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There is considerable evidence that Bisphenol S (BPS) induces various toxicological effects and is an industrial health issue. However, little data are available on the in vivo effects of BPS on the liver, a major target of drug toxicity. In this study, we evaluated the potential harmfulness of low levels of BPS in the liver of male mice. Also, we investigated the interaction between BPS and peroxisome proliferator-activated receptor-gamma (PPARγ) by computational docking approach. PPARγ is a member of the superfamily of nuclear hormone receptors. It acts as a transcription factor and regulates the genes involved in lipid and glucose metabolism and in inflammation and necrosis. Mice were exposed to BPS, in drinking water at 25, 50, and 100 μg/kg for 10 weeks. The protocol was started after weaning. At the time of sacrifice, blood samples were collected for a biochemical analysis, followed by liver tissue collection for histopathological study. Results showed that BPS-induced hypertriglyceridemia, increased liver injury markers, and initiated histopathological changes, including inflammatory cell infiltration, hepatocellular necrosis, and steatosis. BPS did not affect glycated hemoglobin (HbA1C). Interestingly, data showed that BPS could interact with the PPARγ ligand-binding pocket by hydrogen bonds with Asn 219, Cys 276, Ser 280, and Thr 283. We suggest that PPARγ is among the targets of BPS and could play a key role in the cascade reaction of BPS-induced liver disruption. These findings support the hypothesis that the post-weaning period is sensitive to low-dose BPS exposure that can lead to dyslipidemia signature later in life.

Variations of PON1 activity (PON1) were studied according to the type of liver injury, to assess the interest of this parameter in the diagnosis of liver diseases. The study was performed in population of patients with different liver damages. The liver diseases adopted during our investigation were grouped into different syndromes and pathologies. The classification by pathology, according to the clinical, biological and radiological context, made it possible to distinguish five types of hepatic impairment. The determination of the activity of PON1 was carried out on Konélab, and the assay the other enzymes as well as of the biochemical parameters were carried out on the Cobas 6000 system.The PON1 activity was lower in patients compared to control group (p

Epoxiconazole is a worldwide fungicide used to control fungal diseases. Although to its hazardous effects in non-target species, little information is available in the literature to show the cardiotoxic effects of EPX in male rats. Thus, our investigation aimed to assess the outcomes of EPX exposure on some biochemical parameters, the generation of oxidative stress, DNA fragmentation and histopathological alterations in the heart tissue. EPX was administered orally at doses of 8, 24, 40 and 56 mg/kg body weight, representing, respectively NOEL (No observed effect level), NOEL× 3, NOEL× 5 and NOEL× 7 for 28 consecutive days in male Wistar rats. Our results show that EPX induced a significant decrease of cardiac acetylcholinesterase, an increase of biochemical markers, such as creatinine phosphokinase (CPK) and a perturbation of the lipid profile. Furthermore, EPX caused diverse histological modifications in the myocardium, including congestion of cardiac blood vessels, cytoplasmic vacuolization, leucocytic infiltration and hemorrhage. Indeed, we have shown that EPX induces increase of lipid peroxidation, protein oxidation levels and DNA damage. On the other hand, we have found an increase of the antioxidant enzymes activity such as catalase (CAT) and superoxide dismutase (SOD) activities. The glutathione peroxidase and glutathione S tranferase initially enhanced at the doses of 8, 24, and 40 mg/kg b.w. and then decreased at the dose of 56 mg/kg b.w. In conclusion, our work has shown that EPX causes cardiotoxic effects by altering redox status and damaging heart tissue.

Di (2-ethylhexyl) phthalate (DEHP) is a plasticizer that gives flexibility to various polyvinyl chloride products. It is a pollutant easily released into the environment and can cause many adverse effects to living organisms including hepatotoxicity. The thioredoxin system is a determining factor in the redox balance maintaining in the liver, which is a vulnerable tissue of reactive oxygen species overproduction because of its high energy needs. In order to determine if the thioredoxin system is a target in the development of DEHP hepatotoxicity, Balb/c mice were administered with DEHP intraperitoneally daily for 30 days. Results demonstrated that after DEHP exposure, biochemical profile changes were observed. This phthalate causes oxidative damage through the induction of lipid peroxydation as well as the increase of superoxide dismutase and catalase activities. As new evidence provided in this study, we demonstrated that the DEHP affected the thioredoxin system by altering the expression and the activity of thioredoxin (Trx) and thioredoxin Reductase (TrxR1). The two enzyme activities of the oxidative phase of the pentose phosphate pathway: Glucose-6-phosphate dehydrogenase and 6-Phosphogluconate dehydrogenase were also affected by this phthalate. This leads to a decrease in the level of nicotinamide adenine dinucleotide phosphate used by the TrxR1 to maintain the regeneration of the reduced Trx. We also demonstrated that such effects can be responsible of DEHP-induced DNA damage.

AIM OF THE STUDY The diagnosis of heart failure in the emergency department (ED) is challenging. The aim of this study was to evaluate systolic time intervals (STIs) using phonoelectrocardiography for the diagnosis of heart failure (HF) in ED patients with undifferentiated dyspnea. METHODS A total of 855 patients with dyspnea and suspected HF were prospectively enrolled. They underwent echocardiographic measurements of left ventricular ejection fraction (LVEF), B-type natriuretic peptide (BNP) testing and computerised phonoelectrocardiography to assess STIs including electromechanical activation time (EMAT), left ventricular ejection time (LVET) and EMAT/LVET ratio. Diagnosis accuracy of STIs was calculated including sensitivity, specificity, likelihood ratio and receiver operating characteristic (ROC) curve. RESULTS Patients with HF (n = 530) had significantly higher EMAT and lower LVET compared with non-HF patients. ROC curve c-statistic was 0.74, 0.72 and 0.78 for EMAT, LVET and EMAT/LVET respectively. Sensitivity and specificity of EMAT/LVET at a cut-off = 40% were 72% and 88% respectively. EMAT/LVET had the highest correlation with LVEF (r = 0.48). In patients with intermediate BNP (n = 107), positive likelihood ratio increased from 1.8 with BNP alone to 3.6 with BNP combined to EMAT/LVET. Patients without HF had STIs values not significantly different from those with preserved LVEF (≥45%). CONCLUSIONS Given their immediate availability, phonoelectrocardiography STIs' parameters and particularly EMAT/LVET ratio could have an important role in the diagnosis approach of HF in patients with undifferentiated dyspnea in the ED.

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)

This study reports the clinical and biological signs, as well as the morphological aspect and the chemical composition of the calculus during the biliary stones. The study population consisted of 31 patients with an average age of 49 years (30 women and one man) with biliary lithiasis and who had cholecystectomy. Hepatic colic and epigastralgia were the most evocative clinical signs. The calculus were pigmentary (n=6), cholesterolic and mostly single (n=18), and mixed (n=6) and one infectious multiple lithiasis. Cholesterol was found in 22 calculi (70.96%). We have found a significant increase in liver enzymes and total bilirubin, which is more pronounced in pigmentary lithiasis. Our results showed that most gallstones were composed of cholesterol. These results indicate the influence of diet and chronic hemolysis in calculus formation. More investigation should allow knowing the nutritional and environmental factors influencing gallstones formation in Tunisia, in order to prevent this disease.

Objective: To investigate the potential adverse effects of imidacloprid on biochemical parameters, oxidative stress and liver damage induced in the rat by oral sub-chronic imidaclopride exposure. Methods: Rats received three different doses of imidacloprid (1/45, 1/22 and 1/10 of LD50) given through gavage for 60 days. Two dozen of male Wistar rats were randomly divided into four experimental groups. Liver damage was determined by measuring aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase leakages. The prooxidant-antioxydant status in hepatic tissue homogenate was evaluated by measuring the degree of lipid peroxidation, the antioxidant enzymes activities such as catalase, superoxide dismutase and glutathione peroxidase (GPx). Results: The relative liver weight was significantly higher than that of control and other treated groups at the highest dose 1/10 of LD50 of imidacloprid. Additionally, treatment of rats with imidacloprid significantly increased liver lipid peroxidation (P ≤ 0.05 or 0.01) which went together with a significant decrease in the levels of superoxide dismutase and catalase activities. Parallel to these changes, imidacloprid treatment enhanced liver damage as evidence by sharp increase in the liver enzyme activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase. These results were also confirmed by histopathology. Conclusions: In light of the available data, it is our thought that after imidacloprid sub-chronic exposure, depletion of antioxidant enzymes is accompanied by induction of potential oxidative stress in the hepatic tissues that might affect the function of the liver which caused biochemical and histopathological alteration.

Primary hyperoxalurias (PH) are inborn errors in the metabolism of glyoxalate and oxalate with recessive autosomal transmission. As a result, an increased endogenous production of oxalate leads to exessive urinary oxalate excretion. PH type 1, the most common form, is due to a deficiency of the peroxisomal enzyme alanine: Glyoxylate aminotransferase (AGT) in the liver. PH type 2 is due to the deficiency of the glyoxylate reductase/hydroxypyruvate reductase, present in the cytosol of hepatocytes and leucocytes. PH type 3 is linked to the gene HOGA1, encoding a mitochondrial enzyme, the 4-hydroxy-2-oxo-glutarate aldolase. Recurrent urolithiaisis and nephrocalcinosis are the markers of the disease. As a result, a progressive dysfunction of the kidneys is commonly observed. At the stage of severe chronic kidney disease, plasma oxalate increase leads to a systemic oxalosis. Diagnostic is often delayed and it based on stone analysis, cristalluria, oxaluria determination and DNA analysis. Early initiation of conservative treatment including high fluid intake and long-term co-administration of inhibitors of calcium oxalate crystallization and pyridoxine, could efficiently prevent end stage renal disease. In end stage renal failure, a combined liver-kidney transplantation corrects the enzyme defect.

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 Elevated osteoprotegerin (OPG) levels have been reported in patients with diabetes complications. We investigated whether plasma OPG levels can be used as a marker of cardiovascular risk in children and adolescents with type 1 diabetes (T1D). Methods Plasma blood samples were obtained from 243 subjects (143 children and adolescents with T1D and 100 healthy controls). OPG concentrations were measured by enzyme-linked immunosorbent assay (ELISA) method. All data were analyzed by using PASW statistics 18. Results A significant higher plasma OPG level was found in children with T1D compared to controls (p

Resume Objectif Le but de notre etude est de verifier si la PON1 pourrait constituer un facteur du risque cardiovasculaire chez des patients diabetiques type 2. Patients et methodes Il s’agit d’une etude transversale qui a porte sur 114 patients diabetiques type 2 dont 71 ayant un retrecissement du diametre de la coronaire superieur a 50 % et 53 temoins indemnes de toute pathologie. Resultats L’activite de la PON1 est significativement diminuee chez les patients par rapport aux temoins ( p = 0,021) et chez les patients stenose+ par rapport aux temoins ( p = 0,013). Aucune variation significative de l’activite de la PON1 en fonction de l’âge n’a ete notee aussi bien chez les temoins que chez les patients. Lorsque le HDLc ≥ 1,03 mmol/L, l’activite de la PON1 etait significativement plus elevee chez les patients stenose– et les temoins par rapport aux patients stenose+ ( p respectifs 0,030 et 0,008). En cas de stenose+, une diminution non significative de 12,23 % de l’activite de la PON1 a ete notee chez les fumeurs par rapport aux non-fumeurs. L’activite de la PON1 ne varie pas d’une facon significative selon la presence ou l’absence de l’hypertension arterielle chez les patients stenose+. Uniquement chez les patients stenose–, une augmentation proche de la significativite de l’activite de la PON1 a ete notee ( p = 0,051) Conclusion L’implication du diabete dans la diminution de l’activite de la PON1 parait hautement probable mais la PON1 ne semble pas etre en elle seule un marqueur du risque cardiovasculaire.

Objectives Smoking is one of the main risk factors for cardiovascular disease (CVD). The mechanism(s) of the effects of smoking on CVD are not clearly understood; however, a number of atherogenic characteristics, such as insulin resistance have been reported. We aim to investigate the effects of cigarette smoking on insulin resistance and to determine the correlation between this parameter with smoking status characteristics. Study design This study was conducted on 138 non-smokers and 162 smokers aged respectively 35.6 ± 16.0 and 38.5 ± 21.9 years. All subjects are not diabetic. Methods Fasting glucose was determined by enzymatic methods and insulin by chemiluminescence method. Insulin resistance (IR) was estimated using the Homeostasis Model of Assessment equation: HOMA-IR = [fasting insulin (mU/L) × fasting glucose (mmol/L)]/22.5. IR was defined as the upper quartile of HOMA-IR. Values above 2.5 were taken as abnormal and reflect insulin resistance. Results Compared to non-smokers, smokers had significantly higher levels of fasting glucose, fasting insulin and HOMA-IR index. These associations remained significant after adjustment for confounding factors (age, gender, BMI and alcohol consumption). A statistically significant association was noted between the smoking status parameters, including both the number of cigarettes smoked/day and the duration of smoking, and fasting insulin levels as well for HOMA-IR index. Among smokers, we noted a positive correlation between HOMA-IR index and both plasma thiocyanates and urinary cotinine. Conclusion Our results show that smokers have a high risk to developing an insulin resistance and hyperinsulinemia, compared with a matched group of non-smokers, and may help to explain the high risk of cardiovascular diseases in smokers.

Tebuconazole is an effective systemic fungicide that belongs to the triazoles family. It has been widely used in both agricultural and medical sectors for the control of fungal diseases. Although TEB poses serious threats to mammals health, studies regarding its cardiotoxicity are very limited. Thus, we aimed to evaluate the effects of TEB on some biochemical parameters, the induction of apoptosis and DNA damage in the heart tissue. Male Wistar rats were treated with TEB at varied oral doses for 28 consecutive days. This study demonstrates that TEB decreased cardiac acetylcholinesterase, increased serum marker enzymes such as creatinine phosphokinase (CPK) and lactate dehydrogenase (LDH), and altered the lipid profile by increasing serum levels of total cholesterol (T-CHOL), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and reduced high-density lipoprotein cholesterol (HDL-C) levels. Furthermore, TEB increased levels of p53 and Bax/Bcl2 ratio, released the cytochrome c into the cytosol and activated caspase-9 and caspase-3. Besides, our results showed that TEB induced genotoxic effects. TEB induced DNA fragmentation and increased the frequency of micronucleated bone marrow cells. Moreover, TEB treatment developed fibrosis in the myocardium. Our results suggest that TEB exposure may affect myocardial cells normal functioning and triggers apoptosis.

Because of the extensive use of phthalates for domestic, medical, and industrial applications, the evaluation of their toxic effects is of major concern to public health. The aim of the present study was to assess the propensity of di (2-ethylhexyl) phthalate (DEHP), one of the most used phthalates, to cause oxidative cardiac damage in mice. DEHP was administered intraperitoneally at doses of 5, 50, and 200 mg/kg body weight for 30 consecutive days in BALB/c mice. We assessed the effect of DEHP on cardiac injury using biochemical profile (such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatinine phosphokinase (CPK), total cholesterol (T-CHOL), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)), parameters related to myocardiac oxidative stress, such as malondialdehyde (MDA) level, protein carbonyl (PC) concentration, and DNA fragmentation. In addition, we evaluated antioxidant status; enzymatic (catalase (CAT) and superoxide dismutase (SOD) activities) and non-enzymatic (protein-bound sulfhydryl concentration (PSH)) antioxidants. Acetylcholinesterase (AChE) activity and histopathological changes were also assessed in heart mice treated with DEHP. Our results showed that DEHP induced an elevation of serum marker enzymes and perturbated the lipid profile. In addition, this phthalate increased lipid peroxidation, protein carbonyl levels, and DNA fragmentation in the heart in a dose-dependent manner. Antioxidant status was also perturbated by the increase of the CAT and SOD activities and the decrease of the protein-bound sulfhydryl concentration. AChE activity was also inhibited in the heart following the treatment with DEHP. These biochemical alterations were also confirmed by histopathological changes. Increased free radical production at various doses of DEHP would result in impairment of the redox status leading to an enhanced dose-dependent cardiotoxicity.

Triflumuron (TFM) is one of the most widely used insecticides over the world. It is a benzoylphenyl urea that belongs to the class of insect growth regulators. This insecticide acts by inhibiting insect's chitin synthesis and by consequences, making insect more susceptible to pathogens and malformations. TFM effects have been reported in mammalians and crops. However, studies that reveal its toxicity mechanisms are limited. In this line, the current study aimed to determine the implication of oxidative stress in the toxicity induced by TFM and particularly in the perturbation of biochemical parameters in male Balb/C mice. Male Balb/C mice were divided into three groups receiving TFM at doses of 250, 350, and 500 mg/kg bw respectively. The occurrence of oxidative stress in both kidney and liver tissues was monitored by measuring of oxidative stress markers. TFM caused an increase as protein carbonyls generation, malondialdehyde induction (MDA) and catalase (CAT), superoxide dismutase (SOD), glutathion peroxidase (Gpx), as well as glutathion S transferase (GST) activities. In the same conditions, we have evaluated the effect of TFM treatment on biochemical parameters. In response to the three TFM doses, we showed significant dose dependent inductions in all tested oxidative stress markers. However, TFM caused an increase in the liver enzyme activities as aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), g-glutamyltranspeptidase (GTT), and total bilirubin (BILT) in a dose-dependent manner. Equally, renal markers as urea, uric acid, albumin, and creatinine were increased in the same manner. We can conclude that oxidative damage seems to be a key determinant of TFM-induced toxicity in both liver and kidney of male Balb/C mice. Moreover, the oxidative stress is more pronounced in the liver than in the kidney. Thus, TFM may be considered as a hepatotoxic insecticide.

Poisoning and accidental oral intoxication are major health problems worldwide. Considering the insufficient efficacy of the currently available detoxification treatments, a pioneering oral detoxifying adsorbent agent based on a single biocompatible metal-organic framework (MOF) is here proposed for the efficient decontamination of drugs commonly implicated in accidental or voluntary poisoning. Furthermore, the in vivo toxicity and biodistribution of a MOF via oral administration have been investigated for the first time. Orally administered upon a salicylate overdose, this MOF is able to reduce the salicylate gastrointestinal absorption and toxicity more than 40-fold (avoiding histological damage) while exhibiting exceptional gastrointestinal stability (

Zearalenone (ZEN) is a mycotoxin from Fusarium species commonly found in food commodities and is known to cause reproductive disorders. Several in vivo studies have shown that ZEN is haematotoxic and hepatotoxic and causes several alterations of immunological parameters. Meantime, the available information on the cardiotoxic effects of ZEN is very much limited. In the present study, we investigated the toxic effects of ZEN in heart tissues of Balb/c mice. We demonstrated that ZEN (40 mg kg−1 body weight (b.w.)) increased creatine phosphokinase, lactate dehydrogenase, aspartate transaminase, alanine transaminase, total cholesterol and triglyceride levels and induced oxidative stress as monitored by measuring the malondialdehyde level, the generation of protein carbonyls, the catalase and superoxide dismutase activity and the expression of the heat shock proteins (Hsp 70). We also demonstrated that acute administration of ZEN triggers apoptosis in cardiac tissue. Furthermore, we aimed to evaluate the safety and efficacy of crocin (CRO), a natural carotenoid, to prevent ZEN-induced cardiotoxicity in mice. In fact, combined treatment of ZEN with different doses of CRO (50, 100, and 250 mg kg−1 b.w.) showed a significant reduction of ZEN-induced toxicity for all tested markers in a dose-dependent manner. It could be concluded that CRO was effective in the protection against ZEN-induced toxicity in cardiac tissue.

Patulin (PAT) is a mycotoxin produced by several species of the genera of Penicillium, Aspergillus, and Byssochlamys principally by Penicillium expansum. This mycotoxin is suspected to affect several organs including kidney and liver. However, its toxic effect on heart remains unknown. The present study investigated for the first time the cardiotoxic effect of PAT in mice. We demonstrated that PAT increased creatinin phosphokinase (CPK) level, induced lipoperoxydation and protein oxidation, and triggered the antioxidant enzymes such as superoxide dismutase and catalase activities. We also demonstrated that acute administration of PAT triggers apoptosis via P53 overexpression and caspase 3 activation. We further investigated the antioxidant efficiency of crocin (CRO), a carotenoid pigment, against PAT-induced cardiotoxicity. We found that pretreatment with CRO prevents cardiac impairment by reducing CPK levels, restoring the redox statute and suppressing apoptosis. Collectively, our data provide new preventive effect of CRO toward PAT-induced cardiotoxicity in mice.

The aim of this study was to determine the impact of combat sports practice on bone mineral density (BMD) and to analyze the relationship between bone parameters and anthropometric measurements, bone markers, and activity index (AI). In other words, to detect the most important determinant of BMD in the adolescent period among combat sports athletes. Fifty athletes engaged in combat sports, mean age 17.1±0.2 yr, were compared with 30 sedentary subjects who were matched for age, height, and pubertal stage. For all subjects, the whole-body BMD, lumbar spine BMD (L2-L4), and BMD in the pelvis, arms, and legs was measured by dual-energy X-ray absorptiometry, and anthropometric measurements were evaluated. Daily calcium intake, bone resorption, and formation markers were measured. BMD measurements were greater in the combat sports athletes than in the sedentary group (p0.01). Weight, body mass index, and lean body mass were significantly correlated with BMD in different sites. Daily calcium consumption lower than daily calcium intake recommended in both athletes and sedentary group. AI was strongly correlated with all BMD measurements particularly with the whole body, legs, and arms. Negative correlations were observed between bone markers and BMD in different sites. The common major predictor of BMD measurements was AI (p0.0001). AI associated to lean body mass determined whole-body BMD until 74%. AI explained both BMD in arms and L2-L4 at 25%. AI associated to height can account for 63% of the variance in BMD legs. These observations suggested that the best model predicting BMD in different sites among adolescent combat sports athletes was the AI. Children and adolescents should be encouraged to participate in combat sports to maximize their bone accrual.

The role of alpha-tocopherol on nephrotoxicity and hepatotoxicity induced by methamidophos (MT) was investigated in wistar rats. Animals were given via gavage, for four weeks, a low dose of MT (MT1), a high dose of MT (MT2), vitamin E (200 mg/kg of bw) or both MT2 plus vitamin E (Vit E) and control group was given distillate water. MT treatment resulted in a significant decrease in the body weight of MT2-treated group. Moreover, MT-treated groups had significantly lower butyrylcholinesterase (p < 0.01) and paraoxonase 1 (PON1) activities compared with the control group (p < 0.05). However, MT2-treated group had significantly higher alkaline phosphatase activity compared with untreated rats (p < 0.05). Both MT-treated groups had significantly higher urea (p < 0.01) and uric acid levels (p < 0.05) compared with the control group. However, significant low uric acid level (p < 0.05) was noted in MT2 plus vit E-treated rats compared with MT2-treated group. Histopathological changes in organ tissues were observed in both MT-treated groups and MT2 plus vit E-treated rats. However, the damage was reduced in MT2 plus vit E-treated rats. Therefore, this study deduces that alpha-tocopherol administration may ameliorate the adverse effects of subacute exposure to MT on rat liver and kidney and this antioxidant can protect PON1 from oxidative stress induced by this organophosphorus pesticide. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 842-854, 2016.

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

Objective This study aimed to investigate the variations of paraoxonase 1 (PON1) activity and lipid profile in patients with schizophrenia and the association of this activity with the sociodemographic, clinical and therapeutical characteristics of this population. Patients and methods Our cross-sectional study included 140 schizophrenic patients and 119 control subjects aged respectively 37.3 ± 10.4 and 41.4 ± 10 years. PON1 activity was determined using Konelab 30™ equipment (Thermo Electron Corporation). Plasma total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (c-HDL) and low-density lipoprotein cholesterol (c-LDL) concentrations were determined using Cobas 6000™ (Roche Diagnostics), apolipoproteins (ApoA1, ApoB) and lipoprotein (a) (Lp(a)) were determined using Integra 400 plus (Roche Diagnostics). Results Compared to controls, patients had no significant decrease of PON1 activity and significantly lower ApoA1, c-HDL levels, and significantly higher levels of TG, ApoB, Lp(a) and TC/c-HDL and ApoB/ApoA1 ratios. Furthermore, PON1 activity was correlated with TG/c-HDL ratio. The lowest PON1 activity was noted in obese patients, in paranoid sub-type and in patients treated with combination of typical and atypical antipsychotics without significant difference. Moreover, it was associated with gender and cigarette smoking but not with alcohol consumption status. Conclusion Schizophrenic patients had a decrease in PON1 activity and perturbations in their lipid profiles that contribute to increase the risk of cardiovascular diseases. In addition, our results revealed that there was no association between the decrease of PON1 activity and any demographic or clinical characteristics. Therefore, such patients require specific care, particularly with regard to their lipid profile.

Background Only a few studies have focused on the possible modulatory role of paraoxonase 1 (PON1) polymorphisms in lipid profiles, especially in children and in adolescents with type 1 diabetes (T1D). Objective We propose to study the association between PON1 polymorphisms (PON1-55 and PON1-192) and a lipid profile in a young Tunisian population with T1D. Methods The study compared 122 children and adolescents with T1D with 97 controls. Genomic DNA was collected from 116 patients and 91 controls. Lipid parameters were determined by automated methods. PON1 activity was measured by a spectrophotometric method and genotyping of the PON1 gene was assessed by multiplex polymerase chain reaction followed by restriction fragment-length polymorphism. Results A significant increase in total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol (LDL-C), apolipoprotein B (ApoB), and lipoprotein (a) (Lp(a)) and a significant decrease in apolipoprotein A1 (ApoA1), ApoA1/ApoB ratio, and PON1 activity/HDL-C ratio were observed in children with T1D compared with controls. In the LLQR haplotype, the group with diabetes showed significantly higher values of total cholesterol, LDL-C, apoB, Lp(a), and apoA1/apoB ratio compared with the control group. Those with diabetes with the LLQQ haplotype showed a significant decrease in LDL-C and Lp(a) compared with controls ( P Conclusion PON1 polymorphisms (PON1-55 and PON1-192) seem to be involved in the altering the lipid profile in T1D. The LLQR haplotype provided an atherogenic lipid profile in children with T1D compared with controls. LLQQ haplotype seemed to have a protective effect against the increase in LDL-C and Lp(a) that are heavily involved in the development of cardiovascular diseases.

Summary Objective The purpose of this study was to examine the effect of cigarettes smoking on lipid profile. Methods The initial study was conducted with 300 healthy subjects, among them, 138 non-smokers aged 38.47 ± 21.91 years and 162 smokers aged 35.55 ± 16.03 years. TG, TC, cHDL, cLDL were determined by enzymatic colorimetric method; ApoA1, ApoB, Lp(a) were determined by immunoturbidimetry on Konelab 30™. Results We noted a significant increase in smokers compared to non-smokers, in TG (1.79 ± 1.03 vs. 1.40 ± 1.24 mmol/L; P ≤ 10 −3 ), TC (4.13 ± 1.18 vs. 3.70 ± 1.04 mmol/L; P ≤ 10 −3 ), c-LDL (1.35 ± 0.56 vs. 1.16 ± 0.61 mmol/L; P ≤ 10 −3 ), Lp (a) (230 ± 226 vs. 179 ± 190 UI/L; P = 10 −3 ) and ApoB/ApoA1 (0.83 ± 0.52 vs. 0.52 ± 0.15; P = 0.03) and significant decrease in c-HDL (0.94 ± 0.25 vs. 1.07 ± 0.27 mmol/L; P ≤ 10 −3 ). TG values were higher in heavy than mild smokers (2.30 ± 0.96 vs. 1.63 ± 1.11 mmol/L; P ≤ 10 −3 ) and c-HDL levels decreased particularly in heavy smokers. We found a strong correlation between TC, TG and c-LDL levels and consumption duration ( r = 0.957, r = 0.991, r = 0.954; respectively). Conclusion Cigarette smoking is associated with perturbations in lipid profile, especially low levels of c-HDL, increase of TG which can explain the atherosclerosis risk.

Serum cystatin C concentration was recently reported as a marker of cardiovascular disease (CVD). In the present study, we evaluated the association between the increase of serum cystatin C levels and the risk of CVD in type 2 diabetes. 42 patients with type 2 diabetes were included in the present study; 27 of them have CVD. The control group consisted of 30 healthy adults. Cystatin C, creatinine, microalbuminuria and CRP were measured on Cobas 6000(TM). Cystatine C level was significantly higher in patients with CVD. A significant difference in serum cystatin C was found in patients with and without CVD among albuminuria. No difference in serum cystatin C levels was found according to number of affected vessels. A cystatin C level above 1.10 mg/L was associated with increase of risk of CVD with significant difference (OR = 42.52; IC 95% 1.455 to 1242.827 and p = 0.029). Our results suggested that the increase of serum cystatin C concentrations is a potential marker for CVD in diabetes.

L’activite de la cholinesterase plasmatique (ChE) peut varier dans certaines circonstances pathologiques. Nous avons etudie les variations de l’activite de cette enzyme en fonction du type d’atteinte hepatique, afin d’evaluer l’interet de ce parametre dans le diagnostic des pathologies hepatiques. Notre etude a ete effectuee sur 102 patients presentant differentes atteintes hepatiques et 53 temoins indemnes de toute pathologie. L’activite de la ChE etait plus basse chez les patients par rapport aux temoins (p < 0,0001) et plus nette chez les cirrhotiques par rapport a ceux presentant une hepatite. Une elevation de la bilirubinemie et des activites de l’AST, de l’ALT, de la GGT et de la PAL, et une diminution de l’albuminemie ont ete notees chez les patients par rapport aux temoins (p < 0,001). L’hypoalbuminemie etait nettement plus marquee chez les cirrhotiques par rapport aux malades qui souffrent de cholestase ou d’hepatite. Une correlation entre la ChE et la bilirubine, l’albumine et la protidemie a ete retrouvee chez les patients cirrhotiques ou ceux atteints d’une hepatite. Une activite significativement plus basse de cette enzyme a ete retrouvee chez les patients presentant une insuffisance hepatocellulaire (IHC). En cas de suspicion d’IHC, la prescription de l’activite de la ChE pourrait orienter ou confirmer le diagnostic de l’atteinte.

Summary Objective This study aimed to investigate the variations of the plasma TBARS levels (lipid peroxidation marker) and of the non-enzymatic antioxidants (uric acid, bilirubin and albumin) and their associations with the clinical and therapeutic characteristics in schizophrenic patients. Patients and methods A case control study included 121 schizophrenic patients and 88 control subjects aged respectively, 37.3 ± 10.3 and 33.5 ± 13,9 years. TBARS was determined by spectrophotometric method based on the reaction between malonedialdehyde (MDA) and thiobarbituric acid (TBA). Plasma uric acid (UA) and total bilirubin (TB) concentrations were determined using Cobas 6000 TM and albumin level was determined using Konelab 30 TM equipment. Results Compared to controls, patients had significantly higher levels of UA (270 ± 68 vs. 220 ± 73; P P Conclusion Schizophrenic patients had an increase in TBARS levels and perturbations in their non-enzymatic antioxidant status that contribute to increase the risk of oxidative stress. In addition, our results revealed that there was no association between the increase of TBARS levels, non-enzymatic antioxidants and any clinical or therapeutic characteristics. Therefore, such patients require specific care, particularly with regard to their lipid peroxidation and their non-enzymatic antioxidant.

The effect of cadmium chloride (150 mg/l) and mercury (II) chloride (80 mg/l) either alone or in combination in drinking water for 4 weeks on function and structure of the liver of male rats was studied. Results indicated that the ratio of liver weight to body weight and the activities of serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase noted in rats co-exposed to cadmium and mercury were intermediate between those noted in the individually metal treated rats. The histopathological study showed that the individual metal and the combined metal treatments caused severe liver damage. The degree of these changes noted in rats co-exposed to cadmium and mercury was not higher than those signalized in individual treatment. The biochemical and the histological changes observed in rats co-exposed to cadmium and mercury show that there is not an additive effect between these two metals.

Summary Aims We aim to investigate the variations of some oxidative stress markers (TBARs, uric acid, bilirubin and albumin) in Tunisian bipolar I patients and to explore the association of these parameters to clinical and therapeutic characteristics of this population. Methods Our study included 90 patients with bipolar I disorder and 92 controls. Uric acid, TBARs, bilirubin and albumin concentrations were determined by enzymatic and colorimetric methods. Results Compared with controls, patients had significantly higher values of uric acid and TBARs and significantly lower values of bilirubin. However, no significant change in albumin values was observed. Furthermore, bipolar I disorder was significantly associated with hyperuricemia (OR, 3.64; 95% CI: 1.96–6.75; P Conclusion Bipolar I disorder was significantly associated with hyperuricemia, hypobilirubin, and hyperTBARs, reflecting the existence of oxidative stress. This risk was significantly associated with treatment by mood stabilizers, the illness episode and duration, and the total number of illness episodes.

We identified and quantified a variety of mineral elements in 18 tobacco samples purchased from a Tunisian market. In total, 25 mineral elements have been measured in cigarettes, water pipe tobacco, and smokeless tobacco using inductively coupled plasma-optical emission spectroscopy following microwave-assisted digestion. Statistical analyses were performed using SPSSTM, version 18.0. The lowest concentrations of all studied elements were observed in water pipe tobacco. Significantly higher concentrations of Al, Fe, Mg, Na, Ca, Cr, and Co were found in smokeless tobacco, while cigarettes brands contained the highest concentrations of K, Mn, Ni, Ba, and Sr. There was no significant difference between the mineral contents of local and foreign cigarettes and conventional and light cigarettes. Our findings demonstrated that local smokeless tobacco appears to be the most hazardous tobacco type. The concentration of minerals in light cigarettes was not significantly different from the concentration in conventional cigarettes.

Background Major depressive disorder (MDD) is a common psychiatric disorder with considerable mortality. Death from unnatural causes, largely suicidal or quasi-suicidal, has a particularly high risk for the functional disorders, especially depression and schizophrenia. One of the prospective risk factors for this disease is hyperhomocysteinemia and folate deficiency. The methylenetetrahydrofolate reductase (MTHFR) gene encodes for a 5-methylenetetrahydrofolate reductase involved in folate metabolism and neurotransmitter synthesis. The aim of this research is to study the association between the C677T polymorphism of MTHFR gene and depression in Tunisian population, to explore their relationship with clinical and therapeutic characteristics of this disease. And it may lead to discover a novel marker to identify a patient with a higher risk of development of depressive disorder to be. This marker can be used for better therapeutic management and prevent disease installation. Methods Our study included 208 depressive patients, 187 controls aged between 44.1 ± 13.5 and 38.9 ± 13.2 years, respectively. MTHFR gene polymorphisms were determined by PCR–RFLP (polymerase chain reaction–restriction fragment length polymorphism). Results No significant difference was detected in the distribution of the genotype frequencies of MTHFR C677T polymorphisms (χ2 = 5.443, df = 2, p = 0.066) between patients and controls. But when we study the risk of these genotypes, CT genotype is significantly more frequent in controls compared to patients, it may be a protection from depression (OR = 0.655, CI 95 % = 0.432–0.995, p = 0.047, OR* = 0.638, CI 95 %* = 0.415–0.983, p* = 0.04, before and after adjustment). Women, TT Genotype can increase four times the risk to be depressive. Addictive behavior seems to be associated with CT genotype and there was no significant association between clinical and therapeutic characteristics and this polymorphism. Conclusion This paper is the first study to prove that CT genotype of MTHFR C677T polymorphism may protect from depression and TT genotype seems to be associated with women’s depression. Further studies are required with other polymorphisms and biochemical factors that must be investigated to clarify the implication of MTHFR C677T polymorphism in the pathophysiology of depression.

Resume But Les etudes qui ont evalue l’influence de l’âge et du sexe sur la composition des calculs urinaires dans le monde arabe sont rares. L’objectif de cette etude a ete d’identifier la composition des calculs urinaires dans la population du centre tunisien et d’etudier leur evolution en fonction du sexe et l’âge. Patients et methodes Notre travail a porte sur 1200 patients lithiasiques tunisiens (729 de sexe masculin et 471 de sexe feminin) âges de six mois a 92 ans, qui ont ete admis dans les services d’urologie et de chirurgie pediatrique entre 2001–2010. L’analyse des calculs urinaires a ete realisee respectivement a l’aide d’un stereomicroscope et par spectroscopie infrarouge afin de determiner, respectivement, le type morphologique et de la composition moleculaire de chaque calcul. Resultats Nous avons observe une predominance de la lithiase renale qui a represente 48,6 % de l’ensemble des calculs. Les enfants et les personnes âgees ont ete les plus touches par la lithiase vesicale. L’analyse de la composition a montre que l’oxalate de calcium monohydrate (whewellite) etait majoritaire dans 51,8 % des calculs et dans 39,6 % des noyaux, sa frequence a diminue en fonction de l’âge de 61,4 % chez les jeunes adultes a 47,7 % chez les personnes âgees en faveur de l’augmentation des calculs d’acide urique (16,4 % et 35,6 % respectivement [ p Conclusion L’analyse de ces donnees a montre que les calculs urinaires en Tunisie avaient les memes caracteristiques physico-chimiques analogues a celles qui ont ete observees dans les pays developpes.

This study aimed to evaluate the interference of tobacco smoke on immunochromatography assay of urinary drug detection.Our study included 256 voluntary subjects (143 passive smokers and 113 current smokers). Cotinine was measured by immunoenzymatic method and thiocyanates (SCN(-)) by selective electrode. Urinary drug was detected by immunochromatography assay. A positive result is completed by an analytical method with an immunometric assay.False positive results for benzodiazepines are significantly more frequent in smokers compared with passive smokers (90.2% Vs 22.4%; χ(2) = 116.62, p 10(-3)). For smokers, the number of cigarettes was significantly higher in subjects with falsely positive results for benzodiazepines compared with subjects with negative results (32 ± 11 Vs 20 ± 10; p = 0.04). Between these two groups, we established a significant difference for urinary cotinine (345 ± 211 Vs 117 ± 54 μg/μmol; p 10(-3)) and for plasma SCN(-) (101.6 ± 3.4 Vs 98.8 ± 2.1 μmol/L; p = 10(-3)). Urinary cotinine and consumption duration present the highest values of areas under curves (AUC) of the receiver-operating-characteristic (ROC) curves. The cut-off of 167.6 μg/μmol and 10.5 years were found as predictive factors of false positive results.Tobacco smoke interferes with immunochromatography assay of urinary drug detection; therefore, all subjects must be questioned about their smoking status to avoid such false results during results interpretation.

Summary Objectives This study aims to investigate the variation of malondialdehyde (MDA) in smokers and to determine the correlation between this parameter with smoking status parameters (number of cigarettes smoked per day and consumption duration). Methods This study was conducted on 138 non smokers and 162 smokers aged respectively 35.55 ± 16.03 and 38.47 ± 21.91 years. For the determination of MDA, we used the thiobarbituric acid method. Results We found significant increase in MDA (8.22 ± 2.52 vs 6.60 ± 3.77; P −4 ) in smokers compared to non smokers before and after adjustment. After adjustment for potentials confounder factors such as lipid profile, BMI, age and gender, we noted a significant association between smoking status and higher levels of MDA levels. In smokers, we found a positive significant correlation between MDA and number of cigarette smoked per day ( r = 0.535; P −4 ). MDA levels were significantly higher in subjects smoking more than 40 cigarettes per day compared to those smoking less than 20 cigarettes per day. Moreover, we found that smoking multiplies by 2.8 the risk of an increase in MDA. In addition, among smokers, we found that the risk of an increase in MDA increases with the number of cigarettes smoked per day and with consumption duration. Conclusion The evaluation of oxidative stress in smokers may then be regarded as a key element to integrate into the clinical and laboratory followed smokers for better prevention of cardiovascular disease.

Background Studies that evaluate the effect of age on stone composition are scarce. The aim of this study was to highlight the changes in epidemiological characteristics (stone composition and location) of urolithiasis according to patients' age. Methods We studied 1,301 urolithiasis patients with age ranging from 6 months to 92 yr (781 males and 520 females). Stone analysis was performed using a stereomicroscope and infrared spectroscopy to determine the morphological type and molecular composition of each stone. Results The annual average incidence of new stone formation was 31.7 per 100,000 persons. In 71.8% of cases, calculi were located in the upper urinary tract. Compared to other age groups, children and old men were more affected by bladder stones. Calcium oxalate monohydrate was the most frequent stone component, even though its frequency decreased with age (59.5% in young adults and 43.7% in the elderly, 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.

Objectifs : Etudier les effets du tabac sur les concentrations de la TSH et la FT4, la variation de ces concentrations selon les caracteristiques de la consommation (nombre de cigarettes fumees/j et anciennete de l’exposition/an) et leurs associations avec les deux marqueurs biologiques du tabagisme (cotininurie et thiocyanates plasmatiques (SCN -)). Materiel et methodes : Notre etude a concerne 162 fumeurs (F), 27 anciens fumeurs (AF) et 111 non-fumeurs (NF) âges respectivement de 35,4 ± 16 ; 31,6 ± 1,8 et 38,0 ± 14,6 ans. La TSH et la FT4 ont ete determinees par electrochimiluminescence, la cotininurie par immunoenzymologie et les thiocyanates par electrode selective. Resultats : Une diminution significative de la TSH et une augmentation progressive de la FT4 en fonction du statut tabagique ont ete notees avant et apres ajustement. La TSH est significativement plus basse et la FT4 significativement plus elevee chez les F et AF par rapport aux NF. La TSH etait significativement plus basse chez les sujets fumant plus de 40 cigarettes/j par rapport a ceux fumant moins de 20. Elle etait egalement significativement plus basse chez les F dont le tabagisme datait de plus de 5 ans par rapport a ceux fumant depuis moins de 5 ans. La cotininurie et les thiocyanates presentent une correlation negative avec la TSH et une correlation positive avec la FT4. Conclusion : Chez les F, les variations de la FT4 et de la TSH refletent un risque d’hyperthyroidie plus eleve, et sont etroitement correlees aux caracteristiques de la consommation. De plus, l’arret du tabac peut entrainer de legeres reductions de la FT4 et des augmentations de la TSH, par consequent des effets reversibles du tabac sur la thyroide.

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

Elevated osteoprotegerin (OPG) levels have been reported in patients with diabetes complications. We investigated whether plasma OPG levels can be used as a marker of cardiovascular risk in children and adolescents with type 1 diabetes (T1D).Plasma blood samples were obtained from 243 subjects (143 children and adolescents with T1D and 100 healthy controls). OPG concentrations were measured by enzyme-linked immunosorbent assay (ELISA) method. All data were analyzed by using PASW statistics 18.A significant higher plasma OPG level was found in children with T1D compared to controls (p 0.001). A significant increase of OPG levels has been related to the glucose level ≥ 7 mmol/L (2.44 [0.01-6.22] vs. 2.16 [0.13-6.22] pmol/L, p = 0.019), microalbuminuria ≥ 30 mg/24 h (3.71 [0.160-6.03] vs. 2.26 [0.01-6.22] pmol/L, p 0.001), and cystatin-C ≥ 0.789 mg/L (2.64 [0.37-6.22] vs. 2.11 [0.01-5.82] pmol/L, p 0.001). We noted a significant higher frequency of children with increased cystatin-C levels in the group with elevated plasma level of OPG compared with those with normal levels (49 vs. 18%, respectively) with an odds ratio (OR) = 4.42 [1.41-13.84] (p = 0.006). We showed a significant increase of OPG levels when the number of cardiovascular risk factors exceeds 3 (p = 0.001).OPG may be a potential biomarker of cardiovascular risk in T1D. Implementation of OPG determination in the clinical laboratory setting would be useful in order to better stratify patients and to assess the most adequate treatment.

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.

Aims: The aim of the present study was to investigate hyperhomocysteinemia in Tunisian bipolar I patients according to 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism. Methods: The subjects consisted of 92 patients with bipolar I disorder diagnosed according to DSM-IV, and 170 controls. Plasma total homocysteine, folate and vitamin B12 were measured. MTHFR C677T polymorphism was determined by polymerase chain reaction–restriction fragment length polymorphism. Results: Compared with controls, patients had a significantly higher homocysteine level (16.4 ± 9.8 vs 9.6 ± 4.5 µmol/L; P 12 years. Hypofolatemia was seen in all patients on lithium and in the majority of patients on carbamazepine, and the highest prevalence of hypovitamin B12 was noted in patients taking carbamazepine. Conclusion: Hyperhomocysteinemia was more frequent in bipolar I patients independent of C677T polymorphism. Patients had reduced levels of folate, which modulates homocysteine metabolism. Indeed, this finding indicates that folate supplementation may be appropriate for bipolar patients with hyperhomocysteinemia.

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

Resume Objectif L’homocysteine (Hcys) est un acide amine soufre, incrimine dans la genese de differentes affections neuropsychiatriques et recemment dans la schizophrenie (SZ). Les objectifs de ce travail etaient de determiner les concentrations plasmatiques de l’Hcys, du folate et de la vitamine B12 (vit B12), d’estimer la frequence et la severite de l’hyperhomocysteinemie chez les patients schizophrenes et de rechercher les associations entre l’Hcys et les caracteristiques de ces patients. Patients et methodes Notre population d’etude comportait 61 patients schizophrenes et 46 temoins sains. La concentration plasmatique de l’Hcys a ete determinee par une methode immunologique utilisant la polarisation de fluorescence (FPIA) adaptee sur AxSYM™ (Abbott). Le dosage de la vit B12 et des folates a ete effectue par electrochimiluminescence sur Elecsys 2010™ (Roche Diagnostics). Resultats Une augmentation statistiquement significative des concentrations plasmatiques de l’Hcys (16,1 μmol/L versus 10,9 μmol/L, p = 0,028) et une diminution statistiquement significative de la folatemie (4,2 μg/L versus 8,2 μg/L, p Conclusion Chez les patients schizophrenes, il existe une hyperhomocysteinemie moderee, associee a l’absence d’antecedents psychiatriques familiaux et a la diminution de la vit B12. L’Hcys devrait etre consideree comme un facteur a prendre en consideration dans le suivi et la prise en charge chez les patients schizophrenes.

Nowadays, people’s exposure to chemical compounds such as organophosphorus insecticides is continuously on the rise more and more. Theses compounds have induced an excessive production of free radicals which are responsible for several cell alterations in the organism. Recent investigations have proved the crucial role of nutritional antioxidants to prevent the damage caused by toxic compounds. In this study, we investigate the role of date palm fruit extract (Phoenix dactylifera L.) in protection against oxidative damage and hepatotoxicity induced by subchronic exposure to dimethoate (20 mg/kg/day). Oral administration of dimethoate caused hepatotoxicity as monitored by the increase in the levels of hepatic markers enzymes (transaminases, alkaline phosphatase, gamma-glutamyl transferase and lactate dehydrogenase), as well as in hepatic malondialdehyde thus causing drastic alteration in antioxidant defence system. Particularly, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) were found increased by dimethoate while catalase (CAT) activity was reduced significantly. These biochemical alterations were accompanied by histological changes marked by appearance of vacuolization, necrosis, congestion, inflammation, and enlargement of sinusoids in liver section. Pretreatment with date palm fruit extract restored the liver damage induced by dimethoate, as revealed by inhibition of hepatic lipid peroxidation, amelioration of SOD, GPx and CAT activities and improvement of histopathology changes. The present findings indicate that in vivo date palm fruit may be useful for the prevention of oxidative stress induced hepatotoxicity.

Renal tubular acidosis (RTA) is a tubulopathy characterized by metabolic acidosis with normal anion gap secondary to abnormalities of renal acidification. RTA can be classified into four main subtypes: distal RTA, proximal RTA, combined proximal and distal RTA, and hyperkalemic RTA. Distal RTA (type 1) is caused by the defect of H(+) secretion in the distal tubules and is characterized by the inability to acidify the urine below pH 5.5 during systemic acidemia. Proximal RTA (type 2) is caused by an impairment of bicarbonate reabsorption in the proximal tubules and characterized by a decreased renal bicarbonate threshold. Combined proximal and distal RTA (type 3) secondary to a reduction in tubular reclamation of bicarbonate and an inability to acidify the urine in the face of severe acidemia. Hyperkalemic RTA (type 4) may occur as a result of aldosterone deficiency or tubular insensitivity to aldosterone. Clinicians should be alert to the presence of RTA in patients with an unexplained normal anion gap acidosis, hypokalemia, recurrent nephrolithiasis and nephrocalcinosis. The mainstay of treatment of RTA remains alkali replacement.

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.

Objective This study aims to evaluate the prevalence of thyroid dysfunctions and to explore their association with perturbations in lipid profile in bipolar I patients. Patients and methods Our study included 130 bipolar I patients diagnosed according to the DSM IV, and 124 control subjects aged respectively 37.9 ± 12.1 and 37.6 ± 13.2 years. TSH and FT4 were determined using electrochemiluminescence. Total cholesterol, triglycerides, c-LDL and c-HDL were determined by enzymatic colorimetric methods and ApoA1, ApoB and Lp(a) by immunoturbidimetric techniques on Konelab 30™. Results Patients had significantly higher TSH values than controls and had perturbations in lipid profile. 0.7% and 28.5% of patients had respectively hyperthyroidism and hypothyroidism. Hypothyroidism was associated with obesity and perturbations in lipid profile particularly increase in total cholesterol, c-LDL, ApoB, ApoB/ApoA1 and Lp(a) and decrease in ApoA1 and c-HDL. Moreover, it was associated with lithium and valproic acid treatment. Conclusions Hypothyroidism was frequent in bipolar patients. It was significantly associated with obesity and perturbations in lipid profile. Therefore, bipolar patients require specific care, particularly for thyroid, lipid profile and weight; the effectiveness of this care will be evaluated during follow-up period.

Nous avons etudie l’influence de certains facteurs sur l’activite de la butyrylcholinesterase (BChE), evalue le statut sanitaire des travailleurs agricoles et l’effet de l’exposition chronique aux pesticides, dans le but de determiner les facteurs a prendre en consideration lors de l’interpretation de l’activite de la BChE dans le cadre de surveillance professionnelle systematique de ces travailleurs agricoles. Notre etude a ete realisee chez 110 travailleurs agricoles et 97 temoins. Chaque individu a beneficie d’un examen clinique. La determination de l’activite de BChE a ete realisee par une methode cinetique spectrophotometrique. L’activite moyenne de la BChE est apparue significativement plus faible chez les travailleurs par rapport aux temoins ( p < 0,001). Parmi les 44 % des travailleurs rapportant au moins un signe neurologique ou neuropsychique, 29 % avaient une activite de BChE inferieure a 6000 UI/L. Les cephalees representent le symptome neurologique le plus souvent mentionne (20 %). La variation de l’activite de la BChE est non seulement liee a la nature du pesticide utilise, mais aussi aux differentes modalites d’exposition. Une anciennete d’exposition excedant dix ans, une exposition depassant 150 heures par an a des melanges de pesticides organophosphores-carbamates interviennent dans la diminution significative de cette enzyme et peuvent etre considerees comme des facteurs de risque des effets toxiques cholinergiques. L’activite de BChE est un biomarqueur pour la surveillance des travailleurs agricoles. Cependant, elle doit etre accompagnee par un examen clinique systematique, prenant en consideration ces facteurs de risque, pour une identification precoce des travailleurs a haut risque.