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Anthelmintic effects of cyclosporin A on protoscoleces and secondary hydatid cysts of Echinococcus granulosus in the mouse.

Cyclosporin A (CsA), employed primarily as an immunosuppressant during the management of organ and graft transplants, exhibits anthelmintic properties. However, its efficacy against tapeworm infections in laboratory models is variable. A preliminary investigation has been undertaken to assess the action of CsA on the establishment and growth of protoscoleces and secondary hydatid cysts of ovine Echinococcus granulosus in mice. Administration of CsA in five consecutive daily doses, beginning 2 days prior to infection, resulted in significant reduction in cyst establishment (measured in terms of cyst masses, cyst numbers and cyst wet weights), when mice were autopsied 20 weeks post-infection. None of these parameters were significantly reduced when the drug was administered 18 weeks post-infection, although wet weight decreased by 42%. Ultrastructural examination of the germinal membrane and laminated layer of late-treated E. granulosus revealed abnormalities in all cysts studied whereas control and early-treated hydatids were normal. A case is made for the consideration of a clinical use for CsA for post-operative control of secondary hydatidosis and its efficacy against hydatid cysts is discussed.

Animals↗

A cytochemical study of the nervous system of the proteocephalidean cestode, Proteocephalus pollanicola.

The localization and distribution of cholinergic, serotoninergic and peptidergic nerve elements in the proteocephalidean tapeworm, Proteocephalus pollanicola, have been investigated by enzyme histochemistry, and by an indirect immunofluorescence technique interfaced with confocal scanning laser microscopy. Cholinesterase (ChE) activity was localized in the major components of the central nervous system (CNS) and the peripheral nervous system (PNS), including the innervation of the reproductive structures of the worm. Serotoninergic (5-HT) nerves were found in the paired cerebral ganglia, transverse commissure and in the 10 longitudinal nerve cords. Antisera to 17 mammalian regulatory peptides and the invertebrate peptide FMRFamide have been used to explore the peptidergic nervous system of the worm. The most extensive immunostaining occurred with antisera raised to members of the neuropeptide Y superfamily, namely neuropeptide Y (NPY), peptide YY (PYY) and pancreatic polypeptide (PP). In all cases, intense immunoreactivity was found in numerous cell bodies and fibres of both the CNS and PNS, including the innervation of the reproductive apparatus. FMRFamide antisera stained the same structures to a comparable degree as those raised to the NPY superfamily. Cholinergic and peptidergic elements were much more prevalent within the CNS, while the serotoninergic nerve fibres tended to dominate in the PNS. The overlap obtained in staining patterns for the peptidergic and cholinergic components suggests that there may be a certain amount of co-localization of peptides with small-molecule transmitter substances in the same neurone. Weak staining for the tachykinin, substance P and for calcitonin gene-related peptide (CGRP) was confined to the major longitudinal nerve cords.

Animals↗

Application of metabolic control analysis to the pathways of carbohydrate breakdown in Hymenolepis diminuta.

The application of metabolic control theory to carbohydrate breakdown in the tapeworm Hymenolepis diminuta shows that it is not necessary for both phosphoenolpyruvate carboxykinase and pyruvate kinase to be modulated in order to control the relative fluxes through the two arms of the phosphoenolpyruvate branchpoint. Changes in activity of enzymes outside of the two branches also influence the flux ratio. Control coefficients of individual enzymes for the fluxes through phosphoenolpyruvate carboxykinase and pyruvate kinase are not fixed, but vary as the flux ratio between the two arms of the branchpoint changes. The metabolic model can also be used to evaluate the role of the fructose-1,6-bisphosphate loop and to calculate metabolite transition time control coefficients.

Acetates↗

Platyhelminth FMRFamide-related peptides.

Platyhelminths are the most primitive metazoan phylum to possess a true central nervous system, comprising a brain and longitudinal nerve cords connected by commissures. Additional to the presence of classical neurotransmitters, the nervous systems of all major groups of flatworms examined have widespread and abundant peptidergic components. Decades of research on the major invertebrate phyla, Mollusca and Arthropoda, have revealed the primary structures and putative functions of several families of structurally related peptides, the best studied being the FMRFamide-related peptides (FaRPs). Recently, the first platyhelminth FaRP was isolated from the tapeworm, Moniezia expansa, and was found to be a hexapeptide amide, GNFFRFamide. Two additional FaRPs were isolated from species of turbellarians; these were pentapeptides, RYIRFamide (Artioposthia triangulata) and GYIRFamide (Dugesia tigrina). The primary structure of a monogenean or digenean FaRP has yet to be deduced. Preliminary physiological studies have shown that both of the turbellarian FaRPs elicit dose-dependent contractions of isolated digenean and turbellarian somatic muscle fibres. Unlike the high structural diversity of FaRPs found in molluscs, arthropods and nematodes, the complement of FaRPs in individual species of platyhelminths appears to be restricted to 1 or 2 related molecules. Much remains to be learnt about platyhelminth FaRPs, particularly from peptide isolation, molecular cloning of precursor proteins, receptor localization, and physiological studies.

Amino Acid Sequence↗

Water demand and schistosomiasis among the Gumau people of Bauchi State, Nigeria.

A helminthological study of stool and urine samples from 1037 people from 4 rural communities in Gumau District of Bauchi State, Nigeria, was carried out using formol-ether concentration and direct centrifugation methods respectively. 39.0% of persons examined were infected. Ova of Ascaris lumbricoides, Schistosoma haematobium and S. mansoni were the most common. Trichuris trichiura, hookworm, tapeworm and Strongyloides stercoralis were also encountered. 17.9% and 10.8% of examined persons had S. haematobium and S. mansoni infections respectively. A significant relationship was found between water demand index (number of persons per well) and infection with S. haematobium (r = 0.95) and S. mansoni (r = 0.88) (P less than 0.01). Such a relationship was not found with other helminth infections. A significant association was also found between distance from a river and prevalence of S. haematobium (r = 0.94) and S. mansoni (r = 0.95) (P less than 0.01), but not with the other helminth infections. These findings suggest that the water demand index may be an important factor in the epidemiology of schistosome infections in rural communities.

Helminthiasis↗

Albendazole treatment in human taeniasis.

The results are presented of albendazole trials on human taeniasis infections in Honduras, involving 56 of 68 individuals (2% of the inhabitants) found to be infected during surveys conducted in 15 rural communities. Of the 3 methods used for diagnosis of infection, the Kato cellophane thick smear showed 80% reliability, a combination of Kato and 'Scotch' tape perianal swab 88%, and clinical history of proglottid expulsion less than 50%. Individuals were treated with a dose of 400 mg of albendazole per day for 3 d, followed for 5 d to verify tapeworm expulsion, and evaluated again at 60 and 90 d to assess drug efficacy. All 56 treated individuals remained stool-negative after 60 and 90 d; a partial strobila or segments were recovered from 21 of them (37.5%). Of these, Taenia saginata was identified from 4, and T. solium from 15; 2 specimens could not be specifically identified. Based on negative stool examinations and clinical history after 60 and 90 d, albendazole seems to be a well tolerated, very effective drug for treating infections with Taenia spp. However, confirmation of these results is needed due to the difficulty of making a reliable diagnosis of such infections.

Adolescent↗

Single dose treatment with praziquantel for human Diphyllobothrium nihonkaiense infections.

Diphyllobothrium nihonkaiense is a large pseudophyllid cestode and one of the commonest parasites derived from fish in Japan. Three Japanese patients infected with D. nihonkaiense were treated with a single oral dose of 7, 23 or 25 mg/kg of praziquantel. All patients expelled the tapeworm with scolex, and no side effect was noted. This study indicates that single-dose treatment with praziquantel is effective against D. nihonkaiense infection.

Adult↗

Mechanical integration of muscle, tegument, and subtegumental tissues by anchoring fibrils and microfibrils in the cestode Hymenolepis diminuta.

Electron microscopic examination of the epidermal basement membrane region of the rat tapeworm, Hymenolepis diminuta, has revealed specialized connective tissue structures that appear to anchor the epidermis, or tegument, to the parenchymal tissues of the helminth, as well as interconnect subtegumental muscle fibers, tegument, and parenchyma. Anchoring fibrils-cross-banded bundles of ca. 3 nm diameter filaments--were observed to directly interlink tegument and muscle, muscle and muscle, and tegument, muscle, and parenchymal connective tissue. Anchoring fibrils therefore appear to mechanically integrate epidermal tissue movements in response to subtegumental muscle contraction. A well-developed stratum of microfibrils, forming the lamina reticularis of the tegumental basement membrane, may also help anchor the tegument as well as to serve as a flexible, reinforcing sheath that protects parenchymal tissues from excessive radial displacement due to muscle contraction.

Animals↗

Thromboxane A2 generation by the larval cestode, Taenia taeniaeformis.

The larval stage of the tapeworm, Taenia taeniaeformis, was incubated in different concentrations of arachidonic acid. At various times after incubation, aliquots were removed for bioassay on either 38 microM aspirin or non-aspirin-treated equine platelets and by radioimmunoassay for the thromboxane A2 breakdown product, thromboxane B2 (TXB2). Platelet agonist activity was detected as early as 30 sec after addition of the arachidonic acid. In aspirin-treated platelets, this agonist activity peaked at 1 to 4 min and thereafter decayed rapidly with a time course that was both worm and arachidonic acid dependent. When assayed on non-aspirin-treated platelets the agonist activity was again detectable as early as 30 sec after addition of arachidonic acid, peaked at 1 to 3 min and then decayed very slowly over a 30-min period of incubation. It was found that levels of TXB2 were detected which increased over time concomitant with the decay of the platelet agonist activity. The most consistent detection of TXB2 generation was at 30 min with a mean of 49.6 pg and a range of 22.1 to 84.8 pg for four experiments. This report presents the first evidence for arachidonic acid utilization by a cestode or trematode and could in part provide an explanation for the marked cellular inflammation noted around dead or dying parasites.

Animals↗

Swine immunity to selected parasites.

Swine parasitism exerts a significant economic impact worldwide. In the United States, the greatest losses are due directly or indirectly to the costs of zoonotic parasitisms. Three of the six most common foodborne parasitic diseases of humans in the United States are associated with pork consumption. These include toxoplasmosis, taeniasis or cysticercosis (caused by the pork tapeworm Taenia solium), and trichinellosis. Toxoplasmosis is of particular concern because of the fulminating disease that occurs in immunocompromised people. Generalizations and extrapolations of information derived from rodent and human studies, to swine parasitisms, are complicated by immunological differences between the hosts, and by the diverse biological characteristics of internal and external parasites studied. Swine studies thus far reported have demonstrated that protective immunity to helminth infection involves both cellular and humoral mechanisms, with antibodies and antibody-mediated responses playing important roles in preventing establishment of newly acquired larvae. Protection against protozoan parasites is primarily by cell-mediated strategies, whereas protective immunity to arthropod infestation is primarily through humoral mechanisms, principally those associated with type 1 hypersensitivity.

Animals↗

Benzoquinones in stages of the life-cycle of the cestode Spirometra mansonoides.

Ubiquinone-10 and rhodoquinone-10 were detected in stages of the life-cycle of a pseudophyllidean cestode, Spirometra mansonoides, by chromatographic, UV spectrophotometric, proton nuclear magnetic resonance spectrometric and electron impact mass spectrometric methods. Ubiquinone-10 was identified in 1-day-old eggs and coracidia, and rhodoquinone-10 in coracidia, plerocercoids and adult tapeworms. Tentative identification were also made of ubiquinone-10 in procercoids and rhodoquinone-10 in 10-day-old eggs. The roles of benzoquinones in helminth aerobic and anaerobic metabolism are discussed in relation to their distribution in stages of the S. mansonoides life-cycle.

Animals↗

Developmental and immune regulation of gene expression in Hymenolepis diminuta.

Gene expression and its regulation was studied in the rat tapeworm, Hymenolepis diminuta, during strobilization. RNAs extracted from the different developmental stages of the parasite were translated in vitro in a rabbit reticulocyte lysate system. Two-dimensional patterns of the translational products were compared with the 2-dimensional patterns obtained by metabolic labelling with [35S]methionine. The results indicated a post-transcriptional regulation of gene expression during strobilization in this parasite. Gene expression and its regulation was also studied in H. diminuta obtained from 'non-permissive' hosts (mice) and immune suppressed mice and compared with the parasites of the same age obtained from 'permissive' rats hosts. The 2-dimensional patterns of the in vitro translation products, obtained by translating the RNA of different groups of parasites, were compared with the patterns of gene products obtained from parasites using [35S]methionine metabolic labelling. The results indicated a massive post-transcriptional regulation of gene expression, the latter inhibited in parasites obtained from normal mice, but not in immune suppressed mice.

Animals↗

In vivo 31P NMR spectrum of Hymenolepis diminuta and its change on short-term exposure to mebendazole.

The 31P NMR spectrum of the adult tapeworm, Hymenolepis diminuta, at 37 degrees C during perfusion with physiological saline was composed of 10 peaks. Based on chemical shifts and analysis of worm extracts, the phosphorus components included glucose-6-phosphate, fructose-6-phosphate, phosphorylcholine, glycerophosphoryl choline and -ethanolamine, nucleotide monophosphate-diphosphate and -triphosphate, nicotinamide adenine dinucleotide and uridine diphosphate glucose. The mean level of nucleotide triphosphate was 0.86 nmol (mg fresh weight)-1 and the nucleotide triphosphate/-diphosphate ratio 3.9. Based on the nucleotide triphosphate level, worms were viable for at least 3 h and the intracellular pH was maintained constant at approximately 6.7. Short-term exposure to mebendazole perfused at 11 or 27 microM solubilized in physiological saline containing 0.5% Tween 80 or 0.1% dimethyl sulphoxide had little effect on the nucleotide triphosphate level. Some cytological changes, however, were evident following perfusion of mebendazole. In contrast, exposure to 2,4-dinitrophenol caused a rapid decline in nucleotide triphosphate level. It was concluded that mebendazole does not exert its primary effect on oxidative phosphorylation.

Animals↗

Effect of phenothiazines on Hymenolepis diminuta with special reference to the brush border Ca2+-dependent ATPase.

Incubation of Hymenolepis diminuta with the calmodulin antagonist trifluoperazine causes lesions in the brush border of the cestode. Exposure to a phenothiazine of lower lipophilicity, trifluoperazine sulphoxide, had little effect. Characterisation of isolated brush border revealed two forms of Ca2+-ATPase which exhibited maximum activity at pH 5.5 and 7.5. Both forms were Ca2+-dependent but only the latter was influenced by calmodulin and trifluoperazine. It is suggested that the Ca2+-ATPase present in the tapeworm brush border may be the site of trifluoperazine toxicity.

Animals↗

The primary structure of neuropeptide F (NPF) from the garden snail, Helix aspersa.

Neuropeptide F (NPF), originally isolated from the sheep tapeworm, Moniezia expansa, consists of 39 amino acid residues terminating in a phenylalaninamide. An analogous neuropeptide has been isolated and sequenced from extracts of circumoesophageal ganglia of the garden snail, Helix aspersa. This neuropeptide exhibits partial primary structural similarity to members of the vertebrate neuropeptide Y (NPY)/pancreatic polypeptide (PP) superfamily. NPF is thus of widespread occurrence in the nervous systems of invertebrates from different phyla and may represent the phylogenetic precursor of the vertebrate NPY/PP superfamily.

Amino Acid Sequence↗

Molecular characterization of the Spirometra mansonoides genome: renaturation kinetics, methylation, and hybridization to human cDNA probes.

High molecular weight DNA from pleroceroid larvae of the tapeworm Spirometra mansonoides was purified from isolated nuclei by conventional techniques. The DNA so isolated has a melting temperature (Tm) of 87 degrees C and a guanine plus cytosine (G/C) content of 44%. 5-Methyl cytosine could not be detected in plerocercoid DNA by HPLC analysis of DNA hydrolysates, by radiolabeling 5'-termini of MspI digests with polynucleotide kinase, or by comparing restriction patterns generated by MspI and HpaII. Renaturation kinetics demonstrated that the genome of S. mansonoides contains repetitive as well as single copy sequences and has a genome size estimated at approx. 1.6 X 10(9) bp. Hybridization was carried out between plerocercoid DNA and cDNAs for human beta-actin, alpha-tubulin and growth hormone (hGH). Rationale for this analysis was based on known homologies among actin and tubulin genes in numerous species and on apparent similarities between hGH and a plerocercoid growth factor that may be reflected in similar DNA sequence. Scanning densitometry of dot blots demonstrated that the hGH probe annealed to the same extent at low stringency (1 M NaCl, 55 degrees C) to DNA from plerocercoids, rat liver and chicken erythrocytes; but this interaction was less than to DNA from human lymphocytes, calf thymus and mouse skin. Similar results were obtained when restriction endonuclease digests of these DNAs were analyzed by Southern transfer. Little or no hybridization of the growth hormone probe to plerocercoid DNA was evident at higher stringency (1 M NaCl, 65 degrees C). In contrast, human tubulin and actin probes showed extensive hybridization to pleroceroid restriction fragments under the high stringency conditions.

Actins↗

Hydatidosis: changing concepts in epidemiology and speciation.

Hydatidosis, caused by dog tapeworms of the genus Echinococcus, is one of the most important cestode infections of man. It is widely distributed and recent information points to a spread of the disease into areas previously free of it. This article reviews recent advances in understanding the biology of Echinococcus, relating these developments to the epidemiology of hydatid disease and its control.

Journal Article↗

Plerocercoid growth factor: a homologue of human growth hormone.

Plerocercoids of the tapeworm, Spirometra mansonoides, produce a factor with characteristics similar to those of mammalian growth hormone (GH). Plerocercoid growth factor (PGF) stimulates growth and mimics other actions of GH but does not possess the anti-insulin/diabetogenic activities intrinsic to mammalian growth hormones. Duplication of activities unique to human GH, chemical and physical similarities, plus crossreactivity with strictly specific anti-hGH monoclonal antibodies, underlie the hypothesis that S. mansonoides has obtained and expresses a human gene for GH. In this article, Kirk Phares discusses the similarities between the two hormones.

Journal Article↗