Asma Kassab

Update in chronic obstructive pulmonary disease: role of antioxidant and metabolizing gene polymorphisms

ABSTRACT Chronic obstructive pulmonary disease (COPD) is characterized by systemic and local chronic inflammation and oxidative stress. The sources of the increased oxidative stress in COPD patients derive from the increased burden of inhaled oxidants such as cigarette smoke and other forms of particulate or gaseous air pollution and from the increase in reactive oxygen species (ROS) generated by several inflammatory, immune, and structural airways cells. There is increasing evidence that genetic factors may also contribute to the pathogenesis if COPD, particularly antioxidant genes, which may confer a susceptibility to environmental insults such as cigarette smoke and thereafter development of COPD. Consequently, heme oxygenase-1 (HO-1), superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), microsomal epoxide hydrolase (EPHX1), and cytochrome P450 (CYP) genetic polymorphisms may have an important role in COPD pathogenesis. In this review the authors summarized the most recent findings dealing with these antioxidant genes contributing to the free radical neutralization and xenobiotic enzymes playing a role in different phases of cell detoxification reactions related to the redox status imbalance in COPD, with an emphasis on their possible roles in disease progression.

Homocysteine enhances LDL fatty acid peroxidation, promoting microalbuminuria in type 2 diabetes

Background We aimed to establish the relationship between glycated haemoglobin (HbA1c), hypertension and microalbuminuria onset in type 2 diabetes. We also intended to ascertain the metabolic action of homocysteine on LDL fatty acids and on renal function. Methods The study was carried out on 200 patients with type 2 diabetes and 200 healthy subjects. HbA1c, apolipoprotein B (apo B) and microalbuminuria were measured using immunoturbidimetric methods. Cholesterol, peroxide, urea and uric acid were assayed using colorimetric methods. Creatinine clearance was calculated using the Cockroft-Gault equation. Homocysteine was measured by immunological fluorescence polarization. LDL fatty acids were quantified by gas chromatography. Results Creatinine and microalbuminuria significantly increased in type 2 diabetes when compared with controls. Microalbuminuria was significantly correlated with HbA1c and with the presence of high blood pressure. Homocysteinaemia significantly correlated with creatinine clearance in diabetes. Linoleic acid (C18:2ω6) did not differ between groups. C18:2ω6/C18:3ω3 ratio was three times higher in diabetics than in controls. Total saturated fatty acids, homocysteine, H2O2 and LDL-thiobarbituric reactive substances significantly increased in microalbuminuric when compared with normoalbuminuric diabetes. Total polyunsaturated fatty acids, arachidonic acid (C20:4ω6), LDL-cholesterol, apo B and creatinine clearance significantly decreased in microalbuminuric when compared with normoalbuminuric diabetes. Conclusion Microalbuminuria onset is associated with renal protein oxidation that is preceded by LDL fatty acid oxidation. The latter is initiated by H2O2 produced from an auto-oxidation of homocysteine and increased metabolism of arachidonic acid towards its pro-inflammatory eicosanoids. An oxidative stress state is the common ground of diffused vasculopathy.

Molecular analysis of mucopolysaccharidosis type I in Tunisia: identification of novel mutation and eight Novel polymorphisms

Mucopolysaccharidosis type I (MPS I) is an autosomal recessive lysosomal storage disorder caused by a genetic defect in alpha-L-iduronidase (IDUA) which is involved in the degradation of dermatan and heparan sulfates. The disease has severe and milder phenotypic subtypes. The aim of this study was the detection of mutations in the IDUA gene from 12 additional MPS I patients with various clinical phenotypes (severe, 8 cases; intermediate, 3 cases; mild, 1 case).Patients and methodsIn this study, the IDUA mutations in eight unrelated Tunisian families were performed by amplifying and sequencing the IDUA exons and intron-exon jonctions.ResultsFive IDUA mutations were detected: one is the L578Q, a novel mutation found, in milder patient. The others were the previously described: P533R, Y581X, F602X and R628X that produce a severe and intermediate phenotype. In addition, eighteen variants, including eight previously unreported polymorphisms (IVS6+21c > a, IVS7+79c > t, IVS7-45 g > c, IVS9+36t > c, IVS10+140c > a, IVS11+33c > t, IVS12+13c > t and IVS12-31c > g), were detected.ConclusionThis paper, showed a heterogeneous pattern of mutations and polymorphisms among Tunisian patients.

CRP relevance in clinical assessment of chronic spontaneous urticaria Tunisian patients

Abstract Background: Chronic spontaneous urticaria (CSU) is a common dermatological condition defined by the sudden occurrence of daily wheals and pruritus for at least six weeks. Multifactorial origin is suggested such as oxidative stress. This latter may play a double role as a trigger and remnant agent. Objectives: The first aim of this study is to investigate antioxidant status, inflammatory proteins, hematologic counts and clinical assessment in CSU patients. The second aim is to evaluate the effect of a first-line treatment: desloratadine 5 mg/d on these different parameters. Patients and Methods: This study enrolled 30 CSU patients and same number of controls. We assessed the urticaria activity score (UAS), total antioxidant status (TAS), glutathione S-transferase (GST), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), albumin, alpha1, alpha2, beta1 beta2, gamma globulins, c-reactive protein (CRP) and hematologic numeration. Results: At baseline alpha1, alpha2, beta1, beta2, gamma globulins, CRP, SOD activity, leukocytes and basophils were significantly higher in patients versus controls (p < 0.05). TAS, GST, CAT, GPx and albumin were significantly low in patients versus controls (p < 0.05). After treatment, TAS, GST and GPx were significantly increased in patients versus patients before treatment (p < 0.001). SOD, alpha1, alpha2, beta1, beta2, gamma globulins, CRP, albumin, leukocytes and basophils were significantly decreased after treatment versus before treatment (p < 0.05). A significant correlation between CRP and UAS (r = 0.3; p = 0.011) was noted. UAS assessment revealed the efficacy of 30 d-antihistaminic treatment. Conclusions: Desloratadine exerted anti-inflammatory and antioxidant effects on CSU patients revealed by CRP. Patients’ remission was synergistic to CRP attenuation emphasizing CRP relevance for CSU clinical assessment.

Alu-repeat Polymorphism in the Tissue Plasminogen Activator Gene andRisks of Myocardial Infarction in Tunisian Population

This study aimed to determine whether I/D polymorphism predispose to the development of MI in Tunisia. 50 patients with coronary artery disease complicated by MI and 70 healthy controls were analyzed. Quantitative analyses lipids are founded. DNA was isolated from blood samples. Polymorphisms were assessed by polymerase chain reaction method. Statistical differences between groups were determined by Chi-square test. Compared to controls, cases have significantly higher levels of total cholesterol, triglycerides and LDL-cholesterol and lower level of HDL-cholesterol. There are no significant differences between patients and controls in terms of allelic and genotypic frequencies. However, the frequency of the “I” allele is higher in cases which have 2 MI (p=0.0354). Additionally, a statistically significant association between diabetes, arterial high blood pressure, family history and cigarette smoking with MI was founded (p<0.01). I/D polymorphism of t-PA gene is not associated with MI in this sample of Tunisian population.

BRCA1 and BRCA2 Mutations are they Related to Breast Cancer in a Sample of Tunisian Population

Mutations in the BRCA1/BRCA2 genes account for varying proportions of breast cancer families studied, and demonstrate considerable variation in mutational spectra coincident with ethnic and geographical diversity. This work aimed to identify mutations in BRCA1 and BRCA2 genes to explore the existence of population-specific recurrent or founder mutations, in Tunisian breast cancer families. We have screened for germline mutations in seventeen Tunisian high-risk breast cancer patients using direct sequencing. Index patients, diagnosed before age 45, possessing a positive family history or bilateral breast cancer were asked for detailed information on family history of breast or any other cancer type in their families. One family out of 17 (6%) carried BRCA 1 mutations and no BRCA2 mutations was found. One recurrent mutation in BRCA 1 was identified, c.798-799delTT, which appear to represent founder mutation in this population. Thirty-one variants were considered of unknown clinical significance according to BIC and UMD-BRCA1/BRCA2 databases.

Is Folate an Aetiological Factor for Colorectal Cancer Onset? A Case- Control Study

The aim of this study was to investigate the correlation of serum folate concentration in newly diagnosed patients with colorectal cancer. Patient population consisted of 101 sporadic colon cases, newly diagnosed, non-alcoholic and non-multivitamins users. Control population consisted of 130 healthy subjects. Venous blood was collected prior to the first chemotherapy intervention. Folate, vitamin B12 and homocysteine were measured using an automated analyzer system. Vitamin B6 was quantified using an enzyme immunoassay. Insulin and leptin were measured using immunoradiometric assay. Folic acid and vitamin B12 were significantly increased in cases compared to controls (15 ± 7 ng/ml vs. 10 ± 4 ng/ml, P=0.01; 330 ± 200 pg/ml vs. 220 ± 100 pg/ml, P=0.02) respectively. Folic acid and BMI were inversely correlated in controls (r=-0.32; P=0.05). There was no significant difference of homocysteine and vitamin B6 between cases and controls. Leptin and insulin were significantly higher in cases with BMI ≥ 27 than in controls with BMI ≥ 27 (16 ± 7 ng/ml vs. 14 ± 7 ng/ml; 32 ± 18 μIU/ml vs. 29 ± 11 μIU/ml). However, stratifying leptin and insulin by cancer stages yielded to no clear pattern. Folate may be implicated as a potential aetiological factor for colorectal cancer.

Alpha-Fetoprotein Producing Breast Cancer Cells: Case Report and Review of Literature

Aim : In this paper we report a rare case of breast carcinoma followed by liver metastasis associated to alpha fetoprotein (AFP) secretion by tumor cells. Methods : Carcino-embryonic antigen (CEA), carbohydrate antigen (CA) 15-3, serum AFP and AFP immunohistochemistry staining were detected using commercial kits in 44 year-old woman with breast cancer. Results : CEA and CA 15-3 were within normal limits. AFP baseline was 14000 ng/l. There was no chronic hepatic viral disease. Biopsy revealed invasive carcinoma ductal cells. Histologic examination of the tumor showed invasive carcinoma, nuclear grade was 2, the tumour cells were negative for oestrogen and progesterone receptor positive for Her-2/neu. The immunohistochemistry stainig for AFP revealed positive reactivity. After chemotherapy, AFP level was within the normal range and abdominal ultrasonography showed a partial response evaluated at 50 %. The patient was in good condition at the time of our report (May 2013). Conclusion : We presume that the increased serum AFP level is responsible for the cancer evolution with good prognosis for breast cancer and poor one for gastric cancer and colon cancer.