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Hospital effluent (HE) is one of the most important sources of pharmaceuticals released into the environment. This kind of pollution is a recognized problem for both human health and aquatic life. Consequently, in the present study, we assessed the effects of untreated hospital effluent on mice via biochemical and histopathological determinations. Female mice were given free access to water bottles containing untreated HE at different dilutions for 21 days. Then clinical biochemistry and histopathology evaluation were conducted. Serum biochemistry analysis showed the presence of significant increase in cholesterol, triglycerides, glycaemia and total bilirubin. However, phosphatase alkaline and urea activities have been significantly decreased compared to the control group. No significant variation was observed for the rest of the studied parameters (high-density lipoproteins; low-density lipoproteins and uric acid). Additionally, multiple alterations, including cellular necrosis, leucocyte infiltration and congestion, were observed in different tissues of mice exposed to the tested HE. HIGHLIGHTS Hospital effluent (HE) exposure did not influence the total body weight of mice.; Sub-chronic exposure to the HE disturbed biochemical parameters in mice.; Histological abnormalities were observed in mice liver, kidney and heart sections.; Effluent toxicology.; Water contamination.

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

Background: The increased degradation of tryptophan (Trp) along the kynurenine (Kyn) pathway due to inflammation and/or activation of the hypothalamic-pituitary–adrenal (HPA) axis has been reported among the biological factors involved in the pathophysiology of major depressive disorder (MDD) and suicide. However, the interaction among these multiple factors is not yet completely clarified. Method: We studied plasma levels of Trp, Kyn, cortisol and proinflammatory cytokines (IL-1, IL- 6, IL-12, IL-20) and calculated the ratio Kyn/Trp as an index of the breakdown of Trp into Kyn in 31 suicidal MDD patients and 67 non-suicidal MDD patients. Result: We confirmed that suicidal MDD patients have reduced plasma Trp, higher Kyn and Kyn/Trp ratio, and no difference in cortisol levels than non-suicidal MDD patients. IL-1 and IL-12 levels were significantly higher in suicidal MDD than in non-suicidal MDD (p=0.034 and p=0.023, respectively), whereas Il-6 and IL-20 levels were equal in the two groups. The Kyn/Trp ratio was positively correlated with a pro-inflammatory cytokines index (r=0.309, p=0.002) and cortisol (r=0.368, p=0.001). Notably, the variance in the Kyn/Trp ratio explained by the model including both cortisol and inflammatory parameters as dependent variables, substantially improved compared with the models in which the two parameters were considered separately. Conclusion: These findings show that both cortisol and proinflammatory cytokines are involved in the enhanced breakdown of Trp into Kyn occurring in suicidal MDD patients, thus adding new knowledge on the biological mechanisms leading to the activation of the Kyn pathway in MDD and suicide.

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.

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.

Background Nutritional choices, which include the source of dietary fatty acids (FA), have an important significant impact on coronary artery disease (CAD). We aimed to determine on patients with CAD the relationships between Trans fatty acids (Trans FA) and different CAD associated parameters such as inflammatory and oxidative stress parameters in addition to Gensini score as a vascular severity index. Methods Fatty acid profiles were established by gas chromatography from 111 CAD patients compared to 120 age-matched control group. Lipid peroxidation biomarkers, oxidative stress, inflammatory parameters and Gensini score were studied. Results Our study showed a significant decrease of the antioxidant parameters levels such as erythrocyte glutathione peroxydase (GPx) and superoxide dismutase (SOD) activities, plasma antioxidant status (FRAP) and thiol (SH) groups in CAD patients. On the other hand, catalase activity, conjugated dienes and malondialdehyde were increased. Plasmatic and erythrocyte Trans FA were also increased in CAD patients compared to controls. Furthermore, divergent associations of these Trans FA accumulations were observed with low-density lipoprotein-cholesterol/ high-density lipoprotein-cholesterol (LDL-C/HDL-C) ratio, Apolipoprotein B (ApoB), lipid peroxidation parameters, high-sensitivity C Reactive Protein (hs-CRP), Interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) and Gensini score. Especially, elaidic acid (C18:1 trans 9), trans C18:2 isomers and trans 11 eicosanoic acid are correlated with these parameters. Trans FA are also associated with oxidative stress, confirmed by a positive correlation between C20:1 trans 11 and GPx in erythrocytes. Conclusions High level of Trans FA was highly associated with the induction of inflammation, oxidative stress and lipoperoxidation which appear to be based on the vascular severity and might be of interest to assess the stage and progression of atherosclerosis. The measurement of these Trans FA would be of great value for the screening of lipid metabolism disorders in CAD patients.

Hamdi Boubaker,1,2 Mohamed Habib Grissa,1,2 Kaouther Beltaief,1,2 Zohra Dridi,3 Mohamed Fadhel Najjar,4 Wahid Bouida,1,2 Riadh Boukef,5 Soudani Marghli,6 Semir Nouira1,2 1Department of Emergency, Fattouma Bourguiba University Hospital, 2Research Laboratory (LR12SP18), University of Monastir, 3Department of Cardiology, 4Department of Biochemistry, Fattouma Bourguiba University Hospital, Monastir, 5Department of Emergency, Sahloul University Hospital, Sousse, 6Department of Emergency, Tahar Sfar University Hospital, Mahdia, Tunisia Background: The goal of this study was to determine the value of systolic time intervals and their change during Valsalva maneuver (VM) in the diagnosis of left ventricular dysfunction (LVD) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Methods: We included 166 patients admitted to the emergency department for AECOPD. Measurement of systolic time intervals included electromechanical activation time (EMAT), left ventricular ejection time (LVET), and EMAT/LVET ratio. These were performed at baseline and during the first strain phase of the VM using a computerized phonoelectrocardiographic method. The diagnosis of LVD was determined on the basis of clinical examination, echocardiography, and brain natriuretic peptide. The values of systolic time intervals were compared between patients with and without LVD; their diagnostic performance was assessed using the area under receiver operating characteristic (ROC) curve.Results: Patients with LVD (n=95) had a significantly higher EMAT and lower LVET and EMAT/LVET ratio compared to patients without LVD (n=71); the area under ROC curve was 0.79, 0.88, and 0.90, respectively, for EMAT, LVET, and EMAT/LVET ratio. All baseline systolic time intervals changed significantly during VM in patients without LVD but they did not change in patients with LVD. The area under ROC curve increased to 0.84 and 0.93,­respectively, for EMAT and EMAT/LVET ratio but did not change for LVET.Conclusion: Simple and noninvasive measurements of systolic time intervals combined with VM could be helpful to detect or rule out LVD in patients admitted to the emergency room for COPD excacerbation. The EMAT/LVET ratio seems to have the best diagnostic value. Keywords: chronic obstructive pulmonary disease, exacerbation, systolic time intervals, Valsalva maneuver&nbsp

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.

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 (

Background A number of factors may offset the cardioprotective effects of glucose‐insulin‐potassium (GIK) on outcome of patients with acute coronary syndrome, such as hyperglycemia induced by this cocktail infusion. We performed a study to evaluate the effect of intensive insulin therapy in association with GIK on 1‐year outcome in patients hospitalized for acute coronary syndrome. Methods and Results In a randomized prospective controlled trial we included 772 patients with non–ST‐segment elevation acute coronary syndrome. Patients were randomized into 3 groups: GIKI 2 group, who received GIK with intensive insulin therapy for 24 hours; GIK group, who received GIK with nonintensive insulin therapy; and control group, who received usual care. The primary outcome criteria were the rates of major cardiovascular events combining death, reinfarction, and stroke rate at 1 year. In addition, we measured platelet function assay‐100 and plasminogen activator inhibitor‐1 at admission and 24 hours later. Based on an intention‐to‐treat analysis, major cardiovascular events at 1 year was 12.8% in the GIKI 2 group, 15.5% in the GIK group, and 20.5% in the placebo group; the difference was significant between the GIK 2 and control groups ( P =0.01). Platelet function assay‐100 at 24 hours decreased significantly from baseline in the control group but not in the GIKI 2 group. Plasminogen activator inhibitor‐1 decreased significantly in the GIKI 2 group but significantly increased in the control group. Minor hypoglycemic events were more frequent in the GIKI 2 group compared with other groups. Conclusions GIKI 2 led to improvement of 1‐year outcome rates in patients with non–ST‐segment elevation acute coronary syndrome. This beneficial effect was associated with a decrease in platelet reactivity and an increase on fibrinolysis tests. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT00965406.

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

Background Adipose tissue is an important endocrine organ that secretes a number of adipokines, like Resistin (RETN); it's an adipocytes-secreted cytokine and has been proposed as a link between obesity and diabetes. Many resistin gene polymorphisms were described and their implication in obesity was controversial. This study was to investigate the prevalence of single nucleotide polymorphisms (SNPs) in RETN gene 420C/G; 44G/A; 62G/A; 394C/G and 299 G/A and their association with Resistin level and obesity in Tunisian volunteers. Methods We recruited 169 nonobese (mean age=42.16-14.26 years; mean body mass index [BMI]=24.51-3.69 kg/m2) and 160 obese (mean age=47.86-11.17 years; mean BMI=36-4.78 kg/m2). Genotyping was performed using polymerase chain reaction–restriction fragment length polymorphism. Anthropometric parameters, lipid levels, Glycemia and insulinemia were measured, BMI was calculated and insulinresistance was evaluated with the homeostasis model assessment insulin resistance (HOMA-IR) and resistin level was measured by ELISA. Statistical analyses were performed by SPSS19.0. Results After adjustment for confounding parameters; the Odds Ratio (OR) of obesity associated with mutated genotypes at 420C/G compared with normal genotype was as: OR=2.17; 95% CI [1.28-3.68], P=.004. The serum Resistin levels present no significant association with all RETN polymorphisms and it was significantly associated with BMI (P=.047). In our haplotype analysis, one haplotype seems to be protective and one other seems to be the highest risk to obesity. Conclusion The 420 C/G Polymorphism were associated with obesity and Leptin concentration in our population.

Background There have been many studies on psychiatric disorders, but very little is known about the biology of suicide with schizophrenia. In the present study, we are looking for a possible connection between altered lipid profile and suicidal behavior in schizophrenic Tunisian patients. Methods Assay of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and triglycerides (TG) has been done for 126 schizophrenic patients with and without suicide attempts and 131 healthy controls recruited in the University Hospital of Monastir. Results TC and LDL-c levels were significantly higher in schizophrenic patients compared to controls. TC was significantly lower in schizophrenic patients with suicide attempt compared to those without suicide attempt. Depending to the sonority of suicide attempt, TC was significantly lower in patients with recent suicide attempt compared to those with lifetime suicide attempt and without suicide attempt (p

We evaluated the metabolic and the nutritional aspects of 134 urolithiasis children in order to outline the characteristics of idiopathic urolithiasis in children. This prospective study group of 134 children (56 females, 78 males) with renal calculi was evaluated. The age range of the patients was six months to 16 years. A dietary survey was performed on every child. All patients were investigated with respect to stone localization and serum and urine risk factors. Statistical analysis of data was carried out using software SPSS 11.0 for Windows. Hypercalciuria was the most common risk factor detected in this group (28.3%). A decrease of water intake was noted in all age groups, especially in the rural area (549.6 mL/day vs. 1150.6 mL/day), and there was an increase in animal protein intake in 17 cases (mean: 1.9 g/kg). In addition, increased intake of starchy foods and food with high oxalate content (sorgum) were detected in the ten to 16 years age group (51%) of our study. Calcium oxalate monohydrate represents the principal component of idiopathic stone (58.2%), which is more frequent in children (68%) than in infants (51.7%) (P

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.

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.

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

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

Introduction: Paraoxonase 1 (PON1) polymorphisms have been largely involved in diabetes complications. The aim of the study is to evaluate the effects of PON1 polymorphisms (L55M and Q192R) on diabetic nephropathy (DN). Material and methods: The study involved 116 children and adolescents with type 1 diabetes (T1D) and 91 healthy subjects. Albumin excretion rate (AER) was determined by immunoturbidimetry. PON1 activity was measured by a spectrophotometric method, and genotyping of PON1 gene was assessed by multiplex PCR followed by RFLP. Results: PON1 activity was inversely correlated to AER (r = –0.245, p = 0.008). A significant decrease (p = 0.037) in PON1 activity was shown between patients with nephropathy and those without (162 [57–618] vs. 316 [37–788] IU/L, respectively). The distribution of AER was, for L55M polymorphism MM > LM > LL (p = 0.002), and for Q192R polymorphism QQ > QR > RR (p < 0.001). The opposite distribution was noted for PON 1 activity (p < 0.001). LMQQ and MMQQ haplotypes seem to increase AER (p = 0.004, p = 0.003, respectively) and to reduce PON1 activity (p = 0.011, p = 0.052, respectively) in youths with T1D. However, LLRR haplotype seems to have the opposite effect. Conclusions: This study demonstrated that PON1 polymorphisms L55M and Q192R seem to be genetic markers involved in the development of DN in T1D. (Endokrynol Pol 2017; 68 (1): 35–41)

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.

La clozapine, principal neuroleptique indique dans le traitement de la schizophrenie resistante, est a l’origine de nombreux cas d’intoxications accidentelles ou volontaires, d’ou l’interet de son dosage. Notre travail a pour objectif la mise au point d’une methode de dosage permettant le diagnostic d’une intoxication par la clozapine. La methode est basee sur la lecture de l’absorbance, a 365 nm, du produit de la reaction entre la clozapine et l’iode dans le dichloromethane. Les resultats ont montre que cette methode de dosage est lineaire de 15 a 400 mg/L (r = 0,995), avec une limite de detection de 10,42 mg/L. La precision et l’exactitude ont ete meilleures dans la zone de 120 a 400 mg/L. Le rendement de l’extraction, par l’ether, a partir des urines est en moyenne de 77,7 %. Cette methode permet le dosage de la clozapine dans les urines, les comprimes et dans les echantillons post mortem en cas d’intoxication mortelle a la clozapine.

Mycotoxins are bioactive compounds that are noxious to human. Their effects on oncogenesis have been satisfactorily elucidated, and some of mycotoxins have been classified as carcinogenic to humans. Nevertheless, patulin (PAT) is considered by the International Agency of Research on Cancer as 'not carcinogenic to humans'. The present study was designed to understand the effect of this mycotoxin on melanoma cells (B16F10) by measuring cell proliferation and assessing the anti-tumour effect in vivo in Balb/c mice. Our results revealed that intraperitoneally administration of PAT for 20 days significantly induces tumour regression in B16F10 cell-implanted mice. This effect was evidenced by the activation of apoptosis which is supported by the increase in p53 and Bax expressions, the downregulation of the protein levels of Bcl2, and the increase in caspase-3 activity. Moreover, systemic toxicity analysis demonstrated that there is no potential toxicity following PAT treatment unlike untreated melanoma mice which suffer from anaemia, inflammation and liver dysfunction. Remarkably, this is the first published report demonstrating the therapeutic efficacy of PAT in vivo models.

Background: Vitamin D defiiency may increase the risk of various autoimmune diseases. But few studies focused on its role in Behcet syndrome. Objectives: The aims of our study were to assess the vitamin D status of Behcet patients and to analyze the correlation of this status with the activity and the severity of the disease as well as the quality of life of patients. Patients and methods: The vitamin D status was assessed in 40 patients with Behcet syndrome (average age: 37.5 years, sex ratio: 1.85) in comparison with 40 healthy control subjects matched by age, sex and by season of assessment. A correlation study was realized between vit D levels and duration of disease progression, its activity, its severity as well as the quality of life of patients. Results: The average rate of vit D was 14.64 ng/ml (3-44.29 ng/ml). 94.6% of them had hypovitaminose D. Vit D defiiency has been attested in 35.1% and insuffiiency in 59.5% of the cases. There was no signifiant difference between rates of vit D in Behcet patients and those of healthy controls. There was also no signifiant association between vit D levels in Behcet patients and duration of disease progression, activity and severity as well as their quality of life. Conclusion: we made the evidence of hypovitaminose D in Behcet patients. Even if its role in the determination of Behcet syndrome is not obvious, this track remains to be explored.

Cardiac biomarkers are used to distinguish acute dyspnea due to left-heart dysfunction from that of pulmonary origin. However, they have not been assessed in the specific setting of acute exacerbation of chronic obstructive pulmonary disease (AECOPD), where they might be released without left-heart impairment.To assess the accuracy of troponin T and of amino-terminal pro-brain natriuretic peptide (NT-proBNP) in the diagnosis of AECOPD associated with left ventricular (LV) dysfunction.Both biomarkers were measured in 148 consecutive patients on intensive care unit admission for AECOPD. A panel of physicians adjudicated blindly the cause of AECOPD to be unlikely, possibly associated, or definitely associated with LV dysfunction.The final diagnosis was AECOPD definitely associated with acute left-heart dysfunction in 31.1%, possibly associated with LV dysfunction in 13.5%, and probably not associated with LV dysfunction in 55.4%. Both NT-proBNP and troponin T levels were significantly different among the three groups. The area under the receiver operating characteristic curve was greater for NT-proBNP (0.95 vs. 0.67). A cutoff of 1,000 pg/ml was accurate to rule out left-heart involvement in AECOPD (sensitivity, 94%; negative predictive value, 94%; negative likelihood ratio, 0.08). A cutoff of 2,500 pg/ml had the best operating characteristics to rule in the diagnosis (positive likelihood ratio, 5.16). Left-heart involvement in AECOPD was the only variable independently associated with increased secretion of NT-proBNP (odds ratio, 74; 95% confidence interval, 15-375; p = 0.0001).NT-proBNP and troponin T are useful in excluding AECOPD associated with left ventricular dysfunction. NT-proBNP was the more accurate of the two.

Many species of the genus Astragalus have been long used in folk medicine because of their biological properties. The aim of this study was to investigate the antibacterial and cytotoxic activities of extracts from the leaves of wild Astragalus gombiformis Pomel. Antibacterial activity was assayed against several common human pathogenic bacterial strains using the paper disk-agar diffusion method. Cytotoxicity was measured against human lung carcinoma cells using the colorimetric MTT assay. The strongest cytotoxic activity against the human A549 lung epithelial carcinoma cell line was detected for dichloromethane extracts at IC50 = 85 ± 21.7 µg/mL. The best incubation time for this extract was 48 h. Most of the tested extracts were active against the tested bacterial strains. The methanol extract was found to be the most active against Pseudomonas aeruginosa and Salmonella typhimurium. This study is the first report on the biological activity of leaf extracts of Astragalus gombiformis with respect to antibacterial activity as well as cytotoxicity.

We evaluated the metabolic and the nutritional aspects of 134 urolithiasic children, in order to outline the risk factors that contribute to idiopathic stone formation in children.In this prospective study 134 children (56 females, 78 males) with renal calculi were evaluated. The age of the patients ranged 6 months to 16 years. A dietary survey was performed on every child. All patients were investigated with respect to stone localization, serum and urine risk factors. Statistical analysis of data was carried out using software SPSS 11.0 for Windows. Statistical significance was determined using chi-square test.Hypercalciuria was the commonest risk factor detected in this group (28.3%). A decrease of water intake was noted in all age group specially in the rural area (549.6 vs 1150.6 ml/day), and an increase in animal protein intake in 17 cases (mean 1.9 g/kg). In addition, increased intake of starchy foods and food with high oxalate content (sorgum) was observed in our 10-16 years group (51%). Calcium oxalate monohydrate represents the principal component of idiopathic stone (58.2%), which is more frequent in children (68%) than infants (51.7%) (P0.02).The high frequency of idiopathic urolithiasis highlights the influence of dietary habit in stone formers in our country. The increase in calcium oxalate stones in school-age children confirms the change in the etiology of urolithiasis according to age.

The aim of the present study was to investigate hyperhomocysteinemia in Tunisian bipolar I patients according to 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism.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.Compared with controls, patients had a significantly higher homocysteine level (16.4 ± 9.8 vs 9.6 ± 4.5 µmol/L; P0.001) and a significantly lower folate level (3.2 ± 0.9 vs 6.5 ± 3.2 µg/L; P0.001). C677T MTHFR polymorphism genotype frequencies were in Hardy-Weinberg equilibrium. After adjustment for MTHFR C677T genotypes, hypofolatemia, hypovitamin B12 and for potential confounding factors, the odds ratio (OR) of hyperhomocysteinemia associated with bipolar disorder remained significant (OR, 5.53; 95% confidence interval: 1.92-15.86; P = 0.001). In patients, there was no significant change in hyperhomocysteinemia, hypofolatemia and hypovitamin B12 with regard to the clinical and therapeutic characteristics, whereas the highest prevalence of hyperhomocysteinemia was found in depressive patients and when illness duration was12 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.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.

Objective Since 1980s, the clinical and biological characteristics of urolithiasis in Tunisian children have continuously evolved. This retrospective study defines the current status of urolithiasis among children and adolescents in Tunisia. Methods We retrospectively reviewed the records of 310 children and adolescents (age: 3 months - 19 years) between 2003 and 2010, holding urolithiasis. A first-line metabolic, urine and plasma work-up was performed in all patients. Physical and chemical analysis of the stones was performed respectively by stereomicroscopy and infrared spectroscopy. Statistical analysis of the results was performed with SPSS 11.0 software. The Chi-square test was used for comparison of percentages. Findings Our study shows a male predominance of urolithiasis with a sex ratio of 1.5. Stones were located in the upper urinary tract in 70.7% of cases. Calcium oxalate was the predominant constituent in 52.6% of stones. There was an increasing prevalence of calcium oxalate stones according to age in both genders (48.6% in infants vs 68.5% in teenagers (P

The essential oils obtained by hydrodistillation (Clevenger apparatus) from aerial parts of Astragalus gombiformis were analysed by gas chromatography coupled with mass spectrometry (GC/MS). This study showed that the A. gombiformis essential oils are complex mixtures of important natural compounds, which varied qualitatively and quantitatively between cultivated and wild plants and between phenological stages of development. All analysed oils are characterized by the constant presence of phytol, 6,10,14-trimethyl-2-pentadecanone, 4-terpineol, and γ-terpinene. This study is the fi rst report on the chemical composition of essential oils from A. gombiformis and indicates that these oils should be more studied.

Studies evaluating the influence of age and gender on the distribution of the various types of paediatric urinary calculi are scarce. Aim of our study was to high-light the modification of epidemiological characteristics of this pathology depending on patients' age and gender.We present the results of a study based on 205 calculi (from 122 boys and 83 girls) analyzed by infrared spectroscopy between 1993 and 2007. 54.6% of the patients were under 5 years.Calcium oxalate (CaOx) was the predominant constituent in 54.7% of stones, followed by calcium phosphate and ammonium urate (14.6% each). We found a male preponderance for struvite stones (12.3% vs 1.2%), and an increasing prevalence of calcium oxalate stones with age (42.9% in infants vs 59.3% in older children). Purines stones were observed in 20% of cases, but their prevalence decreases with age (28.6% in infants vs 18.5% in old children).The increase of calcium oxalate stone rate in school age children and the decrease of purines stones confirm the change on the etiology of urolithiasis according to age.

Objectives: Agricultural workers chronically exposed to complex mixtures of pesticides are at increased risk of acute and chronic toxicity of these compounds. Enzyme activities are among the biomarkers that may be used to detect the effects of pesticides before adverse clinical health effects occur. The aims of this study were to ascertain the relationships between paraoxonase 1 (PON1) and other serum enzymes and to investigate whether long-term exposure to pesticides affects these relationships in Tunisian agricultural workers. Methods: The activities of butyrylcholinesterase (BChE), aminotransferases, gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and creatine kinase (CK) were measured in plasma from workers chronically exposed to pesticides using an Integra 400 plusTM system. PON1 activity was measured using konelab 30TM system. Results: Significant increases in aminotransferases, CK, LDH and ALP activities were found in workers exposed to pesticides. However, BChE and PON1 activities were decreased significantly in these subjects. In addition, PON1 activity was positively correlated with both BChE and GGT activities in these workers. Conclusion: This study suggests that pesticides lead to alteration of serum enzymes and that chronic exposure to pesticides might contribute to explain the positive correlation between PON1 and GGT, perhaps in order to protect BChE and simultaneously induce detoxification of pesticides.

To show an outline of the clinical and biological characteristics of paediatric urolithiasis among Tunisian children in the coast region.This retrospective study included 168 children under the age of 16 years presented with urinary stones (100 boys and 68 girls). Patients were reviewed in a multi-centric study with regard to age at diagnosis, sex, history, and physical, laboratory, and radiologic findings. The physical and chemical analysis of stones was carried out respectively by a stereomicroscope and by infra-red spectroscopy.The sex ratio was 1.47. The clinical presentation of this pathology was dominated by abdominal pain (28%), hematuria (25.6%), dysuria (16.7%) and urinary tract infection (14.3%). Stones were located in the upper urinary tract in 75.6% of cases. Of the urine cultures, 14.3% were positive. Whewellite was more frequent in children stones than in infants (p0.05) and was the main component in 46.4% of stone section and 55.4% in stone surface.The male prevalence of paediatric urolithiasis is progressively decreasing in Tunisia. The epidemiological profile of renal stones in our country has changed towards a predominance of calcium oxalate stone and upper tract location.

The purpose of this study was to examine the effect of cigarette smoking on plasma uric acid concentration and to determine the correlation between this parameter and the biological tobacco markers, plasma thiocyanate and urinary cotinine.The initial study was conducted on 300 subjects; 138 of them were nonsmokers (62 men and 76 women) aged 14-72 years and 162 were current smokers (145 men and 17 women) aged 16-85 years. Uric acid, creatinine, and urinary cotinine were determined by the enzymatic colorimetric method and plasma thiocyanate by selective electrode.Plasma uric acid concentration was significantly lower in smokers than in nonsmokers. A statistically significant negative correlation was noted between the smoking status parameters, including both the number of cigarettes smoked/day (F (3-161) = 12.063; r = -0.9968; p = 0.0001) and the duration of smoking (F (3-161) = 1.305; r = -0.9406; p = 0.0274), and the plasma uric acid. Among smokers, we noted a negative correlation between uric acid and both plasma thiocyanates (r = -0.437; p 0.05) and urinary cotinine (r = -0.580; p 0.05).After excluding the other factors affecting the uric acid levels, the significant low plasma uric acid in smokers was attributed to a reduction of the endogenous production as a result of the chronic exposure to cigarette smoke that is a significant source of oxidative stress. Therefore, it is recommended to stop or reduce smoking and to introduce plasma uric acid estimation as a routine test, since it is cheap and simple to reflect the antioxidant level.

Background: The aim of this work is to study the effects of lead on pituitary-testicular axis. It is about a direct toxicity on testicular cells or an indirect toxicity via abnormalities of the hypothalamic-pituitary axis?Methods: Forty male rats were divided equitably into four groups. One of these groups received tap water containing 0.3% lead acetate for one month. A second group was assigned to the same protocol but the intoxication was conducted for two months. The third and the fourth groups were used as reference. At the end of the experiment, the rats were anaesthetized and blood was collected for the proportioning of the FSH, the LH, testosterone and lead. The testes and epididymides were removed quickly and weighed. For the determination of testosterone in testicular fluids, a cruciate incision was made in the tunica albuginea of each right testis and centrifuged at 54xg for the extraction of interstitial fluid. Thereafter, the seminiferous tubules were extruded and centrifuged at 6000xg to collect seminiferous tubule fluid. The left testis of each animal was cut in two halves, one half was used for the histological examination and the other was suitably treated for the determination of the lead concentration. The epididymides were homogenized in solution containing Triton X-100 and spermatozoa were counted using Malessez cells. The plasma FSH and LH were determined by RIA using reagents from a commercial kit (BioInternational, France), while testosterone was determined by electrochemiluminescence (Elecsys, rochediagnostics). The lead concentration in blood and Tissues was measured by flameless atomic absorption spectrophotometry with the Zeeman effect background (Hitachi Z- 9000).Results: In the rats poisoned for one month, no notable effect was noted in spite of a blood lead concentration of 0.721 μg/ml. On the contrary, in animals exposed to lead acetate for two months, the blood level passed to 2.721 μg/ml and plasma testosterone, FSH and LH dropped by about 45%. In parallel, the secretion of testosterone by the Leydig cells fell by 35% and epididymal sperm count dropped by 14%. The histological examination showed lead deposits in the walls of the seminiferous tubules. Conclusions: Although we do not exclude a directly toxic action of lead on the interstitial cells and on the Sertoli cells, it seems that the hypothalamic-pituitary axis is the major target of lead since the decrease in the plasmatic LH and FSH was associated with a reduction in testosterone secretion and with a reduction in the number of the epididymal spermatozoa.

International studies may not reflect the real changes of stone disease in our own country. In this retrospective work, we describe the evolution of this pathology in Tunisia during the last 12 years.The records of 133 children with urolithiasis treated in Tunisia between 1994 and 2006 were reviewed. The physical and chemical analysis of stones was carried out respectively by a stereomicroscope and by infra-red spectroscopy and the epidemiologic data were collected.The male prevalence of this pathology is progressively declining. The male to female ratio, passed from 1.7 in the 1994-97 period to 1.5 in 2006. Upper urinary tract was most frequently affected by this pathology. Over the last 12 year period urinary tract infection was in continuous increase and currently reaches 50% being 21.9% in 1994. This explains the increasing frequency of struvite stones which passed from 15.6% in 1994 to 37.5% in 2006. Ammonium urate stones became more frequent in the last few years being the main component in 25% of cases (12.5% in 1994-97). Calcium oxalate monohydrate remains the most frequent stone component even if its frequency fell (59.4% in 1994 and 12.5% in 2006) in favour of the increase of phosphatic and phospho-calcic stones.The rise in the frequency of struvite and ammonium urate stone reflects an increase in the infectious risk factors in our country.

Background This study aimed to evaluate the interference of tobacco smoke on immunochromatography assay for urinary benzodiazepines detection and the interest of two biological markers and smoking status parameters as predictive factors of false results. Methods Our study included 256 voluntary subjects (143 passive smokers and 113 smokers). Cotinine was measured by homogenous immunoenzymatic assay and SCN- by selective electrode. Urinary drugs were detected by immunochromatographic assay. A positive result is completed by an analytical method with an immunometric assay. Results False positive results for benzodiazepines are significantly more frequent in smokers compared with passive smokers (90.2% Vs 22.4%, p Conclusions Tobacco smoke interferes with immunochromatographic assay of urinary drug detection; therefore, all subjects must be questioned about their smoking status to avoid such false results during results interpretation.