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Biomedical subjects

M Rudolph

Publications and source records attributed to M Rudolph.

At least 19 recordsLinked to original sources
PubMed1992

Analysis of [14C]-saterinone and its metabolites in dog plasma, urine and bile by high-performance liquid chromatography with radioactivity and fluorescence detection and by mass spectrometry.

An HPLC method was developed for the direct on-line radioactivity determination of [14C]-saterinone and its metabolites in biological canine fluids after intravenous and intraduodenal administration. After direct injection of 200 microliters of sample, the metabolites were separated on a semi-preparative reverse-phase column. The metabolites were identified by HPLC reference standards, enzymatic hydrolysis and mass spectrometry. Besides a small amount of unchanged saterinone, six metabolites could be detected, both in bile and urine. The main fraction (about 80-90% of the sum of detected metabolites) contained the phase II metabolites of saterinone, the sulphate and glucuronide. Ring hydroxylated saterinone and three metabolites that were not identified made up about 1-4% each. In plasma, only the major compounds could be detected because of the lower absolute concentrations. The metabolic pathway of saterinone in dogs was elucidated and compared with other species. Results from previous studies concerning a first-pass metabolism could be confirmed.

Animals↗
PubMed1992

Determination of moxonidine (BDF 5895) in plasma by gas chromatography-negative ion chemical ionization mass spectrometry.

For the measurement of the pharmacokinetic behaviour of moxonidine, 4-chloro-5-(2-imidazolin-2-yl-amino)-6-methoxy-2-methylpyrimidine, an extremely sensitive analytical method was needed. The GC-MS method developed is specific and reliably detects moxonidine plasma levels down to 40 pg ml-1. Using negative ion chemical ionization (NICI) the M- fragment of the ditrifluoromethyl benzamide derivative of moxonidine (m/z 721) and the [M-HCl]- fragment of the ditrifluoromethyl benzamide derivative of clonidine (internal standard, m/z 673) were monitored in the selected ion monitoring mode, ensuring a specific and sensitive detection of the compounds. The validation process carried out included assay precision, repeatability, linearity, accuracy, stability and estimation of the detection and determination limits. The plasma-level time-curves and pharmacokinetic parameters from two volunteers after oral administration of 0.2 mg moxonidine are presented and demonstrate the practicability of the method in, for example, clinical studies.

Antihypertensive Agents↗
PubMed1992

[Absolute bioavailability of beta-acetyldigoxin from tablets and drops in healthy subjects].

In a crossover design in random order 12 healthy male volunteers were given either beta-acetyldigoxin (Novodigal, CAS 5511-98-8) tablets, oral solution or i.v. application at a digoxin equivalent dose of 0.284 mg. To reach steady state each preparation was given for 10 days on a once-daily schedule. On days 8, 9 and 10 of each observation period blood was sampled to determine trough concentrations of digoxin in steady state. In addition, on day 10 blood was collected repeatedly at appropriate time intervals and urine was sampled concomitantly for 24 h. Trough values during steady state and 24 h AUC were used to calculate digoxin bioavailability for tablets and oral solution. From trough values, the mean bioavailability for beta-acetyldigoxin tablets was 91.2% (range 73.1-118.1) and for solution 93.8% (range 65.7-114.8). Using the AUCs 0-24 h at steady state bioavailability was calculated 77.7% for the tablets and 84.5% for the solution. Since trough values in steady state represent the body burden of digoxin which is supposed responsible for the therapeutic effect, trough values should be given priority for the determination of digoxin bioavailability from beta-acetyldigoxin tablets and solution. All formulations were well tolerated. No clinically relevant side effects were observed.

Acetyldigoxins↗
PubMed1990

[Fine structure studies and identification of lectin receptors on the viral envelope of two HIV-isolates].

The electron microscopic particle findings were compared with the levels of revertase in corresponding samples over a longer period of time, and a good correlation was found. Comparative investigations of the fine-structure of two HIV isolates did not reveal any morphological differences. It can be assumed, on the basis of the comparative studies on lectin receptors using Helix pomatia lectin, that the viral envelopes of the two isolates are equipped similarly with N-acetyl-d-galactosamine. The differences are not significant with mature particles.

Animals↗
PubMed1979

Isolation of a SV40-like Papovavirus from a human glioblastoma.

A human glioblastoma multiforme (M27) tested in early cell cultures by indirect immunofluorescence staining showed SV40-related tumor (T)-antigen, 95% of the cells being positive. SV40-related viral capsid (V)-antigen was absent in all cells tested. Experiments to rescue this virus were performed by fusing M27 cells with CV-I monkey cells, which were permissive for SV40, using polyethylene glycol (PEG) as fusion factor. We succeeded in isolating virus particles SV40-GBM which electron microscopy showed to correspond in size and morphology to papovaviruses. Serological tests (hemagglutination, neutralization, fluorescent antibody) revealed that the virus is indistinguishable from SV40. Despite this apparent antigenic identity SV40-GBM differs slightly from SV40 wild type. This virus can propagate and produce CPE in both CV-I cells and primary fetal human kidney cells. Furthermore digestion of SV40-GBM DNA with the HindII/III restriction endonucleases revealed minor differences compared with the SV40 DNA. Therefore the virus SV40-GBM obtained from glioblastoma cells seems to be closely related to the SV40-PML viruses described earlier.

Antigens, Viral↗
PubMed1979

Lack of sequence homology between the nucleic acids of Rauscher leukaemia virus and polyoma virus Y8e produced simultaneously in a continuous mouse cell line.

In a continuous cell line (Y8e) from spleen and thymus cells of mice, infected with RLV, the presence of both RLV and polyoma virus Y8e in a single cell could be demonstrated by electron microscopy. A comparison of the nucleic acids of RLV and polyoma virus from Y8e cells by two molecular hybridization methods showed lack of sequence homology between the viral nucleic acids.

Animals↗
PubMed1978

Evidence that triiodothyronine and reverse triiodothyronine are sequentially deiodinated in man.

We have demonstrated that in patients given a single iv injection of T3, rT3, or, to a lesser extent, T4, all labeled with 125I in the outer or phenolic ring, chromatography of serum on columns of Sephadex G-25 superfine revealed the presence of a labeled material, separate from the administered hormone and from both iodide and iodoprotein. This peak has been termed pre-T3 because it elutes just before the T3 peak. Identification of the various compounds in pre-T3 was carried out by cation exchange chromatography. Pre-T3 generated from [125I]T3 consistently contained labeled compounds with the chromatographic behavior of 3,3'-diiodothyronine and 3'-monoiodothyronine, while pre-T3 generated from [125I]rT3 contained labeled products with the chromatographic mobility of 3',5'-diiodothyronine, 3,3'-diiodothyronine, and 3'-monoiodothyronine. In addition, pre-T3 also contained the glucuro- and sulfoconjugates of these several labeled products. These studies demonstrate that T3 and rT3 undergo progressive and probably sequential deiodination in the peripheral tissues, resulting in the formation of a variety of diiodothyronines and monoiodothyronine, as well as their glucuro- and sulfoconjugates.

Animals↗
PubMed1978

Appearance of labeled metabolites in the serum of man after the administration of labeled thyroxine, triiodothyronine (T3), and reverse triiodothyronine (rT3).

Chromatography of serum on columns of Sephadex G-25 superfine after the iv administration of 125I-labeled T4 consistently yielded labeled iodide, iodoprotein, T3, and a labeled peak that eluted from the column before the T3, termed "pre-T3." Much larger quantities of pre-T3 were generated after the iv administration of 125I-labeled T3 and rT3. The ratio of [125I]pre T3:[125I]T3 and [125I]pre T3:[125I]rT3 plateaued at approximately 10 h and 2 h, respectively, after the iv administration of the labeled hormone, and averaged approximately 15% in euthyroid subjects. As pre-T3 behaves like its precursors in the TCA precipitation-ethanol extraction or anion exchange chromatographic procedures used to separate labeled iodide and iodoprotein from administered labeled T3 and rT3, concentrations of labeled hormone measured by these techniques will be in error, because pre-T3 will be included. Thus, the MCR of labeled T3 and rT3 measured by Sephadex chromatography will always be higher than values obtained by the other two separative techniques and the magnitude of change will be similar to the ratio of pre-T3 to precursor T3 or rT3. The Sephadex chromatographic technique is laborious, but appears to be the method of choice where greatest accuracy of measurement is required. As the generation of pre-T3 from labeled T4 is sufficiently slow, the present chromatographic technique is not necessary in studying peripheral T4 turnover.

Chromatography, Gel↗
PubMed1978

[Isolation of foamy virus type II out of haematopoetic cells from baboons with haematoblastoses and from healthy animals (author's transl)].

Foamy virus Type II persists in the haematopoetic organs of 75 percent of baboons in the Suchumi flock. A mixed infection with foamy virus types I and II seems to be possible. Foamy viruses are isolated as well from monkeys with haemoblastoses as from healthy animals. New information concerning the intrauterine transmission of foamy viruses were obtained.

Animals↗
PubMed1977

Effect of starvation on the production and metabolism of thyroxine and triiodothyronine in euthyroid obese patients.

The metabolic clearance and production rates of thyroxine (T4) and triiodothyronine (T3) were measured in 9 obese euthyroid patients prior to and during prolonged starvation. The metabolic clearance rates (MCR) and serum concentrations of T4, and, therefore, the metabolic degradation or production rates of T4 were unchanged during starvation. Serum T3 concentrations decreased strikingly during starvation, from 145 +/- 7 ng/dl (mean +/- SE) to 66 +/- 9 ng/dl (P < 0.001), while the mean MCR of T3 was unchanged, with the result that T3 degradation or production rates were markedly decreased (36.4 +/- 4.5 μg/d vs. 11.2 +/- 0.7 μg/d; P < 0.001). These findings suggest that the decrease in serum T3 concentration observed during starvation results from a decrease in the peripheral conversion of T4 to T3.

Adult↗
PubMed1976

[Pharmacological influence on central serotonergic mechanisms in man and its consequences on sleep (author's transl)].

Central serotonergic mechanisms were investigated in three experiments: 1. Chronic administration (four weeks) of L-5-hydroxytryptophan (L-5 HTP 600 mg/day) plus decarboxylase inhibitor (Ro 4-4602) reduces slow-wave sleep (stages 3 + 4 = SWS) without influencing other sleep parameters. 2. Clozapine reduces SWS, increases paradoxical sleep (REM) and dissociates sleep mechanisms so that increased REM in NREM stage 1 occurs. Central serotonin levels seem to remain unaffected. 3. Parachlormethylamphetamine, a serotonin synthesis inhibitor, normalises irregular sleep and narcoleptic and cataleptic attacks of narcoleptic syndrome as well. 4. Central serotonergic mechanisms are described as having a boundary-setting function.

5-Hydroxytryptophan↗
PubMed1976

[Oncogenic viruses: progress and problems (author's transl)].

Oncogenic RNA viruses have been found in many species of mammals. The presence of oncogenic viruses in man is probable. DNA viruses suspectable to oncogenic action are increasingly studied. The importance of actual studies on the viral etiology of tumors is presented.

Animals↗
PubMed1976

[Elimination of a paramyxo-type virus from oncornavirus-producing human cell lines (author's transl)].

A virus of the paramyxo-type was eliminated from cell-free material of human oncornavirus-producing cell lines (PMF). After transmission of this paramyxovirus-free inoculum to a human permanent cell strain (Tu 197/Tr 1) oncornaviruses were permanently formed and no paramyxoviruses could be detected. The paramyxovirus-free, oncornavirus-producing PMF-39 cell line could be established after inoculation of the TU 197/Tr 1 line with cell-free material containing both oncorna- and paramyxovirus diluted 1 to 1000. A second way of elimination of the paramyxovirus was the treatment of cell-free material containing both viruses with antisera against paramyxovirus. In the Tu 197/Tr 1 line inoculated with such material only oncornaviruses were formed. The second paramyxovirus-free oncornavirus-producing cell line was designated PMF 50.

Animals↗
PubMed1975

Diversion of peripheral thyroxine metabolism from activating to inactivating pathways during complete fasting.

In 9 euthyroid obese volunteers, as previously reported, 4 weeks of total caloric deprivation resulted in a striking decrease in serum 3,5;3'-triiodothyronine (T3) concentration. The present studies reveal that this decrease in serum T3 is accompanied by a proportionately similar increase in the serum concentration of 3,3',5' -T3 (reverse T3; rT3). In four additional obese volunteers given suppressive doses of sodium-Lthyroxine (T4) for 1 month prior to fasting, serum T3 concentration declined sharply during a 6-11 day period of fast, while rT3 concentration increased strikingly. Concentrations of both T3 and rT3 returned to control values during a 5 day period of refeeding. The findings indicate that caloric deprivation results in an alteration in peripheral T4 metabolism away from generation of T3 and toward the generation of rT3. Since the former is more active than T4, and the latter is essentially inactive, caloric deprivation appears to shunt peripheral T4 metabolism from activating to inactivating pathways.

Adult↗
PubMed1975

[A transplantable myeloid hamster leukemia with high peripheral leukocyte counts and C-particles. I. Transplantation experiments, pathogenesis, and electron-microscopic observations (author's transl)].

In this article is reported a generalized leukemia of the myeloproliferative system of golden hamsters capable of cellular transmission. Cellfree transmissions to 83 golden hamsters after a 6-month latency period, have so far yielded the same result in three cases. After cellular transplantation leukocyte counts of 180,000 on the average occured abruptly in the end-phase of the disease. Latencies were between 4 and 10 days. Electronmicroscopically, oncorna-viruses were demonstrated in hamsters inoculated with either the cellular or the cellfree preparation that bear close resemblance to the murine C-particles.

Animals↗