The effects of 2 mg chlormadinone acetate/30 mcg ethinylestradiol, alone or combined with spironolactone, on cardiovascular risk markers in women with polycystic ovary syndrome

Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder associated with metabolic dysfunction and changes in cardiovascular risk markers, and using oral contraceptives (OCs) may exert a further negative effect on these alterations in patients with PCOS. Thus, the primary objective of this study was to assess the effects on arterial function and structure of an OC containing chlormadinone acetate (2 mg) and ethinylestradiol (30 mcg), alone or combined with spironolactone (OC+SPL), in patients with PCOS. Study Design: This was a randomized, controlled clinical trial. Fifty women with PCOS between 18 and 35 years of age were randomized by a computer program to use OC or OC+SPL. Brachial artery flow-mediated vasodilation, carotid intima-media thickness and the carotid artery stiffness index were evaluated at baseline and after 6 and 12 months. Serum markers for cardiovascular disease were also analyzed. The intragroup data were analyzed using analysis of variance with Tukey's post hoc test. A multivariate linear regression model was used to analyze the intergroup data. Results: At 12 months, the increase in mean total cholesterol levels was greater in the OC+SPL group than in the OC group (27% vs. 13%, respectively; p=.02). The increase in mean sex hormone-binding globulin levels was greater in the OC group than in the OC+SPL group (424% vs. 364%, respectively; p=.01). No statistically significant differences between the groups were found for any of the other variables. Conclusion: The addition of spironolactone to an OC containing chlormadinone acetate and ethinylestradiol conferred no cardiovascular risk-marker advantages in young women with PCOS. (C) 2012 Elsevier Inc. All rights reserved.

GLUT4 content decreases along with insulin resistance and high levels of inflammatory markers in rats with metabolic syndrome

Background: Metabolic syndrome is characterized by insulin resistance, which is closely related to GLUT4 content in insulin-sensitive tissues. Thus, we evaluated the GLUT4 expression, insulin resistance and inflammation, characteristics of the metabolic syndrome, in an experimental model. Methods: Spontaneously hypertensive neonate rats (18/group) were treated with monosodium glutamate (MetS) during 9 days, and compared with Wistar-Kyoto (C) and saline-treated SHR (H). Blood pressure (BP) and lipid levels, C-reactive protein (CRP), interleukin 6 (IL-6), TNF-alpha and adiponectin were evaluated. GLUT4 protein was analysed in the heart, white adipose tissue and gastrocnemius. Studies were performed at 3 (3-mo), 6 (6-mo) and 9 (9-mo) months of age. Results: MetS rats were more insulin resistant (p<0.001, all ages) and had higher BP (3-mo: p<0.001, 6-mo: p = 0.001, 9-mo: p = 0.015) as compared to C. At 6 months, CRP, IL-6 and TNF-alpha were higher (p<0.001, all comparisons) in MetS rats vs H, but adiponectin was lower in MetS at 9 months (MetS: 32 +/- 2, H: 42 +/- 2, C: 45 +/- 2 pg/mL; p<0.001). GLUT4 protein was reduced in MetS as compared to C rats at 3, 6 and 9-mo, respectively (Heart: 54%, 50% and 57%; Gastrocnemius: 37%, 56% and 50%; Adipose tissue: 69%, 61% and 69%). Conclusions: MSG-treated SHR presented all metabolic syndrome characteristics, as well as reduced GLUT4 content, which must play a key role in the impaired glycemic homeostasis of the metabolic syndrome.

Proinflammatory and oxidative stress markers in patients submitted to Roux-en-Y gastric bypass after 1 year of follow-up

BACKGROUND/OBJECTIVES: This study examined the effect of weight loss after 3, 6 and 12 months of Roux-en-Y Gastric Bypass (RYGB) on energy intake and on several biomarkers of oxidative stress such as levels of vitamin C, beta-carotene, vitamin E (diet/blood), nitric oxide metabolites (NOx), myeloperoxidase (MPO), thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and activity of catalase (CAT). SUBJECTS/METHODS: Study with a control group (CG), assessed once, and a bariatric group (BG) assessed at the basal period as well as at 3, 6 and 12 months post-surgery; both groups were composed of 5 men and 31 women (n = 36). Age was 38.7 +/- 9.4 and 39.6 +/- 9.2 years old and body mass index (BMI) was 22.2 +/- 2.1 and 47.6 +/- 9.1 kg/m(2), respectively. The variance measure quoted was SEM. RESULTS: The body weight at 12 months was 35.8 +/- 1.0% (P<0.001) lower than that of the basal period. At the basal period BG showed higher levels of NOx (P=0.007) and TBARS (P<0.001) and lower levels of vitamins C and E (P<0.001) compared with CG. After 3 months the activity of MPO was decreased (P<0.001). Six months after surgery GSH levels were decreased (P=0.037), whereas CAT activity was increased (P=0.029). After 12 months levels of NOx (P=0.004), TBARS (P<0.001), beta-carotene (P<0.001) and vitamin E (P<0.001) were decreased, whereas those of vitamin C (P<0.001) were increased compared with controls. CONCLUSION: RYGB followed by a daily vitamin supplement apparently attenuated pro-inflammatory and oxidative stress markers 1 year after surgery, but additional antioxidant supplementation appears necessary.

Autoantibodies and High-Risk HLA Susceptibility Markers in First-Degree Relatives of Brazilian Patients with Type 1 Diabetes Mellitus: A Progression to Disease Based Study

The objective of this study was to determine the frequencies of autoantibodies to heterogeneous islet-cell cytoplasmic antigens (ICA), glutamic acid decarboxylase(65) (GAD(65)A), insulinoma-associated antigen-2 (IA-2A) and insulin (IAA)-and human leukocyte antigen (HLA) class II markers (HLA-DR and -DQ) in first degree relatives of heterogeneous Brazilian patients with type I diabetes(T1DM). A major focus of this study was to determine the influence of age, gender, proband characteristics and ancestry on the prevalence of autoantibodies and HLA-DR and -DQ alleles on disease progression and genetic predisposition to T1DM among the first-degree relatives. IAA, ICA, GAD(65)A, IA-2A and HLA- class II alleles were determined in 546 first-degree-relatives, 244 siblings, 55 offspring and 233 parents of 178 Brazilian patients with T1DM. Overall, 8.9% of the relatives were positive for one or more autoantibodies. IAA was the only antibody detected in parents. GAD(65) was the most prevalent antibody in offspring and siblings as compared to parents and it was the sole antibody detected in offspring. Five siblings were positive for the IA-2 antibody. A significant number (62.1%) of siblings had 1 or 2 high risk HLA haplotypes. During a 4-year follow-up study, 5 siblings (expressing HLA-DR3 or -DR4 alleles) and 1 offspring positive for GAD(65)A progressed to diabetes. The data indicated that the GAD(65) and IA-2 antibodies were the strongest predictors of T1DM in our study population. The high risk HLA haplotypes alone were not predictive of progression to overt diabetes.

Age-dependent changes in rat lacrimal gland anti-oxidant and vesicular related protein expression profiles

Purpose: Anti-oxidation and exocytosis are important for maintaining exocrine tissue homeostasis. During aging, functional and structural alterations occur in the lacrimal gland (LG), including oxidative damage to proteins, lipids, and DNA. The aims of the present study were to determine in the aging LG: a) the effects of aging on LG structure and secretory activity and b) changes in the expression of oxidative stress markers. Methods: To address these goals, tear secretion composition and corneal impression cytology were compared between male Wistar rats of 2 (control) and 24 (aged) months. LG morphology and the expression levels of vitamin E and malonaldehyde (MDA) were evaluated to determine the anti-oxidant activity and lipid peroxidation, respectively. RT-PCR and western blot analysis were used for the analysis of Ras related in brain GTPase protein (Rab) and soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins of the secretory machinery (i.e.; Rab 3d, Rab 27, vesicle-associated membrane protein-2 (Vamp-2), and syntaxin). Results: Histological analysis of aged rats revealed a higher frequency of corneal epithelia metaplasia. In the acinar cells, organelles underwent degeneration, and lipofucsin-like material accumulated in the cytoplasm along with declines in the anti-oxidant marker vitamin E. Rab3d and Rab27b mRNA levels fell along with Rab3d protein expression, whereas syntaxin levels increased. Conclusions: These findings indicate that exocytotic and anti-oxidant mechanisms become impaired with age in the rat LG. In parallel with these structural alterations, functional declines may contribute to the pathophysiology caused by tear film modification in dry eye disease.

Ultrasonographic and laboratory markers of metabolic and cardiovascular disease risk in obese women with polycystic ovary syndrome

Objective To evaluate whether the presence of polycystic ovary syndrome (PCOS) alters multiple ultrasonographic and laboratory markers of metabolic and cardiovascular disease risk in obese women without any other health condition that could interfere with combined oral contraceptive (COC) eligibility criteria. Methods This was a case- control study evaluating 90 obese women ( body mass index ( BMI) = 30.0 kg/m2 and < 40 kg/m2) aged between 18 and 40 years without any other health condition that could interfere with COC eligibility criteria, of whom 45 had PCOS and 45 were age- matched controls. BMI, waist and hip circumference, arterial blood pressure, fasting insulin and glucose, quantitative insulin sensitivity check index ( QUICKI), highdensity lipoprotein cholesterol, low- density lipoprotein cholesterol, total cholesterol, triglycerides, testosterone, sex hormone- binding globulin, free androgen index ( FAI), carotid stiffness index, intima media thickness, flowmediated dilatation ( FMD) of the brachial artery and non- alcoholic fatty liver disease ( NAFLD) were assessed. Results In women with PCOS, we observed a higher frequency of NAFLD ( 73.3 vs. 46.7%, P < 0.01) and higher FAI ( 10.4 vs. 6.8%, P < 0.01). We also observed a trend towards increased insulin levels ( 10.06 +/- 6.66 vs. 7.45 +/- 5.88 mu IU/mL, P = 0.05), decreased QUICKI ( 0.36 +/- 0.06 vs. 0.39 +/- 0.07, P = 0.05) and decreased FMD ( 7.00 +/- 3.87 vs. 8.41 +/- 3.79%, P = 0.08). No other significant difference was observed. Conclusions NAFLD is frequent in obese women without any other health condition that could interfere with COC eligibility criteria, especially in those with PCOS. This should be considered when choosing the best contraceptive option. Copyright (C) 2012 ISUOG. Published by John Wiley & Sons, Ltd.

Six minute walk test Z score: Correlations with cystic fibrosis severity markers

Background: The six-minute-walk-test (6MWT) has been increasingly used in cystic fibrosis (CF) patients. However, few studies in children have correlated 6MWT with current parameters used to evaluate CF severity. Moreover, no study transformed the values of distance walked from meters into Z scores to avoid bias like age and gender, which are sources of 6MWT variability. Methods: A cross-sectional descriptive study was performed to analyze the correlations (Spearman) among forced expiratory volume in one second (FEV1), body mass index (BMI), chest radiography (CXR), chest tomography (CT), and 6MWT Z score (Z-6MWT). Clinically stable CF patients, aged 6-21 years, were included. Results: 34 patients, 14F/20M, mean age 12.1 +/- 4.0 years were studied. The mean Z-6MWT was -1.1 +/- 1.106. The following correlations versus Z-6MWT were found: FEV1 (r=0.59, r(2)=0.32, p=0.0002), BMI Z score (r=0.42, r(2)=0.17, p=0.013), CXR (r=0.34, r(2)=0.15, p=0.0472) and CT (r=-0.45, r(2)=0.23, p=0.0073). Conclusions: In conclusion there was a significant, but poor, correlation between the six minute walk test Z score and the cystic fibrosis severity markers currently in use. (C) 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Antismooth Muscle and Antiactin Antibodies Are Indirect Markers of Histological and Biochemical Activity of Autoimmune Hepatitis

Reactivity and titers of autoantibodies vary during the course of autoimmune hepatitis (AIH), and some autoantibodies have been associated with disease activity and adverse outcomes after treatment. The aim of this study was to assess the autoantibody behavior in AIH and its significance as predictors of biochemical and histological remission. A total of 117 patients with AIH (mean age 18.6 [4-69] years) were evaluated and tested for auto- antibodies at disease onset and successively (mean 3.2 [2-6] times) after a mean follow-up evaluation of 70 [20-185] months. Antismooth muscle (ASMA), antiliver kidney micro- some type 1 (anti-LKM1), antiliver cytosol type 1 (anti-LC1), antimitochondrial, antinu- clear (ANA), and antiactin antibodies (AAA) were determined at disease onset and 379 other times during the follow-up evaluation through indirect immunofluorescence in rodent tissues, HEp-2 cells, and human fibroblasts. Anti-SLA/LP were assessed 45 times in the follow-up evaluation of 19 patients using enzyme-linked immunosorbent assay (ELISA). Upon admission, AIH types 1 and 2 were observed in 95 and 17 patients, respectively. Five subjects had AIH with anti-SLA/LP as the sole markers. Patients initially negative for AAA did not develop these antibodies thereafter. ANA were detected de novo in six and three subjects with AIH types 1 and 2, respectively. After treatment, only ASMA ( > 1:80) and AAA ( > 1:40) were significantly associated with biochemical (76.9% and 79.8%) and histological features (100% and 100%) of disease activity ( P < 0.001). Conclusion: With the exception of ANA, the autoantibody profile does not markedly vary in the course of AIH. The persistence of high titers of ASMA and/or AAA in patients with AIH is associated with disease activity.