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العنوان
Evaluation of the Therapeutic Effect of Cysteine Protease Inhibitors and Nitazoxanide on Mice Infected with Cryptosporidium /
المؤلف
Farag, Shaimaa Abdel Mageed Abdel Hakim.
هيئة الاعداد
باحث / شيماء عبد المجيد عبد الحكيم فرج
مشرف / اميمة كامل الشافعي
مشرف / عبد الجواد السيد سعد
مشرف / نانسي محمود حربه
الموضوع
Parasitology.
تاريخ النشر
2018.
عدد الصفحات
251 p. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
الطب
تاريخ الإجازة
25/4/2018
مكان الإجازة
جامعة المنوفية - كلية الطب - علم الطفيليات
الفهرس
Only 14 pages are availabe for public view

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from 271

Abstract

The intestinal coccidian parasite Cryptosporidium has emerged as one of the most common opportunistic parasites. This disease is known to cause self-limiting diarrhea in immunocompetent individuals. However, in immunocompromised patients (e.g., AIDS, malnutrition, or chronic liver disease) it causes severe and life-threatening diarrhea and may also infect the biliary tract.
Chemotherapeutic options for cryptosporidiosis are extremely limited, and they depend on the clinical context. Thus, although paromomycin may be used with HIV-positive subjects infected with C. parvum, success with the agent is not guaranteed. Likewise, NTZ which is the only FDA approved drug for the treatment of cryptosporidiosis in immunocompetent patients older than one year, is not approved for HIV-infected patients. New drugs are clearly needed.
Hence, the present work was carried out to study the effect of C. parvum infection on immunocompetent and immunosuppressed mice and compare the intensity of the infection between both conditions. Also to evaluate the therapeutic efficacy of PVS (as CPIs) compared with Nitazoxanide (as a commercial standard drug for treatment of cryptosporidiosis) regarding parasitological, histopathological and immunohistochemical parameters. Evaluation of their efficacies when used in combination was also carried out.
The study was conducted on 200 laboratory bred Swiss albino female mice weighing approximately 20-25 g. Mice were purchased from the Schistosome Biological Supply Program (SBSP) in Theodor Bilharz Research Institute (TBRI).
The mice were divided into two major divisions; immunocompetent and immunosuppressed with the following groups for each one respectively: negative control (I and VIII), infected control (II and IX), infected and treated with PVS (V and X), infected and treated with NTZ (VI and XI) and infected and treated with both drugs (VII and XII). In addition to two drug control groups present only in immunocompetent division (III and IV).
Immunosuppression was induced by giving synthetic corticosteroids (dexamethasone) orally for 14 successive days prior to inoculation with Cryptosporidium oocysts. The immunosuppressed mice continued to receive dexamethasone at the same dose throughout the experiment.
Mice were orally infected with Cryptosporidium oocysts. Treatment with NTZ, PVS or combined treatment started 10 days PI and lasted for 10 days for treated groups.
from each mouse in all groups of the study fresh faecal pellets were collected separately. Collection was carried out every other day over the 30 days of the experiment, according to the different groups. Specimens were subjected to parasitological examination using the modified Z-N stain to count the number of Cryptosporidium oocysts per mg of faeces.
Mice were sacrificed at 18 and 30 days PI (subgroup a, subgroup b respectively).
The terminal 2 cm of the ileum of all sacrificed mice were submitted to routine histopathological processing and stained by H&E. Also, Giemsa, Periodic-Acid Schiff (PAS) and immunohistochemical staining of Caspase 3 were carried out on ileal sections from subgroups a only (sacrificed at 18 days PI).