203 results on '"Mohamed, Bejaoui"'
Search Results
2. Theoretical Modeling of Sr(q+) He (q = 0, 1, 2) van der Waals Systems Including Spin–Orbit Coupling
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Mohamed Bejaoui, Wissem Zrafi, Jamila Dhiflaoui, and Hamid Berriche
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Chemistry ,QD1-999 - Published
- 2024
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3. Effect of PERLA®, a new cold-storage solution, on oxidative stress injury and early graft function in rat kidney transplantation model
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Mohamed Bejaoui, Chérifa Slim, Carmen Peralta, and Hassen Ben Abdennebi
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Oxidative stress ,Preservation solutions ,Kidney transplantation ,Ischemia reperfusion injury ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Abstract Background The composition of organ preservation solutions is crucial for maintaining graft integrity and early graft function after transplantation. The aim of this study is to compare new organ preservation solution PERLA® with the gold standard preservation solution University of Wisconsin (UW) regarding oxidative stress and early graft injury. Methods In order to assess oxidative stress after cold storage, kidney grafts have been preserved for 18 h at 4° C in either UW solution or PERLA® solution and then assessed for oxidative stress injury (protocol 1). To assess kidney injuries and oxidative stress after reperfusion, rat kidneys were harvested, stored in cold UW or in PERLA® solutions for 18 h at 4 °C and then transplanted heterotopically for 6 h (protocol 2). PERLA® is a high Na+/low K+ solution including PEG-35 (1 g/L), trimetazidine (1 µM), carvedilol (10 µM) and tacrolimus (5 µM). Results Our results showed that preservation of kidneys in PERLA® solution significantly attenuates oxidative stress parameters after cold storage and reperfusion. We found a significant decrease in oxidative damage indicators (MDA, CD and CP) and a significant increase in antioxidant indicators (GPx, GSH, CAT, SOD and PSH). Moreover, PERLA® solution decreased kidney injury after reperfusion (creatinine, LDH and uric acid). Conclusion PERLA® solution was more effective than UW storage solution in preserving rat’s kidney grafts.
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- 2024
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4. Pairwise Model Potential and DFT Study of Li+Nen Clusters (n = 1–20): The Structural, Electronic, and Thermodynamic Properties
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Nesrine Mabrouk, Jamila Dhiflaoui, Mohamed Bejaoui, Samah Saidi, and Hamid Berriche
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Chemistry ,QD1-999 - Published
- 2023
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5. Diagnostic challenge in a series of eleven patients with hyper IgE syndromes
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Roukaya Yaakoubi, Najla Mekki, Imen Ben-Mustapha, Leila Ben-Khemis, Asma Bouaziz, Ilhem Ben Fraj, Jamel Ammar, Agnès Hamzaoui, Hamida Turki, Lobna Boussofara, Mohamed Denguezli, Samir Haddad, Monia Ouederni, Mohamed Bejaoui, Koon Wing Chan, Yu Lung Lau, Fethi Mellouli, Mohamed-Ridha Barbouche, and Meriem Ben-Ali
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STAT3 deficiency ,DOCK8 deficiency ,differential diagnosis ,candidate gene strategy ,WES ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Hyper IgE syndromes (HIES) is a heterogeneous group of Inborn Errors of Immunity characterized by eczema, recurrent skin and lung infections associated with eosinophilia and elevated IgE levels. Autosomal dominant HIES caused by loss of function mutations in Signal transducer and activator of transcription 3 (STAT3) gene is the prototype of these disorders. Over the past two decades, advent in genetic testing allowed the identification of ten other etiologies of HIES. Although Dedicator of Cytokinesis 8 (DOCK8) deficiency is no more classified among HIES etiologies but as a combined immunodeficiency, this disease, characterized by severe viral infections, food allergies, autoimmunity, and increased risk of malignancies, shares some clinical features with STAT3 deficiency. The present study highlights the diagnostic challenge in eleven patients with the clinical phenotype of HIES in a resource-limited region. Candidate gene strategy supported by clinical features, laboratory findings and functional investigations allowed the identification of two heterozygous STAT3 mutations in five patients, and a bi-allelic DOCK8 mutation in one patient. Whole Exome Sequencing allowed to unmask atypical presentations of DOCK8 deficiency in two patients presenting with clinical features reminiscent of STAT3 deficiency. Our study underlies the importance of the differential diagnosis between STAT3 and DOCK8 deficiencies in order to improve diagnostic criteria and to propose appropriate therapeutic approaches. In addition, our findings emphasize the role of NGS in detecting mutations that induce overlapping phenotypes.
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- 2023
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6. Biochemical, Cellular, and Proteomic Characterization of Hereditary Spherocytosis Among Tunisians
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Nawel Trabelsi, Ghada Bouguerra, Faten Haddad, Monia Ouederni, Imen Darragi, Imen Boudrigua, Dorra Chaouachi, Mbarka Barmat, Chaker Fouzai, Mohamed Bejaoui, Samia Menif, Imen Kraiem, and Salem Abbes
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Physiology ,QP1-981 ,Biochemistry ,QD415-436 - Published
- 2021
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7. Consanguineous unions and endogamy in families of beta-thalassaemia patients from two Mediterranean populations: Tunisia and Italy
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Ramla Weslati, Monia Ouederni, Giovanbattista Ruffo, Monia Ben Khaled, Ridha Kouki, Caterine Di Girgenti, Zelia Borsellino, Irene Sammartano, Mohamed El Gazzah, Safia El- Bok, and Mohamed Bejaoui
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beta-thalassaemia ,tunisia ,italy ,consanguinity ,endogamy ,Biology (General) ,QH301-705.5 ,Human anatomy ,QM1-695 ,Physiology ,QP1-981 - Abstract
Background: Consanguinity increases the incidence of recessive diseases such as beta-thalassaemia major (βTM), one of the most prevalent lethal inherited diseases in the world. Aim: This study aims to identify the frequency of endogamy and consanguinity in two Mediterranean βTM populations and to study the implication of socio-economic factors. Subjects and methods: A trans-sectional study was conducted in 203 Tunisian families and 75 Italian families. Data were collected using a questionnaire completed by patients and parents. Results: Complete endogamy and consanguinity were observed in 82.75% and 62.56% of Tunisian families, respectively. Complete endogamy was found in 90.67% of Italian families, no consanguinity was noted. The low occupation status of Tunisian mothers was associated with an increasing frequency of consanguinity (p = .01) and endogamy (p = .0003). Consanguinity was associated with low education level (p = .012) and low occupation status (p=.047) of fathers. No significant association was found between endogamy and socio-economic factors in the Italian sample. Conclusions: High consanguinity and endogamy rates in Tunisian families may explain the frequency of βTM in Tunisia. The high endogamy rate in Italian families could also increase the frequency of βTM. Identification of geographical distribution and socio-economic factors leading to endogamy and consanguinity in these populations might help to improve βTM prevention.
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- 2019
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8. Spectroscopic, Structure, and Thermodynamic Properties of the Lithium Cation Emerged in the Small Neon Clusters Li+-Nen (n=1-20)
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Nesrine Mabrouk, Jamila Dhiflaoui, Mohamed Bejaoui, Samah Saidi, and Hamid Berriche
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The geometric structures and the relative stability of the Li+−Nen clusters, with n = 1–20, have been computed using pairwise model potential and density functional theory (DFT) method. The potential energy surface employed in these calculations is based on the Li+-Ne, Ne-Ne and many body interactions V3B. A series of methods and basis sets have been tested by reproduce correctly the experimental Li+-Ne and Ne-Ne potential energies. In addition, both Li+-Ne and Ne-Ne numerical potentials have been fitted by several analytical expressions as Tang and Toennies (TT), Extended Lennard Jones (ELJ) and Lennard-Jones (LJ) formula. The most stable structures of Li+-Nen clusters up to n = 20 have been optimized at Basin Hopping Monte Carlo (BHMC) method. The accuracy of our pairwise potential model has been confirmed by re-optimization at the DFT level of theory. The relative stabilities of Li+-Nen clusters are discussed by calculating the energy per neon atom, the first derivative, the fragmentation energy and the second derivative as well as the Highest Occupied Molecular orbital (HOMO)–Lowest Unoccupied Molecular Orbital(LUMO) energy gap with the size of the clusters. It was shown that n=6, 8, 12, 14, 16 and 17 correspond to the magic numbers. Finally, thermodynamic properties are calculated and showed that the formation process of Li+-Nen clusters is endothermic and non-spontaneous.
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- 2023
9. Long-Term Observational Study of Chronic Granulomatous Disease About 41 Patients From Tunisia and Comparison to Other Long-Term Follow-Up Studies
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Fethi Mellouli, Habib Ksouri, Maïssa Lajhouri, Monia Ben Khaled, Samia Rekaya, Elhem Ben Fraj, Monia Ouederni, Mohamed Ridha Barbouche, and Mohamed Bejaoui
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Tunisia ,Anti-Infective Agents ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Leukocytes, Mononuclear ,Quality of Life ,Humans ,Granulomatous Disease, Chronic ,Follow-Up Studies - Abstract
Chronic granulomatous disease (CGD) is an inherited autosomal recessive or X-Linked primitive immunodeficiency (PID), due to a defective nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex impairing anti-infectious and anti-inflammatory role of peripheral blood mononuclear cells. It is characterized by severe bacterial and fungal infections and by excessive inflammation leading to granulomatous complications. This work was made over a period of 34 years on 41 Tunisian patients suffering from CGD. Cumulative follow-up of patients was 2768.5 months, median 31 months. Survival was studied by survival curves according to Kaplan-Meier method. Lymphatic nodes, pulmonary and cutaneous infections predominate as revealing manifestations and as infectious events during patients’ monitoring. At study end 12 patients died mainly of invasive pulmonary aspergillosis and septicemia. Median age of death was 30 months. CGD remains compatible with a decent quality of life. Early diagnosis, anti-infectious prophylaxis, and initiation of adequate management, as soon as complication is perceived, promote pretty good evolution.
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- 2022
10. Phenotypic and molecular genetic analysis of Pyruvate Kinase deficiency in a Tunisian family
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Mouna, Jaouani, Nadia, Hamdi, Leila, Chaouch, Miniar, Kalai, Fethi, Mellouli, Imen, Darragi, Imen, Boudriga, Dorra, Chaouachi, Mohamed, Bejaoui, and Salem, Abbes
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- 2016
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11. Effect of the Non-steroidal Anti-inflammatory Drug Diclofenac on Ischemia–Reperfusion Injury in Rat Liver: A Nitric Oxide-Dependent Mechanism
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Roua Chaabani, Mohamed Bejaoui, Ikram Ben Jeddou, Mohamed Amine Zaouali, Zohra Haouas, Sameh Belgacem, Carmen Peralta, and Hassen Ben Abdennebi
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Immunology ,Immunology and Allergy - Published
- 2023
12. Electronic structure, cold ion–atom elastic collision properties and possibility of laser cooling of BeCs+ molecular ion
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Hela Ladjimi, Wissem Zrafi, Mohamed Farjallah, Mohamed Bejaoui, and Hamid Berriche
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General Physics and Astronomy ,Physical and Theoretical Chemistry - Abstract
We highlight the spectroscopic and electronic structure of BeCs+ ion, theoretically investigating ground and low lying excited states as well as the cold ion–atom elastic collisions proprieties and laser cooling possibility.
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- 2022
13. CUTANEOUS MANIFESTATIONS OF PRIMARY IMMUNODEFICIENCY DISEASES IN TUNISIAN CHILDREN
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Naouel GUIRAT, Monia Ben Khaled, Monia Ouederni, Imen Ben-Mustapha, Ridha Kouki, Habib Besbes, Mohamed Ridha Barbouche, Fethi Mellouli, and mohamed bejaoui
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Primary Immunodeficiency ,Skin ,Child ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Abstract. Skin manifestations are frequent among patients with primary immunodeficiency diseases (PIDs). Their prevalence varies according to the type of immunodeficiency. This review provides the reader with an up-to-date summary of the common dermatologic manifestations of PIDs among Tunisian children. We conducted a prospective study on two hundred and ninety children with immune deficiency. Demographic details (including age, sex, and consanguinity) with personal and family history were recorded. Special attention was paid to cutaneous manifestations. Dermatological involvements were grouped according to the etiology of their most prominent sign. Cutaneous manifestations were found in 164 patients (56.5%). They revealed the diagnosis of PIDs in 71 patients (24.5 %). The mean age at presentation was 21 months. Overall the most prominent cutaneous alterations were infectious. They accounted for 106 cases (36.55%). The most prevalent causes of cutaneous infections were bacterial: 93 cases (32.06%). Immuno-allergic skin diseases were among the common findings in our study. These include eczematous dermatitis found in 62 cases (21.38%). Malignancy related PIDs was seen in a boy with Wiskott Aldrich syndrome. He developed Kaposi’s sarcoma at the age of 14 months. Cutaneous changes are common among children with PIDs. In pediatric patients with failure to thrive, chronic refractory systemic manifestations often present in other family members, recurrent cutaneous infections unresponsive to adequate therapy, atypical forms of eczematous dermatitis or unusual features should arouse the suspicion of PIDs and prompt specialized immunologic consultation should be made.
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- 2018
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14. Clinical activity is an independent risk factor of ischemic heart and cerebrovascular arterial disease in patients with inflammatory bowel disease.
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Guillaume Le Gall, Julien Kirchgesner, Mohamed Bejaoui, Cécilia Landman, Isabelle Nion-Larmurier, Anne Bourrier, Harry Sokol, Philippe Seksik, and Laurent Beaugerie
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Medicine ,Science - Abstract
BACKGROUND AND AIMS:In inflammatory bowel disease (IBD), the impact of established cardiovascular risk factors and disease-related factors on the risk of acute arterial events is still unclear. We aimed to identify risk factors of acute arterial events in patients with IBD. METHODS:All consecutive patients followed at Saint-Antoine Hospital between 1996 and 2015 with subsequent occurrence of acute arterial events (acute coronary syndrome or ischemic stroke) were identified. Traditional cardiovascular risk factors, treatment exposure, systemic inflammation (mean serum CRP level greater than or equal to 5 mg/L) and IBD clinical activity were assessed. A nested case-control study was performed including cases and controls without arterial ischemic event, matched on age, gender, and disease extent. RESULTS:A total of 30 patients (median age at acute vascular event occurrence: 42 years (interquartile range: 25-59)) developed acute coronary syndrome (n = 22) or ischemic stroke (n = 8). In univariate analysis, clinical disease activity and the persistence of systemic inflammation, diabetes, dyslipidemia and hypertension were significantly associated with an increased risk of acute arterial events. Neither protective nor aggravating effects associated with treatment exposure were identified. In multivariate analysis, the presence of diabetes (Odds ratio (OR): 14.5, 95% confidence interval (CI): 1.1-184.7) and clinical disease activity (OR: 10.4, 95% CI: 2.1-49.9) remained significantly associated with the risk of acute arterial event. CONCLUSION:Disease activity may have an independent impact on the risk of acute arterial events in patients with IBD. These findings may highlight new potential benefits of optimizing anti-inflammatory treatment in patients with persisting clinical activity.
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- 2018
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15. Containment of Local COVID-19 Outbreak Among Hematopoietic Stem Cell Transplant Recipients and Healthcare Workers in a Pediatric Stem Cell Unit
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Ikram Zaiter, Agnes Hamzaoui, Sahar Ben Ammar, Yosr Chebbi, Ilhem Ben Fradj, Wafa Achour, Nessrine Zekri, Oussema Bouabdallah, Fethi Mellouli, Asma Lachiheb, Takwa Lamouchi, Monia Ouederni, Ridha Kouki, Mohamed Bejaoui, Siwar Laajili, Monia Ben Khaled, and Samia Rekaya
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medicine.medical_specialty ,Tunisia ,Coronavirus disease 2019 (COVID-19) ,Health Personnel ,medicine.medical_treatment ,Immunology ,Hematopoietic stem cell transplantation ,Letter to Editor ,Disease Outbreaks ,Unit (housing) ,Medical microbiology ,Health care ,medicine ,Humans ,Immunology and Allergy ,Intensive care medicine ,SARS-CoV-2 ,business.industry ,Hematopoietic Stem Cell Transplantation ,COVID-19 ,Hematopoietic stem cell ,Outbreak ,Hospitals, Pediatric ,Transplant Recipients ,medicine.anatomical_structure ,Stem cell ,business - Published
- 2021
16. A 9month-old-boy with atypical hemophagocytic lymphohistiocytosis
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Monia Ouederni, MONIA BEN KHALED, Samia Rekaya, Ilhem Ben Fraj, Fethi Mellouli, and Mohamed Bejaoui
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Anemia, Neutropenia, , thrombocytopenia, hyperfeeeritinemia, Haemophagocytic lymphohistiocytosis ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Hemophagocytic lymphohistiocytosis is a life-threatening hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and histiocytes. Often, Hemophagocytic lymphohistiocytosis is an acquired syndrome. We report a case of a 9 month-old-boy presented with hepatosplenomegaly, severe anemia requiring repeated transfusions, thrombocytopenia, hypertriglyceridemia and very high hyperferritinemia. These clinical features of Hemophagocytic lymphohistiocytosis prompted a wide infectious and auto-immune request to be performed. After a wide diagnostic workup, he was referred to the immune hematologic unit, for hemophagocytic lymphohistiocytosis suspicion with unknown cause.
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- 2017
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17. Nitrite enhances liver graft protection against cold ischemia reperfusion injury through a NOS independent pathway
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Amani Cherif-Sayadi, Kaouther Hadj Ayed-Tka, Mohamed Amine Zaouali, Mohamed Bejaoui, Najet Hadj-Abdallah, Ahlem Bouhlel, and Hassen Ben Abdennebi
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Sodium nitrite ,NOS ,IGL-1 ,ischemia reperfusion injury ,antioxidant enzymes ,Medicine - Abstract
Introduction: Nitrite has been found to protect liver graft from cold preservation injury. However, the cell signaling pathway involved in this protection remains unclear. Here, we attempt to clarify if the NOS pathway by using the NOS inhibitor, L-NAME (L-NG-Nitroarginine methyl ester). Animals and methods: Rat livers were conserved for 24 h at 4°C in (IGL-1) solution enriched or not with nitrite at 50 nM. In a third group, rats were pretreated with 50 mg/kg of L-NAME before their liver procurement and preservation in IGL-1 supplemented with nitrite (50 nM) and L-NAME (1 mM). After 24 h of cold storage, rat livers were ex-vivo perfused at 37°C during 2 h. Control livers were perfused without cold storage. Results: Nitrite effectively protected the rat liver grafts from the onset of cold I/R injury. L-NAME treatment did not abolish the beneficial effects of nitrite. Liver damage, protein oxidation and lipid peroxidation remained at low levels in both nitrite-treated groups when compared to IGL-1 group. Antioxidant enzyme activities and functional parameters were unchanged after NOS inhibition. Conclusion: Despite NOS inhibition by L-NAME, nitrite can still provide hepatic protection during cold I/R preservation. This suggests that nitrite acts through a NOS-independent pathway.
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- 2017
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18. Genetic Approaches for Definitive Diagnosis of Agammaglobulinemia in Consanguineous Families
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Yu-Lung Lau, Najla Mekki, Lamia Gargouri, Imen Ben-Mustapha, Rachida Boukari, Abdelhamid Barakat, Mohamed Bejaoui, Zahra Aadam, Jouda Gamara, Koon Wing Chan, Nabil BelHadj-Hmida, Aziz Bousfiha, Beya Larguèche, Houcine Ben Ameur, Jing Yang, Fethi Mellouli, Amel Nedri, Nadia Kechout, Mohamed-Ridha Barbouche, and Meriem Ben-Ali
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Male ,0301 basic medicine ,Candidate gene ,Immunology ,Nonsense mutation ,Consanguinity ,Biology ,Gene mutation ,medicine.disease_cause ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,symbols.namesake ,0302 clinical medicine ,Agammaglobulinemia ,Exome Sequencing ,medicine ,Humans ,Immunology and Allergy ,Exome ,Exome sequencing ,Sanger sequencing ,Genetics ,Mutation ,Homozygote ,Infant, Newborn ,Infant ,Sequence Analysis, DNA ,CD79B ,Pedigree ,Phenotype ,030104 developmental biology ,Codon, Nonsense ,Child, Preschool ,North America ,symbols ,Female ,030215 immunology - Abstract
Autosomal recessive agammaglobulinemia (ARA) is a primary immunodeficiency characterized by absent peripheral B cells, severe hypogammaglobulinemia, and absent BTK gene mutations. In ARA, mutations occur in genes encoding the pre-B cell receptor (pre-BCR) or downstream signaling proteins. In this work, we used candidate gene and whole-exome sequencing to investigate the molecular basis of ARA in 6 patients from 4 consanguineous North-African families. Sanger sequencing of candidate genes encoding the pre-BCR components (ΙGΗΜ, CD79A, CD79B, IGLL1, and VPREB1) was initially performed and determined the genetic defect in five patients. Two novel mutations in IGHM (p.Val378Alafs*1 and p.Ile184Serfs*21) were identified in three patients from two unrelated kindred and a novel nonsense mutation was identified in CD79A (p.Trp66*) in two siblings from a third kindred. Whole-exome sequencing (WES) was performed on the sixth patient who harbored a homozygous stop mutation at position 407 in the RAG2 gene (p.Glu407*). We concluded that conventional gene sequencing, especially when multiple genes are involved in the defect as is the case in ARA, is costly and time-consuming, resulting in delayed diagnosis that contributes to increased morbidity and mortality. In addition, it fails to identify the involvement of novel and unsuspected gene defects when the phenotype of the patients is atypical. WES has the potential to provide a rapid and more accurate genetic diagnosis in ARA, which is crucial for the treatment of the patients.
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- 2019
19. Melatonin Modulates Endoplasmic Reticulum Stress and Akt/GSK3-Beta Signaling Pathway in a Rat Model of Renal Warm Ischemia Reperfusion
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Kaouther Hadj Ayed Tka, Asma Mahfoudh Boussaid, Mohamed Amine Zaouali, Rym Kammoun, Mohamed Bejaoui, Sonia Ghoul Mazgar, Joan Rosello Catafau, and Hassen Ben Abdennebi
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Cytology ,QH573-671 - Abstract
Melatonin (Mel) is widely used to attenuate ischemia/reperfusion (I/R) injury in several organs. Nevertheless, the underlying mechanisms remain unclear. This study was conducted to explore the effect of Mel on endoplasmic reticulum (ER) stress, Akt and MAPK cascades after renal warm I/R. Eighteen Wistar rats were randomized into three groups: Sham, I/R, and Mel + I/R. The ischemia period was 60 min followed by 120 min of reperfusion. Mel (10 mg/kg) was administrated 30 min prior to ischemia. The creatinine clearance, MDA, LDH levels, and histopathological changes were evaluated. In addition, Western blot was performed to study ER stress and its downstream apoptosis as well as phosphorylation of Akt, GSK-3β, VDAC, ERK, and P38. Mel decreased cytolysis and lipid peroxidation and improved renal function and morphology compared to I/R group. Parallely, it significantly reduced the ER stress parameters including GRP 78, p-PERK, XBP 1, ATF 6, CHOP, and JNK. Simultaneously, p-Akt level was significantly enhanced and its target molecules GSK-3β and VDAC were inhibited. Furthermore, the ERK and P38 phosphorylation were evidently augmented after Mel administration in comparison to I/R group. In conclusion, Mel improves the recovery of renal function by decreasing ER stress and stimulating Akt pathway after renal I/R injury.
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- 2015
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20. Correction: Carbonic Anhydrase Protects Fatty Liver Grafts against Ischemic Reperfusion Damage.
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Mohamed Bejaoui, Eirini Pantazi, Viviana De Luca, Arnau Panisello, Emma Folch-Puy, Georgina Hotter, Clemente Capasso, Claudiu T Supuran, and Joan Roselló-Catafau
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Medicine ,Science - Published
- 2015
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21. Carbonic Anhydrase Protects Fatty Liver Grafts against Ischemic Reperfusion Damage.
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Mohamed Bejaoui, Eirini Pantazi, Viviana De Luca, Arnau Panisello, Emma Folch-Puy, Georgina Hotter, Clemente Capasso, Claudiu T Supuran, and Joan Roselló-Catafau
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Medicine ,Science - Abstract
Carbonic anhydrases (CAs) are ubiquitous metalloenzymes that catalyze the reversible hydration of carbon dioxide to bicarbonate and a proton. CAs are involved in numerous physiological and pathological processes, including acid-base homeostasis, electrolyte balance, oxygen delivery to tissues and nitric oxide generation. Given that these processes are found to be dysregulated during ischemia reperfusion injury (IRI), and taking into account the high vulnerability of steatotic livers to preservation injury, we hypothesized a new role for CA as a pharmacological agent able to protect against ischemic damage. Two different aspects of the role of CA II in fatty liver grafts preservation were evaluated: 1) the effect of its addition to Institut Georges Lopez (IGL-1) storage solution after cold ischemia; 2) and after 24h of cold storage followed by two hours of normothermic ex-vivo perfusion. In all cases, liver injury, CA II protein concentration, CA II mRNA levels and CA II activity were determined. In case of the ex-vivo perfusion, we further assessed liver function (bile production, bromosulfophthalein clearance) and Western blot analysis of phosphorylated adenosine monophosphate activated protein kinase (AMPK), mitogen activated protein kinases family (MAPKs) and endoplasmic reticulum stress (ERS) parameters (GRP78, PERK, IRE, eIF2α and ATF6). We found that CA II was downregulated after cold ischemia. The addition of bovine CA II to IGL-1 preservation solution efficiently protected steatotic liver against cold IRI. In the case of reperfusion, CA II protection was associated with better function, AMPK activation and the prevention of ERS and MAPKs activation. Interestingly, CA II supplementation was not associated with enhanced CO2 hydration. The results suggest that CA II modulation may be a promising target for fatty liver graft preservation.
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- 2015
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22. 422.3: Using a New Preservation Solution Called Perla for Kidney Transplantation
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Marc Micó-Carnero, Mohamed Bejaoui, Charifa Slim, Cristina Maroto-Serrat, Silvina Ramella-Virieux, Javier Aguirrezabalaga, Carmen Peralta, and Hassen Ben-Abdennebi
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Transplantation - Published
- 2022
23. Retentissement psychosocial et scolaire de la bêta-thalassémie majeure en Tunisie
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Saïda Aroua, Mohamed Bejaoui, Manel Barouni, Fethi Mellouli, and Salem Abbes
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medicine.medical_specialty ,Social integration ,Public health ,medicine ,Psychology ,Psychiatry ,Pediatrics - Abstract
In Tunisia, beta-thalassemia major is a real public health problem. A study carried out of patients affected shows that for them, this chronic haemoglobinopathy is a disability hampering their physical activities, their social integration, their academic results and their emotional life.
- Published
- 2019
24. Biochemical, Cellular, and Proteomic Characterization of Hereditary Spherocytosis Among Tunisians
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Mohamed Bejaoui, Samia Menif, Mbarka Barmat, Salem Abbes, Imen Boudrigua, Imen Darragi, Imen Kraiem, Nawel Trabelsi, Dorra Chaouachi, Monia Ouederni, Faten Haddad, Ghada Bouguerra, and Chaker Fouzai
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Hemolytic anemia ,Adult ,Male ,Proteomics ,medicine.medical_specialty ,Tunisia ,Adolescent ,Physiology ,Physical examination ,Spherocytosis, Hereditary ,Gastroenterology ,lcsh:Physiology ,Hereditary spherocytosis ,lcsh:Biochemistry ,Internal medicine ,medicine ,Humans ,lcsh:QD415-436 ,Family history ,Child ,Band 3 ,biology ,medicine.diagnostic_test ,lcsh:QP1-981 ,business.industry ,Erythrocyte Membrane ,Erythrocyte fragility ,Infant ,Membrane Proteins ,Gel electrophoresis of proteins ,medicine.disease ,Flow Cytometry ,Osmotic Fragility ,Membrane protein ,Child, Preschool ,biology.protein ,Eosine Yellowish-(YS) ,Female ,business - Abstract
Background/Aims: Hereditary Spherocytosis (HS) is the most common erythrocyte membrane disorder causing hemolytic anemia. The wide heterogeneity of both clinical and laboratory manifestations of HS contributes to difficulties associated with the diagnosis of this disorder. Although massive data previously reported worldwide, there is yet no data on HS among the Tunisian population. Here we aim to characterize HS in Tunisian patients at biochemical and cellular levels, identify the membrane protein deficiency, and compare the accuracy of the diagnostic tests to identify the most appropriate assay for HS diagnosis. Methods: We investigated 81 patients with hemolytic anemia and 167 normal controls. The exploration of HS based on clinical and family history, physical examination, and the results of laboratory tests: blood smear, osmotic fragility test (OFT), cryohemolysis test (CT), pink test (PT), eosine-5’-maleimide (EMA) test, and erythrocyte membrane protein electrophoresis. Results: We identified 21 patients with HS, classified as severe (6/21;28.5%), moderate (10/21;47.6%), and mild (5/21;23.8%). The most prevalent protein deficiency was the band 3 protein detected in ten Tunisian HS patients. The EMA test showed a high specificity (97.5%) and sensitivity (94.7%) for HS diagnosis compared to the other screening tests. Interestingly, fourteen among sixteen patients presenting with homozygous sickle cells HbSS showed an increase of EMA fluorescence intensity compared to other anemic patients. Conclusion: Our study highlights the efficiency of the EMA dye for the detection of HS whatever the nature of the involved protein deficiency. We report for the first time, the most prevalent protein deficiency among Tunisians with HS. Moreover, we found that the combination of the EMA-binding test with PT or incubated OFT improves the diagnosis sensitivity while maintaining a good specificity.
- Published
- 2021
25. BETA THALASSEMIA MAJOR IN A DEVELOPING COUNTRY: EPIDEMIOLOGICAL, CLINICAL AND EVOLUTIONARY ASPECT
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Mohamed Bejaoui and Naouel Guirat
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Beta-thalassemia major, transfusions, iron overload, chelation, Tunisia ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Beta-thalassemia major (TM) remains to be one of the major health problems particularly in developing countries. Tunisia is a part of the Mediterranean countries mostly affected by this disease which is highly concentrated in small towns in families with low-income earners. The main objectives of this study are to provide a description of the demographic, clinical features and transfusion-related complications in patients with TM living in Tunisia. A standardized questionnaire was sent to clinicians throughout 33 different medical institutions caring for thalassemic patients. 391 transfusion dependant thalassemic patients with a median age of 10.7 years (range 3 months- 31 years) were included in the study.The majority were originated from the north west of the country .A moderate overload between 1501 and 2500ng/ml was found in 61patients, while 81 patients (26.9%) had ferritin level more than 2500 ng/ml and greater than 5000ng/ml in 21 patients (6.9%). 51 patients died from complications related to their disease. Heart failure was the main cause of death. The incidence of cardiac, endocrine, and infectious complications will be reviewed. Preventive measures such as health education, carrier screening and premarital screening remain the best ways for lowering the incidence of these diseases, which might be reflected in financial saving, social benefits and health benefits.
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- 2013
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26. Polyethylene glycol as a potential adjuvant treatment for COVID-19-induced ARDS
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Mohamed Bejaoui
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myalgia ,ARDS ,Lung ,business.industry ,medicine.medical_treatment ,Polyethylene glycol ,Pharmacology ,medicine.disease_cause ,medicine.disease ,chemistry.chemical_compound ,medicine.anatomical_structure ,Cytokine ,chemistry ,PEG ratio ,medicine ,medicine.symptom ,business ,Adjuvant ,Coronavirus - Abstract
Coronavirus disease 2019 (COVID-19), an infectious disease caused by the novel coronavirus SARS-CoV-2, represent an ongoing global health emergency. Common symptoms are mild including fever, cough, myalgia and difficulty breathing. In patients most severely affected, COVID-19 can be complicated by the acute respiratory distress syndrome (ARDS). The management of ARDS mainly focuses on the provision of supportive care, e.g., oxygenation, ventilation, and fluid management. Polyethylene glycol (PEG) is a water soluble non-toxic polymer approved by FDA and widely used in food, cosmetics and pharmaceutics. PEG has interesting properties that makes it suitable for use as an adjuvant treatment in COVID-19 patient with ARDS: (1) PEG could create a physical barrier that inhibits virus entry and invasion; (2) PEG reduces inactivation and enhances the surface activity of pulmonary surfactant; (3) PEG decrease cytokine release and (4) PEG preserve lung endothelial cells integrity.
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- 2020
27. Effect of oleuropein on oxidative stress, inflammation and apoptosis induced by ischemia-reperfusion injury in rat kidney
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Victoria Wilke, Hana Nasrallah, Mohamed Bejaoui, Hichem Ben Jannet, Imen Aissa, Mohamed Amine Zaouali, Habib Mosbah, Mohamed Ali Boujbiha, Chérifa Slim, and Hassen Ben Abdennebi
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0301 basic medicine ,Male ,Time Factors ,Iridoid Glucosides ,Ischemia ,Anti-Inflammatory Agents ,Apoptosis ,Pharmacology ,medicine.disease_cause ,Kidney ,030226 pharmacology & pharmacy ,General Biochemistry, Genetics and Molecular Biology ,Antioxidants ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Enos ,Lactate dehydrogenase ,medicine ,Animals ,Iridoids ,General Pharmacology, Toxicology and Pharmaceutics ,Rats, Wistar ,Inflammation ,Creatinine ,biology ,Dose-Response Relationship, Drug ,Chemistry ,General Medicine ,medicine.disease ,biology.organism_classification ,Rats ,Oxidative Stress ,030104 developmental biology ,medicine.anatomical_structure ,Reperfusion Injury ,Uric acid ,Reperfusion injury ,Oxidative stress - Abstract
Aims This study aimed to evaluate the effect of oleuropein (OLE), the main phenolic compound present in olive leaves, on kidney ischemia-reperfusion injury (IRI) and to explore the underlying protective mechanism. Main methods Rat kidneys were subjected to 60 min of bilateral warm ischemia followed by 120 min of reperfusion. OLE was administered orally 48 h, 24 h and 30 min prior to ischemia at doses of 10, 50 and 100 mg/kg body weight. The creatinine, urea, uric acid concentrations and lactate dehydrogenase (LDH) activity in plasma were evaluated. Oxidative stress and inflammation parameters were also assessed. Renal expression of AMP-activated protein kinase (p-AMPK), endothelial nitric oxide synthase (eNOS), mitogen-activated protein kinases (MAPK), inflammatory proteins and apoptotic proteins were evaluated using Western blot. Key findings Our results showed that OLE at 50 mg/kg reduced kidney IRI as revealed by a significant decrease of plasmatic creatinine, urea, uric acid concentrations and LDH activity. In parallel, OLE up-regulated antioxidant capacities. Moreover, OLE diminished the level of CRP and the expression of cyclooxygenase 2 (COX-2). Finally, OLE enhanced AMPK phosphorylation as well as eNOS expression whereas MAPK, and cleaved caspase-3 implicated in cellular apoptosis were attenuated in the ischemic kidneys. Significance In conclusion, this study shows that OLE could be used as therapeutic agent to reduce IRI through its anti-oxidative, anti-inflammatory and anti-apoptotic properties.
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- 2020
28. Evaluation of the efficacy and safety of deferiprone compared with deferasirox in paediatric patients with transfusion-dependent haemoglobinopathies (DEEP-2): a multicentre, randomised, open-label, non-inferiority, phase 3 trial
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Oscar Della Pasqua, Laila M. Sherief, Amal El-Beshlawy, Paul Telfer, Adriana Ceci, Liana Cuccia, Bianca Tempesta, Donato Bonifazi, Hoda Hassab, Mohamed Bejaoui, Yu Chung Tsang, Carlo Cosmi, Giovanni Carlo Del Vecchio, Antonis Kattamis, Soteroula Christou, Angela Vitrano, Giorgio Reggiardo, Ariana Zaka, Manika Kreka, Raffaella Origa, Aldo Filosa, Mariagrazia Felisi, Fernando Tricta, Aurelio Maggio, Michael Spino, and Maria Caterina Putti
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Male ,Administration, Oral ,law.invention ,chemistry.chemical_compound ,0302 clinical medicine ,Randomized controlled trial ,law ,Deferiprone ,Child ,education.field_of_study ,Greece ,Hematology ,Magnetic Resonance Imaging ,Deferoxamine ,Treatment Outcome ,Italy ,030220 oncology & carcinogenesis ,Child, Preschool ,Albania ,Egypt ,Female ,Erythrocyte Transfusion ,medicine.drug ,Agranulocytosis ,Urologic Diseases ,medicine.medical_specialty ,Iron Overload ,Tunisia ,Adolescent ,Anemia ,Population ,Anemia, Sickle Cell ,Iron Chelating Agents ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,education ,Adverse effect ,business.industry ,Deferasirox ,beta-Thalassemia ,Infant ,medicine.disease ,United Kingdom ,Clinical trial ,Hemoglobinopathies ,Cardiac Imaging Techniques ,chemistry ,Cyprus ,Ferritins ,Patient Compliance ,business ,030215 immunology - Abstract
Transfusion-dependent haemoglobinopathies require lifelong iron chelation therapy with one of the three iron chelators (deferiprone, deferasirox, or deferoxamine). Deferasirox and deferiprone are the only two oral chelators used in adult patients with transfusion-dependent haemoglobinopathies. To our knowledge, there are no randomised clinical trials comparing deferiprone, a less expensive iron chelator, with deferasirox in paediatric patients. We aimed to show the non-inferiority of deferiprone versus deferasirox.DEEP-2 was a phase 3, multicentre, randomised trial in paediatric patients (aged 1 month to 18 years) with transfusion-dependent haemoglobinopathies. The study was done in 21 research hospitals and universities in Italy, Egypt, Greece, Albania, Cyprus, Tunisia, and the UK. Participants were receiving at least 150 mL/kg per year of red blood cells for the past 2 years at the time of enrolment, and were receiving deferoxamine (100 mg/kg per day) or deferasirox (40 mg/kg per day; deferasirox is not registered for use in children aged2 years so only deferoxamine was being used in these patients). Any previous chelation treatment was permitted with a 7-day washout period. Patients were randomly assigned 1:1 to receive orally administered daily deferiprone (75-100 mg/kg per day) or daily deferasirox (20-40 mg/kg per day) administered as dispersible tablets, both with dose adjustment for 12 months, stratified by age (10 years and ≥10 years) and balanced by country. The primary efficacy endpoint was based on predefined success criteria for changes in serum ferritin concentration (all patients) and cardiac MRI T2-star (T2*; patients aged10 years) to show non-inferiority of deferiprone versus deferasirox in the per-protocol population, defined as all randomly assigned patients who received the study drugs and had available data for both variables at baseline and after 1 year of treatment, without major protocol violations. Non-inferiority was based on the two-sided 95% CI of the difference in the proportion of patients with treatment success between the two groups and was shown if the lower limit of the two-sided 95% CI was greater than -12·5%. Safety was assessed in all patients who received at least one dose of study drug. This study is registered with EudraCT, 2012-000353-31, and ClinicalTrials.gov, NCT01825512.435 patients were enrolled between March 17, 2014, and June 16, 2016, 393 of whom were randomly assigned to a treatment group (194 to the deferiprone group; 199 to the deferasirox group). 352 (90%) of 390 patients had β-thalassaemia major, 27 (7%) had sickle cell disease, five (1%) had thalassodrepanocytosis, and six (2%) had other haemoglobinopathies. Median follow-up was 379 days (IQR 294-392) for deferiprone and 381 days (350-392) for deferasirox. Non-inferiority of deferiprone versus deferasirox was established (treatment success in 69 [55·2%] of 125 patients assigned deferiprone with primary composite efficacy endpoint data available at baseline and 1 year vs 80 [54·8%] of 146 assigned deferasirox, difference 0·4%; 95% CI -11·9 to 12·6). No significant difference between the groups was shown in the occurrence of serious and drug-related adverse events. Three (2%) cases of reversible agranulocytosis occurred in the 193 patients in the safety analysis in the deferiprone group and two (1%) cases of reversible renal and urinary disorders (one case of each) occurred in the 197 patients in the deferasirox group. Compliance was similar between treatment groups: 183 (95%) of 193 patients in the deferiprone group versus 192 (97%) of 197 patients in the deferisirox group.In paediatric patients with transfusion-dependent haemoglobinopathies, deferiprone was effective and safe in inducing control of iron overload during 12 months of treatment. Considering the need for availability of more chelation treatments in paediatric populations, deferiprone offers a valuable treatment option for this age group.EU Seventh Framework Programme.
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- 2020
29. A phase 3 trial of luspatercept in patients with transfusion-dependent β-thalassemia
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Antonis Kattamis, Soo-Min Lim, Silverio Perrotta, Jeevan K Shetty, Yesim Aydinok, Matthew L. Sherman, Kevin H. Kuo, Ersi Voskaridou, John Porter, Gian Luca Forni, Vip Viprakasit, Peter G. Linde, Abderrahmane Laadem, Pencho Georgiev, Jun Zou, Mohamed Bejaoui, Lee-Ping Chew, Meng-Yao Lu, Efthymia Vlachaki, Penka Ganeva, Believe Investigators, Ashutosh Lal, Olivier Hermine, Idit Pazgal-Kobrowski, Antonio Piga, Farrukh Shah, M. Domenica Cappellini, Liana Gercheva, Alexis A. Thompson, Ali T Taher, Adisak Tantiworawit, Raffaella Origa, Ellis J Neufeld, Abderrahim Khelif, P Joy Ho, Thomas D. Coates, Jennie Zhang, Hong-Keng Liew, Ping Chong Bee, Dimana Miteva, Tatiana Zinger, Domenica Cappellini, M., Viprakasit, V., Taher, A. T., Georgiev, P., Kuo, K. H. M., Coates, T., Voskaridou, E., Liew, H. -K., Pazgal-Kobrowski, I., Forni, G. L., Perrotta, S., Khelif, A., Lal, A., Kattamis, A., Vlachaki, E., Origa, R., Aydinok, Y., Bejaoui, M., Joy Ho, P., Chew, L. -P., Bee, P. -C., Lim, S. -M., Lu, M. -Y., Tantiworawit, A., Ganeva, P., Gercheva, L., Shah, F., Neufeld, E. J., Thompson, A., Laadem, A., Shetty, J. K., Zou, J., Zhang, J., Miteva, D., Zinger, T., Linde, P. G., Sherman, M. L., Hermine, O., Porter, J., Piga, A., and Ege Üniversitesi
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Male ,Immunoglobulin Fc Fragment ,Intention to Treat Analysi ,medicine.medical_treatment ,Thalassemia ,Activin Receptors, Type II ,030204 cardiovascular system & hematology ,Gastroenterology ,law.invention ,0302 clinical medicine ,Randomized controlled trial ,law ,Odds Ratio ,030212 general & internal medicine ,General Medicine ,Middle Aged ,Intention to Treat Analysis ,Luspatercept ,Recombinant DNA ,Splenectomy ,Female ,Erythrocyte Transfusion ,Human ,Adult ,medicine.medical_specialty ,Adolescent ,Recombinant Fusion Proteins ,03 medical and health sciences ,Young Adult ,Double-Blind Method ,Hematinic ,Internal medicine ,medicine ,Humans ,Least-Squares Analysis ,Aged ,Least-Squares Analysi ,Ferritin ,business.industry ,beta-Thalassemia ,medicine.disease ,Fusion protein ,Immunoglobulin Fc Fragments ,Clinical trial ,Ferritins ,Hematinics ,business ,Transforming growth factor ,Recombinant Fusion Protein - Abstract
BACKGROUND Patients with transfusion-dependent ?-thalassemia need regular red-cell transfusions. Luspatercept, a recombinant fusion protein that binds to select transforming growth factor ? superfamily ligands, may enhance erythroid maturation and reduce the transfusion burden (the total number of red-cell units transfused) in such patients. METHODS In this randomized, double-blind, phase 3 trial, we assigned, in a 2:1 ratio, adults with transfusion-dependent ?-thalassemia to receive best supportive care plus luspatercept (at a dose of 1.00 to 1.25 mg per kilogram of body weight) or placebo for at least 48 weeks. The primary end point was the percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval. Other efficacy end points included reductions in the transfusion burden during any 12-week interval and results of iron studies. RESULTS A total of 224 patients were assigned to the luspatercept group and 112 to the placebo group. Luspatercept or placebo was administered for a median of approximately 64 weeks in both groups. The percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval was significantly greater in the luspatercept group than in the placebo group (21.4% vs. 4.5%, P, Abbott Laboratories Novartis Alexion Pharmaceuticals Terumo BCT Celgene FibroGen: 7,988,973, 8,007,809, 8,895,016 Novartis Pharma Acceleron Vifor Pharma, Supported by Celgene in collaboration with Acceleron Pharma. Dr. Cappellini reports receiving grant support, paid to her institution, and advisory board fees from Celgene; Dr. Viprakasit, receiving consulting fees from Celgene; Dr. Taher, receiving research funding and consulting fees from Celgene; Dr. Georgiev, receiving grant support from Celgene; Dr. Kuo, receiving advisory board fees from Agios Pharmaceuticals, Apellis Pharmaceuticals, and Celgene, lecture fees and advisory board fees from Alexion Pharmaceuticals, fees for serving on a data and safety monitoring board from Bioverativ Therapeutics, consulting fees from Bluebird Bio, lecture fees and consulting fees from Novartis, and grant support and consulting fees from Pfizer; Dr. Coates, receiving advisory board fees from Agios Pharmaceuticals and Celgene and advisory board fees and consulting fees from ApoPharma; Dr. Liew, receiving grant support, paid to his institution, from Celgene; Dr. Forni, receiving advisory board fees from Bluebird Bio, Celgene, and Novartis Pharma; Dr. Lal, receiving grant support, paid to his institution, from Bluebird Bio, Insight Magnetics, La Jolla Pharmaceutical Company, Novartis, Protagonist Therapeutics, and Terumo BCT, and grant support, paid to his institution, and advisory board fees from Celgene; Dr. Kattamis, receiving advisory board fees, fees for serving on a steering committee, and travel support from Celgene, grant support, paid to his institution, and advisory board fees from Novartis, fees for serving on a trial steering committee from Vertex Pharmaceuticals, and advisory board fees from Vifor Pharma; Dr. Origa, receiving grant support from Celgene; Dr. Aydinok, receiving grant support, paid to Ege University Hospital, from Celgene; Dr. Shah, receiving advisory board fees from Bluebird Bio and Roche, advisory board fees, lecture fees, and fees for serving on a steering committee from Celgene, advisory board fees and lecture fees from Novartis, and lecture fees from Sobi; Dr. Neufeld, receiving fees for serving on a data and safety monitoring board and consulting fees from Acceleron Pharma, fees for serving on a data and safety monitoring board from ApoPharma, advisory board fees and fees for serving on a steering committee from Celgene, and advisory board fees and consulting fees from Novartis Pharma; Dr. Thompson, receiving grant support, paid to her institution, from Baxalta and BioMarin Pharmaceuticals, and grant support, paid to her institution, and consulting fees from Bluebird Bio, Celgene, and Novartis Pharma; Dr. Shetty, being employed by Celgene; Dr. Zhang, being employed by and owning stock and stock options in Celgene; Dr. Miteva, being employed by Celgene; Dr. Zinger, being employed by and owning stock options in Celgene; Dr. Linde, being employed by and owning stock in Acceleron Pharma and owning stock in Abbott Laboratories and FibroGen; Dr. Sherman, being employed by and receiving consulting fees from Acceleron Pharma and Deciphera Pharmaceuticals, receiving consulting fees from Fusion Pharma and Mersana Therapeutics and fees for serving as a board member from Newlink Genetics, Pieris Pharmaceuticals, and Pulmatrix, and holding patents 10,093,707, 8,007,809, 8,895,016, and 7,988,973 on antagonists of activin-ActRIIA and uses for increasing red-cell levels, licensed to Acceleron Pharma; Dr. Hermine, receiving grant support from Alexion Pharmaceuticals, Celgene, and Takeda California; Dr. Porter, receiving lecture fees and advisory board fees from Agios Pharmaceuticals, advisory board fees and presentation fees from Bluebird Bio, advisory board fees from Celgene, and fees for serving on a steering committee from Vifor Pharma; and Dr. Piga, receiving grant support, paid to his institution, from Acceleron and grant support, paid to his institution, and advisory fees from Celgene. No other potential conflict of interest relevant to this article was reported. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. A data sharing statement provided by the authors is available with the full text of this article at NEJM.org. We thank the patients and families who participated in the BELIEVE trial; the investigators who collaborated in the trial; personnel at Acceleron Pharma, including Kenneth M. Attie, Xiaosha Zhang, Carolyn J. Barron, Joseph G. Reynolds, John Oram, and Tad Akers; and Daria I. Grisanzio of Excerpta Medica and Khaled Musallam and Hannah Wills of AMICULUM for writing assistance with an earlier version of the manuscript.
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- 2020
30. Consanguineous unions and endogamy in families of beta-thalassaemia patients from two Mediterranean populations: Tunisia and Italy
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Mohamed Bejaoui, Ramla Weslati, Monia Ben Khaled, Ridha Kouki, Monia Ouederni, Giovanbattista Ruffo, Safia El-Bok, Caterine Di Girgenti, Zelia Borsellino, Mohamed El Gazzah, and Irene Sammartano
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0301 basic medicine ,Mediterranean climate ,Adult ,Male ,Aging ,Tunisia ,Adolescent ,Physiology ,Epidemiology ,Consanguinity ,Biology ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Genetics ,Humans ,030216 legal & forensic medicine ,Marriage ,Child ,Incidence (epidemiology) ,beta-Thalassemia ,Public Health, Environmental and Occupational Health ,Infant ,Beta-thalassaemia ,030104 developmental biology ,Italy ,Socioeconomic Factors ,Endogamy ,Child, Preschool ,Female ,Demography - Abstract
Background: Consanguinity increases the incidence of recessive diseases such as beta-thalassaemia major (βTM), one of the most prevalent lethal inherited diseases in the world.Aim: This study aims ...
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- 2019
31. Investigation of the electronic structure of Be2+He and Be+He, and static dipole polarisabilities of the helium atom
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Mohamed Farjallah, Hamid Berriche, Mohamed Bejaoui, and J. Dhiflaoui
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Physics ,010304 chemical physics ,Helium atom ,Biophysics ,Electronic structure ,Electron ,010402 general chemistry ,Condensed Matter Physics ,01 natural sciences ,Potential energy ,0104 chemical sciences ,chemistry.chemical_compound ,Dipole ,symbols.namesake ,chemistry ,Excited state ,0103 physical sciences ,symbols ,Physical and Theoretical Chemistry ,Atomic physics ,van der Waals force ,Ground state ,Molecular Biology - Abstract
The potential energy and spectroscopic constants of the ground and many excited states of the Be+He van der Waals system have been investigated using a one-electron pseudo-potential approach, which is used to replace the effect of the Be2+ core and the electron-He interactions by effective potentials. Furthermore, the core–core interactions are incorporated. This permits the reduction of the number of active electrons of the Be+He van der Waals system to only one electron. Therefore, the potential energy of the ground state as well as the excited states is performed at the SCF level and considering the spin–orbit interaction. The core–core interaction for Be2+He ground state is included using accurate CCSD (T) calculations. Then, the spectroscopic properties of the Be+He electronic states are extracted and compared with the previous theoretical and experimental studies. This comparison has shown a very good agreement for the ground and the first excited states. Moreover, the transition dipole mome...
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- 2018
32. Les modèles explicatifs de causalité de la beta-thalassémie majeure
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Mohamed Bejaoui, Manel Barouni, Salem Abbes, Fethi Mellouli, and Saïda Aroua
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- 2017
33. Prevalence and predictive factors of splenic sequestration crisis among 423 pediatric patients with sickle cell disease in Tunisia
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Monia Ben Khaled, Ilhem Ben Fraj, N. Dhouib, Ridha Kouki, Mohamed Bejaoui, Fethi Mellouli, Samia Rekaya, Monia Ouederni, and Yosra Mankai
- Subjects
0301 basic medicine ,Male ,Risk ,medicine.medical_specialty ,Multivariate analysis ,Tunisia ,Reticulocytosis ,Spleen ,Disease ,Anemia, Sickle Cell ,Pallor ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Splenic sequestration ,Prevalence ,Humans ,Public Health Surveillance ,Child ,Molecular Biology ,Splenic Diseases ,First episode ,business.industry ,Proportional hazards model ,Incidence ,Infant ,Cell Biology ,Hematology ,Prognosis ,030104 developmental biology ,medicine.anatomical_structure ,Phenotype ,Child, Preschool ,Acute Disease ,Splenomegaly ,Molecular Medicine ,Female ,medicine.symptom ,business ,Biomarkers ,030215 immunology - Abstract
This study was aimed to identify the predictors of splenic sequestration crisis (SSC) among pediatric patients with sickle cell disease (SCD). This prognosis study was carried out in the pediatric immuno-hematology unit, over 20 years (1998 to 2017), enrolling patients with SCD. The cox model was used in multivariate analysis. Among 423 patients with SCD (240 S/S phenotype, 128 S/B0, 30 S/B+, 14 S/O arab and 11 S/C), 150(35.4%) had at least one episode of SSC. The average age of patients at the first episode was 48.3 months ± 32.4(2–168). Recurrence of SSC was observed in 117 patients (78%). Spleen size ≥3 cm at baseline was the strongest predictor of SSC occurrence (HR = 7.27, CI: 4.01–13.20, p = 0.05) and recurrence (HR = 6.37, CI: 1,46–27.83, p = 0.01). Pallor revealing the disease, age at onset of symptoms In conclusion, this study confirmed the high prevalence of SSC in SCD and the high frequency of recurrence after a first episode. The SSC occurrence and recurrence were intimately linked to the presence of splenomegaly, chronic pallor revealing the disease as well as reticulocytosis.
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- 2019
34. [Psychosocial and academic consequences of beta-thalassemia major in Tunisia]
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Manel, Barouni, Saida, Aroua, Fethi, Mellouli, Mohamed, Bejaoui, and Salem, Abbes
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Academic Success ,Tunisia ,beta-Thalassemia ,Humans - Abstract
In Tunisia, beta-thalassemia major is a real public health problem. A study carried out of patients affected shows that for them, this chronic haemoglobinopathy is a disability hampering their physical activities, their social integration, their academic results and their emotional life.
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- 2019
35. Primary Immunodeficiencies: Epidemiology in the Maghreb
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Ahmed Aziz, Bousfiha, Abderrrahmane, Errami, Leila, Jeddane, Fethi, Mellouli, Shereen M, Reda, Mehdi, Adeli, Waleed, Al-Herz, Raed, Zyoud, Nahla, Erwa, Yousif, Suleiman, Rachida, Boukari, Meriam, Dakkoune, Abdelghani, Yagoubi, Hamoud, Al-Mousa, Rand, Arnaout, Suleiman, Alhamadi, Mohamed, Bejaoui, Mohamed Ridha, Barbouche, Bander, AlSaoud, and Hasan, Al-Dhekri
- Subjects
Asia ,Tunisia ,Incidence ,Statistics as Topic ,Immunologic Deficiency Syndromes ,United States ,Europe ,Consanguinity ,Middle East ,Morocco ,Africa, Northern ,Algeria ,Africa ,Prevalence ,Humans ,Registries - Abstract
Primary Immunodeficiency (PIDs) is a set of 330 rare hereditary diseases that increase susceptibility to infections, allergies, autoimmunity, and neoplasia. North American registries give higher prevalence than Maghreb ones, whereas consanguinity is high. The purpose of this study is to compare prevalence and coverage rate of Maghreb PID registries with estimates based on USA.We searched the prevalence of PIDs in the Maghreb registers. Next, we estimated the expected values based on recent publications. Finally, we calculated the coverage rate of the Maghreb registries compared to the new estimates and we evaluated the impact of consanguinity.The total number is N1 = 2456 patients. The current Maghreb PID Prevalence is 2.56 / 100,000 inhabitants (population of 94,804,694 Million in 2017). Tunisia leads with a prevalence of 8.70 followed by Morocco 2.09, Libya 1.65 and Algeria 1.46/100.000 habitants. We did not find values for Mauritania. If we extrapolate the prevalence of the USA to the Maghreb population, the number of patients in the Maghreb would be N2 = 27,588 and the coverage rate (N1 / N2) would be 8.90%. This low coverage rate is however better than the World average (1.21%), that of Latin America 1.19% and Africa 0.36%. The Maghreb prevalence is close to that of the Arab world 2.04 / 100,000 (population of 391,449,544 in 2017). Using the incidence found in the USA, the number of patients would be 9765 new patients per year in the Maghreb and 40,319 in Arab countries.PID Maghreb patients number is very low compared to global estimates, whereas consanguinity is very high. Special attention should be given to PIDs by governments and research teams in this region.
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- 2019
36. Unexpected relevant role of gene mosaicism in patients with primary immunodeficiency diseases
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Laia Alsina, José Carlos Rodríguez-Gallego, Pere Soler-Palacín, Weng Tarng Cham, Enrique Gómez de la Fuente, Rebeca Rodríguez-Pena, Jordi Yagüe, Luis Ignacio Gonzalez-Granado, José M. Morales, Osvaldo M. Mutchinick, Roger Colobran, Luz Yadira Bravo Gallego, Angélica Balderrama-Rodríguez, Alejandro Souto, Pablo Mesa-del-Castillo, María Bravo García-Morato, Kieron S. Leslie, Consuelo Modesto, Juan I. Aróstegui, Naouel Guirat Dhouib, María Teresa Martínez-Saavedra, Carine Wouters, Catalina Mosquera, Marketa Bloomfield, María Teresa Bosque, Maria Teresa Terreri, Daniel Clemente, Jeronima Cañellas, Natalia Palmou, Eva González-Roca, Josep M. Campistol, Lívia Almeida Dutra, Cecilia Gonzalez-Santesteban, Eduardo Ramos, Eduardo López-Granados, Ferran Casals, Norberto Ortego-Centeno, Jose Luis Fuster, Luis M. Allende, Jaime de Inocencio, Mohamed Bejaoui, Laura Martínez-Martínez, Clara Franco-Jarava, Anna Mensa-Vilaro, Santiago Jimenez-Treviño, Rebeca Pérez de Diego, Oscar de la Calle-Martin, Agustin Remesal, Tatiana González, and Natalia Martínez-Pomar
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Male ,0301 basic medicine ,Genetic counseling ,Immunology ,Postzygotic variants ,Biology ,Germline ,Deep sequencing ,03 medical and health sciences ,0302 clinical medicine ,Gene Frequency ,medicine ,Humans ,Immunology and Allergy ,Family ,amplicon-based deep sequencing ,gene mosaicism ,next-generation sequencing ,Allele frequency ,Alleles ,Genetics ,Mosaicism ,Incidence (epidemiology) ,Immunologic Deficiency Syndromes ,primary immunodeficiency diseases ,High-Throughput Nucleotide Sequencing ,Amplicon ,autoinflammatory diseases ,medicine.disease ,Minor allele frequency ,030104 developmental biology ,Primary immunodeficiency ,Female ,030215 immunology - Abstract
BACKGROUND: Postzygotic de novo mutations lead to the phenomenon of gene mosaicism. The 3 main types are called somatic, gonadal, and gonosomal mosaicism, which differ in terms of the body distribution of postzygotic mutations. Mosaicism has been reported occasionally in patients with primary immunodeficiency diseases (PIDs) since the early 1990s, but its real involvement has not been systematically addressed. OBJECTIVE: We sought to investigate the incidence of gene mosaicism in patients with PIDs. METHODS: The amplicon-based deep sequencing method was used in the 3 parts of the study that establish (1) the allele frequency of germline variants (n = 100), (2) the incidence of parental gonosomal mosaicism in families with PIDs with de novo mutations (n = 92), and (3) the incidence of mosaicism in families with PIDs with moderate-to-high suspicion of gene mosaicism (n = 36). Additional investigations evaluated body distribution of postzygotic mutations, their stability over time, and their characteristics. RESULTS: The range of allele frequency (44.1% to 55.6%) was established for germline variants. Those with minor allele frequencies of less than 44.1% were assumed to be postzygotic. Mosaicism was detected in 30 (23.4%) of 128 families with PIDs, with a variable minor allele frequency (0.8% to 40.5%). Parental gonosomal mosaicism was detected in 6 (6.5%) of 92 families with de novo mutations, and a high incidence of mosaicism (63.9%) was detected among families with moderate-to-high suspicion of gene mosaicism. In most analyzed cases mosaicism was found to be both uniformly distributed and stable over time. CONCLUSION: This study represents the largest performed to date to investigate mosaicism in patients with PIDs, revealing that it affects approximately 25% of enrolled families. Our results might have serious consequences regarding treatment and genetic counseling and reinforce the use of next-generation sequencing-based methods in the routine analyses of PIDs. ispartof: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY vol:143 issue:1 pages:359-368 ispartof: location:United States status: published
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- 2019
37. Zinc mitigates renal ischemia-reperfusion injury in rats by modulating oxidative stress, endoplasmic reticulum stress, and autophagy
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Mohamed Bejaoui, Safa Ben Mimouna, José C. Fernández-Checa, Najet Hadj Abdallah, Hassen Ben Abdennebi, Mohamed Amine Zaouali, Carmen García Ruiz, Ahlem Bouhlel, Imed Messaoudi, Anna Baulies, Ministère de l’Enseignement Supérieur et de la Recherche Scientifique (Tunisie), Ministerio de Economía y Competitividad (España), Generalitat de Catalunya, National Institute on Alcohol Abuse and Alcoholism (US), and National Institutes of Health (US)
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Physiology ,Endoplasmic ,Clinical Biochemistry ,Reticulum stress ,Ischemia ,Ischemia/reperfusion ,Apoptosis ,medicine.disease_cause ,Kidney ,Antioxidants ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Chlorides ,Internal medicine ,medicine ,Autophagy ,Animals ,Humans ,Endoplasmic Reticulum Chaperone BiP ,chemistry.chemical_classification ,Inflammation ,Reactive oxygen species ,Renal ischemia ,Chemistry ,Endoplasmic reticulum ,Cell Biology ,Glutathione ,Acute Kidney Injury ,medicine.disease ,Endoplasmic Reticulum Stress ,Rats ,Zinc ,030104 developmental biology ,Endocrinology ,Zinc Compounds ,Oxidative stress ,030220 oncology & carcinogenesis ,Reperfusion Injury ,Unfolded protein response ,Reactive Oxygen Species - Abstract
Oxidative stress is a major factor involved in the pathogenesis of renal ischemia/reperfusion (I/R). Exogenous zinc (Zn) was suggested as a potent antioxidant; however, the mechanism by which it strengthens the organ resistance against the effects of reactive oxygen species (ROS) is not yet investigated. The present study aims to determine whether acute zinc chloride (ZnCl2) administration could attenuate endoplasmic reticulum (ER) stress, autophagy, and inflammation after renal I/R. Rats were subjected to either sham operation (Sham group, n = 6), or 1 hr of bilateral ischemia followed by 2 hr of reperfusion (I/R groups, n = 6), or they received ZnCl2 orally 24 hr and 30 min before ischemia (ZnCl2 group, n = 6). Rats were subjected to 1 hr of bilateral renal ischemia followed by 2 hr of reperfusion (I/R group, n = 6). Our results showed that ZnCl2 enhances renal function and reduces cytolysis (p, The Tunisian Ministry of Higher Education and Scientific Research, Tunisia, Grant number: UR12ES11; Plan Nacional de I +D, Spain, Grant numbers: SAF-2014-57674- R, SAF-2015-69944-R; The Generalitat de Catalunya, Spain, Grant number: 2014- SGR785; NIAAA/NIH, Grant number: P50AA011999
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- 2018
38. Successful Haploidentical Stem Cell Transplantation with Post-Transplant Cyclophosphamide in a Severe Combined Immune Deficiency Patient: a First Report
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Houda Kaabi, Capucine Picard, Monia Ben Khaled, Fethi Mellouli, Monia Ouederni, and Mohamed Bejaoui
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Oncology ,medicine.medical_specialty ,Post transplant cyclophosphamide ,business.industry ,medicine.medical_treatment ,Immunology ,MEDLINE ,Hematopoietic stem cell transplantation ,Transplantation ,03 medical and health sciences ,0302 clinical medicine ,Medical microbiology ,Immune system ,030220 oncology & carcinogenesis ,Internal medicine ,Immunology and Allergy ,Medicine ,Transplantation Conditioning ,Stem cell ,business ,030215 immunology - Published
- 2016
39. Theoretical Investigation of the Electronic Structure and Spectra of Mg2+He and Mg+He
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Mohamed Bejaoui, Hamid Berriche, J. Dhiflaoui, R. El Ouelhazi, and N. Mabrouk
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010304 chemical physics ,Chemistry ,Electron ,Electronic structure ,010402 general chemistry ,01 natural sciences ,0104 chemical sciences ,Pseudopotential ,symbols.namesake ,Dipole ,Excited state ,0103 physical sciences ,symbols ,Physical and Theoretical Chemistry ,van der Waals force ,Atomic physics ,Ground state ,Valence electron - Abstract
The ground and many excited states of the Mg(+)He van der Waals molecular system have been explored using a one-electron pseudopotential approach. In this approach, effective potentials are used to consider the Mg(2+) core and the electron-He effects. Furthermore, a core-core interaction is included. This has reduced the number of active electrons of the Mg(+)He, to be considered in the calculation, to a single valence electron. This has permitted to use extended Gaussian basis sets for Mg and He. Therefore, the potentianl energy and dipole moments calculations are carried out at the Hartree-Fock level of theory, and the spin-orbit effect is included using a semiclassical approach. The core-core interaction for the Mg(2+)He ground state is included using accurate CCSD(T) calculations. The spectroscopic constants of the Mg(+)He electronic states are extracted and compared with the existing theoretical works, where very good agreement is observed. Moreover, the transition dipole function has been determined for a large and dense grid of internuclear distances including the spin-orbit effect.
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- 2016
40. Effectiveness of a single versus repeated administration of trimetazidine in the protection against warm ischemia/reperfusion injury of rat liver
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Mohamed Bejaoui, Mohamed Amine Zaouali, Rabi Selmi, Hassen Ben Abdennebi, Asma Mahfoudh Boussaid, Kaouther Hadj Ayed, and Ministère de l’Enseignement Supérieur et de la Recherche Scientifique (Tunisie)
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0301 basic medicine ,Ischemia/reperfusion injury,liver,trimetazidine,adenosine monophosphate activated protein kinase,endothelial nitric oxide synthase,apoptosis ,Trimetazidine ,Apoptosis ,Adenosine monophosphate activated protein kinase ,Ischemia/reperfusion injury ,03 medical and health sciences ,medicine ,Animals ,Warm Ischemia ,Rats, Wistar ,Endothelial nitric oxide synthase ,business.industry ,General Medicine ,medicine.disease ,Warm ischemia ,Rats ,030104 developmental biology ,Liver ,Reperfusion Injury ,Anesthesia ,Rat liver ,Christian ministry ,business ,Administration (government) ,Reperfusion injury ,medicine.drug - Abstract
[Background/aim] The aim of this study was to compare the effects of single and repeated trimetazidine (TMZ) administration against warm hepatic ischemia/reperfusion (I/R) injury and to explore the possible mechanisms affected by TMZ. [Materials and methods] Wistar rats were divided into 4 groups (n = 6). Sham: rats were subjected to dissection. I/R: rats were subjected to 60 min of partial hepatic ischemia followed by 24 h of reperfusion. TMZ1: Same as I/R group but rats were pretreated with a single dose of TMZ (10 mg/kg, intraperitoneal injection) 30 min before warm ischemia. TMZ3: Same as I/R but rats were treated with 10 mg/ kg TMZ for 3 successive days. [Results] TMZ treatment decreased liver injury, lipid peroxidation, and apoptosis. The repeated administration of TMZ conferred more protection than the single dose treatment concerning all studied parameters. In parallel, we noted a significant increase in phosphorylated adenosine monophosphate activated protein kinase (p-AMPK) and endothelial nitric oxide synthase (eNOS) levels in TMZ3 as compared to TMZ1. [Conclusion] Repeated administration of TMZ for 3 days was more efficient than a single dose of TMZ in protecting the liver against I/R induced apoptosis and lipid peroxidation. These effects implicate AMPK and eNOS activation., This study was funded by the Tunisian Ministry of Higher Education and Scientific Research.
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- 2016
41. The effect of zinc acexamate on oxidative stress, inflammation and mitochondria induced apoptosis in rat model of renal warm ischemia
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Carmen García Ruiz, Imed Messaoudi, Anna Baulies, Mohamed Amine Zaouali, Safa Ben Mimouna, Hassen Ben Abdennebi, José C. Fernández-Checa, Mohamed Bejaoui, Najet Hadj Abdallah, Ahlem Bouhlel, Ministère de l’Enseignement Supérieur et de la Recherche Scientifique (Tunisie), Ministerio de Economía y Competitividad (España), Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (España), National Institute on Alcohol Abuse and Alcoholism (US), National Institutes of Health (US), and Generalitat de Catalunya
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Male ,0301 basic medicine ,medicine.medical_specialty ,Antioxidant ,medicine.medical_treatment ,Ischemia ,Apoptosis ,Inflammation ,Mitochondrion ,Kidney ,medicine.disease_cause ,Antioxidants ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,medicine ,Animals ,Warm Ischemia ,Rats, Wistar ,Aminocaproates ,Pharmacology ,chemistry.chemical_classification ,Dose-Response Relationship, Drug ,General Medicine ,Glutathione ,medicine.disease ,Mitochondria ,Disease Models, Animal ,Zinc ,030104 developmental biology ,Enzyme ,Endocrinology ,chemistry ,Oxidative stress ,Reperfusion Injury ,030220 oncology & carcinogenesis ,Cytokines ,Zinc acexamate ,medicine.symptom ,Ischemia reperfusion injury - Abstract
Aim: Zinc has proved its efficacy in many models of ischemia reperfusion (I/R) injury. In this study, we used zinc acexamate (ZAC) as an exogenous source of zinc against renal I/R injury and we investigated whether its protective effects are mediated by the decrease of oxidative stress, inflammation, and mitochondria inducedapoptosis. Methods: Rats were orally pretreated with vehicle or ZAC (10 or 100 mg/kg) 24 h and 30 min prior to 1 h of bilateral renal warm ischemia and 2 h of reperfusion. Results: Our data showed that 10 mg/kg of ZAC, but not 100 mg/kg, improved renal architecture and function. Also, the low dose of ZAC up-regulated antioxidant enzymes activities and glutathione level and decreased lipids and proteins oxidation. Interestingly, the use of ZAC resulted in a significant reduce of pro-inflammatory cytokines (IL-1ß, IL-6 and MCP-1), enhanced mitochondria integrity and decreased expression of the pro-apoptotic protein caspase-9. Conclusion: We conclude that renal I/R induced oxidative stress, inflammation and apoptosis and that the use of ZAC at 10 mg/kg, but not 100 mg/kg, protects rat kidneys from I/R injury by down-regulating these processes., This work was supported by grants from: The Tunisian Ministry of Higher Education and Scientific Research (UR12ES11); SAF-2014- 57674-R, SAF-2015-69944-R from Plan Nacional de I + D, Spain and CIBEREHD; the center grant P50AA011999 Southern California Research Center for ALPD and Cirrhosis funded by NIAAA/NIH; and AGAUR of the Generalitat de Catalunya2014-SGR785.
- Published
- 2018
42. Randomized Controlled Trial of the Efficacy and Safety of Deferiprone in Iron-Overloaded Patients with Sickle Cell Disease or Other Anemias
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M. A. Badr, Theresa Chan, Julie Kanter, Janet L. Kwiatkowski, Baba Inusa, Alshehri Abdulrahman, Suzan Williams, Michael Spino, Mohsen Saleh Elalfy, Fernando Tricta, Anna Rozova, David M. Lee, Mohamed Bejaoui, Anne Stilman, Fatma Soliman Elsayed Ebeid, Amal El-Beshlawy, Dian Shaw, Yurdanur Kilinç, Caroline Fradette, Yu-Chung Tsang, Jodie Sinclair, Mona Hamdy, Noemi Toiber Temin, and Mônica Pinheiro de Almeida Veríssimo
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medicine.medical_specialty ,business.industry ,Anemia ,Surrogate endpoint ,Immunology ,Deferasirox ,Cell Biology ,Hematology ,Neutropenia ,medicine.disease ,Biochemistry ,law.invention ,chemistry.chemical_compound ,chemistry ,Randomized controlled trial ,law ,Internal medicine ,Clinical endpoint ,Medicine ,business ,Deferiprone ,Adverse effect ,medicine.drug - Abstract
Background: Patients with sickle cell disease (SCD) or other rare anemias whose care includes chronic blood transfusions must receive iron chelation to prevent the morbidity of iron overload. Currently, only deferoxamine (DFO) and deferasirox (DFX) are approved chelators in these patient populations. This randomized open-label trial evaluated if the efficacy of deferiprone (DFP) was non-inferior to DFO. DFO was used as the comparator product since DFX was not approved as first-line treatment for SCD at trial initiation. Methods: Participants at 27 sites in 8 countries were randomized in a 2:1 ratio to receive either DFP or DFO for up to 12 months. Those with lower transfusional iron input and/or less severe iron load were prescribed either DFP 25 mg/kg of body weight t.i.d. or DFO 20 mg/kg (children) or 40 mg/kg (adults); those with higher iron input and/or more severe iron load received either DFP 33 mg/kg t.i.d. or DFO up to 40 mg/kg (children) or 50 mg/kg (adults). Dosages could be adjusted over the course of the trial if necessary. Efficacy endpoints were the changes from baseline in liver iron concentration (LIC), cardiac iron, and serum ferritin (SF) at Month 12. The primary endpoint was based on LIC, and for the demonstration of non-inferiority of DFP to DFO, the upper limit of the 95% confidence interval for the difference between treatments had to be no more than 2 mg/g dry weight (dw). All patients had their neutrophil count monitored weekly, whereas other safety assessments and compliance with study therapy were evaluated monthly. Acceptable compliance was defined as taking 80% to 120% of the prescribed dosage. Results: A total of 228 of the targeted 300 patients were dosed with 152 receiving DFP and 76 receiving DFO, to assess non-inferiority. There were no significant differences between the groups in any demographic measures: in each treatment group, 84% of patients had SCD and the remainder had other, rarer forms of transfusion-dependent anemia. Mean age at enrollment was 16.9 years (± 9.6); 53.1% of patients were male; and 77.2% were white, 16.2% black, and 6.6% multi-racial. Over the course of the study, 69% of patients in the DFP group and 79% in the DFO group had acceptable compliance with treatment. Based on the Pocock's α spending function, a more stringent confidence level of 96.01% was applied to the calculation of confidence interval for the evaluation of non-inferiority. For the primary efficacy endpoint, the least squares (LS) mean change in LIC (measured as mg/g dw) was -4.04 for DFP, -4.45 for DFO; the upper limit of the 96.01% confidence interval for the difference was 1.57, thereby demonstrating non-inferiority of DFP to DFO. The upper limit for the subpopulation of patients with SCD also met the non-inferiority criterion. For the secondary endpoints, the change in cardiac iron (measured as ms on MRI T2*, log-transformed) was approximately -0.02 for both; and for SF (measured as μg/L), it was -415 vs. -750 for DFP vs. DFO, respectively. The difference between the groups was not statistically significant for both endpoints. With respect to safety, there was no statistically significant difference between the groups in the overall rate of adverse events (AEs), treatment-related AEs, serious AEs, or withdrawals from the study due to AEs. Agranulocytosis was seen in 1 DFP patient vs. no DFO patients, while events of less severe episodes of neutropenia occurred in 4 vs. 1, respectively. All episodes of agranulocytosis and neutropenia resolved. There was no significant treatment group difference in the rates of any of the serious AEs. Conclusion: The efficacy of DFP for the treatment of iron overload in patients with SCD or other rare anemias is not inferior to that of DFO, as assessed by changes in liver iron concentration. non-inferiority was supported by the endpoints on cardiac iron load and SF. The safety profile of DFP was acceptable and was similar to that previously seen in thalassemia patients, and its use was not associated with unexpected serious adverse events. The results of this study support the use of DFP for the treatment of iron overload in patients with SCD or other rare transfusion-dependent anemias. Note: The authors listed here are presenting these findings on behalf of all investigators who participated in the study. Disclosures Kwiatkowski: Terumo: Research Funding; Imara: Consultancy; bluebird bio, Inc.: Consultancy, Research Funding; Agios: Consultancy; Novartis: Research Funding; Celgene: Consultancy; Apopharma: Research Funding. Fradette:ApoPharma: Employment. Kanter:Sangamo: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Imara: Consultancy; Guidepoint Global: Consultancy; GLG: Consultancy; Cowen: Consultancy; Jeffries: Consultancy; Medscape: Honoraria; Rockpointe: Honoraria; Peerview: Honoraria; SCDAA: Membership on an entity's Board of Directors or advisory committees; NHLBI: Membership on an entity's Board of Directors or advisory committees; bluebird bio, Inc.: Consultancy; Modus: Consultancy, Honoraria. Tsang:Apotex Inc.: Employment. Stilman:ApoPharma: Employment. Rozova:ApoPharma: Employment. Sinclair:ApoPharma: Employment. Shaw:ApoPharma: Employment. Chan:ApoPharma: Employment. Toiber Temin:ApoPharma: Employment. Lee:ApoPharma: Employment. Spino:ApoPharma: Employment. Tricta:ApoPharma: Employment. OffLabel Disclosure: Deferiprone is an oral iron chelator.
- Published
- 2019
43. Predictors of autoimmune hemolytic anemia in beta-thalassemia patients with underlying red blood cells autoantibodies
- Author
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Monia Ben Khaled, N. Dhouib, Monia Ouederni, Nessrine Sahli, Ahmed Ben Abdelaziz, Ridha Kouki, H. Kaabi, Mohamed Bejaoui, Samia Rekaya, Fethi Mellouli, and Hmida Slama
- Subjects
Adult ,Male ,0301 basic medicine ,Erythrocytes ,Tunisia ,Blood transfusion ,Thalassemia ,medicine.medical_treatment ,Splenectomy ,ABO Blood-Group System ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,hemic and lymphatic diseases ,mental disorders ,Humans ,Medicine ,Blood Transfusion ,Longitudinal Studies ,Family history ,Medical History Taking ,Molecular Biology ,Autoantibodies ,business.industry ,Proportional hazards model ,beta-Thalassemia ,Autoantibody ,Beta thalassemia ,Cell Biology ,Hematology ,Middle Aged ,Prognosis ,medicine.disease ,Coombs Test ,030104 developmental biology ,Immunology ,Molecular Medicine ,Female ,Anemia, Hemolytic, Autoimmune ,Leukocyte Reduction Procedures ,Autoimmune hemolytic anemia ,business ,030215 immunology - Abstract
In beta-thalassemia patients, erythrocyte autoantibodies can remain silent or lead to Autoimmune Hemolytic Anemia (AIHA).The aim of this study was to identify predictors of AIHA in beta-thalassemia patients with positive Direct Antiglobulin Test (DAT), in Tunisia. This longitudinal prognosis study was carried out on beta-thalassemia patients with a positive confirmed DAT. Predictors of AIHA were identified the Kaplan-Meier method. A Cox model analysis was used to identify independent predictors. Among 385 beta thalassemia patients, 87 developed positive DAT (22.6%). Autoimmune hemolytic anemia was occurred in 25 patients. Multivariate analysis showed that AIHA was independently associated with beta-thalassemia intermedia and similar family history of AIHA. Splenectomy in patients with positive DAT was independently associated with an increased risk of AIHA (HR = 6.175, CI: 2.049-18.612, p 0.001). The risk of developing AIHA was higher during the first 72 transfusions. Autoimmune hemolytic anemia was significantly associated with polyspecific DAT (anti-complement and anti-IgG), blood group AB and prior alloimmunization. Whereas transfusion by phenotypic and leukoreduced blood was a protective factor. In summary, splenectomy after autoimmunization, prior alloimmunization, DAT specificity (IgG with complement), thalassemia intermedia, AB blood group and family history of AIHA were strongly associated with AIHA. Leukoreduced blood transfusion had a proven preventive role.
- Published
- 2019
44. Thymoquinone protects rat liver after partial hepatectomy under ischemia/reperfusion through oxidative stress and endoplasmic reticulum stress prevention
- Author
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Najet Hadj Abdallah, Anne Corlu, Mohamed Bejaoui, Hassen Ben Abdennebi, Catherine Ribault, Ahlem Bouhlel, Hassen Hentati, Ismail Ben Mosbah, Roselyne Viel, Université de Monastir ( UM ), Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Bioprédic International, Nutrition, Métabolismes et Cancer ( NuMeCan ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), H2P2 - Histo Pathologie Hight Precision ( H2P2 ), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ), Université de Monastir - University of Monastir (UM), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), H2P2 - Histo Pathologie Hight Precision (H2P2), Université de Rennes (UR)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Tunisian Ministry of Higher Education and Scientific Research, Jonchère, Laurent, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Université de Rennes 1 (UR1)
- Subjects
0301 basic medicine ,Physiology ,medicine.medical_treatment ,thymoquinone ,Pharmacology ,medicine.disease_cause ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,hepatectomy ,Physiology (medical) ,medicine ,oxidative stress ,Thymoquinone ,Liver injury ,[ SDV ] Life Sciences [q-bio] ,Chemistry ,Endoplasmic reticulum ,apoptosis ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,medicine.disease ,Liver regeneration ,[SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,030104 developmental biology ,Apoptosis ,030220 oncology & carcinogenesis ,[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,Unfolded protein response ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,endoplasmic reticulum stress ,Hepatectomy ,Oxidative stress ,Ischemia reperfusion injury - Abstract
International audience; Ischemia reperfusion (I/R) is associated with liver injury and impaired regeneration during partial hepatectomy (PH). The aim of this study was to investigate the effect of thymoquinone (TQ), the active compound of essential oil obtained from Nigella sativa seeds, on rat liver after PH. Male Wistar rats were equally divided into four groups (n=6) receiving an oral administration of either vehicle solution (Sham and PH groups) or TQ at 30 mg/kg (TQ and TQ+PH groups) for ten consecutive days. Then, rats underwent PH (70%) with 60 min of ischemia followed by 24h of reperfusion (PH and TQ+PH groups). Alanine aminotransferase (ALT) activity and histopathological damage were determined. Also, antioxidant parameters, liver regeneration index, hepatic adenosine triphosphate (ATP) content, endoplasmic reticulum (ER) stress and apoptosis were assessed. In response to PH under I/R, liver damage was significantly alleviated by TQ treatment as evidenced by the decrease in ALT activity (P < 0.01) and histological findings (P < 0.001). In parallel, TQ preconditioning increased hepatic antioxidant capacities. Moreover, TQ improved mitochondrial function (ATP, P < 0.05), attenuated ER stress parameters and repressed the expression of apoptotic effectors. Taken together, our results suggest that TQ preconditioning could be an effective strategy to reduce liver injury after PH under I/R. The protective effects were mediated by the increase of antioxidant capacities and the decrease of ER stress and apoptosis. This article is protected by copyright. All rights reserved.
- Published
- 2018
45. S144 A MULTICENTRE, RANDOMIZED, NON-INFERIORITY TRIAL COMPARING THE EFFICACY OF DEFERIPRONE VERSUS DEFERASIROX IN PEDIATRIC PATIENTS AFFECTED BY TRANSFUSION-DEPENDENT HEMOGLOBINOPATHIES (DEEP-2 TRIAL)
- Author
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Adriana Ceci, A. Zaka, Giorgio Reggiardo, Laila M. Sherief, Angela Maggio, Hoda Hassab, Manika Kreka, M. C. Putti, Aldo Filosa, Raffaella Origa, Amal El-Beshlawy, Antonis Kattamis, O. Della Pasqua, Donato Bonifazi, Paul Telfer, Bianca Tempesta, Michael Spino, Mariagrazia Felisi, G.C. Del Vecchio, Yu-Chung Tsang, Carlo Cosmi, Mohamed Bejaoui, Fernando Tricta, and Soteroula Christou
- Subjects
chemistry.chemical_compound ,medicine.medical_specialty ,chemistry ,business.industry ,Internal medicine ,Transfusion dependence ,Deferasirox ,Medicine ,Non inferiority trial ,Hematology ,Deferiprone ,business ,medicine.drug - Published
- 2019
46. Electronic structure and spectra of the RbHe van der Waals system including spin orbit interaction
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Mohamed Bejaoui, J. Dhiflaoui, and Hamid Berriche
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Physics ,02 engineering and technology ,Electronic structure ,Spin–orbit interaction ,021001 nanoscience & nanotechnology ,01 natural sciences ,Potential energy ,Atomic and Molecular Physics, and Optics ,Pseudopotential ,symbols.namesake ,Dipole ,Excited state ,0103 physical sciences ,Physics::Atomic and Molecular Clusters ,symbols ,Atomic physics ,van der Waals force ,010306 general physics ,0210 nano-technology ,Ground state - Abstract
The potential energy interaction, the spectroscopic properties and dipole functions of the RbHe van der Waals dimer have been investigated. We used a one-electron pseudopotential approach and large Gaussian basis sets to represent the two atoms Rb and He. The Rb+ core and the electron-He interactions were replaced by semi-local pseudopotentials and a core-core interaction is included. Therefore, the number of active electrons of RbHe is reduced to only one electron. Consequently, the potential energy curves and dipole moments for many electronic states dissociating into Rb(5s,5p,4d,6s,6p,5d,7s)+He are performed at the SCF level. In addition, the spin-orbit coupling is included in the calculation. The Rb+He interaction, in its ground state, is taken from accurate CCSD (T) calculations and fitted to an analytical expression for a better description of the potential in all internuclear ranges. The spectroscopic properties of the RbHe electronic states are extracted. The comparison of these constants has shown a very good agreement for the ground state as well as for the lower excited states when compared with existing theoretical and experimental studies.
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- 2017
47. Methodology for Tracing a Coastal Flood Risk Card in the Coastal Area of Hammam Lif
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Samir Medhioub, Mohamed Bejaoui, Abir Baklouti, Zied Rekhiss, and Chokri Yaich
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Hydrology ,Flood myth ,Urbanization ,Threatened species ,Flooding (psychology) ,Environmental science ,Storm ,General Medicine ,Coastal flood ,Hazard ,Natural (archaeology) - Abstract
Hammam lif is a Tunisian coastal area threatened by the flooding for years, it underwent exceptional meteorological events which are manifested in 4 major storms 1931, 1981,2003 and 2012. From the study of the anthropogenic and natural damage resulting from each storm, one can deduce the parameters generating the flood in Hammam Lif and generally in each coastal zone threatened by the risk of flooding. The parameters are: rainfall, wave run-up, urbanization and infrastructure. How to highlight the generating parameters of the coastal flood with the aim of mapping a map with detailed flood risk areas that will serve as a flood risk prevention plan for the Hammam Lif area ? and what census methods and tools to use ?
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- 2017
48. Report of the Tunisian Registry of Primary Immunodeficiencies: 25-Years of Experience (1988–2012)
- Author
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Lamia Boughammoura, T. Sfar, Meriem Ben Ali, S. Hassayoun, J. Bouguila, Jalel Chemli, Fethi Bayoudh, Raoudha Boussoffara, Abdelmajid Mahfoudh, Imen Chabchoub, Abdelaziz Harbi, Najla Mekki, Agnes Hamzaoui, Imen Ben Mustapha, Fethi Mellouli, A. Bouaziz, Beya Larguèche, F. Amri, Zakia Habboul, Mohamed-Ridha Barbouche, Saida Ben Becher, Neji Tebib, Habib Besbes, Siheme Barsaoui, N. Gueddiche, Jamel Ammar, Monia Ben Khaled, Mongia Hachicha, Monia Ouederni, Lamia Ben Mansour, Azza Sammoud, Najla Ben Jaballah, Najoua Guandoura, Hajer Aloulou, A. Meherzi, Khadija Boussetta, Mohamed Bejaoui, Saber Hammami, Faculté de Médecine de Tunis, Université de Tunis El Manar (UTM), Ctr Natl Greffe Moelle Osseuse -Tunis, Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP), Hedi Chaker Hospital [Sfax], Serv Pediat, Hopital Mehdia, Département pédiatrique [Hôpital Fattouma Bourguiba - Monastir], CHU Fattouma Bourguiba [Monastir] (HFB), Béchir Hamza Children's Hospital, Serv Pediat B, Serv Pediat C, Serv Pediat PUC, Centre Hospitalier Universitaire Mongi Slim [La Marsa], hopital bizerte, Hôpital Farhat Hached, Sousse, Hopital Sahloul Sousse, Hôpital de Kairouan, Hôpital militaire-Tunis, Serv Reanim Pediat, Hôpital La Rabta [Tunis], and Hôpital de Nabeul
- Subjects
Male ,Primary immunodeficiencies ,Pediatrics ,medicine.medical_specialty ,Tunisia ,diagnosis ,[SDV]Life Sciences [q-bio] ,T-Lymphocytes ,Immunology ,Consanguinity ,medicine.disease_cause ,Antibodies ,Immunodeficiency Syndrome ,Combined immunodeficiencies ,Prevalence ,Humans ,Immunology and Allergy ,Medicine ,Registries ,Age of Onset ,Immunodeficiency ,B-Lymphocytes ,business.industry ,Mortality rate ,Immunologic Deficiency Syndromes ,Infant ,Complement System Proteins ,Immune dysregulation ,medicine.disease ,Survival Analysis ,3. Good health ,treatments ,Primary immunodeficiency ,Female ,Age of onset ,business ,management - Abstract
International audience; Primary immunodeficiencies (PIDs) are a large group of diseases characterized by susceptibility to not only recurrent infections but also autoimmune diseases and malignancies. The aim of this study was to describe and analyze the distribution, clinical features and eventual outcome of PID among Tunisian patients. We reviewed the record of 710 patients diagnosed with Primary Immunodeficiency Diseases (PIDs) from the registry of the Tunisian Referral Centre for PIDs over a 25-year period. The male-to-female ratio was 1.4. The median age at the onset of symptoms was 6 months and at the time of diagnosis 2 years. The estimated prevalence was 4.3 per 100,000 populations. The consanguinity rate was found in 58.2 % of families. According to the International Union of Immunological Societies classification, spectrums of PIDs were as follows: combined T-cell and B-cell immunodeficiency disorders account for the most common category (28.6 %), followed by congenital defects of phagocyte (25.4 %), other well-defined immunodeficiency syndromes (22.7 %), predominant antibody deficiency diseases (17.7 %), diseases of immune dysregulation (4.8 %), defect of innate immunity (0.4 %) and complement deficiencies (0.4 %). Recurrent infections, particularly lower airway infections (62.3 %), presented the most common manifestation of PID patients. The overall mortality rate was 34.5 %, mainly observed with combined immunodeficiencies. The distribution of PIDs was different from that reported in Western countries, with a particularly high proportion of Combined Immunodeficiencies and phagocyte defects in number and/or function. More is needed to improve PID diagnosis and treatment in our country.
- Published
- 2015
49. Acute lactic acidosis as a complication of thiamine-free parenteral nutrition in two neutropenic children
- Author
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Myriam Razgallah Khrouf, Habib Besbes, Selima Zaouali, Monia Ouederni, Fethi Mellouli, Manel Turki, Mohamed Bejaoui, Monia Ben Khaled, and Mohamed Ali Soussi
- Subjects
medicine.medical_specialty ,Chemotherapy ,Pediatrics ,Nutrition and Dietetics ,business.industry ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,food and beverages ,medicine.disease ,chemistry.chemical_compound ,Parenteral nutrition ,chemistry ,Lactic acidosis ,Internal Medicine ,Medicine ,Thiamine ,Respiratory system ,medicine.symptom ,business ,Intensive care medicine ,Complication ,Thiamine deficiency ,Acidosis - Abstract
Following a national out-of-stock of pharmaceutical speciality made with multivitamins formula for intravenous infusion, two hospitalized children with immuno-hematological disorder receiving vitamins-unsupplemented total parenteral nutrition (TPN), had acute lactic acidosis associated with neurological and respiratory symptoms. Clinical and biological signs had quickly resolved after the intravenous administration of thiamine. The thiamine deficiency is an uncommon complication of TPN. This complication remains unrecognized especially in patients with serious diseases in which acidosis could be multifactorial.
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- 2015
50. Fetal Hemoglobin in Tunisian Sickle Cell Disease Patient: Relationship with Polymorphic Sequences Cis to the β-Globin Gene
- Author
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Dorra Chaouachi, Sarah Sassi, Maha Ben Mustapha, Fethi Mellouli, Imen Moumni, Kais Douzi, Ikbel Ben Mansour, Amine Zorai, Salem Abbes, and Mohamed Bejaoui
- Subjects
Genetics ,Haplotype ,Single-nucleotide polymorphism ,Hematology ,Biology ,medicine.disease ,Molecular biology ,Sickle cell anemia ,03 medical and health sciences ,0302 clinical medicine ,Genetic marker ,Polymorphism (computer science) ,hemic and lymphatic diseases ,030220 oncology & carcinogenesis ,Fetal hemoglobin ,Gene cluster ,medicine ,Original Article ,Gene ,030215 immunology - Abstract
Fetal hemoglobin (HbF) plays a dominant role in ameliorating morbidity and mortality of hemoglobinopathies. We evaluated the effects of polymorphic markers within the β-globin gene cluster to identify the genetic mechanics that influence HbF on Tunisian sickling patients (n = 242). Haplotype analysis was carried out by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) and the framework polymorphism was established by PCR-sequencing, four independent regions of interest were identified: the 5′ region of β-LCR-HS2 site, the intervening sequence II (IVSII) region of two fetal (Gγ and Aγ) genes and the 5′ region of β-globin gene. The correlation of these various Haplotypes and SNPs with HbF expression and clinical data was studied. Our data showed that among the various polymorphic markers analyzed, only the sequence (AT)xN12(AT)y in LCR HS2 region was significantly associated (p
- Published
- 2015
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