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Biomedical subjects

S Mundt

Publications and source records attributed to S Mundt.

At least 19 recordsLinked to original sources
PubMed2005

Development and application of a scintillation proximity assay (SPA) for identification of selective inhibitors of 11beta-hydroxysteroid dehydrogenase type 1.

Pre-receptor metabolism of glucocorticoids by the 11beta-hydroxysteroid dehydrogenase (11betaHSD) enzymes has been implicated in the etiology of the metabolic syndrome. Recent studies have shown that alterations in the activity of the type 1 isozyme can affect many aspects of the disease. This paper describes the optimization and application of a high-throughput scintillation proximity assay (SPA) developed to identify selective specific inhibitors of 11betaHSD1. Microsomes containing 11betaHSD1 were incubated in the presence of NADPH and [3H]cortisone, and the product, [3H]cortisol, was specifically detected in the mixture by a monoclonal antibody coupled to protein A-coated SPA beads with greater than 2 log higher affinity for cortisol than cortisone. Dimethyl sulfoxide and NADPH co-substrate additions were optimized for 11betaHSD1 reductase activity. Titrated test compound, when introduced into the optimized assay, reproducibly inhibited the enzyme and yielded consistent IC50 data in either 96- or 384-well format. An 11betaHSD2 counterscreen was performed by incubating 11betaHSD2 microsomes with [3H]cortisol and NAD+ and monitoring substrate disappearance.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗
PubMed2002

Cyanobacteria a potential source of antiviral substances against influenza virus.

Aqueous and methanolic extracts of cultured cyanobacteria of several genera, Microcystis, Nodularia, Oscillatoria, Scytonema, Lyngbya and Calothrix were evaluated for their in vitro antiviral activity against influenza A virus in Madin Darby canine kidney cells. None of the methanolic extracts showed cytotoxic effects. The inhibitory concentration (IC(50)) of antiviral activity ranged between 20.0 micro g to 79.0 micro g extract/ml. The most active extract in this screening derived from genus Microcystis. The further analysis of methanolic extracts of cultured strains of genus Microcystis revealed a remarkable antiviral activity against influenza A virus for M. aeruginosa, M. ichthyoblabe and M. wesenbergii. The observed antiviral activity was associated with protease inhibitory activity of approximately 90% and suggest that protease inhibitory activity may be responsible for reducing virus replication. These results show that cyanobacteria are able to produce compounds with biological activity that may be of potential clinical interest.

Animals↗
PubMed2001

ApoE(-/-) mice develop atherosclerosis in the absence of complement component C5.

Previous studies have suggested that the terminal complex of complement may contribute to the pathogenesis of atherosclerosis. C5b-9 complexes colocalize with the extracellular lipid in the aortic intima of hypercholesterolemic rabbits, and C6-deficient rabbits develop less atherosclerosis than controls. To test the role of complement in atherosclerosis in a different animal model, C5 deficient (C5def) mice were cross-bred with atherosclerosis susceptible apoE(-/-) mice, generating mice deficient in both apoE and C5 and control apoE(-/-) mice. Progeny were typed for C5 titer and serum cholesterol levels. Both male and female mice were fed a high fat diet from weaning until 22 weeks of age. At that time there were no significant differences in plasma cholesterol or triglycerides between apoE(-/-) control and apoE(-/-)/C5def groups. Morphometric analysis of the aortic root lesions gave mean (+/-SEM) lesion areas for male apoE(-/-) and apoE(-/-)/C5def mice of 468,176 +/- 21,982 and 375,182 +/- 53,089 microm(2), respectively (n = 10 each, P value = 0.123). In female apoE(-/-) mice (n = 5), the mean lesion area was 591,981 +/- 53,242 microm(2), compared to 618,578 +/- 83,457 microm(2) for female apoE(-/-)/C5def mice (n = 10) (P value = 0.835). Thus neither male nor female mice showed a significant change in lesion area when C5 was not present. In contrast to the case in the hypercholesterolemic rabbit, activation of the terminal complex of complement does not play a major role in the development of atherosclerosis in apoE(-/-) mice.

Animals↗
PubMed2001

Biochemical and pharmacological investigations of selected cyanobacteria.

Cyanobacteria are a very old group of prokaryotic organisms that produce a variety of secondary metabolites with antibiotic, algicide, cytotoxic, immunosuppressive and enzyme inhibiting activities. In the last decades structures of pure compounds have been determined as phenols, peptides, alkaloids or terpenoids (Falch, 1996). Screening of lipophilic and hydrophilic extracts from cultured cyanobacteria or waterbloom material, isolated from German lakes and the Baltic sea for antiviral, antibiotic, immunomodulating and enzyme inhibiting activity in different in vitro systems revealed strains with interesting effects. These strains were cultivated in 45 litre photobioreactors to produce enough biomass for bioassay-guided isolation of the active substances. First results characterising active substances are reported.

Biological Assay↗
PubMed2001

Simvastatin has anti-inflammatory and antiatherosclerotic activities independent of plasma cholesterol lowering.

Inhibitors of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase, such as simvastatin, lower circulating cholesterol levels and prevent myocardial infarction. Several studies have shown an unexpected effect of HMG-CoA reductase inhibitors on inflammation. Here, we confirm that simvastatin is anti-inflammatory by using a classic model of inflammation: carrageenan-induced foot pad edema. Simvastatin administered orally to mice 1 hour before carrageenan injection significantly reduced the extent of edema. Simvastatin was comparable to indomethacin in this model. To determine whether the anti-inflammatory activity of simvastatin might affect atherogenesis, simvastatin was tested in mice deficient in apoE. Mice were dosed daily for 6 weeks with simvastatin (100 mg/kg body wt). Simvastatin did not alter plasma lipids. Atherosclerosis was quantified through the measurement of aortic cholesterol content. Aortas from control mice (n=20) contained 56+/-4 nmol total cholesterol/mg wet wt tissue, 38+/-2 nmol free cholesterol/mg, and 17+/-2 nmol cholesteryl ester/mg. Simvastatin (n=22) significantly (P<0.02) decreased these 3 parameters by 23%, 19%, and 34%, respectively. Histology of the atherosclerotic lesions showed that simvastatin did not dramatically alter lesion morphology. These data support the hypothesis that simvastatin has antiatherosclerotic activity beyond its plasma cholesterol-lowering activity.

Administration, Oral↗
PubMed2000

Deficiency in inducible nitric oxide synthase results in reduced atherosclerosis in apolipoprotein E-deficient mice.

Inducible NO synthase (iNOS) present in human atherosclerotic plaques could contribute to the inflammatory process of plaque development. The role of iNOS in atherosclerosis was tested directly by evaluating the development of lesions in atherosclerosis-susceptible apolipoprotein E (apoE)-/- mice that were also deficient in iNOS. ApoE-/- and iNOS-/- mice were cross-bred to produce apoE-/-/iNOS-/- mice and apoE-/-/iNOS+/+ controls. Males and females were placed on a high fat diet at the time of weaning, and atherosclerosis was evaluated at two time points by different methods. The deficiency in iNOS had no effect on plasma cholesterol, triglyceride, or nitrate levels. Morphometric measurement of lesion area in the aortic root at 16 wk showed a 30-50% reduction in apoE-/-/iNOS-/- mice compared with apoE-/-/iNOS+/+ mice. Although the size of the lesions in apoE-/-/iNOS-/- mice was reduced, the lesions maintained a ratio of fibrotic:foam cell-rich:necrotic areas that was similar to controls. Biochemical measurements of aortic cholesterol in additional groups of mice at 22 wk revealed significant 45-70% reductions in both male and female apoE-/-/iNOS-/- mice compared with control mice. The results indicate that iNOS contributes to the size of atherosclerotic lesions in apoE-deficient mice, perhaps through a direct effect at the site of the lesion.

Animals↗
PubMed2000

Infectious agents are not necessary for murine atherogenesis.

Recent work has revealed correlations between bacterial or viral infections and atherosclerotic disease. One particular bacterium, Chlamydia pneumoniae, has been observed at high frequency in human atherosclerotic lesions, prompting the hypothesis that infectious agents may be necessary for the initiation or progression of atherosclerosis. To determine if responses to gram-negative bacteria are necessary for atherogenesis, we first bred atherosclerosis-prone apolipoprotein (apo) E(-/)- (deficient) mice with animals incapable of responding to bacterial lipopolysaccharide. Atherogenesis was unaffected in doubly deficient animals. We further tested the role of infectious agents by creating a colony of germ-free apo E(-/)- mice. These animals are free of all microbial agents (bacterial, viral, and fungal). Atherosclerosis in germ-free animals was not measurably different from that in animals raised with ambient levels of microbial challenge. These studies show that infection is not necessary for murine atherosclerosis and that, unlike peptic ulcer, Koch's postulates cannot be fulfilled for any infectious agent in atherosclerosis.

Animals↗
PubMed1999

Cyanobacteria--a potential source of new biologically active substances.

Hydrophilic and lipophilic extracts of twelve cyanobacterial strains, isolated from fresh and brackish water, and two waterblooms, collected during the summer from the Baltic Sea, were investigated for their antibiotic activities against seven microorganisms. No inhibitory effects were found against the three Gram-negative bacteria Escherichia coli, Proteus mirabilis and Serratia marcescens and the yeast Candida maltosa. Of all cyanobacterial samples, extracts from seven species inhibited the growth of at least one of the Gram-positive bacteria Micrococcus flavus, Staphylococcus aureus and Bacillus subtilis. M. flavus proved to be the most sensitive bacterium in the agar diffusion test system. In particular, the hexane and dichlormethane extracts showed antimicrobial effects. But only one water extract, prepared from material of a natural waterbloom, was found to be active.

Anti-Bacterial Agents↗
PubMed1994

[Anesthesia in cats using tiletamine/zolazepam in minimal doses].

The object of this study was to evaluate minimal dose anesthesia with Tiletamine/Zolazepam for castration, dental treatments and other minor surgical procedures in cats. The study included 264 cats treated either at the Department of Veterinary Surgery, Ludwig-Maximilians University of Munich or under private practice conditions, in a small animal clinic in Hamburg (Germany). The drug dose needed for anesthesia for a 10 minute surgical procedure was calculated in each case using a formula. Side effects that occurred with doses recommended by the manufacturer could not be eliminated by decreasing the drug dose, but could be reduced considerably in severity and duration. Tiletamine/Zolazepam was found to be a useful drug for short anesthesia in cats at an average dose of 4.2 mg/kg.

Anesthesia↗
PubMed1991

[Investigations of the immunomodulatory effect of cyanobacterial extracts].

Resulting from the knowledge that cyanobacteria (blue-green algae) are able to produce pharmacologically active substances the aqueous extracts from several cyanobacteria species and strains (Microcystis aeruginosa, Synechocystis aquatilis, Oscillatoria redekei, Anabaena flos-aque, Aphanizomenon flos-aquae, Oscillatoria rubescens, Oscillatoria tenuis) were tested for their immunomodulating activity. Extracts from Oscillatoria redekei 051, Oscillatoria tenuis 01 and Synechocystis aquatilis 428 caused an immunosuppression. They inhibited not only the incorporation of 3H-thymidine into mitogen stimulated lymphocytes but reduced also the number of plaque-forming cells of mice as shown by hemolysis-plaque-assay. Only extracts from Oscillatoria redekei 051 did not show any cytotoxic effects in lymphocyte cytotoxic test. This may be an evidence for a specific action on the proliferation of lymphocytes.

Antibody Formation↗
PubMed1988

[Cultivated aortic cells--demonstration of muscarinic receptors and reaction behavior in the presence of acetylcholine].

Using the muscarinic ligand 3H-quinuclidinyl benzilate the presence of muscarinic receptors on cells isolated from aortas of newborn rats and cultivated for 6 d could be shown. The number of receptors per cell was estimated with 17,400 on cells of confluent and with 87,100 on cells of nonconfluent cultures. Incubation of cells with increasing concentrations of acetylcholine in the range of 10(-13)-10(-7) mol.l-1 resulted in the reaction of growing numbers of cells following the all-or-nothing-law. Physiological concentrations of acetylcholine lead to contractions, showing that dilatations of blood vessels after application of acetylcholine in situ are caused by reaction products of endothelial cells, being absent in the cultures.

Acetylcholine↗
PubMed1986

[Detection of muscarinic receptors on cultivated endothelial cells].

In order to contribute to the verification of the hypothesis of Furchgott et al. that the effect of acetylcholine on blood vessels is mediated by factors produced by endothelial cells, the authors tried to provide evidence for the existence of muscarinic receptors on these cells. Using cultivated cells of the endothelium of calve aortas, a specific saturable binding of the potent muscarinic antagonist 3H-Quinuclidinyl benzilate and therewith the existence of muscarinic receptors on the cells could be demonstrated. Long time cultivation leads to the disappearance of the receptors.

Animals↗