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Biomedical subjects

O Pelkonen

Publications and source records attributed to O Pelkonen.

At least 181 records · Page 10Linked to original sources
PubMed1983

Placental transfer and hormonal effects of metoclopramide.

In order to study the transplacental transfer of metoclopramide, and its endocrine effects, measurements were made of its concentration in maternal and fetal blood, and in the amniotic fluid, together with maternal and fetal plasma concentrations of prolactin, TSH and oestradiol, during delivery by selective Caesarean section. The drug, 10 mg, was injected i.m. 12 and 2 h and just before the onset of anaesthesia. Metoclopramide was detectable in all the umbilical arterial and venous and amniotic fluid samples, in mean concentrations of 50, 63 and 75 ng/ml, respectively. The mean ratio between the umbilical venous and maternal plasma concentrations was 0.63. Accurate maternal plasma half-lives could not be established but they must have averaged 2 to 4 h. The high amniotic fluid concentrations and relatively high umbilical venous and arterial concentrations soon after administration suggest that metoclopramide equilibrates relatively rapidly between the mother and fetus. Metoclopramide raised the maternal plasma prolactin levels from 315 +/- 128 ng/ml (SD) before therapy to 357 +/- 112 ng/ml at the time birth. No statistically significant difference in cord arterial or venous plasma prolactin levels was seen between the control and metoclopramide-treated groups. Metoclopramide did not affect maternal plasma TSH or oestradiol levels. The only change was a slight but significant increase in TSH level in cord blood taken from the umbilical artery after metoclopramide treatment.

Anesthesia, Obstetrical↗
PubMed1983

Cigarette smoking and drug metabolism.

Cigarette smoking appeared to induce total body drug metabolism, as indicated by decreased antipyrine t 1/2 and increased antipyrine clearance. The in vitro parameters of liver drug metabolism used (benzo(a)pyrene hydroxylase and cytochrome P-450 levels), however, were not changed. This implicates induction of drug metabolism in some other organ(s). Serum thiocyanate levels were higher in smokers than in exsmokers and nonsmokers. There was a certain amount of overlap between these groups; whether this reflects unreliability of smoking anamnesis or unspecificity of thiocyanate assay in discriminating between smokers and nonsmokers is not known. There was no significant correlation between serum thiocyanate and the other parameters studied.

Antipyrine↗
PubMed1983

Genetically determined differences in the response to carcinogens of aryl hydrocarbon hydroxylase and ornithine decarboxylase.

Carcinogenesis involves a complex interplay of both hereditary and environmental factors. With the exception of some cancers which may be inherited through an autosomal dominant gene (e.g., retinoblastoma), cancer causation is controlled by a multitude of genes. The murine Ah complex is an example of a well-characterized model system for studying genetic factors for carcinogenesis in mice. The Ah complex controls the induction of several xenobiotic-metabolizing enzyme activities by, e.g., polycyclic aromatic hydrocarbons (PAHs). Allelic differences at the Ah locus are associated with increased individual risk for cancer and mutation. The polyamines and their biosynthetic enzymes, especially ornithine decarboxylase (ODC), are useful probes in the study of carcinogenesis. The available evidence supports the theory that the induction of ODC activity is an essential factor in mouse skin tumorigenesis. In contrast, ODC induction is not an essential prerequisite in the induction of enzymes involved in converting carcinogens of the PAH-type to reactive intermediates capable of binding to DNA. The possible involvement of the polyamines and ODC in cancer initiation and promotion, in DNA repair processes and in genetic factors that might influence them are discussed in this review.

Animals↗
PubMed1983

Effect of polycyclic aromatic compounds and phorbol esters on ornithine decarboxylase and aryl hydrocarbon hydroxylase activities in mouse liver.

Single i.p. injections of 3-methylcholanthrene (MC; 50 mg/kg) administered to inbred C57BL/6 mice or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 100 micrograms/kg) to DBA/2 mice gave an increase in the hepatic activities of ornithine decarboxylase (ODC) and aryl hydrocarbon hydroxylase (AHH) with peaks occurring by 12 and 48 hr, respectively. A single i.p. dose of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA; 100 micrograms/kg) enhanced the activity of ODC about 70-fold within 12 hr in C57BL/6 mice and 18-fold within 24 hr in DBA/2 mice without affecting AHH activity markedly. 4-O-Methyl-12-O-tetradecanoylphorbol-13-acetate (100 micrograms/kg) raised ODC activity to about 25% of the TPA-treated value in C57BL/6 mice; in DBA/2 mice, TPA and 4-O-methyl-12-O-tetradecanoylphorbol-13-acetate induced ODC activity to roughly the same level. Benzo(e)pyrene (50 mg/kg) failed to affect ODC and AHH activities significantly in either strain. The inducing effect of TPA on ODC activity was potentiated by a simultaneous administration of MC to C57BL/6 mice; combined TPA and TCDD to DBA/2 mice exerted an additive effect on hepatic ODC activity. Difluoromethylornithine administered i.p. effectively inhibited the induction of ODC activity elicited by TPA, MC, or TCDD either alone or in various combinations but did not interfere with AHH induction. These data indicate that different regulatory factors are involved in the ODC induction process elicited by TPA and polycyclic aromatic compounds and that MC and TCDD may induce ODC activity by different mechanisms. The results also confirm our earlier findings in rat skin and cells in culture which suggest that the ODC and AHH induction processes can occur independently of each other. Additionally, there is a strain-related difference in sensitivity with regard to ODC-inducing activity of TPA in the livers of C57BL/6 and DBA/2 mice.

Animals↗
PubMed1982

Dissociation between ornithine decarboxylase activity and aryl hydrocarbon hydroxylase induction in cell cultures treated with benz[a]anthracene and inhibitors of ornithine decarboxylase.

The induction of aryl hydrocarbon and ornithine decarboxylase by benz[a]-anthracene in the presence or absence of ornithine decarboxylase inhibitors was studied in three different cell culture systems. An almost complete abolishment of ornithine decarboxylase activity by 1,3-diamino-2-propanol or alpha-difluoremethyl ornithine before the addition of the inducer did not affect appreciably the induction of aryl hydrocarbon hydroxylase by benz[a]anthracene in human embryo, HeLa and Rueber H-II-4-E cells in culture. These results suggest that the induction of aryl hydrocarbon hydroxylase does not require ornithine decarboxylase activity per se and can be expressed in the absence of continuous polyamine synthesis.

Aryl Hydrocarbon Hydroxylases↗
PubMed1982

Aryl hydrocarbon hydroxylase activity in cultured lymphocytes of psoriatic patients.

To evaluate further the metabolic capacity of psoriatics, the activities and inducibility of aryl hydrocarbon hydroxylase (AHH) were measured in cultured mitogen-stimulated lymphocytes from the peripheral blood of 68 psoriatic and 39 control patients. There was no significant difference in the mean basal and induced AHH activities between the psoriatics and the controls, although the former showed a slight tendency towards a higher inducibility ratio. In both, the basal and induced AHH values decreased significantly with increasing age. The cigarette smokers in both groups had significantly higher AHH activities than the nonsmokers. Antipsoriatic treatment (Anthralin, PUVA) did not seem to influence the lymphocyte AHH activities. No association was demonstrable between the AHH activities and the duration of the disease.

Adult↗
PubMed1982

Placental transfer of clenbuterol early in human pregnancy.

After administration of clenbuterol 80 microgram p.o., a beta-adrenoceptor agonist, the concentrations of (14C-labelled) clenbuterol in fetus, placenta and maternal plasma in 9 patients at 9-12 weeks gestation were measured during therapeutic abortion. The time interval between the administration and abortion ranged from 120 to 280 min. The mean concentrations of clenbuterol in maternal plasma, fetus and placenta were 0.37 (range 0.22-0.56), 0.32 (0.14-0.48) and 0.91 (0.12-1.73) ng equivalents per ml or per gram of tissue wet weight. The mean concentration ratio of clenbuterol between fetus and maternal plasma was 0.84 (6 cases); it did not vary with time. The concentration of clenbuterol in three amniotic fluid samples ranged from 0.06 to 0.16 ng/ml (mean 0.11). Maternal plasma concentrations showed wide variability of the pharmacokinetic phase at the time of abortion. The studies indicate that clenbuterol crosses the placenta early in human pregnancy and that it accumulates in the placenta.

Adolescent↗
PubMed1982

Drug metabolism in alcoholics.

The effects of chronic use of alcohol on drug metabolism are dependent on many variables, which determine the final outcome. The degree of liver injury, the inducing effect of long-term alcohol use and also macromorphological changes connected with advanced stages of alcohol-induced liver injury are of importance. Alcohol may also affect the toxification of foreign chemicals by the liver, thus rendering an individual more susceptible to chemical-induced toxic reactions. It is not possible to predict drug-metabolizing capacity of an alcoholic from clinical history, liver histology or serum biochemistry, although generally correlations among these parameters and hepatic drug-metabolizing enzymes are statistically significant. Consequently, direct assays for drug metabolism, e.g. the elimination of a test drug (e.g. antipyrine) or the drug under study itself, or enzyme measurements in biopsy samples, are needed if one wants to pursue "tailor-made" drug therapy for an alcoholic.

Alcoholism↗
PubMed1982

Effect of maternal cigarette smoke exposure on foetuses of inbred strains of mice responsive and non-responsive to polycyclic aromatic hydrocarbons.

To evaluate the role of genetically controlled responsiveness to polycyclic aromatic hydrocarbons (PAH) in the effect of cigarette smoke on birth weight, pregnant mice were exposed to cigarette smoke from day 1 to day 17 of pregnancy and the offspring studied on day 18. An unequivocal phenotyping of foetuses with respect to responsiveness was achieved by measuring the activity of aryl hydrocarbon hydroxylase (AHH) in the foetal liver and corresponding placenta after pretreatment of the dam with beta-naphthoflavone. The foetuses of dams exposed to standard non-filter cigarettes were consistently smaller than those of the controls, whereas smoke from commercial filter cigarettes was only marginally effective. No statistically significant association with the responsiveness to PAH could be found with respect to this effect on weight. These results suggest that genetically determined responsiveness to PAH, although of importance for PAH foetotoxicity in mice, is not important in the effect of cigarette smoke on birth weight in the strains studied.

Animals↗
PubMed1982

Independent induction and inhibition of ornithine decarboxylase and aryl hydrocarbon hydroxylase activities in rat epidermis.

Changes in the activities of ornithine decarboxylase (ODC) and aryl hydrocarbon hydroxylase (AHH) were investigated in rat epidermis after wounding the skin and application of 7,12-dimethylbenz(a)anthracene (DMBA), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and several enzyme inhibitors. Wounding of the skin by vigorous shaving led to a marked induction of ODC activity with a peak at 6 hr. Topical application of a single dose of tetradecanoylphorbol-13-acetate to wounded skin did not affect the activities of ODC and AHH. Application of single large dose (2.5 mg) of DMBA increased AHH activity 7-fold without affecting ODC activity. DL-alpha-difluoromethyl ornithine, a specific irreversible inhibitor of ODC, almost completely abolished ODC activity but did not inhibit DMBA- or TCDD-induced AHH activity. Several potential modifiers, including retinoic acid, indomethacin, 1,3-diamino-2-propranol, alpha-naphthoflavone, and SKF 525 A had unequal effects on ODC and AHH activities. These data indicate that ODC and AHH induction processes in the epidermis are independent biochemical events that are not causally related.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1982

Is aryl hydrocarbon hydroxylase induction 'systemically' regulated in man?

We demonstrated recently that, in smokers, placental activity of aryl hydrocarbon hydroxylase (AHH) is statistically significantly correlated with cord-blood lymphocyte AHH inducibility, whereas the correlation between maternal lymphocyte AHH inducibility and placental AHH activity is poor. These findings suggest that AHH induction in man may be 'systemically' regulated. In hospital patients, however, correlations among lymphocyte-AHH induction, hepatic mono-oxygenase activities and antipyrine elimination were poor, even in groups with no indication of liver injury. It seems that the 'systemic' regulation of AHH induction in man can be demonstrated only in special, favourable situations.

Aryl Hydrocarbon Hydroxylases↗
PubMed1981

A relationship between cord blood and maternal blood lymphocytes and term placenta in the induction of aryl hydrocarbon hydroxylase activity.

Correlations between lymphocyte aryl hydrocarbon hydroxylase (AHH) inducibility in cord blood and maternal lymphocytes and placental AHH activity were studied in 15 smokers and 11 non-smokers. Placental AHH activity was extremely low in the non-smokers regardless of the lymphocyte AHH induction ratio, but was elevated to a variable extent in the smokers, in whom it showed a statistically significant correlation (r = 0.75, P less than 0.01) with cord blood lymphocyte AHH inducibility. The correlation between maternal lymphocyte AHH inducibility and placental AHH activity was poor (r = 0.04, not significant). These findings suggest that AHH induction in man may be 'systematically' regulated and that the genetic background will determine the extent of induction at a given level of exposure to polycyclic aromatic hydrocarbons.

Adolescent↗
PubMed1981

Aryl hydrocarbon hydroxylase induction in maternal and cord blood mitrogen-treated lymphocytes.

The inducibility of aryl hydrocarbon hydroxylase was measured in mitrogen-activated peripheral lymphocytes from smoking and nonsmoking mothers and their newborn infants (cord blood). The mean inducibility ratio in lymphocytes from smoking women was 4.02 and that for nonsmokers 2.87. Benz(a)anthracene-induced and noninduced AHH activities were 3-6 times higher in the lymphocytes from the cord blood than in those from the mothers. The inducibility ratio in the cord blood lymphocytes from the smoking mothers was 3.65 and did not differ significantly from that for the nonsmokers, 3.54. There was a significant correlation in the induction ratio between maternal and cord blood lymphocytes from the nonsmokers, but not in the smokers. Thymidine incorporation was about twice as high on average in the cord blood lymphocytes as in the maternal lymphocytes. The results demonstrate that the extent and distribution of inducibility were very similar in the maternal and cord blood lymphocytes.

Adolescent↗