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Biomedical subjects

S Menzel

Publications and source records attributed to S Menzel.

At least 55 records · Page 3Linked to original sources
PubMed1994

Is the formation of R-ibuprofenyl-adenylate the first stereoselective step of chiral inversion?

Coenzyme A thioester formation is reported to be the first step of chiral inversion of R-ibuprofen. In order to investigate the mechanism of this reaction adenylate derivatives of the ibuprofen enantiomers were synthesized chemically. R- and S-ibuprofenyl-adenylates as well as free acids were incubated with rat liver mitochondria in the presence of coenzyme A, MgCl2 with or without ATP. The optical antipodes formed by inversion and the coenzyme A thioester derivatives of both enantiomers were found after incubation of both R- or S-ibuprofenyl-adenylate and R-ibuprofen. By contrast, after incubation with S-ibuprofen neither R-enantiomer nor coenzyme A thioesters were detected. These experiments suggest that the formation of R-ibuprofenyl-adenylate may be the first stereoselective step of chiral inversion.

Animals↗
PubMed1994

Is the inversion from R- to S-ketoprofen concentration dependent? Investigations in rats in vivo and in vitro.

The effects of dose on the pharmacokinetics of ketoprofen (KT) enantiomers were investigated in rats in vivo and in hepatoma cells in continuous culture in vitro following administration of the optically pure enantiomers and the racemate of KT. With the exception of AUC (area under the curve) no pharmacokinetic differences could be found following i.v. administration of various doses of KT enantiomers (2.5, 5 and 10 mg/kg) and of racemic KT (5, 10 and 20 mg/kg) and between single enantiomer and racemate administration in rats in vivo. Independent of the dose administered the fraction inverted was about 66%. In line with the findings in vivo good correlation between incubation concentration and AUC of R- and S-KT was found in the hepatoma cells in vitro. The ratios of AUC(S)/AUC(R) were not significantly affected by concentration after R-KT (2.5-20 micrograms/mL) and racemate incubation (5-40 micrograms/mL) in the concentration ranges investigated. However, unlike in rats in vivo enhanced inversion was observed following racemate as compared to single enantiomer incubation in vitro.

Animals↗
PubMed1994

Localization of the glucagon receptor gene to human chromosome band 17q25.

The gene encoding the human glucagon receptor (GCGR) was mapped to chromosome band 17q25 by fluorescence in situ hybridization to metaphase chromosomes. An Alu variable poly(A) DNA polymorphism was identified in this gene. Studies in the CEPH families showed significant evidence of linkage between DNA polymorphism and markers localized to the distal long arm of chromosome 17.

Base Sequence↗
PubMed1994

Antinociceptive actions of R(-)-flurbiprofen--a non-cyclooxygenase inhibiting 2-arylpropionic acid--in rats.

Intraperitoneal administration of R(-)- and S(+)-flurbiprofen resulted in dose dependent antinociceptive behavior in the rat paw formalin test. S(+)-flurbiprofen was significantly more potent than the non-cyclooxygenase inhibiting R(-)-enantiomer with a potency ratio of about 3 to 1. Chiral inversion was very low and does not seem to account for the action of R(-)-flurbiprofen. In a modified Randall Selitto assay also both enantiomers were active in a dose dependent manner following systemic administration. Following local administration into the inflamed paw only S(+)-flurbiprofen showed significant dose related antinociceptive effects. R(-)-flurbiprofen was unable to block prostaglandin E2 induced hyperalgesia following local administration. Consequently, a central site of action independent of prostaglandin synthesis inhibition has to be discussed with respect to antinociceptive activity following systemic administration.

Analgesics↗
PubMed1994

Stereoselective disposition of flurbiprofen in healthy subjects following administration of the single enantiomers.

Plasma concentrations of the enantiomers of flurbiprofen were measured following oral administration of (S)-flurbiprofen 50 mg and (R)-flurbiprofen 50 mg and 100 mg to sixteen healthy subjects. Chiral inversion did not occur to a measurable extent. Significantly higher values of AUC (55.2 +/- 17.0 vs 44.6 +/- 11.2 micrograms ml-1h) elimination half-life (5.6 +/- 1.4 vs 4.0 +/- 1.0 h) and mean residence time (7.5 +/- 1.6 vs 5.7 +/- 1.2 h) were observed after 50 mg (S)-flurbiprofen as compared with 50 mg (R)-flurbiprofen. With the exception of Cmax and AUC values pharmacokinetic data for the 50 mg and the 100 mg dose of (R)-flurbiprofen did not differ significantly. The data are of clinical relevance if (R)-flurbiprofen also has analgesic activity in humans and is to be developed as an analgesic.

Administration, Oral↗
PubMed1993

Stereoselectivity of biliary excretion of 2-arylpropionates in rats.

To examine the stereoselectivity of biliary excretion, the optically pure enanatiomers of ketoprofen (KT), ibuprofen (IBU), and flurbiprofen (FLU) were intravenously administered to normal and bile duct-cannulated rats at 10 mg/kg. The recovery of total KT in bile was significantly higher after administration of (S)-KT than after (R)-KT [90.1 +/- 3.5% vs 68.8 +/- 8.2%, n = 3, P < 0.05]. In normal rats the terminal half-life of (R)-KT was significantly shorter than that of (S)-KT after administration of (R)-KT (2.2 +/- 0.6 h vs 14.3 +/- 4.9 h, n = 3, P < 0.05). The terminal half-life of both enantiomers was significantly shorter in rats with continuous bile drainage as compared to normal rats. No significant differences in pharmacokinetic parameters could be found between both enantiomers in bile duct-cannulated animals. The total amount of IBU in bile was slightly higher after administration of (S)-IBU than after (R)-IBU administration. The percentage of (R)-IBU after (R)-IBU administration, however, was very low [(R)-IBU: 1.5 +/- 0.9%, (S)-IBU: 23.4 +/- 5.8%]. In normal rats the clearance of (R)-IBU was significantly higher as compared to (S)-IBU. Differences in pharmacokinetic parameters between normal and bile duct-cannulated rats were not statistically significant due to high interindividual variability. The total recovery of FLU, which was excreted in bile to a lower extent than either KT or IBU, also tended to be greater after S-enantiomer administration. Only small amounts of (S)-FLU could be recovered in bile after (R)-FLU administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Bgl II-restriction fragment length polymorphism of the insulin receptor gene in patients with type-II diabetes mellitus.

As an approach to estimate the involvement of the insulin receptor gene in the etiopathogenesis of type-II diabetes mellitus we determined the distribution of the alleles of a restriction fragment length polymorphism of this gene (Bgl II-RFLP) in a group of type-II diabetics. The patients had been characterized by insulin and C-peptide values during OGTT and insulin receptor binding indices. The difference in allelic distribution to a healthy control group (10% "+"-allele in diabetics versus 18% in control persons), was not significant in chi 2-analysis.

Alleles↗
PubMed1987

Antibodies to a synthetic analog of phenolic glycolipid-I of Mycobacterium leprae in healthy household contacts of patients with leprosy.

Fifty-four household contacts of lepromatous patients, 39 household contacts of tuberculoid patients, and 99 control persons were examined with an enzyme-linked immunosorbent assay for their antibody responses to phenolic glycolipid-I (PGL-I) of Mycobacterium leprae using a synthetic analog (PGL-ISA) with the same terminal sugar epitope, namely, O-(3, 6-di-O-methyl-beta-D-glucopyranosyl)-(1----4)-O-(alpha-L-rhamnopyranosyl )-(1----9)-oxynonanoyl-BSA. This study was conducted in the Gurage area of Ethiopia in 15 households with a leprosy patient and 15 matched control households. Household contacts with more than 1 year of exposure to a lepromatous patient had antibodies to PGL-ISA significantly more often (19 of 34 persons) than did household contacts with less than 1 year of exposure to a lepromatous patient (4 of 20 persons), household contacts of tuberculoid patients (8 of 39 persons), and persons without exposure to leprosy in the household (33 of 99 persons). No significant association was found between the prevalence of antibodies to PGL-ISA in the household contacts and disease activity in the lepromatous index patients at the time of examination; nor was there a significant association between antibody responses and age or sex of the contacts. The increased prevalence of antibodies to M. leprae antigen in healthy persons with more than 1 year of contact with a lepromatous patient provides further evidence that subclinical infection in leprosy is common, and is related to the type of leprosy in the index patient. The fact that antibodies to PGL-ISA were detected in one third of the persons without household exposure to leprosy emphasizes the necessity to always include comparable controls from the same endemic area in studies of leprosy contacts.

Adolescent↗
PubMed1987

[Therapy of leprosy today].

The rise in the incidence of dapsone-resistant leprosy requires new therapeutic approaches. Based on the recommendations of the WHO and the experiences from many countries where leprosy is endemic, a standardized treatment regimen is presented. It is based on the combination of three chemotherapeutically active substances.

Clofazimine↗
PubMed1983

A clinical and immunological study of four babies of mothers with lepromatous leprosy, two of whom developed leprosy in infancy.

One hundred thirteen women and 27 healthy controls were studied throughout pregnancy, at delivery, and followed up with their babies during lactation. Thirty-eight of the mothers with lepromatous leprosy were found to have solid-staining bacilli in skin smears or biopsies, and hence were considered potentially highly infectious to their unborn children by hematogenous spread via the placenta. Two babies of mothers within this group were diagnosed as having leprosy on clinical and histological grounds. A third baby could well have had leprosy, but the case was not proven. The fourth baby did not have leprosy and, although it did have ringworm, was thus deemed to be a reasonable control. The leprosy skin lesions were first observed at a special followup clinic when the children were between the aged of 9 and 17 months. The demonstration of IgA and IgM anti-M. leprae antibodies in cord sera was taken as an indication of intrauterine immunologic stimulation, and hence transplacental transmission of M. leprae. The two babies with proven leprosy showed an early and significant increase in serum IgA and in particular serum IgM anti-M. leprae antibody activity. A third baby, suspected of having leprosy but in whom the diagnosis was not proven, showed a similar but less marked increase in serum IgA and IgM activity. The fourth baby showed no such rise in anti-M. leprae activity. A decrease in serum IgG anti-M. leprae antibody activity could be demonstrated in one of the babies with leprosy after healing of the leprosy lesions, but not in the second baby.

Antibodies, Bacterial↗
PubMed1979

Lymphocyte transformation test in healthy contacts of patients with leprosy. I. Influence of exposure to leprosy within a household.

Fifty-three household contacts of lepromatous patients, 37 household contacts of tuberculoid patients, and 91 control persons were examined with the lymphocyte transformation test (LTT) for their responses to whole and sonicated antigen preparations from M. leprae, to BCG, M. avium, M. gordonae, and phytohemagglutinin (PHA). The study was carried out in the Gurage area of Ethiopia in 15 households with a leprosy patient and 15 matched control households. Household contacts of lepromatous patients showed significantly greater LTT responses to antigens from M. leprae than the controls, whereas household contacts of tuberculoid patients did not respond differently from controls. Household contacts of lepromatous patients had significantly greater responses to M. leprae antigens when the index patients were "active," i.e., highly bacilliferous, than when they were "inactive," i.e., having a low bacillary load. The degree of sensitization, as indicated by the LTT response, in different exposure groups paralleled the degree of probable infectivity of the index patient. A preparation of antigen from whole M. leprae proved to be more sensitive and more specific in the LTT than did a sonicated preparation. A significant degree of cross-reactivity was found among the various mycobacteria in their LTT responses.

Adolescent↗
PubMed1979

Lymphocyte transformation test in healthy contacts of patients with leprosy. II. Influence of consanguinity with the patient, sex, and age.

The study was carried out in the Gurage area of Ethiopia, where 53 household contacts of lepromatous patients, 37 household contacts of tuberculoid patients, and 91 control persons were examined with the lymphocyte transformation test (LTT) for their responses to whole and sonicated antigen preparation from M. leprae to BCG, M. avium, M. gordonae and phytohemagglutinin. The potential influence of host factors, namely the state of consanguinity with the leprosy patient, sex and age on the LTT responses was evaluated. In the 35 household contacts of "active," i.e., highly bacilliferous, lepromatous patients, consanguinity with a lepromatous patient was not associated with a significant depression of the LTT responses to M. leprae antigens. Male household contacts of active lepromatous patients showed significantly greater LTT responses to M. leprae antigens than female household contacts. Possible confounding factors for this finding are discussed. Sensitization of M. leprae antigens was present already in a high proportion of the 6 to 14 year old household contacts of active lepromatous patients, which was the youngest age group examined in our study. No significant results were found in any of the other patient contact groups with regard to the host factors examined.

Adolescent↗
PubMed1978

Antibody responses in patients with cutaneous leishmaniasis of the Old World.

74 persons of Northern European origin with recent primary exposure to Leishmania tropica in Saudi Arabia were examined for their antibody responses to leishmaniae with the fluorescent antibody test (FAT), the complement fixation reaction. (CFR), and the indirect hemagglutination test (IHA). The FAT detected antibodies to L. donovani in 19 of the 41 individuals with acute lesions or scars characteristic of cutaneous leishmaniasis but in none of the 33 individuals without lesions. Our data suggest that the high proportion of persons with antibodies, as compared to other studies of cutaneous leishmaniasis of the Old World, may be the result of the relatively severe course of the disease in the majority of our patients. The CFR and the IHA did not prove to be useful for the diagnosis of this disease.

Adolescent↗
PubMedDate not supplied

Restriction fragment length polymorphism of the insulin receptor gene, type 2 diabetes and insulin binding.

In searching for a genetic marker of type 2 diabetes we estimated the frequency of alleles of the Bgl II restriction fragment length polymorphism (RFLP) of the insulin receptor gene in a group of type II diabetic patients (n = 50), characterized by OGTT (glucose, insulin, C-peptide) and insulin receptor binding parameters. Leucocyte DNA was incubated with restriction endonuclease Bgl II and specific fragments were determined by Southern blot technique, using radioactive plasmid pINSR 13.1 as insulin receptor gene probe for hybridization. Insulin receptor numbers and receptor affinity were estimated by 125I-(Tyr-A-14)- insulin binding to red blood cells. Among control subjects the 20 kb fragment (allele Bgl II+) had a frequency of 0.21. In our group of diabetic patients this allele had a frequency of 0.10 (n.s., p greater than 0.05). In our study the insulin receptor genotype had no influence on body mass index, insulin and C-peptide during OGTT as well as insulin receptor binding data. So far, etiopathogenetic linkage between diabetes and insulin receptor variants (mutants) could unambiguously be proved in patients with extreme insulin resistance only. In our opinion, the estimation of the role of the gene as the reason underlying the disease inevitably requires the investigation of large families with multiple occurrence of type 2 diabetes.

Bacterial Proteins↗