PREDICTING THE BIODEGRADABILITY NATURE OF IMIDAZOLE AND ITS DERIVATIVES BY MODULATING TWO HISTIDINE DEGRADATION ENZYMES (UROCANASE AND FORMIMINOGLUTAMASE) ACTIVITIES

Objectives: The biodegradation pathway of substituted imidazole ring compounds has been reported to have close analogy to the histidine degradation pathway. This prompted the present study to be carried out on 12 selected imidazole and its derivatives which are 1-imidazole, 1, 2-dimethylimidazole, 1-ethyl imidazole, 2-ethyl-4-methylimidazole, 2-isopropylimidazole, 2-Isopropyl-4-nitro-1H-imidazole, 1-methylimidazole, 2-methyl-5-nitroimidazole, 2-methyl-1-vinylimidazole, 1-nitro imidazole, 1-phenyl imidazole, and 1-vinylimidazole.Methods: The imidazole and its derivatives were evaluated on the docking behavior of urocanase and formiminoglutamase using PatchDock. In addition, molecular physicochemical, drug-likeness, absorption, distribution, metabolism, and excretion analyses (ADME) were done.Results: The molecular physicochemical analysis revealed that all the tested ligands showed nil violation and complied well with the Lipinski's rule of five. ADME analysis showed that 1-phenylimidazole alone predicated to have cytochrome P450 1A2 inhibition effect. Docking studies revealed that 1-nitroimidazole showed the least atomic contact energy with both targeted enzymes (urocanase and FIGase).Conclusion: Inhibition of both enzymes (urocanase and FIGase) might show poor biodegradability nature. Thus, we can predict biodegradability nature of imidazloe and its derivatives by modulating two histidine degradation enzymes activities

Exploratory use of fluorescent SmartProbes for the rapid detection of microbial isolates causing corneal ulcer

PURPOSE:To explore the use of optical SmartProbes for the rapid evaluation of corneal scrapes from patients with suspected microbial keratitis, as a clinical alternative to Gram stain. DESIGN:Experimental study with evaluation of a diagnostic technology. METHODS:Corneal scrapes were collected from 267 patients presenting with microbial keratitis at a referral cornea clinic in South India. Corneal scrapes were flooded with SmartProbes (BAC One or BAC Two) and evaluated by fluorescence microscopy (without the need for sample washing or further processing). The SmartProbe labelled samples were scored as bacteria/fungi/none (BAC One) or gram-negative bacteria/none (BAC Two) and compared to Gram stain results. RESULTS:Compared to Gram stain, BAC One demonstrated sensitivity and specificity of 80.0 and 87.5 percent respectively, positive and negative predictive values (PPV, NPV) of 93.8 and 65.1 percent, and an accuracy of 82.2. BAC Two demonstrated sensitivity and specificity of 93.3 and 84.8 percent respectively, a NPV of 99.2 percent and an accuracy of 85.6 percent. When the corresponding culture results were compared to the Gram stain result, the sensitivity and specificity were 73.4 and 70.7 percent, the PPV and NPVs were 86.5 and 51.0 percent, and an overall accuracy of 72.6. CONCLUSIONS:Fluorescent SmartProbes offer a comparative method to Gram stain for delineating gram-positive or gram-negative bacteria or fungi within corneal scrapes. We demonstrate equivalent or higher sensitivity, specificity, PPV and NPVs, and accuracy than culture to Gram stain. Our approach has scope for point-of-care clinical application to aid in the diagnosis of microbial keratitis

A prospective cohort study on glucose variability and clinical outcomes in comatose children due to acute central nervous system infections admitted in the pediatric intensive care unit

Background: Pediatric acute central nervous system (CNS) infections are associated with severe neuromorbidity. This study aimed to study the effect of glucose variability on clinical outcomes in comatose children due to acute CNS infections admitted in pediatric intensive care unit (PICU). Subjects and Methods: A prospective cohort study enrolled comatose children aged 1 month to 12 years due to acute CNS infection. Within 6 h, continuous glucose monitoring was started (Freestyle Libre Pro, Abbott). The unit practice was targeting blood glucose (BG, mg/dL) of 126, >140, >180, >200, and 126). The primary outcome was new-onset organ dysfunction. The secondary outcomes were organ support, length of mechanical ventilation, hospital (including PICU) stay, and 90-day composite poor outcome (mortality or severe neurodisability). Results: Total BG values measured were 27,792 from 66 patients (mean [standard deviation (SD)] 421.1 [212.6] values per patient). The mean (SD) BG was 103.2 (37.7) (minimum: 42.1; maximum: 228.8). The new-onset organ dysfunction has occurred in 83.3% (n = 55/66), and no difference was noted among normoglycemic and abnormal glycemic groups (84.4% vs. 80.9%; relative risk = 1.09, 95% confidence interval: 0.67–1.76). The median (interquartile range) PICU stay (days) was higher in the normoglycemic group (7, 5–14 vs. 4, 3.5–8.5; P = 0.014). No difference was noted in other outcomes. Conclusions: Glucose variability was not significantly associated with new-onset organ dysfunction and poor outcome in comatose children due to acute CNS infections