Hepatoprotective properties of oleanolic and ursolic acids in anti-tubercular drug-induced liver damage

Objective:To estimate to what extent the mixture of ursolic acid and oleanolic acid,in addition to the antitubercular standard regime,affects the hepatotoxicity profile.Methods:Liver injury was induced in male BALB/c mice by administering,per os and daily for 11 weeks,a combination of anti-Tubercular(anti-TB) agents Rifampicin(10 mg/kg),Isoniazid(10 mg/kg),and Pyrazinamide(30 mg/kg).The ursolic acid and oleanolic acid mixture at doses of 100 or 200 μg/mouse/day was subcutaneously injected throughout the entire study period(11 weeks).Biochemical and hematological analysis was supplemented by liver histological examination.Results:Animals treated with the mixture of triterpenic acids exhibited significantly decreased aspartate transaminase and alanine aminotransferase levels and amelioration of the histopathological alterations produced by the anti-TB drugs.Conclusions:The triterpene mixture is able to prevent the steatosis induced by the anti-TB drugs.

Arrhythmogenic cardiomyopathy with left ventricular involvement versus ischemic heart disease: lessons learned from the family study and the reviewed autopsy of a young male

Ischemic heart disease (IHD) is the leading cause of sudden cardiac death (SCD) and often non-thrombosed severe coronary stenoses with or without myocardial scars are detected.Left dominant arrhythmogenic cardiomyopathy (LDAC) is a life-threating rare disease which has been more thoroughly studied in the last 10years.The macroscopic study of an SCD victim was conducted and re-evaluated 9years later.The cardiological work-up in his firstdegree relatives initially comprised an electrocardiogram (ECG) and an echocardiogram.When they were re-evaluted 9years later,a cardiac magnetic resonance,an ECG-monitoring,an exercise testing and a genetic study were performed and the pedigree was extended accordingly.In 2008,an IHD was suspected in the sports-triggered SCD of a 37-year-old man upon the postmortem (75% stenosis of the left main and circumflex coronary arteries;the subepicardial left ventricular fibrofatty infiltration with mild myocardial degeneration was assumed to be a past myocardial infarction).No cardiomyopathy was identified in any of the two proband's sisters.Nine years thereafter,distant relatives were diagnosed with LDAC due to a pathogenic desmoplakin mutation.The reanalysis of the two sisters showed ventricular arrhythmias in one of them without structural heart involvement and the reviewed postmortem of the proband was reclassified as LDAC based on the fibrofatty infiltration;both were mutation carriers.The completion of the family study on 19 family members yielded one SCD due to LDAC (the proband),three living patients diagnosed with LDAC (two with a defibrillator),one mutation carrier without structural ventricular involvement,and 14 healthy relatives (who were discharged) with a very good co-segregation of the mutation.Although rare,LDAC exists and sometimes its differential diagnosis with iHD has to be faced.Modifying previous postmortem misdiagnoses can help family screening to further prevent SCDs.