Calcium intake and metabolic bone disease after eight years of Roux-en-Y gastric bypass

Background Roux-en-Y gastric bypass (RYGBP) has been found to be the most efficient way to lose weight and maintain the weight loss in morbid obesity. However, with the formation of a new stomach and the modification of intestinal anatomy, there are significant changes on physiological properties of these organs that lead to nutrient deficiency, including calcium. The objectives of this study were to evaluate calcium intake, bone metabolism, and prevalence of metabolic bone disease in women subjected to RYGBP after 8 years. Methods Food frequency questionnaire and 3-day dietary recall, laboratory tests of bone metabolism and bone mineral density were accessed. Results Calcium intake was below the recommendation in all women. Serum PTH and alkaline phosphatase were elevated, whereas vitamin D and urinary calcium were significantly lower. Also, a higher prevalence of metabolic bone disease than the one expected for the normal population at the same age was noted. Conclusion These data suggest that metabolic bone disease could be a complication of this type of surgery.

Metabolic differences between male and female adolescents with non-alcoholic fatty liver disease, as detected by ultrasound

Background: Age, developmental stage and gender are risk factors for paediatric non-alcoholic fatty liver disease (NAFLD). Aims: The aim of this study was to identify differences in clinical or laboratory variables between sexes in adolescents with NAFLD. Methodology: Ninety obese adolescents including 36 males and 54 females were evaluated. Inclusion criteria for this study were a Body Mass Index above the 95th percentile, as set forth by the National Center for Health Statistics, and an age of 10-19 years. A clinical and laboratory evaluation was conducted for all adolescents. Results: The variables that were found to be predictive of NAFLD in adolescence were visceral fat, Aminotransferase, Gamma-Glutamyl Transferase, triglyderides, cholesterol and LDL-cholesterol. We also observed that cholesterol and LDL-cholesterol variables were influenced by gender, i.e. there was a significant statistical difference in the values of these variables between male and female adolescents. With regard to cholesterol serum concentrations, the risk was 6.99 times greater for females, compared with 1.2 times for males; and for LDL-cholesterol serum concentrations the risk was 8.15 times greater for females, compared with and 1.26 times for males. Conclusion: Female adolescents with NAFLD showed a significantly different metabolic behaviour than males.

Effect of Exercise Training on Plasma Levels and Functional Properties of High-Density Lipoprotein Cholesterol in the Metabolic Syndrome

Intense lifestyle modifications can change the high-density lipoprotein (HDL) cholesterol concentration. The aim of the present study was to analyze the early effects of short-term exercise training, without any specific diet, on the HDL cholesterol plasma levels and HDL functional characteristics in patients with the metabolic syndrome (MS). We studied 30 sedentary subjects, 20 with and 10 without the MS. The patients with the MS underwent moderate intensity exercise training for 3 months on bicycle ergometers. Blood was sampled before and after training for biochemical analysis, paraoxonase-1 activity, and HDL subfraction composition and antioxidative capacity. Lipid transfer to HDL was assayed in vitro using a labeled nanoemulsion as the lipid donor. At baseline, the MS group had greater triglyceride levels and a lower HDL cholesterol concentration and lower paraoxonase-1 activity than did the controls. Training decreased the plasma triglycerides but did not change the low-density lipoprotein or HDL cholesterol levels. Nonetheless, exercise training increased the HDL subfractions` antioxidative capacity and paraoxonase-1 activity. After training, the MS group had compositional changes in the smallest HDL subfractions associated with increased free cholesterol and cholesterol ester transfers to HDL, reaching normal values. In conclusion, the present investigation has added relevant information about the dissociation between the quantitative and qualitative aspects of HDL after short-term exercise training without any specific diet in those with the MS, highlighting the importance of evaluating the functional aspects of the lipoproteins, in addition to their plasma levels. (C) 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;107:1168-1172)

Age-Related Metabolic Profiles in Cognitively Healthy Elders: Results from a Voxel-Based [(18)F]Fluorodeoxyglucose-Positron-Emission Tomography Study with Partial Volume Effects Correction

BACKGROUND AND PURPOSE: Functional brain variability has been scarcely investigated in cognitively healthy elderly subjects, and it is currently debated whether previous findings of regional metabolic variability are artifacts associated with brain atrophy. The primary purpose of this study was to test whether there is regional cerebral age-related hypometabolism specifically in later stages of life. MATERIALS AND METHODS: MR imaging and FDG-PET data were acquired from 55 cognitively healthy elderly subjects, and voxel-based linear correlations between age and GM volume or regional cerebral metabolism were conducted by using SPM5 in images with and without correction for PVE. To investigate sex-specific differences in the pattern of brain aging, we repeated the above voxelwise calculations after dividing our sample by sex. RESULTS: Our analysis revealed 2 large clusters of age-related metabolic decrease in the overall sample, 1 in the left orbitofrontal cortex and the other in the right temporolimbic region, encompassing the hippocampus, the parahippocampal gyrus, and the amygdala. The division of our sample by sex revealed significant sex-specific age-related metabolic decrease in the left temporolimbic region of men and in the left dorsolateral frontal cortex of women. When we applied atrophy correction to our PET data, none of the above-mentioned correlations remained significant. CONCLUSIONS: Our findings suggest that age-related functional brain variability in cognitively healthy elderly individuals is largely secondary to the degree of regional brain atrophy, and the findings provide support to the notion that appropriate PVE correction is a key tool in neuroimaging investigations.

Metabolic consequences of intermittent hypoxia: Relevance to obstructive sleep apnea

Obstructive sleep apnea (OSA) is recurrent obstruction of the upper airway leading to sleep fragmentation and intermittent hypoxia (IH) during sleep. There is growing evidence from animal models of OSA that IH is independently associated with metabolic dysfunction, including dyslipidemia and insulin resistance. The precise mechanisms by which IH induces metabolic disturbances are not fully understood. Over the last decade, several groups of investigators developed a rodent model of IH, which emulates the oxyhemoglobin profile in human USA. In the mouse model, IH induces dyslipidemia, insulin resistance and pancreatic endocrine dysfunction, similar to those observed in human USA. Recent reports provided new insights in possible mechanisms by which IH affects lipid and glucose metabolism. IH may induce dyslipidemia by up-regulating lipid biosynthesis in the liver, increasing adipose tissue lipolysis with subsequent free fatty acid flux to the liver, and inhibiting lipoprotein clearance. IH may affect glucose metabolism by inducing sympathetic activation, increasing systemic inflammation, increasing counter-regulatory hormones and fatty acids, and causing direct pancreatic beta-cell injury. IH models of USA have improved our understanding of the metabolic impact of USA, but further studies are needed before we can translate recent basic research findings to clinical practice. (C) 2010 Elsevier Ltd. All rights reserved.

Consequences of Comorbid Sleep Apnea in the Metabolic Syndrome-Implications for Cardiovascular Risk

Study Objectives: Metabolic syndrome (MetSyn) increases overall cardiovascular risk. MetSyn is also strongly associated with obstructive sleep apnea (OSA), and these 2 conditions share similar comorbidities. Whether OSA increases cardiovascular risk in patients with the MetSyn has not been investigated. We examined how the presence of USA in patients with MetSyn affected hemodynamic and autonomic variables associated with poor cardiovascular outcome. Design: Prospective clinical study. Participants: We studied 36 patients with MetSyn (ATP-III) divided into 2 groups matched for age and sex: (1) MetSyn+OSA (n = 18) and (2) MetSyn-OSA (n = 18). Measurements: USA was defined by an apnea-hypopnea index (AHI) > 15 events/hour by polysomnography. We recorded muscle sympathetic nerve activity (MSNA - microneurography), heart rate (HR), and blood pressure (BP - Finapres). Baroreflex sensitivity (BRS) was analyzed by spontaneous BP and HR fluctuations. Results: MSNA (34 +/- 2 vs 28 +/- 1 bursts/min, P = 0.02) and mean BP (111 +/- 3 vs. 99 +/- 2 mm Hg, P = 0.003) were higher in patients with MetSyn+OSA versus patients with MetSyn-USA. Patients with MetSyn+OSA had lower spontaneous BRS for increases (7.6 +/- 0.6 vs 12.2 +/- 1.2 msec/mm Hg, P = 0.003) and decreases (7.2 +/- 0.6 vs 11.9 +/- 1.6 msec/mm Hg, P = 0.01) in BP. MSNA was correlated with AHI (r = 0.48; P = 0.009) and minimum nocturnal oxygen saturation (r = -0.38, P = 0.04). Conclusion: Patients with MetSyn and comorbid USA have higher BP, higher sympathetic drive, and diminished BRS, compared with patients with MetSyn without USA. These adverse cardiovascular and autonomic consequences of USA may be associated with poorer outcomes in these patients. Moreover, increased BP and sympathetic drive in patients with MetSyn+OSA may be linked, in part, to impairment of baroreflex gain.

The use of sodium-chloride difference and chloride-sodium ratio as strong ion difference surrogates in the evaluation of metabolic acidosis in critically ill patients

Purpose: Inorganic apparent strong ion difference (SIDai) improves chloride-associated acidosis recognition in dysnatremic patients. We investigated whether the difference between sodium and chloride (Na+-C1-) or the ratio between chloride and sodium (Cl-/Na+) could be used as SIDai surrogates in mixed and dysnatremic patients. Patients and Methods: Two arterial blood samples were collected from 128 patients. Physicochemical analytical approach was used. Correlation, agreement, accuracy, sensitivity, and specificity were measured to examine whether Na(+)-C1(-) and CI(-)/Na(+) could be used instead of SIDai in the diagnosis of acidosis. Results: Na(+)-C1(-) and CF/Na+ were well correlated with SIDai (R = 0.987, P < 0.001 and R = 0.959, P < 0.001, respectively). Bias between Na(+)-C1(-) and SIDai was high (6.384 with a limit of agreement of 4.4638.305 mEq/L). Accuracy values for the identification of SIDai acidosis (<38.9 mEq/L) were 0.989 (95% confidence interval [CI], 0.980-0.998) for Na+-C1- and 0.974 (95% CI, 0.959-0.989) for Cr/Na+. Receiver operator characteristic curve showed that values revealing SIDai acidosis were less than 32.5 mEq/L for Nata- and more than 0.764 for C17Na+ with sensitivities of 94.0% and 92.0% and specificities of 97.0% and 90.0%, respectively. Nata- was a reliable S IDai surrogate in dysnatremic patients. Conclusions: Nata- and CI-/Na+ are good tools to disclose S IDai acidosis. In patients with dysnatremia, Nata- is an accurate tool to diagnose SIDai acidosis. (C) 2010 Elsevier Inc. All rights reserved.

The incremental role of obstructive sleep apnoea on markers of atherosclerosis in patients with metabolic syndrome

Objective: Metabolic syndrome (MS) is associated with subclinical atherosclerosis, but the relative role of obstructive sleep apnoea (OSA) is largely unknown. The main objective of this study is to determine the impact of OSA on markers of atherosclerosis in patients with MS. Methods: Eighty-one consecutive patients with MS according to the Adult Treatment Panel III underwent a clinical evaluation, polysomnography, laboratory and vascular measurements of carotid intima media thickness (IMT), carotid-femoral pulse wave velocity (PWV) and carotid diameter (CD) in a blind fashion. OSA was defined as an apnoea-hypopnoea index (AHI) >= 15 events/hour. Multiple linear regression was performed to determine the variables that were independently associated with the vascular parameters. Results: Fifty-one patients (63%) had OSA. No significant differences existed in age, sex, MS criteria, and cholesterol levels between patients with (MS+OSA) and without OSA (MS-OSA). Compared with MS-OSA patients, MS+OSA patients had higher levels of IMT (661 +/- 117 vs. 767 +/- 140 mu m), PWV (9.6 +/- 1.0 vs. 10.6 +/- 1.6 m/s), and CD (6705 +/- 744 vs. 7811 +/- 862 mu m) (P < 0.001 for each comparison). Among patients with MS+OSA, all vascular parameters were similar in patients with and without daytime sleepiness. The independent parameters associated with IMT, PWV, and CD were AHI, abdominal circumference, and systolic blood pressure (R(2) = 0.42); AHI and systolic blood pressure (R(2) = 0.38); and AHI, age, abdominal circumference and systolic blood pressure (R(2) = 0.45), respectively. The R(2) of AHI for IMT, PWV and CD was 0.12, 0.10 and 0.20, respectively. Conclusions: OSA is very common and has an incremental role in atherosclerotic burden in consecutive patients with MS. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Impact of metabolic syndrome on the outcome of patients with stable coronary artery disease: 2-year follow-up of the MASS II study

Objective We characterized the impact of the metabolic syndrome (MetS) and its components on cardiovascular adverse events in patients with symptomatic chronic multivessel coronary artery disease, which have been followed prospectively for 2 years. Methods Patients enrolled in the MASS II study were evaluated for each component of the MetS, as well as the full syndrome. Results The criteria for MetS were fulfilled in 52% of patients. The presence of MetS (P < 0.05), glucose intolerance (P=0.007), and diabetes (P=0.04) was associated with an increased mortality in our studied population. Moreover, despite a clear tendency for each of its components to increase the mortality risk, only the presence of the MetS significantly increased the risk of mortality among nondiabetic study participants in a multivariate model (P=0.03, relative risk 3.5, 95% confidence interval 1.1-6). Finally, MetS was still associated with increased mortality even after adjustment for diabetes status. These results indicate a strong and consistent relationship of the MetS with mortality in patients with stable coronary artery disease. Conclusion Although glucose homeostasis seems to be the major force driving the increased risk of MetS, the operational diagnosis of MetS still has information for stratifying patients when diabetes information is taken into account.

In Vivo Effects of Bothrops jararaca Venom on Metabolic Profile and on Muscle Protein Metabolism in Rats

This study investigated the in vivo effects of the Bothrops Jararaca venom (BjV) on general metabolic profile and, specifically. oil muscle protein metabolism in rats. The crude venom (0.4 mg/kg body weight, IV) was infused in awake rats, and plasma activity of enzymes and metabolites levels were determined after 1, 2, 3, and 4 hours. BjV increased urea, lactate, and activities of creatine kinase. lactate dehydrogenase. and aspartate aminotransferase after 4 hours. The content of liver glycogen was reduced by BjV. Protein metabolism was evaluated by means of microdialysis technique and in isolated muscles. BjV induced increase in the muscle interstitial-arterial tyrosine concentration difference. indicating a high protein catabolism. The myotoxicity induced by this venom is associated with reduction of protein synthesis and increase in rates of overall proteolysis, which was accompanied by activation of lysosomal and ubiquitin-proteasome systems without changes in protein levels of cathepsins and ubiquitin-protein conjugates.

Genetic Susceptibility Loci in Rheumatoid Arthritis Establish Transcriptional Regulatory Networks with Other Genes

Linkage studies have identified the human leukocyte antigen (HLA)-DRB1 as a putative rheumatoid arthritis (RA) susceptibility locus (SL). Nevertheless, it was estimated that its contribution was partial, suggesting that other non-HLA genes may play a role in RA susceptibility. To test this hypothesis, we conducted microarray transcription profiling of peripheral blood mononuclear cells in 15 RA patients and analyzed the data, using bioinformatics programs (significance analysis of microarrays method and GeneNetwork), which allowed us to determine the differentially expressed genes and to reconstruct transcriptional networks. The patients were grouped according to disease features or treatment with tumor necrosis factor blocker. Transcriptional networks that were reconstructed allowed us to identify the interactions occurring between RA SL and other genes, for example, HLA-DRB1 interacting with FNDC3A (fibronectin type III domain containing 3A). Given that fibronectin fragments can stimulate mediators of matrix and cartilage destruction in RA, this interaction is of special interest and may contribute to a clearer understanding of the functional role of HLA-DRB1 in RA pathogenesis.

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.

Enhanced concentrations of relevant markers of nitric oxide formation after exercise training in patients with metabolic syndrome

Metabolic syndrome (MetS) denotes a clustering of risk factors that may affect nitric oxide (NO) bioavailability and predispose to cardiovascular diseases, which are delayed by exercise training. However, no previous study has examined how MetS affects markers of NO formation, and whether exercise training increases NO formation in MetS patients. Here, we tested these two hypotheses. We studied 48 sedentary individuals: 20 healthy controls and 28 MetS patients. Eighteen MetS patients were subjected to a 3-month exercise training (E+group), while the remaining 10 MetS patients remained sedentary (E-group). The plasma concentrations of nitrite, cGMP, and ADMA (asymmetrical dimethylarginine: an endogenous nitric oxide synthase inhibitor), and the whole blood nitrite concentrations were determined at baseline and after exercise training using an ozone-based chemiluminescence assay, and commercial enzyme immunoassays. Thiobarbituric acid reactive species (TBA-RS) were measured in the plasma to assess oxidative stress using a fluorometric method. We found that, compared with healthy subjects, patients with MetS have lower concentrations of markers of NO formation, including whole blood nitrite, plasma nitrite, and plasma cGMP, and increased oxidative stress (all P < 0.05). Exercise training increased the concentrations of whole blood nitrite and cGMP, and decreased both oxidative stress and the circulating concentrations of ADMA (both P < 0.05). These findings show clinical evidence for lower endogenous NO formation in patients with MetS, and for improvements in NO formation associated with exercise training in MetS patients. (C) 2008 Elsevier Inc. All rights reserved.

Intermittent hypoxia-induced sensitization of central chemoreceptors contributes to sympathetic nerve activity during late expiration in rats

Molkov YI, Zoccal DB, Moraes DJ, Paton JF, Machado BH, Rybak IA. Intermittent hypoxia-induced sensitization of central chemoreceptors contributes to sympathetic nerve activity during late expiration in rats. J Neurophysiol 105: 3080-3091, 2011. First published April 6, 2011; doi:10.1152/jn.00070.2011.-Hypertension elicited by chronic intermittent hypoxia (CIH) is associated with elevated activity of the thoracic sympathetic nerve (tSN) that exhibits an enhanced respiratory modulation reflecting a strengthened interaction between respiratory and sympathetic networks within the brain stem. Expiration is a passive process except for special metabolic conditions such as hypercapnia, when it becomes active through phasic excitation of abdominal motor nerves (AbN) in late expiration. An increase in CO(2) evokes late-expiratory (late-E) discharges phase-locked to phrenic bursts with the frequency increasing quantally as hypercapnia increases. In rats exposed to CIH, the late-E discharges synchronized in AbN and tSN emerge in normocapnia. To elucidate the possible neural mechanisms underlying these phenomena, we extended our computational model of the brain stem respiratory network by incorporating a population of presympathetic neurons in the rostral ventrolateral medulla that received inputs from the pons, medullary respiratory compartments, and retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG). Our simulations proposed that CIH conditioning increases the CO(2) sensitivity of RTN/pFRG neurons, causing a reduction in both the CO(2) threshold for emerging the late-E activity in AbN and tSN and the hypocapnic threshold for apnea. Using the in situ rat preparation, we have confirmed that CIH-conditioned rats under normal conditions exhibit synchronized late-E discharges in AbN and tSN similar to those observed in control rats during hypercapnia. Moreover, the hypocapnic threshold for apnea was significantly lowered in CIH-conditioned rats relative to that in control rats. We conclude that CIH may sensitize central chemoreception and that this significantly contributes to the neural impetus for generation of sympathetic activity and hypertension.

Genes that code for T cell signaling proteins establish transcriptional regulatory networks during thymus ontogeny

Gene expression profiling by cDNA microarrays during murine thymus ontogeny has contributed to dissecting the large-scale molecular genetics of T cell maturation. Gene profiling, although useful for characterizing the thymus developmental phases and identifying the differentially expressed genes, does not permit the determination of possible interactions between genes. In order to reconstruct genetic interactions, on RNA level, within thymocyte differentiation, a pair of microarrays containing a total of 1,576 cDNA sequences derived from the IMAGE MTB library was applied on samples of developing thymuses (14-17 days of gestation). The data were analyzed using the GeneNetwork program. Genes that were previously identified as differentially expressed during thymus ontogeny showed their relationships with several other genes. The present method provided the detection of gene nodes coding for proteins implicated in the calcium signaling pathway, such as Prrg2 and Stxbp3, and in protein transport toward the cell membrane, such as Gosr2. The results demonstrate the feasibility of reconstructing networks based on cDNA microarray gene expression determinations, contributing to a clearer understanding of the complex interactions between genes involved in thymus/thymocyte development.