Endocrine Disruptors and Polycystic Ovary Syndrome: Phthalates

Objective:We aimed to investigate a possible role of the endocrine disruptors phthalates, di-2-ethylhexyl phthalate (DEHP) and mono (2-ethylhexyl) phthalate (MEHP), in polycystic ovary syndrome (PCOS) aetiopathogenesis. We also wished to evaluate the relationship between phthalates and metabolic disturbances in adolescents with PCOS.Methods:A total of 124 adolescents were included. Serum MEHP and DEHP levels were determined by high-performance liquid chromatography. Insulin resistance was evaluated using homeostasis model assessment-insulin resistance, quantitative Insulin Sensitivity Check Index, fasting glucose/insulin ratio, Matsuda index, and total insulin levels during oral glucose tolerance test. Participants were further subdivided into lean and obese subgroups according to body mass index (BMI).Results:Sixty-three PCOS and 61 controls, (mean age 15.2±1.5; range: 13-19 years) were enrolled. Serum DEHP and MEHP concentrations were not significantly different between PCOS and control groups. The mean (95% confidence interval) values of DEHP and MEHP were 2.62 (2.50-2.75) μg/mL vs 2.71 (2.52-2.90) μg/mL and 0.23 (0.19-0.29) μg/mL vs 0.36 (0.18-0.54) μg/mL in PCOS and the control groups respectively, p>0.05. Correlation analysis, adjusted for BMI, showed that both phthalates significantly correlated with insulin resistance indices and serum triglycerides in adolescents with PCOS.Conclusion:Serum DEHP and MEHP concentrations were not different between adolescents with or without PCOS. However, these phthalates are associated with metabolic disturbances such as dyslipidemia and insulin resistance, independently of obesity, in girls with PCOS.     

QTc-Prolongation in Posterior Circulation Stroke

Background and Purpose

To evaluate the relationship between infarct location and QTc-prolongation in patients with posterior circulation strokes.

Methods

Admission electrocardiograms (ECG) of 131 patients among a prospective sample of 407 consecutive adult patients in the New England Medical Center Posterior Circulation Registry were retrospectively analyzed. The QT interval (ms) was measured and corrected using Bazett’s formula (QTc_Bazett) as well as linear regression functions (QTc_Linear). QTc_Bazett > 440 ms and QTc_Linear ≥ 450 ms for men (≥460 ms for women) were considered prolonged. Multivariable linear and logistic regression analyses were used to identify independent predictors of the QTc.

Results

Overall, 34 % of patients had a prolonged QTc_Bazett and 7 % had a prolonged QTc_Linear noted on the admission ECG. There was a significant association between temporal lobe infarction and QTc_Bazett and QTc_Linear (p < 0.001 for both) in multivariable linear regression analyses adjusting for demographics, ECG parameters, and preadmission medication use. In multivariable logistic regression analysis, temporal lobe infarction emerged as an independent predictor of prolonged QTc_Bazett (p = 0.009) and QTc_Linear (p = 0.008), respectively. Sensitivity analyses excluding patients with transient ischemic attack yielded similar results. Exploratory analyses indicated that patients with temporal lobe infarction had worse functional 30-day outcomes in multivariable logistic regression (p = 0.022). However, there was no significant association between QTc and 30-day functional outcome.

Conclusions

QTc-prolongation is common after posterior circulation stroke and associated with temporal lobe infarction. Prospective studies are needed to confirm these preliminary findings and to examine potential long-term consequences.     

Arg-Phe-amide-related peptides influence gonadotropin-releasing hormone neurons

The hypothalamic Arg-Phe-amide-related peptides, gonadotropin-inhibitory hormone and orthologous mammalian peptides of Arg-Phe-amide, may be important regulators of the hypothalamus-pituitary-gonadal reproductive axis. These peptides may modulate the effects of kisspeptins because they are presently recognized as the most potent activators of the hypothalamus-pituitary-gonadal axis. However, their effects on gonadotropin-releasing hormone neurons have not been investigated. In the current study, the GT1-7 cell line-expressing gonadotropin-releasing hormone was used as a model to explore the effects of Arg-Phe- amide-related peptides on kisspeptin activation. Intracellular calcium concentration was quantified using the calcium-sensitive dye, fura-2 acetoxymethyl ester. Gonadotropin-releasing hormone released into the medium was detected via enzyme-linked immunosorbent assay. Results showed that 100 nmol/L kisspeptin-10 significantly increased gonadotropin-releasing hormone levels (at 120 minutes of exposure) and intracellular calcium concentrations. Co-treatment of kisspeptin with 1 μmol/L gonadotropin-inhibitory hormone or 1 μmol/L Arg-Phe-amide-related peptide-1 significantly attenuated levels of kisspeptin-induced gonadotropin-releasing hormone but did not affect kisspeptin-induced elevations of intracellular calcium concentration. Overall, the results suggest that gonadotropin-inhibitory hormone and Arg-Phe-amide-related peptide-1 may have inhibitory effects on kisspeptin-activated gonadotropin-releasing hormone neurons independent of the calcium signaling pathway.     

Assessment of the left atrial volume index and plasma NT-proANP level in patients with acute ST-elevation myocardial infarction

OBJECTIVES:

Acute ST-elevation myocardial infarction is associated with ventricular dysfunction due to ischemia-induced progressive myocardial damage. The decrease in ventricular compliance causes left atrial dilatation and stretching of the atrial myocardium, which are the main stimuli for the secretion of atrial natriuretic peptide. The aim of this study was to evaluate left atrial dimensions and atrial natriuretic peptide levels in patients early after their first acute ST-elevation myocardial infarction and assess the probable interaction between coronary lesions and these measurements.

METHODS:

A total of 110 patients with acute myocardial infarction and 50 controls were studied. Plasma atrial natriuretic peptide was measured at admission. Left ventricular function, diameter, and volume index were evaluated using transthoracic echocardiography. Gensini and vessel scores of the patients who underwent coronary angiography were calculated.

RESULTS:

Plasma atrial natriuretic peptide in the patients with myocardial infarction was increased compared with that in controls (3.90±3.75 vs. 1.35±0.72 nmol/L, p<0.001). Although the left atrial diameter was comparable in patients and controls, the left atrial volume index was increased in patients with acute myocardial infarction (26.5±7.1 vs. 21.3±4.9 mL/m², p<0.01). Multivariate regression analysis showed a strong independent correlation between the left atrial volume index and the plasma atrial natriuretic peptide level (β = 0.23, p = 0.03).

CONCLUSIONS:

The left atrial volume index and plasma atrial natriuretic peptide level were correlated in patients with acute myocardial infarction.     

Effect of Agitation of EDTA with 808-Nanometer Diode Laser on Removal of Smear Layer

Introduction

Near-infrared diode lasers can be used for several applications, which range from disinfection to smear layer removal in endodontics. This study evaluated the efficacy of agitation of 15% EDTA with an 808-nm diode laser on removal of the smear layer.

Methods

Sixty extracted human maxillary central incisor teeth were instrumented up to ProTaper F4 (Dentsply Maillefer, Ballagues, Switzerland) and then randomly divided into 6 groups (n = 10 for each group) according to the different final irrigating protocols as follows: 5% sodium hypochlorite for 120 seconds performed with the NaviTip (Dentsply Maillefer, Ballaigues, Switzerland) (control group); 15% EDTA for 120 seconds performed with the NaviTip; and agitation of 15% EDTA with an 808-nm diode laser for 10, 20, 30, and 40 seconds. Specimens were observed under a scanning electron microscope, and open dentinal tubules were counted using Adobe Photoshop software (Adobe Systems, San Jose, CA). The data were analyzed with 1-way analysis of variance and Tukey post hoc tests (P = .05).

Results

The number of open dentinal tubules was higher in the middle thirds than in the apical thirds. The differences between the apical and middle thirds were statistically significant (P < .05). Statistically significant differences were also found between the control group and the other groups in both the middle and apical thirds of the root canals (P < .05).

Conclusions

The results indicated that agitation of 15% EDTA with an 808-nm diode laser for 20 seconds was effective in removing the smear layer in the apical thirds of root canals.     

FcγRIIa and FcγRIIIa genetic polymorphisms in a group of pediatric immune thrombocytopenic purpura in Egypt

Immune thrombocytopenic purpura (ITP) is an acquired autoimmune disorder caused by the production of antiplatelet antibodies. The current case-control study aimed at detecting the frequency of FcγRIIa-131H/R and FcγRIIIa-158F/V genes polymorphism in Egyptian children with ITP as genetic markers for ITP risk, and to clear out their possible role in choosing the treatment protocols of ITP. To achieve this aim, FcγRIIa genotyping was tested by PCR-restriction fragment length polymorphism (RFLP) technique, whereas FcγRIIIa genotyping was tested by nested PCR followed RFLP analysis. The current case-control study was conducted on 92 children with ITP; 12 acute and 80 chronic cases and 90 controls. The V allele and FcγRIIIa FV heterotype were significantly higher in ITP patients and conferred increased ITP risk [odds ratio (OR) = 1.96 and 2.55, respectively]. The frequency of FcγRIIa H allele was significantly higher among chronic ITP patients. In conclusion, FcγRIIIa gene polymorphism may contribute to susceptibility to ITP. Moreover, analysis of the FcγR polymorphisms in ITP patients could influence the effectiveness of medications and selection of the line of treatment.     

Variation in PTX3 Is Associated with Primary Graft Dysfunction after Lung Transplantation

Rationale: Elevated long pentraxin-3 (PTX3) levels are associated with the development of primary graft dysfunction (PGD) after lung transplantation. Abnormalities in innate immunity, mediated by PTX3 release, may play a role in PGD pathogenesis. Objectives: Our goal was to test whether variants in the gene encoding PTX3 are risk factors for PGD. Methods: We performed a candidate gene association study in recipients from the multicenter, prospective Lung Transplant Outcomes Group cohort enrolled between July 2002 and July 2009. The primary outcome was International Society for Heart and Lung Transplantation grade 3 PGD within 72 hours of transplantation. Targeted genotyping of 10 haplotype-tagging PTX3 single-nucleotide polymorphisms (SNPs) was performed in lung transplant recipients. The association between PGD and each SNP was evaluated by logistic regression, adjusting for pretransplantation lung disease, cardiopulmonary bypass use, and population stratification. The association between SNPs and plasma PTX3 levels was tested across genotypes in a subset of recipients with idiopathic pulmonary fibrosis. Measurements and Main Results: Six hundred fifty-four lung transplant recipients were included. The incidence of PGD was 29%. Two linked 5' region variants, rs2120243 and rs2305619, were associated with PGD (odds ratio, 1.5; 95% confidence interval, 1.1 to 1.9; P = 0.006 and odds ratio, 1.4; 95% confidence interval, 1.1 to 1.9; P = 0.007, respectively). The minor allele of rs2305619 was significantly associated with higher plasma PTX3 levels measured pretransplantation (P = 0.014) and at 24 hours (P = 0.047) after transplantation in patients with idiopathic pulmonary fibrosis. Conclusions: Genetic variants of PTX3 are associated with PGD after lung transplantation, and are associated with increased PTX3 plasma levels.     

Atrial conduction time and atrial mechanical function in patients with impaired fasting glucose

Background

Prolonging atrial conduction time, as measured by tissue Doppler imaging (TDI), is an independent predictor of new onset or recurrent atrial fibrillation (AF). We investigated atrial conduction time and cardiac mechanical function in patients with impaired fasting glucose (IFG) using echocardiography.

Methods

Thirty patients with IFG (19 males and 11 females; age, 46.9?±?9.5?years) and 30 control subjects (18 males and 12 females; age, 46.7?±?8.2?years) were included. Atrial conduction time was determined from the lateral mitral annulus (PA lateral), septal mitral annulus (PA septal), and lateral tricuspid annulus (PA tricuspid) by TDI. Inter- and intra-atrial electromechanical delays (EMDs) were calculated. Left atrial (LA) volumes were determined according to the biplane area?Clength method. LA mechanical function parameters were calculated.

Results

LA passive emptying volume and LA passive emptying fraction decreased significantly in patients with IFG as compared with control subjects (p?<?0.001 and p?<?0.001, respectively). PA lateral and PA septal durations were significantly higher in patients with IFG than in the control group. However, no difference in PA tricuspid duration was observed between the two groups. Inter- and intra-atrial EMDs were significantly higher in patients with IFG as compared with the control subjects (median [interquartile range], 34.0 [17.0] vs. 17.0 [4.0], p?<?0.001 and 15.0 [8.5] vs. 7.5 [2.0], p?<?0.001, respectively). Positive correlations were detected between both inter- and intra-atrial EMD and glucose levels (r?=?0.76, p?<?0.001 and r?=?0.68, p?<?0.001, respectively). Additionally, a multiple linear regression analysis revealed that glucose levels were independently associated with inter-atrial EMD (???=?0.753, p?<?0.001).

Conclusion

We showed that IFG was associated with inter- and intra-atrial EMD. Our findings suggest that IFG is an etiological factor for the development of AF.