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Epoxiconazole (EPX) is a triazole fungicide commonly used in agriculture and for domestic purposes around the world. The excessive application of this pesticide may result in a variety of adverse effects on non-target organisms, including humans. Since, the liver and kidneys are the target organs of this fungicide, potential hepatotoxic and nephrotoxic effects are of high relevance. Thus, our study aimed to investigate the toxic effects of EPX on the liver and kidney of Wistar rats. The exposure of rats to EPX at these concentrations (8, 24, 40, 56 mg/kg bw representing, respectively, NOEL (no observed effect level), NOEL × 3, NOEL × 5, and NOEL × 7) for 28 days significantly enhances hepatic and renal lipid peroxidation which is accompanied by an increase in the level of protein oxidation. Furthermore, the results of the present study clearly indicated that EPX administration induces an increase in the levels of DNA damage in a dose-dependent manner. In addition, the activities of liver and kidney antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione S-transferase (GST) are increased significantly in EPX-treated rats at concentrations of 8, 24, and 40 mg/kg bw. However, with the dose NOEL × 7 (56 mg/kg bw of EPX), the activities of CAT, GPx, and GST are decreased. Indeed, EPX-intoxicated rats revealed a significant reduction in acetylcholinesterase (AChE) activity in both liver and kidney compared with the control group. Also, our results demonstrated that the EPX administration leads to a disruption of the hepatic (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH)) and renal (uric acid and creatinine) functions. The biochemical perturbations obtained in the present study are corroborated with the histopathological modifications. Since EPX treatment caused severe damage in the overall histo-architecture of liver and kidney tissues, these results suggest that administration of EPX induced a marked deregulation of liver and kidney functions. Graphical abstract.

Clopidogrel non-responsiveness is multifactorial; several genetic and non-genetic factors may contribute to impaired platelet inhibition. The goal of this study is to determine the effect of the cytochrome P450 CYP2C19*2 polymorphism on the platelet response to clopidogrel in patients with and without diabetes mellitus (DM). We conducted an observational study in patients with coronary artery disease and consequent exposure to clopidogrel therapy (75 mg/day for at least 7 consecutive days). We have analyzed two groups of patients: group I (DM patients) and group II (non-diabetes mellitus patients). Platelet reactivity was assessed by the VerifyNow P2Y12 assay and high on clopidogrel platelet reactivity (HPR) was defined as P2Y12 reaction units (PRU) ≥ 208. Genotyping for CYP2C19*2 polymorphism was performed by PCR-RFLP. We have included 150 subjects (76 DM and 74 non-diabetes mellitus patients). The carriage of CYP2C19*2 allele, in DM patients, was significantly associated to HPR (odds ratio (OR) 4.437, 95% confidence interval (CI) 1.134 to 17.359; p = 0.032). Furthermore, 8.4% of the variability in percent inhibition by clopidogrel could be attributed to CYP2C19*2 carrier status. However, in non-diabetes mellitus patients, there was no significant difference in platelet response to clopidogrel according to the presence or absence of CYP2C19*2 allele carriage (OR 1.260, 95% CI 0.288 to 5.522; p = 0.759). Our study suggests that the carriage of CYP2C19*2 polymorphism, in DM patients, might be a potential predictor of persisting HPR in these high-risk individuals. Clinical Trials.gov NCT03373552 (Registered 13 December 2017)

Acetamiprid is one of the most widely used neonicotinoids. This study investigates toxic effects of repeated oral administration of three doses of acetamiprid (1/20, 1/10, and 1/5 of LD50) during 60 days. For this, male Wistar rats were divided into four different groups. Hematological, biochemical, and toxicopathic effects of acetamiprid were evaluated. According to the results, a significant decrease in the body weight gain at the highest dose 1/5 of LD50 of acetamiprid was noticed. An increase in the relative liver weight was also observed at this dose level. The hematological constituents were affected. A significant decrease in RBC, HGB, and HCT in rats treated with higher doses of acetamiprid (1/10 and 1/5 of LD50) was noted. However, a significant increase in WBC and PLT were observed at the same doses. Furthermore, acetamiprid induced liver toxicity measured by the increased activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphates (ALPs), and lactate dehydrogenase (LDH) which may be due to the loss of hepatic membrane architecture and hepatocellular damage. In addition, exposure to acetamiprid resulted in a significant decrease in the levels of superoxide dismutase and catalase activities (p ≤ 0.01) with concomitant increase in lipid peroxidation in rat liver. These findings highlight the subchronic hepatotoxicity of acetamiprid.

Background Some factors related to diet are known to be involved in the progression of atherosclerosis in humans. Methods The relationship between plasma fatty acid (FA) levels and the severity of coronary artery disease (CAD), evaluated by Gensini score (GS), was investigated in CAD Tunisian patients compared to controls. Lipid profiles were analyzed, GS was calculated in CAD and non-CAD patients and compared to controls. Results CAD patients showed an alteration of conventional lipid parameters. In fact, a significant increase of plasmatic triglycerides (TG) level, atherogenic lipid ratios (TC/HDL-C,TG/HDL-C, LDL-C/HDL-C); and ApoB/ApoA1 was observed in the CAD group comparatively to controls (p

To evaluate and compare the performance of NT-proBNP levels, plasma protein concentration, hematocrit, and fluid balance for the preceding 24 h in predicting the outcome of the two steps of weaning: (1) spontaneous breathing trial (SBT), (2) extubation.This was a prospective observational study of 143 patients who were mechanically ventilated for more than 48 h (55% COPD) and were ready to wean. They underwent an SBT and were extubated when they passed the trial. Immediately before the SBT, we measured the evaluated diagnosis tools.Of 143 patients, 80 (56%) passed the SBT and were extubated. Of these, two were reintubated for laryngeal dyspnea, 57 had no respiratory problem during the next 48 h, and 21 developed post-extubation respiratory distress (26%). Rescue noninvasive ventilation (NIV) prevented reintubation in 15 (71%). None of the tested diagnosis tools predicted the outcome of the SBT. Patients who developed post-extubation respiratory distress were older, had lower values of plasma protein concentration and higher values of NT-proBNP than those who did not. Only NT-proBNP was an independent predictor of the occurrence of post-extubation respiratory distress (OR 1.2; 95% CI 1.09-1.4; p = 0.003); the area under the ROC curve for NT-proBNP to predict post-extubation respiratory distress was 0.78 (95% CI 0.67-0.89; p = 0.0001). NT-proBNP was more accurate to rule out (negative likelihood ratio 0.09 for a cutoff of no greater than 1,000 pg/ml) than to rule in the risk of post-extubation respiratory distress (positive likelihood ratio 3.45 for a cutoff of at least 2,000 pg/ml).NT-proBNP levels at SBT help in the prediction of post-extubation respiratory distress and could identify the subgroup of extubated patients requiring close observation and/or prophylactic NIV.

Biomonitoring of effects in agricultural workers is necessary to assess the individual risk of handling pesticides. In this study, biochemical and haematological parameters were measured to evaluate the effects of exposure to these compounds in agricultural workers. The study was carried out in 110 workers and 97 control subjects. Several haematological and biochemical parameters were analysed. Assessment of haematological parameters revealed that the mean cell volume and haematocrit levels were significantly lower in workers than in controls (P=0.002 and 0.013, respectively), while mean corpuscular haemoglobin concentrations were higher in workers (P

This study aims to investigate the effect of cigarette smoking on paraoxonase 1 (PON1) activity according to PON1 L55M and PON1 Q192R gene polymorphisms. Our sample included 300 voluntary subjects: 138 nonsmokers and 162 current smokers aged 38.47 ± 21.91 and 35.55 ± 16.03 years, respectively. PON1 activity was determined by kinetic methods. L55M and Q192R gene polymorphisms of PON1 were determined by multiplex polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP). We found in smokers a significant decrease of PON1 activity before and after adjustment. We noted a significant association between smoking status and lower PON1 activity [odds ratio (OR) = 3.03, confidence interval 95% = 1.5–5.9, p = 0.001]. In smokers, there was significant association between PON1 activity and PON1 L55M polymorphisms (p = 0.01). Also, the 55MM genotype presented the lowest paraoxonase activity, while the 55LL genotype showed the highest one. After adjustment for confounding variables, smokers with PON1 L55M polymorphism had the highest risk for lower PON1 activity; however, PON1 Q192R genotype might protect smokers from decrease in PON1 activity. We found significant interaction between the effect of cigarette smoking and both PON1 L55M and PON1 Q192R polymorphisms on lower PON1 activity. Cigarette smoking was significantly associated with decrease in PON1 activity. Moreover, PON1 L55M polymorphism predisposes smokers to decreased PON1 activity in contrast to PON1 Q192R genotype.

Recent investigations have proved the crucial role of nutritional antioxidants to prevent the damage caused by toxic compounds. In this study, the antioxidant effect of date palm fruit extract on dimethoate-induced oxidative stress and nephrotoxicity in rat is investigated and compared with the effect of the well-known antioxidant vitamin C. Male Wistar rats were randomly divided into six groups of ten each: a control group (C), a group that received dimethoate (20 mg/kg body weight) (D), a group given Deglet Nour extract (DNE), a group treated with DNE 30 min before the administration of dimethoate (DNE + D), a group which received VitC (100 mg/kg body weight) plus dimethoate (Vit C + D), and a group given dimethoate for the first month and DNE 30 min after administration of dimethoate, during the second month (D + DNE). These components were daily administered by gavage for 2 months. After completing the treatment period, blood samples from rats were collected under inhaled diethyl ether anesthesia for serum urea, uric acid, and creatinine levels, while the rat kidneys were obtained for enzyme assays and histology. Oral administration of dimethoate in rats induced a marked renal failure characterized by a significant increase in serum creatinine and urea levels (p

The calcium-sensing receptor (CASR), a plasma membrane G-protein coupled receptor, is expressed in parathyroid gland and kidney, and controls systemic calcium homeostasis. Inactivating CASR mutations have previously been identified in patients with familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT). The aim of the present study is to determine the underlying molecular defect of FHH/NSHPT disease in a consanguineous Tunisian family. Mutation screening was carried out using RFLP-PCR and direct sequencing. We found that the proband is homozygous for a novel 15 bp deletion in the exon 7 (c.1952_1966del) confirming the diagnosis of NSHPT. All the FHH members were found to be heterozygous for the novel detected mutation. The mutation, p.S651_L655del, leads to the deletion of 5 codons in the second trans-membrane domain of the CASR which is thought to be involved in the processes of ligand-induced signaling. This alteration was associated with the evidence of mental retardation in the FHH carriers and appears to be a novel inactivating mutation in the CASR gene. Our findings provide additional support for the implication of CASR gene in the FHH/NSHPT pathogenesis.

The epidemiology of renal stones has changed all over the world toward a predominance of calcium oxalate stones. However, studies evaluating the influence of age and gender on the distribution of the various types of urinary calculi are scarce. We will present the results of a study based on 205 calculi (from 122 boys and 83 girls) analyzed by infrared spectroscopy between 1993 and 2007. 90% of stones were collected by surgery, whereas only 6% by spontaneous passage. The biological exploration was performed in only 126 cases. Etiology was metabolic in 13.5%. 10.7% of stones were infectious, 13.1% were endemic and 54.9% were idiopathic. 7.8% were secondary to urinary stasis with malformation but no infection. Calcium oxalate (CaOx) was the predominant constituent in 54.7% of stones, followed by calcium phosphate and purines 14.6% in each of the cases. We found an increasing prevalence of calcium oxalate stones with age in both genders (42.9% in infant vs. 59.3% in child) (P < 0.05). Struvite stones were more frequent in infant than children. Purine stones were predominant in 20% of cases, but its prevalence decreases with age. The increase in calcium oxalate stone in school age children and the decrease in struvite and purine stones confirm the change on the etiology of urolithiasis according to age.

To explore adrenal function in severe West Nile virus (WNV) infection.Prospective interventional cohort study in a medical ICU of a teaching hospital.Ten consecutive patients (seven men, mean age 64+/-12years, mean SAPS II 26+/-6) with definite diagnosis of WNV related meningoencephalitis and variable proportion of organ/system failure. All patients had fever (mean body temperature 39+/-1 degrees C) and altered mental status (mean Glasgow Coma Score 11+/-2). Mean SOFA score was 9+/-2; eight patients had systemic inflammatory response syndrome, five septic shock, and six acute respiratory failure (usually from central origin) requiring mechanical ventilation.A short corticotropin test was performed in each patient to assess the adrenal function.Cortisol response was defined as the difference between baseline and corticotropin-stimulated peak. Absolute adrenal insufficiency was defined by a baseline cortisol level below 15 microg/dl (415 nmol/l). Relative insufficiency was defined by a cortisol response of 9 microg/dl (250 nmol/l) or less. Relative adrenal insufficiency, defined by a corticotropin response below 9 microg/dl, was observed in seven while the remaining three had normal cortisol response; six out of these seven died in the ICU. All patients with normal adrenal function survived.Adrenal insufficiency is frequent in severe WNV infection and carries a poor outcome. In the absence of specific effective treatment, our data provide a rational to investigate a supplemental corticosteroid treatment in a controlled trial.

Objective: to determine the incidence of Hellp syndrome (HS) and the maternal fetal outcome associated with its occurrence.Design: a prospective study during a 6-month period.Setting: the department of obstetrics and gynecology and the Intensive Care Unit of a 700 bed teaching hospital.Patients: Sixty-two consecutive preeclamptic and eclamptic women.Measurements and results: all patients were systematically investigated for the biological markers of HS. The effects of the occurrence of HS on maternal and fetal prognosis were evaluated by comparing for prognosis indicators usually assessed in gravidic hypertension, pre-eclamptic and eclamptic women who exhibited HS (HS+subgroup) with HS free patients (HS-subgroup). HS was found in 12 out of the 62 pre-eclamptic and eclamptic women (19.3%). Its occurrence was associated with higher maternal mortality (16.7% vs 0%;p=0.03), a greater incidence of eclamptic crisis (50% vs 20%;p=0.03), severe hypertension (33% vs 8%;p=0.03) and episodes of acute renal failure (66% vs 30%;p=0.02). Mean proteinuria was also higher in HS+patients (4.6±3.3 vs 2.2±2.5 g/day;p=0.001). However, fetal outcome was not significantly altered.Conclusion: Pre-eclampsia and elampsia may be more severe in the presence of HS with a worsening of maternal prognosis while fetal outcome seems not altered.