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The aim of this study was to determine the antidotal potential of the chlorinated oxime K870 compared to obidoxime, as a monotherapy and in combination with atropine, in paraoxon (POX)-poisoned rats. The treatment doses of oximes were chosen as 20% of their LD 50 values. The protective ratio (PR) of oxime K870 with atropine was significantly higher than that of obidoxime with atropine (68.8 and 125.0, respectively). In the biochemical part of the experiment POX subcutaneously (s.c.) (0.75% LD 50 ) was administered and followed by oxime K870 or obidoxime i.m. 1 min later. Acetylcholinesterase (AChE) activity was determined spectrophotometrically in cerebrum, cerebellum, brainstem, diaphragm, and erythrocytes. Carboxylesterase activity was determined in plasma and liver. Both oximes successfully reactivated AChE in brain (cerebrum, cerebellum, and brainstem), diaphragm and erythrocytes, but the oxime K870 performed better than obidoxime. Both oximes reactivated carboxylesterase, obidoxime better in plasma and oxime K870 better in liver. In conclusion, the oxime K870, when co-administered with atropine, is a more effective antidote than the obidoxime-atropine combination in POX-poisoned rats.

Patients suffering from cholelithiasis have an increased risk of developing cardiovascular complications, particularly ischemic myocardial disease. Ursodeoxycholic acid (UDCA), already used in clinical practice for the treatment of cholelithiasis and related conditions, has proven antioxidative, anti-inflammatory, and cytoprotective effects. Therefore, the aim of this study was to investigate the cardioprotective effect of UDCA pre-treatment on isoprenaline-induced myocardial injury in rats. Male Wistar albino rats were randomized into four groups. Animals were pre-treated for 10 days with propylene glycol + saline on days 9 and 10 (control), 10 days with propylene glycol + isoprenaline on days 9 and 10 (I group), 10 days with UDCA + saline on days 9 and 10 (UDCA group), and 10 days with UDCA + isoprenaline on days 9 and 10 (UDCA + I group). UDCA pre-treatment significantly reduced values of high-sensitivity troponin I (hsTnI) and aspartate aminotransferase (AST) cardiac markers ( p < 0.001 and p < 0.01, respectively). The value of thiobarbituric acid reactive substances (TBARS) was also decreased in the UDCA + I group compared to the I group ( p < 0.001). UDCA also significantly increased glutathione (GSH) levels, while showing a tendency to increase levels of superoxide dismutase (SOD) and catalase (CAT). The level of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) expression, a key regulatory gene of inflammation, was diminished when UDCA was administered. A reduction of cardiac damage was also observed in the UDCA pre-treated group. In conclusion, UDCA pre-treatment showed a cardioprotective effect on isoprenaline-induced myocardial injury in rats, primarily by reducing oxidative stress and inflammation.

Takotsubo syndrome (TTS) is an acute heart failure syndrome characterised by catecholamine-induced oxidative tissue damage. Punica granatum , a fruit-bearing tree, is known to have high polyphenolic content and has been proven to be a potent antioxidant. This study aimed to investigate the effects of pomegranate peel extract (PoPEx) pre-treatment on isoprenaline-induced takotsubo-like myocardial injury in rats. Male Wistar rats were randomised into four groups. Animals in the PoPEx(P) and PoPEx + isoprenaline group (P + I) were pre-treated for 7 days with 100 mg/kg/day of PoPEx. On the sixth and the seventh day, TTS-like syndrome was induced in rats from the isoprenaline(I) and P + I groups by administering 85 mg/kg/day of isoprenaline. PoPEx pre-treatment led to the elevation of superoxide dismutase and catalase ( p < 0.05), reduced glutathione ( p < 0.001) levels, decreased the thiobarbituric acid reactive substances ( p < 0.001), H 2 O 2 , O 2 - ( p < 0.05), and NO 2 - ( p < 0.001), in the P + I group, when compared to the I group. In addition, a significant reduction in the levels of cardiac damage markers, as well as a reduction in the extent of cardiac damage, was found. In conclusion, PoPEx pre-treatment significantly attenuated the isoprenaline-induced myocardial damage, primarily via the preservation of endogenous antioxidant capacity in the rat model of takotsubo-like cardiomyopathy.

Pesticide poisonings, intentional as well as accidental, are common, especially in undeveloped and developing countries. The goal of this study was to analyze the clinical presentation of patients hospitalized due to acute organophosphate (OPP) or carbamate pesticide (CP) poisoning as well as to analyze the factors that potentially influenced the severity and outcome of the poisonings. A retrospective cross-sectional study was performed. The age and gender of each patient were recorded, the type of ingested pesticide, whether the poisoning was intentional or accidental, number of days of hospitalization, the severity of the poisoning, and the outcome of the treatment (i.e., whether the patient survived or not). Clinical aspects of poisonings were analyzed, as well as the therapeutic measures performed. 60 patients were hospitalized due to acute OPP or CP poisoning, out of 51 (85.00%) were cases of intentional self-poisoning. The majority of patients were poisoned by OPPs (76.67%), in one-third the causative agent was malathion, followed in frequency by chlorpyrifos and diazinon. Dimethoate poisonings were manifested with the most severe clinical picture. A 70% or lower activity of reference values of acetylcholinesterase and butyrylcholinesterase was found in 50% and 58% of patients, respectively. The most common symptom was miosis (58.33%), followed by nausea and vomiting. Pralidoxime reactivated acetylcholinesterase inhibited by chlorpyrifos or diazinon, but not with malathion or dimethoate. Impairment of consciousness and respiratory failure, as well as the degree of acetylcholinesterase and butyrylcholinesterase inhibition, were prognostic signs of the severity of poisoning. The lethal outcome was more often found in older patients ( t  = 2.41, p  = 0.019). The type of ingested pesticide significantly affects the severity and outcome of poisoning as well as the effectiveness of antidotes.

Background and Objectives : Benzodiazepines (BZDs) are among the most prescribed psychotropic drugs and significant number of patients use these drugs for longer periods than recommended. The objective of this study was to determine the factors associated with prescribing of BZDs at the primary healthcare level. Materials and Methods : A retrospective analysis of family physicians' prescriptions from the databases of family medicine teams of the Republic of Srpska was performed. The number of BZDs users, as well as the total number of prescriptions, were determined. Thereafter, it was determined which specific BZD had been prescribed, in which dose, for how long, as well as the specific social and demographic characteristics of patients to whom the drugs were prescribed. Results : The results showed that 38.47% of patients used the BZDs for a period longer than six months. The most frequent BZDs prescribed were the intermediate-acting BZDs, primarily bromazepam (58.69%). Two thirds of patients were women. The average age of the patients was 60, 60.46% of patients were single, and 69.68% lived in urban areas. The longer uses of BZDs were recorded in women, the elderly, single people and those who lived in urban areas, while higher doses of BZDs were prescribed to men, as well as younger and married people. The highest positive correlation was found between the dose and length of use of BZD. Conclusions : A significant percentage of patients used BZDs for a time period longer than recommended. Caution is necessary when prescribing BZDs to women, the elderly, patients that live in urban areas and patients who are single. When prescribing BZDs, family physicians should be aware of their potential interactions and addictive potentials.

Organophosphorus compounds induce irreversible inhibition of acetylcholinesterase, which then produces clinically manifested muscarinic, nicotinic and central effects. The aim of the study was to analyse the clinical signs of acute paraoxon poisoning in rats and to determine the relationship between the intensity of signs of poisoning and the dose of paraoxon and/or the outcome of poisoning in rats. Animals were treated with either saline or atropine (10 mg/kg intramuscularly). The median subcutaneous lethal dose (LD50) of paraoxon was 0.33 mg/kg and protective ratio of atropine was 2.73. The presence and intensity of signs of poisoning in rats (dyspnoea, lacrimation, exophthalmos, fasciculations, tremor, ataxia, seizures, piloerection, stereotypic movements) were observed and recorded for 4 h after the injection of paraoxon. Intensity of these toxic phenomena was evaluated as: 0 - absent, 1 - mild/moderate, 2 - severe. Fasciculations, seizures and tremor were more intense at higher doses of paraoxon and in non-survivors. In unprotected rats piloerection occurred more often and was more intense at higher doses of paraoxon as well as in non-survivors. In atropine-protected rats, piloerection did not correlate with paraoxon dose or outcome of poisoning. The intensity of fasciculations and seizures were very strong prognostic parameters of the poisoning severity.