Congenital deficiency of the mitochondrial respiratory chain complex I (CI) is a common defect of oxidative phosphorylation (OXPHOS). Despite major advances in the biochemical and molecular diagnostics and the deciphering of CI structure, function assembly and pathomechanism, there is currently no satisfactory cure for patients with mitochondrial complex I defects. Small molecules provide one f...

Transporters of the ATP-binding cassette (ABC) family such as MDR1 play a pivotal role in persistence of brain homeostasis by contributing to the strict permeability properties of the blood-brain barrier. This barrier on one hand compromises treatment of central nervous system diseases by restricting access of drugs; on the other hand, an impaired or altered function of barrier building cells h...

Gunn rats glucuronidate acetaminophen (APAP) at reduced rates and show increased susceptibility to APAP-induced hepatotoxicity. This defect is presumed to involve UDP-glucuronosyltransferase (UGT) 1A6, which is nonfunctional in Gunn rats, but it is currently unclear whether other 1A family members are also involved. In humans, two 1A isoforms are known to be active (1A6 and 1A9) but 1A6 form ha...

BACKGROUND Pleomorphic adenoma (benign mixed tumor) is one of the most common salivary gland tumors. However, the processes involved in its carcinogenesis are not well defined. This study aimed to define the contribution of Nfr2 (nuclear factor (erythroid-derived 2)-like 2) to pleomorphic adenoma pathology. The Nrf2-controlled gene system is one of the most critical cytoprotective mechanisms, p...

Treatment with the microsomal enzyme inducer trans-stilbene oxide (TSO) can decrease biliary excretion of acetaminophen-glucuronide (AA-GLUC) and increase efflux of AA-GLUC into blood. The hepatic canalicular multidrug resistance protein (Mrp) 2 and sinusoidal protein Mrp3 transport AA-GLUC conjugates into bile and blood, respectively. Thus, TSO-induced alterations in the vectorial excretion of...

The effects of aflatoxin B₁ (AFB₁), aflatoxin M₁ (AFM₁), deoxynivalenol (DON) and zearalenone (ZEA) on the viability, chemiluminescent (CL) response and expression of cytokine mRNA of bovine neutrophils (PMNs) were evaluated. The opsonized zymosan (OPZ)-stimulated CL response of PMNs was significantly (P < 0.05) decreased by AFB₁ ( > 50 pg/ml), AFM₁ ( > 50 pg/ml) and ZEA (>50 pg/ml). The phorbo...

Sulfur mustard (SM) is a powerful cytotoxic agent as well as a potent vesicant, mutagen, and carcinogen. This compound reacts with glutathione (GSH) and forms GSH-SM conjugates that appear to be excreted through the mercapturic acid pathway in mammals. The question of whether glutathione-S-transferases (GST) are involved in enzymatic formation of these conjugates remains unresolved. In previous...

Omeprazole (OPZ) and β-naphthoflavone (BNF) are cytochrome P450 (CYP)1A inducers and have liver tumor promoting effects. In this study, we investigated the co-promoting and co-initiating effects of OPZ and BNF in rats. In Experiment 1, male rats were subjected to partial hepatectomy (PH), and given oral doses of 138 or 276 mg/kg OPZ, 0.125% or 0.25% BNF or 138 mg/kg OPZ+0.125% BNF (n = 9~12) fo...

This paper introduces a new bilingual Czech-English verbal valency lexicon (called CzEngVallex) representing a relatively large empirical database. It includes 20,835 aligned valency frame pairs (i.e., verb senses which are translations of each other) and their aligned arguments. This new lexicon uses data from the Prague Czech-English Dependency Treebank and also takes advantage of the existin...

Oxidative metabolism of eosinophils has generally been studied in cells from patients with eosinophilia. We isolated eosinophils with purity of greater than 95% from normal donors. Oxygen metabolism of eosinophils and neutrophils was compared using O2-. production as a measure of the stimulus-induced respiratory burst. During 10 min of stimulation, using phorbol myristate acetate (PMA) or opson...