Alpha-Melanocyte-Stimulating Hormone and Agouti-Related Protein: Do They Play a Role in Appetite Regulation in Childhood Obesity?

Objective:

The hypothalamus plays a crucial role in the regulation of feeding behavior. The anorexigenic neuropeptide alpha-melanocyte-stimulating hormone (α-MSH) and the orexigenic neuropeptide agouti-related protein (AgRP) are among the major peptides produced in the hypothalamus. This study investigated the plasma concentrations of α-MSH and AgRP in underweight and obese children and their healthy peers. The associations between α-MSH and AgRP levels and anthropometric and nutritional markers of malnutrition and obesity were also assessed.

Methods:

Healthy sex-matched subjects aged 2 to 12 years were divided into 3 groups, as underweight (n=57), obese (n=61), and of normal weight (n=57). Plasma fasting concentrations of α-MSH and AgRP were measured by enzyme-linked immunosorbent assay. The differences between the three groups as to the relationships between plasma concentrations of α-MSH and AgRP and anthropometric data, serum biochemical parameters and homeostatic model assessment of insulin resistance were evaluated.

Results:

Obese children had significantly lower α-MSH levels than underweight (1194±865 vs. 1904±1312 ng/mL, p=0.006) and normal weight (1194±865 vs. 1762±1463 ng/mL, p=0.036) children; there were no significant differences in the α-MSH levels between the underweight and normal weight children (p=0.811). Also, no significant differences were observed between the underweight and obese children regarding the AgRP levels (742±352 vs. 828±417 ng/mL, p=0.125). We found a significant positive correlation between plasma α-MSH and AgRP levels across the entire sample.

Conclusion:

This study is the first to demonstrate body weight-related differences in α-MSH and AgRP levels in children. Circulating plasma α-MSH levels in obese children were markedly lower than those of underweight and normal-weight children. This suggests that α-MSH could play a role in appetite regulation.     

Coronary Adventitial and Perivascular Adipose Tissue Inflammation in Patients With Vasospastic Angina

Background

Recent studies suggested that perivascular components, such as perivascular adipose tissue (PVAT) and adventitial vasa vasorum (VV), play an important role as a source of various inflammatory mediators in cardiovascular disease.

Subclinical Intestinal Inflammation in Siblings of Children with Crohn’s Disease

Background  

Intestinal permeability and altered inflammatory responses, along with genetic and environmental factors, likely contribute to the pathogenesis of Crohn’s disease.     

Phasic and Tonic Stress–Strain Data Obtained in Intact Intestinal Segment In Vitro

The function of the small intestine is to a large degree mechanical, and it has the capability of deforming its shape by generating phasic (short-lasting) and tonic (sustained) contraction of the smooth muscle layers. The aim of this study was to obtain phasic and tonic stress-strain (normalized force-length) curves during distension of isolated rat jejunum and ileum (somewhat similar to the isometric length-tension diagram known from in vitro studies of muscle strips). We hypothesized that the circumferential stress-strain data depend on longitudinal stretch of the intestine. Intestinal segments were isolated from ten Wistar rats and put into an organ bath containing 37 degrees C aerated Krebs solution. Ramp distension was done on active and passive intestinal segments at longitudinal stretch ratios of 0, 10, and 20%. Ramp pressures from 0 to 7.5 cmH(2)O were applied to the intestinal lumen at each longitudinal stretch ratio. Passive conditions were obtained by adding the calcium antagonist papaverine to the solution. Total and passive circumferential stress and strain were computed from the length, diameter and pressure data and from the zero-stress state geometry. The active stress was defined as the total stress minus the passive stress. The total and passive circumferential stresses increased exponentially as a function of the strain. The amplitude of both the total and passive stress was biggest in the jejunum. The total circumferential stress decreased whereas the passive circumferential stress increased when the intestine was stretched longitudinally. Consequently, longitudinal stretching caused the active circumferential stress to decrease. The passive circumferential stress during longitudinal stretching increased more in the jejunum than in the ileum. Therefore, the active circumferential stress decreased most in the jejunum. In conclusion, the circumferential active-passive stress and strain depend on the longitudinal stretch and differs between the jejunum and ileum.     

Effect of Bacterial Chemotactic Peptides on Intestinal Inflammation in Animal Models of Acute and Chronic “Relapsed” Colitis

It is known that bacterial chemotactic peptides such as formyl-methionyl-leucyl-phenylalanine (fMLP) exacerbate colitis during the acute phase, but the precise role of fMLP during chronic “relapse” is unknown. In this study we examined the effect of bacterial peptides in animal models of acute and chronic “relapsed” colitis. Different parameters were evaluated, such as tissue damage, myeloperoxidase activity, and mucosal function. In acute trinitrobenezene sulfonic acid colitis, fMLP had significant adverse effects on mucosal function and worsened several parameters. In contrast, in chronic “relapsed” colitis the ability of fMLP to exacerbate the inflammation was dependent on whether it was confined to the lumen of the colon. Bacterial peptides such as fMLP appear to play a different role in the acute phase of inflammation compared with the chronic phase, depending on the integrity of the mucosal barrier.The experiments reported herein were performed in accordance with the principles described in the “Guide for the Care and Use of Laboratory Animals,” Publication No. DHHS (NIH) 86-23.This work was supported by National Institutes of Health grants including National Research Service Award F31DK60245 from the NIDDK (G.A.H.), S06-GM08239 (C.B.A.), and G12-RR03050 (C.B.A.).     

Inflammation,infection and coronary heart disease

It has become clear that inflammation is an important component of coronary heart disease. Atherosclerotic dis- ease usually begins with injury to endothelial cells. This injury can occur upon exposure to many injurious agents such as high levels of low density lipoprotein cholesterol (LDL-C), hypertension, diabetes mellitus, and tobacco smoke as well as infectious agents. Once the injury occurs, lipo- proteins and inflammatory cells are attracted to the area. Activated macrophages and T lymphocytes contribute to the inflammatory process and release cytokines into the circulation attracting further inflammatory cells to the area of injury. Many of these inflammatory cytokines can be measured in the plasma and correlate with both the extent of coronary disease and complications of the disease.     

Gene Delivery to Intestinal Epithelial Cells In vitro and In vivo with Recombinant Adeno-Associated Virus Types 1, 2 and 5

Intestinal disorders such as inflammatory bowel disease (IBD) result in chronic illness requiring lifelong therapy. Our aim was to evaluate the efficacy of recombinant adeno-associated virus (AAV) vector-mediated gene delivery to intestinal epithelial cells in vitro and in vivo. Human colon epithelial cell lines and colon biopsies were transduced using AAV pseudotypes 2/1, 2/2, and 2/5 encoding green fluorescence protein (GFP). Mice were administered the same vectors through oral, enema, intraperitoneal (IP) injection and superior mesenteric artery (SMA) injection routes. Tropism and efficiency were determined by microscopy, flow cytometry, immunohistochemistry and PCR. Caco2 cells were more permissive to AAV transduction. Human colon epithelial cells in organ culture were more effectively transduced by AAV2/2. SMA injection provided the most effective means of vector gene transfer to small intestine and colonic epithelial cells in vivo. Transgene detection 80 days post AAV treatment suggests transduction of crypt progenitor cells. This study shows the feasibility of AAV-mediated intestinal gene delivery, applicable for the investigation of IBD pathogenesis and novel therapeutic options, but also revealed the need for further studies to identify more efficient pseudotypes. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

The Relation of Atrial Fibrillation and Inflammation Do Inflammation Imply the Pathogenesis of Atrial Fibrillation？

Atrial fibrillation （AF）, the most commonly encountered arrhythmia in clinical practice, is associated with a 2-fold increase in total cardiovascular mortality, as well as the potential for substantial morbidity, including stroke, congestive heart failure, and cardiomyopathy. Its incidence and prevalence are increasing, and it represents a growing clinical and economic burden. Owing to relative inefficacy and side effects of current pharmacological and non-pharmacological therapy for AF, it remains a great challenge to improve primary and secondary AF prevention strategies to reduce this potentially enormous health burden.