HLA class I and class II polymorphisms in Tunisian Berbers.

BACKGROUND: The HLA polymorphism is a powerful genetic tool to study population origins. By analysing allele frequencies and haplotypes in different populations, it is possible to identify ethnic groups and establish the genetic relationships among them. AIM: The Berber (endogenous Tunisians) HLA class I and class II genotypes were analysed and compared with those of Mediterranean and Sub-Saharan African communities using genetic distances, Neighbour-Joining dendrograms, correspondence and haplotype analysis. SUBJECTS AND METHODS: One hundred and five unrelated Berbers were typed for HLA class I (A, B) and class II (DRB1, DQB1) gene alleles using reverse dot-blot hybridization. RESULTS: High frequencies of A*0201 (24.76%), A*3402 (22.38%) and B*44 (32.85%) alleles were recorded for Berbers, the highest recorded for Mediterranean and North African populations. This study shows a close relatedness of Tunisian Berbers to other Tunisians, North Africans and Iberians. CONCLUSION: The apparent relatedness of Tunisian Berbers to present-day (North African) Tunisians, Algerians and Moroccans suggests that the Arab invasion of North Africa (7(th)-11(th) centuries AD) did not significantly impact the genetic makeup of North Africans. Furthermore, Tunisian Berbers appear to be closely related to Iberians (Spaniards and Basques), indicating that the 7(th) century AD gene flow of invaders was low in Iberians and that the main part of their genetic pool came after the Northward Saharan migration, when hyper-arid conditions were established in Sahara (before 6000 BC). Other studied populations belong to the old Mediterranean substratum, which has been present in the area since pre-Neolithic times. This study indicates a higher proportion of Iberian than Arab ancestry in Tunisian Berbers, which is of value in evaluating the evolutionary history of present-day Tunisians. Greeks seem to share genetic HLA features (Chr 6) with Sub-Saharans. The relatedness of Greeks to Sub-Saharans has been confirmed by other studies based on chromosome 7 genetic markers.

Transfusion safety in the Maghreb region.

The Maghreb region comprises five countries: Algeria Libya, Morocco, Mauritania, and Tunisia. This is a review aiming at providing an update on the situation of transfusion in the five countries. Three countries have developed regulations covering all transfusion-related activities including policy development. All the countries are running blood safety activities using a National Blood Service as the main entity. Except for Mauritania and Lybia, all the blood safety activities are centralized and conducted regularly. The blood safety indicators are globally better compared to those of sub-Saharan Africa. Despite the efforts of the states of the Maghreb region, and the progress made in the field of transfusion in these countries, shortcomings persist and concern virtually all the key elements of a national blood supply system mainly in the quality management system.

HLA genes in Southern Tunisians (Ghannouch area) and their relationship with other Mediterraneans.

South Tunisian HLA gene profile has studied for the first time. HLA-A, -B, -DRB1 and -DQB1 allele frequencies of Ghannouch have been compared with those of neighboring populations, other Mediterraneans and Sub-Saharans. Their relatedness has been tested by genetic distances, Neighbor-Joining dendrograms and correspondence analyses. Our HLA data show that both southern from Ghannouch and northern Tunisians are of a Berber substratum in spite of the successive incursions (particularly, the 7th-8th century A.D. Arab invasion) occurred in Tunisia. It is also the case of other North Africans and Iberians. This present study confirms the relatedness of Greeks to Sub-Saharan populations. This suggests that there was an admixture between the Greeks and Sub-Saharans probably during Pharaonic period or after natural catastrophes (dryness) occurred in Sahara.

[HFE gene mutations in Tunisian major beta-Thalassemia and iron overload]. / Mutations du gène HFE chez des beta-thalassémiques majeurs tunisiens et surcharge en fer.

OBJECTIVES: In this study we have determined the allele frequency of HFE mutations H63D and C282Y in a group of Tunisian beta-thalassemia major patients. These two mutations are implicated in hereditary hemochromatosis among Caucasians. In this study we wanted to correlate these mutations with the iron status in major beta-thalassemia patients. DESIGN AND METHODS: Fifty Tunisian major beta-thalassemia were screening for the C282Y and H63D by digestion of polymerase chain reaction products (RFLP). Serum ferritin level was measured by immunoenzymatic microparticular essay. RESULTS: The allele frequency of H63D mutation was 17%. C282Y mutation was not present in our studied patients. No statistically significant difference of serum ferritin level was found between major beta-thalassemia with and without HFE mutations. CONCLUSION: Our results suggest that H63D mutation is so frequent in Tunisian major beta-thalassemia patients than in the general population and that the coinheritance of H63D mutation does not influence the severity of iron overload in these patients.

Detection of serum hemolysins in autoimmune hemolytic anemia.

BACKGROUND: Some patients with autoimmune hemolytic anemia (AIHA) have in their sera autohemolysins able to hemolyze RBCs in vitro by activation of complement. We describe three autohemolysins in patients with AIHA and we study clinical correlations. STUDY DESIGN AND METHODS: Thirty-two patients with AIHA were explored by immuno-hematological investigations (DAT, elution and serum testing). RESULTS: Three autohemolysins were detected in three patients. All of these autoantibodies were likely IgM and reacted in vitro only with enzyme-treated RBCs. Two warm autohemolysins were detected in patients with warm-type AIHA. The first one was active at neutral pH with low title. The second, having a wide thermal amplitude reacting at 22 degrees C and a title of 16, was acid. The hemolysin detected in patient 3 with cold hemagglutinin disease, was active at 4 and 22 degrees C, at acid pH. The thermal optimum was 4 degrees C and the title 64. It was also detected at 37 degrees C with the same title, but only at neutral pH. CONCLUSION: Although these autohemolysins were incomplete, hemolyzing in vitro only enzyme-treated RBCs, they were associated for the three patients with severe hemolysis.

First-line thalidomide-dexamethasone therapy in preparation for autologous stem cell transplantation in young patients (<61 years) with symptomatic multiple myeloma.

Thalidomide-dexamethasone therapy was given in patients (<61 years) with previously untreated symptomatic multiple myeloma. The aim of this study was to assess the efficacy and toxicity of this combination as first-line therapy, and to determine its effect on stem cell collection and engraftment. During first-line therapy, thalidomide and dexamethasone were administered for 75 days (200 mg/day) and 3 months, respectively. The monthly dose of dexamethasone was 20 mg/m2/day for 4 days, with cycles repeated on days 9 to 12 and 17 to 20 on the first and the third month of therapy. After first-line therapy, a collection of peripheral blood stem cells (PBSC) was performed. Between May 2003 and September 2004, 60 patients were included. On an intent-to-treat basis, the overall response (> or =partial response) rate was 74%, including 24% of patients who obtained a complete remission. Grade 3-4 toxicities consisted of infections (12%), deep-vein thrombosis (3%), constipation (5%), and neuropathy (5%). A total of 58 patients (96%) proceeded to PBSC mobilisation and yielded a median number of 8 x 10(6) CD34+ cells/kg. First-line thalidomide-dexamethasone therapy is effective and relatively well tolerated in young patients with symptomatic multiple myeloma. This combination does not affect PBSC mobilisation.

Contribution of flow cytometry to acute leukemia classification in Tunisia.

The precision of immunological characterization of leukemias was improved by a certain number of technical innovations, particularly hybridoma production and standardization, resulting in monoclonal antibodies and definition of recognised cellular antigens (designated by CD: Cluster of Differentiation). The aim of this work was to determine the immunophenotyping profile of patients with leukemia, by means of a flow cytometric method: 66 blood samples coming from leukemic persons in the Sahel region were studied by flow cytometry, using about thirty monoclonal antibodies all marked with a fluorochrome, in one or two colour systems to assess their distribution according to type (lymphoid B or T / myeloid) and age, and to search for possible co-expressions of markers of different lineages. The marked preponderance of childhood B-ALL in our series is, at least partly, attributable to the age distribution of the Tunisian population. In agreement with studies from other countries, the majority of AML cases occurred among adults. A high proportion of AML cases in our series co-expressed markers of other lineages. Overall, accurate classification of acute leukemias was possible from a simple peripheral blood sample in 62 of 66 cases (93.9%).

Rapid high-performance liquid chromatography analysis for the quantitative determination of oleuropein in Olea europaea leaves.

Olea europaea (Oleaceae) leaves of 14 different cultivars have been studied by a new isocratic HPLC method. Qualitative and quantitative determinations of principal compounds were established for each cultivar. Oleuropein concentration was determined for each sampled tree, using coumarin as internal standard. Bid el Haman, Chemlali, Meski, Cailletier, Tanche, a Verdale-Picholine hybrid, and Lucques, in particular, had high oleuropein concentrations and could be useful sources for industrial extractions.

[Screening and confirmation of anti-HCV antibodies in Tunisian blood donors]. / Dépistage et confirmation des anticorps anti-VHC chez les donneurs de sang tunisiens.

Antibodies to Hepatitis C virus (HCV) were tested in 43000 Tunisian blood donors by using enzyme immuno-assay. Our results show that 0.7% (304/43000) were anti-HVC positive. Of these 304.78 were confirmed anti-HCV positive (0.18%) by immuno-blot, and 99 displayed an indeterminate profile. Different immune responses were observed: In donors with positive serologic pattern (78/304), 25.6% response towards whole antigens (C + NS3 + NS4 + NS5) was frequently observed (44/78) 56.4%. Reactivity to 2 antigens was observed in 28.2% (22/78) and with 3 antigens in only 15.4% (12/78), with systematic reactivity to core. In donors with indeterminate serologic pattern (99/304) 32.5%, reactivity to non-structural antigen NS5 was the most frequently observed (54/99) 54.5%, reactivity to non-structural NS3 antigen was noted in 27.3% (27/99) and to core antigen in 18.2% (18/99). No donors with isolated reactivity to NS4 were observed in our series.

[Study of class I HLA polymorphism in the Tunisian population]. / Etude du polymorphisme HLA de classe I dans la population tunisienne.

The HLA class I gene polymorphism (HLA-A, -B) was investigated in a population of 102 Tunisians. Allele and haplotype frequencies as well as linkage disequilibrium between HLA-A and HLA-B loci were calculated and compared with other populations. The most frequent alleles were A2 (23%), A30 (12.5%), A3 (10.2%), A1 (8.5%), A23 (7.4%) for the HLA-A locus and B21 (14.3%), B44 (11.4%), B35 (9.6%), B5 (8.5%) for the HLA-B locus. The most frequent haplotype was A3 B21 (2.6%) and a positive linkage disequilibrium was found for the following allelic associations: A11 B35 (X2 = 6.8), A28 B35 (X2 = 5.3), and A30 B35 (X2 = 5). In conclusion, a specific distribution of HLA class I components in terms of antigen and haplotype frequencies characterizes the Tunisian population. This specific pattern may reflect the great ethnical diversity of this community. All these informations may be helpful in the future for HLA and disease association studies.

[ABO system polymorphism in the Tunisian population]. / Polymorphisme du système ABO dans la population tunisienne.

A survey carried out on 18820 Tunisian blood donors enabled us to evaluate the distribution of ABO blood group in Tunisia. The genic frequencies in ABO system were as follows: A(0,192), B(0,122), O(0,686).

[Bioavailability of acetylsalicylic acid administered orally or rectally in the rabbit]. / Biodisponibilité de l'acide acétylsalicylique administré par voie orale et rectale chez le lapin.

The aim of this study is to compare the bioavailability of acetylsalicylic acid administered rectally in suppositories form and orally in tablets form to the rabbit. Acetylsalicylic acid was given to 8 males rabbits rectally and orally in a balanced crossover design with 15 days of interval between each study. In blood samples, acetylsalicylic acid is determined by Trinder's method. It has been established that the rectal route has a faster absorption than the oral route however it displayed a more intense first pass effect than that of the oral route.

[Chromopharmacokinetics of acetylsalicylic acid administered rectally the rabbit]. / Chronopharmacocinétique de l'acide acétylsalicylique administré par voie rectale chez le lapin.

Five white rabbits are given by rectal route a single dose of 100 mg of Aspirin at regular hours: 7 a.m.; 10 a.m. and 2 p.m. the 7 a.m. administration results in lowest CMAX and AUC and the slowest elimination, whereas 10 a.m. and 2 p.m. administration results in the highest CMAX and AUC and shortest elimination time.

[The effect of certain active principles and excipients on the biodisposition of rectally administered acetylsalicylic acid in the rabbit]. / Influence de certains principes actifs et excipients sur la biodisponibilité de l'acide acétylsalicylique administré par voie rectale chez le lapin.

In this work, we have studied in the rabbit, bioavailability of acetylsalicylic acid contained respectively in three forms of suppositories which are made as follows: for the first by only acetylsalicyclic acid (0.1 g); for the second by the association: acetylsalicylic acid (0.1 g) and phenobarbital (0.01 g); and for the third by acetylsalicylic acid (0.01 g), ascorbic acid (0.02 g) and thiamine chloride (0.002 g). It has been shown that ascorbic acid and thiamine chloride do not change the bioavailability of acetylsalicylic acid, while phenobarbital decreases it. In this work we have also compared two pharmaceutical forms of suppositories containing acetylsalicylic acid, ascorbic acid and thiamine chloride. In one of the two forms, acetylsalicylic acid is buffered by glycocolle. The study which consisted in giving the two forms to the rabbit rectally was concerned with the effect of glycocolle on the bioavailability of acetylsalicylic acid. It was shown that making glycocolle a buffer to acetylsalicylic acid resulted in an improved absorption as well as a delayed elimination of acetylsalicyclic acid. In this study too, we have evaluated the bioavailability of acetylsalicylic acid which is released from two types of suppositories containing respectively base witepsol W31 and base cocoa butter. In order to study this bioavailability whole suppositories were administered by rectal route to the rabbits after 24 hours of fasting (balanced crossover design with 15 days of interval after each study). Statistical analysis does not reveal any significant difference between the two forms of suppositories.

[NA, a specific system for polymorphonuclear neutrophils: localization, biochemistry, genetics, frequency role in pathology]. / Na, le système spécifique des polymorphonucléaires neutrophiles: localisation, biochimie, génétique, fréquence et rôle en pathologie.

Among the neutrophil polynuclear specific antigens (NA, NB, ND, NE, ...), NA antigen is the most common. It is a glycoprotein situated on the neutrophils FcRIIIb-receptor and presents 2 forms: NA1 and NA2. The epitope responsible of that polymorphism has got an amino acids composition that is unknown. The first techniques used for their analysis were the microagglutination and the granulocytotoxicity-later, the immunofluorescence, the chemiluminescence and the MAIGA (Monoclonal Antibody Immobilized granulocyte Antigen) were introduced. These last years, more efficient techniques appeared like Flow Cytometry and Polymerase Chain Reaction (PCR) that allowed phenotyping and genotyping of neutrophil polymorphonuclear specific antigens. The studies indicated that NA antigen frequency varies according to the populations and the ethnics. NA2 allelic form is more frequent than NA1 in the caucasian population (88% VS 46%). In human pathology, NA antigen is implicated in the physiopathological mechanisms of the alloimmune and probably auto-immune neutropenies.

[Valeriana officinalis and Crataegus oxyacantha: toxicity from repeated administration and pharmacologic investigations]. / Valeriana officinalis et Crataegus oxyacantha: toxicité par administrations réitérées et investigations pharmacologiques.

The aim of this work is to study the toxicity of Valeriana officinalis and Crataegus oxyacantha after reiterated administrations. The study has been carried on the rat which received 300 and 600 mg/kg/24 h of the drugs for 30 days. During the period of the treatment, animals weight and blood pressure have been measured. On the end of the treatment the animals have been sacrificed. The principal organs have been weighed and in blood samples collected hematological and biochemical parameters have been determined. This work is concerned by pharmacological properties which are related to the two plants. The influence of the drugs on the behaviour, the pain, the intestinal peristalsis and strychnine convulsions are reported.

[A human recombinant erythropoietin produced in human lymphoblastoid cells]. / L'érythropoïétine humaine recombinante produite dans des cellules lymphoblastoïdes humaines.

A human recombinant erythropoietin is produced by transfection of a human EBV immortalised lymphoblastoid cell line by human erythropoietin gene. This cell line was selected because it is eucaryotic, human, able to grow in suspension and neither clonogenic nor tumorigenic. Purification of erythropoietin from culture supernatants of lymphoblastoid cells was described and structural, biochemical and functional characteristics were investigated in several studies. Results obtained for this kind of recombinant erythropoietin were similar to those obtained regarding the protein expressed in CHO cells suggesting that both molecules have the same efficiency in clinical applications.

[Calendula arvensis L. Impact of saponins on toxicity, hemolytic effect, and anti-inflammatory activity]. / Calendula arvensis L. Impact des saponines sur la toxicité, le pouvoir hémolytique et l'activité anti-inflammatoire.

The study of the chemical composition of Calendula arvensis var. eu arvensis Maire reveals the presence of saponins. These saponins confer a haemolytic property on the plant. In our work we have, first determined the saponin responsible for the haemolytic property; and then we have studied the impact of the saponins on the acute toxicity and the anti-inflammatory activity induced by carrhageenin oedema.

[Autologous transfusion program]. / La transfusion autologue programmee.

The term autologous transfusion describes transfusion of any blood component that was donated by intended recipient. A recipient who serves as his or her own donor receives the safest possible transfusion in that the risks of transfusion-transmitted infection and alloimmunization are eliminated. A preoperative autologous transfusion program provides many benefits to the donor-patient the blood donor center and the hospital transfusion service; requires a good communication between the transfusion physician and the collecting facility and needs a rigorous technical organization of the blood bank to ovoid the human errors of testing and labeling. Underutilizaton of autologous blood programs in our country is possibly related to a lack of awareness on the part of all the contributors.

[Toxic effects induced by the repeat administration of Allium sativum L]. / Effets toxiques engendrés par une administration réitérée d'Allium sativum L.

Female and male rats were given 300 and 600 mg/kg/24 h of a Garlic bulb aqueous extract for 21 days. The results showed that garlic extract causes toxic effects affecting weight growth, biologic parameters and histologic structures.