Our findings showed an important influence of diet composition in the orexigenic system, being essential consider that the excessive saturated fatty acids intake could be a determinant factor to increase nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol 22:557-563 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Sildenafil improves the beneficial haemodynamic effects of intravenous nitrite infusion during acute pulmonary embolism

Acute pulmonary embolism produces acute pulmonary hypertension, which can be counteracted by activating the nitric oxide-cyclic guanosine 3`,5`-monophosphate (cGMP) pathway. While previous studies have shown that sildenafil (an inhibitor of cGMP-specific phosphodiesterase type 5) or nitrite (a storage molecule for nitric oxide) produces beneficial effects during acute pulmonary embolism, no previous study has examined whether the combination of these drugs can produce additive effects. Here, we expand previous findings and examine whether sildenafil enhances the beneficial haemodynamic effects produced by a low-dose infusion of nitrite in a dog model of acute pulmonary embolism. Haemodynamic and arterial blood gas evaluations were performed in non-embolized dogs treated with saline (n = 4), and in embolized dogs (intravenous injections of microspheres) that received nitrite (6.75 mu mol/kg intravenously over 15 min. followed by 0.28 mu mol/kg/min.) and sildenafil (0.25 mg/kg over 30 min.; n = 8), or nitrite followed by saline (n = 8), or saline followed by sildenafil (n = 7), or only saline (n = 8). Plasma thiobarbituric acid-reactive substances (TBARS) concentrations were determined using a fluorometric method. Acute pulmonary embolism increased pulmonary artery pressure by similar to 24 mmHg. While the infusion of nitrite or sildenafil infusions reversed this increase by similar to 42% (both P < 0.05), the combined infusion of both drugs reversed this increase by similar to 58% (P < 0.05). Similar effects were seen on the pulmonary vascular resistance index. Nitrite or sildenafil alone produced no significant hypotension. However, the combined infusion of both drugs caused transient hypotension (P < 0.05). Both dugs, either alone or combined, blunted the increase in TBARS concentrations caused by acute pulmonary embolism (all P < 0.05). These results suggest that sildenafil improves the beneficial haemodynamic effects of nitrite during acute pulmonary embolism.

Hemodynamic effects of inducible nitric oxide synthase inhibition combined with sildenafil during acute pulmonary embolism

While endogenous nitric oxide (NO) may be relevant to the beneficial hemodynamic effects produced by sildenafil during acute pulmonary embolism (APE), huge amounts of inducible NO synthase (iNOS)derived NO may contribute to lung injury. We hypothesized that iNOS inhibition with S-methylisothiourea could attenuate APE-induced increases in oxidative stress and pulmonary hypertension and, therefore, could improve the beneficial hemodynamic and antioxidant effects produced by sildenafil during APE. Hemodynamic evaluations were performed in non-embolized dogs treated with saline (n = 4), S-methylisothiourea (0.01 mg/kg followed by 0.5 mg/kg/h, n = 4), sildenafil (0.3 mg/kg, n = 4), or S-methylisothiourea followed by sildenafil (n = 4), and in dogs that received the same drugs and were embolized with silicon microspheres (n = 8 for each group). Plasma nitrite/nitrate (NOx) and thiobarbituric acid reactive substances (TBARS) concentrations were determined by Griess and a fluorometric assay, respectively. APE increased mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance index (PVRI) by 25 +/- 1.7 mm Hg and by 941 +/- 34 dyn s cm(-5) m(-2), respectively. S-methylisothiourea neither attenuated APE-induced pulmonary hypertension, nor enhanced the beneficial hemodynamic effects produced by sildenafil after APE (>50% reduction in pulmonary vascular resistance). While sildenafil produced no change in plasma NOx concentrations, S-methylisothiourea alone or combined with sildenafil blunted APE-induced increases in NOx concentrations. Both drugs, either alone or combined, produced antioxidant effects. In conclusion, although iNOS-derived NO may play a key role in APE-induced oxidative stress, our results suggest that the iNOS inhibitor S-methylisothiourea neither attenuates APE-induced pulmonary hypertension, nor enhances the beneficial hemodynamic effects produced by sildenafil. (C) 2010 Elsevier Inc. All rights reserved.

Improved endothelial function with simvastatin but unchanged insulin sensitivity with simvastatin or ezetimibe

In addition to their expected effects on lipid profile, lipid-lowering agents may reduce cardiovascular events because of effects on nonclassic risk factors such as insulin resistance and inflammation. Ezetimibe specifically blocks the absorption of dietary and biliary cholesterol as well as plant sterols. Although it is known that an additional reduction of low-density lipoprotein cholesterol (LDL-C) levels can be induced by the combination of ezetimibe with statins, it is not known if this can enhance some pleiotropic effects, which may be useful in slowing the atherosclerotic process. This study assessed the effects of simvastatin and ezetimibe, in monotherapy or in combination, on markers of endothelial function and insulin sensitivity. Fifty prediabetic subjects with normo- or mild-to-moderate hypercholesterolemia were randomly allocated to 2 groups receiving either ezetimibe (10 mg/d) or simvastatin (20 mg/d) for 12 weeks, after which the drugs were combined for both groups for an additional 12-week period. Clinical and laboratory parameters were measured at baseline and after 12 and 24 weeks of therapy. Homeostasis model assessment of insulin resistance index and the area under the curve of insulin were calculated. As expected, both groups receiving drugs in isolation significantly reduced total cholesterol, LDL-C, apolipoprotein B, and triglyceride levels; and additional reductions were found after the combination period (P <.05). After 12 weeks of monotherapy, plasminogen activator inhibitor-1 levels and urinary albumin excretion were lower in the simvastatin than in the ezetimibe group. No change in homeostasis model assessment of insulin resistance index, area under the curve of insulin, and adiponectin levels was observed tiller either the monotherapies or the combined therapy. However, simvastatin combined with ezetimibe provoked significant reductions in E-selectin and intravascular cellular adhesion molecule-1 levels that were independent of LDL-C changes. Our findings support claims that simvastatin may be beneficial in preserving endothelial function in prediabetic subjects with normo- or mild-to-moderate hypercholesterolemia. Alternatively, a deleterious effect of ezetimibe on the endothelial function is suggested, considering the increase in intravascular cellular adhesion molecule I and E-selectin levels. Simvastatin and ezetimibe, in isolation or in combination, do not interfere with insulin sensitivity. (C) 2010 Elsevier Inc. All rights reserved.

Can the Insulin Sensitivity Index (ISI) in Association with Insulin-like Growth Factor Binding Protein-1 Identify Insulin Resistance Early in Overweight Children?

Association between insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) has been reported. This prompted us to evaluate the power of the insulin sensitivity index (ISI) in association with IGFBP-1 to identify IR early in obese children/adolescents. OGTT was performed in 34 obese/overweight children/adolescents. Glucose, insulin and IGFBP-1 were measured in serum samples and ISI was calculated. Considering the presence of three or more risk factors for IR as a criterion for IR, ISI <4.6 showed 87.5% sensitivity and 94.5% specificity in diagnosing IR. IGFBP-1 was lower in the group with ISI <4.6 (p <0.01). In this group, three patients had higher than expected IGFBP-1, suggesting hepatic IR, while three patients with ISI >4.6 showed very low IGFBP-1 levels. Conclusion: ISI <4.6 is a good indicator of early peripheral IR and, associated with IGFBP-1, can identify increased risk of hepatic IR. Low IGFBP-1 levels among non-IR children may indicate increased portal insulin levels.

Body trunk fat and insulin resistance in post-pubertal obese adolescents

CONTEXT AND OBJECTIVE: Insulin resistance is a metabolic disorder commonly associated with excess body fat accumulation that may increase chronic disease risk. The present study was undertaken to evaluate the relationship between body composition and insulin resistance among obese adolescents. DESIGN AND SETTING: Cross-sectional study, at the Adolescence Center, Pediatric Department, Universidade Federal de São Paulo. METHODS: Body composition was assessed using dual-energy X-ray absorptiometry. Dietary intake was evaluated using a three-day dietary record. The biochemical evaluation comprised glucose, insulin, serum lipid, leptin and ghrelin measurements. Insulin resistance was calculated by means of the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Forty-nine post-pubertal obese adolescents participated in the study: 12 boys and 37 girls of mean age 16.6 (1.4) years and mean body mass index (BMI) of 35.0 (3.9) kg/m². The mean glucose, insulin and HOMA values were 90.3 (6.4) mg/dl, 16.6 (8.1) µIU/ml and 3.7 (1.9), respectively. Hyperinsulinemia and insulin resistance were observed in 40.2% and 57.1% of the subjects, respectively. Adolescents with insulin resistance had higher BMI and body trunk fat. There was a trend towards higher leptin concentration in obese individuals with insulin resistance. Insulin resistance was positively correlated with body trunk fat, BMI, body fat mass (kg), leptin and body fat percentage. Furthermore, there was a negative correlation between HOMA-IR and lean body mass. The body composition predicted 30% of the HOMA-IR levels, according to linear regression models. CONCLUSION: Body trunk fat was significantly associated with insulin resistance, demonstrating the clinical importance of abdominal obesity during adolescence.

The relationship between cortisol concentrations in pregnancy and systemic vascular resistance in childhood

Objective. To assess the relationship between cortisol concentrations in the last trimester of pregnancy and systemic vascular resistance — SVR in childhood. Materials and methods. This study is part of a cohort involving 130 Brazilian pregnant women and their children, ages 5 to 7 years. Maternal cortisol was determined in saliva by an enzyme immunoassay utilizing the mean concentration of 9 samples of saliva (3 in each different day), collected at the same time, early in the morning. SVR was assessed by the HDI/PulseWave CR-2000 Cardiovascular Profiling System®. Socioeconomic and demographic characteristics and life style factors were determined by a questionnaire. The nutritional status of the women and children was assessed by the body mass index — BMI. The association between maternal cortisol and SVR in childhood was calculated by multivariate linear regression analysis. Results.There were statistically significant associations between maternal cortisol and SVR (p = 0.043) and BMI-z score of the children (p = 0.027), controlling for maternal BMI, birth weight, age, and gender of the children. Conclusion. As far as we know this is the first study in the literature assessing the association between cortisol concentrations in pregnancy and SVR in childhood. Overall, the data suggest that exposure to excess glucocorticoid in the prenatal period is associated to vascular complications in childhood, predisposing to cardiovascular diseases in later life

The relationship between birth weight and insulin resistance in childhood

Chronic diseases that are typical of adulthood may originate in intra-uterine life through inadequate fetal development. The present epidemiological cohort study of 506 healthy children aged 5\20138 years evaluated the relationship between birth weight and insulin resistance in an age group that has been assessed in few similar studies. Insulin concentration was determined by chemiluminescence and insulin resistance by the homeostasis model assessment (HOMA). Blood glucose, total cholesterol and fractions (LDL cholesterol and HDL cholesterol) and TAG concentrations were determined by automated enzymatic methods. Linear regression analysis investigated the relationship between birth weight (assessed as a continuous variable and in three categories: small for gestational age, SGA; adequate for gestational age and large for gestational age) and the HOMA index, using backward stepwise selection and biological models to explain the causal pathway of the relationship. There were negativeassociations between birth weight (P < 0·001), SGA (P = 0·027) and the HOMA index, and a positive association between waist circumference (P < 0·001) and the HOMA index. Considering the significant associations between birth weight and waist circumference (P < 0·001) and waist circumference and insulin resistance (P < 0·001), we can probably suspect that lower birth weight is a common cause of higher waist circumference and insulin resistance. In summary, the results of the present study showed increased insulin resistance in apparently healthy, young children, who had lower weight at birth and higher measurements of waist circumference. There is a need to develop public health policies that adopt preventive measures to promote adequate maternal-fetal and child development and enable early diagnosis of metabolic abnormalities

Radial variation of anatomical features, wood density and decay resistance in teak (Tectona grandis) from two qualities of growing sites and two climatic regions of Costa Rica

The objective of this study was to show the radial variation of some anatomic characteristics, wood density and natural durability of teak (Tectona grandis L.F.) growing in Costa Rica. Samples of trees 13 years old were obtained from two growing sites (high and low growing) of plantations established in a humid tropical climate (CHT) and dry tropical climate (CST). The variables measured of the fibers as well as for the rays were not affected by the climate or the type of growing site, except for the length of the fibers. The fibers of teak wood from the best growing site were significantly larger. Vessels were found with a greater frequency for the CST but mostly solitary in comparison with the CBT. Average density, maximum density and the variation within the ring presented a light higher magnitude for the CST. The quality of the growing site did not affect these variables. The resistance of fungus attack was similar in the area of heartwood near the pith compared to the heartwood near the sapwood for all the conditions evaluated. Nevertheless, it was observed in some trees a similar resistance of fungus attack for areas of sapwood compared to similar areas of heartwood.

Effect of eight weeks of strength training on fatigue resistance in men and women

The purpose of the present study was to compare the effects of eight weeks of strength training on fatigue resistance in men and women. Thirty-three men and twenty-three women performed eight weeks of strength training in three weekly sessions. Subjects performed four sets using 80% of 1-RM tests on bench press, squat and arm curl. Fatigue index (FI) was used for analysis of decline in motor performance along the sets. The sum of the number of repetitions accomplished in the four sets in each exercise was used to indicate the fatigue resistance. Anova or Ancova two-way ( time x gender) was employed for statistical analysis ( P < 0.05). Eight weeks of strength training increased significantly 1-RM strength, fatigue resistance and total number of repetitions in both genders. FI decreased significantly in both genders after training ( men = 50% vs. women = Time x gender interaction was observed in the total number of repetitions in squat ( P = 0.04) and arm curl exercises, regarding gains to women ( P = 0.01). In conclusion, eight weeks of ST improved strength, FR, FI and total number of repetitions performed. However, women obtained greater adaptations than men.

Laparoscopic treatment of type 2 diabetes mellitus for patients with a body mass index less than 35

Background Type 2 diabetes mellitus (T2DM) is a common disease with numerous complications. Bariatric surgery is an efficient procedure for controlling T2DM in morbidly obese patients. In T2DM, the incretin effect is either greatly impaired or absent. This study aimed to evaluate the preliminary results from interposing a segment of ileum into the proximal jejunum associated with a sleeve or diverted sleeve gastrectomy to control T2DM in patients with a body mass index (BMI) less than 35 kg/m(2). Methods For this study, 39 patients (16 women and 23 men) underwent two laparoscopic procedures comprising different combinations of ileal interposition into the proximal jejunum via a sleeve or diverted sleeve gastrectomy. The mean age of these patients was 50.3 years (range, 36-66 years). The mean BMI was 30.1 kg/m(2) (range, 23.4-34.9 kg/m(2)). All the patients had a diagnosis of T2DM that had persisted for at least 3 years and evidence of stable treatment with oral hypoglycemic agents or insulin for at least 12 months. The mean duration of T2DM was 9.3 years (range, 3-22 years). Results The mean operative time was 185 min, and the median hospital stay was 4.3 days. Four major complications occurred in the short term (30-days), and the mortality rate was 2.6%. The mean postoperative follow-up period was 7 months (range, 4-16 months), and the mean percentage of weight loss was 22%. The mean postoperative BMI was 24.9 kg/m(2) (range, 18.9-31.7 kg/m2). An adequate glycemic control was achieved for 86.9% of the patients, and 13.1% had important improvement. The patients whose glycemia was not normalized were using a single oral hypoglycemic agent. No patient needed insulin therapy postoperatively. All the patients except experienced normalization of their cholesterol levels. Targeted triglycerides levels were achieved by 71% of the patients, and hypertension was controlled for 95.8%. Conclusions The laparoscopic ileal interposition via either a sleeve gastrectomy or diverted sleeve gastrectomy seems to be a promising procedure for the control of T2DM and the metabolic syndrome. A longer follow-up period is needed.

Effects of estradiol and norethisterone on lipids, insulin resistance and carotid flow

Objectives: To evaluate the lipid profile, insulin resistance and vasomotricity, and the interaction between these factors, in postmenopausal women receiving hormone therapy. Methods: A prospective, randomized, double-blind study was carried out in which 77 postmenopausal women received one of the three treatment regimens: (A) 2 mg oral micronized estradiol (E(2)) (n = 25); (B) 2 mg oral E(2) + 1 mg oral norethisterone acetate (NETA) (n = 28); or Q placebo (n = 24), daily for 6 months. Evaluations were carried out at baseline and at the end of treatment on lipid and lipoprotein profiles, homeostasis model assessment of insulin resistance (HOMA-IR) and pulsatility index (PI) of the internal carotid artery by Doppler ultrasonography. Results: Mean increases of 15.6% and 2.4% and a reduction of 6.4% in high-density lipoprotein (HDL) levels were found for the E(2), E(2) + NETA and placebo groups, respectively. Reductions of 9.5% and 3.7% and an increase of 12.1% in low-density lipoprotein (LDL), and reductions of 20.0% and 3.8% and an increase of 28.8% in the LDL:HDL ratio were found for the E(2), E(2) + NETA and placebo groups, respectively (p < 0.001 in all cases). Insulin levels and HOMA-IR decreased 12.8% and 12.3% in the E2 group and increased 12.9% and 16.0% in the E(2) + NETA group (p < 0.05), respectively. Carotid PI following treatment was 1.18 +/- 0.23, 1.38 +/- 0.20 and 1.41 +/- 0.21 for the E(2), E(2) + NETA and placebo groups, respectively (p = 0.0006). Conclusions: Oral estrogen therapy led to an improvement in lipid profile, insulin resistance and carotid blood flow, which was cancelled when NETA was associated. (c) 2008 Elsevier Ireland Ltd. All rights reserved.