الفهرس 
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Abstract
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Chapter VI SUMMARY
Bilharziasis represents one of the major important healths especially affecting the maternal tissues which intern influenced on fetuses growth and differentiation. Praziquantel represent one of the more affecting drug of treatment causing cytotoxic effect in both maternal and fetal tissues. The present study deals with illustrating the effects of Praziquantel in pregnant mothers with or without bilharzial infestation and assessment the maternal fetal relation-ship. Ninety female albino mice were used and arranged into six groups, 15 per each. The animal groups were; control pregnant mice, Praziquantel-treatment pregnant mice, bilharzial infested non-pregnant mice, Praziquantel-treatment and bilharzial infested non-pregnant mice, bilharzial infested pregnant mice, as well as Praziquantel-treatment and bilharzial infested pregnant mice. Bilharzial infestation was carried on two-months before starting experiment by subcutaneous injection with 60 ± 10 S. mansoni cercariae, meanwhile praziquantel-treatment started on the 8th day of gestation for the pregnant mice and on the 68th day post infection for non-pregnant mice by a repeated 300mg/kg body weight dose at intervals of 8 hours. Animals were scarified at 14 and 16 days of gestation as well as at parturition. As well as, the non-pregnant mice were scarified at days parallel to that in the pregnant mice.
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The following parameters were summarized as follows: 1. Maternal body weight gain during pregnancy: There was a steady increase in the body weight of all pregnant mice in the different experimental groups during the gestation period. Comparing with the control, praziquantel-treatment showed increase in body weight but at low rate comparing with the control. In bilharzial infested pregnant revealed marked amelioration of body weight gain but was still not matched with the control and appeared to be higher from the infested-treated group.
2. Effects on pregnant mice and their fetuses and pups: It was obvioused that praziquantel-treatment and schistosomal infestation causing abortion and when both together the abortion rate increase. The total number of fetuses and the number of fetuses per dam in all experimental groups showed a decrease as compared with controls, it was minimal in the infected treated group. In all experimental groups, morphological examintion of 14th and 16th d-old fetuses as well as delivered pups showed morphological abnormalities including edematous skin , kinky tail, superficial hematomas and abnormal forelimb. In experimental groups with either schistosomal infestation alone or with praziquantel-treatment, some fetuses exhibited kyphotic body, cyanosed skin and abnormal hind limb. Besides, the body weight, crown-rump length, the fetal / placental index and umbilical cord length measurements of 14th and 16th d-old fetuses as well as delivered pups in experimental groups were significantly decreased compared to the control.
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3. Ossification of axial and appendicular region: Examining the sequence of ossification and chondrification of axial and appendicular region including forelimb and hind limb regions as well as in ribs. There was a marked reduction of ossification as well as decrease in percentages of chondrification and ossifications in 14th and 16th d-old fetuses and newly-delivered pups of experimental groups. On the other hands, there was a detected increased incidence of absence or partially ossified skull bones included frontal, parietal, interparietal, squamosal, exoccipital, suparoccipital and basioccipital. 4. Histopathological observations of liver and bone of mother mice: Experimental PZQ-treated mother exhibited hepatotoxicity associated with disruption of the normal integrity of hepatic lobules. Focal necrotic foci of hepatocytes were detected characterized by dissolutions of hepatic cords and lysis of hepatocytes and marked hypertrophy of Kupffer cells. Many mitotic figures of and leukocytic infiltrations around central vein were detected. In bilharzial infested mother, there were well defined large fibrocellular granulomatous lesions centered around living ova, including living miracidium and surrounded by lymphocytes, epithelioid cells, eosinophils, polymorphonuclear cells and fibrous tissue. Multiple granulomatous lesions, focal areas of hepatic necrosis, cloudy swelling as well as hydropic degeneration of hepatocytes were seen in some parts. Many focal area of leukocytic infiltaration with karyomegaly of hepatocytes and hypertrophied Kupffer cells having dark-brown bilharzial pigment become clearly evident.
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In experimental bilharzial infested mother treated with PZQ, there was a detected dissolution of the granulomatous lesions around the dissolute ova. The cytoplasm of hepatocytes contained empty vacuole-like spaces, and were enlarged which more characteristic of vacuolar degeneration. In another specimens, there was a marked increased of cells with pyknotic nuclei in the form of increased density and very compact nuclear chromatin. Walls of most sinusoids showed numerous Kupffer cells. The blood vessels become congested. Concerning femoral region, PZQ-treatment exhibited marked resorption of the epiphyseal cartilage with deranged epiphyseal line. The cartilage column cells lacked regular arrangement associated with moderate loss of most of them. The cartilage stromata become widened and separated the cartilage cells. Bone trabeculae attained considerably thinning .On the other hand, experimental bilharzial infested mothers exhibited massive resorption of the epiphyseal cartilage. The chondrocytes sparsely distributed within matrix and lacked columnar arrangement of cartilage cells. The cartilage stomata were increased and regenerated cartilage cells are detected. In experimental bilharzial infested mother treated with PZQ, there was a marked amelioration of the epiphyseal cartilage but lacked regular cartilage column arrangement. The cartilage stomata become reduced and bone trabeculae retained to almost normal pattern. 5. Histopathologiocal observation of hind limb of 14 d-old fetuses:
Fetuses of praziquantel-treated mother exhibited delayement of cartilage cells in different parts of femur and tibia. There is a slight decreased zone of periosteal ossification ensheathed by periosteal sheath formed of connective tissue and osteoprogenitor cells. The phalanges
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were formed of less differentiated cartilage elements and ensheathed by developed cellular perichondrial sheath. Fetuses of bilharzial infested mother exhibited the more advanced periosteal ossification of femur and tibia but less developed comparing with the control. Periosteal ossified regions become ensheathed by periosteal sheath formed of connective tissue and osteoprogenitor cells. The phalanges were formed of hypertrophied cartilage elements and ensheathed by developed cellular perichondrial sheath. In fetuses of bilharzial infested mother and received praziquantel exhibited moderated periosteal ossification of femur and tibia but less affected comparing with Praziquantel alone and less developed comparing with the control. Periosteal ossified regions become ensheathed by periosteal sheath formed of connective tissue and osteoprogenitor cells. The phalanges were formed of less developed cartilage elements and ensheathed by developed cellular perichondrial sheath. 6. Sodium dodecylsulfate–polyacrylamide gel electrophoresis (SDS-PAGE): Sodium dodecylsulfate–polymerase gel electrophoresis of Placenta and amniotic fluid of 14 and 16 d-old fetuses maternally-treated with either praziquantel or received bilharzial infestation or both showed a decreased expression of protein bands. 7. Quantitative and isoenzyme LDH electrophoresis:
Quantitative analysis of LDH activities revealed markedly increased in the placenta and amniotic fluid of either infested or praziquantel-treated group and ameliorated in infested group treated with
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praziquantel. On the other hand, differential LDH isoenzymes of either placenta or amniotic fluids revealed expression of five fractions of isoenzymes (LDH1-LDH5). Concerning placenta and amniotic fluid, the isoenzyme fraction I was markedly decreased in 14 d-old fetuses of infested mother. Also, the isoenzyme fraction IV was markedly inhibited or reduced in fetuses of bilharzial infested mother alone or received praziquantel treatment. 8. Genomic DNA fragmentation and Comet assay: The genomic expression of the degree of laddering (total DNA fragmented) showed apparent damage in placental cells at 14 and 16 days prenatal post-treatment with praziquantel with or without schistosomal infestation as well as in case of only schistosomal infestation. Genomic DNA damage was characterized by increased tail length and DNA percentages. 9. Parasitological studies: · The total number of worm burden recovered from schistosomal infested groups and subjected to pregnancy was lower as compared to the numbers recovered from their corresponding schistosomal infested non-pregnant groups. Also, the total number of worm burden recovered from schistosomal infested groups and treated with praziquantel was lower as compared to the numbers recovered from their corresponding schistosomal infested groups reflecting the efficiency of pregnancy and drug treatment.
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There was a marked decrease of the percentages of living ova in infested pregnant mice. While, infested pregnant mice showed highest incidence of dead ova comparing with non-pregnant infested mice. Praziquantel-treatment was found to reduce the percentages of living ova and revealed an increase in the percentages of dead ova compared with infected untreated group. In conclusion, the present study recorded that PZQ-treatment of Schistosomal infested mice during gestation showed serious fetal defects and also show hazardous impacts on both maternal and fetal body organs which recommended that PZQ-treatment should not be used during pregnancy until cure from Schistosomiasis for reducing the risk to their health and to the health of their babies.