مورد إلكتروني
Clinical and experimental studies of organ-specific autoimmune diseases : With special reference to Addison's disease and autoimmune hepatitis : by Gennet Gebre-Medhin
| العنوان: | Clinical and experimental studies of organ-specific autoimmune diseases : With special reference to Addison's disease and autoimmune hepatitis : by Gennet Gebre-Medhin |
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| بيانات النشر: | Institutionen för medicinska vetenskaper Uppsala : Acta Universitatis Upsaliensis 2001 |
| تفاصيل مُضافة: | Gebre-Medhin, Gennet |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | Organ-specific autoimmunity constitutes a large health problem, where both the clinical management and our understanding of the pathogenetic mechanisms need to improve. Women with Addison's disease have abnormally low levels of dehydroepiandrosterone (DHEA), its sulphate ester (DHEA-S) and androgens relative to age, and many patients complain of physical and mental fatigue and low stress tolerance. To define a suitable dose, the effect of oral DHEA replacement was evaluated in women with Addison's disease. DHEA was administered for three months to nine women with Addison's disease in either of two doses, 50 mg (n=5) or 200 mg (n=4). A dose of 50 mg restored the DHEA(S) and androgen levels to normal without altering the insulin sensitivity, body composition or serum lipid profile. Autoimmune polyendocrine syndrome type I (APS I) is a rare but useful model disorder of autoimmunity, characterised by multiple organ-specific autoimmune manifestations and high-titre autoantibodies and with adrenocortical insufficiency, Addison's disease, as one of its cardinal manifestations. Approximately 10-20% of APS I patients suffer from autoimmune hepatitis, which carries a high mortality, if untreated. The presence of putative antigenic targets in the liver was investigated. Cytochrome P4501A2 (CYP1A2) and aromatic L-amino acid decarboxylase (AADC) were identified as hepatic autoantigens with the use of APS I sera for immunofluorescent staining of normal human liver, Western blot of microsomal and cytosol fractions of human liver homogenate, and immunoprecipitation of in vitro transcribed and translated radioactively labelled proteins. The presence of CYP1A2- and AADC-antibodies was significantly correlated to AIH, and CYP1A2 antibodies inhibited enzyme activity in vitro. In conclusion, a daily replacement dose of 50 mg of DHEA sufficiently restores levels of DHEA, DHEA(S) and androgens in women with Addison's disease, without severe side-effects. We have further identified CYP1A2 |
| مصطلحات الفهرس: | Medical sciences, Addison's Disease, replacement therapy, DHEA, autoimmune hepatitis, APS I, autoantigen, cytochrome P4501A2, aromatic L-amino acid decarboxylase, MEDICIN OCH VÅRD, Medical and Health Sciences, Medicin och hälsovetenskap, Doctoral thesis, comprehensive summary, info:eu-repo/semantics/doctoralThesis, text |
| URL: | Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 0282-7476 ; 1045 |
| الإتاحة: | Open access content. Open access content info:eu-repo/semantics/openAccess |
| ملاحظة: | application/pdf English |
| أرقام أخرى: | UPE oai:DiVA.org:uu-674 urn:isbn:91-554-5043-1 1234581136 |
| المصدر المساهم: | UPPSALA UNIV LIBR From OAIster®, provided by the OCLC Cooperative. |
| رقم الانضمام: | edsoai.on1234581136 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |