Progression of Postprandial Blood Plasma Phospholipids Following Acute Intake of Different Dairy Matrices: A Randomized Crossover Trial

Studies have indicated that the dairy matrix can affect postprandial responses of dairy products, but little is known about the effect on postprandial plasma phospholipid levels. This study investigated postprandial plasma phospholipid levels following consumption of four different dairy products that are similar in micro and macro nutrients, but different in texture and structure: cheddar cheese (Cheese), homogenized cheddar cheese (Hom. Cheese), micellar casein isolate with cream (MCI Drink) or a gel made from the MCI Drink (MCI Gel). The study was an acute randomized, crossover trial in human volunteers with four test days. Blood samples were collected during an 8 h postprandial period and the content of 53 plasma phospholipids was analysed using liquid chromatography-mass spectrometry (LC-MS). No meal–time interactions were revealed; however, for nine of the 53 phospholipids, a meal effect was found. Thus, the results indicated a lower plasma level of specific lyso-phosphatidylethanolamines (LPEs) and lyso-phosphatidylcholines (LPCs) following consumption of the MCI Gel compared to the MCI Drink and Hom. Cheese, which might be attributed to an effect of viscosity. However, further studies are needed in order to reveal more details on the effect of the dairy matrix on postprandial phospholipids.

The relationship between exacerbated diabetic peripheral neuropathy and metformin treatment in type 2 diabetes mellitus

Metformin-treated diabetics (MTD) showed a decrease in cobalamin, a rise in homocysteine, and methylmalonic acid, leading to accentuated diabetic peripheral neuropathy (DPN). This study aimed to determine whether or not metformin is a risk factor for DPN. We compared MTD to non-metformin-treated diabetics (NMTD) clinically using the Toronto Clinical Scoring System (TCSS), laboratory (methylmalonic acid, cobalamin, and homocysteine), and electrophysiological studies. Median homocysteine and methylmalonic acid levels in MTD vs. NMTD were 15.3 vs. 9.6 µmol/l; P < 0.001 and 0.25 vs. 0.13 µmol/l; P = 0.02, respectively with high statistical significance in MTD. There was a significantly lower plasma level of cobalamin in MTD than NMTD. Spearman’s correlation showed a significant negative correlation between cobalamin and increased dose of metformin and a significant positive correlation between TCSS and increased dose of metformin. Logistic regression analysis showed that MTD had significantly longer metformin use duration, higher metformin dose > 2 g, higher TCSS, lower plasma cobalamin, and significant higher homocysteine. Diabetics treated with metformin for prolonged duration and higher doses were associated with lower cobalamin and more severe DPN.

Proteomic analysis reveals sex-specific biomarker signature in postural orthostatic tachycardia syndrome

Background Postural orthostatic tachycardia syndrome (POTS) is a variant of cardiovascular (CV) autonomic disorder of unknown etiology characterized by an excessive heart rate increase on standing and orthostatic intolerance. In this study we sought to identify novel CV biomarkers potentially implicated in POTS pathophysiology. Methods We conducted a nested case-control study within the Syncope Study of Unselected Population in Malmö (SYSTEMA) cohort including 396 patients (age range, 15–50 years) with either POTS (n = 113) or normal hemodynamic response during passive head-up-tilt test (n = 283). We used a targeted approach to explore changes in cardiovascular proteomics associated with POTS through a sequential two-stage process including supervised principal component analysis and univariate ANOVA with Bonferroni correction. Results POTS patients were younger (26 vs. 31 years; p < 0.001) and had lower BMI than controls. The discovery algorithm identified growth hormone (GH) and myoglobin (MB) as the most specific biomarker fingerprint for POTS. Plasma level of GH was higher (9.37 vs 8.37 of normalised protein expression units (NPX); p = 0.002), whereas MB was lower (4.86 vs 5.14 NPX; p = 0.002) in POTS compared with controls. In multivariate regression analysis, adjusted for age and BMI, and stratified by sex, lower MB level in men and higher GH level in women remained independently associated with POTS. Conclusions Cardiovascular proteomics analysis revealed sex-specific biomarker signature in POTS featured by higher plasma level of GH in women and lower plasma level of MB in men. These findings point to sex-specific immune-neuroendocrine dysregulation and deconditioning as potentially key pathophysiological traits underlying POTS.

Association of Interleukin-18 Gene Polymorphism with Susceptibility to Visceral Leishmaniasis in Endemic Area of Bihar, an Indian Population

Interleukin-18 (IL-18) is a cytokine that mediates Th1 response by inducing interferon-gamma (IFN-γ) production in T cells and natural killer cells. Genetic polymorphisms in the IL-18 gene have been found to be associated with its expression in cancer, tuberculosis, HBV infection, and various other diseases. Lower plasma level of IL-18 in visceral leishmaniasis (VL) patients might be associated with polymorphisms in the regulating or coding region of the gene. Three single nucleotide polymorphisms (SNPs), rs1946519 (−656 G/T) and rs187238 (−137 G/C) in the promoter region and rs549908 (+105 A/C) in the codon region, were genotyped in 204 parasitological confirmed VL patients and 267 controls with no past history of VL. For each locus, polymerase chain reaction (PCR) followed by restriction digestion was performed. IL-18 expression in peripheral blood mononuclear cells (PBMC) collected from VL patients and controls was measured by quantitative real-time RT-PCR. Distribution of G allele at position −656(P<0.0001)and double haplotypes GGC/GGA(P=0.05)were found to be significantly associated with controls while genotypes TT(P<0.0001)and single haplotypes TGA(P=0.0002), with cases. The inheritance of G allele at the position −656 might be considered as a protective allele for VL.

The effect of membrane biocompatibility on plasma beta 2-microglobulin levels in chronic hemodialysis patients.

Several studies have shown that patients who have been dialyzed with high-flux biocompatible membranes have a lower plasma level of beta 2-microglobulin and a lower incidence of amyloid disease compared with patients who have been dialyzed with low-flux bioincompatible membranes. However, because high-flux membranes are associated with significant dialytic removal of beta 2-microglobulin, the specific role of membrane biocompatibility in influencing the rate of increase of beta 2-microglobulin has not been previously determined. This study investigated the effect of biocompatibility on the rate of increase of plasma levels of beta 2-microglobulin in 159 new hemodialysis patients from 13 dialysis centers (ten centers affiliated with Dallas Nephrology Associates and three with Vanderbilt University Medical Center) by using two low-flux membranes with widely different biocompatibilities. These patients were prospectively randomized to be dialyzed with either a low-flux biocompatible membrane or a low-flux bioincompatible membrane. Plasma beta 2-microglobulin levels were measured at 0, 3, 6, 9, 12, and 18 months. Sixty-six patients completed the 18-month study. Plasma beta 2-microglobulin increased in all patients; however, the increase was not significantly different from baseline at any time point in the group that used the biocompatible membrane. In this group, beta 2-microglobulin increased from (mean +/- SD) 27.8 +/- 14.8 mg/L to 34.0 +/- 10.0 mg/L at 18 months (P = not significant), and the mean increase at 18 months was 2.6 +/- 14.7 mg/L. In contrast, the increase in plasma beta 2-microglobulin level in the bioincompatible membrane group became significant in Month 6 when the levels had increased from a baseline of 24.8 +/- 9.6 mg/L to 29.5 +/- 12.2 mg/L (P < 0.001); these increases continued to be significant until Month 18, when serum beta 2-microglobulin reached 36.8 +/- 13.9 mg/L with an average increase of 11.8 +/- 11.2 mg/L (P < 0.0001). The higher rate of plasma B2-microglobulin increase in the group that had been dialyzed with the bioincompatible membrane was also evident when only patients who had completed the study were analyzed. There were no significant differences in the actual level of beta 2-microglobulin or in residual renal function between the two groups during the 18 months of the study. It was concluded that over a period of 18 months, the use of biocompatible membranes, even in the low-flux configuration, is associated with a significantly slower increase in plasma beta 2-microglobulin, independent of the influence of residual renal function.

THe Effect Of The Synthetic Thrombin Inhibitor, No. 805, On An Experimental DIC In Rabbits

Our studies of synthetic thrombin inhibitors of arginine derivatives yielded very recently No. 805 (MCI-9038 or MD-805) having a specific stereostructure of 4-methyl-2- piperidinecarboxylic acid at its carboxamide portion which showed an extremely potent and selective inhibition of thrombin with a Ki of 0.019 μM.The effect of No. 805 on an experimental DIC was studied. An experimental DIC in rabbits was generated by a constant i.v. infusion of 0.1 M lactic acid and crude bovine placental tissue thromboplastin. A rapid decrease in platelet number and a gradual decrease in fibrinogen content in plasma were observed over the experiment period of 5 hrs. The i.v. infusion of No. 805 suppressed the decrease in platelet number and fibrinogen content dose- dependently from 1.0 to 31.6 μg/kg/min and the suppression of ca. 50% was attained at a dose of 3.16 μg/kg/min showing a plasma level as low as ca. 0.3 μM, while heparin given at a dose of 100 or 1,000 u/kg i.v. (x2) did not show a notable suppression of the platelet number decrease but a significant suppression of the fibrinogen content decrease. Thus, No. 805 was shown to be effective on the experimental DIC at lower plasma level, exhibiting more dominant effects on platelets than heparin. This result was carefully compared with those on other animal thrombosis.