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The effects of fascioliasis on the activities of some drug-metabolizing enzymes in desert sheep liver.

Desert sheep experimentally or naturally infected with Fasciola gigantica were used to study the influence of infection on the activities of some drug-metabolizing enzymes found in the liver. The enzymes investigated were aminopyrine N-demethylase, aniline 4-hydroxylase and UDP-glucuronyltransferase. The experimental infection was confirmed histologically by detection of Fasciola eggs in faeces and by measuring the activities of sorbitol dehydrogenase (SD), glutamate dehydrogenase (GD) and aspartate aminotransferase (AST) in plasma during the course of the disease. Liver specimens from naturally infected sheep were obtained from the slaughter house. The activities of aminopyrine N-demethylase and aniline 4-hydroxylase were significantly decreased in sheep either naturally infected or during the acute stage of experimental fascioliasis (killed 5 weeks post-infection). The activity of UDP-glucuronyltransferase was decreased in naturally infected sheep and those killed 9 or 13 weeks post-experimental infection.

Aminopyrine N-Demethylase↗

Chemotherapy of ovine fascioliasis: use of an analytical model to assess the impact of a series of discrete doses of anthelmintic on the prevalence and intensity of infection.

An analytical model of ovine fascioliasis is described. The model describes the essential features of the epidemiological patterns observed in the field and is used to assess the impact of a series of discrete doses of anthelmintic on the prevalence and intensity of infection in the flock. The reduction in prevalence after treatment with anthelmintics is shown to be critically dependent on the distribution of flukes amongst the ewes. The model is further used to define the optimum dosing times for a 2- or 3-dose regime. Model predictions concerning the optimum regime are in accord with usual treatment practices in the United Kingdom. The usefulness of analytical models of this kind in the assessment of disease control strategies is discussed.

Animals↗

Studies on fascioliasis in four selected sites in Ethiopia.

The incidence of fascioliasis was studied in Asela, Awasa, Debre Zeit and Debre Berhan by using 153 experimental sheep divided up into 4 groups designated tracer sheep, Controls I, II and III. Fasciola hepatica was encountered in Debre Berhan, Asela and Awasa, but it was not detected at Debre Zeit. In all areas, it was most frequently recovered after heavy rains. Altitude, soil type, salt content and local crowding of animals in watering sites appear to have influenced the varying degrees of incidence and intensity of infection.

Animals↗

An improved passive hemagglutination test for the serological diagnosis of bovine fascioliasis using the specific antigen f2.

Optimum conditions for coupling the specific antigen f2 of Fasciola hepatica to sheep red cells and for the preparation of control cells coated with an unrelated protein are described. With a careful selection of donor sheep for erythrocytes, the problem of anti-species antibodies in bovine sera has been overcome and results may be obtained within 1 h as only one step is required in the assay system. Incorporation of a concentration of 25 mM CaCl2 in the diluent achieved increased stability of the agglutinates and enabled a more precise estimation of the end-point to be made. Analyses performed on bovine sera obtained at slaughter provided results in good agreement with the presence of flukes or fascioliasis lesions in livers at routine slaughter inspection. The developed assay is simpler, faster, more sensitive (P less than 0.01) and has a cut-off between populations of negative sera more easy to define than a recently marketed enzyme-linked immunosorbent assay.

Animals↗

Impaired in vitro metabolism of the flukicidal agent nitroxynil by hepatic microsomal cytochrome P-450 in bovine fascioliasis.

In vitro metabolism by liver tissue of the flukicidal agent nitroxynil has been studied in cattle naturally infected with Fasciola hepatica. A dramatic impairment of the cytochrome P-450-dependent nitroxynil metabolism both in the acute and in the milder stage of the disease has been observed and this is due to a loss in the integrity and functionality of the cytochrome P-450 enzyme system. These results suggest that in bovine fascioliasis the in vivo metabolism of nitroxynil will be decreased with consequent increase of nitroxynil retention in the animal's body.

Animals↗

Combined effect of fascioliasis and diethylnitrosamine carcinogenesis on the activity of the rat liver monooxygenase system.

1. The activity of the rat liver monooxygenase system after single and combined treatment with Fasciola hepatica and diethylnitrosamine (DENA) has been studied in a 27-week experiment. 2. The changes in lever drug metabolism were due mainly to F. hepatica with DENA having a modulating effect only. 3. The results are discussed with reference to earlier data of ours concerning the effects of stimulation or inhibition of DENA-induced liver carcinogenesis against a background of acute or chronic fascioliasis.

Animals↗

Alterations induced by fascioliasis and cirrhosis on the biliary excretion of cefmetazole in Wistar rats.

1. Alterations induced by fascioliasis and cirrhosis on the biliary excretion of cefmetazole have been studied in Wistar rats. 2. Both infestation with Fasciola hepatica and experimental cirrhosis originated a significant decrease in the biliary excretion and in bile flow increase induced by the drug. 3. Administration of the beta-lactam antibiotic induced a lower degree of uncoupling of biliary lipid secretion in the cirrhotic and fasciolotic animals, but the effect was evident in all experimental groups.

Animals↗

Participation of lipid peroxidation in the loss of hepatic drug-metabolizing activities in experimental fascioliasis in the rat.

Fascioliasis causes a dramatic decrease in drug-metabolizing ability of the hepatic monooxygenase (MFO) and glucuronosyltransferase (GT) enzyme systems in the rat. The present study was undertaken to determine whether lipid peroxidation is involved in the enzymatic loss. Peroxidative damage of membrane lipids (as assessed by the tissue content of malonic dialdehyde, MDA, and the diene conjugation absorption in microsomal membranes) was found to occur over the entire course of the liver infection (concomitant to a decrease in glutathione levels), and to different degrees in relation to the various steps of the parasite cycle. The onset (MDA six times the controls; delta E 1% = 1.55 at the 20th day) coincides with the beginning of the loss of MFO (-30%) and GT (-20% at the 20th day), and peaks between the 30th and 40th day (MDA eight times the controls; delta E 1% = 1.96), when the loss in the enzyme activities is maximal (MFO - 60/70%; GT - 65/95%). There was a strict correlation at all the observation times between the extent of lipid peroxidation and the decrease in drug metabolizing ability: this supports the view that lipid peroxidation is the major agent in the impairment of MFO and GT enzyme activities, and very likely in the initiation of the pathological degeneration of the liver tissue. As evidenced by histological examination, the phagocytic response of the liver tissue to the parasite invasion and growth leads to oxidative stress, which is the causative agent in the initiation and development of lipid peroxidation.

Alanine Transaminase↗

Potent epitopes derived from Fasciola gigantica cathepsin L1 in peptide-based immunoassay for the serodiagnosis of human fascioliasis.

A peptide-based enzyme-linked immunosorbent assay (ELISA) was developed and evaluated for its diagnostic ability to detect human IgG antibodies against Fasciola gigantica cathepsin L1. Two previously identified B-cell epitopes of cathepsin L1 were synthesized as single synthetic peptides (acetyl-DKIDWRESGYVTEVKDQGNC-carboxamide and acetyl-DKIDWRESGYVTELKDQGNC-carboxamide) and their diagnostic potential was evaluated. The peptide-based ELISA was compared with an indirect ELISA with crude excretory-secretory products or with partially purified specific 27-kDa (FG27) antigen from adult F. gigantica. In an analysis of the sera of 13 patients infected with F. gigantica, 212 patients with other parasitic infections, 32 patients with cholangiocarcinoma, and 57 healthy controls, the sensitivity, specificity, accuracy, and positive and negative predictive values of this peptide-based ELISA with both peptides had the same performance and were shown to be 100%, 97.3%, 97.5%, 61.9%, and 100%, respectively. When 4 different ELISAs were compared, the results revealed that the specificity, sensitivity, accuracy, and negative predictive values of all antigens were similar except for the positive predictive value that was highest in the ELISA with the FG27 antigen. These results demonstrated that peptide antigens can be used in the serodiagnosis of human fascioliasis with the additional advantage that they are relatively cheap and easy to produce. This rapid, highly sensitive and specific peptide-ELISA has the potential to be used in future large-scale prevalence surveys throughout Southeast Asia.

Animals↗

Occurrence of a sibling species complex within neotropical lymnaeids, snail intermediate hosts of fascioliasis.

The delimitation of cryptic species within the genus Lymnaea, which are the main vectors of fascioliasis, remains a topic of controversy. An analysis of genetic variability based on 12 enzyme loci revealed different fixed alleles at 9 loci between two sympatric samples of Lymnaea viatrix at the type locality in Lima, Peru. The absence of heterozygotes within this locality indicates the presence of isolated populations or cryptic species within L. viatrix. Significant genetic differences were also found between these two L. viatrix samples from Lima and other populations of L. viatrix in South America and in addition to species such as L. truncatula, L. cubensis and L. columella. Moreover, the lack of variability within each Lymnaea samples studied indicates the existence of a high selfing rate in each species.

Animals↗

The laparoscopic diagnosis of the liver fascioliasis.

The laparoscopic findings in 18 cases of liver fascioliasis are described. The characteristic lesions are white and yellow cords on the liver surface that delineate the necrotic tunneliform areas created by the parasite as it penetrates the hepatic tissue. The peritoneum adjacent to the liver also is frequently involved. There was ascites in the 22.2% of the cases. Guided laparoscopic biopsy of peritoneal nodules and of visible liver lesions yielded significant findings more often that percutaneous liver biopsy alone.

Biopsy↗

Immunodiagnosis of human fascioliasis with Fasciola hepatica cysteine proteinases.

The immunodiagnosis of human infections with Fasciola hepatica using purified parasite cysteine proteinases as antigens is reported in this paper. IgG enzyme-linked immunosorbent assays (ELISAs) with 2 cysteine proteinases of 26 kDa (Fas1) and 25 kDa (Fas2), obtained from the regurgitated material of adult worms, were evaluated with serum samples from 38 patients infected with F. hepatica, from 54 patients with other parasitic infections and from 46 healthy volunteers. The diagnostic sensitivities for detection of F. hepatica infection at a serum dilution of 1 in 500 were 89% and 95% with Fas1 and Fas2 respectively. The specificity of the ELISAs was 98% for Fas1 and 100% for Fas2. IgG ELISA with Fas2 is a highly sensitive and specific assay for the immunodiagnosis of human fascioliasis.

Animals↗

High endemicity of human fascioliasis between Lake Titicaca and La Paz valley, Bolivia.

Over a 6-year period, an epidemiological study of human infection by Fasciola hepatica in the Northern Bolivian Altiplano was carried out. Prevalences and intensities were analysed from coprological results obtained in 31 surveys performed in 24 localities and proved to be the highest known so far. The global prevalence was 15.4%, with local prevalences ranging from 0% to 68.2%. Significant differences between prevalence rates were detected and the highest prevalences were in subjects aged < 20 years. However, prevalences showed no gender difference. The global intensity (eggs per gram of faeces, epg) ranged from 24 to 5064 epg and showed arithmetic and geometric means respectively of 446 and 191 epg, with highest local arithmetic and geometric means of 1345 and 678 epg. Significant differences in mean egg output were detected between localities. The significantly higher F. hepatica egg counts shown by girls in school surveys is worth mentioning. Although the distributions of intensities according to age-groups did not show any significant difference, a decrease of egg output counts with an increase of age was detected. It is concluded that fascioliasis is a very important human health problem in this region.

Adolescent↗

A praziquantel-ineffective fascioliasis case successfully treated with triclabendazole.

Human fascioliasis cases in Japan have been reported infrequently and the most appropriate therapy for this disease remains to be determined. This case report describes a patient with the infection unsuccessfully treated with multiple high doses of praziquantel for over 1 year and eventually cured by the administration of triclabendazole in two single doses of 10 mg/kg and 12.5 mg/kg 5 months apart.

Animals↗

Clinico-pathological studies on naturally-occurring bovine fascioliasis in the Sudan.

An investigation was made of the pathological, haematological and biochemical aspects of naturally-occurring bovine fascioliasis in the Sudan. 228 animals infected with Fasciola gigantica and 25 non-infected controls were used in the study. The infected cattle revealed emaciation, typical liver pathology, and, occasionally, lesions in the lung and the pancreas. Analysis of their sera also showed reduced albumin values, increased globulin concentrations and decrease albumin/globulin ratio, in addition to increased arginase activity. The serum iron concentration, on the other hand, was decreased, while the total iron binding capacity increased and the resultant iron saturation values reduced. Haematological findings in the infected animals included reduced erythrocyte counts, decreased haematocrit values, increased mean corpuscular volumes, eosinophilia and decreased neutrophil, lymphocyte and monocyte counts. Other parameters were similar in infected and control cattle.

Animals↗

Fractionation of Fasciola hepatica tegument antigens and their application to the serodiagnosis of experimental fascioliasis by the enzyme-linked immunosorbent assay.

A Fasciola hepatica tegument antigen preparation was obtained from intact adult worms by solubilization with a non-ionic detergent, Nonidet P-40. This antigen preparation contains antigens useful for the serodiagnosis of infection with this parasite. However, the antigen preparation is inadequate for use in the enzyme-linked immunosorbent assay (ELISA). The present work demonstrates that fractionation by demulsification of this antigen preparation with ammonium sulphate results in a soluble aqueous phase which contains F. hepatica serodiagnostic antigens which can then be applied to the ELISA. This F. hepatica tegument antigen preparation when used in the ELISA can detect rabbit fascioliasis two weeks after infection, with antibody levels peaking by 10 to 12 weeks of infection.

Animals↗

Decrease in human fascioliasis in Gipuzkoa (Spain).

From 1981 to 2000 sixty-one cases of human fascioliasis were detected in the province of Gipuzkoa (Spain), most of them during the period of parenchymal invasion. Four family outbreaks were recorded. Thirty, 15, 13 and three cases were detected during the four consecutive 5-year periods. The decrease in this infection over the years is probably related to the change in eating habits.

Adult↗

Detection of circulating E/S antigens in the sera of patients with fascioliasis by IELISA: a tool of serodiagnosis and assessment of cure.

An IELISA was developed to evaluate the performance of Fasciola E/S antigens in diagnosis and cure assessment of human Fasciola infection. Twenty patients with acute (prepatent) fascioliasis and another 20 with patent infection were enrolled in the study. Patients were treated with TCZ and followed at 1, 3 and 6 months after therapy. At inspection, the sensitivity of the test to diagnose prepatent cases was 100% compared to 70% for patent infections. There was a gradual decrease of antigenaemia over the follow-up period in acute cases. In chronic cases antigen disappeared from 13 cases (65%) at 1 month; this proportion did not change at 3 or 6 months.

Acute-Phase Reaction↗