[Only professionals can interpret medical data on prescriptions].
Explore the source record for details and available documents.
Clinical Competence↗
Biomedical subjects
S Henningsson
Publications and source records attributed to S Henningsson.
[Local drug information--who is responsible?].
Explore the source record for details and available documents.
Drug Information Services↗
Comparison of human fetal hepatic and adrenal cytochrome P450 activities with some major gestational steroids and ethylmorphine as substrates.
The immunoidentified human fetal liver and adrenal microsomal contents of cytochromes P450IIIA and P450XVIIA1 were compared to the metabolism of steroids and ethylmorphine. In fetal liver microsomes, 16 alpha-hydroxylation of dehydroepiandrosterone (DHA) was catalyzed at a high rate in almost all investigated specimens and accompanied by a high ethylmorphine N-demethylase activity. Progesterone 16 alpha- and 17 alpha-hydroxylation was found only in the livers with the highest DHA 16 alpha-hydroxylation activities, while 21-hydroxylation of progesterone was catalyzed only occasionally in these samples. In fetal adrenal microsomes, 21-hydroxylation of progesterone to 11-desoxycorticosterone (DOC) and 11-desoxycortisol (DOCOL) was catalyzed. In contrast to fetal liver, the adrenals also catalyzed the 17 alpha-hydroxylation of pregnenolone and the formation of DHA from 17 alpha-OH-pregnenolone. 16 alpha-hydroxylation of DHA and ethylmorphine N-demethylation were modest in the adrenals. P450IIIA/HLp was immunoidentified in all investigated liver specimens except two (18/20) in which no ethylmorphine N-demethylation or 16 alpha-hydroxylation of DHA was found. P450XVIIA1 bands were observed in 8/20 blots of liver specimens, but there was no correlation between the density of these bands and the 17 alpha-hydroxylation of progesterone. All 11 fetal adrenal samples catalyzed DHA 16 alpha-hydroxylation, although only 8 were positive for P450IIIA/HLp. All investigated adrenals were positive in regard of the P450XVIIA1 band, except one (8/9) with a low 17 alpha-hydroxylation of progesterone. All adrenal specimens catalyzed 21-hydroxylation of progesterone and contained P450C21 bands in immunoblots and all samples catalyzed the formation of DOC and DOCOL from progesterone. Our findings in the fetal livers show a correlation between the DHA 16 alpha-hydroxylation and immunoidentified P450IIIA/HLp bands. In adrenals, there was a correlation between the immunoidentified P450XVIIA1 bands and the 17 alpha-hydroxylation of progesterone.
Adrenal Glands↗
Cerebrospinal fluid exchange after intrathecal methotrexate overdose. A report of two cases.
Two patients aged 11 and four years, were accidentally given a 10-fold overdose of intrathecal methotrexate while being treated for malignant disease. Neither patient developed any signs of neurotoxicity and exchange of lumbar cerebro-spinal fluid was started 3 and 5 h later, respectively. In one of the patients, who received 120 mg of methotrexate intrathecally, 31% of the given dose was recovered during 2 h of cerebrospinal fluid exchange that was started 3 h after the accidental overdosage. No sequelae were observed in any of the patients. Cerebrospinal fluid exchange is safe and can be recommended in all cases of intrathecal methotrexate overdosage. Ventriculo-cisternal perfusion is not necessary in cases of a 10-fold overdose if the patient has no signs of acute neurotoxicity.
Cerebrospinal Fluid↗
Autoradiography of 3H-alpha-fluoromethyl histidine in mice: correlation with the kidney histidine decarboxylase activity.
Tritium-alpha-fluoromethyl histidine (3H-alpha-FMH), designed as a kcat-inhibitor of mammalian histidine decarboxylase (EC 4.1.1.22), was administered intravenously in male and pregnant female mice of the NMRI strain and the distribution of tritium in the body recorded by whole-body and microautoradiography. The results showed penetration of radioactivity into most tissues within 5 min. after the injection. After 4 hrs the highest levels of radioactivity were present in the intestinal content and in the kidneys. In the pregnant animal there was also a high labelling of the foetal tissues. When whole-body sections were washed in TCA prior to the autoradiographic exposure to retain only protein-bound radioactivity, a distinct labelling pattern was seen in the kidneys of the pregnant female mice but not in those of the male mice. Microautoradiography of the kidneys showed that the cells involved were located within the proximal convoluted tubuli. In several mouse strains, including the NMRI, the activity of kidney histidine decarboxylase is low in the males but high in females during a transient period of pregnancy. Incorporation of tritium into kidney protein after treatment with 3H-alpha-FMH, was correlated to a loss in histidine decarboxylase activity. The isotopic labelling was confined mainly to a component which cofractionated with histidine decarboxylase in polyacrylamide gel electrophoresis (PAGE) under non-denaturing conditions. Our data indicate that the cells described above represent the location of kidney histidine decarboxylase.
Animals↗
Hyperplasia and hypertrophia in the denervated and distended rat urinary bladder.
The parasympathetically denervated and distended rat urinary bladder was found to have increased fourfold in weight when examined 3 weeks postoperatively. Both in muscularis and mucosa of such a bladder the synthesis of proteins, RNA and DNA was increased severalfold. An increase in the polyamines putrescine, spermidine and spermine was also found; these polyamines are usually linked to protein synthesis. The results suggest that the cells of the two layers increase both in size and number. Hyperplasia was, in a previous study, suggested as a possible explanation for a right-ward shift of the active length-tension curve of muscle strips in the denervated rat urinary bladder.
Animals↗
In vitro metabolism of cadaverine in the pregnant rat.
The in vitro metabolism of 14C-cadaverine by diamine oxidase was investigated in various tissues of pregnant and non-pregnant rats. The metabolites formed were: delta 1-piperideine, delta-aminovaleric acid, carbon dioxide and some unidentified compound(s). In most of the tissues investigated delta 1-piperideine was the predominant metabolite, but considerable amounts of delta-aminovaleric acid and the unidentified compound(s) were also formed. The oxidative products of cadaverine might be of importance in various physiological and pathophysiological connections associated with elevated diamine oxidase levels.
Amine Oxidase (Copper-Containing)↗
Affinity of putrescine, spermidine and spermine for pigmented tissues.
Explore the source record for details and available documents.
Animals↗
Effect of His-Phe, a competitive inhibitor of histidine decarboxylase, on gastric acid secretion in chronic gastric fistula rats: delay in acid secretion response to pentagastrin.
The dipeptide His-Phe, earlier shown to inhibit mammalian histidine decarboxylase, was analysed concerning its effect in vivo on pentagastrin-induced gastric acid secretion. Chronic gastric fistula rats were used and the effectors in saline were given as continuous i.v. infusions while acid was collected from the fistula. Addition of pentagastrin to the infusion solution resulted in an immediate increase in the acid output of the control runs. In the His-Phe experiments the dipeptide was introduced one hour before pentagastrin. A significant decrease in the acid output was obtained. This effect was optimal at a dose of about 6 mg/h and during the first few hours of the experiments. In spite of the continuous His-Phe infusion the acid secretion increased with time to the control values. These results are discussed in relation to preliminary observations on effects of alpha-fluoromethyl histidine on gastric acid secretion and the effect of this and His-Phe on gastric histamine content and histidine decarboxylase activity.
Animals↗
Changes in cadaverine and putrescine metabolism in the mouse kidney induced to growth by an anabolic steroid.
The formation of cadaverine and putrescine was studied in the kidneys of gonadectomized male mice stimulated to growth by nandrolone, an anabolic steroid with low androgenic activity. Administration of nandrolone resulted in an increased kidney weight and elevated activities of lysine and ornithine decarboxylase (assayed by measurement of the formation of 14CO2 from the 1-14C-labelled amino acids). The responses were dose and time dependent. The elevated enzyme activities were reflected by an increased endogenous kidney content of cadaverine and putrescine as well as in an increased urinary excretion of the diamines. Further, the kidney content and the urinary excretion of the polyamines spermidine and spermine were elevated on nandrolone treatment. Fractionation of kidney extracts on pore gradient electrophoresis revealed an apparent molecular weight of about 95 000 Daltons of the lysine decarboxylase as well as of the ornithine decarboxylase. On electrofocusing it was evident that both enzymes were present as more than one isoelectric form. However, the main form in both cases focused at a pH of about 5.0.
Animals↗
Metabolism of putrescine in the pregnant rat.
The in vivo metabolism of 14C-putrescine injected to rats before, during and after pregnancy was studied. Within 30 min of the administration of the isotope 9-12% of the injected radioactivity was recorded as 14CO2 in the expired air and after 5 h 60% was expired. The radioactivity excreted in the urine during the first day following the 14C-putrescine administration consisted of unmetabolized putrescine, gamma-aminobutyric acid (GABA) and some unidentified compound(s). No radioactive polyamines were detected in the urine. After treatment of pregnant rats with the diamine oxidase inhibitor aminoguanidine the expiration of 14CO2 was almost completely inhibited. In the urine increased amounts of unmetabolized putrescine were excreted while the excretion of GABA and the unidentified compound(s) were decreased. In addition 14C-spermidine appeared in the urine. The in vitro metabolism of putrescine was determined by the incubation of different tissues of pregnant and non-pregnant rats with 14C-putrescine. The 14C-metabolites derived via the diamine oxidase pathway (delta 1-pyrroline, GABA, some unidentified compound(s) and carbon dioxide) varied in magnitude with the tissue investigated. GABA was found to be a main metabolite of putrescine in several tissues of the pregnant rat. The content of putrescine and spermidine was elevated in several tissues as well as the blood on the 19th day of pregnancy in rats treated with aminoguanidine, while the content of spermine was unchanged.
Animals↗
On the biogenesis of diamines and polyamines in the pregnant rat.
The urinary excretion of the diamines histamine, methylhistamine, putrescine and cadaverine and the polyamines spermidine and spermine was studied in rats which on the 19th day of pregnancy were subjected to various ectomizing operations. In sham-operated rats the urinary excretion of all the amines studied except spermine was highly elevated on the day preceding the sham-operation and on the 3 days studied post-operatively, i.e. sham-operation did not affect the elevated urinary amine excretion during pregnancy. Foetectomy resulted in an abolished increase in the urinary excretion of histamine and methylhistamine while the excretion of putrescine, cadaverine and spermidine was still significantly increased. Removal of both the foetuses and placentae reduced the excretion of putrescine, cadaverine and spermidine towards the level of non-pregnant rats. Combined hysterectomy and ovariectomy did not cause any additional effects to those after removal of the foetuses and the placentae except for cadaverine, the excretion of which was further reduced.
Animals↗
Polyamine metabolism as related to growth and hormones.
Previous work had revealed a connection between high histamine formation and certain types of rapid growth. Since then evidences have accumulated that diamines abd polyamines affect an impressive number of reactions pertinent to cell growth and proliferation. In studies on polyamine metabolism as related to growth and hormones we have preferentially been working with three types of biological model systems, i.e. the pregnant rat, the gonadotrophin stimulated rat ovary and the mouse kidney induced to growth by androgenic or anabolic steroids.
Amine Oxidase (Copper-Containing)↗
Diamine oxidase activity and gamma-aminobutyric acid formation in medullary carcinoma of the thyroid.
The formation of different metabolites from 14C-putrescine via oxidative deamination has been studied in patients with medullary carcinoma of the thyroid (MCT) and in control subjects. The neoplastic tissue from MCT patients produced in addition to delta 1-pyrroline, large quantities of GABA and some unidentified compound(s), whereas the formation of these metabolites in normal thyroid tissue was almost negligible. Plasma from patients with MCT contained higher diamine oxidase activity than plasma from control subjects, but there was a considerable overlap between the two groups. Determination of the as yet unidentified compound(s) could possibly become a sensitive tool in the diagnosis and follow-up of carcinomas associated with a high diamine oxidase activity.
Adult↗
In vitro metabolism of putrescine by diamine oxidase in tissues of the pregnant rat.
The metabolism of 14C-putrescine by diamine oxidase was tested on the 19th day of pregnancy in different organs of rats. The highest turnover was found in maternal placenta and uterus where 94% of the reaction product was identified as delta 1-pyrroline. Considerable deamination rates were also observed in ovary, liver and fetal placenta where, however, gamma-aminobutyric acid was the predominant product. In the kidney only a small diamine oxidase activity was measured. No formation of spermidine or spermine from 14C-putrescine was detected.
Amine Oxidase (Copper-Containing)↗
Formation of GABA via oxidative deamination of putrescine in ovaries of immature rats after gonadotrophin stimulation.
The diamine oxidase catalyzed metabolism of 14C-putrescine was studied in the ovaries of immature rats with and without stimulation by gonadotrophin. This stimulation resulted in a statistically significant increase in the deamination rate of putrescine with a very predominant production of gamma-aminobutyric acid. No formation of polyamines was observed which indicated an importance of putrescine or of products of its oxidative deamination during this cellular activity.
Amine Oxidase (Copper-Containing)↗
Biosynthesis and accumulation of cadaverine and putrescine in rat ovary after administration of human chorionic gonadotrophin.
In the ovaries of pre-pubertal rats stimulated by human chorionic gonadotrophin (hCG) the temporal changes in cadaverine and putrescine formation were investigated. In addition, the dose-response relationship of hCG and its effect on the diamine formation and the effect of hCG on the content of diamines and polyamines in the ovaries and the urine were studied. The results show that the ovary stimulated by hCG, in addition to putrescine, forms cadaverine at a highly increased rate. The elevated diamine formation was parallelled by an increased content of cadaverine and putrescine in the ovary. Treatment with aminoguanidine elevated the content of cadaverine in the ovary, suggesting that diamine oxidase has a role as a regulator of the intra-ovary level of cadaverine. These results confirm that cadaverine can be synthesized in an inducible manner in mammalian tissues. This is, virtually, the first report of elevated formation of cadaverine in response to an exogenous gonadotrophin.
Animals↗
Polyamine metabolism in the kidneys of castrated and testosterone-treated mice after administration of methylglyoxal bis(guanylhydrazone).
The effects of methylglyoxal bis(guanylhydrazone) on S-adenosyl-L-methionine decarboxylase (EC 4.1.1.50) activity were studied in the mouse kidney stimulated to growth by testosterone administration. The drug was found a potent inhibitor of the enzyme in vitrol Administration of methylglyoxal bis(guanylhydrazone) in vivo resulted in a transient inhibition followed by a strong enhancement of the enzyme activity. Dialysis of the kidney extract, to remove remaining methylglyoxal bis(guanylhydrazone), revealed a great and rapid increase in the activity of S-adenosyl-L-methionine decarboxylase. Injections of testosterone to castrated mice resulted in a marked increase in kidney weight and an accumulation of renal putrescine, spermidine and spermine. These effects of testosterone could not be blocked by simultaneous injections of methylglyoxal bis(guanylhydrazone). It appears that due to secondary effects by which the inhibition of methylglyoxal bis(guanylhydrazone) on S-adenosyl-L-methionine decarboxylase activity is circumvented the inhibitor seems to be of uncertain value in attempts to decrease selectively the in vivo levels of polyamines.
Animals↗