Fadoua Neffati

In depth analysis of the in vivo toxicity of nanoparticles of porous iron(III) metal–organic frameworks

In vivo acute toxicity of high doses of nanoparticles of three different porous iron(III) carboxylate Metal–Organic Frameworks (nanoMOFs) was intravenously investigated in rats by evaluating their distribution, metabolism and excretion. All studied parameters (serum, enzymatic, histological, etc.) are in agreement with a low acute toxicity. The mechanism of degradation and excretion of the nanoMOFs has been evidenced and shows that the nanoparticles are rapidly sequestered by the liver and spleen, then further biodegraded and directly eliminated in urine or feces without metabolization and substantial toxicity.

Effect of cigarette smoking on plasma homocysteine concentrations

Abstract Background: Cigarette smoking has been recognized as a major risk factor for cardiovascular disease, while the role of homocysteine is still not clear. This study investigated the effects of smoking on plasma homocysteine concentration and determined the correlation between this parameter and biological markers of tobacco use, such as plasma thiocyanate and urine cotinine. Methods: Folate, vitamin B12 and homocysteine were measured in 300 subjects: 138 non-smokers and 162 smokers using immunoassay methods. Cotinine was measured using an enzymatic colorimetric method and thiocyanate by a selective electrode. Results: In smokers, we found a significant increase in homocysteine and a decrease in folate and vitamin B12 levels compared to non-smokers. Homocysteine was strongly correlated with the duration of use and the number of cigarettes consumed. Folate and vitamin B12 were significantly reduced in subjects smoking for more than 20 years compared to those who smoked less than 5 years. Among smokers, we noted a positive correlation between homocysteine and both plasma thiocyanates and cotininuria, and a negative-correlation between cotininuria and plasma folate. Conclusions: Cigarette smoking increases homocysteine, which is strongly correlated with cotininuria and plasma thiocyanates. Moreover, smokers had tendency to develop hypofolatemia and hypovitamin B12, particularly when the duration of consumption exceeded 20 years.

Hyperhomocysteinemia in Tunisian bipolar I patients

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.

Fenugreek seeds, a hepatoprotector forage crop against chronic AlCl3 toxicity

BackgroundHaving considered how bioavailable aluminium (Al) may affect ecological systems and animals living there, especially cattle, and in search for a preventive dietary treatment against Al toxicity, we aimed to test the protective role of fenugreek seeds against chronic liver injury induced by aluminum chloride (AlCl3) in Wistar rats.ResultsFive months of AlCl3 oral exposure (500 mg/kg bw i.g for one month then 1600 ppm via drinking water) caused liver atrophy, an inhibition of aspartate transaminase (AST), alanine transaminase (ALT) and glutamyl transpeptidase (GGT), an enhancement of both lipid peroxidation and lactate dehydrogenase (LDH) activity and an increase of total protein level in liver. Moreover, histopathological and histochemical examinations revealed moderate alterations in the hepatic parenchyma in addition to a disrupted iron metabolism. Co-administration of fenugreek seed powder (FSP) at 5% in pellet diet during two months succeeded to antagonize the harmful effects of AlCl3 by restoring all tested parameters.ConclusionThis study highlighted the hepatotoxicity of AlCl3 through biochemical and histological parameters in one hand and the hepatoprotective role of fenugreek seeds on the other hand. Thus this work could be a pilot study which will encourage farmers to use fenugreek seeds as a detoxifying diet supplement for domestic animals.

Paraoxonase 1 activity and lipid profile in schizophrenic patients

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.

Association between bipolar I disorder and the L55M and Q192R polymorphisms of the paraoxonase 1 (PON1) gene

BACKGROUND The purpose of this work was to study the association between the PON1 L55M and Q192R polymorphisms and bipolar I disorder in Tunisian patients and to explore their relation to the sociodemographic, clinical and therapeutic characteristics of this disease. PATIENTS AND METHODS Our study included 109 patients with bipolar I disorder and 110 controls aged 39.4±11.8 and 37.3±9.2 years, respectively. L55M and Q192R of the PON1 gene polymorphisms were determined by multiplex polymerase chain reaction. RESULTS Significant difference was detected in the distribution of the genotype frequencies of L55M and Q192R polymorphisms (χ²=6.32, df=2, p=0.04; χ²=10.15, df=2, p=0.006 respectively) between patients and controls. We noted significant association between bipolar I disorder and QR and RR genotypes (OR 2.06, CI 95% 1.10-3.84, p=0.02; OR 1.72, CI 95% 1.07-2.75, p=0.02 respectively) and between this disease and LM and MM genotypes (OR 2.22, CI 95% 1.19-4.15, p=0.012; OR 3.04, CI 95% 1.60-5.77, p=0.01 respectively). There were no significant differences in gender, age at onset, illness episode and treatment among all genotypes. However, Q192R polymorphism was significantly associated with age and patients with RR genotype were the youngest. CONCLUSION Bipolar I disorder was significantly associated with L55M and Q192R polymorphisms, suggesting that these polymorphisms may play a role for development of bipolar I disorder. There was no significant association between the clinical and therapeutic characteristics of this population and these polymorphisms. Further studies are required to clarify the implication of these polymorphisms in the pathophysiology of bipolar I disorder.

Thyroid function and lipid profile in bipolar I patients

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 Konélab 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.

A novel nonsense mutation in the albumin gene (c.1275 C>A) causing analbuminemia in a Tunisian boy

Gianluca Caridi, Maha Kacem, Monica Campagnoli, Monica Dagnino, Wided Debbabi, Ines Kochtali, Fadoua Neffati, Monica Galliano and Lorenzo Minchiotti* 1 Laboratory on Pathophysiology of Uremia, Istituto Giannina Gaslini IRCCS, Genova, Italy 2 Service de Medicine Interne et D’Endocrinologie, CHU Fattouma Bourguiba, Monastir, Tunisia 3 Department of Biochemistry ‘‘A.Castellani’’, University of Pavia, Pavia, Italy 4 Department of Biochemistry CHU Fattouma Bourguiba, Monastir, Tunisia

Evaluation of the renal function in type 2 diabetes: clearance calculation or cystatin C?

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.

Hepatoprotective effect of Opuntia microdasys (Lehm.) Pfeiff flowers against diabetes type II induced in rats

Opuntia sp. has long been used as a folk medicine to treat hepatitis and diabetes in Sicile (Italy). To extract the polyphenols from the flower of Opuntia microdasys Lehm. at post flowring stage and evaluate the antidiabetic activity in vitro and in vivo. The hepatoprotective activity of Opuntia microdasys aqueous flowers extract at post flowering stage (OFP) has been tested for their antidiabetic activity. On fructose-alloxan induced diabete in rat model, evaluating the inhibitory effects of OFP on some carbohydrate metabolizing enzymes, pancreatic α-amylase and intestinal α-glucosidase activities in vitro. The OFP extract showed inhibitory activity against α-glucosidase (IC50=0.17±0.012mg/ml) and α-amylase (IC50=2.55±0.41mg/ml). The inhibitory potential of OFP extract on these enzymes suggests a positive and probable role of this extract in the management and treatment of diabetes mellitus, particularly, for type 2. Oral administration of the OFP at 200mg/kg to diabetic male rats for 28days demonstrated a significant protective effect by lowering the levels of glucose (123.21±1.38mg/dL) and hepatic marker enzymes (AST, ALT, LDH, γ-GT, BT, PAL, TC, LDL-C, HDL-C and TG). OFP attenuated oxidative stress by decreasing the SOD, CAT, GPX activity and the levels of PC and MDA in the liver and restored the histological architecture of the rat liver. OFP has protective effects on the protection of liver, thereby reducing some of the causes of diabetes in experimental animals.