Anti-BSA polyclonal antibody

Drug-induced kidney injury (DIKI) is a frequent occurrence in nonclinical drug development. It is well established that novel urine kidney safety biomarkers will outperform urea nitrogen (BUN) and serum creatinine (sCr) for monitoring direct drug injury to the kidney across numerous compounds spanning diverse mechanisms and efforts are underway for a formal regulatory clinical qualification. However, it remains unclear how these novel biomarkers will perform under prerenal azotemia when BUN and sCr are elevated but no infra-renal injury is suspected. This lack of knowledge is largely due to the dearth of such nonclinical animal models. We report here that treatment of dogs with a potent antihypertensive compound MK-5478 at a suprapharmacologic dose for up to 9 days results in the development of prerenal azotemia and, in some dogs, kidney toxicity through the dual sustained effects of MK-5478 as a nitric oxide donor and an angiotensin II receptor blocker (ARB). While conventional serum biomarkers BUN, and often sCr as well, were highly elevated in these dogs with or without kidney damage, urine kidney biomarkers clusterin (CLU) and neutrophil gelatinase-associated lipocalin (NGAL) showed increases only in dogs with kidney histopathologic changes following the sustained period of prerenal azotemia. Urine albumin (ALB) and total protein also tracked with kidney lesions but with less sensitivity. Thus, we present evidence for the first time that urine kidney safety biomarkers used together with BUN and sCr can distinguish infra-renal injury among dogs with prerenal azotemia while the conventional serum biomarkers alone are ambiguous, either being interpreted as false positives of kidney injury, or dismissed under circumstances as benign without appreciation for a threshold of impending injury.

Objective: To conduct a meta-analysis evaluating the effect of combining traditional Chinese medicine (TCM) with Western medicine in treating hepatitis C, and to provide an evidence-based medical strategy. Methods: Randomized controlled trials (RCTs) comparing the effect of pegylated interferon (Peginterferon) combined with ribavirin (PR) alone and its combination with TCM were manually retrieved from the Weipu Information Resources System (VIP), Wan Fang Database, PubMed, and the Chinese Journal Full Text Database (CNKI). Studies meeting the inclusion criteria were selected and analyzed using the Review Manager 5.3 software. Suitable tests were also performed to determine the quality, heterogeneity, and sensitivity of the studies included in the meta-analysis. Results: Twenty-eight RCTs met the inclusion criteria. The combination therapy or intervention group showed significantly greater HCV-RNA negative rate post-treatment compared to the monotherapy or the control group (P < .05). In addition, the serum levels of the liver function indicators alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin (ALB) were significantly improved after the combination therapy compared to PR alone (P < .05), while total bilirubin (TB) and r-glutamyltransferase (GGT) levels were not affected by TCM (P > .05). Finally, the parameters of liver fibrosis were also reduced by the combination therapy more effectively than the monotherapy. Conclusion: The combination of TCM and PR can improve the Comprehensive Clinical Efficacy of hepatitis C and have a better negative rate of HCV-RNA with a better benefit in the liver function. The effect of TCM + PR is better than that of PR alone in treating hepatitis C.