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Volume 7, Problème 1 (2017)

article de recherche

Association 0f Gpx-198C/T Gene Polymorphism (rs1050450-198C/T) in Sudanese with Diabetic Retinopathy

Albadawi NMN*, Tarazawi EA, Ismail AM, Altoum S and Bakheet KH

Background: Diabetic retinopathy is the common micro-vascular complication of diabetes mellitus. It is the main cause of blindness among young adults worldwide. Poor glycemic control in addition to longer diabetic duration is the main risk factors for diabetic retinopathy. Many genes have been postulated as candidates for diabetic retinopathy. Little is known about anti-oxidative enzyme gene polymorphism and its association with diabetic retinopathy, mainly for catalase enzyme and manganese superoxide dismutase and glutathone genes. The study aims to assess the role of glutathone GPX-198C/T (rs1050450) gene polymorphism in diabetic retinopathy Sudanese patients and its relation with GPX level. In addition to determine the association of FBS, HbA1c and lipid in the pathogenesis of diabetic retinopathy. Methodology: The number of subjects involved were 130 which were classified into (n 60) clinically diagnosed as diabetic retinopathy and (n 70) diabetes mellitus without retinopathy as control group, age ranged from 22 to 80 years old, from Makkah Eye Complex. DNA was extracted and PCR product for GPX, gene segment were digested by Aba1 enzymes, moreover gene polymorphisms were determined. Serum GPX, activity and FBS, TG, CHOL and HbA1c level were analyzed using Cobas Int 400 using absorption photometer and immunoassay methods respectively. Results: The results revealed that, retinopathy is common in female than male by approximately 2 fold =1.9:1. Type II is more common in our population that type 1. The majority of the patients had type II diabetes (128, 98.5%) and only 2(1.5%) patients were type I diabetes mellitus. The activity of GPX, was significantly higher in DNR when compared with DR (p=0.003). Mean HbA1c and FBG concentration were significantly higher among DR than DNR p=0.001 and p=0.001 respectively. In contrast, mean serum CHOL and TG level revealed insignificant differences when compared DR with DNR. The genotyping for GPX-198C/T showed that, the frequency of CC was observed in 33(47%) in control higher than cases 13(22%), theses Associations for CCs, GPX-198C/T SNP rs1050450, decreased risk after correction for multiple testing (OR=0.310, 95% CI=0.176-0.486, p=0.001), While TT genotype was detected in 25(42%) cases and only 14(20%) in controls, these Associations for SNPs, TTs, GPX-198C/T SNP rs1050450, increased risk after correction for multiple testing (OR=2.4, 95% CI=1.10-5.90, p=0.004). The frequency of the allele C protective allele was found to be 48% among cases group while allele T-risky allele was higher among cases group 72%, OR=0.357 (0.216-0.433), p=0.001. Conclusion:The study concludes that there is a significant association between GPX-198C/T (rs1050450) gene polymorphism and the occurrence of diabetic retinopathy in Sudanese population. There is a significant decrease in GPX levels and glycemic control in patients with the mutant allele T.

article de recherche

An Optimal Approach for Fluoroquinolone Garenoxacin Prophylaxis in Patients with Hematological Malignancies and Chemotherapy-induced Neutropenia

Mushino T, Hanaoka N, Murata S, Kuriyama K, Hosoi H, Nishikawa A, Tamura S, Nakakuma Hand Sonoki T

Antibiotic prophylaxis such as that with fluoroquinolone reportedly reduces infectious episodes in patients receiving chemotherapy regimens with the risk of febrile neutropenia. However, optimum patient characteristics, the timing of initiation, and antibiotics for prophylactic treatments have yet to be identified. We herein conducted a single-arm monocenter clinical study to elucidate the therapeutic profiles of fluoroquinolone garenoxacin prophylaxis for patients with hematological malignancies (HMs). Fever was not present for the duration of chemotherapyinduced neutropenia in 29 (43.9%) out of 66 patients. A shorter duration of prophylaxis until chemotherapy-induced neutropenia had a more potent effect on delaying febrile episodes, even in patients with fever. Excessive neutropenia (minimum zero neutrophils/l) negatively affected prophylactic effects. Garenoxacin accounted for 4.5% of the minor adverse events observed such as mild renal damage and skin reactions. Therefore, the study suggests that the initiation of garenoxacin prophylaxis from the introduction of neutropenia could be an effectual strategy for preventing chemotherapy-induced febrile episodes in HM patients with moderate neutropenia.

article de recherche

A Method to Predict the Yield of Peripheral Blood Stem Cells Collected by Large Volume Leukapheresis

Chen J*, Burns K, Kennedy M, Segura FJ, Garcia S and Leveque C

Background: Collection of peripheral blood stem cells (PBSC) by leukapheresis has become the dominant method in allogeneic hematopoietic stem cell donation and also overpassed bone marrow donation in autologous transplantations. The circulating CD34 positive cells immediately prior to PBSC collection strongly correlate with the PBSC yield and have used to monitor donor’s response to bone marrow mobilization. Methods: In this prospective study, a prediction method for PBSC collection that has been used in our facility was provided. Prediction accuracy is evaluated by comparison of predicted CD34 values to real PBSC yield. Results: The prediction method was used to determine first if a standard procedure with 12 L of blood processing could achieve the collection goal. Thirty seven donors were considered to have adequate PBSCs. Thirty four of them had a CD34 count above the target and only one donor had a CD34 count significantly below the target. For the donors whose PBSC were considered inadequate, an extended collection was performed based on the predicted blood volume that needed to be processed. The number of overestimated predictions was essentially the same as the number of underestimated predictions. Conclusion: The proposed prediction method was successful in identifying donors who needed extended collection without causing unnecessary prolongation of the leukapheresis procedure.

article de recherche

Haematological Indices of Nigerian Pregnant Women

Michael OA*, Theresa OA and Tyodoo MM

Haematological profile to a large extent, reflects the overall well-being or otherwise of an individual. Anaemia, thrombocytopaenia and leucocytosis are among the most common changes observed in the haematological parameters of pregnant women. Paucity of documented reference values for pregnant women from this region necessitated this study, considering the importance of these parameters, the potential implication of its wrong interpretation and application and their effects on pregnancy and its outcome. A total of 253 women, aged 15-50 years were recruited. Two hundred and eleven of them were pregnant and 42 were non pregnant control. Assessment of some key haematological parameters showed higher WBC and ANC and lower platelets, Hb and ALC in the pregnant compared to the non-pregnant women (p<0.05). It also showed higher WBC and ANC and lower platelets and haemoglobin concentration with increasing trimester (p<0.05).

article de recherche

Targeting Protein Arginine Methyltransferase 1 Blocks RBM15-MKL1 Fusion-Initiated Human Stem Cell Transformation

Jin S, Yao Z, Mi Y, Wang H, Yao S, Song J, Zhang P, Zhang J, Zhou W, Ma J, Guo Y and Liu Y*

Objective: The chromosome translocation t (1;22), which generates the RBM15-MKL1 fusion gene, is found in approximately 10% of pediatric acute megakaryoblastic leukemia cases. Given that PRMT1 downregulation is critical for megakaryocyte differentiation, we propose the use of the PRMT1 inhibitor furamidine to stimulate RBM15- MKL1-transformed human cord blood cells to undergo megakaryocyte differentiation. Materials and methods: Human CD34+ cells were purified from umbilical cord blood with anti-CD34 magnetic beads. Lentivirus-infected CD34+ cells were sorted using flow cytometry. The methylcellulose colony replating assay was performed to evaluate the transformation efficiency. Cell viability was calculated using a CellTiter-Glo® luminescent cell viability assay kit. Results: The simultaneous transduction of RBM15-MKL1 and MPLW515L, a mutated MPL gene found in AMKL patients, into human CD34+ cells resulted in long-term growth in the presence of a cytokine mix that maintains a population of hematopoietic stem progenitor cells. Elevated expression of PRMT1 was detected in cells transduced with RBM15-MKL1 together with MPLW515L. The PRMT1 inhibitor furamidine (aka DB75) reversed the inhibition of RBM15-MKL1-mediated megakaryocytic differentiation and impeded the replating capability of the transformed cells. Conclusion: PRMT1 facilitates the transformation induced by RBM15-MKL1, and inhibiting PRMT1 activity promotes MK differentiation. Given that furamidine has been used for treating trypanosomiasis in clinical trials and proven to be safe, using furamidine to treat AMKL may be a new curative option for RBM15-MKL1-associated leukemia.

Rapport de cas

A Trichosporon asahii Bloodstream Infection in a Preterm Newborn with a Successful Outcome: A Case Report

Bukhari MA*, Abdelrazek SAM, El-Shalakany AH and Faiz A

Trichosporon asahii is a rare opportunistic fungal pathogen that causes fatal systemic infections in immunocompromised patients. We have reported a case of T. asahii fungemia in a low birth weight preterm newborn baby in the neonatal intensive care unit (NICU). This case of T. asahii fungemia was unresponsive to treatment with a combination of Amphotericin B and Fluconazole. However, Treatment with a combination of Voriconazole and Caspofungin was successfully eliminated the fungus from the blood of the infected patient.

article de recherche

Establishing Reference Ranges of Hematological Parameters from Malian Healthy Adults

Kone B, Maiga M, Baya B, Sarro YDS*, Coulibaly N, Kone A, Diarra B, Sanogo M, Togo ACG, Goita D, Dembele M, Polis MA, Warfield J, Belson M, Dao S, Orsega S, Murphy RL, Diallo S and Siddiqui S

Introduction: Measurement of immuno-hematological parameters has been historically helpful in the diagnosis and treatment monitoring of many infectious diseases and cancers. However, these parameters have not yet been established in many developing countries where patient care strongly relies on such low-cost tests. This study describes the immuno-hematological parameter ranges for Malian healthy adults.
Methods: A cross sectional study was conducted from August 2004 to May 2013. We included 213 healthy volunteers (173 male and 40 female), aged between 18-59 years. Median, 2.5 and 97.5 percentile ranges for each immuno-hematological parameter are presented.
Results: In our study population, the hematological parameters’ ranges were mostly different to the universal established ranges. We found in our population a Median white blood cell (WBC) count of 5200 cells/μL [3237.5- 11900], Red Blood Cell (RBC) count of 4.94 10^6 [3.56-6.17], hemoglobin (Hb) of 14.2 g/dL [12.2-17.38], platelet count (Plt) of 275 10^3/μL [145.4-614.4], lymphocytes 2050/μL [1200-3800], neutrophils 2200/μL [1040-6220]; monocytes 200/μL [100-660]; eosinophils 131/μL [0-1026]; CD4 902 cells/μL [444-1669] and CD8 485 cells/μL [0- 1272]. We found significant gender differences in RBC, Hb level and MPV. However, RBC and Hb were higher in males median values compared to females (median values) (p<0.001), whereas the Mean platelet volume lower values (MPV) in males than females (P<0.047). The hemoglobin level for some West African countries (Mali, Burkina Faso, Togo, and Nigeria) ranged from 13.5 to 15.1 g/dL for males and 12 to 13 g/dL for females. However in East and Southern Africa, the values were anywhere from 14.1 to 16.1 for males and 11.2 to 14.4 for females.
Conclusion: Our data may help physicians to better define hematological abnormalities in patients. They may also be used to define new “normal hematological values” in Malian population or in the whole West African population.

Article de révision

Noneosinophilic Severe Asthma

Peter B*, Kirey G, Naessens B and Johan B

Asthma could be a type-I allergic airway illness characterized by Th2 cells and immunoglobulin. Episodes of cartilaginous tube inflammation, white corpuscle in nature and promoting bronchoconstriction, could become chronic and result in persistent metabolism symptoms and irreversible structural airway changes. Representative largely of delicate to moderate bronchial asthma, this clinical definition fails to account for the atypical and infrequently additional severe makeup found during a tidy proportion of asthmatics United Nations agency have augmented white blood cell counts within the airways as a characteristic attribute. Neutrophilic inflammation could be a hallmark of another sort of allergic airway pathology, hypersensitivity redness. Thought-about as associate degree immune counterpart of bronchial asthma, hypersensitivity redness could be a prototypic type-III allergic inflammatory reaction involving the alveoli and respiratory organ interstitium, steered by Th1 cells and immune serum globulin and, in its chronic type, among pathology. Though pathologically terribly completely different and ordinarily approached as separate disorders, as mentioned during this review, clinical studies also as information from animal models reveal simple parallels between each airway diseases. Danger communication induced by the matter agent or by incidental to microorganism patterns emerges as vital in facultative immune sensitization and in deciding the sort of sensitization and succeeding allergic illness. On this basis, we have a tendency to propose that allergens cause severe noneosinophilic asthma attributable to sensitization within the presence of hypersensitivity pneumonitispromoting danger communication.

Rapport de cas

Role of BIRC5 Gene as a Prognostic Marker in Pediatric Acute Lymphoblastic Leukemia

Al-Sharkawy E, Ghobrial AG, Eldin AMK, Saber MM, Aboul-Fotoh LE and El-Deen HTG

Background and objectives: Acute lymphoblastic leukaemia (ALL) is the most common malignancy diagnosed in children. Survivin, a small inhibitor-of-apoptosis protein (IAP) encoded by the baculoviral inhibitor of apoptosis repeat-Containing 5 (BIRC5) gene, plays critical roles in malignancy by preventing apoptosis through blocking caspase activity. The aim of this study was to assess the prognostic role of BIRC5 gene in paediatric ALL.
Subjects and methods: The present study was carried out on 42 children with the’ novo ALL who were followed up for two years and 10 apparently healthy children of matched age and sex (controls). Each child was subjected to complete history taking, clinical examination, laboratory investigations the form of CBC, Leishman-stained peripheral blood smears, Lactate dehydrogenase (LDH), Bone marrow (BM) aspiration and examination of Leishman-stained smears, Immunophenotyping on BM samples for routine panel of ALL determined by flow cytometer and quantitative determination of survivin gene expression by real time PCR on BM samples.
Results: Patients with ALL had a significantly higher BIRC5 expression than did the control group (P=0.0004). There was a significant increase in survivin gene expression level in T-ALL when compared to common BALL and pre B-ALL (P=0.001). A significant positive correlation was found between survivin expression and LDH, uric acid and white blood cells (WBCs) (r=0.47, P=0.002; r=0.31, P=0.05, r=0.62, P=0.001), respectively. A significant higher survivin expression levels, LDH and WBCs was found in children with unfavorable outcome. 94.5% of ALL patients with high survivin expression had an unfavorable outcome while, in ALL children with low survivin expression, only 25% had an unfavorable outcome (P=0.001).
Conclusion: BIRC5 gene expression was correlated with unfavorable outcome of childhood ALL. So, its measurement at diagnosis may detect a high risk ALL subgroup.

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