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Take a quick interactive quiz on the concepts in What is Schistosomiasis? - Definition, Types A blood fluke parasite is likely to live in _____. Icy cold water. Gene function in schistosomes: recent advances towards a cure . Freshwater snails ingest the eggs; the parasite (and related flukes, above) undergoes transformations within the snail host, culminating .. Relationship between schistosomiasis and bladder cancer. 11, e1; quiz e doi: /j. cgh Around million people every year are infected with blood or liver flukes from the genus Schistosoma [shist-oh-soh-mah], so the diseases they cause are.
The better-known hypothesis is that the estrogen receptor mediates cell proliferation, increasing errors in DNA replication Clemons and Goss, ; Yager and Davidson, ; Botelho et al. Another interpretation postulates that estrogen metabolites react covalently with DNA bases by redox cycling or by forming an abasic site.
Subsequent error-prone repair of the modified DNA generates oncogenic mutations that initiate cancer. The two mechanisms may act in concert. According to the second mechanism, P metabolism of estrone and estradiol generates the catechol estrogens, 2-hydroxyestrogen and 4-hydroxyestrogen.
Further oxidation leads to 2, 3-catechol-estrogen quinine and 3, 4-catechol-estrogen quinone, respectively, which can react directly with DNA via a Michael addition or indirectly via generation of reactive oxygen species. Methylation of catechol estrogens by catechol-O-methyltransferase, conjugation of the catechol estrogen quinones with glutathione, and enzymatic reduction to reform catechol estrogens are processes that prevent accumulation of the highly reactive metabolites.
However, if the latter protective processes are insufficient, catechol estrogen quinones accumulate, which damage DNA either by oxidation or depurination, and release of catechol estrogen modified purines Liehr et al.
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Carcinogenesis mediated by steroid hormone like molecules derived from S. These mutations ultimately would transform the target cell, leading to hyperplasia and ultimately to neoplasia, i. Image contributed by co-author Banchob Sripa. Human metaphase chromosomes — image from Tang et al.
While examining human cases of urogenital schistosomiasis from Angola, we observed elevation in levels of estradiol in sera but not luteinizing hormone LH or testosterone Botelho et al.
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Estradiol is a steroid hormone secreted principally by the ovarian follicles in vertebrates. It seemed implausible that the elevated levels could be attributed to hypothalamic—pituitary—gonadal axis regulation. Rather, we speculated that schistosomes produced the estradiol-related metabolites that contributed to the elevated estradiol levels. Using mass spectrometry approaches Gouveia et al.
Catechol-estrogens are formed by hydroxylation on the steroid aromatic ring A. Hydroxylation of both C-2 and C-3 on a steroid ring was apparent and, further, oxidation to an estradiol-2,3-quinone. The schistosome estrogenic metabolites readily seen in urine and in vitro appear to arise by reactions of quinones of catechol estrogens with chromosomal DNA Botelho et al.
In addition, we exposed non-cancerous CHO Chinese hamster ovary cells to secretions and lysates of S.
If similar phenomena also occur in human urogenital schistosomiasis, we speculate that they contribute to the abnormal proliferation and accumulation of genetic changes that occur in schistosomiasis-associated carcinogenesis [Figure 2 ; Mostafa et al. Opisthorchiasis is associated with elevation of bile acids, including deoxycholic acid Vale et al.
Bile acids are synthesized in the liver from cholesterol, and the majorities are conjugated with either glycine or taurine Haswell-Elkins et al. Increased levels of nitrate and nitrite, which reflect endogenous generation of NO, occur during O. Oxysterols, which are oxidation products of cholesterol generated by enzymatic P or non-enzymatic processes Jaworski et al. Investigation of binding domains in human genes has demonstrated an association between different types of oxysterols and the development and progression of cancer of the colon, lung, breast and bile ducts Jaworski et al.
Bile acids constitute a large family of steroids carrying a carboxyl group in the side chain. Bile alcohols have similar products in bile acid biosynthesis or as end products.
We found these compounds in extracts of O. The effects of these individual species can be anticipated to be structure-dependent, and metabolic conversions will result in a complex mixture of biologically active and inactive forms Vale et al. Current understanding of how infections with these flukes lead to cancers has been reviewed recently Sithithaworn et al. In brief, in regions of high prevalence of opisthorchiasis, the risk factors for bile duct cancers are chronic inflammation and concomitant chronic injury of the biliary epithelium as the consequence of persistent parasitism by these fish-borne pathogens Sripa et al.
The risk of SSC of the bladder during urogenital schistosomiasis appears to be promoted by concurrent risk factors associated with bladder cancer where infection with S. Thus there are likely to be multiple factors including a diet rich in nitrosamines, spillover effects from local and systemic chronic inflammation reactive oxygen species, reactive nitrogen species directed against the worms, the secretion of mitogens and other mediators by the parasite Satarug et al.
To this list, we now include another potential mechanism: These processes contribute to urogenital schistosomiasis associated SCC during chronic urogenital schistosomiasis, and to CCA during chronic opisthorchiasis Figure 2. Overall, the structures that we have identified in S. Notably, a relation between putative oxysterol or bile acid metabolites from O.
Concluding Comments Infection with helminth parasites remains a persistent public health problem in developing countries. Three of these pathogens, C. Infection with these worms is definitively associated with cancer.
What is Schistosomiasis? - Definition, Types & Transmission
We have reported novel sterol-like metabolites and DNA-adducts in S. Because these molecules are metabolized to active quinones that can modify DNA, helminth parasite associated catechol estrogens might induce tumor-like phenotypes in the epithelia of the bile ducts and bladder. Whereas the roles of these new metabolites in bile duct cancer and SSC of the bladder remain to be examined in depth, this clearly is worthy of deeper investigation.
The urinary blood fluke S. Eggs, laid in the veins, break through the vein wall into the bladder and are voided during urination.
Schistosome and liver fluke derived catechol-estrogens and helminth associated cancers
The larval fluke develops in the body of a snail chiefly of the genera Bulinus and Physopsisthe intermediate host. The mature larva makes its way into the body of the final host, man, through the skin or the mouth. The intestinal blood fluke S.
The eggs pass from the host with the feces.
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The larva enters the body of a snail any of several generathe intermediate host, and returns to a human host through the skin. Snails of the genus Oncomelania are the intermediate host.
The adult occurs in the veins of the small intestine. Some eggs are carried in the bloodstream to various organs and may cause a variety of symptoms, including enlargement of the liver.
Human hosts may die from severe infestations. Flukes of detrimental economic significance to man include the widely occurring giant liver fluke of cattle Fasciola hepatica and the Chinese, or Oriental, liver fluke Opisthorchis sinensisor Clonorchis sinensis.A Novel Toll-Like Receptor (TLR) Influences Compatibility between the Gastropod Biomphalaria
Man may become infested with this fluke by eating uncooked vegetables. The Chinese liver fluke infests a variety of mammals, including man. In addition to the snail as an intermediate host, the Chinese liver fluke infests fish as a second intermediate host before passing to the final host. The cat liver fluke, Opisthorchis felineus, which may also infest man as the final host, also requires a freshwater snail Bithynia leachii and a carp as its secondary intermediate hosts.