RESUMEN
Anti-tumour efficacy of doxorubicin is hindered by the cumulative dose-dependent cardiotoxicity induced by reactive oxygen species during its metabolism. As Cinnamomum zeylanicum has proven antioxidant potential, objective of this study was to investigate the cardioprotective activity of Cinnamomum bark extract against doxorubicin induced cardiotoxicity in Wistar rats. Physicochemical and phytochemical analysis was carried out and dose response effect and the cardioprotective activity of Cinnamomum were determined in vivo. 180 mg/kg dexrazoxane was used as the positive control. Plant extracts were free of heavy metals and toxic phytoconstituents. In vivo study carried out in Wistar rats revealed a significant increase (p < 0.05) in cardiac troponin I, NT-pro brain natriuretic peptide, AST and LDH concentrations in the doxorubicin control group (18 mg/kg) compared to the normal control. Rats pre-treated with the optimum dosage of Cinnmamomum (2.0 g/kg) showed a significant reduction (p < 0.05) in all above parameters compared to the doxorubicin control. A significant reduction was observed in the total antioxidant capacity, reduced glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase activity while the lipid peroxidation and myeloperoxidase activity were significantly increased in the doxorubicin control group compared to the normal control (p < 0.05). Pre-treatment with Cinnamomum bark showed a significant decrease in lipid peroxidation, myeloperoxidase activity and significant increase in rest of the parameters compared to the doxorubicin control (p < 0.05). Histopathological analysis revealed a preserved appearance of the myocardium and lesser degree of cellular changes of necrosis in rats pre-treated with Cinnamomum extract. In conclusion, Cinnamomum bark extract has the potential to significantly reduce doxorubicin induced oxidative stress and inflammation in Wistar rats.
RESUMEN
BACKGROUND: Etiology of and outcomes following idiosyncratic drug-induced liver injury (DILI) vary geographically. We conducted a prospective study of DILI in India, from 2013 to 2018 and summarize the causes, clinical features, outcomes and predictors of mortality. METHODS: We enrolled patients with DILI using international DILI expert working group criteria and Roussel Uclaf causality assessment method. Follow-up was up to 3 months from onset of DILI or until death. Multivariate logistics regression was carried out to determine predictors of non-survival. RESULTS: Among 1288 patients with idiosyncratic DILI, 51.4% were male, 68% developed jaundice, 68% required hospitalization and 8.2% had co-existing HIV infection. Concomitant features of skin reaction, ascites, and encephalopathy (HE) were seen in 19.5%, 16.4%, and 10% respectively. 32.4% had severe disease. Mean MELD score at presentation was 18.8 ± 8.8. Overall mortality was 12.3%; 65% in those with HE, 17.6% in patients who fulfilled Hy's law, and 16.6% in those that developed jaundice. Combination anti-TB drugs (ATD) 46.4%, complementary and alternative medicines (CAM) 13.9%, anti-epileptic drugs (AED) 8.1%, non-ATD antimicrobials 6.5%, anti-metabolites 3.8%, anti-retroviral drugs (ART)3.5%, NSAID2.6%, hormones 2.5%, and statins 1.4% were the top 9 causes. Univariate analysis identified, ascites, HE, serum albumin, bilirubin, creatinine, INR, MELD score (p < 0.001), transaminases (p < 0.04), and anti-TB drugs (p = 0.02) as predictors of non-survival. Only serum creatinine (p = 0.017), INR (p < 0.001), HE (p < 0.001), and ascites (p = 0.008), were significantly associated with mortality on multivariate analysis. ROC yielded a C-statistic of 0.811 for MELD and 0.892 for combination of serum creatinine, INR, ascites and HE. More than 50 different agents were associated with DILI. Mortality varied by drug class: 15% with ATD, 13.6% with CAM, 15.5% with AED, 5.8% with antibiotics. CONCLUSION: In India, ATD, CAM, AED, anti-metabolites and ART account for the majority of cases of DILI. The 3-month mortality was approximately 12%. Hy's law, presence of jaundice or MELD were predictors of mortality.
RESUMEN
The overall 5-year survival for melanoma is 91%. However, if distant metastasis occurs (stage IV), cure rates are < 15%. Hence, melanoma detection in earlier stages (stages I-III) maximises the chances of patient survival. We measured the expression of a panel of 17 microRNAs (miRNAs) (MELmiR-17) in melanoma tissues (stage III; n = 76 and IV; n = 10) and serum samples (collected from controls with no melanoma, n = 130; and patients with melanoma (stages I/II, n = 86; III, n = 50; and IV, n = 119)) obtained from biobanks in Australia and Germany. In melanoma tissues, members of the 'MELmiR-17' panel were found to be predictors of stage, recurrence, and survival. Additionally, in a minimally-invasive blood test, a seven-miRNA panel (MELmiR-7) detected the presence of melanoma (relative to controls) with high sensitivity (93%) and specificity (≥ 82%) when ≥ 4 miRNAs were expressed. Moreover, the 'MELmiR-7' panel characterised overall survival of melanoma patients better than both serum LDH and S100B (delta log likelihood = 11, p < 0.001). This panel was found to be superior to currently used serological markers for melanoma progression, recurrence, and survival; and would be ideally suited to monitor tumour progression in patients diagnosed with early metastatic disease (stages IIIa-c/IV M1a-b) to detect relapse following surgical or adjuvant treatment.