Risk factor paradox in wasting diseases.

Purpose of reviewEmerging data indicate that conventional cardiovascular risk factors (e.g. hypercholesterolemia and obesity) are paradoxically associated with better survival in distinct populations with wasting. We identify these populations and review survival paradoxes and common pathophysiologic mechanisms.Recent findingsA 'reverse epidemiology' of cardiovascular risk is observed in chronic kidney disease, chronic heart failure, chronic obstructive lung disease, cancer, AIDS and rheumatoid arthritis, and in the elderly. These populations apparently have slowly progressive to full-blown wasting and significantly greater short-term mortality than the general population. The survival paradoxes may result from the time differential between the two competing risk factors [i.e. over-nutrition (long-term killer but short-term protective) versus undernutrition (short-term killer)]. Hemodynamic stability of obesity, protective adipokine profile, endotoxin-lipoprotein interaction, toxin sequestration of fat, antioxidation of muscle, reverse causation, and survival selection may also contribute.SummaryThe seemingly counterintuitive risk factor paradox is the hallmark of chronic disease states or conditions associated with wasting disease at the population level. Studying similarities among these populations may help reveal common pathophysiologic mechanisms of wasting disease, leading to a major shift in clinical medicine and public health beyond the conventional Framingham paradigm and to novel therapeutic approaches related to wasting and short-term mortality

Capability of polygonum cuspidatum extract in inhibiting AGEs and preventing diabetes

Diabetes is a metabolic disorder disease associated with advanced glycation end products (AGEs) and protein glycation. The effect of polygonum cuspidatum extract (PE) on AGEs and Nε‐(Carboxymethyl)‐L‐lysine formation, protein glycation, and diabetes was investigated. Six primary phenolics in a range of 12.36 mg/g for ellagic acid to 0.01 mg/g for piceid were determined in PE. In an intermediate‐moisture‐foods model, inhibition rate of PE was as high as 54.2% for AGEs and 78.9% for CML under aw 0.75. The protein glycation was also inhibited by PE. In a diabetic rat model, the levels of blood glucose, serum malondialdehyde, cholesterol, triglycerides, and low‐density lipoproteins were effectively reduced by PE treatment. The antioxidation capacity (T‐AOC) and superoxide dismutase (SOD) activity were also mediated by PE. Additionally, the activates of liver function‐related enzymes including alkaline phosphatase (ALP), glutamate pyruvate transaminase (GPT), and glutamate oxaloacetate transaminase (GOT) in diabetic rat were improved by PE

Methylated N-(4-N,N-Dimethylaminobenzyl) Chitosan, a Novel Chitosan Derivative, Enhances Paracellular Permeability Across Intestinal Epithelial Cells (Caco-2)

The aim of this study was to investigate the effect of methylated N-(4-N,N-dimethylaminobenzyl) chitosan, TM-Bz-CS, on the paracellular permeability of Caco-2 cell monolayers and its toxicity towards the cell lines. The factors affecting epithelial permeability, e.g., degree of quaternization (DQ) and extent of dimethylaminobenzyl substitution (ES), were evaluated in intestinal cell monolayers of Caco-2 cells using the transepithelial electrical resistance and permeability of Caco-2 cell monolayers, with fluorescein isothiocyanate dextran 4,400 (FD-4) as a model compound for paracellular tight-junction transport. Cytotoxicity was evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide viability assay. The results revealed that, at pH 7.4, TM-Bz-CS appeared to increase cell permeability in a concentration-dependent manner, and this effect was relatively reversible at lower doses of 0.05–0.5 mM. Higher DQ and the ES caused the permeability of FD-4 to be higher. The cytotoxicity of TM-Bz-CS depended on concentration, %DQ, and %ES. These studies demonstrated that this novel modified chitosan has potential as an absorption enhancer