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Article
Activated Peripheral Blood Lymphocyte Subpopulation in Newly Diagnosed Type 1 Diabetes Mellitus Children

Author: Eman Mahdi Saleh
Journal: Iraqi Academic Scientific Journal المجلة العراقية للاختصاصات الطبية ISSN: 16088360 Year: 2008 Volume: 7 Issue: 2 Pages: 112-120
Publisher: The Iraqi Borad for Medical Specialization المجلس العراقي للاختصاصات الطبية

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Abstract

SUMMARY:BACKGROUND:In Type 1 Diabetes Mellitus (T1DM), numerous changes in the cellular as well humoral immune response have been identified. However, it is not known whether both the CD4+ and CD8+ subpopulation or only one of these or CD19+contains increased numbers of activated cells.OBJECTIVE:The aim was to study the activated lymphocyte subpopulation by use of monoclonal antibodies to T-cell and B-cell antigens which is known to be expressed on activated cells.METHODS:A total of 60 T1DM patients who had newly onset of the disease (diagnosed was from one week up to five months) were included in the present study, all the patients were treated with daily replacement doses of insulin. Fifty apparently healthy control subjects underwent the PBL phenotyping. Phenotyping of surface antigens was done by direct Immunoflurocent (IFT) technique using mouse antihuman CD3, CD4, CD8, CD45RA, CD19, and activated markers CD45RO, DR-antigen and CD38.RESULTS:T1DM patients showed a remarkable lowering in CD3+, CD8+, and CD45RA+ cells (p<0.0001), but the decrease in CD4+ cells percentage was not significant. In contrast, a significant elevation of activation markers includes (CD45RO+, HLA-DR+ and CD38+ cells) were observed in patients in addition to a significant increase of CD19+ cell percentage and CD4+: CD8+ ratio in the patients.CONCLUSION:This study provides evidence that abnormalities of T-cells regulation are detectable in patients with T1DM.

Keywords

T1DM --- CD markers --- immunophenotyping


Article
Human Leukocyte Antigens class II influence the expression of Glutamic Acid Decarboxylase auto antibodies in Type Diabetic children and their Siblings

Author: Eman Mahdi Saleh ايمان مهدي صالح
Journal: Al-Kindy College Medical Journal مجلة كلية الطب الكندي ISSN: 18109543 Year: 2010 Volume: 6 Issue: 1 Pages: 52-61
Publisher: Baghdad University جامعة بغداد

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Abstract

Background: The immunogenetic predisposition may be considered as an important factor for the development of Type 1 Diabetes Mellitus (T1DM) in association with the HLA antigens. Objective:This study was designed to investigate the role of HLA-class II antigens in the etiology of type T1DM and in prediction of this disease in siblings, and its effect on expression of glutamic acid decarboxylase autoantibodies (GADA). methods:Sixty children who were newly diagnosed type 1 diabetes (diagnosed less than five months) were selected. Their age ranged from 3-17 years. Another 50 healthy siblings were available for this study, their ages range from 3-16 years. Eighty apparently healthy control subjects, matched with age (4-17) years, sex and ethnic backgrounds (Iraqi Arabs) underwent the HLA-typing examination. Finally 50 healthy individuals were selected randomly to undergo GADA test.Results:At HLA-class II region, DR3 and DR4 were significantly increased in patients (53.33 vs.26.25% and 50.0 vs. 12.5% respectively) as compared to controls. In addition to that, T1DM was significantly associatedwith DQ2 (33.33 vs.15%) and DQ3 (40.0 vs.20%) antigens as compared to controls, suggesting that these antigens had a role in disease susceptibility, while the frequency of DR2 and DQ1 antigens were significantly lowered in patients compared to controls (6.66 vs.25% and 6.66 vs.22.5% respectively). These molecules might have protective effect. In siblings a significant increase frequency of DR4 antigen (34.0 vs.12.5%) was observed in comparison to controls, suggesting that it might be much useful for predicting T1DM in affected families.Anti-GAD autoantibodies were present in 50% of Type 1Diabetic children, and in 16% of their siblings. High proportion of GADA was found in the patients carrying HLA-DR3/DR4 heterozygous.conclusion:Both the T1DM patients and their siblings shared the HLA- DQ1 as protective antigens, while DR3 and DR4 were susceptible one, and high proportion of GADA was found in the T1DM patients and siblings carrying HLA-DR3/DR4 heterozygous.


Article
T-Cells Proliferation and Serum Cytokine levels in Type 1 Diabetic Children

Author: Eman Mahdi Saleh ايمان مهدي صالح
Journal: Al-Kindy College Medical Journal مجلة كلية الطب الكندي ISSN: 18109543 Year: 2011 Volume: 7 Issue: 2 Pages: 16-26
Publisher: Baghdad University جامعة بغداد

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Abstract

Background: There is plenty of evidence suggesting that involvement of several groups of viruses in the development and / or acceleration of Type 1 Diabetes Mellitus (T1DM). Objective: To analyze the T- cell proliferation in the presence of Coxsackie virus B5 (CVB5), Polio and Adenovirus antigens in addition to assessment of Interferon- gamma (IFN-γ), Interleukins (IL-10 and IL-6). Methods: In 60 Iraqi T1DM children with recent onset of T1DM, Lymphocyte proliferation was analyzed using Methylthiazol tetrazolium (MTT) assay by culturing Peripheral Blood Lymphocytes (PBLs) with Coxsackie Virus B5 (CVB5), Adenovirus, and Polio vaccine. Serum Interferon-γ, IL-10 and IL-6 were quantified by sandwich ELISA. Results: No significant differences were shown in the PBL proliferative percentage in response to Con-A mitogen and tested viruses (CVB5 and Adenovirus) between T1DM and healthy controls, but it showed a significant decline in patients in response to Polio vaccine. Higher significant serum levels of IFN-γ, IL-10, and Il-6 were observed in the investigated patients compared to controls (p<0.05). Mean PBL proliferative percentage in response to tested viral antigens was correlated with the serum IFN-γ, IL-6 and IL-10 levels. Conclusions: In children with new- onset diabetes, mean proliferative percentage of Peripheral Blood Lymphocytes was generally decreased. A significant elevation of serum levels of IFN-γ, IL-10 and IL-6 were observed, which is significantly correlated to mean proliferative responses of PBL to viral antigens.


Article
Levels of Some Proinflammatory Cytokines in Obese Women with Polycystic Ovary Syndrome after Metformin Therapy
مستويات بعض السيتوكينات قبيل الالتهاب في النساء البدينات المصابات بمتلازمة المبيض المتعدد الأكياس بعد العلاج بالمتفورين.

Author: Yaser Abbas Ateia, Eman Mahdi Saleh, Thikra N. Abdullah, Zynab Al Musawee.
Journal: Al-Kindy College Medical Journal مجلة كلية الطب الكندي ISSN: 18109543 Year: 2013 Volume: 9 Issue: 2 Pages: 45-48
Publisher: Baghdad University جامعة بغداد

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Abstract

Background: Polycystic ovary syndrome is a heterogeneous disorder and its etiology appears to be complex and multifactorial; characterized by hyperandrogenism, chronic anovulation and infertility. It’s associated with evidence of low-grade chronic inflammation, as indicated by the presence of elevated levels of high sensitive C- reactive protein levels, interleukin-6 and tumor necrosis factor-α. The source of excess circulating tumor necrosis factor-α in obese Polycystic ovary syndrome patient is likely to be the adipose tissues while in lean women increased visceral adiposity has been proposed as a source of excess tumor necrosis factor-α.Objectives: to evaluate the levels of high sensitive C- reactive protein, tumor necrosis factor-α and interleukin-6 in patients with polycystic ovary syndrome before and after treatment with metformin; with emphasis on their relationship with the improvement in ovulation rate and body mass index in Iraqi women.Methods: 69 Iraqi females with PCOS, with mean age of 25.8±4.4 years, body mass index 31.14±2.23 kg/m2 and insulin resistant equal to 3.15±0.25. Additionally, 30 healthy fertile women BMI= 26.87±3.1 kg/m2 and mean age 23.4±2.8 years), the patients were treated with metformin 1500 mg/day for 3 months. Blood samples were obtained in the morning subsequent to an overnight fasting at baseline and at the end of the 12 weeks period of treatment, the samples were analyzed for plasma glucose level estimated by enzymatic colorimetric kit, while serum insulin , TNF-α, IL-6 , hs-CRP, Progesterone and sex hormone binding globulin . Results: BMI values were significantly increased at baseline value in patients (P<0.05) compared with healthy controls, then significantly decreased (12.9%) after treatment compared with baseline values, HOMA-IR index were significantly elevated in patients group at baseline compared with control, and significantly decreased by 17.4% after treatment. Regarding the influence of metformin on inflammatory markers, the present study demonstrated significant elevation of baseline levels (P<0.05) of TNF-α, hs-CRP and IL-6 compared with controls, and the baseline levels significantly decreased after treatment by 16%, 38% and 37% respectively. Meanwhile, sex hormone binding globulin levels were significantly decreased in PCOS patients compared with healthy controls, and significantly increased after treatment by 16.6%, also progesterone levels decline at baseline compared with control group, and it was increased significantly after treatment by 24%.Conclusions: The study detects an increased level of inflammatory cytokines, SHBG and decrease level of progesterone in Iraqi females with PCOS, and metformin therapy improves serum levels of the inflammatory cytokines associated with increased ovulation rate.

الأهداف : متلازمة المبيض المتعدد الأكياس هي مرض غير متجانس ومسبباته معقدة ومتعددة ويتميز بزيادة مستوى الأندروجين في الدم وعدم التبويض المزمن والعقم. وتصاحبه دلائل درجات منخفضة من الألتهابات المزمنة كما يبدو من ارتفاع مستويات TNf-αو IL-6وhs-crp. إن منشأ زيادة مستوى إل TNf-α في البدينات المصابات بمتلازمة المبيض متعددة الأكياس هو عل الأرجح النسيج ألدهني، بينما في النحيفات فأن الدهون في منطقة البطن قد اقترحت كمنشأ لزيادته. الدراسة الحالية صممت لتخمين مستويات TNf- α و IL-6وhs-crp. .في المصابات بمتلازمة المبيض المتعدد الأكياس قبل وبعد العلاج بالمتفورمين مع التشديد على علاقته بتحسين التبويض ومؤشر كتلة الجسم .طرق البحث:69 مصابة بمتلازمة المبيض المتعدد الأكياس وبمعدل عمر 25.8±4.4 سنة ومؤشر كتلة الجسم 31.14± 2.23ومؤشر مقاومة الأنسولين 3.15±0.25 علاوة على ذلك 30 أمرأة وبمعدل عمر23.4±2.8 سنة ومؤشر كتلة الجسم26.87±3.1 اعتبرت كمجموعة ضابطة.المريضات تم علاجهن بالمتفورمين بجرعة 1500 ملغم يوميا ولمدة 3 اشهر. تؤخذ نماذج الدم حبات بعد صيام منذ الليلة الفائتة ويعتبر هذا هو خط البداية , وكذلك يؤخذ نموذج الدم في نهاية فترة الدراسة , ويتم قياس كل من مستوى السكر والأنسولين واال TNf-α IL-6وhs-crp والبروجستيرون وSHBG.النتائج : قيمة مؤشر كتلة الجسم للمريضات في بداية الدراسة ظهرت اكبر من المجموعة الضابطة ثم انخفضت بنسبة 12.9% بعد العلاج مقارنة مع مؤشر كتله الجسم للمريضات ,إما مؤشر مقاومة الأنسولين فأنه يرتفع بصورة معبرة في مجموعة المريضات مقارنة مع المجموعة الضابطة ثم ينخفض بنسبة 17.4% بعد العلاج وبالأخذ بنظر الاعتبار تأثير المتفورمين على مستوى علامات الاألتهابات أظهرت الدراسة ارتفاعها عند مستوى خط البداية بالنسبة ل TNf- αو IL-6 و hs-crp عند المريضات مقارنة مع المجموعة الضابطة, وينخفض عن مستوى خط البداية بالنسبة للمريضات بعد العلاج بنسبة16%,38%,37% بالتتابع, في حين آن SHBG.يقل بنسبة 16,6%وكذلك والبروجستيرون عند المريضات مقارنة مع المجموعة الضابطة ويزداد بصورة معبرة بنسبة24%.الاستنتاج: الدراسة حددت زيادة في مستوى السيتوكينات الالتهابية وانخفاض في مستوى آل SHBG. والبروجستيرون لدى النساء العراقيات. وعقار المتفورين يحسن مستوى السيتوكينات الالتهابية وزيادة مستوى ال SHBG.والبروجستيرون مصاحبة مع زيادة التبويض .

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