RESUMO
Organophosphate and carbamate (OPC) poisoning is a major global health hazard requiring immediate medical intervention. Atropine (ATR) is an essential antidote in organophosphate and carbamate poisoning, with the inclusion of cholinesterase reactivators and other anticholinergics, namely pralidoxime (PAM) and glycopyrrolate (GPR). This study aimed to compare the efficacy of various treatment regimens and identify the factors affecting mortality. The data of patients presented at the emergency unit with the consumption of OPC compounds between the years 2013 and 2017 were retrospectively reviewed. The study population was then categorized into four treatment patterns (1) ATR alone, (2) ATR and PAM, (3) ATR and GPR, (4) ATR, PAM and GPR. The outcome of the patients was assessed in terms of survival, intubation, ICU days, and days of ventilation and hospitalization. Univariate and multivariate analyses were performed to investigate the risk factors associated with mortality and odds ratio (OR). A total of 441 patients were included in the study, of which 69.16% were males, and 375 patients survived. Consumption of poison with a suicidal intention was reported in 98.19% of the patients, and the treatment with ATR and PAM (42.86%) was observed to have lower days of ventilation in comparison to the treatment with ATR and GPR (p = 0.003). Patients requiring intubation were also lowest in the group treated with ATR and PAM (27.51%). The age group of > 50 years (OR 4.275 [CI 2.179-8.387]), male gender (OR 2.608 [CI 1.258-5.406]), and the treatment pattern with ATR, PAM and GPR (OR 2.233 [CI 1.002-4.040]) were independently associated with mortality. In summary, male gender, elderly population, and treatment patterns followed adversely affected the outcome in patients with OPC poisoning.
RESUMO
Cancer pathogenesis has been attributed to the minor and major disruptions in the cell cycle, with a key role being played by several of the recently discovered epigenetic factors. Lately, UHRF1 (Ubiquitin-like with containing PHD and RING Finger domains 1), an epigenetic regulator has been shown to be evidently over expressed in numerous malignancies through an in-depth review of literature. Molecular docking studies have found that existing drugs such as propranolol, naphthazarin and thymoquinone have favourable interactions with specific domains of UHRF1. However, these findings would need large scale clinical trials to confirm their potency and safety during chemotherapy. UHRF1 (Ubiquitin-like with containing PHD and RING Finger domains 1), an epigenetic factor, plays a crucial role as an important checkpoint in the cell machinery. Basic science continues to unravel multiple facets of this five domain protein which includes a detailed elucidation of its roles and mechanisms of interaction with various enzymes during DNA replication. The gene has recently begun to be also termed as the "Universal Oncogene" in response to the results of research conducted in heterogenous populations and in over 17 cancers displaying heightened mRNA and protein expression in breast, liver, lung, head and neck cancers and many more. This gene could therefore, be a potential biomarker for diagnosis and for the prediction of the prognosis and survival of the diseased. A scientifically established solution in the form of targeted treatment must follow such a discovery and therefore, several natural and synthetic compounds such as thymoquinone and the well-known antihypertensive, propranolol have been docked and reported to have favourable interactions with the SRA (Set and Ring Associated) domain of UHRF1 in this review. This comprehensive review is thus, a brief synopsis of details regarding the structure and heightened levels of UHRF1 in several malignancies. Furthermore, pharmacogenomic research revolving around this oncogene is a potential sphere for clinical studies to be conducted in much larger and heterogenous populations to not only validate these therapeutic docking results but to also to bring personalised medicine to the bedside for the benefit of the patients.
RESUMO
The figure describes the location of UHRF1 (Ubiquitin-like with containing PHD and RING Finger domains 1) gene, mRNA and protein synthesis in the tumor cell and its structural domains with a focus on the docking of Naphthazarin on the SRA domain of UHRF1, resulting in reduction of tumor size.
