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Biomedical subjects

H Schenk

Publications and source records attributed to H Schenk.

At least 37 records · Page 2Linked to original sources
PubMed2000

Structure of CnCn+2Cn-type (n = even) beta'-triacylglycerols.

The crystal structures of the beta' phase of CLC (1, 3-didecanoyl-2-dodecanoylglycerol) and MPM (1, 3-ditetradecanoyl-2-hexadecanoylglycerol) have been determined from single-crystal X-ray diffraction and high-resolution X-ray powder diffraction data, respectively. Both these crystals are orthorhombic with space group Iba2 and Z = 8. The unit-cell parameters of beta'-CLC are a = 57.368 (6), b = 22.783 (2) and c = 5.6945 (6) A and the final R value is 0.175. The unit-cell parameters of beta'-MPM are a = 76.21 (4), b = 22.63 (1) and c = 5.673 (2) A and the final R(p) value is 0.057. Both the beta'-CLC and beta'-MPM molecules are crystallized in a chair conformation, having a bend at the glycerol moiety. The zigzag planes of the acyl chains are orthogonally packed, as is typical for a beta' phase. Furthermore, unit-cell parameters of some other members of the C(n)C(n+2)C(n)-type triacylglycerol series have been refined on their high-resolution X-ray powder diffraction pattern. Finally, the crystal structures are compared with the currently known structures and models of triacylglycerols.

Crystallography, X-Ray↗
PubMed1999

Characterization of the binding site of the histamine H3 receptor. 1. Various approaches to the synthesis of 2-(1H-imidazol-4-yl)cyclopropylamine and histaminergic activity of (1R,2R)- and (1S,2S)-2-(1H-imidazol-4-yl)-cyclopropylamine.

Various approaches to the synthesis of all four stereoisomers of 2-(1H-imidazol-4-yl)cyclopropylamine (cyclopropylhistamine) are described. The rapid and convenient synthesis and resolution of trans-cyclopropylhistamine is reported. The absolute configuration of its enantiomers was determined by single-crystal X-ray crystallographic analysis. The distinct trans-cyclopropylhistamine enantiomers were tested for their activity and affinity on the histamine H3 receptor. (1S,2S)-Cyclopropylhistamine (VUF 5297) acts as an agonist both on the rat cortex (pD2 = 7.1; alpha = 0.75) and on guinea pig jejunum (pD2 = 6.6; alpha = 0.75). Its enantiomer, (1R, 2R)-cyclopropylhistamine (VUF 5296), is about 1 order of magnitude less active. Both enantiomers show weak activity on H1 and H2 receptors. All synthetic attempts to cis-cyclopropylhistamine were unsuccessful. Nevertheless, the results of this study provide an ideal template for molecular modeling studies of histamine H3 receptor ligands.

Animals↗
PubMed1999

Structure of mono-acid even-numbered beta-triacylglycerols.

The crystal structure of the beta polymorph of tripalmitin (1,2,3-trihexadecanoylglycerol, beta-PPP) has been determined by single-crystal X-ray diffraction. The molecules crystallize in space group P1; in an asymmetric tuning-fork conformation. This structure and the already-known crystal structures of beta-tricaprin (beta-CCC) and beta-trilaurin (beta-LLL) could be matched in an overlap model. Apart from a difference in chain length, the three structures are almost identical. The overlap model can be used to predict the crystal structure of the other members of the C(n)C(n)C(n)-type (n = even) TAG series reasonably accurately. This is demonstrated by predicting the crystal structure for beta-trimyristin (beta-MMM) and successively comparing the experimental and calculated X-ray powder diagrams.

Journal Article↗
PubMed1997

Pharmacodynamic modelling of the analgesic effects of piritramide in postoperative patients.

BACKGROUND: The concentration-effect relationship of piritramide, a synthetic opioid analgesic predominantly used for postoperative analgesia and analgosedation, has not been reported so far. METHODS: Twenty-four patients of both genders aged 58.1 (11.7) yr (mean (SD)) received inhalational anaesthesia for abdominal surgery. Postoperative pain was assessed with a visual analogue scale (VAS). Analgesia was provided with piritramide, infused at a rate of 7 micrograms.kg-1.min-1 until analgesia was considered sufficient (VAS < 25) or up to a maximum dose of 0.2 mg/kg. The plasma concentrations of piritramide were determined by gas chromatography. An inhibitory fractional sigmoid Emax-model was used to describe the relation between effect site concentration and perceived pain. RESULTS: The equilibration half-life between plasma and effect site concentrations (T1/2 (keo)) was 16.8 min (median; range: 4.4-41.6 min). The steady-state plasma concentration required to produce 50% of maximum analgesia (EC50) was 12.1 ng/ml (range: 2.9-29.8 ng/ml) and correlated with initial pain intensity. The slope factor gamma was 1.9 (range: 0.5-6.1) and increased with age. Clinically relevant respiratory depression did not occur. Due to the relatively large equilibration half-life of the effect compartment, the context-sensitive half-time of the effect site concentrations after short-time administration (< 2 h) clearly exceeded those of alfentanil, sufentanil, and fentanyl. CONCLUSIONS: The analgesic effect of piritramide was adequately described by an inhibitory fractional Emax-model. In order to overcome the pronounced hysteresis, piritramide should initially be administered as an intravenous bolus of at least 5 mg.

Adult↗
PubMed1996

Thioredoxin as a potent costimulus of cytokine expression.

Reduction/oxidation (redox) processes have been implicated in various biologic processes, including signal transduction, gene expression, and cell proliferation. Thioredoxin is one of the major redox-regulatory molecules which because of its dithiol/disulfide exchange activity determines the oxidation state of protein thiols. In this study, we report that treatment of several cell types with thioredoxin strongly enhances the expression of various cytokines. In monocytic Mono Mac6 cells stimulated with the phorbolester tetradecanoyl phorbolacetate (TPA), thioredoxin was found to augment the expression of TNF at the protein and mRNA levels. In this and other cell lines, such as fibrosarcoma and endothelial cells, thioredoxin also dose-dependently increased the synthesis of IL-6. Treatment of TPA-stimulated Mono Mac6 cells resulted in a strong potentiation of secreted IL-1 bioactivity and expression of IL-1 alpha and IL-8 mRNA. In addition, in TPA-activated Molt-4 T cells, an increased expression of IL-2 and IL-2-specific transcripts was detected. These data demonstrate that cytokine synthesis may be tightly controlled by redox-dependent processes. As thioredoxin is readily secreted and taken up by cells, it may play an important role as a costimulatory molecule involved in immune processes.

Animals↗
PubMed1995

IL-2 gene expression and NF-kappa B activation through CD28 requires reactive oxygen production by 5-lipoxygenase.

Activation of the CD28 surface receptor provides a major costimulatory signal for T cell activation resulting in enhanced production of interleukin-2 (IL-2) and cell proliferation. In primary T lymphocytes we show that CD28 ligation leads to the rapid intracellular formation of reactive oxygen intermediates (ROIs) which are required for CD28-mediated activation of the NF-kappa B/CD28-responsive complex and IL-2 expression. Delineation of the CD28 signaling cascade was found to involve protein tyrosine kinase activity, followed by the activation of phospholipase A2 and 5-lipoxygenase. Our data suggest that lipoxygenase metabolites activate ROI formation which then induce IL-2 expression via NF-kappa B activation. These findings should be useful for therapeutic strategies and the development of immunosuppressants targeting the CD28 costimulatory pathway.

Arachidonate 5-Lipoxygenase↗
PubMed1995

Requirement of an ICE/CED-3 protease for Fas/APO-1-mediated apoptosis.

The Fas/APO-1 receptor is one of the major regulators of apoptosis. We report here that Fas/APO-1-mediated apoptosis requires the activation of a new class of cysteine proteases, including interleukin-1 beta-converting enzyme (ICE), which are homologous to the product of the Caenorhabditis elegans cell-death gene ced-3 (refs 11, 12). Triggering of Fas/APO-1 rapidly stimulated the proteolytic activity of ICE. Overexpression of ICE, achieved by electroporation and microinjection, strongly potentiated Fas/APO-1-mediated cell death. In addition, inhibition of ICE activity by protease inhibitors, as well as by transient expression of the pox virus-derived serpin inhibitor CrmA or an antisense ICE construct, substantially suppressed Fas/APO-1-triggered cell death. We conclude that activation of ICE or an ICE-related protease is a critical event in Fas/APO-1-mediated cell death.

Amino Acid Sequence↗
PubMed1994

Distinct effects of thioredoxin and antioxidants on the activation of transcription factors NF-kappa B and AP-1.

The transcription factors NF-kappa B and AP-1 have been implicated in the inducible expression of a variety of genes involved in responses to oxidative stress and cellular defense mechanisms. Here, we report that thioredoxin, an important cellular protein oxidoreductase with antioxidant activity, exerts different effects on the activation of NF-kappa B and AP-1. Transient expression or exogenous application of thioredoxin resulted in a dose-dependent inhibition of NF-kappa B activity, as demonstrated in gel shift and transactivation experiments. AP-1-dependent transactivation, in contrast was strongly enhanced by thioredoxin. A similar increase of AP-1 activity was also observed with other, structurally unrelated antioxidants such as pyrrolidine dithiocarbamate and butylated hydroxyanisole, indicating that the thioredoxin-induced increase of AP-1 activation was indeed based on an antioxidant effect. Moreover, the stimulatory effect on AP-1 activity was found to involve de novo transcription of the c-jun and c-fos components but to be independent of protein kinase C activation. These results suggest that thioredoxin plays an important role in the regulation of transcriptional processes and oppositely affects NF-kappa B and AP-1 activation.

Animals↗
PubMed1994

Functions of glutathione and glutathione disulfide in immunology and immunopathology.

Even a moderate increase in the cellular cysteine supply elevates the intracellular glutathione (GSH) and glutathione disulfide (GSSG) levels and potentiates immunological functions of lymphocytes in vitro. At low GSSG levels, T cells cannot optimally activate the immunologically important transcription factor NF kappa B, whereas high GSSG levels inhibit the DNA binding activity of NF kappa B. The effects of GSSG are antagonized by reduced thioredoxin (TRX). As the protein tyrosine kinase activities p56lck and p59fyn are activated in intact cells by hydrogen peroxide, they are likely targets for GSSG action. These redox-regulated enzymes trigger signal cascades for NF kappa B activation and transduce signals from the T cell antigen receptor, from CD4 and CD8 molecules, and from the IL-2 receptor beta-chain. The effector phase of cytotoxic T cell responses and IL-2-dependent functions are inhibited even by a partial depletion of the intracellular GSH pool. As signal transduction is facilitated by prooxidant conditions, we propose that the well-known immunological consequences of GSH depletion ultimately may be results of the accompanying GSSG deficiency. As HIV-infected patients and SIV-infected rhesus macaques have, on the average, significantly decreased plasma cyst(e)ine and intracellular GSH levels, we also hypothesize that AIDS may be the consequence of a GSSG deficiency as well.

Amino Acid Sequence↗
PubMed1991

Morphometric study of synaptic patterns in the rat caudate nucleus and hippocampus under haloperidol treatment.

A morphometric study of the synapses on dendritic shafts and spines was performed in the rat caudate nucleus and the CAI area of the hippocampus under chronic haloperidol treatment. In the nucleus caudatus, the synaptic density on dendritic shafts increased by 83% and those on spines by 53%. Most of the parameters measured in axospinous synapses were significantly increased: the area of presynaptic axon terminals (20%), the number of mitochondria per axon terminal (51%), the length of active zone (11%), the area of postsynaptic density (23%), and the perimeter of postsynaptic density (12.5%). The area of postsynaptic spines showed no changes. In the synapses on dendritic shafts, the area of presynaptic terminals decreased (31%), the area of mitochondria per terminal decreased (40%), the length of active zone increased (14%), and other parameters were unchanged. There were no significant differences in the same parameters measured in the hippocampus. The data are discussed as morphological correlates of behavioral supersensitivity and dopamine D2 receptor up-regulation.

Animals↗
PubMed1991

Changes of brain gangliosides in the frontal cortex of rats chronically treated with amphetamine, clozapine, haloperidol and ethanol.

Rats were injected intraperitoneally daily for 20 days with amphetamine, haloperidol, clozapine and ethanol to investigate the participation of gangliosides in the reactivity of the brain to these drugs. All of these substances are able to modulate the ganglioside pattern of the frontal cortex. The major changes were observed after amphetamine and clozapine treatment. In both cases, GQ1b was significantly increased, whereas GM2 and GM3 were significantly diminished. Moreover, GD1a (after amphetamine) and GM1 (after clozapine) were decreased with respect to the controls. After haloperidol treatment both GQ1b and GT1b augmented, while after ethanol, only GM3 was increased.

Amphetamine↗
PubMed1991

[Rumania January 1990: acute medical deficits and chronic shortage--an evaluation at the site].

Between January 4 and 8, 1990, a medical delegation of the University Hospital Zurich (three surgeons, one OT-nurse) was sent to Bukarest. They escorted a large sending of surgical and pharmacological equipment. The assignment was 1. to evaluate the situation in the hospitals around the Bukarest area; 2. to determine the feasibility and the need of medical emergency support; 3. to assess the usefulness and practicability of medium-term relief. A total of 11 hospitals were visited in Bukarest, Pitesti, Racovita and Schitu-Golesti. It was found that 1. a sufficient number of doctors and medical personnel is available; 2. emergency aid is important regarding pharmaceuticals (local anesthetics, analgetics, insulin), infusions, dressing material, surgical instruments and external fixation equipment; 3. medium-term support is need for the complete medical equipment (syringes, injection and infusion sets, probes, suture material, etc.). Local medical literature and journals are worthless. Doctors long for high-quality medical books and periodicals. We can help!

Developing Countries↗
PubMed1990

The effect of abstinence in alcoholics of erythrocyte gangliosides.

The pattern of gangliosides in membranes of erythrocytes was examined in healthy and in alcoholic subjects on the second and on the 28th day of detoxification therapy. The GM3 and GD3 fraction were decreased significantly in alcoholics on the 2nd day. After 4 weeks of abstinence all changes had returned to the level of healthy subjects.

Adult↗
PubMed1990

[Use of computer technique in occupational health inspection].

An organisation concept of an inspectorate of occupational hygiene is described. Its development was started any years ago, but it is reached a temporary optimum just by the introduction of computers. The present state is described in characteristics, also is concise indicated the possible and desirable further development. Interested persons may demand comprehensive informations about the total concept and documentations about the individual part-programs from the authors under send in of a diskette.

Documentation↗
PubMed1990

[Altered composition of gangliosides in the erythrocyte membrane and in the plasma of alcoholic patients].

Gangliosides were isolated from plasma and membranes of erythrocytes of alcoholics. The pattern of gangliosides were compared with the data of healthy donors. Up to 7 fractions of gangliosides could been detected after extraction, purification by column chromatography and fractionation by TLC. In alcoholics the main ganglioside fractions of plasma GM3 were increased (52.6%) and GD3 were decreased (17.5%). The GM3 and GD1b fraction of erythrocytes membranes were decreased significantly in alcoholics.

Adult↗