Red blood cell distribution width as a predictor of outcome in Intensive Care Unit: a retrospective cohort study.

Aim To evaluate the predictive significance of the red blood cell distribution width (RDW) >14.5 at admission to the Intensive Care Unit (ICU) on outcome parameters: length of hospital stay (LOHS), incidence of hospital mortality, 30-day mortality and 30-day survival after hospital discharge in unselected (surgical and non-surgical) critically ill patients. Methods A total of 325 surgical and non-surgical critically ill patients were divided based on the RDW value at admission to the ICU into two groups: Group 1 (RDW >14.5) and Group 2 (RDW ≤14.5). Demographic and clinical parameters, laboratory findings,treatment and outcome parameters were compared between the groups. The predictive significance of RDW>14.5 on outcome parameters was analysed using linear regression analysis and univariate and multivariate logistic regression analysis, as appropriate. Results In Group 1, LOHS was higher (19.77±15.15; p<0.000) as was the prevalence of hospital mortality (46.6%; p<0.0523), while 30-day survival after hospital discharge was lower (52.9%; p>0.026) compared to Group 2. RDW >14.5 was positively linearly related (r=0.64; r2=0.40; p=0.000) with LOHS. RDW >14.5 predicted the prevalence of in-hospital mortality with a 73.7% positive predictive value (AUC 0.62; sensitivity 70.1%; specificity 59.5%; p<0.05) and 30-day survival after hospital discharge with a 34.5% negative predictive value (AUC 0.45; sensitivity 58.3%; specificity 68.7%; p<0.05). Conclusions RDW value >14.5 at admission to the ICU can predict prolonged hospital stay, higher mortality and lower survival rate. RDW >14.5 may be an inexpensive and widely available early warning to redirect diagnostic and therapeutic decisions and improve outcomes.

The effect of three polyphenols and some other antioxidant substances on amyloid fibril formation by Human cystatin C.

Human cystatin C (CysC) is an amyloid forming protein involved in the hereditary cerebral amyloid angiopathy (HCCAA) that affects arteries in the brain and the peripheral nervous system. In this study we measured the influence of several substances on human CysC aggregation and amyloid fibril formation, induced at pH 4 in vitro. The effect of three polyphenols: resveratrol, quercetin and curcumin and of two antioxidants: vitamin C (VitC) and N-acetyl-L-cysteine (NAC) was explored as well as the effect of sulphoraphane (SF) and α-lipoic acid (AL). The formation of amyloid fibrils was followed by Thioflavin T (ThT) fluorescence and by transmission electron microscopy (TEM). Effects on the length of the lag phase were revealed by following the increase of ThT fluorescence intensity with time. The amount and morphology of fibrils in comparison to prefibrillar aggregates and globular oligomers were evaluated by TEM at the plateau stage of the reaction. Thermal stabilization of the CysC monomer by the small compounds was measured by differential scanning fluorimetry (DSF). NAC, VitC and SF exhibited the largest inhibitory effect on amyloid fibril growth. The effects of polyphenols were not significant, apart from resveratrol, which partly inhibited the amyloid fibril growth.

Inhibition of Protein Aggregation by Several Antioxidants.

Amyloid fibril formation is a shared property of all proteins; therefore, model proteins can be used to study this process. We measured protein aggregation of the model amyloid-forming protein stefin B in the presence and absence of several antioxidants. Amyloid fibril formation by stefin B was routinely induced at pH 5 and 10% TFE, at room temperature. The effects of antioxidants NAC, vitamin C, vitamin E, and the three polyphenols resveratrol, quercetin, and curcumin on the kinetics of fibril formation were followed using ThT fluorescence. Concomitantly, the morphology and amount of the aggregates and fibrils were checked by transmission electron microscopy (TEM). The concentration of the antioxidants was varied, and it was observed that different modes of action apply at low or high concentrations relative to the binding constant. In order to obtain more insight into the possible mode of binding, docking of NAC, vitamin C, and all three polyphenols was done to the monomeric form of stefin B.

THE ROLE OF CYSTEINE PROTEASE IN ALZHEIMER DISEASE.

INTRODUCTION: Cysteine protease are biological catalysts which play a pivotal role in numerous biological reactions in organism. Much of the literature is inscribed to their biochemical significance, distribution and mechanism of action. Many diseases, e.g. Alzheimer's disease, develop due to enzyme balance disruption. Understanding of cysteine protease's disbalance is therefor a key to unravel the new possibilities of treatment. Cysteine protease are one of the most important enzymes for protein disruption during programmed cell death. Whether protein disruption is part of cell deaths is not enough clear in any cases. Thereafter, any tissue disruption, including proteolysis, generate more or less inflammation appearance. REVIEW: This review briefly summarizes the current knowledge about pathological mechanism's that results in AD, with significant reference to the role of cysteine protease in it. Based on the summary, new pharmacological approach and development of novel potent drugs with selective toxicity targeting cysteine protease will be a major challenge in years to come.