Effect of angiotensin converting enzyme inhibitor enalapril on body weight and composition in young rats

Obesity is considered a worldwide public health problem showing an increased prevalence in developing countries, with urgent need for new and more efficient drugs and therapies. Enalapril, an angiotensin-I converting enzyme inhibitor (ACEi), is classically used in antihypertensive therapies, however, earlier publications have shown that this drug could also have significant impact on body weight in rats as well as in humans, besides reducing blood pressure. The effect of this drug in the white adipose tissue has been neglected for long time, even considering that most components of the renin-angiotensin and kallikrein-kinin system are expressed in this tissue. Furthermore, the adipose tissue is considered today as one of the most important sites for endocrine/inflammatory regulation of appetite and energy output and AngII has been linked to the metabolism in this tissue. Therefore, we analyzed the influence of chronic enalapril treatment in normotensive rats at earlier ages, evaluating body weight, energy homeostasis, lipid profile and serum levels of the hormones leptin and insulin, in the presence of a standard or a palatable hyperlipidic diet regimen for one month. Our results show that enalapril treatment is able to reduce body fat on both diets, without alteration in serum lipid profile. Furthermore, animals receiving enalapril showed reduction in food intake, leptin level and energy intake. In summary, these findings show for the first time that the ACEi enalapril reduces body fat in young normotensive rats and highlights a novel target to treat obesity and associated diseases. (c) 2007 Elsevier B.V. All rights reserved.

Insulin-like peptide genes in honey bee fat body respond differently to manipulation of social behavioral physiology

Nutrient sensitive insulin-like peptides (ILPs) have profound effects on invertebrate metabolism, nutrient storage, fertility and aging. Many insects transcribe ILPs in specialized neurosecretory cells at changing levels correlated with life history. However, the major site of insect metabolism and nutrient storage is not the brain, but rather the fat body, where functions of ILP expression are rarely studied and poorly understood. Fat body is analogous to mammalian liver and adipose tissue, with nutrient stores that often correlate with behavior. We used the honey bee (Apis mellifera), an insect with complex behavior, to test whether ILP genes in fat body respond to experimentally induced changes of behavioral physiology. Honey bee fat body influences endocrine state and behavior by secreting the yolk protein precursor vitellogenin (Vg), which suppresses lipophilic juvenile hormone and social foraging behavior. In a two-factorial experiment, we used RNA interference (RNAi)-mediated vg gene knockdown and amino acid nutrient enrichment of hemolymph (blood) to perturb this regulatory module. We document factor-specific changes in fat body ilp1 and ilp2 mRNA, the bee`s ILP-encoding genes, and confirm that our protocol affects social behavior. We show that ilp1 and ilp2 are regulated independently and differently and diverge in their specific expression-localization between fat body oenocyte and trophocyte cells. Insect ilp functions may be better understood by broadening research to account for expression in fat body and not only brain.

Mars is close to venus - Female reproductive proteins are expressed in the fat body and reproductive tract of honey bee (Apis mellifera L.) drones

Vitellogenin (Vg) and lipophorin (Lp) are lipoproteins which play important roles in female reproductive physiology of insects. Both are actively taken up by growing oocytes and especially Vg and its receptor are considered as female-specifically expressed. The finding that the fat body of in honey bee (Apis mellifera) drones synthesizes Vg and is present in hemolymph has long been viewed as a curiosity. The recent paradigm change concerning the role played by Vg in honey bee life history, especially social division of labor, has now led us to investigate whether a physiological constellation similar to that seen in female reproduction may also be represented in the male sex. By means of Western blot analysis we could show that both Vg and Lp are present in the reproductive tract of adult drones, including the accessory (mucus) glands, but apparently are not secreted. Furthermore, we analyzed the transcript levels of the genes encoding these proteins (vg and lp), as well as their putative receptors (Amvgr and Amlpr) in fat body and accessory glands. Whereas lp, vg and Amlpr transcript levels decreased with age in both tissues. Amvgr mRNA levels increased with age in fat body. To our knowledge this is the first report that vitellogenin and its receptor are co-expressed in the reproductive system of a male insect. We interpret these findings as a cross-sexual transfer of a social physiological trait, associated with the rewiring of the juvenile hormone/vitellogenin circuitry that occurred in the female sex of honey bees. (C) 2010 Elsevier Ltd. All rights reserved.

Preoperative respiratory muscle dysfunction is a predictor of prolonged invasive mechanical ventilation in cardiorespiratory complications after heart valve surgery

Objective: To verify whether preoperative respiratory muscle strength and ventilometric parameters, among other clinically relevant factors, are associated with the need for prolonged invasive mechanical ventilation (PIMV) due to cardiorespiratory complications following heart valve surgery. Methods: Demographics, preoperative ventilometric and manometric data, and the hospital course of 171 patients, who had undergone heart valve surgery at Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto, were prospectively collected and subjected to univariate analysis for identifying the risk factors for PIMV. Results: The hospital mortality was 7%. About 6% of the patients, who had undergone heart valve surgery required PIMV because of postoperative cardiorespiratory dysfunction. Their hospital mortality was 60% (vs 4%, p < 0.001). Univariate analysis revealed that preoperative respiratory muscle dysfunction, characterized by maximal inspiratory and expiratory pressure below 70% of the predicted values combined with respiratory rate above 15 rpm during ventilometry, was associated with postoperative PIMV (p = 0.030, odds ratio: 50, 95% confidence interval (CI): 1.2-18). Postoperative PIMV was also associated with: (1) body mass index (BMI) < 18.5 (odds ratio: 7.2, 95% CI: 1.5-32), (2) body weight < 50 kg (odds ratio: 6.5, 95% CI: 1.6-25), (3) valve operation due to acute endocarditis (odds ratio: 5.5, 95% CI: 0.98-30), and (4) concomitant operation for mitral and tricuspid valve dysfunction (p = 0.047, odds ratio: 5.0, 95% CI: 1.1-22). Conclusion: Our results have demonstrated that respiratory muscle dysfunction, among other clinical factors, is associated with the need for PIMV due to cardiovascular or pulmonary dysfunction after heart valve surgery. (C) 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B. V. All rights reserved.

Folic acid supplementation during early hepatocarcinogenesis: cellular and molecular effects

Folic acid (FA) supplementation during carcinogenesis is controversial. Considering the impact of liver cancer as a public health problem and mandatory FA fortification in several countries, the role of FA supplementation in hepatocarcinogenesis should be elucidated. We evaluated FA supplementation during early hepatocarcinogenesis. Rats received daily 0.08 mg (FA8 group) or 0.16 mg (FA16 group) of FA/100 g body weight or water (CO group, controls). After a 2-week treatment, animals were subjected to the ""resistant hepatocyte"" model of hepatocarcinogenesis (initiation with diethylnitrosamine, selection/promotion with 2-acetylaminofluorene and partial hepatectomy) and euthanized after 8 weeks of treatment. Compared to the CO group, the FA16 group presented: reduced (p < 0.05) number of persistent and increased (p < 0.05) number of remodeling glutathione S-transferase (GST-P) positive preneoplastic lesions (PNL); reduced (p < 0.05) cell proliferation in persistent GST-P positive PNL; decreased (p < 0.05) hepatic DNA damage; and a tendency (p < 0.10) for decreased c-myc expression in microdissected PNL. Regarding all these parameters, no differences (p > 0.05) were observed between CO and FA8 groups. FA-treated groups presented increased hepatic levels of S-adenosylmethionine but only FA16 group presented increased S-adenosylmethionine/S-adenosylhomocysteine ratio. No differences (p > 0.05) were observed between experimental groups regarding apoptosis in persistent and remodeling GST-P positive PNL, and global DNA methylation pattern in microdissected PNL. Altogether, the FA16 group, but not the FA8 group, presented chemopreventive activity. Reversion of PNL phenotype and inhibition of DNA damage and of c-myc expression represent relevant FA cellular and molecular effects.

PREDICTION OF FAT-FREE MASS BY BIOELECTRICAL IMPEDANCE ANALYSIS IN OLDER ADULTS FROM DEVELOPING COUNTRIES: A CROSS-VALIDATION STUDY USING THE DEUTERIUM DILUTION METHOD

Objective: Several limitations of published bioelectrical impedance analysis (BIA) equations have been reported. The aims were to develop in a multiethnic, elderly population a new prediction equation and cross-validate it along with some published BIA equations for estimating fat-free mass using deuterium oxide dilution as the reference method. Design and setting: Cross-sectional study of elderly from five developing countries. Methods: Total body water (TBW) measured by deuterium dilution was used to determine fat-free mass (FFM) in 383 subjects. Anthropometric and BIA variables were also measured. Only 377 subjects were included for the analysis, randomly divided into development and cross-validation groups after stratified by gender. Stepwise model selection was used to generate the model and Bland Altman analysis was used to test agreement. Results: FFM = 2.95 - 3.89 (Gender) + 0.514 (Ht(2)/Z) + 0.090 (Waist) + 0.156 (Body weight). The model fit parameters were an R(2), total F-Ratio, and the SEE of 0.88, 314.3, and 3.3, respectively. None of the published BIA equations met the criteria for agreement. The new BIA equation underestimated FFM by just 0.3 kg in the cross-validation sample. The mean of the difference between FFM by TBW and the new BIA equation were not significantly different; 95% of the differences were between the limits of agreement of -6.3 to 6.9 kg of FFM. There was no significant association between the mean of the differences and their averages (r = 0.008 and p = 0.2). Conclusions: This new BIA equation offers a valid option compared with some of the current published BIA equations to estimate FFM in elderly subjects from five developing countries.

Histoplasma capsulatum Cell Wall beta-Glucan Induces Lipid Body Formation through CD18, TLR2, and Dectin-1 Receptors: Correlation with Leukotriene B(4) Generation and Role in HIV-1 Infection

Histoplasma capsulatum (Hc) is a facultative, intracellular parasite of worldwide significance. Infection with Hc produces a broad spectrum of diseases and may progress to a life-threatening systemic disease, particularly in individuals with HIV infection. Resolution of histoplasmosis is associated with the activation of cell-mediated immunity, and leukotriene B(4) plays an important role in this event. Lipid bodies (LBs) are increasingly being recognized as multifunctional organelles with roles in inflammation and infection. In this study, we investigated LB formation in histoplasmosis and its putative function in innate immunity. LB formation in leukocytes harvested from Hc-infected C57BL/6 mice peaks on day 2 postinfection and correlates with enhanced generation of lipid mediators, including leukotriene B(4) and PGE(2). Pretreatment of leukocytes with platelet-activating factor and BLT1 receptor antagonists showed that both lipid mediators are involved in cell signaling for LB formation. Alveolar leukocytes cultured with live or dead Hc also presented an increase in LB numbers. The yeast alkali-insoluble fraction 1, which contains mainly beta-glucan isolated from the Hc cell wall, induced a dose- and time-dependent increase in LB numbers, indicating that beta-glucan plays a signaling role in LB formation. In agreement with this hypothesis, beta-glucan-elicited LB formation was inhibited in leukocytes from 5-LO(-/-), CD18(low) and TLR2(-/-) mice, as well as in leukocytes pretreated with anti-Dectin-1 Ab. Interestingly, human monocytes from HIV-1-infected patients failed to produce LBs after beta-glucan stimulation. These results demonstrate that Hc induces LB formation, an event correlated with eicosanoid production, and suggest a role for these lipid-enriched organelles in host defense during fungal infection. The Journal of Immunology, 2009, 182: 4025-4035.

Error in body weight estimation leads to inadequate parenteral anticoagulation

Parenteral anticoagulation is a cornerstone in the management of venous and arterial thrombosis. Unfractionated heparin has a wide dose/response relationship, requiring frequent and troublesome laboratorial follow-up. Because of all these factors, low-molecular-weight heparin use has been increasing. Inadequate dosage has been pointed out as a potential problem because the use of subjectively estimated weight instead of real measured weight is common practice in the emergency department (ED). To evaluate the impact of inadequate weight estimation on enoxaparin dosage, we investigated the adequacy of anticoagulation of patients in a tertiary ED where subjective weight estimation is common practice. We obtained the estimated, informed, and measured weight of 28 patients in need of parenteral anticoagulation. Basal and steady-state (after the second subcutaneous shot of enoxaparin) anti-Xa activity was obtained as a measure of adequate anticoagulation. The patients were divided into 2 groups according the anticoagulation adequacy. From the 28 patients enrolled, 75% (group 1, n = 21) received at least 0.9 mg/kg per dose BID and 25% (group 2, n = 7) received less than 0.9 mg/kg per dose BID of enoxaparin. Only 4 (14.3%) of all patients had anti-Xa activity less than the inferior limit of the therapeutic range (<0.5 UI/mL), all of them from group 2. In conclusion, when weight estimation was used to determine the enoxaparin dosage, 25% of the patients were inadequately anticoagulated (anti-Xa activity <0.5 UI/mL) during the initial crucial phase of treatment. (C) 2011 Elsevier Inc. All rights reserved.

Body composition assessment of undernourished older subjects by dual-energy x-ray absorptiometry and bioelectric impedance analysis

The prevention and treatment of diseases related to changes in body composition require accurate methods for the measurement of body composition. However, few studies have dealt specifically with the assessment of body composition of undernourished older subjects by different methodologies. To assess the body composition of undernourished older subjects by two different methods, dual energy x-ray absorptiometry (DXA) and bioelectric impedance (BIA), and to compare results with those of an eutrophic group. The study model was cross-sectional; the study was performed at the University Hospital of the School of Medicine of Ribeiro Preto, University of So Paulo, Brazil. Forty-one male volunteers aged 62 to 91 years. The groups were selected on the basis of anamnesis, physical examination and nutritional assessment according to the Mini Nutritional Assessment (MNA) score. Body composition was assessed by DXA and BIA. Body weight, arm and calf circumference, body mass index (BMI), fat free mass (FFM) and fat mass (FM) were significantly lower in the undernourished group as compared to the eutrophic group. There were no significant differences between FFM and FM mean values determined by DXA and BIA in both groups, but the agreement between methods in the undernourished group was less strong. Our results suggest caution when BIA is to be applied in studies including undernourished older subjects. This study does not support BIA as an accurate method for the individual assessment of body composition.

Comparison of bioelectrical impedance with skinfold thickness and x-ray absorptiometry to measure body composition in HIV-infected with lipodistrophy

Introduction: Human immunodeficiency virus (HIV)associated lipodystrophy syndrome (LS) includes body composition and metabolic alterations. Lack of validated criteria and tools make difficult to evaluate body composition in this group. Objective: The aim of the study was to compare different methods to evaluate body composition between Brazilians HIV subjects with (HIV+LIPO+) or without LS (HIV+LIPO-) and healthy subjects (Control). Methods: in a cross-sectional analyses, body composition was measured by bioelectrical impedance analysis (BIA), skinfold thickness (SF) and dual-energy x-ray absorptiometry (DXA) in 10 subjects from HIV+LIPO+ group; 22 subjects from HIV+LIPO- group and 12 from Control group. Results: There were no differences in age and body mass index (BMI) between groups. The fat mass (FM) (%) estimated by SF did not correlate with DXA in HIV+LIPO+ group (r = 0,46/p >0,05) and had fair agreement in both HIV groups (HIV+LIPO+ =0,35/ HIV+ LIPO- = 0,40). BIA had significant correlation in all groups (p < 0,05) and strong agreement, meanly in HIV groups, for FM (HIV+LIPO+ = 0,79/ HIV+LIPO- = 0,85/Control = 0,60) and for fat free mass (FFM) (HIV+LIPO+ = 0,93/ HIV+LIPO- = 0,92 / Control = 0,73). Discussion: Total fat mass can be measured by BIA with good precision, but not by SF in HIV-infected patients with LS. Segmental BIA, triciptal SF, circumferences of arms, waist and legs maybe alternatives that need more studies.

Cultural consonance and adult body composition in urban Brazil

In previous research in Brazil, we found socioeconomic and gender differences in body mass and percent body fat, consistent with a model in which individuals in higher socioeconomic strata, especially women, could achieve a cultural ideal of body size and shape. In this article, using new data, we examine these processes more precisely using measures of cultural consonance. Cultural consonance refers to the degree to which individuals approximate, in their own beliefs and behaviors, the shared prototypes for belief and behavior encoded in cultural models. We have found higher cultural consonance in several domains to be associated with health outcomes. Furthermore, there tends to be a general consistency in cultural consonance across domains. Here we suggest that measures of body composition can be considered indicators of individuals` success in achieving cultural ideals of the body, and that cultural consonance in several domains will be associated with body composition. Using waist circumference as an outcome, smaller waist size was associated with higher cultural consonance in lifestyle (beta = -0.311, P < 0.01) and higher cultural consonance in the consumption of high prestige foods (beta = -0.260, P < 0.01) for women (n = 161), but not for men (n = 106), controlling for age, family income, tobacco use, and dietary intake of protein and carbohydrates. Similar results were obtained using the body mass index and weight as outcomes, while there were no associations with height. These results help to illuminate the cultural mediation of body composition.

Upper trunk fat assessment and its relationship with metabolic and biochemical variables and body fat in polycystic ovary syndrome

Background: Fat accumulation in the upper region of the body is common in polycystic ovary syndrome (PCOS) and is associated with metabolic complications. The present study aimed to assess the relationship between trunk circumference, metabolic indicators, and abdominal and visceral fat in obese PCOS women. Methods: The weight, fat mass, and subcutaneous arm fat (SAF) of 30 obese PCOS women and 15 healthy controls matched for age and body mass index were evaluated by bioelectrical impedance analysis. Trunk (TrC), neck (NC) and hip circumferences were measured, and the trunk/hip (Tr/H) ratio was determined. Total abdominal fat (TAF), visceral fat (VF) and trunk fat (TrF) were determined by computed tomography. Biochemical evaluation included glycaemia, insulinaemia, testosterone and lipid profile, insulin resistance (IR) was assessed by the QUICKI index. Results: In the PCOS group, there were positive correlations between NC and TAF (r = 0.49, P < 0.0006), TrC and VF (r = 0.62, P = 0.01), and NC and VF (r = 0.70, P < 0.0002). There was good correlation between TrC and TrF (r = 0.69, P = 0.003). TrF correlated with triglycerides levels positively (r = 0.44, P = 0.02). Women with PCOS and IR had a larger quantity of VF and TrF, but a smaller amount of SAF. Within the PCOS group, women with Tr/H ratio above the median had higher basal insulin levels and lower QUICKI indices compared to women presenting a Tr/H ratio below the median. Conclusions: TrC is associated with important metabolic variables in PCOS, proving to be a valuable and innovative tool for assessment of body adiposity distribution in obese PCOS women.

Roux-en-Y Bypass Gastroplasty: Markers of Oxidative Stress 6 Months After Surgery

This study examined the effect of weight loss on energy intake, vitamin C, E, beta-carotene (diet/blood), reduced glutathione (GSH), C-reactive protein (CRP), thiobarbituric acid reactive substances (TBARS), catalase, and myeloperoxidase, in patients with Roux-en-Y bypass gastroplasty. Prospective clinical study with control (C) and bariatric (B) groups (n = 20 each). Age was 38.8 +/- 11.1 (C) and 37.8 +/- 11.2 years (B), and body mass indices (BMI) were 22.4 +/- 2.4 and 48.1 +/- 8.7 kg/m(2), respectively. Group C was assessed on a single occasion and B at three time points (basal period and 3 and 6 months after gastroplasty). BMI was decreased at three (38.3 +/- 1.7, P = 0.018) and 6 months after surgery (34.9 +/- 1.7, P < 0.001). Mean weight loss was 20.53 +/- 1.1 after three and 27.96 +/- 1.3 kg after 6 months. Serum vitamin C and beta-carotene (P < 0.01 and P < 0.001, respectively) were increased at 6 months compared to basal. Basal serum vitamin C (P = 0.001) and beta-carotene (P < 0.001) were lower compared to controls. Serum vitamin E corrected for cholesterol and triglycerides was higher in group B at three (P = 0.01) and 6 months (P = 0.001) and lower at basal (P < 0.001) compared to controls. GSH was higher in controls (P < 0.001) compared to basal. Catalase (P = 0.01) and TBARS (P < 0.001) were higher in group B at 6 months. TBARS were higher (P < 0.001) at basal compared to controls. Myeloperoxidase and CRP decreased in group B after three (P = 0.028, P = 0.010) and 6 months (P < 0.001, P = 0.001), respectively. Roux-en-Y bypass gastroplasty led to decreased proinflammatory parameters together with increased nutritional antioxidants, catalase, and TBARS, and decreased GSH 6 months after surgery.

Dopamine microinjected into brainstem of awake rats affects baseline arterial pressure but not chemoreflex responses

Dopamine (DA) is a neuromodulator in the brainstem involved with the generation and modulation of the autonomic and respiratory activities. Here we evaluated the effect of microinjection of DA intracistema magna (icm) or into the caudal nucleus tractus solitarii (cNTS) on the baseline cardiovascular and respiratory parameters and on the cardiovascular and respiratory responses to chemoreflex activation in awake rats. Guide cannulas were implanted in cisterna magna or cNTS and femoral artery and vein were catheterized. Respiratory frequency (f(R)) was measured by whole-body plethysmography. Chemoreflex was activated with KCN (iv) before and after microinjection of DA icm or into the cNTS bilaterally while mean arterial pressure (MAP), heart rate (HR) and f(R) were recorded. Microinjection of DA icm (n = 13), but not into the cNTS (n = 8) produced a significant decrease in baseline MAP (-15 +/- 1 vs 1 +/- 1 mm Hg) and HR (-55 +/- 11 vs -11 +/- 17 bpm) in relation to control (saline with ascorbic acid, n = 9) but no significant changes in baseline f(R). Microinjection of DA icm or into the cNTS produced no significant changes in the pressor, bradycardic and tachypneic responses to chemoreflex activation. These data show that a) DA icm affects baseline cardiovascular regulation, but not baseline f(R) and autonomic and respiratory components of chemoreflex and b) DA into the cNTS does not affect either the autonomic activity to the cardiovascular system or the autonomic and respiratory responses of chemoreflex activation. (C) 2010 Elsevier B.V. All rights reserved.