SEARCH · PubMed Health

Results for “FASCIOLA HEPATICA”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 739 records · Page 41Linked to original sources

PubMed2002

The efficacy of formulations of triclabendazole and ivermectin in combination against liver fluke (Fasciola hepatica) and gastro-intestinal nematodes in cattle and sheep and sucking lice species in cattle.

OBJECTIVE: To assess the efficacy of two formulations of triclabendazole and ivermectin in combination against liver fluke (Fasciola hepatica), gastro-intestinal nematodes and sucking louse species in cattle and sheep. PROCEDURE: A study of 540 cattle and 428 sheep at 18 sites throughout Victoria and New South Wales was undertaken. At each site, one group of cattle or sheep was treated with a combined formulation (Fasimec Cattle or Fasimec Sheep), another received ivermectin and triclabendazole separately. In trials on lice infestation, an additional group remained untreated. Samples for faecal egg counts were collected on days -7, 0 (treatment day), +7, +14 and +21 after treatment. Lice assessments were carried out on days -7, 0, +7, +14, +28, +42 and +56. RESULTS: Both treatments were highly efficacious (> 98% efficacy) against liver fluke in cattle and sheep, against three sucking lice species of cattle and against gastro-intestinal nematodes in sheep. There was also no significant difference between treatments in efficacy. Against gastro-intestinal nematodes, Fasimec Cattle was significantly (P < 0.01) more effective than the separately applied ivermectin and triclabendazole treatment. Mean efficacy for the Fasimec Cattle and Ivomec/Fasinex 120 groups respectively, was 97.6% and 94.2% on Day +7, 98.9% and 91% on Day +14 and 98.5% and 92.6% on Day +21. CONCLUSION: The efficacy of Fasimec' Cattle and Fasimec Sheep was at least equal to that of currently registered products (with the same active ingredients) used to control these parasites.

Administration, Oral↗

PubMed2004

Cathepsin L1, the major protease involved in liver fluke (Fasciola hepatica) virulence: propetide cleavage sites and autoactivation of the zymogen secreted from gastrodermal cells.

The secretion and activation of the major cathepsin L1 cysteine protease involved in the virulence of the helminth pathogen Fasciola hepatica was investigated. Only the fully processed and active mature enzyme can be detected in medium in which adult F. hepatica are cultured. However, immunocytochemical studies revealed that the inactive procathepsin L1 is packaged in secretory vesicles of epithelial cells that line the parasite gut. These observations suggest that processing and activation of procathepsin L1 occurs following secretion from these cells into the acidic gut lumen. Expression of the 37-kDa procathepsin L1 in Pichia pastoris showed that an intermolecular processing event within a conserved GXNXFXD motif in the propeptide generates an active 30-kDa intermediate form. Further activation of the enzyme was initiated by decreasing the pH to 5.0 and involved the progressive processing of the 37 and 30-kDa forms to other intermediates and finally to a fully mature 24.5 kDa cathepsin L with an additional 1 or 2 amino acids. An active site mutant procathepsin L, constructed by replacing the Cys(26) with Gly(26), failed to autoprocess. However, [Gly(26)]procathepsin L was processed by exogenous wild-type cathepsin L to a mature enzyme plus 10 amino acids attached to the N terminus. This exogenous processing occurred without the formation of a 30-kDa intermediate form. The results indicate that activation of procathepsin L1 by removal of the propeptide can occur by different pathways, and that this takes place within the parasite gut where the protease functions in food digestion and from where it is liberated as an active enzyme for additional extracorporeal roles.

Amino Acid Motifs↗

PubMedDate not supplied

[Arguments and proposals for a new developmental interpretation of Fasciola hepatica L. in Lymnaea (Galba) truncatula Müller (author's transl)].

The authors study the influence of several factors: temperature, drying up of ground, bodily volume of intermediary host on development of the redial generations of Fasciola hepatica in Lymnaea truncatula. Three redial generations are seen in Lymnaea truncatula, whatever environmental factors. The number of rediae of generations 2 and 3 is correlated with bodily volume of the snail host. The temperature affects synchronism of cercarial maturation in rediae of generations 1 and 2.

Animals↗

PubMed1991

Fasciola hepatica: the effect of the microfilament inhibitor cytochalasin B on the ultrastructure of the adult fluke.

The effect of the microfilament inhibitor cytochalasin B (10 and 100 micrograms/ml) on the ultrastructure of adult Fasciola hepatica was determined in vitro by scanning and transmission electron microscopy (SEM, TEM) using both intact flukes and tissue-slice material. SEM revealed that initial swelling of the tegument led to surface blebbing and limited areas of sloughing after 24 h treatment at 100 micrograms/ml. In the tegumental syncytium, basal accumulations of secretory bodies (especially T2s) were evident in the earlier time periods but declined with longer incubations, until few secretory bodies remained in the syncytium overall. Blebbing of the apical plasma membrane and occasional areas of breakdown and sloughing of the tegument were observed over longer periods of treatment at 100 micrograms/ml. In the tegumental cell bodies, the Golgi complexes gradually decreased in size and activity, and few secretory bodies were produced. In the later time periods, the cells assumed abnormal shapes, the cytoplasm shrinking in towards the nucleus. In the vitelline follicles, a random dispersion of shell protein globules was evident within the intermediate-type cells, rather than their being organized into distinct shell globule clusters. Disruption of this process was more severe at the higher concentration of 100 micrograms/ml and again was more evident in tissue-slice material. In the latter, after prolonged (12 h) exposure to cytochalasin B, the intermediate and mature vitelline cells were filled with loosely packed and expanded shell globule clusters, containing few shell protein globules. The mature vitelline cells continued to lay down "yolk" globules and glycogen deposits. Disruption of the network of processes from the nurse cells was evident at the higher concentration of cytochalasin. Spaces began to appear between the vitelline cells and grew larger with progressively longer incubation periods, and the cells themselves assumed abnormal shapes. A number of binucleate stem cells were observed in tissue-slice material at the longest incubation period (12 h).

Animals↗

PubMed2005

Fasciola hepatica: an unusual case of adaptation to a Moroccan population of Galba truncatula.

Parent snails, F1, and F2, originating from a Moroccan population of Galba truncatula, were experimentally subjected to sympatric miracidia of Fasciola hepatica at 20 degrees C to determine the mode of adaptation of this parasite to the local intermediate host via the study of redial burdens and by following cercarial shedding. In spite of an increase in the global prevalences of infections, the frequencies recorded for immature or mature infections in dissected snails did not show any significant variations from parents to F2. If the redial burdens in mature infections were mainly composed of first-generation rediae in parent snails, the numbers of rediae belonging to subsequent generations significantly increased in the F1 and F2 generations. In mature infections, the lengths of first-generation rediae and their contents significantly decreased from parent snails to F2. Conversely, in the first redial cohort of the second generation (R2a rediae), only the intraredial contents increased significantly with snail generation. In mature infections, daughter redia production was ensured by all mother rediae of the first generation in parent snails, whereas it was progressively effected by the first mother redia in the F1 and F2 infections. The numbers of cercariae shed by snails increased significantly from parents to F2. If the cercariae produced by first-generation rediae decreased with snail generation, an inverse finding was noted in the case of R2a rediae. We suggest that snails impose a bottleneck on the development of the first mother redia, so that other mother rediae of the first generation react with greater growth (until 3.9 mm in parent snails), an important daughter redia production and a high cercarial production. As the first mother redia remained alive until day 49 post-exposure but without growth after week 2, this mode of development must be considered as a new developmental pattern of redial generations, and it is useful to determine its frequency in snails, as it has never been found in naturally or experimentally infected snails in central France.

Adaptation, Physiological↗

PubMed1994

Influence of anti-inflammatory treatments on experimental infection of rats with Fasciola hepatica: changes in serum levels of inflammatory markers during the early stages of fasciolosis.

Anti-inflammatory treatments with dexamethasone, indomethacin or aspirin shortly before or immediately after the experimental infection of rats with Fasciola hepatica resulted in an increase in the rats' burden of adult flukes, suggesting that the inflammatory system played an active part in the rats' immune defense against invasive F hepatica. An anti-parasitic effect of cyclosporin A on F hepatica infection in rats was also demonstrated. A weekly study of various inflammatory markers (acute phase proteins, leucocytes and platelets) demonstrated that no inflammatory reaction had occurred after the first two weeks of infection, but that there was a significant increase in acute phase proteins after three and four weeks. These increases indicated that a chronic inflammatory reaction, associated with liver damage and an increasing eosinophilia, had occurred.

Acute-Phase Proteins↗

PubMed2003

The comparative metabolism of triclabendazole sulphoxide by triclabendazole-susceptible and triclabendazole-resistant Fasciola hepatica.

Benzimidazole anthelmintics are widely used against nematode, cestode and trematode parasites. The drugs undergo several enzyme-mediated reactions within the host animal that produce a number of metabolites. Although it has been shown that certain helminths, including Fasciola hepatica, can metabolise albendazole, nothing is known regarding the ability of the liver fluke to metabolise triclabendazole, which is the major flukicidal compound currently on the market. In the current study, adult triclabendazole-susceptible flukes were treated with triclabendazole sulphoxide in vitro, and the metabolism of the drug was monitored by high performance liquid chromatography. The data show that F. hepatica can metabolise triclabendazole sulphoxide into its relatively inert sulphone metabolite. Parallel experiments using triclabendazole-resistant flukes showed that the conversion of triclabendazole sulphoxide to triclabendazole sulphone was on average 20.29% greater in the resistant flukes compared with the susceptible flukes. The results are discussed with regard to the mechanism of triclabendazole resistance in F. hepatica.

Albendazole↗

PubMed1975

Oxidative enzymes in the development of Fasciola hepatica L. IV. The activity of oxidases and dehydrogenases in redia.

The object of the study was to investigate the occurrence and localization of oxidative enzymes in the redia -- the third larval stage of Fasciola hepatica L. The author detected cytochrome oxidase, peroxidase, NADH and NADPH tetrazolium reductases (diaphorases), as well as succinate, isocitrate, malate, lactate, alpha-glycerophosphate, glyceraldehyde phosphate, glucose-6-phosphate, 6-phosphogluconate, beta-hydroxybutyrate, L-glutamate, and alcohol dehydrogenases. The presence and localization of the enzymes in various periods of development of the redia were detected with histochemical methods. Out of the studied oxidases and dehydrogenases only cytochrome oxidase was found to be absent from the stages of young rediae. It was ascertained that the redia uses all three paths of release of energy i.e. the glycolytic, Krebs, and pentose cycles, glycolysis being presumably the principal mode of energy production.

Alcohol Oxidoreductases↗

PubMed2005

Fasciola hepatica: humoral and cytokine responses to a member of the saposin-like protein family following delivery as a DNA vaccine in mice.

The humoral and cellular responses to DNA vaccination of BALB/c mice with a novel antigen from the Fasciola hepatica saposin-like protein family (FhSAP-2) have been investigated. Two constructs were produced containing the FhSAP-2 DNA sequence, one intended for extracellular secretion of FhSAP-2 protein, and one expressing FhSAP-2 in the cytoplasm of a transfected cell. The constructs were tested in HEK 293T cells, with the secretory construct producing less detectable FhSAP-2 relative to cytoplasmic construct when observed by fluorescence. The size of expressed protein was confirmed by Western blot of cell lysate, but FhSAP-2 was undetectable in cell supernatants. Both, secretory and cytoplasmic constructs as well as FhSAP-2 recombinant protein were tested in mice. The antibody response elicited in mice vaccinated with the rFhSAP-2 induced high levels of IgG(1), IgG(2), and IgE as well as high levels of IL-10 and IFNgamma indicating a mixed Th1/Th2 response. Vaccination of mice intramuscularly with the cytoplasmic FhSAP-2 construct resulted in a dominant IgG(2a) isotype antibody as well as a dominant IFNgamma cytokine, with significant IgE, IgG(1), and IL-10 responses also present, suggesting a mixed Th1/Th2 profile. Isotype and cytokine profiles elicited by the FhSAP-2 secretory construct were similar to those obtained with the cytoplasmic construct but at levels that were significantly lower. The results demonstrate that FhSAP-2 can be delivered as a DNA vaccine construct and induces a stronger Th1 response than the recombinant protein alone. This could result in an improvement in the immunoprophylactic potential of this candidate vaccine against F. hepatica.

Animals↗

PubMed1996

Detection of antibodies of Fasciola hepatica excretory--secretory antigens in experimentally infected goats by enzyme immunosorbent assay.

An ELISA with excretory-secretory (ES) antigens has been evaluated as a technique for the early detection of specific antibodies in Fasciola hepatica infections in goats. Goats were experimentally infected with 100 or 200 metacercariae of bovine origin and serum samples were taken periodically over 365 days. The ELISA test was performed with ES antigens (10 micrograms mL-1), a single dilution of sera (1:800) and anti-goat IgG conjugate (1:1000). ES specific antigens were detected in all infected goats between 15 and 30 days postinfection (PI) and maximum antibody levels were reached at 90 days PI. Positive antibody levels (significantly different from those of controls) were still found at 365 days PI. No significant differences were observed between goats infected with 100 or 200 metacercariae. In all infected goats, eggs appeared in faeces between 60 and 90 days PI. ELISA with ES antigens could be a feasible method for the early diagnosis of goat fasciolosis.

Animals↗

PubMed2005

[Some enzymes associated with lipid catabolism in the Fasciola hepatica larvae--Galba truncatula system. I. Esterases and lipases].

Histochemical and cytofotometric techniques were used to detect esterase and lipase in the hepatopancreas of the snail Lymnaea truncatula and in larval stages of its parasite Fasciola hepatica. Activities of both enzymes were shown to increase in the infected hepatopancreas, compared with the control. The effect is ascribed by the authors to compensation processes emerging as a defence mechanism in the snail. Both enzymes, esterase and lipase proved to be highly active in tissues of sporocysts, rediae and cercariae, thus demonstrating the larvae to be capable of katabolism of lipids and utilising them as an energy source.

Animals↗

PubMed1994

Fasciola hepatica: liver microsomal membrane functions in host rat.

Changes in different microsomal membrane functions were measured in the liver of rats 3, 6, or 9 weeks following an oral infection with 20 metacercariae of Fasciola hepatica. The parasitic pathology noted at autopsy was accompanied by increased levels in both plasma aspartate aminotransferase (EC 2.6.1.1) and microsomal gamma-glutamyltransferase (EC 2.3.2.2). Heme oxygenase activity of microsomes was significantly decreased by Weeks 3 and 6 postinfection and this decrease correlates with those of total microsomal cytochrome P450 and certain P450-dependent monooxygenase activities, namely, benzphetamine demethylation, ethoxycoumarin deethylation, and benzopyrene hydroxylation. Microsomal epoxide hydrolase (EC 3.3.2.3) was only altered 6 weeks after the infection. During the early stages of the parasitism, there were decreases in both microsomal calcium uptake and calcium ATPphosphohydrolase activity (EC 2.6.1.1), whereas membrane fluidity, estimated by the order parameter S, was lower in the infected rats than that in the controls. These alterations could be related to the already described increase in liver cytosolic calcium or lipid peroxidation which occurs in experimental fascioliasis.

Animals↗

PubMed1987

Fasciola hepatica in vitro: increased susceptibility to fasciolicides in a defined serum-free medium.

The cidal properties of some phenolic, halogenated diphenyl, salicylanilide, benzimidazole and diaminophenoxyalkane anthelmintics, against 6-week-old worms of Fasciola hepatica were assessed in vitro. In a conventional fluke culture medium containing RPMI 1640, supplemented with serum with or without rabbit erythrocytes or pink-ghosts, only the halogenated diphenyl and salicylanilide compounds showed activity at concentrations equal to or less than 100 microM. However, when basal, serum and cell-free RPMI 1640 was used, all compounds other than diamphenethide were highly active, their minimum lethal concentrations being some 25-125 times lower under these conditions. The inclusion of rabbit liver microsomes in the basal culture medium resulted in diamphenethide exhibiting cidal activity equivalent to that seen when its free-amine active metabolite was assayed. The possibility that the activity of many of these compounds was masked in vitro because of their serum binding properties is discussed. Recommendations are made that in vitro screens for new fasciolicides should be carried out in serum-free medium and that additional replicates containing mammalian liver microsomes and liver cytosolic extracts be included as means for the metabolic activation of certain otherwise undetectable prodrugs.

Animals↗

PubMed1984

Trematodiasis in Turkey: comparative efficacy of triclabendazole and niclofolan against natural infections of Fasciola hepatica and F. gigantica in sheep.

A new fasciolicide, triclabendazole, tested at single oral dose rates of 5 and 10 mg/kg body-weight, proved to be highly effective (greater than 99%) against chronic field infections of Fasciola hepatica and F. gigantica in sheep. The performance of the new drug compared favourably with niclofolan at the recommended dose. Neither product was effective against Dicrocoelium dendriticum and Paramphistomum spp.

Animals↗

PubMed1996

Fasciola hepatica: disruption of the vitelline cells in vitro by the sulphoxide metabolite of triclabendazole.

The effects of the active sulphoxide metabolite of the fasciolicide triclabendazole (Fasinex, Ciba-Geigy) on the vitelline cells of Fasciola hepatica were determined in vitro by transmission electron microscopy using both intact flukes and tissue-slice material. At a triclabendazole concentration of 15 micrograms/ml the vitelline cells of intact flukes showed ultrastructural changes only after prolonged incubation periods (12-24 h). The changes observed were a swelling of the granular endoplasmic reticulum (GER) cisternae with decreased ribosomal covering in the intermediate-type cells and condensation of chromatin and disappearance of the nucleolus in the nucleus of the stem cell. Similar changes were evident more quickly (by 6 h) in whole flukes treated at the higher concentration of 50 micrograms/ml. The shell globule clusters were loosely packed in the intermediate type-2 cells, and the number of intermediate type-1 cells declined with more prolonged incubation. Disruption of the nurse-cell cytoplasm was also observed from 12 h onwards. After only 6 h incubation of tissue-slice material at 50 micrograms/ml, intermediate type-1 cells were absent, shell globule clusters in mature cells were loosely packed and the nurse-cell cytoplasm was badly disrupted. By 12 h the vitelline cells were vacuolated and grossly abnormal. The results are discussed in relation to postulated actions of triclabendazole against the microtubule component of the cytoskeleton and against protein synthesis in the fluke.

Animals↗

PubMed1995

The characteristics of redial generations in Lymnaea truncatula exposed to Fasciola hepatica miracidia after poisoning by sublethal doses of cupric chloride.

Adult Lymnaea truncatula were placed in a sublethal dose of copper chloride (0.1 mg/l) for 1 h, and then in normal water before being exposed to a single Fasciola hepatica miracidium on the 2nd or 9th day of the experiment. Infection rates were higher in untreated snails and in snails infected 9 d after treatment (73.5 and 71.4%) then in snails infected 2 d after copper contact (48.1%). Histological examination of surviving snail on the 30th day after miracidial exposure revealed that the total number of rediae was 25 and 31 per snail in snail groups infected 2 and 9 d respectively after copper contact, and 44 in untreated controls. There was a drop in the number of live, free rediae in infected snails after treatment contact. This decrease was more marked in the first redial generation than in the first cohort of the second generation. These results reveal that the infection rate in snails and the redial burden of F hepatica were reduced by the copper treatment of snails before miracidial exposure but placement of survivors in water for 8 d after treatment limited the consequences of chemical toxicity.

Animals↗

PubMed1997

Crystallization, structural determination and analysis of a novel parasite vaccine candidate: Fasciola hepatica glutathione S-transferase.

Glutathione S-transferases (GSTs) represent the major class of detoxifying enzymes from parasitic helminths. As a result, they are candidates for chemotherapeutic and vaccine design. Indeed, GSTs from Fasciola hepatica have been found to be effective for vaccinating sheep and cattle against fasciolosis. This helminth contains at least seven GST isoforms, of which four have been cloned. The cloned isoforms (Fh51, Fh47, Fh7 and Fh1) all belong to the mu class of GSTs, share greater than 71% sequence identity, yet display distinct substrate specificities. Crystals of Fh47 were obtained using the hanging drop vapour diffusion technique. The crystals belong to space group I4122, with one monomer in the asymmetric unit, which corresponds to a very high solvent content of approximately 75%. The physiological dimer is generated via a crystallographic 2-fold rotation. The three-dimensional structure of Fh47 was solved by molecular replacement using the Schistosoma japonicum glutathione S-transferase (Sj26) crystal structure as a search model. The structure adopts the canonical GST fold comprising two domains: an N-terminal glutathione-binding domain, consisting of a four-stranded beta-sheet and three helices whilst the C-terminal domain is entirely alpha-helical. The presence of Phe19 in Fh47 results in a 6 degrees interdomain rotation in comparison to Sj26, where the equivalent residue is a leucine. Homology models of Fh51, Fh7 and Fh1, based on the Fh47 crystal structure, reveal critical differences in the residues lining the xenobiotic binding site, particularly at residue positions 9, 106 and 204. In addition, differences amongst the isoforms in the non-substrate binding site were noted, which may explain the observed differential binding of large ligands. The major immunogenic epitopes of Fh47 were surprisingly found not to reside on the most solvent-exposed regions of the molecule.

Amino Acid Sequence↗

PubMedDate not supplied

Fasciola hepatica: identification of molecular markers for resistant and susceptible Pseudosuccinea columella snail hosts.

Protein electrophoresis, RAPD-PCR and nuclear rDNA ITS sequencing were performed to search for genetic differences between Pseudosuccinea columella snails susceptible and resistant to Fasciola hepatica infection. Of the 21 enzymatic loci analyzed in both populations, none of them exhibited neither within- or between-group variation. Such an absence of enzyme polymorphism support the hypothesis of selfing as the "prevalent" mating system for this hermaphroditic species. Conversely, the RAPD profiles displayed clear differences between susceptible and resistant isolates for 17 of the 26 primers tested while no within-group variation was detected. rDNA ITS sequence analysis from snails of each isolates showed only two bases that differed between groups accounting for a 0.17% of variation confirming that susceptible and resistant snails belong to the same species. This is the first time that a genetic variation using RAPD markers is demonstrated between susceptible and resistant lymnaeid snails vis-a-vis of F. hepatica infection in absence of experimental selection.

Animals↗