OBJECTIVE: Individuals with decreased thiopurine methyltransferase (TPMT) activity are at risk of adverse effects of thiopurine administration whereas its increased activity may inactivate drugs faster. We evaluated genotype-phenotype correlations in patients with suspected hematological malignancies and inflammatory bowel disease from our region based on findings of nonlinear TPMT enzyme kinetics previously unreported. PATIENTS AND METHODS: The study group comprised 267 individuals. They were screened for the most common variants of low TPMT activity. TPMT activity was measured in erythrocytes using the HPLC rate-blanked method. RESULTS: Thirty-three patients (12.4%) were heterozygous (26 were TPMT*1/*3A, 5 TPMT*1/*2, 2 TPMT *1/*3C) and 1 was a compound heterozygote (*2/*3A). Normal and low normal TPMT activities substantially overlapped in wild-type and heterozygous individuals, whereas high activities were found in 29 wild-type genotyped patients. Extreme and life-threatening toxicity was observed in the compound heterozygote patient. CONCLUSION: Activity measurement performed at diagnosis provides clinicians with information on immediate pharmacokinetic-related adverse events and/or hypermetabolism, and genotyping may indicate the rate of pharmacodynamic thioguanine nucleotide accumulation due to slower overall thiopurine metabolism.
- MeSH
- asparaginasa terapeutické užití MeSH
- cyklofosfamid terapeutické užití MeSH
- cytarabin terapeutické užití MeSH
- daunomycin terapeutické užití MeSH
- erytrocytární membrána enzymologie MeSH
- genetické asociační studie MeSH
- idiopatické střevní záněty krev MeSH
- lidé MeSH
- lymfoblastická leukemie-lymfom z prekurzorových T-buněk farmakoterapie genetika MeSH
- merkaptopurin terapeutické užití MeSH
- methotrexát terapeutické užití MeSH
- methyltransferasy nedostatek genetika metabolismus MeSH
- mladiství MeSH
- polymerázová řetězová reakce MeSH
- prednison terapeutické užití MeSH
- protokoly protinádorové kombinované chemoterapie terapeutické užití MeSH
- vinkristin terapeutické užití MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
- Slovenská republika MeSH
The African freshwater fish of Cichlidae are parasitized by five genera of monogeneans belonging to Dactylogyridea. Ectoparasitic Scutogyrus, Onchobdella, and the highly diversified Cichlidogyrus represent three genera located on the gills, while the endoparasitic Enterogyrus and Urogyrus are located in the stomach and the urinary bladder, respectively. Representatives of four dactylogyridean genera (except for Urogyrus) were collected from seven cichlid species in West Africa. The aim of this study was to investigate the phylogenetic relationships between ectoparasitic and endoparasitic dactylogyridaen monogeneans specific to African freshwater Cichlidae and other representatives of Dactylogyridae, including a wide range of species from both freshwater and marine environments. All phylogenetic analyses point to the polyphyletic origin of the subfamily Ancyrocephalinae. Both Enterogyrus and Onchobdella were found to be monophyletic. The phylogenetic position of Scutogyrus longicornis was placed within the Cichlidogyrus species, which suggests the non-monophyly of Cichlidogyrus. Therefore, we have proposed a taxonomical revision of the species recently considered to be Scutogyrus. However, these four dactylogyridean genera-specific to cichlids do not form a monophyletic group. Using LSU rDNA analyses, we found that Enterogyrus and Onchobdella form a clade with Protogyrodactylus, i.e., the parasite species does not live in cichlids, which suggests that endoparasitism in cichlid monogeneans is not an ancestral feature.
- MeSH
- cichlidy parazitologie MeSH
- DNA helmintů chemie genetika MeSH
- fylogeneze MeSH
- mezerníky ribozomální DNA chemie genetika MeSH
- močový měchýř parazitologie MeSH
- molekulární sekvence - údaje MeSH
- nemoci ryb parazitologie MeSH
- ploštěnci klasifikace genetika izolace a purifikace MeSH
- ribozomální DNA chemie genetika MeSH
- RNA ribozomální 28S genetika MeSH
- sekvenční analýza DNA MeSH
- shluková analýza MeSH
- sladká voda MeSH
- žábry parazitologie MeSH
- žaludek parazitologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- západní Afrika MeSH
