Flow-injection analysis with immobilized chemiluminescent and bioluminescent columns.
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Adenosine Triphosphate↗
Biomedical subjects
T Heinonen
Publications and source records attributed to T Heinonen.
Enhanced peroxisomal beta-oxidation of fatty acids and glutathione metabolism in rats exposed to phenoxyacetic acids.
Peroxisomal beta-oxidation of fatty acids and the activities of glutathione-metabolizing enzymes in rat liver were measured after administration of 2,4-dichlorophenoxyacetic acid (2,4-D), 4-chloro-2-methylphenoxyacetic acid (MCPA), clofibrate [ethyl], 2-(p-chlorophenoxy)-2-methylpropionate], glyphosate (N-phosphonomethyl glycine, a herbicide not structurally related to phenoxy acids) or saline for 14 days. beta-Oxidation increased by 6-fold in the group given clofibrate, 3-fold in the 2,4-D-treated group, and 2-fold in the MCPA-treated group over the level in the controls (saline-treated). Glyphosate did not increase beta-oxidation. No significant change in reduced glutathione content from that in controls was found in any of the treated groups. Glutathione reductase activity increased by about 40% after administration of either 2,4-D or MCPA, and glutathione peroxidase activity increased by 30% in animals given MCPA. A slight decrease in glutathione S-transferase activity was found in the group treated with clofibrate. The marked increases in peroxisomal beta-oxidation of fatty acids were accompanied by only minor changes in the activities of enzymes involved in glutathione-dependent inactivation of organic hydroperoxides and other oxygen-centred reactive agents.
2,4-Dichlorophenoxyacetic Acid↗
DNA binding of [14C]styrene in isolated rat hepatocytes.
Incubation of hepatocytes from phenobarbital-pretreated rats with diethylmaleate (DEM) and 1 mM [14C]styrene for 3 to 5 hours did not result in binding of styrene 7,8-oxide (SO) to DNA as determined by ion exchange chromatography of enzymatic digests of DNA. The elution of substantial amounts of radioactivity together with natural nucleosides and bases suggests that styrene is partly metabolized via splitting of the vinyl bond and that incorporation of C1 fragments into DNA is most likely the result of repair DNA synthesis following DNA damage by styrene itself or one of its metabolites.
Animals↗
Detection of exposure to mutagenic compounds in low-tar and medium-tar cigarette smokers.
A volunteer study was carried out on groups smoking low-tar (5.4 mg/cig.) and medium-tar (16.3 mg/cig.) cigarettes and on non-smokers. The number of cigarettes smoked was recorded daily throughout a 51-day study period, and the effects of smoking were measured in the beginning and after 3-week terms of smoking medium-tar or low-tar cigarettes. The parameters measured were blood carboxyhemoglobin concentration, thioethers excreted into the urine, mutagenic activity in the urine, and the frequency of sister-chromatid exchanges in blood lymphocytes. For all four parameters, the differences between the smokers and the non-smokers were significant. However, within the study design no differences could be detected between low-tar or medium-tar cigarette smoking in the biological-monitoring tests used.
Adult↗
Urinary excretion of thioethers among low-tar and medium-tar cigarette smokers.
The urinary excretion of thioethers was studied among smokers of medium-tar cigarettes (16.3 mg/cig.) and low-tar cigarettes (5.4 mg/cig.). The test persons (26 smokers and 11 nonsmokers) were healthy young men in the military service. The smokers had an increased excretion of thioethers into the urine (P = 0.002 with Mann-Whitney U-test) when compared with the nonsmokers. No differences in the amount of urinary thioethers were detected between the low-tar and medium-tar cigarette smokers. The smokers (varying from 2.0 to 8.5 mmol/mol creatinine) had more individual variation than the nonsmokers (varying from 1.5 to 4.5 mmol/mol creatinine). Furthermore, the individual variation in the group of low-tar cigarette smokers did not markedly differ from the individual variation of medium-tar cigarette smokers.
Adult↗
Subacute toxicity of vinyltoluene vapour: effects on the hepatic and renal drug biotransformation and the urinary excretion of thioether.
Male rats were exposed by inhalation to vinyltoluene at concentrations of 50, 100, or 300 p.p.m. for 8, 12 or 15 weeks. Vinyltoluene was found to be metabolized to glutathione conjugates via the formation of electrophilic intermediates. This metabolic pathway was suggested by the decreased hepatic non-protein sulfhydryl content, with a concomitant increase in the urinary excretion of thioethers. The excretion of thioethers showed no saturation phenomena, suggesting that the formation of electrophilic intermediates capable of conjugating with glutathione is fairly linear, at least with exposure to vinyltoluene vapour up to 300 p.p.m. The slight increase in the activities of hepatic drug biotransformation enzymes (7-ethoxycoumarin 0-deethylase. UDPglucuronosyltransferase) observed after 8 weeks of exposure to vinyltoluene vapour disappeared by week 15 irrespective of the continued intermittent inhalation of vinyltoluene. Histological study revealed that cell size had decreased in the rats exposed to vinyltoluene.
Animals↗
Alkylation of guanosine and 4-(p-nitrobenzyl)-pyridine by styrene oxide analogues in vitro.
In vitro alkylation activity of styrene oxide (SO) and three of its analogues, 4-vinyltoluene oxide (VTO), 3,5-dimethylstyrene oxide (DMSO), and 4-nitrostyrene oxide (NSO) was assayed using 4-(p-nitrobenzyl)pyridine (NBP) and guanosine as nucleophiles. Hydrolysis rates were also determined. The half-lives of VTO, DMSO, SO, and NSO were 8, 11, 40, and 60 h, respectively in aqueous solution. The rate of NBP alkylation correlated with the rate of hydrolysis. By contrast, the rates of guanosine alkylation were quite different: SO greater than VTO greater than DMSO. NSO did not react with guanosine. Fluorescence an ultraviolet spectroscopic data on the guanosine adducts indicated that SO, VTO, and DMSO formed main alkyl products at N-7.
Alkylation↗
Dose-dependent toxicity of ethylene glycol monomethyl ether vapour in the rat.
Wistar male rats were exposed by inhalation to 50, 100 or 400 ppm of ethylene glycol monomethyl ether (EGME) for 1 to 2 weeks. The overall hepatic drug oxidation reactions, O-deethylation of 7-ethoxycoumarin and 7-ethoxyresorufin and cytochrome P-450 content were only slightly affected by the EGME exposures. NADPH cytochrome c reductase activity showed a tendency toward a dose-dependent decrease in liver, the activity being 73% and 64% of that in the controls after one and two weeks of exposure, at 400 ppm respectively. UDP glucuronosyl transferase activity exhibited a dose-dependent enhancement in liver microsomes after exposure for two weeks to EGME. The enhancement was 1.3- 1.7- and 3.0 fold with exposure to 50, 100 and 400 ppm of EGME respectively. After exposure for one week the UDPglucuronosyltransferase activity in kidney microsomes was similarly enhanced. A dose-related increase in measurable UDPglucuronosyltransferase activity was also obtained in Triton X-100 treated hepatic microsomes. GSH levels of the liver and kidneys in EGME treated animals showed a tendency towards a dose-dependent increase. The activities of low-Km and high-Km aldehyde dehydrogenases in liver were decreased 6 - 14% of that in the controls with exposure to 400 ppm of EGME when glycolaldehyde was used as a substrate. Serum alanine aminotransferase activity was not influenced by inhalation exposures to EGME.
Animals↗
Dose-dependent effects of vinyltoluene inhalation on non-protein thiols and drug biotransformation in liver and kidneys of the rat.
1. Male Wistar rats were exposed to atmospheres of 50, 100 or 300 p.p.m vinyltoluene 6h/day, 5 days/week, for one or two weeks. 2. Hepatic non-protein sulphydryl content decreased in a dose-dependent manner when measured 0.5 h after the last exposure, both after one and two weeks. 3. The content of hepatic non-protein sulphydryl groups progressively increased 20 h after stopping the vinyltoluene exposure. 4. The activity of 7-ethoxycoumarin O-deethylase showed a dose-dependent increase both in liver and kidneys. The activity of UDP-glucuronosyltransferase also increased in a dose-related manner in both organs studied.
Animals↗
Vinyltoluene induced changes in xenobiotic-metabolizing enzyme activities and tissue glutathione content in various rodent species.
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Animals↗
Glutathione depletion in isolated rat heaptocytes caused by styrene and the thermal degradation products of polystyrene.
Depletion of reduced glutathione (GSH) was induced in isolated rat hepatocytes incubated with styrene or exposed for 120 min to products from oxidative thermal degradation of polystyrene. The depletion depended on the concentrations of styrene and on the degradation temperature. Styrene (1 mM) or products from degradation of polystyrene at 200 degrees C (concentration of styrene in exposure atmosphere 0.7 ppm) had no detectable effect on glutathione levels in isolated hepatocytes. At higher degradation temperatures (250 degrees C and 300 degrees C, with styrene concentrations of 2.5 and 25 ppm, respectively) a rapid depletion was detected as well as with 3 mM styrene in incubation mixture. The latency of lactate dehydrogenase was affected neither by the polystyrene degradation products nor by the styrene added to the incubation mixture.
Animals↗
Decrease of reduced glutathione in isolated rat hepatocytes caused by acrolein, acrylonitrile, and the thermal degradation products of styrene copolymers.
Decrease of reduced glutathione (GSH) was induced in isolated rat hepatocytes by incubation with acrolein or acrylonitrile for 120 min or exposure to the products of oxidative thermal degradation of acrylonitrile-butadiene-styrene copolymer (ABS), styrene-acrylonitrile copolymer (SAN), and high impact polystyrene (SB). The decrease of GSH by acrolein was rapid but the cells soon recovered at acrolein concentrations of 0.025--0.25 mM. 0.5 mM acrolein depleted the cells of GSH and they were uncapable of further GSH synthesis. At concentrations of 0.25--0.5 mM concomitant lipid peroxidation impaired the integrity of the cell membranes. Also acrylonitrile induced a dose dependent GSH decrease at concentrations of 0.05--1 mM. Neither membrane damage nor lipid peroxidation was detected during 120-min incubations at these acrylonitrile concentrations. The thermal degradation products of ABS, SAN and SB caused a decrease of GSH in hepatocytes. The extent of the decrease depended on the degradation temperature and the type of the plastic. The membrane integrity was impaired in the cases where GSH was depleted almost completely; ABS degraded at 350 degrees C and SB at 250 degrees C. The measurements of lipid peroxidation by the thiobarbituric acid and the diene conjugation methods were impossible because the degradation products contained compounds which interfered with these tests.
Acrolein↗
Dose-related hepatotoxicity of 1,1,2-trichloro-1,2,2-trifluoroethane in short-term intermittent inhalation exposure in rats.
Male Wistar rats were exposed to 200, 1000 or 2000 ppm of 1,1,2-trichloro-1,2,2-trifluoroethane vapor 5 days a week 6 h daily for 1 or 2 weeks. Proliferation and vacuolisation of the smooth endoplasmic reticulum (SER) of the liver was seen electron microscopically after 1 and 2 weeks in the rats exposed to 1000 and 2000 ppm. Among the hepatic drug metabolizing enzymes, NADPH cytochrome c reductase activity showed a dose-related decrease whereas the tightly membrane-bound UDPglucuronosyltransferase exhibited a dose-dependent enhancement in its measurable activity. The overall drug oxidation reaction, 7-ethoxycoumarin O-deethylase was not affected by the 1,1,2-trichloro-1,2,2,-trifluoroethane inhalation at all, either in the liver or in the kidneys. 1,1,2-Trichloro-1,2,2-trifluoroethane binds to cytochrome P-450 with the production of a type I difference spectrum, suggesting that it may act as a substrate for this enzyme. The binding affinity is increased by phenobarbital-treatment of the rats.
Animals↗
Effects of vinyltoluene alone and after pretreatment with polychlorinated biphenyls on hepatocellular morphology and enzyme activities in liver and kidneys in rats.
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7-Alkoxycoumarin O-Dealkylase↗
3D visualization library for multimodal medical images.
This study focuses on three-dimensional (3D) presentations of medical images such as magnetic resonance (MR) images and computed tomography (CT) images. Also multimodal presentations of medical images and signals, including different visualization techniques are considered. A C++ class library together with graphical user interfaces was developed for presenting the results. The implemented software operates in PC/Windows environment. It was tested with various medical images including raw MR and CT data and segmented images, and was applied in a hospital environment. The software operates relatively fast and the quality of resulting pictures is adequate for all tested medical applications. Further applications of 3D presentations in clinical medicine are considered.
Computer Graphics↗
Applicability of semi-automatic segmentation for volumetric analysis of brain lesions.
This project involves the development of a fast semi-automatic segmentation procedure to make an accurate volumetric estimation of brain lesions. This method has been applied in the segmentation of demyelination plaques in Multiple Sclerosis (MS) and right cerebral hemispheric infarctions in patients with neglect. The developed segmentation method includes several image processing techniques, such as image enhancement, amplitude segmentation, and region growing. The entire program operates on a PC-based computer and applies graphical user interfaces. Twenty three patients with MS and 43 patients with right cerebral hemisphere infarctions were studied on a 0.5 T MRI unit. The MS plaques and cerebral infarctions were thereafter segmented. The volumetric accuracy of the program was demonstrated by segmenting Magnetic Resonance (MR) images of fluid filled syringes. The relative error of the total volume measurement based on the MR images of syringes was 1.5%. Also the repeatability test was carried out as inter-and intra-observer study in which MS plaques of six randomly selected patients were segmented. These tests indicated 7% variability in the inter-observer study and 4% variability in the intra-observer study. Average time used to segment and calculate the total plaque volumes for one patient was 10 min. This simple segmentation method can be utilized in the quantitation of anatomical structures, such as air cells in the sinonasal and temporal bone area, as well as in different pathological conditions, such as brain tumours, intracerebral haematomas and bony destructions.
Brain↗
Detailed model of the thorax as a volume conductor based on the visible human man data.
A large number of computerized conductivity models of the human thorax have been created to study bioelectric phenomena in human beings. Devised models have varied greatly in the level of anatomical detail incorporated thus restricting the accuracy and validity of conducted simulations. This paper introduces a highly detailed anatomically accurate three-dimensional computer model of the conductive anatomy of the human thorax for calculating electric fields generated by equivalent bioelectric sources and different externally applied sources. The anatomy of the devised model is based on high resolution colour cryosection images of the US National Library of Medicine's Visible Human Man data set and is comprised of more anatomical detail than prior computer models. The model is based on the finite difference method and is readily applicable for the analysis of a wide range of biomedical field problems, such as electrocardiography, impedance cardiography, tissue stimulations, and especially, in development of measurement systems.
Anatomy, Cross-Sectional↗
Nasal airway volumetric measurement using segmented HRCT images and acoustic rhinometry.
Semiautomatic segmentation methods using High Resolution Computed Tomography (HRCT) or Magnetic Resonance Imaging give accurate and reproducible volumetric measurements in various intracranial diseases. In this prospective study, for the first time in literature, with the help of a new semiautomatic segmentation technique and coronal HRCT, we correlated the volumes and cross-sectional areas of the nasal cavity with those obtained by clinical acoustic rhinometry in 14 patients with chronic sinusitis. The measurements obtained by both techniques showed statistically significant correlations between volumes in the anterior and middle parts, but statistically poor correlations between the volumes in the posterior part of the nasal cavity. Coronal HRCT and our new microcomputer applicable semiautomatic segmentation software proved compatible with daily clinical practice. Based on the promising results of our study, we recommend the use of this technique in the validation studies of acoustic rhinometry and in complicated cases as a complementary examination in the evaluation of nasal cavity.
Acoustics↗