ABSTRACT
Beta-thujaplicin (TP) was studied by in vitro and in vivo tests for teratogenicity using ICR mice. In the in vitro study, TP (0, 3.125, 6.25, 12.5 microg/ml medium) dissolved in dimethyl sulfoxide (DMSO) was administered to cultured embryos on 9 day of gestation. After 24 hr of exposure to TP, the embryos were examined for developmental parameters and external anomalies. Growth retardation and embryos with facial dysplasia or hydrocyst of the tail tip were observed among the embryos given 12.5 microg/ml. In the in vivo study, TP (0, 420, 560, 750 or 1000 mg/kg) dissolved in olive oil was administered orally to pregnant mice on day 9 of gestation. All foetuses were removed from the uterus on day 18 of gestation, and were examined for external and skeletal anomalies. Various types of malformations were observed in the mice given 560 mg/kg or more. The number of litters having foetuses with external or skeletal anomalies increased in proportion to the dose of TP. The regression lines of Y (probit response) on X (log dose) for external anomalies was Y = 4.87X-8.43 . The 1% effective dose (ED1) for the malformation was 190 mg/kg. The present study shows that TP has teratogenic effects on mice.
Subject(s)
Abnormalities, Drug-Induced/etiology , Anti-Infective Agents/toxicity , Food Additives/toxicity , Iron Chelating Agents/toxicity , Monoterpenes , Teratogens/toxicity , Tropolone/analogs & derivatives , Animals , Anti-Infective Agents/blood , Apoptosis/drug effects , Culture Techniques , Dose-Response Relationship, Drug , Embryo, Mammalian , Female , Male , Mice , Mice, Inbred ICR , Pregnancy , Tropolone/blood , Tropolone/toxicityABSTRACT
Evidence is now accumulating that patient medication can adversely affect the radiolabelling of white cells. We have undertaken a survey for the years 1981-97 to examine instances of unusually low labelling efficiencies of 111In-tropolone and 99Tcm-HMPAO labelled white cells. Respondents were asked to ascertain which drugs were being taken on the day of the test. Fifty adverse reports were received during that period. Many patients were taking drugs which are known to affect white cell function, including cephalosporins, azathioprine, prednisolone, cyclophosphamide, nifedipine, suphasalazine, iron salts and heparin. Using Bradford-Hill's criteria to assess whether an association between two variables is also one of causation, it was found that there was a high probability that the above drugs caused the low labelling efficiencies.
Subject(s)
Drug Therapy , Leukocytes , Organometallic Compounds/pharmacokinetics , Radiopharmaceuticals/pharmacokinetics , Technetium Tc 99m Exametazime/pharmacokinetics , Tropolone/analogs & derivatives , Drug Interactions , Humans , Indium Radioisotopes/adverse effects , Indium Radioisotopes/blood , Indium Radioisotopes/pharmacokinetics , Organometallic Compounds/adverse effects , Organometallic Compounds/blood , Radiopharmaceuticals/adverse effects , Radiopharmaceuticals/blood , Technetium Tc 99m Exametazime/adverse effects , Technetium Tc 99m Exametazime/blood , Tropolone/adverse effects , Tropolone/blood , Tropolone/pharmacokineticsABSTRACT
Red blood cells were labelled with 67Ga oxine prepared from 67Ga citrate, a routinely available and relatively inexpensive radiopharmaceutical which is suitable for dual-isotope imaging with 99mTc. Labelling efficiency was 88 +/- 1%, 24-h in vitro stability was 93 +/- 5% in saline at room temperature and 68 +/- 4% in whole blood at 37 degrees C, and the method could be performed within 20-30 min.
Subject(s)
Erythrocytes/metabolism , Gallium Radioisotopes , Humans , Oxyquinoline/chemistry , Pyridines/chemistry , Thiones , Tropolone/blood , Tropolone/metabolismABSTRACT
Pure polymorphonuclear leukocytes (PMNs) have been isolated from a small amount of human blood by a single-step density gradient centrifugation method using a commercially available Ficoll-Hypaque mixture of density 1.114. The cells were labelled with [111In]tropolone in both buffer and plasma. Cell viability, ability to generate superoxide anion, and chemotaxis were found to be unaltered both before and after labeling. The optimum tropolone concentration for labeling was found to be 1 X 10(-4) M. Labeling efficiency was higher at 37 degrees C than at room temperature. Compared to [111In]oxine, tropolone preparation both in buffer and plasma resulted in consistently higher yields. Preliminary experiments of in vivo cell viability of the labeled PMNs were carried out in rabbits. The ability of the cells to localize in experimentally produced inflammatory lesions was found to be intact. The method of cell separation and labeling described has been found to be simple and rapid and could easily be incorporated in routine nuclear medicine laboratory practice.
Subject(s)
Cycloheptanes , Indium , Neutrophils , Radioisotopes , Tropolone , Animals , Cell Survival , Centrifugation, Density Gradient/methods , Chemotaxis, Leukocyte , Ficoll , Humans , Neutrophils/cytology , Rabbits , Superoxides/metabolism , Tropolone/bloodABSTRACT
Catechol-O-methyl transferase (COMT) activity was investigated in human peripheral mononuclear cells and in human lymphoblastoid cells lines. In any case, we have detected enzymatic activity in the membrane fraction of the cells. Km was found to be 4-9 10(-6) M and the enzyme was inhibited by tropolone and the lack of magnesium. The eventual association of COMT with adrenergic receptor-adenylate cyclase system in mononuclear cells is discussed.
