Sulindac (SLD) is a nonsteroidal anti-inflammatory drug (NSAID) that has been associated with a greater incidence of idiosyncratic hepatotoxicity in human patients than other NSAIDs. One hypothesis regarding idiosyncratic adverse drug reactions is that interaction of a drug with a modest inflammatory episode precipitates liver injury. In this study, we tested the hypothesis that lipopolysaccharide (LPS) interacts with SLD to cause liver injury in rats. SLD (50 mg/kg) or its vehicle was administered to rats by gavage 15.5 h before LPS (8.3 3 10 5 endotoxin unit/kg) or its saline vehicle (i.v.). Thirty minutes after LPS treatment, SLD or vehicle administration was repeated. Rats were killed at various times after treatment, and serum, plasma, and liver samples were taken. Neither SLD nor LPS alone caused liver injury. Cotreatment with SLD/LPS led to increases in serum biomarkers of both hepatocellular injury and cholestasis. Histological evidence of liver damage was found only after SLD/LPS cotreatment. As a result of activation of hemostasis induced by SLD/LPS cotreatment, fibrin and hypoxia were present in liver tissue before the onset of hepatotoxicity. Heparin treatment reduced hepatic fibrin deposition and hypoxia and protected against liver injury induced by SLD/LPS cotreatment. These results indicate that cotreatment with nontoxic doses of LPS and SLD causes liver injury in rats, and this could serve as a model of human idiosyncratic liver injury. The hemostatic system is activated by SLD/LPS cotreatment and plays an important role in the development of SLD/LPS-induced liver injury.
Many hepatotoxicants like acetaminophen, chloroform, carbon tetrachloride, halothane, and thioacetamide cause hepatotoxicity through covalent binding of their reactive metabolites to proteins. The covalent binding to proteins may lead to dysfunction of critical proteins such as enzymes, transporters, receptors, and regulatory molecules. Because most reactive metabolites covalently bind to tissue macromolecules and tend to be unstable, they can not be isolated, and direct quantitation of the formation of reactive metabolites is not possible. Measuring their covalent binding to proteins offers a convenient way to estimate the amount of reactive metabolite formation. Such estimates have been used to quantify the bioactivation-based injury due to such hepatotoxicants. There are various methods by which covalent binding may be measured. This unit describes a protocol in which a radiolabeled compound can be utilized to measure covalent binding. Alternate protocols involve immunoblotting and immunohistochemistry. The time and method of measuring covalent binding play an important role in the evaluation.
Objective. To identify trends in pharmacy education during last two decades using text mining. Methods. Articles published in the American Journal of Pharmaceutical Education (AJPE) in the past two decades were compiled in a database. Custom text analytics software was written using Visual Basic programming language in the Visual Basic for Applications (VBA) editor of Excel 2007. Frequency of words appearing in article titles was calculated using the custom VBA software. Data were analyzed to identify the emerging trends in pharmacy education. Results. Three educational trends emerged: active learning, interprofessional, and cultural competency. Conclusion. The text analytics program successfully identified trends in article topics and may be a useful compass to predict the future course of pharmacy education.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.