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PubMed1983

Efficacy of a benzenedisulfonamide against experimental Fasciola hepatica infections in calves.

The anthelmintic efficacy of a benzenedisulfonamide was evaluated by administering the drug parenterally at dosage levels of 2, 4, 8, and 16 mg/kg of body weight to crossbred Brahman calves with experimental Fasciola hepatica infections. In the 3-week period after treatment, fluke ova counts of treated calves were markedly reduced from counts obtained just before treatment. At necropsy, the mean fluke recovery for all 4 benzenedisulfonamide dosages were significantly (P less than 0.01) reduced. The efficacy of benzenedisulfonamide against F hepatica at dosage levels of 2, 4, 8, and 16 mg/kg was 97.5%, 99.5%, 100%, and 100%, respectively.

Animals↗
PubMed1997

Pharmacological effects of nematode FMRFamide-related peptides (FaRPs) on muscle contractility of the trematode, Fasciola hepatica.

The physiological effects of synthetic replicates of the nematode FaRPs, AF1 (KNEFIRFamide), AF2 (KHEYLRFamide), PF1 (SDPNFLRFamide), PF2 (SADPNFLRFamide), AF8/PF3 (KSAYMRFamide) and PF4 (KPNFIRFamide) were examined on muscle preparations of the liver fluke, Fasciola hepatica. Changes in contractility following the addition of the test compound were recorded using a photo-optic transducer system. Unlike the varied effects these peptides have on nematode somatic musculature, all were found to induce excitatory responses in the muscle activity of F. hepatica. While qualitative effects of the nematode peptides were similar in that they induced increases in both the amplitude and frequency of F. hepatica muscle contractions, they varied considerably in the potency of their excitatory effects. The threshold activity for each peptide was as follows: 10 microM, PF1 and PF2; 3 microM, AF1 and PF3; 1 microM, AF2; and 30 nM, PF4. The results demonstrate, for the first time, the cross-phyla activity of nematode neuropeptides on the neuromuscular activity of a trematode.

Animals↗
PubMed2003

Fasciola hepatica: tegumental surface alterations following treatment in vivo and in vitro with nitroxynil (Trodax).

Male Sprague-Dawley rats were dosed orally with nitroxynil at a concentration of 40 mg/kg and adult Fasciola hepatica recovered after 24 h, 48 h and 72 h. Surface changes to the flukes were monitored by means of SEM. After the 24 h treatment, extensive swelling and blebbing of the tegument was observed on both surfaces, although the dorsal anterior region was more severely affected than either the posterior dorsal region or entire ventral surface. At high magnification, microvillus-like projections were evident, giving the surface a roughened appearance. After 48 h, the changes evident at 24 h had become more severe and some tegumental loss had occurred in the oral region of the fluke. Surface disruption was particularly evident along the lateral margins of the fluke in this region. In some specimens a single large swelling was present in the dorsal midbody region. The swelling was a more typical feature of flukes recovered. After 72 h, tegumental loss was more widespread, occurring over the oral cone and anterior midbody on the dorsal surface. Overall the dorsal surface was consistently more severely affected than the ventral surface, and the anterior region of the fluke was more disrupted than the posterior region. After 24 h in vitro incubation, the oral cone and midbody exhibited considerable spine loss and swelling. Overall, the dorsal surface was more disrupted than the ventral surface and the anterior region of the fluke was more disrupted than the posterior region. Regional differences in the response of the fluke to nitroxynil will be compared to previously published data with other fasciolicides. The results indicate that the tegument is an important target for nitroxynil action. Disruption of this, the fluke's main line of defence, would allow the drug access to other internal tissues, leading to more widespread damage.

Animals↗
PubMed2003

Fasciola hepatica: the effect of food quality on the development of redial generations in Galba truncatula infected with allopatric miracidia.

Individual bimiracidial infections of French Galba truncatula with an allopatric (Moroccan) isolate of Fasciola hepatica were carried out under laboratory conditions to count free rediae and intraredial daughter rediae in snails just after their death, and to determine whether feeding the snails on lettuce only or lettuce plus Tetraphyll had an effect on the development of redial generations. Controls consisted of snails infected with sympatric (French) miracidia and reared with lettuce only. In the allopatric group, reared with lettuce only as food, a higher mortality rate of snails in the first 4 weeks of the experiment was noted, and most G. truncatula showed 1-sporocyst infections, with the usual development of redial generations. Compared to the sympatric group, the growth of the first mother redia (R1a redia) in each snail of the allopatric group was significantly slower during the first weeks of infection, whereas a significantly increased formation of intraredial daughter rediae in the other mother rediae (R1b rediae) was noted over the same period. In the allopatric group, reared with cos lettuce and commercial fish food, 1-sporocyst infections (45.5% of snails) and 2-sporocyst infections (53.9%), with the usual development of redial generations, were noted. Compared to the sympatric group, a significantly slower development of the first mother redia during the first weeks of the experiment was noted in the 1-sporocyst infections, whereas the values in the 2-sporocyst infections did not significantly differ from those noted in the sympatric group. Similar results were noted for the production of intraredial daughter rediae in the R1b rediae during the first weeks of the experiment. In all infections derived from the growth of a single sporocyst per snail, the differentiation of numerous daughter rediae inside R1b rediae would be induced by the slow growth of the R1a redia (from which the most important group of R2a rediae originated) during the first weeks of infection and might represent a mechanism to replace free rediae absent from the inside of the snail.

Animal Feed↗
PubMed2003

Fasciola hepatica: effects of the fasciolicide clorsulon in vitro and in vivo on the tegumental surface, and a comparison of the effects on young- and old-mature flukes.

The ultrastructural changes in Fasciola hepatica induced by the fasciolicide clorsulon were assessed using scanning electron microscopy. At 8 and 44 weeks post-infection, male Sprague-Dawley rats infected with F. hepaticawere dosed orally with clorsulon at a concentration of 12.5 mg/kg and mature flukes recovered from the bile duct after 24 h, 48 h, and 72 h in both experiments. An in vitro incubation was also set up using mature fluke (8 weeks old) incubated with clorsulon for 24 h at a concentration of 10 microg/ml. After 24 h in vivo, the young-mature flukes (8 weeks old) showed significant disruption to the tegumental surface, particularly in the anterior mid-body region, where a distinct band of swelling and blebbing was evident. The band began just behind the ventral sucker and ran posteriorly along both margins. The apical cone region of the fluke was characterised by swelling and blebbing of the surface between the spines. Similar changes were evident after 48 h in vivo, but the disruption was more severe and the mid-body band had spread posteriorly. In approximately half of the specimens recovered after 72 h in vivo, widespread disruption had occurred, with sloughing of the apical membrane or the entire syncytium, over almost all of the oral cone and anterior mid-body. For all time periods, the anterior half of the fluke was more severely affected than the posterior half. No differences were seen between the dorsal and ventral surfaces. Old-mature flukes (44 weeks old) showed regionally similar, but more severe and widespread disruption than that seen in the young-mature flukes. The onset of surface changes occurred more quickly in old-mature flukes as well. Eight-week-old flukes which had been incubated for 24 h in vitro showed surprisingly little disruption, but this may be due to the method by which the drug is taken up by the fluke.

Animals↗
PubMed2005

Ultrastructural observations on oral ingestion and trans-tegumental uptake of clorsulon by the liver fluke, Fasciola hepatica.

Three experiments have been carried out in vitro to determine the effect of oral and trans-tegumental uptake of clorsulon on the fine structure of the tegument and gut of Fasciola hepatica. Changes were assessed by transmission electron microscopy. In the first experiment, the flukes were ligatured to prevent the oral ingestion of drug and treated for 24 h in clorsulon (10 microg/ml). Limited swelling of the basal infolds was observed in the tegumental syncytium. Swollen mitochondria were present in the syncytium, the underlying tegumental cells and in the gastrodermal cells. Swelling and vesiculation of the cisternae of the granular endoplasmic reticulum (ger) was evident in the gastrodermal cells, together with a reduction in secretory activity. In the second experiment, flukes were fed for 24 h on red blood cells isolated from rats dosed with clorsulon at 12.5 mg/kg body weight; this experiment was designed to prevent the exposure of the tegumental surface to the drug. There was severe swelling of the basal infolds in the tegumental syncytium and swelling of mitochondria in the syncytium, tegumental cells and gastrodermal cells. In the tegumental cells there was a decrease in the number of Golgi complexes as well. A number of changes were evident in the gastrodermal cells: swelling of the ger cisternae, an increase in the number of autophagic vacuoles, a reduction in the number of secretory bodies and disruption of the lamellae projecting from the surface of the cells. In the third experiment, flukes were incubated for 24 h in clorsulon (10 microg/ml), with both absorptive surfaces being available for drug uptake. There was severe swelling of the basal infolds in the tegumental syncytium and large autophagic vacuoles were present. Swollen mitochondria were a feature of the tegument, tegumental cells and gastrodermal cells, as were swollen cisternae of ger in the tegumental and gastrodermal cells. Fewer Golgi complexes were observed in the tegumental cells and in the gastrodermal cells there were fewer secretory bodies and an increased number of autophagic vacuoles. Overall, the gastrodermal cells were more severely affected than the tegument. Greater disruption of the tegument occurred when the oral route of uptake was available. The results support those of previous studies which point to oral uptake of clorsulon being the major route of entry into the fluke.

Administration, Oral↗
PubMed1989

Comparison of dot enzyme-linked immunosorbent assay (Dot-ELISA), passive haemagglutination test (PHT) and thin layer immunoassay (TIA) in the diagnosis of natural or experimental Fasciola hepatica infections in sheep.

The dot enzyme-linked immunosorbent assay (Dot-ELISA) was compared with the passive haemagglutination test (PHT) and thin layer immunoassay (TIA) for the detection of antibodies against Fasciola hepatica in naturally and experimentally infected sheep. The infected animals gave titres from 1:25,000 to 1:204,000, while control animals gave titres of from 1:100 to 1:800. The titres of the infected sheep obtained by Dot-ELISA were 1000-2000 times higher than the ones obtained using TIA or PHT. Due to its high sensitivity, this technique could be very useful for the diagnosis of ovine fascioliasis.

Animals↗
PubMed2005

Antioxidant potential of rat liver in experimental infection with Fasciola hepatica.

The aim of this paper is to assess the antioxidant properties of rat liver in the course of acute and chronic fasciolosis. Wistar rats were infected per os with 30 metacercariae of Fasciola hepatica. Liver activities of antioxidant enzymes and concentrations of non-enzymatic antioxidants were determined at 4, 7, and 10 weeks post-infection. Activities of superoxide dismutase (Cu,Zn-SOD), glutathione peroxidase (GSH-Px), and glutathione reductase (GSSG-R) were decreased, catalase (CAT) activity was increased and non-enzymatic antioxidant concentrations (reduced glutathione, vitamins C, E and A) were reduced simultaneously with enhancement of lipid peroxidation processes as evidenced by increased levels of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). Changes in the antioxidant abilities of the liver and in the phospholipid structure of the cell membrane were accompanied by rising activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as markers of liver damage.

Alanine Transaminase↗
PubMed1984

Fasciola hepatica: collagen deposition and other histopathology in the rat host's bile duct caused by the parasite and by proline infusion.

Bile ducts were examined histochemically to compare the effects of proline infusion with Fasciola hepatica implantation in rats. After 3 weeks of infusion or implantation, both proline and F. hepatica produced increases in the luminal perimeter and collagen content of the bile duct. However, the effect of the parasite was significantly greater than that of proline, and the parasite produced significant increases in the bile duct wall. These results corroborate earlier biochemical and histological studies indicating the important role of proline in the enlargement of the bile duct in fascioliasis.

Animals↗
PubMed2000

Fasciola hepatica: influence of gender and liver biotransformations on flukicide treatment efficacy of rats infested and cured with either clorsulon/ivermectin or triclabendazole.

Two fasciolicide preparations have been compared in 130 rats experimentally infected with Fasciola hepatica. Parasitological, immunological, and biochemical parameters have been followed to monitor the efficacy of the treatments. While Fascinex (triclabendazole) efficiently cured both male and female rats when administered as soon as 4 weeks postinfection, treatment with Ivomec-D (clorsulon + ivermectin) displayed a low efficacy on either male or female rats at this time point (54 and 0%, respectively). Moreover, when administered 8 weeks postinfection, the Ivomec-D treatment proved highly efficient on male rats while it displayed little effect on the female population (100 and 53%, respectively). This unexpected result has been related to an overexpression of a P4503A isoform that is observed only in females that have been treated with Ivomec-D. The influence of this P4503A cytochrome on drug metabolism and the need for the incorporation of both genders in clinical trials are discussed.

Animals↗
PubMed1975

Oxidative enzymes in the development of Fasciola hepatica L. III. The activities of oxidases and dehydrogenases in the sporocyst.

The object of the study was the investigation of the occurrence and distribution of some oxidative enzymes in the sporocyst of Fasciola hepatica L. The samples were examined for the presence of cytochrome oxidase, peroxidase, NADH and NADPH tetrazolium reductases, as well as succinate, isocitrate, malate, lactate, alpha-glycerophosphate, glyceraldehyde-3-phosphate, glucose-6-phosphate, beta-hydroxybutyrate, L-glutamate and alcohol dehydrogenases. All of them save cytochrome oxidase were found to occur in the sporocyst. The presence and localization of these enzymes were examined by histochemical methods in various stages of development of the sporocyst. These investigations permitted it to be established that glycolytic processes are the principal way of release of energy for all developmental groups of this larva. Moreover, the functions of the tricarboxyl acid and pentose-phosphate cycles were detected and found to play a less important part in processes of energy production in the sporocyst. In addition, the functioning and metabolism of each larval organ in various stages of its development were discussed in so far as was possible on the basis of the analysis of the above-mentioned oxidative enzymes.

Alcohol Oxidoreductases↗
PubMed1984

Seasonal transmission of Fasciola hepatica to cattle in northwestern United States.

Sentinel steers were placed with 3 beef herds on irrigated pastures in southern Idaho for 1-month periods from May until November 1982 to determine the transmission pattern of Fasciola hepatica. Transmission was found to increase through the pasture season, reaching a peak during November. Overwintering of metacercariae or snail-borne stages was not found to contribute to infections in the year under study. A variety of species of Lymnaea were found to be available in southern Idaho as potential intermediate hosts. The enzyme-linked immunosorbent assay was found to be a good serologic indicator of light infections with F hepatica. The serum gamma-glutamyltransferase activity was not diagnostically significant when the degree of fluke infection was low.

Animals↗
PubMedDate not supplied

[Comparison of two different enzyme immunoassays in the diagnosis of Fasciola hepatica infections].

In this study, the serum samples of 37 patients who were diagnosed as fascioliasis (=fasciolosis) by parasitologic, pathologic and/or radiographic methods, 51 patients who were previously infected with parasites other than Fasciola hepatica, and 31 healthy subjects, have been investigated for the presence of F. hepatica specific IgG antibodies with two different enzyme immunoassay (ELISA) methods. For this purpose, in-house DOT-ELISA and excretory-secretory (ES)-ELISA techniques have been performed by using F. hepatica ES antigens. All of the 37 fasciolosis patients found to be seropositive with ES-ELISA, while 36 were found positive with DOT-ELISA method. ES-ELISA method yielded 3 (5.9%) positive results for the patients with other parasitosis (2 toxocariasis, 1 hydatic cyst), and DOT-ELISA method gave positive results for 2 (3.9%) toxocariasis patients. In 31 healthy subjects, the seropositivity rates were detected as 3.2% and 16.1% for ES-ELISA and DOT-ELISA methods, respectively. As a result, the sensitivity and specificity of DOT-ELISA method were found as 97.3% and 93.3%, respectively, while these rates were 100% and 97.0% for ES-ELISA, respectively. The highest positive predictive value was detected for ES-ELISA (90.2%), while both of the methods showed high negative predictive values (100% for ES-ELISA, 99.1% for DOT-ELISA). In conclusion, ELISA methods would be useful especially for the laboratory diagnosis of fasciolosis, in the clinically suspected patients where the etiologic agent could not be identified.

Animals↗
PubMed1975

The occurrence of Lymnaea (pseudosuccinea) columella, an intermediate host of Fasciola hepatica, in Australia.

An established population of the eastern North American freshwater snail Lymnaea (Pseudosuccinea) columella Say is reported from Middle Creek and Centennial Park, Sydney. This species is an important intermediate host of the liver fluke (Fasciola hepatica Linné) and its introduction and spread in New Zealand has resulted in an increase in the liver fluke problem in New Zealand.

Animals↗
PubMed2000

Snail host finding by Fasciola hepatica and Trichobilharzia ocellata: compound analysis of "miracidia-attracting glycoproteins".

The glycoconjugates from snail-conditioned water of Lymnaea truncatula and L. stagnalis which elicit typical host finding behavior in miracidia of Fasciola hepatica and Trichobilharzia ocellata were separated by anion-exchange chromatography and a two-step size-exclusion chromatography. We obtained fractions attractive for the parasites with MW of about 10(6) Da in both snail species. These fractions still contained species-specific information since miracidia responded only to molecules from their respective host snail. Analysis of the amino acid composition from the protein backbone revealed a similar composition in the effective fractions of both snails. Amounts of serine and threonine were higher than 30 mol %, which is typical for mucin-type glycoproteins. The carbohydrate moieties consisted mainly of galactose and fucose, but nine different other monosaccharides also were identified in smaller amounts. The heterogeneity of the molecules was also confirmed by the binding of six different lectins. Because of these characteristics, the effective molecules were termed "miracidia-attracting glycoproteins" (MAGs). MAGs may play an important role for parasite transmission, as they may increase the chance of an encounter between parasite and host and enable the miracidia to discriminate between their specific intermediate host and other unsuitable snail species.

Amino Acids↗
PubMed1998

Location of induction and expression of protective immunity against Fasciola hepatica at the gut level: a study using an ex vivo infection model with ligated gut segments.

In the present study, we investigated the site in the host where protective gut immunity to Fasciola hepatica is induced and expressed, following the infection route of the parasite. Expression of protection was studied in ex vivo gut segments with intact blood and lymph supply that were prepared at different locations along the entire length of the small and large intestine. Four weeks after oral infection, significant protection was detected in the duodenum, upper jejunum, midjejunum, and ileum. Protection at the gut level was expressed as early as 2 wk after oral priming and waned after 27 wk. The possibility that the gut wall plays a role in age-related protection was excluded. The effect of newly excysted juveniles (NEJ) penetrating the gut on the induction of protection was studied by recovering or killing the NEJs of the primary infection immediately after gut migration. Results showed that protection was low (13.9-19.8%). However, when gut migration was by-passed and NEJs of the primary infection were injected into the peritoneal cavity or between the liver lobes, high levels of protection at the gut level were detected (76.5-87.4%). The results indicate that protection expressed at the gut level is induced by the parasite at a young stage, during migration through the peritoneal cavity, or liver, or both and not during penetration of the gut.

Age Factors↗