The association between triglyceride to high-density-lipoprotein cholesterol ratio and insulin resistance in a multiethnic primary prevention cohort

The objective was to explore the clinical utility of triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio in predicting insulin resistance (IR) in 4 ethnic groups and the relationship between IR and TG/HDL-C in comparison to that with other lipid measures. Apparently healthy Aboriginals, Chinese, Europeans, and South Asians (N = 784) were assessed for sociodemographics, lifestyle, anthropometry, lipids, glucose, and insulin. The homeostasis model assessment of IR was used as a measure of IR. Compared with other lipid parameters, TG/HDL-C was the highest correlate of the homeostasis model assessment of IR (age and sex adjusted) in Aboriginals (r = 0.499, P < .001), Chinese (r = 0.432, P < .001), Europeans (r = 0.597, P < .001), and South Asians (0.372, P < .001). For a 1-unit increase in TG/HDL-C, the odds of being insulin resistant increased about 4 times (odds ratio [OR], 3.95; 95% confidence interval [CI], 1.86-8.42; P < .001) in Aboriginals, 3.4 times in Chinese (OR, 3.44; 95% CI, 1.79-6.62; P < .001), 1.9 times in Europeans (OR, 1.94; 95% CI, 1.00-3.75; P = .049), and 1.8 times in South Asians (OR, 1.77; 95% CI, 0.91-3.45; P = .094) (age, sex, smoking, physical activity, body mass index, and waist circumference adjusted). Receiver operating characteristic curve analyses revealed areas under the curve (95% CI) of 0.777 (0.707-0.847) in Aboriginals, 0.723 (0.647-0.798) in Chinese, 0.752 (0.675-0.828) in Europeans, and 0.676 (0.590-0.762) in South Asians. Optimal cutoffs (sensitivity, specificity) of TG/HDL-C for identifying individuals with IR were 0.9 (93.0%, 51.9%), 1.1 (71.7%, 61.5%), 1.1 (73.5%, 70.9%), and 1.8 (52.0%, 77.9%) in Aboriginal, Chinese, European, and South Asian individuals, respectively. The TG/HDL-C ratio may be a good marker to identify insulin-resistant individuals of Aboriginal, Chinese, and European, but not South Asian, origin.     

A case of postpartum eosinophilic gastroenteritis and review of the literature

Eosinophilic gastroenteritis (EG) is a rare disease of unknown etiology that can involve any area of the gastrointestinal (GI) tract. It can be classified into three major types: predominantly mucosal, muscularis, or subserosal form. Diagnosis of EG is confirmed after the exclusion of other disorders having similar features, such as parasitic infection, carcinoma, allergy, and autoimmune conditions such as Churg-Strauss disease. Correct diagnosis hinges on the presence of eosinophilic infiltration of one or more areas of the GI tract, without extraintestinal involvement. We present the case of a 30-year-old female with symptoms of EG 26 days after delivery. After corticosteroid and montelukast treatment for 2 weeks, all symptoms and objective clinical findings disappeared. Although numerous cases of this disorder have been described, to our knowledge this is the first case of postpartum EG. This case highlights the need to include this entity in the differential diagnosis of postpartum GI disorders.     

Prediction of a Good Response to Cardiac Resynchronization Therapy in Patients with Severe Dilated Cardyomyopathy: Could Conventional Echocardiography Be the Answer after All?

Objectives: The aim of this study was to assess the performance of echocardiographic parameters to predict response to cardiac resynchronization therapy (CRT). Background: CRT reduces morbidity and mortality due to the proper selection of candidates for CRT. Methods: The 12‐month trial was performed on 70 optimally medicated patients with standard inclusion criteria: NYHA class III or IV heart failure, left ventricular ejection fraction (LVEF) ≤ 35%, and QRS ≥ 120 ms. All parameters were evaluated by conventional and tissue Doppler‐based methods. Indicator of positive CRT response was more than 20% in improvement of LVEF. Results: LVEF increased >20% in 42 patients. Out of 43 tested baseline echocardiographic parameters, 12 showed statistical difference between responders and nonresponders. Out of these 12 parameters, six (LVSV, LVSI, LVFS, RVd, VPMR, and PISA) had modest to moderately good ability to predict LVEF response with sensitivity ranging from 62.2% to 82.4%, and specificity ranging from 56.5% to 81.2%. For those parameters, the area under the receiver‐operating characteristic curve for positive response to CRT was ≤0.76. Multivariate regression analysis resulted in selection of LVSI and LVFS as possible predictive independent parameters for a good response. The cutoff value for LVSI was 38.7 mL/m² (P = 0.045) and for LVFS was 13% (P = 0.032). Conclusions: Contribution of LVSI and LVFS is to be confirmed in larger trials. Simplicity of their assessment by conventional echocardiography could be an argument for adding them to the inclusion criteria for CRT in severe heart failure patients. (Echocardiography 2012;29:267‐275)     

Alzheimer’s disease and type 2 diabetes: the association study of polymorphisms in tumor necrosis factor-alpha and apolipoprotein E genes

Type 2 diabetes (T2D) and Alzheimer??s disease (AD) are two progressive disorders with high prevalence worldwide. Polymorphisms in tumor necrosis factor-alpha (TNF-??) and apolipoprotein E (ApoE) genes might be associated with both T2D and AD, representing possible genetic markers for the development of the AD in subjects with T2D. The aim was to determine ApoE and G-308A TNF-?? gene polymorphisms in unrelated Croatian Caucasians: 207 patients with sporadic AD, 196 T2D patients and 456 healthy controls. Patients with AD had higher frequency of ApoE4 allele compared to T2D patients and controls. The significant association, observed between ApoE2 allele and T2D, disappeared after the data were adjusted for age and sex. The genotype or allele frequencies of G-308A TNF-?? gene polymorphism were similar among the patients with AD, T2D and healthy controls. In conclusion, these results do not support the hypothesis that the A allele of G-308A TNF-?? gene polymorphism is associated either with AD or T2D. Our data confirm the association between the ApoE4 allele and AD, and point out the E2 allele of ApoE gene as the possible risk factor for T2D.     

EphB4 enhances the process of endochondral ossification and inhibits remodeling during bone fracture repair

Previous reports have identified a role for the tyrosine kinase receptor EphB4 and its ligand, ephrinB2, as potential mediators of both bone formation by osteoblasts and bone resorption by osteoclasts. In the present study, we examined the role of EphB4 during bone repair after traumatic injury. We performed femoral fractures with internal fixation in transgenic mice that overexpress EphB4 under the collagen type 1 promoter (Col1‐EphB4) and investigated the bone repair process up to 12 weeks postfracture. The data indicated that Col1‐EphB4 mice exhibited stiffer and stronger bones after fracture compared with wild‐type mice. The fractured bones of Col1‐EphB4 transgenic mice displayed significantly greater tissue and bone volume 2 weeks postfracture compared with that of wild‐type mice. These findings correlated with increased chondrogenesis and mineral formation within the callus site at 2 weeks postfracture, as demonstrated by increased safranin O and von Kossa staining, respectively. Interestingly, Col1‐EphB4 mice were found to possess significantly greater numbers of clonogenic mesenchymal stromal progenitor cells (CFU‐F), with an increased capacity to form mineralized nodules in vitro under osteogenic conditions, when compared with those of the wild‐type control mice. Furthermore, Col1‐EphB4 mice had significantly lower numbers of TRAP‐positive multinucleated osteoclasts within the callus site. Taken together, these observations suggest that EphB4 promotes endochondral ossification while inhibiting osteoclast development during callus formation and may represent a novel drug target for the repair of fractured bones. © 2013 American Society for Bone and Mineral Research.     

Essential Fatty Acid Plasma Profiles Following Gastric Bypass and Adjusted Gastric Banding Bariatric Surgeries

Background

Although patients experience hair loss and dry skin which may be attributable to deficiency in essential fatty acids (EFAs), the impact of bariatric surgeries on EFA status is unknown.

Methods

This study aimed to assess plasma phospholipid fatty acid profiles following adjustable gastric banding (AGB), which restricts dietary fat intake, versus Roux-en-Y gastric bypass (RYGB), which also promotes fat malabsorption. Serial measures were obtained before and 1 and 6 months from women undergoing RYGB (N?=?13) and AGB (N?=?5). Measures included the composition of plasma fatty acids in phospholipids, dietary intake, and body fat mass. Friedman and Mann–Whitney tests were used to assess differences over time and between groups, respectively, p?<?0.05.

Results

Dietary intake of fats decreased equally at 1 and 6 months following RYGB and AGB. By 6 months, the RYGB group lost more body fat. There were no remarkable changes in EFA in plasma phospholipids following AGB. However, following RYGB, a transient increase in 20:4N6 (+18 %) and a decrease in 20:3N6 at 1 (?47 %) and 6 months (?47 %) were observed. Similar changes were observed in N3 fatty acids following RYGB, including a transient increase in 22:6N3 (+11 %) and decreases in 20:5N3 (?79 and ?67 % at 1 and 6 months, respectively). EFA status improved following surgery in the RYGB group.

Conclusions

We demonstrate alterations in plasma EFA following RYGB. The status of EFA improved, but the decrease in 20:5N3, the precursor for anti-inflammatory eicosanoids, may be a concern.

     

Possible role for interactions between 5-lipoxygenase (5-LOX) and AMPA GluR1 receptors in depression and in antidepressant therapy

Emerging evidence suggests that 5-lipoxygenase (5-LOX) plays a role in central nervous system functioning. It has been shown that 5-LOX metabolic products can decrease the phosphorylation of the glutamate receptor subunit GluR1, and that this effect can be antagonized by 5-LOX inhibitors. Recent concepts about the pathobiological mechanisms of depression and the molecular mechanisms of antidepressant activity postulate a significant role for glutamatergic neurotransmission and the GluR1 receptor. Regulation of GluR1 phosphorylation, i.e., enhancement of this phosphorylation, may be a part of antidepressant activity. On the other hand, reduced GluR1 phosphorylation may be a pathobiological mechanism contributing to depression. Since 5-LOX inhibitors, along with antidepressants share the capacity to increase GluR1 phosphorylation, we hypothesize that they may also have antidepressant properties. Furthermore, we postulate that increased brain 5-LOX expression may lead to decreased GluR1 phosphorylation and favor the development of depression. For example, brain 5-LOX expression is stimulated by stress hormone glucocorticoids, and stress is a known contributing factor in depression.