ABSTRACT
An immunocompromised patient with a known history of cerebrovascular accident (CVA) with right-sided hemiparesis of long duration, type 2 diabetes mellitus, and hypertension presented with signs of rhabdomyolysis and later acute kidney injury (AKI). He subsequently developed Guillain Barre syndrome. Initially, hemodialysis was followed by plasmapheresis. After hemodialysis, the patient presented with multiple episodes of vomiting and weakness of all limbs. A culture showed growth of Enterococcus faecalis, and on Day 6, a bloodstream infection with Candida kefyr and a urinary tract infection with Enterococcus faecalis were diagnosed. We report a rare case of bloodstream infection due to C. kefyr.
ABSTRACT
ABSTRACT Prior studies have shown that argemone oil (AO), responsible for 'Epidemic dropsy', causes inhibition of catalytic activities of Cytochrome P450 (P450). In this study interaction of sanguinarine (SAN) alkaloid, isolated from AO, with rat hepatic P450 was investigated. Hepatic microsomes prepared from 3-methylcholantherene (3MC) treated rats when incubated with SAN (1-3 muM) resulted in a spectral peak at 385 nm and a trough at 415 nm, indicative of Type I binding. Incubation of SAN (50-200 muM) with hepatic microsomes prepared from phenobarbitone (PB) treated rats also showed a Type I spectra with a peak at 395 nm and a trough at 420 nm. Relative binding efficiency (DeltaA(max)/K(s)(app) factor) of SAN with P450 was found to be 1540 and 1030 absorbance units/nmol CYP/M for 3MC and PB induced microsomes, respectively. In a P450 spectral inhibition study SAN showed higher affinity towards 3MC eliciting inhibition at much lesser concentrations (0.25-5 muM) as compared to PB (100-300 muM). The IC50s of SAN with different catalytic markers of P450 isoforms, i.e. ethoxyresorufin-O-deethylase (EROD) for CYP1A1, was 2.8 muM and for methoxyresorufin-O-deethylase (MROD) for CYP1A2 was 2.2 muM in 3MC induced microsomes, while benzoyloxyresorufin-O-deethylase (BROD) for CYP 2B1/1A1 showed an IC50 of 50 muM but pentoxyresorufin-O-deethylase (PROD) for CYP2B1 showed no inhibition even at higher concentrations of SAN (> 60 muM) in PB-induced microsomes. These results indicate that higher affinity of SAN binding towards the CYP1A family may have a role in SAN toxicity.
ABSTRACT
Epidemic dropsy is an acute food adulterant disease caused due to consumption of edible mustard oil contaminated with argemone oil. Our in vitro studies have shown that the toxicity of argemone oil is due to the production of reactive oxygen species. The present study was aimed to evaluate the development of oxidative stress in terms of oxidation of plasma proteins and lipids and its correlation to enzymatic and non-enzymatic antioxidants in epidemic dropsy patients. Total plasma protein and globulin contents were found to be significantly (P<0.05) enhanced with a concomitant decrease (P<0.05) in albumin/globulin ratio in dropsy patients when compared to controls. Total cholesterol, triglycerides, low density lipoprotein cholesterol and very low density lipoprotein cholesterol were found to be significantly (P<0.05) increased with a simultaneous decrease (51%) in high density lipoprotein cholesterol in dropsy patients. The oxidation of plasma proteins and lipids were substantially enhanced (162-175%) in dropsy patients when compared to controls. Further, significant (P<0.05) decrease in superoxide dismutase, catalase, glutathione reductase and glutathione-s-transferase with a concomitant increase (69%) in glutathione peroxidase activity was noticed in dropsy patients. A significant reduction in plasma total antioxidant capacity, alpha-tocopherol, glutathione, retinol and retinyl esters content was observed in dropsy patients when compared to healthy controls. The results suggest that there exists an unproportionate equilibrium between free radicals formation and enzymatic and non-enzymatic antioxidant scavengers, which may cause oxidative damage to proteins and lipids in dropsy patients.
