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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.

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.

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.

Objectives: Patients affected by major depression (MDD) are at high risk of suicide. The metabolism of tryptophan (Trp) along the serotonin (5-HT) and kynurenine (Kyn) pathways was found dysfunctional in MDD and in suicide. However, a clear biological framework linking dysfunctions in Trp metabolism via 5-HT and Kyn, cortisol, and the activities of tryptophan and indoleamino 2,3-dioxygenase (TDO, IDO) enzymes has not been yet clarified in MDD with or without suicidal behaviours. Methods: We analysed peripheral markers of Trp via 5-HT and Kyn pathways, Kyn/Trp ratio as a measure of TDO/IDO activities, cortisol, and psychopathology in 73 non-suicidal and 56 suicidal MDD patients, and in 40 healthy controls. Results: Plasma Trp levels were lower and the ratio Kyn/Trp higher in suicidal MDD than in non-suicidal MDD patients and controls. Trp levels and the ratio Kyn/Trp correlated with suicidal ideation, and cortisol with the Kyn/Trp ratio. Finally, Trp levels discriminated controls from non-suicidal and suicidal MDD patients, and also non-suicidal from suicidal MDD patients. Conclusions: Reduced availability of Trp for 5-HT synthesis and increased activation of the Kyn pathway and cortisol correlate with depression and suicide. Low plasma Trp levels may be a biomarker of MDD and suicide in MDD.

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

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.

Aims: The aim of this study is to assess the neuropsychological manifestations of mercury exposure in dentists. Methods: A cross-sectional study was carried out including 64 dentists matched to a control group according to age and gender. This study protocol included a neurological evaluation, a questionnaire assessing the study groups’ general characteristics and personal factors that may affect mercury urinary excretion in both groups. EUROQUEST questionnaire and Hospital Anxiety and Depression scale (HADS) were used to evaluate the neuropsychological symptoms reported during the last 12 months. In both groups, mercury impregnation was assessed by monitoring urinary mercury. Results: In the exposed group, scores of neurological symptoms, memory disturbances and anxiety were found to be significantly higher than those in controls (p < 0.01). Mean scores of HAD Depression’s scale were higher in the exposed group than in controls. Most of the neurotoxic manifestations were correlated to the levels of urinary mercury excretion in the exposed group. Mean levels of urinary mercury were significantly higher in the dentists group than in controls, with respective values of 21.1 ± 19.6µg/g of creatinine and 0.05 ± 0.9µg/g of creatinine. In nine dentists having urinary mercury levels higher than 35µg/g of creatinine, neurological examination showed a bilateral and symmetric intentional tremor in both upper limbs. In the exposed group, the neuropsychological manifestations and levels of urinary mercury were found to be significantly correlated. Conclusion: Increased levels of urinary mercury observed in dentists suggest that exposure to mercury vapour emissions adversely affects dental professionals, therefore prevention measures should be strengthened, with a special medical supervision program of dentists exposed to mercury vapours should be implemented. We have also outlined some relevant patents in this article.

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.

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.

OBJECTIVES We purpose to verify if paraoxonase 1 (PON1) activity may be a marker of cardiovascular risk in a young Tunisian population with type 1 diabetes (T1D). METHODS PON1 activity was measured by a kinetic method using paraoxon as substrate. The other parameters were determined by automated methods. RESULTS One hundred and nine children and adolescents with T1D and 97 healthy subjects were involved in this study. PON1 activity and PON1/HDL-cholesterol ratio were significantly decreased in diabetics (303 ± 174 vs. 372 ± 180 U/L and 221 ± 139 vs. 298 ± 20 1U/mmol, P=0.006, P=0.002, respectively) compared to controls. A significant increase in total cholesterol, LDL-c and microalbuminuria was observed in diabetics compared to controls. PON1 activity was decreased by 9.5% in patients with diabetes duration ≥ 6 years, by 28.4% for those with fasting glycemia ≥ 7 mmol/L (P

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.

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 The aim of this study was to evaluate the association of ACE, angiotensinogen (AGT) and angiotensin II receptor type I (AGTR1) polymorphisms with diabetic nephropathy (DN) in Tunisians. METHODS The study population comprised 236 type 2 diabetic patients: with nephropathy (DN = 47) and without nephropathy (DM = 189). Genotyping of ACE-I/D-rs1799752, ACE-rs4343G>A, AGT-rs5050A>C, AGT-rs 4762C>T, AGT-rs699A>G, and AGTR1-rs5186A>C was performed by PCR-RFLP. Haplotype and statistical analysis were realized using SNP Analyzer2.0 and SPSS20, respectively. RESULTS Genotype frequencies were in Hardy-Weinberg equilibrium. After adjustment for potential confounding factors (age, gender, diabetes duration, hypertension…), an increased risk for DN was associated with mutated alleles of rs4762 (OR = 10.25, p = 0.001), rs699 (OR = 22.21, p < 0.001), and rs5186 (OR = 11.25, p < 0.001). However, mutated alleles of rs1799752 seemed to be protector (OR = 0.41, p = 0.011). Adjusted ORs of DN associated with the ACE haplotype (DA) was (OR = 9.56, p = 0.047) and with the ACE-AGT haplotype (ATADAA) was (OR = 5.38, p = 0.032). CONCLUSIONS This study indicates that common variants in ACE, AGT, and AGTR1 seem to play a role in genetic susceptibility to DN in Tunisian population and provides evidence for a disease haplotype: ATADAA.

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.

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

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.

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.

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.

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.

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.

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.

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.

Aims Ramadan fasting (RF) may affect aspirin resistance. We conducted this study in patients with cardiovascular risk (CVR) factors to assess the effect of RF on aspirin resistance and explore whether type 2 diabetes mellitus (DM) would influence this effect. Methods A total of 177 stable patients with ≥2 CVR factors were recruited. All patients observed RF and were taking aspirin. Physical exam and standard biological tests including glycaemia and serum lipids data were performed before Ramadan (Pre-R), at the last week of Ramadan (R) and four weeks after the end of Ramadan (Post-R). In the same visits caloric intake was calculated and platelet reactivity to aspirin was assessed using Verify Now point-of-care assay. Results In the overall population, there was no significant change in absolute aspirin reaction unit (ARU) values and in metabolic parameters. In DM patients (n = 127), ARU change from Pre-R values was+19.7 (p = 0.01) and +14.4 (p = 0.02) respectively at R and Post-R. During Ramadan, glycaemia, triglycerides, and cholesterol levels increased significantly and returned to Pre-R values thereafter. These changes were not observed in non-DM patients. Conclusions During RF aspirin resistance increased only in DM patients. This effect persisted one month after Ramadan. Simultaneous alteration of glycemic control and increase of serum lipids levels could potentially be a favorable factor. Study registration The protocol was registered at clinicaltrials.gov under: NCT02720133.

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

Resume Buts Les caracteristiques epidemiologiques sont importantes a prendre en consideration afin de cerner l’etiologie des enfants lithiasiques. Dans cette etude nous avons etudie la composition des calculs en fonction du sexe et de l’âge. Patients et methodes Notre travail portait sur 205 enfants lithiasiques tunisiens âges de trois mois a 16 ans, admis dans notre service entre 1993–2007. Un bilan metabolique urinaire, de premiere intention, a ete realise chez 126 patients. L’analyse physique et chimique des calculs a ete realisee respectivement par un stereomicroscope et par spectroscopie infrarouge. L’analyse statistique des resultats a ete faite a l’aide du logiciel SPSS 11.0. Resultats La localisation des calculs urinaires a ete vesicale dans 30,7 % des cas. Elle a ete plus frequente chez les nourrissons que chez les enfants de plus de dix ans ( p p Conclusion La prevalence plus importante des calculs d’oxalate de calcium et plus faible des calculs de purines chez les grands enfants a suggere la presence de facteurs de risque lithogenes differents en fonction de l’age. Une modification des habitudes alimentaires est probablement en cause.

Renal tubular acidosis are forms of metabolic acidosis characterized by an impairment of urinary acidification due to a lack of urine excretion of protons or loss of bicarbonates. Primary distal renal acidosis (dRTA) is characterized by hyperchloremic metabolic acidosis due to failure in proton excretion, variably severe nephrocalcinosis and/or nephrolithiasis associated with hypercalciuria and hypocitraturia. When the metabolic acidosis is compensated, dRTA can be diagnosed by the failure of urinary acidification after oral ammonium chloride or furosemide administration. dRTA is inherited as either an autosomal dominant or autosomal recessive trait. An autosomal dominant form results from a SLC4A1 gene mutation leading to dysfunction of the anionic exchanger type 1 (AE1). Otherwise, recessive forms are due to mutations of ATP6V1B1 gene encoding the B1-subunit of H+-ATPase expressed in the apical membrane of the alpha intercalated cells in collecting duct and in the cochlea. Those mutations lead to dRTA accompanied by sensorineural deafness. Also, mutations in ATP6V0A4 gene encode the accessory subunit a4 of the H+ATPase, leading to recessive forms of dRTA with preserved hearing or delayed signs of deafness. Molecular approach can identify mutations which are responsible for this pathology. The medical treatment is simple and involves an alkali load which allows curing the metabolic acidosis. Long-term outcome is usually good unless the patient's compliance is low or alkalizing treatment is insufficient.

Resume Introduction Contrairement aux effets systemiques de la corticotherapie generale qui sont bien connus, ceux des infiltrations locales de glucocorticoides sont peu etudies. Le but de notre etude est de rechercher les effets systemiques des infiltrations de glucocorticoides et de comparer ces effets chez les sujets diabetiques et non diabetiques et selon le siege. Methodes Notre etude a porte sur 29 patients (11 hommes et 18 femmes, âges de 18 a 86 ans). Dix-huit souffraient de sciatique discale (quatre diabetiques et 14 non-diabetiques) et ont beneficie de trois infiltrations epidurales de 1,5 ml de cortivazol (soit 5,625 mg de cortivazol, equivalant a 85 mg de prednisone) espacees de trois jours (soit un total d'environ 250 mg d'equivalent prednisone). Onze souffraient de capsulite retractile (huit diabetiques et trois non-diabetiques) et ont egalement beneficie de trois injections d'une meme quantite de cortivazol en intra-articulaire, espacees de trois jours (soit un total d'environ 250 mg d'equivalent prednisone). Parmi les patients diabetiques, 16,6 % requeraient une insulinotherapie. Avant la premiere infiltration (j0), puis a j1, j7 et j21 apres la troisieme infiltration, nous avons realise les examens de laboratoire suivants : cortisolemie et ACTH plasmatique le matin a 8 h, cortisol libre urinaire (CLU) de 24 heures, glycemie a jeun et post-prandiale, cholesterol, triglycerides, natremie et kaliemie. Les patients ont beneficie d'une mesure de la pression arterielle a chaque visite. Resultats La pression arterielle systolique moyenne des 29 patients a cru de maniere significative entre j0 (123 ± 10 mmHg), et tant j1 (127 ± 9 mmHg), que j7 (128 ± 10 mmHg). La glycemie post-prandiale des 29 patients a egalement cru de maniere significative entre j0 (7,5 ± 2,9 mmol/l) et j1 (10,1 ± 5,4 mmol/l). Toutefois, les changements sont restes minimes pour les variations tensionnelles, avec un retour a la normale a j21, y compris dans le groupe des diabetiques. En revanche, les variations de glycemie ont ete plus marquees et plus durables chez les 12 diabetiques, avec persistance d'une elevation significative de la glycemie post-prandiale a j7 (encore a 13,9 ± 4,8 versus 9,4 ± 3,3 mmol/l a j0). Dans la population generale d'etude et dans les differents groupes, un effondrement de la cortisolemie, de l'ACTH et du CLU a j1 et j7, et se poursuivant a j21, a ete observe, sauf dans le groupe infiltrations intra-articulaires, nous avons note une normalisation plus precoce de la cortisolemie et de l'ACTH a j21. Aucune variation significative n'a ete notee pour la glycemie a jeun, la triglyceridemie, la cholesterolemie, la natremie, la kaliemie et la pression arterielle diastolique. Conclusion Apres trois infiltrations de cortivazol, on observe une depression prolongee de l'axe corticotrope qui persiste au-dela de 21 jours. Cette depression disparait plus rapidement dans le groupe infiltrations intra-articulaires que dans le groupe infiltrations epidurales. On note aussi une augmentation transitoire de la tension arterielle systolique et de la glycemie post-prandiale de facon plus prolongee chez les patients diabetiques.

Introduction Whereas the systemic effects of glucocorticoid therapy have been extensively reported, little is known about those of local glucocorticoid injections. The objective of this study was to look for systemic effects of local glucocorticoid injections at two sites in diabetic and non-diabetic patients. Methods We studied 29 patients (18 women and 11 men with an age range of 18–86 years). The injection site was the epidural space in 18 patients (4 with and 14 without diabetes) with disk-related sciatica and the shoulder in 11 patients (8 with and 3 without diabetes) with frozen shoulder. Each patient was given three injections of 1.5 ml cortivazol (5.625 mg of cortivazol or about 85 mg prednisone-equivalent per injection and about 250 mg prednisone-equivalent in all), at 3-day intervals. Of the 12 patients with diabetes, 2 were on insulin therapy. At baseline and at the post-treatment visits 1, 7, and 21 days after the third injection, the following tests were done: plasma cortisol and ACTH at 8 am, urinary free cortisol excretion in 24 hours, fasting and postprandial blood glucose, serum cholesterol and triglycerides, and serum sodium and potassium. Blood pressure was measured at each visit. Results Mean systolic blood pressure increased significantly between baseline (123 ± 10 mmHg) and the first two post-treatment visits (day 1, 127 ± 9 mmHg; and day 7, 128 ± 10 mmHg) but returned to baseline values by the third post-treatment visit (day 21). Mean postprandial blood glucose was significantly higher at the day 1 post-treatment visit (10.1 ± 5.4 mmol/l) than at baseline (7.5 ± 2.9 mmol/l). At the day 7 post-treatment visit, blood glucose remained significantly elevated compared to baseline in the 12 diabetic patients (13.9 ± 4.8 mmol/l versus 9.4 ± 3.3 mmol/l at baseline). In both the overall population and the various subgroups, plasma cortisol and ACTH and urinary free cortisol were markedly reduced at the day 1 and day 7 post-treatment visits, compared to baseline. At the day 21 visit, these variables were diminished in the group given epidural injections, whereas plasma cortisol and ACTH were normal in the group treated intra-articularly. No significant variations were noted for fasting blood glucose or for serum levels of cholesterol, triglycerides, sodium, and potassium. Conclusion The administration of three local cortivazol injections was followed by suppression of the corticotropic axis that persisted beyond 21 days after epidural injection and recovered more rapidly after intra-articular injection. Systolic blood pressure increased transiently. Elevations in postprandial glucose levels lasted longer in diabetic than non-diabetic patients.

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.

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