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.
Bolest hlavy je velmi častý příznak, se kterým přijde pacient do akutní ambulance. Opakovaná bolest hlavy migrenózního charakteru může být zavádějící a vést k částečné bagatelizaci obtíží, ale je samozřejmě na místě provedení zobrazovacího vyšetření, pokud toto provedeno dosud nebylo. Uvádíme zde příklad mladé pacientky, která za obdobných okolností navštívila naši ambulanci s velmi překvapivým nálezem na zobrazovacích vyšetřeních, její diagnostiku, léčbu a vývoj v čase. Dokládáme zde důležitost posouzení senzitivity jednotlivých testů a, i když nebyla naplněna daná diagnostická kritéria, velkou suspekci na onemocnění, které se v našich krajinách vyskytuje velmi raritně.
- 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
- počítačová rentgenová tomografie MeSH
- poruchy senzitivity etiologie MeSH
- spinální punkce MeSH
- terapie neúspěšná MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky 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.
Encephalitozoon cuniculi genotype III disseminated intensively into most of the organs in all strains of mice, followed by a chronic infection with massive microsporidia persistence in immunodeficient mice and a partial decrease in C57Bl/6 mice. Treatment with 0.2 mg Albendazole/mouse/day temporarily reduces the number of affected organs in immunocompetent C57Bl/6 mice, but not in CD4-/- and CD8-/- mice. The application of medication temporarily decreased the spore burden at least by one order of magnitude in all groups. These results demonstrate that the E. cuniculi genotype III infection had a progressive course and surprisingly, Albendazole treatment had only a minimal effect. The E. cuniculi genotype III spore burden in individual organs reached up to 108 or 109 in immunocompetent or immunodeficient mice, respectively; however, these mice did not demonstrate any obvious clinical signs of microsporidiosis, and the immunodeficient mice survived longer. Our findings clearly show that the survival of mice does not correspond to spore burden, which provides new insight into latent microsporidiosis from an epidemiological point of view.
- MeSH
- albendazol terapeutické užití MeSH
- antigeny CD4 genetika MeSH
- antigeny CD8 genetika MeSH
- Cercopithecus aethiops MeSH
- Encephalitozoon cuniculi genetika MeSH
- encephalitozoonóza farmakoterapie mikrobiologie patologie MeSH
- genotyp * MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- Vero buňky MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Echinococcus multilocularis vyvolává agresivní formu hydatidózy, jejíž morfologický obraz není všeobecně znám. Prezentujeme kazuistiku 39leté ženy s neostře ohraničenými uzly v pravém laloku jater, které byla pro podezření na fokální nodulární hyperplazii (FNH) a hepatocelulární adenom provedena punkční biopsie. Histologický nález nekrotické fibrózní tkáně prostoupené úzkými pruhy epitelu a malých dutinek, které obsahovaly cytokeratin pozitivní materiál podporovaly diagnózu cholangiocelulárního karcinomu. Dodatečné vyšetření chirurgicky odstraněných nekrotických uzlů s vitální tkání na periferii odpovídalo reparativní fibróze s nápadnou duktulární proliferací. Serologické a genetické vyšetření prokázalo multilokulárního echinokoka. V našem sdělení chceme upozornit na neobvyklý histologický nález nekrotické fibrózní tkáně s duktulární reakcí v solidních ložiscích alveolární hydatidózy, který může v punkční biopsii připomínat regresivně změněný karcinom.
Echinococcus multilocularis causes an aggressive form of hydatidosis whose histomorphological picture is generally not well recognized. We report a case of 39-year-old women presenting with poorly circumscribed nodules in the right hepatic lobe. Owing to the clinical suspicion of focal nodular hyperplasia and hepatocellular adenoma, a core biopsy was performed. The histological findings of necrotic fibrous tissue infiltrated by narrow epithelial cords and small cysts containing cytokeratin positive material were in concordance with the diagnosis of cholangiocarcinoma. Subsequent examination of the surgically resected necrotic nodules with a vital tissue at the periphery corresponded to a reparative fibrosis accompanied by a striking ductular proliferation. Serological and mo-lecular genetic work-up led to the diagnosis of Echinococcus multilocularis. The aim of this report is to point out the unusual histological features of the solid foci of alveolar hydatidosis, which consisted of necrotic fibrous tissue with ductular reaction. Such findings in a core biopsy may simulate regressively altered carcinoma.
- MeSH
- albendazol terapeutické užití MeSH
- dospělí MeSH
- Echinococcus multilocularis MeSH
- echinokokóza jater * diagnóza patologie terapie MeSH
- imunohistochemie metody MeSH
- játra chirurgie diagnostické zobrazování patologie MeSH
- jehlová biopsie metody MeSH
- lidé MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Of four genotypes of Encephalitozoon cuniculi, E. cuniculi genotype II is considered to represent a parasite that occurs in many host species in a latent asymptomatic form, whereas E. cuniculi genotype III seems to be more aggressive, and infections caused by this strain can lead to the death of even immunocompetent hosts. Although albendazole has been considered suitable for treatment of Encephalitozoon species, its failure in control of E. cuniculi genotype III infection has been reported. This study determined the effect of a 100× recommended daily dose of albendazole on an Encephalitozoon cuniculi genotype III course of infection in immunocompetent and immunodeficient mice and compared the results with those from experiments performed with a lower dose of albendazole and E. cuniculi genotype II. The administration of the regular dose of abendazole during the acute phase of infection reduced the number of affected organs in all strains of mice and absolute counts of spores in screened organs. However, the effect on genotype III was minor. Surprisingly, no substantial effect was recorded after the use of a 100× dose of albendazole, with larger reductions seen only in the number of affected organs and absolute counts of spores in all strains of mice, implying variations in albendazole resistance between these Encephalitozoon cuniculi genotypes. These results imply that differences in the course of infection and the response to treatment depend not only on the immunological status of the host but also on the genotype causing the infection. Understanding how microsporidia survive in hosts despite targeted antimicrosporidial treatment could significantly contribute to research related to human health.
- MeSH
- albendazol aplikace a dávkování farmakologie MeSH
- antifungální látky aplikace a dávkování farmakologie MeSH
- antigeny CD4 genetika MeSH
- antigeny CD8 genetika MeSH
- buněčné linie MeSH
- Cercopithecus aethiops MeSH
- Encephalitozoon cuniculi účinky léků genetika izolace a purifikace MeSH
- encephalitozoonóza farmakoterapie MeSH
- genotyp MeSH
- hostitel s imunodeficiencí imunologie MeSH
- mikrobiální testy citlivosti MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední BALB C MeSH
- myši inbrední C57BL MeSH
- myši knockoutované MeSH
- myši SCID MeSH
- myši MeSH
- počet mikrobiálních kolonií MeSH
- Vero buňky MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
