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Background and aim The effects of Ramadan fasting on health are a little controversial. The present study is aimed at evaluating the metabolic effects on a group of 517 patients with ≥2 cardiovascular risk factors over a period running from 2012 to 2014. Methods Each patient was assessed at three visits: before, during, and after Ramadan. Demographical, clinical and biological tests were performed at each visit. Results Metabolically, we noted a significant and discrete rise in blood glucose level (+1.2 mmol/L), triglycerides (+0.3 mmol/L), cholesterol (+0.12 mmol/L) and creatinine (+3 µmol/L) during Ramadan. These disturbances decreased significantly after Ramadan. The same variations were observed among diabetics (n=323). However, there was a significant decrease in HbA1c after Ramadan (9.0% vs 7.6%, p

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.

Background: Digoxin is a substrate of P-glycoprotein (P-gp) and organic anion transporting polypeptide transporters that are encoded by ABCB1 and SLCO1B3 genes. Genetic polymorphisms in both genes may explain inter-individual variability of serum digoxin concentration (SDC). This study evaluates the possible effect of the most common ABCB1 and SLCO1B3 polymorphisms on SDC after a single oral dose of digoxin in Tunisian atrial fibrillation (AF) patients. Methods:ABCB1 and SLCO1B3 genotypes were analyzed in 102 patients with AF who received digoxin (0.5 mg) without (group I, n = 58) or with the co-administration of P-gp inhibitors (group II, n = 44). SDCs were determined at 6 h following the oral dose. Results: SDCs levels were significantly higher in patients who were co-administered P-gp inhibitors. No influence was noted in ABCB1 and SLCO1B3 polymorphisms on SDC in group I patients. However, SDCs values were significantly different among ABCB1 single nucleotide polymorphisms (SNPs) genotypes of 2677G>T/A (TT, GG>GT, p < 0.05) and 3435C>T (TT, CC>CT, p < 0.05) only in group II with no effect of 1236C>T and SLCO1B3 SNPs. Conclusion: Results suggest that P-gp inhibitors and ABCB1 gene polymorphisms may affect digoxin pharmacokinetics.

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

OBJECTIVES 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

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.

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.

This study aimed to evaluate the relationship between physiological, and parameters of performance analysis during karate contest.Nine elite-level karate athletes participated in this study. Saliva sample was collected pre- and post-karate combat.Salivary cortisol (sC) post-combat 2 raised significantly compared to that recorded at pre-combat 1 (Δ%=105.3%; P=0.04; dz=0.78). The largest decrease of the salivary T/C ratio (sR) compared to pre-combat 1 was recorded post-combat 2 (Δ%=-43.5%; P=0.03). Moreover, blood lactate concentration post-combat 1 correlated positively to sCpost-combat 1 (r=0.66; P=0.05) and negatively to both salivary testosterone (sT) (r=-0.76; P=0.01) and sRpost-combat 1 (r=-0.76; P=0.01). There was no significant relationship between hormonal measures and parameters of match analysis.Although under simulated condition, karate combat poses large physiological stress to the karateka. Additionally, physiological strain to karate combat led to a catabolic hormonal response.

Digoxin is a substrate of P-glycoprotein (P-gp) and organic anion transporting polypeptide transporters that are encoded by ABCB1 and SLCO1B3 genes. Genetic polymorphisms in both genes may explain inter-individual variability of serum digoxin concentration (SDC). This study evaluates the possible effect of the most common ABCB1 and SLCO1B3 polymorphisms on SDC after a single oral dose of digoxin in Tunisian atrial fibrillation (AF) patients.ABCB1 and SLCO1B3 genotypes were analyzed in 102 patients with AF who received digoxin (0.5 mg) without (group I, n = 58) or with the co-administration of P-gp inhibitors (group II, n = 44). SDCs were determined at 6 h following the oral dose.SDCs levels were significantly higher in patients who were co-administered P-gp inhibitors. No influence was noted in ABCB1 and SLCO1B3 polymorphisms on SDC in group I patients. However, SDCs values were significantly different among ABCB1 single nucleotide polymorphisms (SNPs) genotypes of 2677GT/A (TT, GGGT, p0.05) and 3435CT (TT, CCCT, p0.05) only in group II with no effect of 1236CT and SLCO1B3 SNPs.Results suggest that P-gp inhibitors and ABCB1 gene polymorphisms may affect digoxin pharmacokinetics.

There is evidence that diet and variation in lipid metabolism can influence blood coagulation, but little is known about the effect of Ramadan fasting on plasmatic coagulation pattern. We investigated the effect of Ramadan fasting on thrombin generation (TG) in patients with cardiovascular disease (CVD) risks, and we aimed to assess the effect of lipid profile on TG parameters. The study was conducted in 36 adults having at least 2 CVD risks and in 30 healthy controls. Coagulation pattern was assessed by both classical clotting times and TG test. A complete lipid profile was performed simultaneously. Patients were invited 2 times: 1 week before Ramadan and during the last week of the Ramadan. The TG parameters were not different in patients with CVD risks compared to healthy controls. Fasting had no effect on plasmatic coagulation parameters and on TG profile. Individual analysis of the mean rate index (MRI) of TG revealed 3 groups: group 1 with no modification of MRI, group 2 with a significant increase in MRI (81.64 nM/min vs 136.07 nM/min; P < .001), and group 3 with a significant decrease in MRI (125.27 nM/min vs 73.18 nM/min; P = .001). Only in group 2, a significant increase was observed in total cholesterol and low-density lipoprotein cholesterol. Changes in lipid profile during Ramadan fasting did not influence the global coagulation pattern in patients with CVD risks. Whereas, a significant increase in the propagation phase of TG was associated with a significant increase in cholesterol levels, which was not found with the other TG parameters.

We report the case of a 54-year-old man, without particular pathological antecedents admitted to the emergency of the university hospital of Monastir, for right renal colic. Radiography of the urinary tract without preparation and renal echography showed bilateral renal lithiasis and a right ureteral lithiasis. The interrogation revealed concept of vomiting after which the patient felt relieved. The biological assessment objectified an hypochloremic metabolic alcalosis, an increase in the anion gap, a severe impaired renal function of obstructive origin and an hypokaliemia. The presence of the lithiasis did not explain on its own the metabolic disorders of this patient. The other investigations showed that initial pathology was an evolutionary bulb ulcer into pre-stenosis justifying treatment by omeprazole and explaining the biological disorders.

Resume Introduction Le cholesterol libre (CL) est le marqueur d’atherosclerose le moins demande malgre sa mise en evidence dans la plaque d’atherome et dans les vaisseaux des sujets coronariens. L’objectif de notre travail est d’evaluer et de valider une technique enzymatique de dosage du CL afin de l’appliquer en pratique quotidienne dans l’exploration du bilan lipidique et ceci vue la rarete des kits de dosage de ce parametre. Methodes Le CL est oxyde, en presence de cholesterol oxydase, en cholestenone avec liberation de peroxyde d’hydrogene ; ce dernier oxyde l’amino-4-antipyrine, en presence de phenol et de peroxydase en une quinone imine coloree dont l’intensite de la coloration evaluee a 510 nm est proportionnelle a la quantite de CL. Resultats Une parfaite linearite entre l’absorbance et la concentration du CL a ete notee avec une droite d’etalonnage du type Y = aX. Des coefficients de precision et d’exactitude inferieurs a 5 % sont enregistres jusqu’a une concentration de 4,1 mmol/L. Les resultats de l’etude de la repetabilite et de la reproductibilite sont tres satisfaisants avec des CV Conclusion La technique enzymatique colorimetrique pour le dosage du CL est precise, exacte et rapide. Elle peut etre introduite en routine quotidienne pour la determination du CL. Son adaptation au dosage du CL des HDL constitue un second sujet d’etude.

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.

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).PON1 activity was measured by a kinetic method using paraoxon as substrate. The other parameters were determined by automated methods.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 (P0.001), by 14% in those with HbA1c ≥ 8% and by 12.3% for diabetics with dyslipidemia. PON1 activity is reduced when the number of cardiovascular risk factors increases (P0.001).PON1 seems to be associated to cardiovascular risk markers in T1D. This result remains to be seen. Nevertheless, improving PON1 activity could be a significant target for reducing cardiovascular risk.

Capillary electrophoresis of serum proteins is a fast, reliable and simple technique, but many interference exist. The objective of our work is to study the interference of bilirubin on this technique; 70 icteric sera were analysed on Capillarys ™ (Sebia). A second electrophoresis was performed on 40 samples after bilirubin photodegradation. The bilirubin and serum proteins were determinated respectively by Jendrassik and Grof and biuret methods on Konelab 20i ™ (Thermo Electron Corporation). We found abnormal spreading of the albumin fraction of the anode side wich constitute sometimes an isolated fraction in the traditional area of pre-albumin migration. This fraction varies from 2.0 ± 2.0% (0.0 to 7.3%) or 0.98 ± 1.53 g/L (0 to 5.3 g/L) and it seems to be related to the direct bilirubin since, following overloading sera with a solution of bilirubin, no further fraction was recovered. An average decrease of bilirubin after photodegradation of 58 ± 17% (26-89%) is followed by a decrease in the same order 64 ± 38% (10-100%) of the additional fraction. Acetate cellulose electrophoresis of the same samples showed no variation. The high bilirubin levels seem modify slightly the electrophoretic profile. However the impact of the interference on the interpretation of electrophoretic trace is negligible.

Screening for diabetic nephropathy is usually done by albuminuria/24h and the use of creatinine clearance. The objective of this study was to evaluate the renal function in Type 2 diabetes by using different formulas of creatinine clearance and to assess the contribution of cystatin C; 83 adults with type 2 diabetes (23 men and 60 women) and 83 adult controls (40 men and 43 women) were studied. Biochemical parameters were determinated on Coba 6000™ (Roche diagnostics). Diabetics showed a significant increase in blood glucose, cholesterol, triglycerides, LDLc, the ApoB, Lp(a), urea, uric acid, creatinine and cystatin C and lower HDLc. Cystatin was increased in patients with degenerative complications and in hypertensive patients. We found strong correlations of cystatin C with creatinine (r = 0.9454), urea (r = 0.8999) and uric acid (r = 0.8325). We found a significant exponentially increase of creatinine and cystatin C from one stage to another. Cystatin C has a strong association with MDRD (r = 0.8086) and CG (r = 0.7915) and a low one with creatinine clearance (r = 0.1044). In conclusion, the use of cystatin C for screening and early treatment of incipient diabetic nephropathy appears to be adequate. CG and MDRD formulas still hold their place, in regards to the classical determination of creatinine clearance, to monitor patients.

BACKGROUND Paraoxonase 1 (PON1) is important in organophosphates and xenobiotic metabolism and as an antioxidant bio-scavenger. PON1 activity was shown to significantly decrease in depressed patients after antidepressant treatment instauration. Our aim was to investigate the in vitro inhibitory effects of three antidepressants (imipramine, amitriptyline and fluoxetine) on PON1 activity. METHODS Plasma from healthy volunteers was spiked with antidepressant drugs. The working solutions were then diluted with plasma to obtain concentrations that covered the therapeutic margin. PON1 was tested by a kinetic method in triplicate after incubation at 37°C for 2 h. RESULTS Tricyclic antidepressants significantly inhibited PON1. Fluoxetine had no effect. The inhibition percentage for imipramine was 15.6% at 100 μg/L after incubation for 1 h (131±1 vs. 155±2 IU/L; p

Introduction Smoking is one of the main risk factors for cardiovascular disease (CVD). The mechanism(s) for the effects of smoking on CVD are not clearly understood; however, a number of atherogenic characteristics such as insulin resistance have been reported. Aims We aim to investigate the effects of cigarette smoking on insulin resistance and to determine the correlation between this parameter with smoking status characteristics. Methods This study was conducted on 138 nonsmokers and 162 smokers aged respectively 35.55±16.03 and 38.47±21.91 years. All subjects are not diabetics. 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 and discussion Compared to non-smokers, smokers had significantly higher levels of fasting glucose, fasting insulin and HOMA-IR index. 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 The findings show that smokers have a high risk to developing an insulin resistant, hyperinsulinaemic, compared with a matched group of non-smokers, and may help to explain the high risk of cardiovascular diseases in smokers.

Introduction Paraoxonase (PON), an enzyme, is a key process in the pathophysiology of atherosclerosis. Aims We aim to investigate the variations of PON1 activity in Tunisian bipolar I patients treated with thymoregulators. Patients and methods Our study included 78 patients with bipolar I disorder, diagnosed according to the DSM-IV, and 64 controls aged 35.97±11.55 years and 36,31±18.26 years respectively. 41 patients were treated by valproic acid, 16 under carbamazepine and 21 under lithium. PON1 activity was determined by kinetic methods using Konelab 30 equipment. Results Compared to controls, patients treated by thymoregulators had a significantly lower paraoxonase activity (p=0.004). Furthermore, PON1 was significantly correlated with c-HDL values (r=0.5612; P Conclusions Bipolar patients had a significant decrease in PON1 activity that contributes to increased risk of cardiovascular diseases. This perturbation could be related to treatment with thymoregulators and particularly lithium. Therefore, such patients should require specific care and clinics should track the effects of treatment on physical and biological parameters, and should facilitate access to appropriate medical care.