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.

The potential role of C-reactive protein in distinguishing cytomegalovirus from tuberculosis and bacterial infections in renal transplant recipients

Introduction: The delay in the diagnosis of infections can be deleterious in renal transplant recipients. Thus, laboratory tests leading to an earlier diagnosis are very useful for these patients. Purpose: To assess the behavior of C-reactive protein (CRP) in renal transplant recipients with a diagnosis of cytomegalovirus (CMV) infection, tuberculosis (TB) and bacterial infection (BI). Methods: A retrospective analysis of 129 patients admitted at our hospital, from 2006 to 2008 because of CMV, TB or BI, was carried out. Appropriate statistical analysis was done and values were expressed as medians, range. Results: When CRP levels were compared among the groups with CMV disease, TB or BI, the group with CMV disease presented lower levels of CRP (18.4 mg/L, 0.28-44 mg/L) than the TB and BI (p < 0.05) groups. The area under the receiver-operating characteristics curve, distinguishing CMV disease from TB/BI, was 0.96 (p < 0.0001), resulting in 100% sensitivity and 90.63% specificity to detect CMV disease when CRP < 44.5 mg/L. The subgroup analysis of CMV infection showed increasing levels of CRP (0.28, 16 and 29.5 mg/L) in the asymptomatic, symptomatic and invasive disease subgroups, respectively (p < 0.05). Conclusion: The measurement of CRP levels may be a useful tool for differentiating CMV infection from the other types (bacterial or TB) of infection in kidney transplant recipients.

Influence of Single-Nucleotide Polymorphisms on C-Reactive Protein Levels in Chronic Kidney Disease Before and After Kidney Transplantation

Introduction. We sought to evaluate 2 sing] e-nucleotide polymorphisms (SNPs) in the C-reactive protein (CRP) gene promoter region for their effects on CRP levels in chronic kidney disease (CKD) patients before and after a successful kidney transplantation. Methods. Fifty CKD patients were evaluated before and at the first and second years after the graft. Two SNPs were studied, a bi-allelic (G -> A) at the -409 and a tri-allelic (C -> T -> A) variation at the -390 position in the CRP gene. Results. All patients presented the -409GG genotype. At the -390 position, the ""A"" allele was not found; there were 15 ""CC"" patients, 11 ""TT"" patients, and 24 ""CT"" patients. CRP levels were different among patients with various genotypes (P < .019). Also the presence of the allele ""T"" was sufficient to determine differences in CRP levels both in pretransplantation (P = .045) and at 1 year posttransplantation (P = .011), but not at the second year (P = .448). Conclusion. SNPs at the -390 position of the CRP gene promoter region influence CRP basal levels in such a way that the ""C"" allele correlated with the lowest and the ""T"" with the highest. We did not observe this influence in our patients at the second year posttransplantation.

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.

Age-related increase of reactive oxygen species in neat semen in healthy fertile men

OBJECTIVES The effects of advancing paternal age on the male reproductive system are well known, but its effects on fecundity remain controversial. Although oxidative stress is associated with poor semen quality and function, a relationship with advancing male age has not been established. The objective of this study was to analyze the relationship between male age and seminal reactive oxygen species (ROS) levels in men presenting for voluntary sterilization. METHODS We prospectively evaluated 98 fertile men who were candidates for vasectomy. These were divided into 2 age groups: less than 40 years (n = 78) and 40 or more years (n = 20). We used 46 infertile patients as positive controls. Standard semen analysis, seminal leukocyte count and ROS levels were measured in all samples. Fertile men with leukocytospermia were excluded. RESULTS The mean age of the men was 35.1 +/- 5.6 years. Men 40 years and older had significantly higher ROS levels compared with younger men (P < 0.001). We observed a positive correlation between seminal ROS levels and age (r = 0.20; P = 0.040). In addition, ROS was negatively correlated with sperm concentration (r = -0-48; P < 0.001) and motility (r = -0.21; P = 0.030). CONCLUSIONS Reactive oxygen species levels are significant higher in seminal ejaculates of healthy fertile men older than 40 years. ROS levels in whole ejaculate are significantly correlated to age among fertile men. Because ROS are clearly implicated in the pathogenesis of male infertility, these data suggest that delayed fatherhood may reduce the chances of pregnancy as men become progressively less fertile with age.

Non-Human Leukocyte Antigen Antibodies Reactive with Endothelial Cells Could Be Involved in Early Loss of Renal Allografts

Preformed donor-specific human leukocyte antigen (HLA) antibodies have been associated with allograft dysfunction and failure. However, recipients of HLA-identical kidneys can develop acute humoral rejection, implicating putative pathogenic antibodies that are directed against non-HLA antigens. We investigated the presence of endothelial cell reactive antibodies in 11 patients who experienced early loss of their transplanted kidneys owing to humoral rejection and 1 loss from renal venal thrombosis. We examined the potential efficacy of intravenous immunoglobulin to block the binding of these antibodies, as previously suggested for anti-HLA antibodies.

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.

Cross-reactive IgE antibody responses to tropomyosins from Ascaris lumbricoides and cockroach

Background: Evidence indicates that infection with Ascaris lumbricoides may promote development of allergy and asthma. Objective: To study the role of tropomyosin, a pan-allergen in invertebrates, in IgE responses to A lumbricoides. Methods: Recombinant A lumbricoides and Periplaneta americana tropomyosins were expressed in Pichia pastoris. Levels of IgE to tropomyosins from A lumbricoides and P americana were determined by chimeric ELISA in sera from 119 children living in a parasite-endemic area and 112 patients with cockroach allergy from the allergy clinics. Presence of tropomyosin in A lumbricoides larvae at L3 stage was evaluated by immunofluorescence using mAb IA6, directed against mite tropomyosin. Molecular modeling of P americana and A lumbricoides tropomyosins was performed by using the MODELLER program. Results: A lumbricoides tropomyosin showed 69% to 98% sequence identity to tropomyosins from other invertebrates. The predicted structure of A lumbricoides tropomyosin was similar to that of P americana tropomyosin and showed the characteristic coiled-coil structure. Strong correlation was found for IgE antibodies to tropomyosins from A lumbricoides and P americana in sera from children living in a parasite-endemic area and from patients with cockroach allergy. Larvae of A lumbricoides reacted strongly with mAb IA6. Conclusion: Tropomyosin induces IgE responses in A lumbricoides-infected children and in patients allergic to cockroach.

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.

Diagnostic value of interleukin-6 and C-reactive protein on early onset bacterial infection in preterm neonates with respiratory distress

Aims: To evaluate the C-reactive protein (CRP) and interleukin-6 (IL-6) as diagnostic tools for early onset infection in preterm infants with early respiratory distress (RD). Methods: CRP and IL-6 were quantified at identification of RD and 24 h after in 186 newborns. Effects of maternal hypertension, mode of delivery, Apgar score, birth weight, gestational age, mechanical ventilation, being small for gestational age (SGA), and the presence of infection were analyzed. Results: Forty-four infants were classified as infected, 42 as possibly infected, and 100 as uninfected. Serum levels of IL-6 (0 h), CRP (0 h), and CRP (24 h), but not IL-6 (24 h) were significantly higher in infected infants compared to the remaining groups. The best test for identification of infection was the combination of IL-6 (0 h) 36 pg/dL and/or CRP (24 h) 0.6 mg/dL, which yielded 93% sensitivity and 37% specificity. The presence of infection and vaginal delivery independently increased IL-6 (0 h), CRP (0 h) and CRP (24 h) levels. Being SGA also increased the CRP (24 h) levels. IL-6 (24 h) was independently increased by mechanical ventilation. Conclusions: The combination of IL-6 (0 h) and/or CRP (24 h) is helpful for excluding early onset infection in preterm infants with RD but the poor specificity limits its potential benefit as a diagnostic tool.

The Association of Lipodystrophy and Oxidative Stress Biomarkers in HIV-Infected Men

The aim of this study was to describe the status of oxidative stress and antioxidant biomarkers and their association with metabolic and body composition components of HIV-lipodystrophy syndrome. In a cross-sectional study of blood samples from HIV-infected men with lipodystrophy syndrome (HIV+LIPO+ = 10), HIV-infected men without lipodystrophy syndrome (HIV+LIPO- = 22), and healthy subjects (control = 12), the following oxidative stress biomarkers were analyzed: total hydroperoxide, thiobarbituric acid reactive substances (TBARS), and advanced oxidation protein products (AOPP). In addition, antioxidant biomarkers, including total glutathione, uric acid, alpha-tocopherol, and metabolic components were tested. Dual-energy x-ray absorciometry (DXA) was used to measure the fat mass. The duration of HIV infection and the duration and type of highly active antiretroviral therapy were similar between the two HIV-infected groups. Higher levels of total hydroperoxide were observed in the HIV+LIPO+ (50 +/- 33 H(2)O(2)/L) group compared to the HIV+LIPO-(19 +/- 13 H(2)O(2)/L) and control (5 +/- 5 H(2)O(2)/L) groups (p < 0.05). Similarly, higher levels of AOPP were observed in the HIV+LIPO+ (326 +/- 173 mu mol/L) group compared to the HIV+LIPO- (105 +/- 92 mu mol/L) and control groups (80 +/- 20 mu mol/L) (p < 0.05). Total hydroperoxide significantly correlated with insulin serum levels in the HIV+LIPO+ (r = 0.47, p < 0.05) and HIV+LIPO- groups (r = 0.29, p < 0.05), while AOPP significantly correlated with insulin serum levels in the HIV+LIPO+ (r = 0.73, p < 0.05) and HIV+LIPO- (r = 0.54, p < 0.05) groups. Therefore, higher lipid and protein oxidation were found in HIV-infected patients with lipodystrophy syndrome, and both were associated with insulin levels.

Detrimental role of endogenous nitric oxide in host defence against Sporothrix schenckii

We earlier demonstrated that nitric oxide (NO) is a fungicidal molecule against Sporothrix schenckii in vitro. In the present study we used mice deficient in inducible nitric oxide synthase (iNOS(-/-)) and C57BL/6 wild-type (WT) mice treated with N omega-nitro-arginine (Nitro-Arg-treated mice), an NOS inhibitor, both defective in the production of reactive nitrogen intermediates, to investigate the role of endogenous NO during systemic sporotrichosis. When inoculated with yeast cells of S. schenckii, WT mice presented T-cell suppression and high tissue fungal dissemination, succumbing to infection. Furthermore, susceptibility of mice seems to be related to apoptosis and high interleukin-10 and tumour necrosis factor-alpha production by spleen cells. In addition, fungicidal activity and NO production by interferon-gamma (IFN-gamma) and lipopolysaccharide-activated macrophages from WT mice were abolished after fungal infection. Strikingly, iNOS(-/-) and Nitro-Arg-treated mice presented fungal resistance, controlling fungal load in tissues and restoring T-cell activity, as well as producing high amounts of IFN-gamma Interestingly, macrophages from these groups of mice presented fungicidal activity after in vitro stimulation with higher doses of IFN-gamma. Herein, these results suggest that although NO was an essential mediator to the in vitro killing of S. schenckii by macrophages, the activation of NO system in vivo contributes to the immunosuppression and cytokine balance during early phases of infection with S. schenckii.

Safety of the etonogestrel-releasing implant during the immediate postpartum period: a pilot study

Background: The effects of etonogestrel (ETG)-releasing contraceptive implant during the immediate postpartum period on maternal safety are unknown. Study design: Forty healthy women exclusively breastfeeding were randomized to receive either ETG-releasing implant 24-48 h after delivery (n=20) or depot medroxyprogesterone acetate (DMPA group; n=20) at the sixth week postpartum. We measured blood pressure, maternal and neonatal weight, body mass index (BMI; kg/m(2)), waist circumference (WC), complete blood count, C-reactive protein, interleukin-6, tumor necrosis factor (TNF-alpha), lipid profile, fasting serum glucose and maintenance of exclusive lactation up to the 12th week postpartum. Results: Decreases in mean maternal weight, BMI (kg/m(2)) and WC were significantly greater in the ETG-releasing implant group than in the MPA group during the first 6 weeks postpartum (-4.64 +/- 2.71 kg vs. -2.6 +/- 2.45 kg mean +/- SD, p=.017; -1.77 +/- 1.06 kg/m(2) vs. -0.97 +/- 0.95 kg/m(2), p=.026; -15.3 +/- 6.72 cm vs. -9.05 +/- 5.84 cm, p=.003, respectively). In addition, total cholesterol and HDL, were lower in DMPA users, and TNF-alpha and leukocytes were higher in DMPA users compared to in the implant group, between 6 and 12 weeks after delivery. The newborns of implant users showed a trend towards gaining more weight, as compared with the infants of the DMPA mothers during the first 6 weeks of life (implant group: +1460.50 +/- 621.34 g vs. DMPA group: +1035.0 +/- 562.43 g, p=.05). The remaining variables, including the duration of exclusive breastfeeding, were similar between the groups. Conclusion: The insertion of ETG-releasing contraceptive implant during the immediate postpartum period was not associated with deleterious maternal clinical effects or with significant maternal metabolic alterations or decreased infant weight gain. (C) 2009 Elsevier Inc. All rights reserved.

Increased arterial stiffness in nonobese women with polycystic ovary syndrome (PCOS) without comorbidities: one more characteristic inherent to the syndrome?

Background Polycystic ovary syndrome (PCOS) is associated with adverse metabolic effects. Some cardiovascular disease (CVD) risk markers are increased in women with PCOS. However, early markers of atherosclerosis are also associated with obesity and insulin resistance, which are related to PCOS. These markers may result either directly from PCOS or indirectly as a consequence of the comorbidities associated with the syndrome. Context To assess the presence of early CVD markers in young, nonobese women with PCOS. Patients Forty women with PCOS and 50 healthy women with regular menstrual cycles, matched for age and body mass index (BMI). Measurements The following CVD markers were assessed by ultrasonography: common carotid artery (CCA) stiffness index (beta), distensibility and intima-media thickness (IMT), and brachial artery flow-mediated dilatation (FMD). Inflammatory markers, including interleukin (IL)-6, tumour necrosis factor (TNF)-alpha, homocysteine, C-reactive protein (CRP), glycaemia, lipid profile and insulin, were also assessed. Results CCA beta was higher in PCOS than in control women (3 center dot 72 +/- 0 center dot 96 vs. 3 center dot 36 +/- 0 center dot 96, P = 0 center dot 04) and CCA distensibility was lower (0 center dot 31 +/- 0 center dot 08 vs. 0 center dot 35 +/- 0 center dot 09 mmHg(-1), P = 0 center dot 02). Waist circumference, total testosterone and the Free Androgen Index (FAI) were higher in PCOS patients than in controls (78 center dot 2 +/- 10 center dot 0 vs. 71 center dot 5 +/- 7 center dot 2 cm, P = 0 center dot 001; 88 center dot 1 +/- 32 center dot 4 vs. 57 center dot 1 +/- 21 center dot 2 ng/dl, P < 0 center dot 01; 12 center dot 7 +/- 15 center dot 7%vs. 4 center dot 7 +/- 2 center dot 3%, P < 0 center dot 01, respectively), while SHBG was reduced (37 center dot 9 +/- 19 center dot 1 vs. 47 center dot 8 +/- 18 center dot 3 nmol/l, P = 0 center dot 01). The remaining variables did not differ between the groups. Conclusions Young women with PCOS exhibit changes in vascular elasticity even in the absence of classical risk factors for CVD, such as hypertension and obesity.

Progression of Lipid Peroxidation Measured as Thiobarbituric Acid Reactive Substances, Damage to DNA and Histopathological Changes in the Liver of Rats Subjected to a Methionine-Choline-Deficient Diet

Methionine-choline-deficient diet represents a model for the study of the pathogenesis of steatohepatitis. Male rats were divided into three groups, the first group receiving a control diet and the other two groups receiving a methionine-choline-deficient diet for 1 month (MCD1) and for 2 months (MCD2), respectively. The livers of the animals were collected for the determination of vitamin E, thiobarbituric acid reactive substances (TBARS), GSH concentration, DNA damages, and for histopathological evaluation. The hepatic TBARS and GSH content was higher (P < 0.05) in the groups receiving the experimental diet (MCD1 and MCD2) compared to control diet, and hepatic vitamin E concentration differed (P < 0.05) between the MCD1 and MCD2 groups, with the MCD2 group presenting a lower concentration. Damage to hepatocyte DNA was greater (P < 0.05) in the MCD2 group (262.80 DNA injuries/100 hepatocytes) compared to MCD1 (136.4 DNA injuries/100 hepatocytes) and control diet (115.83 DNA injuries/100 hepatocytes). Liver histopathological evaluation showed that steatosis, present in experimental groups was micro- and macro-vesicular and concentrated around the centrolobular vein, zone 3, with preservation of the portal space. The inflammatory infiltrate was predominantly periductal and the steatosis and inflammatory infiltrate was similar in the MCD1 and MCD2 groups, although the presence of Mallory bodies was greater in the MCD2 group. The study describes the contribution of a methionine-choline-deficient diet to the progression of steatosis, lipid peroxidation and hepatic DNA damage in rats, serving as a point of reflection about the role of these nutrients in the western diet and the elevated non-alcoholic steatohepatitis rates in humans.