Associations between follicular fluid high density lipoprotein particle components and embryo quality among in vitro fertilization patients.

PURPOSE: Follicular redox balance is likely to be important for embryo quality during in vitro fertilization (IVF), and the anti-oxidative high desity lipoprotein (HDL) particle is the sole lipoprotein measured in follicular fluid (FF). Therefore, we investigated FF HDL particle components as predictors of embryo quality during IVF. METHODS: Two research follicles collected from each participant were individually tracked, and 103 women having at least one developed embryo were included in the analysis. Concentrations of 15 non-cholesterol HDL particle components and 26 HDL-cholesterol (HDL-C) particle size subfractions were determined. Embryo quality was assessed for embryo cell number, embryo fragmentation, and embryo symmetry. Multivariable Poisson regression with a sandwich variance estimator was used to evaluate associations between HDL particle components and embryo quality, adjusted for covariates. RESULTS: Higher γ-tocopherol concentration was associated with less embryo fragmentation (relative risk [RR] = 4.43; 95 % confidence interval [CI] 1.78, 11.06), and higher apolipoprotein A-1 concentration was associated with full embryo symmetry (RR = 3.92; 95 % CI 1.56, 9.90). Higher concentrations of HDL-C subfractions in the large and medium particle size ranges were associated with poorer embryo quality. CONCLUSIONS: FF HDL lipophilic micronutrients and protein components, as well as HDL-C particle size, may be important predictors of embryo quality during IVF.

Associations between race, lifecourse socioeconomic position and prevalence of diabetes among US women and men: results from a population-based panel study.

BACKGROUND: Few studies have examined the degree to which racial disparities in the development of diabetes are accounted by differences in lifecourse socioeconomic position (SEP). We assessed the association between race, lifecourse SEP measures and prevalence of diabetes in a representative US sample of black and white adults. METHODS: A generalised estimating equations approach was used with a sample of 3497 adults from the Americans' Changing Lives study. Sex-specific models were calculated to compute prevalence ratios (PR) for associations of race and SEP with self-reported diagnoses of diabetes. RESULTS: For men, childhood and adult SEP were unrelated to diabetes, and adjustment for lifecourse SEP had little effect on the excess diabetes in blacks (PR=1.56, 95% CI 1.11 to 2.21). Adjustment for measures of lifecourse SEP reduced the PR for the association between race and diabetes in women from 1.96 (95% CI 1.52 to 2.54) to 1.40 (95% CI 1.04 to 1.87) with the respondent's education responsible for most of the reduction in the association. However, diabetes was also inversely associated with father's education, and low SEP throughout the lifecourse was associated with a nearly threefold increase in diabetes (PR=2.89, 95% CI 2.10 to 3.99). CONCLUSIONS: Racial disparities in diabetes existed among both men and women, but lifecourse SEP was related to diabetes only among women. The pathway and cumulative hypotheses for lifecourse SEP effects on diabetes may be especially salient for women.

The internal consistency of PRO fatigue instruments in sarcoidosis: superiority of the PFI over the FAS.

INTRODUCTION: The Fatigue Assessment Scale (FAS) is a 10-item patient reported outcome (PRO) questionnaire that is used to measure fatigue in sarcoidosis. After several months of use, we began to question the reliability of the FAS in our clinic population. Therefore, we administered an additional fatigue PRO, the Patient Reported Outcomes Measurement Information Systems (PROMIS) Fatigue Instrument (PFI). Our hypothesis was that the internal consistency/reliability (Cronbach's alpha) of the PFI would be superior to the FAS in sarcoidosis patients because two of the ten FAS items (items #4 and #10) required reverse scoring (these items were scaled in the opposite direction to the other 8 items). METHODS: The FAS and PFI were administered during the same clinic visit to consecutive patients in our sarcoidosis clinic. We calculated a) the Cronbach's alpha for a) the FAS; b) the FAS without items #4 and #10; and c) the PFI. RESULTS: 107 consecutive sarcoidosis patients underwent FAS and PFI testing. The Cronbach's alpha was 0.740, 0.911, and 0.963 for the FAS, FAS with items #4 and #10 removed, and the PFI respectively. In female patients, the Cronbach's alpha of the FAS was 0.663, which is considered as "questionable" in terms of internal consistency. CONCLUSION: We found that the PFI had "excellent" consistency in our sarcoidosis clinic. The FAS did not demonstrate the same degree of internal consistency. The Cronbach's estimate of the FAS with items #4 and #10 removed was vastly superior to the FAS. These data support our contention that FAS items #4 and #10 detract from the internal consistency of this PRO. They also suggest that the PFI is superior to the FAS in terms of reliability.

Mixed modeling and multiple imputation for unobservable genotype clusters.

Understanding the genetic contributions to complex diseases will require consideration of interaction across multiple genes and environmental factors. At the same time, capturing information on allelic phase, that is, whether alleles within a gene are in cis (on the same chromosome) or in trans (on different chromosomes), is critical when using haplotypic approaches in disease association studies. This paper proposes a combination of mixed modeling and multiple imputation for assessing high-order genotype-phenotype associations while accounting for the uncertainty in phase inherent in population-based association studies. This method provides a flexible statistical framework for controlling for potential confounders and assessing gene-environment and gene-gene interactions in studies of unrelated individuals where the haplotypic phase is generally unobservable. The proposed method is applied to a cohort of 626 subjects with human immunodeficiency virus (HIV) to assess the potential contribution of four genes, apolipoprotein-C-III, apolipoprotein-E, endothelial lipase and hepatic lipase in predicting lipid abnormalities. A simulation study is also presented to describe the method performance.

Oxidative stress in human in sustained and white coat hypertension.

Oxidative stress is thought to play a critical role in the pathogenesis of hypertension. Protein oxidation is defined here as the covalent modification of a protein induced either directly by reactive oxygen species or indirectly by reaction with secondary by-products of oxidative stress. The aim of our study was to evaluate the protein oxidation and to examine the function of the antioxidative system in sustained and white coat hypertensives (WCH) and compare with normotensives. This study was designed to investigate the protein oxidation parameters [protein carbonyls (PCOs)] in sustained hypertensives (17 males and 20 females) and WCH (18 males and 19 females). PCO and the endogenous antioxidant components protein thiol (P-SH), CuZn-superoxide dismutase (CuZn-SOD) and glutathione (GSH) were analysed using spectrophotometric and kinetic methods. Sustained hypertensive and WCH groups exhibited higher protein oxidation and lower P-SH, CuZn-SOD and GSH activities than normotensives. With regard to these parameters, there was no significant difference between sustained hypertensive and WCH groups. Blood pressure correlates positively with PCO groups and negatively with others. There exists an imbalance between oxidants and antioxidants in WCH because of the increase of oxidants associated with the decrease of antioxidant capacity. This may cause endothelial dysfunction just like in sustained hypertension. It may be necessary to add antioxidants to conventional antihypertensive therapy to balance the oxidative status in WCH.

The effects of experimental hyperthyroidism on hemorheology and plasma fibrinogen concentration.

The present study in female rats determined the effects of experimental hyperthyroidsm on hemorheological parameters and fibrinogen concentration. To induce experimental hyperthyroidism L-thyroxine (0.4 mg/100 g fodder) was added to the fodder of the experimental group rats for 20 d. After experimental duration, T3, T4, and TSH levels, plasma and blood viscosity, hematocrit, erythrocyte rigidity index, and plasma fibrinogen concentration values of both the control and the experimental group animals were determined and evaluated. In the experimental group, T3 and T4 levels were higher and TSH levels lower than that of the control rats (respectively, p < 0.01, p < 0.001, p < 0.001). Plasma viscosity and fibrinogen concentration of hyperthyroid group were found significantly higher than controls (p < 0.01). However there was no significant difference found in blood viscosity, hematocrit, and erythrocyte rigidity index between control and experimental groups. Thus, hyperthyroidism induced increased fibrinogen concentration can alter the rheological structure of blood by inducing increase in plasma viscosity.

Endothelium and angiogenesis in white coat hypertension.

Hypertensive patients are at particular risk of cardiovascular complications, possibly related to endothelial damage or dysfunction, or to abnormal angiogenesis. The aim of this study was to compare the risk conferred by white coat hypertension (WCH) vs sustained hypertension in the development of the endothelial dysfunction and abnormal angiogenesis by evaluating nitric oxide (NO=NO2+NO3), endothelin-1 (ET-1), vascular endothelial growth factor (VEGF), and E-selectin levels in plasma. The study group included 102 subjects, 34 with WCH (17 male and 17 female patients) aged 49+/-11 years, 34 sustained hypertensives (HT) (15 male and 19 female patients) aged 47+/-11 years and 34 normotensive control subjects (NT) (16 male and 18 female patients) aged 48+/-10 years. WCH was defined as clinical hypertension and daytime ambulatory blood pressure less than 135/85 mmHg. The subjects were matched for age, gender, body mass index and the patients with smoking habit, dyslipidaemia, and diabetes mellitus were excluded from the study. The NO, ET-1, VEGF and E-selectin levels were analysed by ELISA technique. The WCH subjects had significantly higher levels of NO than the HT (41.68+/-2.23 vs 32.18+/-2.68 micromol/l; P<0.001) and significantly lower values than the NT (48.24+/-4.29 micromol/l; P<0.001). ET-1 levels of the WCH group were significantly higher than the NT (8.10+/-0.92 vs 5.95+/-0.26 ng/ml; P<0.001) and significantly lower than the HT (11.46+/-0.59 ng/ml; P<0.001). Considering with VEGF, the WCH group had significantly higher levels than the NT (195.88+/-11.84 vs 146.26+/-18.67 pg/ml; P<0.001), but the difference from the HT group was not significant (203.35+/-7.48 pg/ml; P=0.062). E-selectin in the WCH group was significantly lower than the HT (4.77+/-0.52 vs 8.49+/-2.85; P<0.001), but the difference from the NT group was not significant (3.86+/-0.67; P=0.077). Our data demonstrate that WCH is associated with endothelial dysfunction and abnormal angiogenesis. The degree of these changes is not as severe as observed in hypertensive population.

Oxidative stress in white coat hypertension; role of paraoxonase.

Oxidative stress in sustained hypertension was shown with several biochemical parameters. Oxidized low-density lipoprotein (oxLDL) plays an important role during the atherosclerosis process and paraoxonase (PON1) can significantly inhibit lipid peroxidation. Serum PON1 activity, oxLDL and malondialdehyde (MDA) concentrations and their relationship with serum lipid parameters and systolic and diastolic blood pressures (SBP and DBP) were determined in subjects with white coat hypertension (WCH), sustained hypertension (HT) and normotension (NT). The study group consisted of a total of 86 subjects, 30 with WCH (14 male, 16 female subjects), 30 with HT (13 male, 17 female subjects) and 26 with NT (12 male, 14 female subjects). Both white coat hypertensive and hypertensive subjects had significantly higher levels of MDA than normotensives (P<0.026 and P<0.001, respectively). The oxLDL level of the HT group was significantly higher than the NT group (P<0.023). The WCH group had an oxLDL level similar to both hypertensive and normotensive groups. HT and WCH groups had significantly lower PON1 levels than the normotensive group (P<0.001). oxLDL correlated with MDA positively (P=0.008), and PON1 negatively (P=0.008). A negative correlation between MDA and PON1 (P=0.014) was detected. MDA correlated positively with both SBP and DBP (P=0.001), while PON1 correlated with both of them negatively (P=0.01 and P=0.008, respectively). OxLDL correlated with diastolic blood pressure positively (P=0.008). Our data demonstrate that oxidative stress increase in WCH is associated with a decrease in PON1 activity. The reduction in PON1 activity may be one of the factors leading to an increase in oxidative status in WCH.

Functions of the membrane-associated and cytoplasmic malate dehydrogenases in the citric acid cycle of Corynebacterium glutamicum.

Like many other bacteria, Corynebacterium glutamicum possesses two types of L-malate dehydrogenase, a membrane-associated malate:quinone oxidoreductase (MQO; EC 1.1.99.16) and a cytoplasmic malate dehydrogenase (MDH; EC 1.1.1.37) The regulation of MDH and of the three membrane-associated dehydrogenases MQO, succinate dehydrogenase (SDH), and NADH dehydrogenase was investigated. MQO, MDH, and SDH activities are regulated coordinately in response to the carbon and energy source for growth. Compared to growth on glucose, these activities are increased during growth on lactate, pyruvate, or acetate, substrates which require high citric acid cycle activity to sustain growth. The simultaneous presence of high activities of both malate dehydrogenases is puzzling. MQO is the most important malate dehydrogenase in the physiology of C. glutamicum. A mutant with a site-directed deletion in the mqo gene does not grow on minimal medium. Growth can be partially restored in this mutant by addition of the vitamin nicotinamide. In contrast, a double mutant lacking MQO and MDH does not grow even in the presence of nicotinamide. Apparently, MDH is able to take over the function of MQO in an mqo mutant, but this requires the presence of nicotinamide in the growth medium. It is shown that addition of nicotinamide leads to a higher intracellular pyridine nucleotide concentration, which probably enables MDH to catalyze malate oxidation. Purified MDH from C. glutamicum catalyzes oxaloacetate reduction much more readily than malate oxidation at physiological pH. In a reconstituted system with isolated membranes and purified MDH, MQO and MDH catalyze the cyclic conversion of malate and oxaloacetate, leading to a net oxidation of NADH. Evidence is presented that this cyclic reaction also takes place in vivo. As yet, no phenotype of an mdh deletion alone was observed, which leaves a physiological function for MDH in C. glutamicum obscure.

Doppler velocimetry of the uterine arteries after hysteroscopic rollerball endometrial ablation.

The aim of this study was to document the Doppler indices [pulsatility index (PI) and resistance index (RI)] of the uterine arteries in 30 patients who underwent hysteroscopic rollerball endometrial ablation for dysfunctional uterine bleeding by transvaginal pulsed Doppler sonography, and to reveal whether treatment failures (persistent menometrorrhagia) can be predicted by the blood flow characteristics of the uterine arteries in advance. On the basis of the outcome of patients at the end of the first postoperative year, the Doppler indices of the uterine arteries were meaningful 1 year after the operation when PI (1.32 +/- 0.11; mean +/- SD) and RI (0.71 +/- 0.04) in six menometrorrhagic patients were statistically different from PI (2.19 +/- 0.28; 1.95 +/- 0.36 and 1.82 +/- 0.37) and RI (0.87 +/- 0.06; 0.82 +/- 0.06 and 0.81 +/- 0.04) in normally menstruating, amenorrhoeic and hypomenorrhoeic patients respectively (P < 0.05). On the other hand, the patients who would be menometrorrhagic one year after the operation had a thicker endometrium in the first post-operative month. These findings suggest that the angiogenetic role of the persistent endometrial islands after endometrial ablation needs at some time to be reflected as changes in the Doppler parameters of the uterine arteries.