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Biomedical subjects

J Wagner

Publications and source records attributed to J Wagner.

At least 415 records · Page 23Linked to original sources
PubMed1982

Effect on prostatic growth of 2-difluoromethylornithine, an effective inhibitor of ornithine decarboxylase.

2-Difluoromethylornithine (DFMO), an enzyme-activated irreversible inhibitor of ornithine decarboxylase, causes marked changes in the polyamine metabolism of ventral prostate when given to adult rats in drinking water (20 g/l) for 3 consecutive days. A 90% inhibition of ornithine decarboxylase activity is accompanied by approx. 80% decreases of the concentrations of putrescine and spermidine and by a 36% decrease in spermine. Concomitantly, S-adenosylmethionine decarboxylase activity increases 7-fold and the concentration of decarboxylated S-adenosylmethionine 450-fold. When DFMO is given to immature rats for 12 consecutive days the above described changes are accompanied by a marked reduction in the age-dependent increases of the wet weight and RNA and DNA contents of the ventral prostate. In adult rats DFMO decreases the weight and RNA content of the ventral prostate within 4 days by 32% and 24% respectively and maintains them constant for the next 19 days. After 23 days of treatment, the prostatic weight is 46% of that of control animals of the same age, whereas the weights of other organs are only slightly decreased. Cytological studies carried out at this time show that DFMO reduces the size of both prostatic acini and the epithelial cells lining the acini.

Animals↗
PubMed1982

Gallium-67 citrate as an aid to the diagnosis of infection in hip surgery.

We have evaluated the use of Gallium-67 scans as an aid to the diagnosis of infection around the hip joint after operation. We performed 12 gallium-67 scintiscans on six patients with diaphyseal fractures of the femur or tibia reduced by external fixation, and 65 scintiscans on 60 hips after operation, which included 22 Moore's prosthesis, 31 total replacements, three nail-plates and four revisions of total replacements. We also scanned the healing surgical wounds in a further 11 patients. Simple fractures or osteotomies did not lead to abnormal uptake of 67Ga. Although some uptake in the scar was encountered the surgical wound did not complicate the interpretation of the scan. When assessing infection in the hip operations the rate of true-positive was 11/11, or 100%. The false-positive rate could not be assessed until after at least one year's follow-up. It was certainly less than 14% immediately after operation and less than 6% when the scan was performed three months after operation. Four patients were found to have a loose prosthesis but had a normal scintiscan, as had three patients presenting with post-operative pain. It appears that 67Ga is clinically an efficient means for early detection of infection about the operated hip, and is useful in the differential diagnosis of a painful hip after surgery.

Adult↗
PubMed1982

Value of monoamine metabolite determinations in CSF as an index of their concentrations in rat brain following various pharmacological manipulations.

Using reversed-phase high performance liquid chromatography with electrochemical detection it is possible to measure concomitantly the concentration of several monoamines, their metabolites and aminoacid precursors in 100 microliters of rat cerebrospinal fluid. To study the quantitative relationship between CSF and brain, alterations in brain monoamines and monoamine metabolites were effected by treatment with L-DOPA or L-5HTP administered with or without concomitant inhibition of extracerebral aromatic amino acid decarboxylase and by treatment with alpha-monofluoromethyldopa, probenecid, haloperidol, or probenecid plus haloperidol. The concentrations of the monoamine metabolites, 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic acid, and homovanillic acid as well as of the L-DOPA metabolite, 3-methoxy-4-hydroxyphenylalanine in the cerebrospinal fluid were linearly correlated with the concentrations of these metabolites in the brain. However, these correlations need to be interpreted cautiously, since the slopes of the individual regression lines obtained after different pharmacological treatments differed significantly.

5-Hydroxytryptophan↗
PubMed1982

Cholesteryl esters in pig liver during atherogenic diets and foreign serum protein infusions.

Eight-month-old pigs were fed a diet supplemented with 15% lard (group II) or 15% lard plus 1.5% cholesterol (group III) for 4 months. Five of the animals fed the high fat and cholesterol diet received two i.v. infusions of foreign serum protein (group IV). One group of animals was treated with the same infusions without dietary fat or cholesterol supplement (group V). Liver lipids and serum cholesterol levels were determined. In group II the concentration and fatty acid composition of hepatic cholesteryl esters showed no marked differences from controls (group I). The same findings were present in 2 of 5 animals of group III; in the other 3 animals higher hepatic cholesteryl ester concentrations and predominantly an elevation of monoenoic acid fraction, in one case also a rise of trienoic acid fraction were obtained. These alterations were found in the liver of all animals of group IV. The reverse was observed in the animals which were given the same serum infusions but only the stock diet (group V): a reduction of hepatic cholesteryl ester concentration and no striking alteration in fatty acid pattern. In cryostat sections of all liver specimens no stainable lipid could be detected. There was no correlation between liver and serum fatty acid composition of cholesteryl esters. The total cholesterol levels in serum showed no increase in group V, a slight increase in group II, a moderate increase in group IV, and a marked, partly large increase in group III. These results are discussed in relation to the effect of cholesterol and fat feeding on cholesterol metabolism and essential fatty acid requirement.

Animals↗
PubMed1982

The importance of the time of digitalization for the incidence of spasms evoked by ouabain in strips of human saphenous vein.

The extent of contracture induced by ouabain on preparations of the greater saphenous vein obtained from patients undergoing elective coronary bypass surgery was investigated. The medical pretreatment of the various donor patients was similar but differed with regard to the duration of preoperative digitalization ranging from several days to months. Whereas the maximal contraction induced by noradrenaline was not influenced by prior digitalization, the contracture evoked by ouabain showed a strong dependency on the duration of preoperative digitalization. In patients without or with only short-term preoperative digitalization the spasm exerted by ouabain amounted to 48.8% and 49.2%, respectively, of the maximal contraction induced by noradrenaline, and decreased to zero in patients with long-term digitalization. From this result it is concluded that, in patients after coronary artery bypass grafting who did not receive cardiac glycosides for long-term treatment, the acute administration of glycosides may be a mechanism responsible for the early occlusion of saphenous vein bypass grafts.

Adult↗
PubMed1982

Accumulation of decarboxylated S-adenosyl-L-methionine in mammalian cells as a consequence of the inhibition of putrescine biosynthesis.

Biological transmethylation reactions and polyamine biosynthesis share the substrate S-adenosyl-L-methionine. Under normal conditions, decarboxylated S-adenosyl-L-methionine, the aminopropyl donor for polyamine biosynthesis, does not accumulate because of its rapid utilization in spermidine and spermine synthesis. Alteration of polyamine synthesis by DL-alpha-difluoromethylornithine, an enzyme-activated irreversible inhibitor of L-ornithine decarboxylase, leads to a striking accumulation of decarboxylated S-adenosyl-L-methionine in rat hepatoma cells cultured in vitro and in rat ventral prostate. This increase is due both to lack of putrescine and spermidine for the aminopropyltransferase reactions and to the elevation of S-adenosyl-L-methionine decarboxylase activity. The biological implications of accumulation of decarboxylated S-adenosyl-L-methionine are discussed with regard to the regulation of S-adenosyl-L-methionine decarboxylase activity and to the antiproliferative effects of DL-alpha-difluoromethylornithine.

Adenosylmethionine Decarboxylase↗
PubMed1982

Simultaneous determination of 3,4-dihydroxyphenylalanine, 5-hydroxytryptophan, dopamine, 4-hydroxy-3-methoxyphenylalanine, norepinephrine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, serotonin, and 5-hydroxyindoleacetic acid in rat cerebrospinal fluid and brain by high-performance liquid chromatography with electrochemical detection.

A method using reversed-phase ion-pair high-performance liquid chromatography with electrochemical detection for the simultaneous determination of tryptophan (TRP), 3,4-dihydroxyphenylalanine (DOPA), and their metabolites in whole brain, small-brain parts, and cerebrospinal fluid of rats has been developed. The sample preparation requires only homogenization in perchloric acid and centrifugation before injection onto the column. With a LiChrosorb RP-18 (10 micrometer) column and a mobile phase consisting of a phosphate (NaH2PO4, 0.1 M)-methanol mixture with octylsulfonate (2.6 x 10(-3) M) at pH 3.35 and 26 degrees C, the separation of DOPA, dopamine, norepinephrine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, 4-hydroxy-3-methoxyphenylalanine, TRP, 5-hydroxytryptophan (5-HTP), serotonin, and 5-hydroxyindoleacetic acid was achieved. The method has been applied to study the effect of alpha-monofluoromethyldopa alone and in combination with L-DOPA or L-5-HTP, on the catechol and 5-OH indole levels in brain and CSF of the rat.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1982

Pharmacokinetics of cefadroxil and cefaclor during an eight-day dosage period.

The concentrations of cefadroxil and cefaclor in serum were studied in eight healthy volunteers receiving 1,000 mg of both substances three times per day for 8 days. Intraindividual comparisons showed an increase in peak serum levels of cefadroxil from days 1 to 8 in seven of eight volunteers. Cefaclor peak concentrations did not rise during the 8 days.

Adult↗
PubMed1981

[Quinidine-digoxin interaction (author's transl)].

An additional dose of 500 mg of rapidly absorbed quinidine increased the digoxin concentration in serum after 3-5 hours by up to 46% and prolonged digoxin half life from 50 to 100 hours in six probands who were on chronic quinidine-digoxin medication. These effects were not elicited regularly in persons pretreated with digoxin only. The results show that quinidine both diminishes elimination and produces transient redistribution of digoxin. Chronic quinidine medication leads to protracted digoxin elimination resulting in marked prolongation of digoxin half life. This is the reason for persisting increase of digoxin concentration in serum. Estimation of serum digoxin levels should thus be done 8 hours after the last quinidine (and digoxin) medication at the earliest. On cessation of digoxin, as is done preparing for electric cardioversion, one should remember that digoxin elimination is clearly prolonged should quinidine treatment be continued.

Digoxin↗
PubMed1981

[Cefoperazone--a new cephalosporin antibiotic with broader spectrum of activity].

Concentration of Cefoperazone in serum and urine was determined after 1g (bolus injection) and 2g drip-infusion over a 30-minute-period in 10 healthy volunteers. The pharmacokinetic analysis was performed using an open 3-compartment model. Renal clearance was determined in three volunteers and indicates an expansive extrarenal elimination rate. 31 patients mainly with severe bronchopulmonary infections were treated with 2.0--6.0 g/day of Cefoperazone. The therapeutic results were favourable, the toleration of the drug was good.

Adult↗
PubMed1981

On the coexistence of beta 1- and beta 2-adrenoceptors in various organs.

In rabbit left atrium and ileum as well as in guinea-pig tracheal chain preparations dose-response curves for isoprenaline, adrenaline, noradrenaline and fenoterol have been determined. In order to assess the coexistence of beta 1- and beta 2-adrenoceptor subtypes in these tissues the antagonism of the relative selective adrenolytic drugs metoprolol (beta 1-) and H35/25 (beta 2-) against these sympathomimetic agents was tested. The determination of the pD2-values for the agonists showed a relative high affinity of fenoterol and adrenaline to tracheal beta-adrenoceptors whilst noradrenaline was most affine to atrial beta-adrenoceptors. In all three organs isoprenaline showed the highest affinity. On rabbit atrium driven by 1 Hz both beta-adrenolytic drugs competitively inhibited the effects of all sympathomimetic agents. The pA2-values characterizing the antagonism between metoprolol and isoprenaline, adrenaline or noradrenaline were comparable. Those determined for the interaction of H35/25 with these agonists also were in the same range but lower than those for metoprolol. Both adrenolytic drugs showed higher pA2-values to fenoterol. Furthermore for classification of beta-adrenoceptor binding sites the method of Paton and Rang (1965) was applied. The dose-ratio of isoprenaline after combination of metoprolol and H35/25 was multiplicative thus confirming the existence of different binding sites in the atrium. On rabbit ileum pA2-values for both antagonists could only be determined when isoprenaline was the agonist. The effect of the endogenous catecholamines, adrenaline and noradrenaline, was only blocked by metoprolol. On the other hand, fenoterol could not be blocked by either antagonist alone, but only by the combination of both adrenolytic drugs indicating a comparable affinity of fenoterol to both binding sites.--The Schild-plot for the antagonism of propranolol versus noradrenaline or fenoterol supports the view of the existence of different types of adrenoceptors stimulated by either agonist. On the guinea-pig tracheal chain both adrenolytic drugs inhibited competitively the effects of the sympathomimetic agonists. The pA2-values for H35/25 where the highest when compared with those of atrium or ileum. Using the combination of metoprolol and H35/25 the resulting dose-ratio for adrenaline was multiplicative demonstrating again the presence of two binding sites. The present results indicate the coexistence of beta 1- and beta 2-adrenoceptor subtypes on the organs investigated. This conclusion has been reached by the use of at least two methods in parallel, namely the determination of the pA2-values for selective antagonists to selective agonists and that for a nonselective antagonist to selective agonists and furthermore, the calculation of the dose-ratio of agonists after the combined administration of two selective antagonists.

Animals↗