Influence of Ketotifen, Cromolyn Sodium, and Compound 48/80 on the survival rates after intestinal ischemia reperfusion injury in rats

<p>Abstract</p> <p>Background</p> <p>Mast cells were associated with intestinal ischemia-reperfusion injury, the study was to observe the influence of Ketotifen, Cromolyn Sdium(CS), and Compound 48/80(CP) on the survival rates on the third day after intestinal ischemia-reperfusion injury in rats.</p> <p>Methods</p> <p>120 healthy Sprague-Dawley rats were randomly divided into 5 groups, Sham-operated group (group S), model group (group M), group K, group C and group CP. Intestinal damage was triggered by clamping the superior mesenteric artery for 75 minutes, group K, C, and CP were treated with kotifen 1 mg·kg^-1, CS 50 mg·kg^-1, and CP 0.75 mg·kg^-1i.v. at 5 min before reperfusion and once daily for three days following reperfusion respectively. Survival rate in each group was recorded during the three days after reperfusion. All the surviving rats were killed for determining the concentration of serum glutamic-oxaloacetic transaminase(AST), glutamic pyruvic transaminase(ALT), the ratio of AST compare ALT(S/L), total protein(TP), albumin(ALB), globulin(GLB), the ratio of ALB compare GLB(A/G), phosphocreatine kinase(CK), lactate dehydrogenase(LDH), urea nitrogen(BUN) and creatinine(CRE) at the 3^rdday after reperfusion. And ultrastructure of IMMC, Chiu's score, lung histology, IMMC counts, the levels of TNF-α, IL-1β, IL-6 and IL-10 of the small intestine were detected at the same time.</p> <p>Results</p> <p>Intestinal ischemia-reperfusion injury reduced the survival rate. The concentrations of TP, ALB and level of IL-10 in intestine in group M decreased significantly while the concentrations of S/L, LDH and the levels of IL-6 and TNF-α in intestine increased significantly compared with group S (<it>P </it>< 0.05). Treatment with Ketotifen and CS increased the survival rate compared with group M (<it>P </it>< 0.05), attenuated the down-regulation or up-regulation of the above index (<it>P </it>< 0.05). Treatment with CP decreased the survival rate on the 3^rdday after reperfusion compared with group M(<it>P </it>< 0.05). Group K and C had better morphology in IMMC in the small intestine and in the lungs than in group M and CP, although the Chiu's score and IMMC counts remained the same in the five groups(<it>P </it>> 0.05).</p> <p>Conclusion</p> <p>Mast cell inhibition after ischemia prior to reperfusion and following reperfusion may decrease the multi-organ injury induced by intestine ischemia reperfusion, and increase the survival rates.</p

BPR1K653, a Novel Aurora Kinase Inhibitor, Exhibits Potent Anti-Proliferative Activity in MDR1 (P-gp170)-Mediated Multidrug-Resistant Cancer Cells

Over-expression of Aurora kinases promotes the tumorigenesis of cells. The aim of this study was to determine the preclinical profile of a novel pan-Aurora kinase inhibitor, BPR1K653, as a candidate for anti-cancer therapy. Since expression of the drug efflux pump, MDR1, reduces the effectiveness of various chemotherapeutic compounds in human cancers, this study also aimed to determine whether the potency of BPR1K653 could be affected by the expression of MDR1 in cancer cells.BPR1K653 specifically inhibited the activity of Aurora-A and Aurora-B kinase at low nano-molar concentrations in vitro. Anti-proliferative activity of BPR1K653 was evaluated in various human cancer cell lines. Results of the clonogenic assay showed that BPR1K653 was potent in targeting a variety of cancer cell lines regardless of the tissue origin, p53 status, or expression of MDR1. At the cellular level, BPR1K653 induced endo-replication and subsequent apoptosis in both MDR1-negative and MDR1-positive cancer cells. Importantly, it showed potent activity against the growth of xenograft tumors of the human cervical carcinoma KB and KB-derived MDR1-positive KB-VIN10 cells in nude mice. Finally, BPR1K653 also exhibited favorable pharmacokinetic properties in rats.BPR1K653 is a novel potent anti-cancer compound, and its potency is not affected by the expression of the multiple drug resistant protein, MDR1, in cancer cells. Therefore, BPR1K653 is a promising anti-cancer compound that has potential for the management of various malignancies, particularly for patients with MDR1-related drug resistance after prolonged chemotherapeutic treatments

Trace elements in hemodialysis patients: a systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Hemodialysis patients are at risk for deficiency of essential trace elements and excess of toxic trace elements, both of which can affect health. We conducted a systematic review to summarize existing literature on trace element status in hemodialysis patients.</p> <p>Methods</p> <p>All studies which reported relevant data for chronic hemodialysis patients and a healthy control population were eligible, regardless of language or publication status. We included studies which measured at least one of the following elements in whole blood, serum, or plasma: antimony, arsenic, boron, cadmium, chromium, cobalt, copper, fluorine, iodine, lead, manganese, mercury, molybdenum, nickel, selenium, tellurium, thallium, vanadium, and zinc. We calculated differences between hemodialysis patients and controls using the differences in mean trace element level, divided by the pooled standard deviation.</p> <p>Results</p> <p>We identified 128 eligible studies. Available data suggested that levels of cadmium, chromium, copper, lead, and vanadium were higher and that levels of selenium, zinc and manganese were lower in hemodialysis patients, compared with controls. Pooled standard mean differences exceeded 0.8 standard deviation units (a large difference) higher than controls for cadmium, chromium, vanadium, and lower than controls for selenium, zinc, and manganese. No studies reported data on antimony, iodine, tellurium, and thallium concentrations.</p> <p>Conclusion</p> <p>Average blood levels of biologically important trace elements were substantially different in hemodialysis patients, compared with healthy controls. Since both deficiency and excess of trace elements are potentially harmful yet amenable to therapy, the hypothesis that trace element status influences the risk of adverse clinical outcomes is worthy of investigation.</p

Impacts of 21st century climate change on global air pollution-related premature mortality

Climate change modulates surface concentrations of fine particulate matter (PM2.5) and ozone (O-3), indirectly affecting premature mortality attributed to air pollution. We estimate the change in global premature mortality and years of life lost (YLL) associated with changes in surface O-3 and PM2.5 over the 21st century as a result of climate change. We use a global coupled chemistry-climate model to simulate current and future climate and the effect of changing climate on air quality. Epidemiological concentration-response relationships are applied to estimate resulting changes in premature mortality and YLL. The effect of climate change on air quality is isolated by holding emissions of air pollutants constant while allowing climate to evolve over the 21st century according to a moderate projection of greenhouse gas emissions (A1B scenario). Resulting changes in 21st century climate alone lead to an increase in simulated PM2.5 concentrations globally, and to higher (lower) O-3 concentrations over populated (remote) regions. Global annual premature mortality associated with chronic exposure to PM2.5 increases by approximately 100 thousand deaths (95 % confidence interval, CI, of 66-130 thousand) with corresponding YLL increasing by nearly 900 thousand (95 % CI, 576-1,128 thousand) years. The annual premature mortality due to respiratory disease associated with chronic O-3 exposure increases by +6,300 deaths (95 % CI, 1,600-10,400). This climate penalty indicates that stronger emission controls will be needed in the future to meet current air quality standards and to avoid higher health risks associated with climate change induced worsening of air quality over populated regions.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000326944000011&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Environmental SciencesMeteorology &amp; Atmospheric SciencesSCI(E)EI17ARTICLE2239-25312

Computerized decision aid for first-time homebuyers

Technology-mediated assistance in house purchasing decision is evidenced in many developed countries, however, in Malaysia less study was found although the decision challenges faced by first-time homebuyers are undeniable. This study attempts to embed technology assistance in the prominent consumer decision-making process model for the purpose of assisting first time homebuyers to make a house purchasing decision. This study employs mixed method approaches with Klang Valley, Malaysia as case study. 19 housing attributes under Locational, Neighborhood, Structural and Social Cultural group, are surveyed to validate the distinctive nature of the attributes to be part of the decision-making criteria. Factor analysis is performed on 320 data from the potential first-time homebuyers in Klang Valley. Two key factors are confirmed from the analysis; which are needs (i.e. Locational and Structural) and preferences (i.e. Neighborhood and Social Cultural). Both factors are later embedded in the proposed design model of computerized decision aid for homebuyers. The model is then evaluated through expert reviews and data was analysed qualitatively using thematic analysis. Four themes emerged from the analysis, which are Suggestion, Concern, Strength, and Limitation. Meaningful discovery on how would the future applications may have an impact is made through analysing themes with negative connotation like Concern and Limitation. The focused themes also reflect actual insights from the industry’s key players, which are useful for improvement of the proposed design model and towards more effective computerized decisionaid for first-time homebuyers