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Biomedical subjects

M Kuhnt

Publications and source records attributed to M Kuhnt.

8 recordsLinked to original sources
PubMed1998

Microbial conversion products of leptomycin B.

Leptomycin B (LMB), a secondary metabolite produced by Streptomyces sp. strain ATS 1287, with known antifungal and antitumor effects, inhibits the nucleo-cytoplasmic translocation of the human immunodeficiency virus type 1 regulatory protein Rev and exhibits significant antiproliferative activity. Since LMB itself turned out to be distinctly cytotoxic, a bioconversion screening with a selected set of 29 bacterial and 72 fungal strains was performed in order to obtain metabolites of LMB with reduced antiproliferative effects. Several derivatives of LMB, more polar than the parent compound and produced in yields of > 5%, were detected. Liquid chromatography-mass spectroscopy analysis indicated the type of bioconversion. Fermentations (1-liter scale) of those strains with high rates of transformation were suitable for isolation and characterization of the most prominent metabolites. Thus, bioconversion of LMB with Aspergillus flavus ATCC 9170 and Emericella unguis ATCC 13431 served for isolation of the novel derivatives 26-hydroxy-LMB (30% was the concentration of the metabolite [with respect to LMB] used for bioconversion) and LMB-24-glutaminamide (90%), respectively. Streptomyces rimosus ATCC 28893 converted LMB into 4,11-dihydroxy-LMB (13%) and 2,3-dihydro-LMB (55%). Although the antiproliferative effects of the LMB metabolites could be reduced through microbial conversion, none of these metabolites inhibited the nuclear export of Rev better than LMB itself.

Antibiotics, Antineoplastic↗
PubMed1997

Sesquiterpene lactone containing Mexican Indian medicinal plants and pure sesquiterpene lactones as potent inhibitors of transcription factor NF-kappaB.

The potential inhibitory effect of 54 Mexican Indian medicinal plants on the activation of transcription factor NF-kappaB was studied. Band-shift experiments identified the ethanolic leaf extracts of Artemisia ludoviciana ssp. mexicana, Calea zacatechichi, and Polymnia maculata (all rich in sesquiterpene lactones) as inhibitors of NF-kappaB down to a concentration of 25 microg/ml. The sesquiterpene lactones isohelenin and parthenolide prevented NF-kappaB activation completely as low as 5 microM. Treatment of HeLa cells with leaf extract of A. ludoviciana ssp. mexicana, isohelenin and parthenolide prevented the induction of transcription on the IL-6 promoter. These experiments identify the eudesmanolide and germacranolide type of sesquiterpene lactones as potent non-antioxidant inhibitors of NF-kappaB. All plants active in the NF-kappaB assay also showed a delay in the onset of capillary reactions of the allantois membrane in a physiological model for anti-inflammatory activity - the HET-CAM assay.

Animals↗
PubMed1996

Effects of L-carnitine supplementation on physical performance and energy metabolism of endurance-trained athletes: a double-blind crossover field study.

A double-blind crossover field study was performed to investigate the effects of acute L-carnitine supplementation on metabolism and performance of endurance-trained athletes during and after a marathon run. Seven male subjects were given supplements of 2 g L-carnitine 2 h before the start of a marathon run and again after 20 km of the run. The plasma concentration of metabolites and hormones was analysed 1 h before, immediately after and 1 h after the run, as well as the next morning after the run. In addition, the respiratory exchange ratio (R) was determined before and at the end of the run, and a submaximal performance test was completed on a treadmill the morning after the run. The administration of L-carnitine was associated with a significant increase in the plasma concentration of all analysed carnitine fractions (i.e. free carnitine, short-chain acylcarnitine, long-chain acylcarnitine, total acid soluble carnitine, total carnitine) but caused no significant change in marathon running time, in R, in the plasma concentrations of carbohydrate metabolites (glucose, lactate, pyruvate), of fat metabolites (free fatty acids, glycerol, beta-hydroxybutyrate), of hormones (insulin, glucagon, cortisol), and of enzyme activities (creatine kinase, lactate dehydrogenase). Moreover, there was no difference in the result of the submaximal performance test the morning after the run. In conclusion, acute administration of L-carnitine did not affect the metabolism or improve the physical performance of the endurance-trained athletes during the run and did not alter their recovery.

Adult↗
PubMed1996

Microbial biotransformation products of cyclosporin A.

In order to mimic the human metabolic pathway of cyclosporin A (CyA) a total of 28 bacterial and 72 fungal strains was screened for their ability to transform CyA. Among 3 bacteria and 11 fungi, which produced the main human metabolite OL-17 [eta HyMeBmt1]CyA, Actinoplanes sp. (ATCC 53771) achieved the best transformation rate (5.4%). Furthermore, the two N-demethylated minor products [Leu4]CyA (3.2%) and [Leu9]CyA (4.7%) were isolated, both known as minor natural metabolites and the first one also as a human biotransformation product. Microbial conversion of CyA using the actinomycete Sebekia benihana (NRRL 11111) yielded [gamma HyMeLeu4]CyA (35%), [gamma HyLeu4]CyA (4.5%) and [gamma HyMeLeu4, gamma HyMeLeu6]CyA (8.6%). The structures of these derivatives correspond with those of the human metabolic pathway. The related compounds [Nva2]CyA (CyG) and [D-MeSer3]CyA were similarly converted to the corresponding 4-gamma-hydroxylated analogues. None of the biotransformation products showed a better immunosuppressive effect than CyA, although in various cases the cyclophilin binding affinity was comparable to that of CyA.

Bacteria↗
PubMed1995

Biological and pharmacological activities and further constituents of Hyptis verticillata.

Several extracts of Hyptis verticillata and isolated compounds were evaluated for their anti-inflammatory, antibacterial, antisecretory, and cytotoxic properties. The aerial parts yielded (R)-5-hydroxypyrrolidin-2-one and essential oil with the main components alpha-pinene, beta-pinene, and thymol. Spectroscopic methods (UV, IR, 1H-NMR, 13C-NMR, mass, CD) fully characterized (R)-5-hydroxypyrrolidin-2-one, as it was isolated by a bioassay guided fractionation. The essential oil, (R)-5-hydroxypyrrolidin-2-one, as well as the previously isolated rosmarinic acid and dehydropodophyllotoxine contributed to the antibacterial effects of H. verticillata. Furthermore, rosmarinic acid showed significant capillary stabilizing effects. Sideritoflavone inhibited prostaglandin synthase to a significant extent and had antisecretory effects comparable to those of NPPB. The cytotoxicity of the aqueous extract, as demonstrated using KB and HT 29 cell lines, may be of toxicological relevance in cases of internal application.

Animals↗
PubMed1993

[Methodological studies of the estimation of loss of sodium, potassium,calcium and magnesium through the skin during a 10 km run].

An estimation of the electrolytic losses through the skin was evaluated in a run over a distance of 10 km on a 400 m Tartan-trac. Na, K, Ca, and Mg excreted by the skin were collected in standardised clothing and thereafter washed out. The remaining electrolytes on the skin were collected by washing the body with deionized water. In addition, the concentrations of hormones and metabolites in blood before and after the race were ascertained. Mean ambiant temperature and relative humidity amounted to 21 degrees C and 35%, respectively. The mean performance was 40.5 min. and the average body weight loss was 1.45 kg. The only significant changes in the serum concentrations were the increases of free fatty acids and glycerol. This can be explained, together with a slight increase of glucose and a decrease of insulin, by a higher sympathoadrenergic activity. In the mean 20 mg calcium, 5 mg magnesium, 200 mg potassium, and 800 mg sodium were lost by the skin per kg body weight loss. Those amounts compared well with corresponding data found in literature. The described method can be proposed for further experiments.

Adult↗
PubMed1992

Parasitological and microbiological evaluation of Mixe Indian medicinal plants (Mexico).

Medicinal plants are an important health resource in many regions of the Americas and are of particular importance to many Indian communities. Based on a recent ethnobotanical study in Mexico, we investigated the activity of 29 plant extracts against Entamoeba histolytica, three bacteria (Bacillus subtilis, Escherichia coli, and Micrococcus luteus) and two fungi (Cladosporium cucumerinum and Penicillium oxalicum). After separation of these extracts between CH2Cl2 and H2O the resulting phases were also evaluated.

Amebicides↗