ABSTRACT
The constitutive androstane receptor(CAR) activation is connected with mitogenic effects leading to liver hyperplasia and tumorigenesis in rodents. CAR activators, including phenobarbital, are considered rodent non-genotoxic carcinogens. Recently, trans-3,4,5,4´-tetramethoxystilbene(TMS), a potential anticancer drug (DMU-212), have been shown to alleviate N-nitrosodiethylamine/phenobarbital-induced liver carcinogenesis. We studied whether TMS inhibits mouse Car to protect from the PB-induced tumorigenesis. Unexpectedly, we identified TMS as a murine CAR agonist in reporter gene experiments, in mouse hepatocytes, and in C57BL/6 mice in vivo. TMS up-regulated Car target genes Cyp2b10, Cyp2c29 and Cyp2c55 mRNAs, but down-regulated expression of genes involved in gluconeogenesis and lipogenesis. TMS did not change or down-regulate genes involved in liver proliferation or apoptosis such as Mki67, Foxm1, Myc, Mcl1, Pcna, Bcl2, or Mdm2, which were up-regulated by another Car ligand TCPOBOP. TMS did not increase liver weight and had no significant effect on Ki67 and Pcna labeling indices in mouse liver in vivo. In murine hepatic AML12 cells, we confirmed a Car-independent proapoptotic effect of TMS. We conclude that TMS is a Car ligand with limited effects on hepatocyte proliferation, likely due to promoting apoptosis in mouse hepatic cells, while controlling Car target genes involved in xenobiotic and endobiotic metabolism.
Subject(s)
Anticarcinogenic Agents/pharmacology , Cell Proliferation/drug effects , Hepatocytes/drug effects , Liver Neoplasms/prevention & control , Liver/drug effects , Receptors, Cytoplasmic and Nuclear/agonists , Stilbenes/pharmacology , Animals , Anticarcinogenic Agents/metabolism , Apoptosis/drug effects , Aryl Hydrocarbon Hydroxylases/genetics , Aryl Hydrocarbon Hydroxylases/metabolism , Binding Sites , Constitutive Androstane Receptor , Cytochrome P450 Family 2/genetics , Cytochrome P450 Family 2/metabolism , Gene Expression Regulation, Enzymologic/drug effects , Gluconeogenesis/drug effects , Gluconeogenesis/genetics , Hep G2 Cells , Hepatocytes/metabolism , Hepatocytes/pathology , Humans , Lipogenesis/drug effects , Lipogenesis/genetics , Liver/metabolism , Liver Neoplasms/enzymology , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Male , Mice, Inbred C57BL , Molecular Docking Simulation , Protein Binding , Pyridines/pharmacology , Receptors, Cytoplasmic and Nuclear/genetics , Receptors, Cytoplasmic and Nuclear/metabolism , Signal Transduction/drug effects , Steroid Hydroxylases/genetics , Steroid Hydroxylases/metabolism , Stilbenes/metabolismABSTRACT
Authors deal with practice of nursing care provided to Muslim clients in the Czech Republic. They use the explorative research design. By means of analyses of 21 semi-structured interviews with important social actors in the area of health care (spa resorts and hospitals). The study shows that Muslims are not homogeneous in their behaviour in the field of health care. In the spa environment, three interpretation perspectives can be found: the economic interpretation of a Muslim as the source of income of the Czech spa industry, which faces economic problems, the cultural interpretation developed within the spas (the experience capital of the staff and other clients), and the (a) cultural interpretation of Muslims and Islam brought to spas from the outside (the public opinion). However, in the area of hospitals, Muslims are not separated from the remaining categories of students; Muslim patients represent a small group of persons, and their treatment being conditioned by the distance or closeness of cultures, language skills, adaptation, and experiences with treatment in the Czech environment as perceived by the staff.
Subject(s)
Attitude of Health Personnel , Islam , Nursing Care/methods , Nursing Staff , Religion and Medicine , Czech Republic , Humans , Interviews as TopicABSTRACT
OBJECTIVE: Clinical case of extremely elevated levels of alkaline phosphatase (ALP) enzyme detected in the 3rd trimester of gestation, the diagnostic and therapeutic procedures, delivery and puerperium are presented. The paper also offers a review of the currently available bibliographical data of the issue. METHODS AND RESULTS: The case presents a 23-year-old secundipara with clinical problems in her 3rd trimester, namely a generalized pruritus. The gestation had signs of asymmetrical fetal hypotrophy induced by placental insufficiency. Laboratory tests showed elevated (as much as a 10.5-fold increase) values of alkaline phosphatase enzyme, 94.05% of which was placental isoenzyme. The patient also had clinical symptoms of a preterm delivery. The spontaneous delivery occurred in 36 week of gestation. The postpuerperium values of alkaline phosphatase returned to normal. CONCLUSION: The authors point out the potential relationship between elevated placental isoenzyme of alkaline phosphatase levels and placental insufficiency and the onset of a preterm delivery.
