Anthelmintic drugs are widespread environmental contaminants, but their impact is still poorly understood. Although contact of parasitic nematode Haemonchus contortus with traces of anthelmintic drug albendazole (ABZ) altered the expression and activity of several UDP-glycosyl transferases (UGTs) and P-glycoproteins (Pgps, belonging to ABC-transporters), key enzymes in endogenous and xenobiotic metabolism, it is not known whether these changes will last during the life cycle and pass to the next generations. In the present study simulating the environmental-like exposure, free-living stages of H. contortus were exposed or unexposed to a sub-lethal dose of ABZ and its transformation products (ABZs) during L3 development. The L3 served for lambs' infection and obtaining of H. contortus adults and eggs, which were again exposed or unexposed to ABZs during L3 development. The expression pattern of UGTs and Pgps was analysed and compared in the first generation of L3, in the adults, and in the second generation of L3. The results showed that ABZs exposition during larvae development altered the expression of several ugt and pgp genes in L3 and adults. The intrageneration stability of ABZs-evoked changes was observed in the case of three genes, four genes maintained the intergeneration stability. Interestingly, ABZs-induced changes in the expression of some genes became apparent only in the second generation of L3. Taking together, contact of free-living stages of H. contortus with traces of ABZs in the environment evokes changes in the expression of certain UGTs and Pgps, with some of these changes being intra- and inter-generation stable.
- MeSH
- albendazol aplikace a dávkování terapeutické užití MeSH
- Echinococcus granulosus MeSH
- echinokokóza * diagnóza parazitologie terapie MeSH
- lidé MeSH
- mladý dospělý MeSH
- nemoci orbity MeSH
- neurochirurgické výkony metody MeSH
- počítačová rentgenová tomografie MeSH
- prednisolon aplikace a dávkování terapeutické užití MeSH
- Check Tag
- lidé MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Headache is a very common symptom that a patient presents with in the acute outpatient clinic. Repeated migraine-like headache can be misleading and lead to partial downplaying of the difficulty, but it is of course appropriate to perform an imaging examination if this has not already been done. We present here an example of a young patient who visited our outpatient clinic in similar circumstances with very surprising findings on neuroimaging, her diagnosis, treatment, and evolution over time. We demonstrate here the importance of assessing the sensitivity of individual tests and, even if the diagnostic criteria were not met, the high suspicion of a disease that is very rare in our country.
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- MeSH
- albendazol aplikace a dávkování MeSH
- bolesti hlavy * diagnostické zobrazování etiologie farmakoterapie mozkomíšní mok MeSH
- diferenciální diagnóza MeSH
- dospělí MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mozek diagnostické zobrazování patologie MeSH
- neurocysticercosis diagnostické zobrazování farmakoterapie mozkomíšní mok patologie terapie MeSH
- neúspěšná terapie MeSH
- počítačová rentgenová tomografie MeSH
- poruchy senzitivity etiologie MeSH
- spinální punkce MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
A total of 1,724 beef and 2,941 dairy cattle older than one year from 66 beef and 67 dairy farms in the Czech Republic were examined for the presence of rumen and liver fluke eggs in 2019-2022. Out of 227 positive animals, all were positive for paramphistome and five for fasciolid eggs. Molecular analysis of the ITS2 rDNA revealed the presence of Calicophoron daubneyi (Dinnik, 1962) and Fasciola hepatica Linnaeus, 1758. Faecal egg count (FEC) showed low infection intensity (12 EPG) in animals infected with F. hepatica and high variability in C. daubneyi infections (2-589 EPG). Efficacy of oxyclozanide, albendazole, ivermectin, and closantel against C. daubneyi infection was evaluated at eight beef cattle herds. Faecal samples were collected from all positive animals at 0 and 21days post-treatment. Based on FEC, albendazole, ivermectin and closantel reduced the number of C. daubneyi eggs shed by 0-9.9%, with no effect on the number of infected animals. The use of oxyclozanide on two beef farms showed 100% efficacy against C. daubneyi and F. hepatica. Follow-up examination 5-6 months after drug application showed reinfection of most animals with C. daubneyi, but the FEC was significantly lower. The finding of four dairy cows infected with C. daubneyi housed in a stable without pasture suggests the possibility of the infection being introduced through roughage.
- MeSH
- albendazol MeSH
- Fasciola hepatica * genetika MeSH
- feces MeSH
- infekce červy třídy Trematoda * epidemiologie veterinární MeSH
- ivermektin terapeutické užití MeSH
- oxyklozanid MeSH
- Paramphistomatidae * genetika MeSH
- prevalence MeSH
- skot MeSH
- Trematoda * MeSH
- zvířata MeSH
- Check Tag
- skot MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
Albendazole (ABZ) is an anthelmintic frequently used to treat haemonchosis, a common parasitosis of ruminants caused by the gastrointestinal nematode Haemonchus contortus. This parasite is able to protect itself against ABZ via the formation of inactive ABZ-glycosides. The present study was designed to deepen the knowledge about the role of UDP-glycosyltransferases (UGTs) in ABZ glycosylation in H. contortus. The induction effect of phenobarbital, a classical inducer of UGTs, as well as ABZ and ABZ-sulphoxide (ABZSO, the main active metabolite of ABZ) on UGTs expression and UGT activity toward ABZ was studied ex vivo in isolated adult nematodes. The effect of three potential UGT inhibitors (5-nitrouracil, 4,6-dihydroxy-5-nitropyrimidine and sulfinpyrazone) on ABZ glycosylation was tested. Pre-incubation of nematodes with ABZ and ABZSO led to increased expression of several UGTs as well as ABZ-glycosides formation in subsequent treatment. Phenobarbital also induced UGTs expression, but did not affect ABZ biotransformation. In the nematode's subcellular fraction, sulfinpyrazone inhibited UGT activity toward ABZ, although no effect of other inhibitors was observed. The inhibitory potential of sulfinpyrazone on the formation of ABZ-glycosides was also proved ex vivo in living nematodes. The obtained results confirmed the role of UGTs in ABZ biotransformation in H. contortus adults and revealed sulfinpyrazone as a potent inhibitor of ABZ glycosylation in this parasite. The possible use of sulfinpyrazone with ABZ in combination therapy merits further research.
- MeSH
- albendazol MeSH
- anthelmintika * terapeutické užití MeSH
- fenobarbital metabolismus farmakologie terapeutické užití MeSH
- glykosidy metabolismus farmakologie terapeutické užití MeSH
- glykosyltransferasy MeSH
- Haemonchus * MeSH
- hlístice * MeSH
- nemoci ovcí * farmakoterapie MeSH
- ovce MeSH
- sulfinpyrazon metabolismus farmakologie terapeutické užití MeSH
- uridindifosfát MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Out of three genotypes of Encephalitozoon cuniculi (I-III) available for experimental studies, E. cuniculi genotype I remains the less characterized. This study describes for the first time individual phases of microsporidiosis caused by E. cuniculi genotype I and efficacy of albendazole treatment in immunocompetent BALB/c and C57Bl/6 mice and immunodeficient SCID, CD4-/- and CD8-/- mice using molecular detection and quantification methods. We demonstrate asymptomatic infection despite an intense dissemination of microsporidia into most organs within the first weeks post infection, followed by a chronic infection characterized by significant microsporidia persistence in immunocompetent, CD4-/- and CD8-/- mice and a lethal outcome for SCID mice. Albendazole application led to loss E. cuniculi genotype I infection in immunocompetent mouse strains, decreased spore burden by half in CD4-/- and CD8-/- mice, and prolongation of survival of SCID mice. These results showed Encephalitozoon cuniculi genotype I infection extend and albendazole sensitivity was comparable to E. cuniculi genotype II, but the infection onset speed and mortality rate was similar to E. cuniculi genotype III. These imply that differences in the course of infection and the response to treatment depend not only on immunological status of the host, but also on the genotype causing the infection.
- MeSH
- albendazol aplikace a dávkování MeSH
- antigeny CD4 genetika MeSH
- antigeny CD8 genetika MeSH
- antiinfekční látky aplikace a dávkování MeSH
- Encephalitozoon cuniculi klasifikace genetika MeSH
- encephalitozoonóza imunologie parazitologie MeSH
- genotyp MeSH
- imunokompetence MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- myši inbrední BALB C MeSH
- myši inbrední C57BL MeSH
- myši knockoutované MeSH
- myši SCID MeSH
- myši MeSH
- polymerázová řetězová reakce MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- albendazol terapeutické užití MeSH
- dospělí MeSH
- klinické laboratorní techniky MeSH
- lidé MeSH
- neurocysticercosis * diagnóza terapie MeSH
- neurozobrazování metody MeSH
- Taenia solium izolace a purifikace účinky léků MeSH
- výsledek terapie MeSH
- záchvaty diagnóza etiologie terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Albendazole (ABZ), a widely used anthelmintic drug, enters the environment mainly via livestock excrements. To evaluate the environmental impact of ABZ, the knowledge of its uptake, effects and metabolism in all non-target organisms, including plants, is essential. The present study was designed to identify the metabolic pathway of ABZ and to test potential ABZ phytotoxicity in fodder plant alfalfa, with seeds and in vitro regenerants used for these purposes. Alfalfa was chosen, as it may meet manure from ABZ-treated animals in pastures and fields. Alfalfa is often used as a feed of livestock, which might already be infected with helminths. The obtained results showed that ABZ did not inhibit alfalfa seed germination and germ growth, but evoked stress and a toxic effect in alfalfa regenerants. Alfalfa regenerants were able to uptake ABZ and transform it into 21 metabolites. UHPLC-MS/MS analysis revealed three new ABZ metabolites that have not been described yet. The discovery of the parent compound ABZ together with the anthelmintically active and instable metabolites in alfalfa leaves shows that the contact of fodder plants with ABZ-containing manure might represent not only a danger for herbivorous invertebrates, but also may cause the development of ABZ resistance in helminths.
The efficacy of anthelmintic therapy of farm animals rapidly decreases due to drug resistance development in helminths. In resistant isolates, the increased expression and activity of drug-metabolizing enzymes (DMEs), e.g. cytochromes P450 (CYPs), UDP-glycosyltransferases (UGTs) and P-glycoprotein transporters (P-gps), in comparison to sensitive isolates have been described. However, the mechanisms and circumstances of DMEs induction are not well known. Therefore, the present study was designed to find the changes in expression of CYPs, UGTs and P-gps in adult parasitic nematodes Haemonchus contortus exposed to sub-lethal doses of the benzimidazole anthelmintic drug albendazole (ABZ) and its active metabolite ABZ-sulfoxide (ABZSO). In addition, the effect of ABZ at sub-lethal doses on the ability to deactivate ABZ during consequent treatment was studied. The results showed that contact of H. contortus adults with sub-lethal doses of ABZ and ABZSO led to a significant induction of several DMEs, particularly cyp-2, cyp-3, cyp-6, cyp-7, cyp-8, UGT10B1, UGT24C1, UGT26A2, UGT365A1, UGT366C1, UGT368B2, UGT367A1, UGT371A1, UGT372A1 and pgp-3, pgp-9.1, pgp-9.2, pgp-10. This induction led to increased formation of ABZ metabolites (especially glycosides) and their increased export from the helminths' body into the medium. The present study demonstrates for the first time that contact of H. contortus with sub-lethal doses of ABZ (e.g. during underdose treatment) improves the ability of H. contortus adults to deactivate ABZ in consequent therapy.
