الفهرس 
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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. For example
although paromomycin may be used with HIV-positive subjects infected with C.
parvum, success with this 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. Accordingly, new drugs are clearly needed.
The present work was carried out to evaluate the therapeutic efficacy of a proton
pump inhibitor omeprazole compared with NTZ (as a commercial standard drug
for treatment of cryptosporidiosis) and their combination regarding parasitological,
histopathological, ultrastructure, biochemical and molecular parameters.
The current study was conducted on 80 laboratory bred Swiss albino female mice
weighing approximately 20-25 g. Mice were purchased from the Schistosome
Biological Supply Program in Theodor Bilharz Research Institute. The eighty mice
used in this study were classified into the following groups:
- group I (Negative Control): Non infected non treated group.
- group II (Positive Control): Infected non treated group.
- group III (Drug Control): Non infected group which is subdivided into:
group III a: Mice were not infected and received oral NTZ.
group III b: Mice were not infected and received oral omeprazole.
group III c: Mice were not infected and received combination of oral NTZ
and omeprazole.
- group IV: Mice were infected and treated by NTZ.
- group V: Mice were infected and treated by omeprazole.
- group VI: Mice were infected and treated by combination of NTZ and
omeprazole.
Immunosuppression was induced by giving a synthetic corticosteroid
(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, omeprazole or
combined treatment started 10 days P. I. and lasted for 7 concecutive days for
treated groups.
from each mouse in all groups of the study, fresh fecal pellets were collected
separately. Collection was carried out every 3 days over the 24 days of the
experiment. Specimens were subjected to parasitological examination using the
modified Zeil Neelsen stain to count the number of Cryptosporidium oocysts per
gram of feces.
Mice were sacrificed on the 24th day P.I. Peripheral blood was aseptically collected
from sacrificed mice. Sera were separated after centrifugation and stored at - 20 ºC
for biochemical studies. The terminal one cm of the ileum and lung tissues were
taken from each mouse, then fixed in 10% neutral formalin for histopathological
examination. Also, parts of the ileum were taken and fixed in glutaraldehyde 5%
for transmission electron microscope. Other samples from the ileum were stored at
– 80 ºC for PCR.
Rgarding parasitological results, in positive control group (GII) there was a gradual
increase in oocyst shedding. The maximum oocyst shedding occurred on the 21st
day P.I. (mean 129.5±3.3) and then there was a decrease in oocyst shedding until it
reached 94.4±2.7 on the 24th days P.I. In the treated groups (IV, V and VI), the decrease in oocyst shedding was the best in group VI (combined- treated group)
(mean7.3±1.5), while it reached 14.2±1.8 in group V (OMP- treated group) and
41.4±2.2 in group IV (NTZ- treated group) with high statistically significant
difference between them (P4<0.001). At time of sacrification (24th day P.I.) the
highest reduction rate (92.3%) was observed in GVI (combined- treated group)
followed by (84.9%) in GV (OMP- treated group). The lowest reduction rate
(56.1%) was observed in GIV (NTZ- treated group).