Archives de l'Institut Pasteur de Tunis最新文献

The scorpionic and ophidian envenomations are a serious public health problem in Tunisia especially in Southeastern regions. In these regions Artemisia campestris L is a plant well known which has a very important place in traditional medicine for its effectiveness against alleged venom of scorpions and snakes. In this work, we tested for the first time, the anti-venomous activity of Artemisia campestris L against the scorpion Androctonus australis garzonii and the viper Macrovipera lebetina venoms. Assays were conducted by fixing the dose of extract to3 mg/mouse while doses of venom are variable. The leaves of Artemisia campestris L were extracted by various organic solvents (Ether of oil, ethyl acetate, methanol and ethanol) and each extract was tested for its venom neutralizing capacity. For the ethanolic extract, a significant activity with respect to the venoms of scorpion Androctonus australis garzonii (Aag), was detected. Similarly, a significant neutralizing activity against the venom of a viper Macrovipera lebetina (Ml), was obtained with the dichloromethane extract. These results suggest the presence of two different type of chemical components in this plant: those neutralizing the venom of scorpion are soluble in ethanol whereas those neutralizing the venom of viper are soluble in dichloromethane.

Biochemistry and pharmacology of snake venoms reveal structural and functional polymorphisms of proteins they contain. These lead their effects by their enzymatic activities (proteases, phospholipases A2, L-amino acid oxydases...) or by binding to membrane receptors. Disintegrin from snake venoms play a role as antagonists of cell adhesion and migration by binding integrins and blocking their function. Characterization of integrin antagonists from snake venom allows us understanding the function of some integrins providing new information to develop new therapeutic agents. In this review, we report classification and therapeutic implications of disintegrins. In particular the structural and the functional characteristics of lebestatin; a short disintegrin isolated from Tunisian Macrovipera lebetina snake venom.

Insulin is a hormone which has an essential role in lipids metabolism by modulating the activity of many key enzymes and by its intervention on the production and the catabolism of lipoproteins. The aim of this study was to determine the influence of insulin resistance on lipid profile in a diabetic group. The study group consists of 118 diabetic patients. We assayed for each patient total cholesterol, high density lipoprotein cholesterol, triglycerides and insulin. Insulin resistance was determined by HOMA index. Insulin was found correlated to body mass index, triglycerides, waist circumference, and glycated haemoglobin. Triglycerides and glycated haemoglobin were significantly more elevated in insulin resistant group than in insulin sensitive group. Insulin resistance may be the initial anomaly in type 2 diabetes and incite us to search on molecular anomalies in the insulin action.

Unlabelled: The purpose of this study was to compare the efficacy, in terms of bacterial biofilm penetration and killing, of some chemical disinfectants against E. coli and P. aeruginosa. This study was undertaken to examine the efficacy of some disinfectants including sodium hypochlorite, povidine and tryad detergent against E. coli biofilms and the efficacy of sodium hypochlorite and tryad detergents against P. aeruginosa. Two species biofilm of E. coli and P. aeruginosa were grown by flowing a dilute tryptic soy broth medium over an inclined cement, polyethylene, fiberglass and galvanized steel slides, 2.25 x 2.25 cm2 for 15 days. Biofilm formation was evaluated by scanning electron microscopy (SEM) and standard plate counts procedures through selective media for both E. coli and P. aeruginosa. In addition, some disinfectants were selected through disk diffusion susceptibility test. The disinfectants which gave higher zone of inhibitions, were applied to remove of E. coli and P. aeruginosa biofilms from cement, fiberglass, polyethylene and galvanized steel slide surfaces. Results showed that all disinfectants tested gave high inhibition of biofilm adhesion to tank surfaces with some being significant.

Conclusion: polyethylene and galvanized steel are strongly recommended as alternative drinking house holds water tanks in Saudi Arabia. The choice of disinfectants or cleaning agents along with optimum concentrations and the time of action is very important when destroying microbes. It is also important that resistance of microbes to some disinfectants and cleaning agents is take into consideration when planning the cleaning process.

A matched case-control study was undertaken in 2004 in Béja, north-western Tunisia, to evaluate potential risk factors for hepatitis C infection. Cases were anti-HCV positive subjects screened in 1996 serosurvey. HCV seronegative controls (5 per case) were selected in the proximity of cases and matched for age and gender. A standardized questionnaire was used to collect demographic, socioeconomic, social behavior, medical and surgical history information. Matched odds ratios (OR) and adjusted OR (AOR) and their 95% CI were calculated in multivariate analysis using logistic regression. 57 HCV positive cases (mean age 61.63 +/- 14,84; 68.4 % female) and 285 HCV negative controls (mean age 60.95 +/- 14.66; 68.4 % female) were enrolled. Multivariate analysis revealed that intravenous drug injections (AOR=1.96; 95%CI[1.02-3.8] p=0.045), past history of invasive procedures (AOR=2.53; 95%CI[1.21-5.29] p=0.0014) and medical history of hypertension (AOR=2.31; 95%CI [1.17-4.56]p=0.015) were significantly associated to HCV infection. These results suggest that nosocomial transmission of HCV infection in north-west Tunisia is common.

Gaucher disease is the most common lysosomal storage disorder, it results from the inherited deficiency of the enzyme glucocerebrosidase, the accumulation of its substrate causes many clinical manifestations. Since the discovery of GBA gene, more than 200 different mutations have been identified, but only handful mutations are recurrent (N370S, L444P and c.84insG). In order to determine the mutation spectrum in Tunisia, we performed recurrent mutation screening in ten unrelated Tunisian children with Gaucher disease. Screening of recurrent mutation by PCR/RFLP and direct sequencing, has shown that N370S is the most frequent mutation (6/20 mutant alleles, 30%), followed by recombinant allele (RecNciI) which is found in five patients (5/20 mutant alleles, 25%), the L444P mutation represent 20% (4/20 mutant alleles). Our findings revealed that five among ten studied patients, were compound heterozygous N370S/RecNciI (50%). The screening of these mutations provides a simple tool for molecular diagnosis of Gaucher disease in Tunisian patients and allows also genetic counselling for their family members.

Cholinergic receptors have an essential physiological role in the central nervous system because of their implication in higher functions in the neuromuscular junction within the brain and also in the peripheral nervous system by activating nicotinic (nAChRs) or muscarinic (mAChRs) receptors. Moreover, cholinergic receptors could be recognized by animal toxins isolated from snake venoms or alkaloids having animal or vegetal origin. In this context, we aim to find such molecules in a non toxic venom fraction of Buthus occitanus tunetanus scorpion, M1, which could therefore constitute promising medical tool. We present here a physiological study in skeletal muscle cells that regroups data that have been recently published and some new results reinforcing the last ones. The global effect of M1, was firstly studied on isolated nerve-muscle preparation. In cultured myotubes, we have found that the intracellular calcium increase, induced by M1 was blocked when ryanodine or inositol 1,4,5-triphosphate receptors are inhibited. Moreover, we have shown that M1 application on myotubes, induced a membrane depolarization as seen with acetylcholine. The treatment of myotubes with alpha-bungarotoxin blocked in most parts the depolarization amplitude. Thus, these results confirm the presence of at least one component in M1 active in nAChRs.

The G-protein coupled receptors (GPCRs) form a large protein family in the human genome that have been widely studied and classified into classes and phylogenetic subfamilies. However, there still exist orphan GPCRs that are not classified in any of the known subfamilies and new bioinformatics approaches are still needed to address this issue. One of the interesting features of GPCRs is that a large proportion of these proteins are encoded by intronless genes. In this work, we are interested in the study of Rhodpsin-like GPCRs proteins encoded by this kind of genes. After a manual validation of their gene structure, we studied some of their properties including the number of exons, chromosomal location and protein length. The same trend was found for intronless GPCRs as compared to total GPCRs, particularly the uneven chromosomal distribution with a large number (one third) of GPCRs on chromosomes 1 and 11. The proportion of intronless GPCRs among all Rhdopsin-like GPCRs was estimated to about 26% which is significantly less than previously reported. Significant differences in protein length were found between subfamilies. We then used composition properties of DNA and protein sequences to classify intronless Rhodopsin-like GPCRs. Principal component analysis was used to identify key variable and then a discriminant analysis was used to compute discriminant functions that best separates the phylogenetic subfamilies. We found that the most important features to separates the groups is the proportion of aromatic amino acids in protein sequence and the contrast between (A+T) versus (G+C) in coding sequence. These functions are finally used to classify fourteen putative or unclassified GPCRs.

The molecular analysis of chromosomal abnormalities associated with hematological malignancies allowed the identification of genes involved in theses rearrangements as well as of some recurrent mechanisms. Polymerase chain reaction (PCR) tools are now available to detect these rearrangements, allowing a better follow-up of these diseases. Chronic myeloid leukemia is a myeloproliferative disorder characterized by a reciprocal translocation t(9;22)(q34;q11) which results in a bcr-abl fusion gene. Retro-transcription polymerase chain reaction (RT-PCR) is used to detect bcr-abl to establish diagnosis and to monitor patients. We report here the results of 30 patients samples tested in the hematology laboratory at Pasteur Institute, diagnosed as chronic myeloid leukemia and monitored with RT-PCR. Our results highlight the interest of molecular tools to diagnose and monitor patients mainly when cytogenetic techniques are irrelevant such as cases with complex chromosomal rearrangements or when patients achieve Philadelphia negativity after treatment.

The study of triacylglycerols synthesis using 1,3-regiospecific immobilized Rhizomucor miehei lipase (lipozyme) or non-regiospecific immobilized Candida antarctica lipase (novozyme) as biocatalyst was carried out in pure substrates conditions. Our results show that long-chain triacylglycerols were synthesized from glycerol and free fatty acids at a higher rate than medium-chain triacylglycerols which were themselves synthesized at a higher rate than short-chain ones. Furthermore, it is clearly shown that linoleic acid is more slowly esterifled than oleic acid which is itself more slowly esterified than octadecanoic acid. The higher the number of unsaturation, the lower the rate of synthesis and the final yield. On the other hand, the final yield of synthesis is comparable when using specific or non-specific lipase, as biocatalyst.