26 results on '"Mohamed Bejaoui"'
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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. 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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9. 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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10. 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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11. 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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12. 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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13. 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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14. 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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15. 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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16. 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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17. Restriction mapping of βS locus among tunisian sickle-cell patients.
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Imen, Moumni, Ikbel, Ben Mansour Mosbehi, Leila, Chaouch, Fethi, Mellouli, Amine, Zorai, Mohamed, Bejaoui, and Salem, Abbes
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LOCUS (Genetics) ,GENETIC polymorphisms ,SICKLE cell anemia ,POPULATION genetics ,GENES ,PATIENTS - Abstract
Objectives: The polymorphism of the β-globin gene haplotypes and frameworks is useful in the determination of the unicentric and multicentric origin of a mutational event. In our study, the haplotypes linked to the Tunisian β
S mutation are determined to improve our knowledge of the chromosomal background of the β-globin gene in sickle-cell anemia in Tunisia. Methods: The authors have investigated 242 unrelated individuals. Haplotype analysis was carried out by polymerase chain reaction-restriction fragment length polymorphism-based methods. Seven polymorphic sites in the β-globin gene cluster were examined. The correlation of these various haplotypes with Hb F expression was studied. Results: The Benin haplotype (Ben) was largely predominant (60.54%) followed by the Atypical haplotype A (8.43%) and Bantu (Ban) (2.71%) haplotypes. A total of 94 chromosomes had atypical haplotypes, 78 (23.49%) had A1 [−−−−−++], 11 (3.31%) had A2 [−−−−−−−], and five (1.5%) had B1 [−−+−−++]. The Benin haplotype is associated with a fairly low HbF levels. Conclusion: The very high frequency of the Benin haplotype in our study suggests that the βS mutation present in Tunisia may have originated from the Benin region and was brought to Tunisia along the slave trade routes. However, another atypical haplotype observed a new emergence in our population and could be considered as specific to Tunisian chromosome βS . Am. J. Hum. Biol., 2011. © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]- Published
- 2011
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18. Serotype Distribution, Antibiotic Resistance and Clonality of Streptococcus pneumoniae Isolated from Immunocompromised Patients in Tunisia.
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Anis Raddaoui, Alexandra S Simões, Rekaya Baaboura, Sofia Félix, Wafa Achour, Tarek Ben Othman, Mohamed Béjaoui, Raquel Sá-Leão, and Assia Ben Hassen
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Medicine ,Science - Abstract
Pneumococcal disease, a major cause of morbidity and mortality globally, has higher incidence among young children, the elderly and the immunocompromised of all ages. In Tunisia, pneumococcal conjugate vaccines (PCVs) are not included in the national immunization program. Also, few studies have described the epidemiology of S. pneumoniae in this country and, in particular, no molecular typing studies have been performed. The aim of this study was to evaluate serotype distribution, antimicrobial resistance and clonality of Streptococcus pneumoniae isolated from neutropenic patients in Tunisia.Fifty-nine S. pneumoniae were isolated from infection (n = 31) and colonization (n = 28) sites of patients (children and adults) attending the National Centre of Bone Marrow Transplantation in Tunis between 2005-2011. All isolates were characterized by serotype, antimicrobial resistance pattern and multilocus sequence typing (MLST).The majority (66.1%) of the isolates belonged to five serotypes all included in PCVs: 6B, 9V, 14, 19F and 23F. The potential coverage of the 10-valent and 13-valent PCV was of 71.2% and 76.3% respectively. Resistance rates were very high and 69.5% of the isolates were multidrug resistant: non-susceptibility rates to penicillin, amoxicillin and cefotaxime were 66.1%, 40.7% and 27.1%, respectively; resistance rates to erythromycin, clindamycin, tetracycline, chloramphenicol and trimethoprim-sulfamethoxazole, were 69.5%, 61.0%, 37.3%, 22.0% and 67.8%, respectively. The most frequent serotypes had STs characteristic of multidrug resistant international clones known to be highly successful and important causes of pneumococcal infection: Spain 23F-ST81, France 9V/14-ST156, Spain 6B-ST90, 19F-ST320, and Portugal 19F-ST177.The majority of S. pneumoniae strains recovered from immunocompromised patients in Tunisia are representatives of multidrug resistant pandemic clones that express serotypes targeted by PCVs. To contain the burden of pneumococcal disease and improve treatment choices among Tunisian immunocompromised patients PCVs should be offered to all of them.
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- 2015
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19. Successful Treatment of Diamond Blackfan Anemia With Metoclopramide.
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Nawel, Guirat, Fethi, Mellouli, Kouki, Ridha, and Mohamed, Bejaoui
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- 2007
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20. Losartan activates sirtuin 1 in rat reduced-size orthotopic liver transplantation.
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Pantazi E, Bejaoui M, Zaouali MA, Folch-Puy E, Pinto Rolo A, Panisello A, Palmeira CM, and Roselló-Catafau J
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- Animals, Apoptosis drug effects, Cytoprotection, Disease Models, Animal, Enzyme Activation, Gene Expression Regulation, Heat-Shock Proteins metabolism, Liver enzymology, Liver pathology, Male, Mitogen-Activated Protein Kinases metabolism, NAD metabolism, RNA, Messenger metabolism, Rats, Sprague-Dawley, Reperfusion Injury enzymology, Reperfusion Injury genetics, Reperfusion Injury pathology, Signal Transduction drug effects, Angiotensin II Type 1 Receptor Blockers pharmacology, Liver drug effects, Liver surgery, Liver Transplantation adverse effects, Losartan pharmacology, Reperfusion Injury prevention & control, Sirtuin 1 metabolism
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Aim: To investigate a possible association between losartan and sirtuin 1 (SIRT1) in reduced-size orthotopic liver transplantation (ROLT) in rats., Methods: Livers of male Sprague-Dawley rats (200-250 g) were preserved in University of Wisconsin preservation solution for 1 h at 4 °C prior to ROLT. In an additional group, an antagonist of angiotensin II type 1 receptor (AT1R), losartan, was orally administered (5 mg/kg) 24 h and 1 h before the surgical procedure to both the donors and the recipients. Transaminase (as an indicator of liver injury), SIRT1 activity, and nicotinamide adenine dinucleotide (NAD(+), a co-factor necessary for SIRT1 activity) levels were determined by biochemical methods. Protein expression of SIRT1, acetylated FoxO1 (ac-FoxO1), NAMPT (the precursor of NAD+), heat shock proteins (HSP70, HO-1) expression, endoplasmic reticulum stress (GRP78, IRE1α, p-eIF2) and apoptosis (caspase 12 and caspase 3) parameters were determined by Western blot. Possible alterations in protein expression of mitogen activated protein kinases (MAPK), such as p-p38 and p-ERK, were also evaluated. Furthermore, the SIRT3 protein expression and mRNA levels were examined., Results: The present study demonstrated that losartan administration led to diminished liver injury when compared to ROLT group, as evidenced by the significant decreases in alanine aminotransferase (358.3 ± 133.44 vs 206 ± 33.61, P < 0.05) and aspartate aminotransferase levels (893.57 ± 397.69 vs 500.85 ± 118.07, P < 0.05). The lessened hepatic injury in case of losartan was associated with enhanced SIRT1 protein expression and activity (5.27 ± 0.32 vs 6.08 ± 0.30, P < 0.05). This was concomitant with increased levels of NAD(+) (0.87 ± 0.22 vs 1.195 ± 0.144, P < 0.05) the co-factor necessary for SIRT1 activity, as well as with decreases in ac-FoxO1 expression. Losartan treatment also provoked significant attenuation of endoplasmic reticulum stress parameters (GRP78, IRE1α, p-eIF2) which was consistent with reduced levels of both caspase 12 and caspase 3. Furthermore, losartan administration stimulated HSP70 protein expression and attenuated HO-1 expression. However, no changes were observed in protein or mRNA expression of SIRT3. Finally, the protein expression pattern of p-ERK and p-p38 were not altered upon losartan administration., Conclusion: The present study reports that losartan induces SIRT1 expression and activity, and that it reduces hepatic injury in a ROLT model.
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- 2015
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21. Sirtuin 1 in rat orthotopic liver transplantation: an IGL-1 preservation solution approach.
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Pantazi E, Zaouali MA, Bejaoui M, Folch-Puy E, Ben Abdennebi H, Varela AT, Rolo AP, Palmeira CM, and Roselló-Catafau J
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- Animals, Autophagy drug effects, Biomarkers blood, Cold Ischemia, Graft Survival drug effects, Liver enzymology, Liver Transplantation adverse effects, Male, Mitochondria, Liver drug effects, Mitochondria, Liver enzymology, Organ Preservation adverse effects, Oxidative Stress drug effects, Rats, Sprague-Dawley, Reperfusion Injury blood, Reperfusion Injury enzymology, Reperfusion Injury etiology, Signal Transduction drug effects, Time Factors, Trimetazidine pharmacology, Up-Regulation, Liver drug effects, Liver surgery, Liver Transplantation methods, Organ Preservation methods, Organ Preservation Solutions pharmacology, Reperfusion Injury prevention & control, Sirtuin 1 metabolism
- Abstract
Aim: To investigate the possible involvement of Sirtuin 1 (SIRT1) in rat orthotopic liver transplantation (OLT), when Institute Georges Lopez 1 (IGL-1) preservation solution is enriched with trimetazidine (TMZ)., Methods: Male Sprague-Dawley rats were used as donors and recipients. Livers were stored in IGL-1 preservation solution for 8h at 4 °C, and then underwent OLT according to Kamada's cuff technique without arterialization. In another group, livers were stored in IGL-1 preservation solution supplemented with TMZ, at 10(-6) mol/L, for 8 h at 4 °C and then underwent OLT. Rats were sacrificed 24 h after reperfusion, and liver and plasma samples were collected. Liver injury (transaminase levels), mitochondrial damage (glutamate dehydrogenase activity) oxidative stress (malondialdehyde levels), and nicotinamide adenine dinucleotide (NAD(+)), the co-factor necessary for SIRT1 activity, were determined by biochemical methods. SIRT1 and its substrates (ac-FoxO1, ac-p53), the precursor of NAD(+), nicotinamide phosphoribosyltransferase (NAMPT), as well as the phosphorylation of adenosine monophosphate activated protein kinase (AMPK), p-mTOR, p-p70S6K (direct substrate of mTOR), autophagy parameters (beclin-1, LC3B) and MAP kinases (p-p38 and p-ERK) were determined by Western blot., Results: Liver grafts preserved in IGL-1 solution enriched with TMZ presented reduced liver injury and mitochondrial damage compared with those preserved in IGL-1 solution alone. In addition, livers preserved in IGL-1 + TMZ presented reduced levels of oxidative stress. This was consistent with enhanced SIRT1 protein expression and elevated SIRT1 activity, as indicated by decreased acetylation of p53 and FoxO1. The elevated SIRT1 activity in presence of TMZ can be attributed to the enhanced NAMPT protein and NAD(+)/NADH levels. Up-regulation of SIRT1 was consistent with activation of AMPK and inhibition of phosphorylation of mTOR and its direct substrate (p-p70S6K). As a consequence, autophagy mediators (beclin-1 and LC3B) were over-expressed. Furthermore, MAP kinases were regulated in livers preserved with IGL-1 + TMZ, as they were characterized by enhanced p-ERK and decreased p-p38 protein expression., Conclusion: Our study shows that IGL-1 preservation solution enriched with TMZ protects liver grafts from the IRI associated with OLT, through SIRT1 up-regulation.
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- 2015
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22. Emerging concepts in liver graft preservation.
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Bejaoui M, Pantazi E, Folch-Puy E, Baptista PM, García-Gil A, Adam R, and Roselló-Catafau J
- Subjects
- Animals, Humans, Liver pathology, Liver Transplantation adverse effects, Organ Preservation adverse effects, Organ Preservation Solutions adverse effects, Perfusion adverse effects, Tissue Survival, Cold Temperature adverse effects, Liver drug effects, Liver surgery, Liver Transplantation methods, Organ Preservation methods, Organ Preservation Solutions therapeutic use, Perfusion methods, Regenerative Medicine methods
- Abstract
The urgent need to expand the donor pool in order to attend to the growing demand for liver transplantation has obliged physicians to consider the use of suboptimal liver grafts and also to redefine the preservation strategies. This review examines the different methods of liver graft preservation, focusing on the latest advances in both static cold storage and machine perfusion (MP). The new strategies for static cold storage are mainly designed to increase the fatty liver graft preservation via the supplementation of commercial organ preservation solutions with additives. In this paper we stress the importance of carrying out effective graft washout after static cold preservation, and present a detailed discussion of the future perspectives for dynamic graft preservation using MP at different temperatures (hypothermia at 4 °C, normothermia at 37 °C and subnormothermia at 20 °C-25 °C). Finally, we highlight some emerging applications of regenerative medicine in liver graft preservation. In conclusion, this review discusses the "state of the art" and future perspectives in static and dynamic liver graft preservation in order to improve graft viability.
- Published
- 2015
- Full Text
- View/download PDF
23. Polyethylene glycol rinse solution: an effective way to prevent ischemia-reperfusion injury.
- Author
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Zaouali MA, Bejaoui M, Calvo M, Folch-Puy E, Pantazi E, Pasut G, Rimola A, Ben Abdennebi H, Adam R, and Roselló-Catafau J
- Subjects
- Adenosine pharmacology, Allopurinol pharmacology, Animals, Autophagy drug effects, Biomarkers metabolism, Cytoprotection, Cytoskeleton drug effects, Cytoskeleton metabolism, Cytoskeleton pathology, Disease Models, Animal, Glutathione pharmacology, Hepatectomy, Insulin pharmacology, Liver metabolism, Liver pathology, Liver Function Tests, Male, Mitochondria, Liver drug effects, Mitochondria, Liver metabolism, Mitochondria, Liver pathology, Oxidative Stress drug effects, Raffinose pharmacology, Rats, Sprague-Dawley, Reperfusion Injury etiology, Reperfusion Injury metabolism, Reperfusion Injury pathology, Signal Transduction drug effects, Time Factors, Cold Ischemia, Liver blood supply, Liver drug effects, Organ Preservation methods, Organ Preservation Solutions pharmacology, Polyethylene Glycols pharmacology, Reperfusion Injury prevention & control
- Abstract
Aim: To test whether a new rinse solution containing polyethylene glycol 35 (PEG-35) could prevent ischemia-reperfusion injury (IRI) in liver grafts., Methods: Sprague-Dawley rat livers were stored in University of Wisconsin preservation solution and then washed with different rinse solutions (Ringer's lactate solution and a new rinse solution enriched with PEG-35 at either 1 or 5 g/L) before ex vivo perfusion with Krebs-Heinseleit buffer solution. We assessed the following: liver injury (transaminase levels), mitochondrial damage (glutamate dehydrogenase activity), liver function (bile output and vascular resistance), oxidative stress (malondialdehyde), nitric oxide, liver autophagy (Beclin-1 and LCB3) and cytoskeleton integrity (filament and globular actin fraction); as well as levels of metalloproteinases (MMP2 and MMP9), adenosine monophosphate-activated protein kinase (AMPK), heat shock protein 70 (HSP70) and heme oxygenase 1 (HO-1)., Results: When we used the PEG-35 rinse solution, reduced hepatic injury and improved liver function were noted after reperfusion. The PEG-35 rinse solution prevented oxidative stress, mitochondrial damage, and liver autophagy. Further, it increased the expression of cytoprotective heat shock proteins such as HO-1 and HSP70, activated AMPK, and contributed to the restoration of cytoskeleton integrity after IRI., Conclusion: Using the rinse solution containing PEG-35 was effective for decreasing liver graft vulnerability to IRI.
- Published
- 2014
- Full Text
- View/download PDF
24. Role of sirtuins in ischemia-reperfusion injury.
- Author
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Pantazi E, Zaouali MA, Bejaoui M, Folch-Puy E, Ben Abdennebi H, and Roselló-Catafau J
- Subjects
- Animals, Apoptosis, Cell Survival, Energy Metabolism, Humans, Inflammation enzymology, Oxidative Stress, Signal Transduction, Sirtuin 1 metabolism, Sirtuin 3 metabolism, Reperfusion Injury enzymology, Sirtuins metabolism
- Abstract
Ischemia-reperfusion injury (IRI) remains an unresolved and complicated situation in clinical practice, especially in the case of organ transplantation. Several factors contribute to its complexity; the depletion of energy during ischemia and the induction of oxidative stress during reperfusion initiate a cascade of pathways that lead to cell death and finally to severe organ injury. Recently, the sirtuin family of nicotinamide adenine dinucleotide-dependent deacetylases has gained increasing attention from researchers, due to their involvement in the modulation of a wide variety of cellular functions. There are seven mammalian sirtuins and, among them, the nuclear/cytoplasmic sirtuin 1 (SIRT1) and the mitochondrial sirtuin 3 (SIRT3) are ubiquitously expressed in many tissue types. Sirtuins are known to play major roles in protecting against cellular stress and in controlling metabolic pathways, which are key processes during IRI. In this review, we mainly focus on SIRT1 and SIRT3 and examine their role in modulating pathways against energy depletion during ischemia and their involvement in oxidative stress, apoptosis, microcirculatory stress and inflammation during reperfusion. We present evidence of the beneficial effects of sirtuins against IRI and emphasize the importance of developing new strategies by enhancing their action.
- Published
- 2013
- Full Text
- View/download PDF
25. Restriction mapping of βS locus among Tunisian sickle-cell patients.
- Author
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Imen M, Ikbel BM, Leila C, Fethi M, Amine Z, Mohamed B, and Salem A
- Subjects
- Adolescent, Child, Child, Preschool, DNA Mutational Analysis, Emigration and Immigration, Female, Fetal Hemoglobin genetics, Humans, Infant, Male, Multigene Family, Polymorphism, Restriction Fragment Length, Restriction Mapping, Tunisia, Anemia, Sickle Cell genetics, Haplotypes genetics, beta-Globins genetics
- Abstract
Objectives: The polymorphism of the β-globin gene haplotypes and frameworks is useful in the determination of the unicentric and multicentric origin of a mutational event. In our study, the haplotypes linked to the Tunisian β(S) mutation are determined to improve our knowledge of the chromosomal background of the β-globin gene in sickle-cell anemia in Tunisia., Methods: The authors have investigated 242 unrelated individuals. Haplotype analysis was carried out by polymerase chain reaction-restriction fragment length polymorphism-based methods. Seven polymorphic sites in the β-globin gene cluster were examined. The correlation of these various haplotypes with Hb F expression was studied., Results: The Benin haplotype (Ben) was largely predominant (60.54%) followed by the Atypical haplotype A (8.43%) and Bantu (Ban) (2.71%) haplotypes. A total of 94 chromosomes had atypical haplotypes, 78 (23.49%) had A1 [-----++], 11 (3.31%) had A2 [-------], and five (1.5%) had B1 [--+--++]. The Benin haplotype is associated with a fairly low HbF levels., Conclusion: The very high frequency of the Benin haplotype in our study suggests that the β(S) mutation present in Tunisia may have originated from the Benin region and was brought to Tunisia along the slave trade routes. However, another atypical haplotype observed a new emergence in our population and could be considered as specific to Tunisian chromosome β(S)., (Copyright © 2011 Wiley-Liss, Inc.)
- Published
- 2011
- Full Text
- View/download PDF
26. [Osteopetrosis with carbonic anhydrase II deficiency: report of 24 cases].
- Author
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Sonia HL, Mohamed F, Mohamed B, Rafika A, Dehmani F, Kossay D, and Azza H
- Subjects
- Adolescent, Carbonic Anhydrase II genetics, Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Introns, Male, Mutation, Osteopetrosis genetics, Tunisia, Carbonic Anhydrase II deficiency, Osteopetrosis etiology
- Abstract
Twenty four patients suffering from osteopetrosis caused by carbonic anhydrase II deficiency are colliged. This pathology seems to be frequent in Tunisia. Mental retardation is present in 52%, 85% of patients have short stature and 25% have optic atrophy. All affected subjects show craniofacial disproportion and dental anomalies. Twenty patients have at least one bone fracture. Metabolic acidosis is constant: it is profound during the first life decade. A severe selective reduction of carbonic anhydrase II in erythrocyte is confirmed in 18 cases. Osteosclerosis and defective skeletal modelling are constant, cerebral calcification can be seen at the scanner approximately at the age of two years and six months. All patients are homozygous for a splice junction mutation in intron 2 of the carbonic anhydrase II gene, this mutation does not seem to protect patients from bone fractures nor induce a severe metabolic acidosis.
- Published
- 2005
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