Association of high-sensitivity C-reactive protein with susceptibility to Schizophrenia in Tunisian population.

The pathogenic mechanisms underlying Schizophrenia (SZ), one of the most frequent mental disorders, are complex and poorly understood. Several evidences suggest that inflammatory processes may underpin some of its neurobiological correlates. The aim of this study was: (i) to analyze the potential association between circulating levels of the C-reactive protein (CRP), a crucial inflammatory marker, and Schizophrenia in Tunisian patients and healthy controls (HC) cohorts; (ii) to investigate the genetic diversity of three CRP variants (rs1417938, rs1130864 and rs1205) and; (iii) to analyze a potential relationship between expression and genetic data and clinical and socio demographical characteristics. CRP polymorphisms were exanimated for 155 patients and 203 HC by taqMan5'-nuclease. High-sensitivity CRP (hs-CRP) serum level was measured in 128 clinically stable out-patient SZ patients and 63 HC subjects via an automated biochemical analyzer. We found that hs-CRP levels were significantly higher in SZ patients as compared to HC. No significant differences were found when the proportions of CRP variants were compared in patients and HC. Further analysis according to clinical and socio demographical characteristics revealed a positive association with age and hypertension. Our data on an original Tunisian sample confirm the previous finding in others population groups.

The CC-genotype of the cyclooxygenase-2 gene associates with decreased risk of nasopharyngeal carcinoma in a Tunisian population.

BACKGROUND: The cyclooxygenase-2 (cox-2) pathway is now recognized to be important in human cancer development and progression. The gene for cox-2 carries a common single nucleotide polymorphism, T8473C, located within a potential functional region in the 3'-UTR of cox-2 gene was identified. We have investigated the frequencies of cox-2 genotypes in Tunisian population to determine whether that polymorphism was associated with the risk of nasopharyngeal carcinoma (NPC) in Tunisian population. MATERIAL AND METHODS: One hundred and eighty-nine NPC patients were compared to 237 healthy controls. RESULTS: The cox-2 T8473C polymorphism was significantly associated with NPC (P=0.031). The CC-genotype and C allele were more frequent in control compared to patients group [CC: OR=0.37; P=0.013; 95% CI: 0.17-0.81; C: OR=0.72; P=0.032; 95% CI: 0.53-0.97]. Multivariate logistic regression analyses revealed that the CC-genotype was associated with a significantly decreased risk of NPC (P=0.013). Tumor sizes, histologic grade, presence of primary lymph node metastases, age or sex were not associated with cox-2 genotypes. CONCLUSION: We conclude that the CC-genotype and C allele of cox-2 T8473C gene polymorphism are associated with decreased risk of nasopharyngeal carcinoma in a Tunisian population.

Rare hemoglobin variants in Tunisian population.

During the last 30 years, many studies concerning hemoglobinopathies were realized among Tunisians. More than twenty different thalassemic alleles were detected on the ß-globin gene, and less are affecting the α-globin genes. Unusual hemoglobin (Hb) variants other than Hb S, Hb C, and Hb O-arab, which are the most frequent variants in Tunisia, were also detected. Eight Tunisian subjects were studied at phenotypic and molecular levels. Hematological indices and hemoglobin (Hb) pattern were performed by alkaline electrophoresis and isoelectric focusing (IEF),and the Hb fractions were quantitated by cation exchange HPLC. On genomic level, coding regions were amplified by polymerase chain reaction (PCR) followed by a sequencing of the purified PCR products using the dye terminator method. Seven uncommon Hb variants were detected and described for the first time among Tunisians. HbA2-Tunis [δ46(CD5), Gly → Glu, GGG → GAG] is the newly described δ-chain variant in our laboratory, and some other variants (Hb Constant Spring, G San Jose, and Hb J-Bangkok) are very uncommon in the Mediterranean region. We present here an updated review of the Hb variants detected among Tunisians. Twenty-one rare Hb variants were detected affecting the α1-, α2-, δ-, γ-, and ß-globin genes, leading in some cases to a severe phenotype especially when the stability is completely altered. The ethnical history of Tunisia could explain this important variability of the observed rare Hb variants.

Association of IL-12p40 +1188 A/C polymorphism with nasopharyngeal cancer risk and tumor extension.

The interleukin 12 (IL-12) cytokine, encoded by polymorphic genes, plays a central role in the T helper 1 cell-mediated immunity against tumors. We investigated whether the 3' untranslated region +1188 A/C polymorphism (rs 3212227) influences the nasopharyngeal carcinoma (NPC) risk in Tunisian patients. DNA analysis of 247 patients and 284 healthy individuals showed a higher frequency of the 1188 C allele and the CC genotype in patients than in controls (P = 0.00001 and P = 0.00005) suggesting that the C variant allele is associated with the susceptibility to NPC. Additional testing showed that the homozygous CC genotype is also associated with advanced stage of the tumor extension at presentation (P = 0.022). Our data suggest that the impaired production of IL-12 behaves as a risk factor for NPC occurrence and progression.

[The C677T polymorphism in the methylene tetrahydrofolate reductase gene among Tunisian population]. / Etude du polymorphisme C677T du gène de la méthylène tétrahydrofolate réductase dans la population tunisienne.

The 5,10 methylene tetrahydrofolate reductase (MTHFR) is an enzyme that catalyzes the irreversible reduction of 5,10 methylene tetrahydrofolate into 5 methyl tetrahydrofolate. It is coded by a gene where several polymorphisms have been identified. The most common is the C677T polymorphism described as presenting an heterogeneous worldwide distribution and associated with different disorders such as cardiovascular and cancerous diseases. The aim of this work was to determine the allelic and genotypic frequencies of the C677T polymorphism among a Tunisian healthy population. The study concerned 185 subjects apparently healthy. It was carried out by the PCR/RFLP method, using the restriction enzyme Hinf I. The results has showed an allelic frequency of 17.8% with a genotype frequency of 5.4%. These values are intermediate between those observed in Africa and those observed in Western countries. They must be considered in the evaluation of the clinic significance of a predisposition to diseases.

[Serum lactate dehydrogenase and its isoenzymes in nasopharyngeal carcinoma in Tunisia]. / Profil serique de la lacticodeshydrogenase et de ses isoenzymes dans le cancer du nasopharynx.

Our prospective study interested 41 patients, from 13 to 70 years old, and present a nasopharyngeal carcinoma confirmed histologically, during the period going from September 1999 to March 2000, and 45 healthy controls. A blood sample was collected from each patient before any treatment, as well as controls to measure serum LDH and its isoenzymes. Two groups of patients were selected after a period varying from 12 to 37 months with a mean of 29 months: 29 with favourable evolution, 12 with non favourable evolution. The mean serum total LDH and its isoenzymes values were significantly higher in patients than those in controls with values of variable p of 0.001 to 0.05. A significant correlation was found between ganglionnary extension and serum values of total LDH, LDH3 and LDH5. No significant difference were observed between the means serum total LDH before treatment and the clinical evolution of patients. Diagnostic contribution of total LDH is limited, by its ubiquitary character, but could constitute for LDH3 a good marker of the disease progression.

IL-18 mRNA expression and IFN-gamma induction in bronchoalveolar lavage from Behçet's disease.

OBJECTIVE: IL-18 expression and functional activity has been identified in several autoimmune and infectious diseases. To clarify the potential role of IL-18 during pulmonary Behçet's disease (BD), we have explored the capacity of IL-18 to induce the expression of IFN-gamma. METHODS: We studied bronchoalveolar lavage (BAL) from 12 patients with BD, 10 patients with silicosis as the control disease and 10 BAL from healthy subjects. BAL fluid, and BAL fluid cell cultures were investigated for IL-18 estimation by ELISA. Analysis of IL-18 and IFN-gamma gene expression was carried out before and after LPS stimulation. RESULTS: BD patients had significantly elevated levels of IL-18 in BAL fluid compared with control disease and healthy subjects. Induction of IFN-gamma and IL-18 were observed from BD-BAL fluid cells both spontaneously and after LPS stimulation, at higher levels compared to silicosis patients and healthy subjects (HC). Spontaneously only BD BAL cells expressed IL-18 mRNA and IFN-gamma mRNA. Forty-eight hours after LPS stimulation IL-18 mRNA and IFN-gamma mRNA were observed in BD, silicosis and HC cells. Recombinant IL-18 induced IFN-gamma production in BD- BAL fluid cells. CONCLUSION: Administration of IL-18 induced greater IFN-gamma production in BD-BAL fluid cells, than in normal BAL fluid cells. Our data indicate that IL-18 up-regulation is a feature of BD and suggest that IL-18 and IFN-gamma may contribute to the local inflammatory response in BD.

[Comparative effects of oral rehydratation solutions in experimental cholera in the rat]. / Effets comparés de solutions de réhydratation par voie orale dans le choléra expérimental chez le rat.

UNLABELLED: The composition of the World Health Organisation (WHO) solution in oral rehydration therapy has remained controversial because of its total osmolarity (303 mosm/L) and higher sodium concentration (90 mEq/L), increasing the risk of hypernatraemia. AIM OF THE STUDY: To compare the efficacy of two reduced-osmolarity oral rehydration solutions (S1: 268 mosm/L and 50 mEq/L Na(+); S2: 240 mosm/L and 60 mEq/L Na(+) ) with the WHO recommended formula taken as the reference solution. Water, electrolytes and glucose fluxes were directly measured in vivo, in isolated ligated loops of rat jejunum (n=12). Intestinal secretion was induced by exposing jejunum to cholera toxin (CT=20 microg/loop). RESULTS: All three test solutions similarly reversed cholera toxin-induced net water absorption (3.37 +/- 1.35; 3.31 +/- 0.43 and 3.13 +/- 0.66 microL/min.cm(2) for S1, S2 and WHO solutions respectively). However, net Na secretion induced by cholera toxin was observed with S1 and S2 while Na absorption occurred with the WHO solution. CONCLUSION: For a same amount of water absorbed, Na absorption from reduced - osmolarity rehydration solutions is lower than with the WHO solution. Our data may contribute to a better rationale for the use of orally administered hydration solutions in man.

[Serum copper levels in obesity: a study of 32 cases]. / Le cuivre serique chez l'obese: une etude a propos de 32 cas.

Abnormalities of copper distribution in tissues and serum has been described in obese subjects. In this prospective study, we evaluated the seric level of copper by atomic absorption in a group of 32 obese (BMI > or = 30 kg/m2) compared to a group of 32 healthy subjects. We have noted an elevation of serum copper in obese with a middle level of 133 mg/dl significantly superior to the middle level of serum copper of healthy subjects, 108 mg/dl (p < 0.001). In another hand, we have noticed that the levels of serum cooper rise with the BMI. In fact, 58.3% of the obese that have a BMI > or = 40 kg/m2 show a high concentration of serum copper although only 5% of obese with BMI < 40 kg/m2 show this high concentration. This work must be completed by the determination of ceruloplasmin levels in a larger group of obese in order to establish correlations between the serum ceruloplasmin levels, the serum copper levels and the obesity.

[The use of neuron specific enolase in the prognosis and followup of neuroblastoma in children. Results of a retrospective series of 21 patients]. / Apport de la neuron specific enolase dans le pronostic et le suivi des neuroblastomes de l'enfant. Résultats sur une série rétrospective de 21 patients.

OBJECTIVE: To report the results of seric neuron specific enolase in pediatric neuroblastoma. PATIENTS AND METHODS: Our retrospective study concerns 21 children treated in our institution from 1992 to 1998 for neuroblastoma. Seric NSE was determined by immunoenzymology technique at different stages of the disease and the treatment. RESULTS: Mean value for the 39 dosages of the whole patients was 127.9 ng/ml with a sensitivity of 56%, five patients has presented normal values. Mean value for the 18 patients in stage IV was 132.38 ng/ml. We also observed in 3 patients, an evolution of the seric NSE parallel to this of the disease under chemotherapy. CONCLUSION: NSE represents a moderate sensitive and specific tumor marker for pediatric neuroblastoma. However, it represents a good value in prognosis and follow-up after chemotherapy.

[HbC/beta-thalassemia association. Eleven cases observed in Tunisia]. / Association HbC/beta-thalassémie. A propos de onze cas observés en Tunisie.

Eleven cases of simultaneous HbC hemoglobinopathy and beta-thalassemia were detected during a study of 11,200 subjects at high risk for inherited hemoglobin anomalies. In seven cases, main clinical manifestations were anemia and enlargement of the spleen, whereas the four other patients were apparently free of symptoms and were diagnosed during routine tests in family members of affected patients. Microcytosis and hypochromia were found in every case. Most of the patients were from the North-Western part of Tunisia. Blood transfusions were required in only one patient, who was an infant with HbC/beta + thalassemia.

[HbD Iran-beta-thalassemia association in a Tunisian family]. / Association HbD Iran-beta-thalassémie dans une famille tunisienne.

A nine-year-old boy from Béjà (North-Western Tunisia) was found to have both HbD Iran and beta-thalassemia. This patient presented with anemia and slight enlargement of the spleen and had a history of acute episodes of hemolysis. Structural studies on this hemoglobin variant used several miniaturized techniques, mainly carboxy-methyl-cellulose chromatography, reverse-phase high performance liquid chromatography and manual peptide sequencing using Chang's technique. The glutamic acid in position 22 on the beta chain was found to be replaced by a glutamine, establishing the diagnosis of HbD Iran. Concomitant presence of a thalassemia trait was suggested by the finding in the index patient of microcytosis, hypochromia and increased HbA2. The family study confirmed this patient's combined heterozygous anomalies, showing the D trait in the father and the beta thalassemia trait in the mother. The same combination was found in the index patient's sister who was, however, free of clinical symptoms. The explanation of this difference in clinical expression was provided by the ADN study which disclosed deletion of an alpha gene in the girl. The resulting alpha chain deficiency counterbalanced the beta chain deficiency.

[Association of Hbo Arab/beta-thalassemia discovered fortuitously in 2 brothers]. / Association d'une HbO Arab/bêta-thalassémie découverte fortuitement chez deux frères.

A four-year-old boy admitted for fever and a skin rash was diagnosed as having a rickettsial infection. Regenerative microcytic anemia and enlargement of the spleen were also found. Hemoglobin electrophoresis and a family study disclosed a combination of two heterozygous hemoglobinopathies, i.e., HbO Arab and beta-thalassemia. A male sibling had the same anomalies as the index patient and was free of symptoms.

Hb Bab-Saadoun or alpha 2 beta (2)48(CD7)Leu----Pro, a mildly unstable variant found in an Arabian boy from Tunisia.

Hb Bab-Saadoun which has a Leu----Pro substitution at position 48 of the beta chain was detected in a young Arabian boy living in Tunisia. His parents did not have the variant which suggests that it occurred as a spontaneous mutation. The substitution is located in the interhelical CD segment; leucine at beta 48 is an invariable amino acid that may be important as part of a spacer sequence between the two helices and its replacement by proline may affect the stability of the hemoglobin molecule. Hb Bab-Saadoun is unstable in heat and isopropanol stability tests and its chain was best isolated by parachloromercuribenzoate precipitation. It appears unlikely that the presence of Hb Bab-Saadoun results in a hemolytic anemia.

Beta-thalassemia, HB S-beta-thalassemia and sickle cell anemia among Tunisians.

We analyzed the mutations present in 19 patients with beta-thalassemia major, in 11 patients with Hb S-beta-thalassemia, and the beta S haplotypes of 34 patients with sickle cell anemia. The study included 84 relatives. Dot-blot analysis of amplified DNA with various specific oligonucleotide probes identified 11 different known beta-thalassemia mutations and frameshifts; a new frameshift at codons 25/26 (+T) was detected through sequencing of amplified DNA. The common beta-thalassemia mutations at codon 39 (C----T) and at IVS-I-110 (G----A) were also most prevalent among the Tunisian patients, while the milder T----C mutation at IVS-I-6 was not found. All mutations cause a beta 0-thalassemia or a severe beta + -thalassemia [T----A at -30; IVS-I-5 (G----A); IVS-I-110 (G----A)] which explains the need for regular blood transfusions in the thalassemia major and S-beta-thalassemia patients. Nearly all sickle cell anemia patients carried the beta S mutation on a chromosome with haplotype 19 (or Benin) and all had severe anemia with sickling complications. Identification of the beta S haplotype was through dot-blot analysis with oligonucleotide probes that detect mutations in the G gamma and A gamma promoter sequences, specific for this haplotype.

[Thalassemia intermedia. Report of two cases]. / Thalassémie intermédiaire. A propos de deux cas.

We report two cases of intermediate beta-thalassemia diagnosed at the age of 2 years and 3 1/2 years respectively. Characteristic features of this disease include delayed onset, moderate blood transfusion requirements, and frequent development of hypersplenism. Major iron overload develops even in patients who have received no transfusions. This disease is further characterized by significant genetic heterogeneity and by a reduction in the imbalance between produced chains and deficient chains.