Biochemical and morphological differences between CA125 isolated from healthy women and patients with epithelial ovarian cancer from Tunisian population.

Analysis of the structure of CA125 is essential for determining the physiological role of this significant tumor antigen. The objectives of this study were: (1) to identify the characteristics of the CA125 isolated from healthy and patient women with epithelial ovarian cancer; and (2) to determine the ferning structure of this antigen. The cancer-derived CA125 antigen (cCA125) purified by gel filtration and affinity chromatography (Concanavalin A) was run on SDS-PAGE and examined using light microscopy and compared with healthy-derived CA125 antigen (hCA125). Both purified antigen cCA125 and hCA125 showed a high molecular mass (> 2,000 kDa) with high mannose glycans. The ferning patterns related to cCA125 and hCA125 revealed distinct differences in the patterns of arborescence. The ferning morphology of cCA125 antigen was denser than that of hCA125 antigen making an obvious difference between cCA125 and hCA125, with respect to length, branching and distribution of crystals. The current study provides the first evidence for a potential functional link between CA125 and its structure which, in the light of a comparison between cCA125 and hCA125, might proof to be of significant biomedical importance in the future.

[Oxidant stress and cardiovascular absolute risk in Tunisian type 2 diabetes]. / Stress oxydant et risque cardiovasculaire absolu chez des diabétiques de type 2 du centre tunisien.

INTRODUCTION: cardiovascular diseases constitute the most hefty complications in diabetes. Absolute cardiovascular risk (ACVR) can be estimated by many equations that are continuously criticised. The aim is, in one hand, to evaluate ACVR in type 2 diabetes and, in the other hand, is to establish correlations between ACVR and oxidant-antioxidant status. MATERIAL AND METHODS: 183 type 2 diabetes and 200 controls were admitted. ACVR assessment was calculated following Laurier equation. Oxidant status was evaluated by the measure of homocysteine, hydrogen peroxide (H2O2) and LDL thiobarbituric reactive oxygen substances (LDL-TBARS). Antioxidant status was evaluated by the measure of superoxide dismutase (SOD) activity, glutathione peroxidase (GPx), total antioxidant status (TAS) vitamins A, E and zinc. Glycated haemoglobin (HbA1c) and microalbuminuria were assessed by turbidimetry. RESULTS: ninety percent of diabetes belonged to moderate and high ACVR groups. In diabetic men ACVR was doubled each elevation of 4 micromol/L homocysteine, of 50 micromol/L of H2O2 and of 20 mg/L of microalbuminuria. High risk ACVR group showed the lowest SOD activity, zincemia and the highest HbA1c. No significant difference was found in LDL-TBARS, TAS, GPx, vitamins A, E between the different ACVR groups. The strong relation between homocysteine and ACVR confirms homocysteine atherosclerotic role. Homocysteine auto-oxidation produces H2O2 leading to LDL-TBARS increase. Microalbuminuria-ACVR association verifies its vasculopathy predictor role. Urinary albumin leakage may be consequent to the hyperhomocysteinemia found in diabetes. CONCLUSION: homocysteine introduction in ACVR assessment equation may ameliorate this estimation.

[Mucopolysaccharidosis type I: identification of alpha-L-iduronidase mutations in Tunisian families]. / La mucopolysaccharidose de type I: identification des mutations du gène alpha-L-iduronidase dans des familles tunisiennes.

UNLABELLED: Mucopolysaccharidosis type I (MPS I) is a lysosomal disease due to mutations in the gene encoding alpha-l-iduronidase (IDUA) leading to variable clinical phenotypes with progressive severe organomegaly, bone and neurological involvement in the most severe forms. The aim of our study was to propose in Tunisia a strategy of molecular and prenatal diagnosis of the MPS I. POPULATION AND METHODS: Our study was carried out on 8 MPS I patients recruited from different Tunisian regions and issued from 5 unrelated families. All the patients were offspring of consanguineous marriages. RESULTS: The clinical and biological study led to diagnose 5 Hurler patients and 3 Hurler-Scheie patients. Three IDUA mutations were identified by molecular analysis within 6 different families: a novel mutation p.F602X and 2 already described mutations p.P533R and p.R628X. DISCUSSION: MPS I is a heterogeneous disease characterized by variability of the phenotypes. The missense mutation p.P533R associated with the intermediate phenotype was the most frequent in the Tunisian but also in the Moroccan population. In Tunisia, the incidence of p.P533R mutation seems to be associated with the high frequency of consanguineous marriages. CONCLUSION: The identification of known MPS I mutations (p.P533R and p.R628X) and of the novel mutation p.F602X permits reliable genetic counselling of at-risk relatives and molecular prenatal diagnosis.