Nephrotoxic Effects of Paraoxon in Three Rat Models of Acute Intoxication

The delayed effects of acute intoxication by organophosphates (OPs) are poorly understood, and the various experimental animal models often do not take into account species characteristics. The principal biochemical feature of rodents is the presence of carboxylesterase in blood plasma, which is a target for OPs and can greatly distort their specific effects. The present study was designed to investigate the nephrotoxic effects of paraoxon (O,O-diethyl O-(4-nitrophenyl) phosphate, POX) using three models of acute poisoning in outbred Wistar rats. In the first model (M1, POX2x group), POX was administered twice at doses 110 µg/kg and 130 µg/kg subcutaneously, with an interval of 1 h. In the second model (M2, CBPOX group), 1 h prior to POX poisoning at a dose of 130 µg/kg subcutaneously, carboxylesterase activity was pre-inhibited by administration of specific inhibitor cresylbenzodioxaphosphorin oxide (CBDP, 3.3 mg/kg intraperitoneally). In the third model (M3), POX was administered subcutaneously just once at doses of LD16 (241 µg/kg), LD50 (250 µg/kg), and LD84 (259 µg/kg). Animal observation and sampling were performed 1, 3, and 7 days after the exposure. Endogenous creatinine clearance (ECC) decreased in 24 h in the POX2x group (p = 0.011). Glucosuria was observed in rats 24 h after exposure to POX in both M1 and M2 models. After 3 days, an increase in urinary excretion of chondroitin sulfate (CS, p = 0.024) and calbindin (p = 0.006) was observed in rats of the CBPOX group. Morphometric analysis revealed a number of differences most significant for rats in the CBPOX group. Furthermore, there was an increase in the area of the renal corpuscles (p = 0.0006), an increase in the diameter of the lumen of the proximal convoluted tubules (PCT, p = 0.0006), and narrowing of the diameter of the distal tubules (p = 0.001). After 7 days, the diameter of the PCT lumen was still increased in the nephrons of the CBPOX group (p = 0.0009). In the M3 model, histopathological and ultrastructural changes in the kidneys were revealed after the exposure to POX at doses of LD50 and LD84. Over a period from 24 h to 3 days, a significant (p = 0.018) expansion of Bowman’s capsule was observed in the kidneys of rats of both the LD50 and LD84 groups. In the epithelium of the proximal tubules, stretching of the basal labyrinth, pycnotic nuclei, and desquamation of microvilli on the apical surface were revealed. In the epithelium of the distal tubules, partial swelling and destruction of mitochondria and pycnotic nuclei was observed, and nuclei were displaced towards the apical surface of cells. After 7 days of the exposure to POX, an increase in the thickness of the glomerular basement membrane (GBM) was observed in the LD50 and LD84 groups (p = 0.019 and 0.026, respectively). Moreover, signs of damage to tubular epithelial cells persisted with blockage of the tubule lumen by cellular detritus and local destruction of the surface of apical cells. Comparison of results from the three models demonstrates that the nephrotoxic effects of POX, evaluated at 1 and 3 days, appear regardless of prior inhibition of carboxylesterase activity.

Methods of forensic medical analysis of acute intoxications with ethyl alcohol (review of literary sources)

The article presents an overview of current literature on the problem of forensic diagnosis of acute poisoning by ethanol and its surrogates. Morphological and forensic chemical criteria for the diagnosis of ethanol intoxication are presented, variants of patho- and thanatogenesis are described, as well as modern methods for diagnosing these poisonings. Aim of the work. Review of current literature data on the problem of forensic diagnosis of acute poisoning by ethanol and its surrogates. Conclusion. In our opinion, it is necessary to introduce into the practical work of the bureau of forensic examinations new promising technologies for the diagnosis of acute intoxication with ethyl alcohol and its surrogates.

Epidemiologic and clinical evaluation of the acute intoxication in pediatric patients

Acute poisoning is a critical and emergent public health problem worldwide among pediatric age group. The common epidemiological observation is required to understand the characteristics of the pediatric intoxication for each location and important for management the poisoning cases. This retrospective study researched the epidemiology of poisoning among children. This study represented the epidemiology of poisonings of children admitted to the pediatric intensive care unit at Afyonkarahisar Health Science University Faculty of Medicine between February 2020 and May 2021. Fifty one pediatric patients were reffered to the PICU due to acute intoxication. 58.9% of the analyzed patients were male and 41.1% were female. The mean age of all patients was 8.57±7.6. The majority of cases were due to drug-related poisonings. The average age of cases of suicidal poisoning was higher than accidental intoxication cases. Paracetamol was the most prevalent cause of drug-related intoxication and more common in children under 5 years of age and selective serotonin reuptake inhibitors were more frequent in adolescent group. All patients survived. Almost all of the patients were discharged from hospital within 3 days. Poisonings are still a serious reason for morbidity and mortality in developing countries among children. Early awareness of poisoning and appropriate management appeared to be effective and to decrease the mortality rate.

Comparative Study of Ethanol Intoxications in the Context of Covid-19 Pandemic Reported to the Year of 2019

Excessive alcohol consumption that causes disorders of social conduct, causes a rejection reaction with the intervention of the authorities. The paper compares trends related to people with the diagnosis of acute intoxication (F10.0) admitted to the "Elisabeta Doamna” Psychiatry Hospital in Galati, from the 1st of January to the 31th of December 2020 with the period from the 1st of January to the 31th of December 2019. In the retrospective study we selected people discharged with acute intoxication, code (F10.0), and harmful use (F10.1), excluding all patients with other psychiatric diagnoses from the database of the "Elisabeta Doamna" Psychiatry Hospital from 2020 to 2019. ICD-10 (Classification of mental and behavioral disorders) was used for diagnosis of psychiatric disorders. The data was processed statistically using: Microsoft Office-Excel, The Jamovi Project (2021). jamovi (Version 1.6) [Computer Software]. In 2020 there were 39.58% fewer discharges by a total of (7973 cases) compared to (13197 cases) in 2019. In 2020, acute intoxication (F10.0) accounted for 7.41% of total discharges compared to a percentage of (8.27%) in 2019, showing a decline by a percentage of 45.92%. Comparing the years 2020 with 2019 by gender (of the total number of discharges with acute intoxication (F10.0), there is an increase in the percentage of discharges by 1.16% (from 86.98% in 2019 to 88.14% in 2020), while in the female gender, the percentage trend has decreased by a percentage of 1.16% (from 13.02% in 2019 to 11.86% in 2020).

Dynamics of Ethanolic Intoxications between the 15th of March 2020 to the 15th of March 2021 in the Context of the Covid-19 Pandemic

In Romania, the consumption of alcoholic beverages has been and still is a cultural mechanism for socializing and reducing anxiety, regardless of age and gender. This paper evaluates the trends related to people diagnosed with acute intoxication (F10.0) and harmful use (F10.1) at the 'Elisabeta Doamna' Psychiatriy Hospital in Galati, during the pandemic, in the period between the 15th of March 2020 and the 15th of March 2021. We analysed the data base of discharges from the 'Elisabeta Doamna' Psychiatry Hospital from the 15th of March 2020 to the 15th of March 2021. ICD-10 (Classification of mental and behavioural disorders) was used for diagnosis of psychiatric disorders. We selected outpatients with the codes for acute intoxication (F10.0) and harmful use (F10.1) and excluded all patients with other psychiatric diagnoses. The data were statistically processed using: Microsoft Office-Excel, The jamovi project (2021) jamovi (Version 1.6) [Computer Software]. During the analysed period, there were 7614 discharges from the 'Elisabeta Doamna' Psychiatriy Hospital of which 1465 (20.08%) disorders were related to alcohol consumption. Disorders related to intoxication and alcohol use represent 13.14% (957 cases) of the total discharges and 65.46% of the total number of disorders related to alcohol. Disorders related to harmful use (F10.1) represent 30.31% (442 cases), and a percentage of 35.15% (515 cases) with disorders due to acute intoxication (F10.0) out of the total cases were related to alcohol consumption. From the view of the dispersion of the number of cases, there is a fluctuation in the tendency to follow the restrictions imposed by the authorities.

Carbon monoxide: mechanism of toxic action, pathogenesis and clinical manifestations of acute intoxication

Introduction. Carbon monoxide (CO) remains one of the most common causes of acute poisoning and death, both in everyday life and in emergency situations, especially in fires.Material and methods. The paper summarizes information about the regulatory effects, mechanisms of toxic action, pathogenesis and clinical picture of intoxication, as well as predictors of the severity of CO poisoning.Results. The main mechanism of the toxic effect of CO is due to its ability to bind to the protohemal iron of hemoglobin (Hb) to form carboxyhemoglobin (HbCO). The toxicity of CO may also be enhanced by impaired functions of the myoglobin of the myocardium and skeletal muscles, mitochondrial cytochrome oxidase, and iron-containing enzymes of the antioxidant system. The leading link in the pathogenesis of acute CO intoxication is a violation of the oxygen transport function of hemoglobin and the associated development of hemic and tissue hypoxia. CO-induced cell and tissue damage due to the induction of mitochondrial dysfunction, oxidative stress, free radical hyperproduction, lipid peroxidation, inflammation, and apoptosis also play a role in the pathogenesis of intoxication.Conclusion. The mechanism of toxic action of CO, associated primarily with the formation of carboxyhemoglobin and the development of hypoxia, determines the clinical manifestations of acute intoxication, which depend on the concentration of CO and the duration of exposure, but are almost always associated with the central nervous system and cardiovascular system.