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Biomedical subjects

U Werner

Publications and source records attributed to U Werner.

At least 55 records · Page 3Linked to original sources
PubMed1993

Stimulated elastase release from human leukocytes: influence of anti-asthmatic, anti-inflammatory and calcium antagonist drugs in vitro.

In the present study the effects of drugs, with different modes of action, on FMLP-stimulated release of elastase from human leukocytes were investigated in vitro. Anti-asthmatic and anti-allergic drugs were compared to well-known anti-inflammatory and anti-histamine agents. The anti-asthmatic/anti-allergic compounds azelastine, astemizole and oxatomide, and the 5-lipoxygenase inhibitor NDGA, were able to suppress the release of elastase from human leukocytes in concentrations between 10 and 100 microM. NSAIDs such as indomethacin, diclofenac and piroxicam and the glucocorticoids dexamethasone and hydrocortisone showed little or no activity. The histamine H1 antagonists mepyramine and ketotifen and the calcium antagonists verapamil, nifedipine and TMB-8 were also ineffective in suppressing FMLP-induced elastase release. Reduction in elastase release by azelastine, that accumulates in lung tissue during long-term treatment in animals, may contribute to its anti-inflammatory and anti-allergic effects which are thought to be central to its use in asthma therapy.

Anti-Inflammatory Agents↗
PubMed1992

Quantification of the disorder in network-modified silicate glasses.

Local order in silicate glasses has been observed by many experimental techniques to be similar to that in crystalline materials. Details of the intermediate-range order are more elusive, but essential for understanding the lack of long-range symmetry in glasses and the effect of composition on glass structure. Two-dimensional 17O dynamic-angle-spinning nuclear magnetic resonance experiments reveal intermediate-range order in the distribution of inter-tetrahedral (Si-O-Si) bond angles and a high degree of order in the disposition of oxygen atoms around the network-modifying cations.

Glass↗
PubMed1992

Calcium is necessary for light excitation in barnacle photoreceptors.

Illumination of barnacle (Balanus amphitrite) photoreceptors is known to increase the membrane permeability to sodium and Ca2+ ions resulting in a depolarizing receptor potential. In this report, we show that lanthanum (La3+), a known inhibitor of Ca-binding proteins, reversibly eliminates the receptor potential of barnacle photoreceptors when applied to the extracellular space. Similar reversible elimination of the light response was obtained by removing extracellular Ca2+ by application of the calcium chelating agent EGTA. Iontophoretic injection of Ca2+, but not K+ into the cells protected both the transient and the steady-state phases of the receptor potential from elimination by EGTA while only the transient phase was protected in the presence of La3+. The EGTA experiments suggest that internal Ca2+ is necessary for light excitation of barnacle photoreceptors while the La3+ experiments suggest that La(3+)-sensitive inward current is necessary to maintain excitation during prolonged light.

Animals↗
PubMed1992

Measurement of the thermal diffusivity of human epidermis by studying thermal wave propagation.

The thermal diffusivity of dry human epidermis was determined in vitro by studying thermal wave propagation in thin epidermal layers at frequencies between 10 and 200 Hz. Transmission measurements were performed on samples applied to a plane copper support at the underside of which thermal waves were generated by means of a square voltage controlled power transistor. Additionally, measurements were performed on epidermal layers with metal and air backing, in which thermal waves were generated by the absorption of intensity modulated light in a thin, superficially applied graphite layer (short and open circuit measurements). Thermal waves were detected by means of the laser beam deflection technique which allows the contactless measurement of the oscillatory surface temperature of a sample with respect to amplitude and phase. A critical discussion of methods shows that the thermal diffusivity is most reliably determined by transmission experiments. From experimental data obtained by this method a mean value alpha = (2.8 +/- 0.9) x 10(-4) cm2 s-1 was evaluated for the thermal diffusivity of dry epidermis.

Diffusion↗
PubMed1992

Anpirtoline, a novel, highly potent 5-HT1B receptor agonist with antinociceptive/antidepressant-like actions in rodents.

1. The purpose of the present study was to relate the effects of the novel drug, anpirtoline, on 5-hydroxytryptamine (5-HT) receptor subtypes to its antinociceptive and antidepressant-like actions in rodents. 2. Binding assays with rat brain membranes have shown that anpirtoline bound with a much higher affinity to 5-HT1B receptor (Ki = 28 nM) than to 5-HT1A (Ki = 150 nM) and 5-HT2 (Ki = 1.49 microM) receptors. 3. Like 5-HT, anpirtoline concentration-dependently inhibited forskolin-stimulated adenylate cyclase activity in homogenates from the rat substantia nigra. Both effects were not additive, and could be prevented by 5-HT1B receptor antagonists such as propranolol and penbutolol. 4. In superfused rat and pig brain cortex slices preincubated with [3H]-5-HT, the electrically evoked tritium overflow was inhibited by anpirtoline and 5-HT. Whereas 5-HT was equipotent in both tissues (EC50 = 69 nM), anpirtoline was markedly less potent in pig brain cortex slices (EC50 = 1190 nM) than in rat brain cortex slices (EC50 = 55 nM). The concentration-response curve for anpirtoline was shifted to the right by metitepine in both preparations. 5. In the social behaviour deficit test, anpirtoline and trifluoromethylphenyl-piperazine were effective in reversing the isolation-induced impairments in mice, an effect shown only by compounds with agonist properties at the 5-HT1B receptor. 6. In the electrostimulated pain test using mice, anpirtoline dose-dependently increased the pain threshold with an ED50 of 0.52 mg kg-1, i.p. The antinociceptive activity of anpirtoline was abolished by pretreatment with cyproheptadine or propranolol.7. In the forced swimming test in rats, anpirtoline induced a dose-related increase in swimming activity. With an ED50 value of 4.6mgkg-1, i.p., anpirtoline was 4 times more potent than the two standard compounds imipramine and desipramine. The decrease of immobility time or the increase of active periods in this model of behavioural despair is suggested to be characteristic of antidepressant drugs.8. Anpirtoline exhibits both antinociceptive and antidepressant-like activities in animals. It is probable that anpirtoline elicits these pharmacological effects via its agonist effect on 5-HT1B and 5-HT1A receptors.

Adenylyl Cyclase Inhibitors↗
PubMed1992

Measurement of MPO activity as model for detection of granulocyte infiltration in different tissues.

Activity of myeloperoxidase (MPO) was determined in different tissues to detect granulocyte infiltration. MPO was measured in the mouse ear after injection of interleukin-1 beta, in the rat paw after carrageenan-induced edema and in the lung of sensitized guinea pigs after ovalbumin inhalation. Pretreatment of the animals with antiinflammatory drugs abolished the increase of MPO activity in tissues induced by this different stimuli.

Animals↗
PubMed1991

[Acute posttraumatic lung failure. Its treatment through pressure-limited respiration and continuous postural change].

Nine patients (4 women and 5 men; mean age 31 [20-48] years) with severe posttraumatic adult respiratory distress syndrome (ARDS) were treated with continuous postural change (kinetic bed) and pressure-limited ventilation. Seven patients survived; only one patient died as a result of pulmonary insufficiency. As compliance was markedly reduced (less than 20 ml/cm H2O), low stroke volumes (up to 380 ml) and high respiratory rate (up to 45/min) were employed to keep airway peak pressure below 40 mmHg. Kinetic treatment lasted for a mean of 14 (2-28) days; artificial ventilation was maintained for 31 (9-49) days. Practical problems of the method are the intensive nursing care required for the kinetic bed and the risk of decubitus ulcers, as well as disconnection of infusion tubing. The results indicate that kinetic treatment with pressure-limited ventilation constitutes a low-risk and, in many cases, effective treatment of severe ARDS.

Adult↗
PubMed1991

Influence of azelastine on IL-1 beta generation in vitro and IL-1 beta-induced effect in vivo.

The effects of the novel antiasthmatic/antiallergic compound azelastine on IL-1 beta were investigated in vitro and in vivo. In leukocytes both, intra- and extracellular IL-1 generation stimulated by LPS was inhibited dose dependently. In contrast azelastine did not prevent IL-1 beta-induced immigration of PMNs into the mouse ear. These findings suggest that azelastine is not an IL-1 antagonist but inhibits IL-1 synthesis and/or release in leukocytes.

Adult↗
PubMed1990

Sequence analysis of the promoter region of the glioblastoma derived T cell suppressor factor/transforming growth factor (TGF)-beta 2 gene reveals striking differences to the TGF-beta 1 and -beta 3 genes.

Human glioblastoma cells secrete a factor termed glioblastoma derived T cell suppressor factor (G-TsF) or transforming growth factor beta 2 (TGF-beta 2) which inhibits the response of T cells to mitogenic or antigenic stimulation. In the present study we isolated the promoter region of the G-TsF/TGF-beta 2 gene. The promoter region shares no homology to the promoter of the TGF-beta 1 or the 5' region of the TGF-beta 3 gene and harbours several familiar DNA motifs, including the cytokine-1 region, an octamer-like sequence, Sp1- and AP-2-like elements and a putative NF-kappa B site. In contrast to the TGF-beta 1 gene, the G-TsF/TGF-beta 2 gene contains three TATA-like sequences but lacks an AP-1 site. To understand the cell type specificity of expression of G-TsF/TGF-beta 2, the individual contribution of the DNA elements detected in the promoter has to be analysed in further studies.

Base Sequence↗
PubMed1990

Chemistry and pharmacology of the non-benzodiazepine anxiolytic enciprazine and related compounds.

In the course of studies on tranquilizers, new non-benzodiazepine-like compounds were synthesized. These are 1-(3,4,5-trimethoxyphenoxy)-3-[4-(2-methoxyphenyl)piperazinyl]prop an-2-ol (INN: enciprazine) and derivatives thereof which were screened pharmacologically in order to evaluate their central nervous system activity. Compounds with marked antiaggressive and anxiolytic properties but without dependence potential could be detected. Enciprazine was selected for clinical investigations.

Aggression↗
PubMed1988

[Multiple colorectal cancers: properties and long-term prognosis].

In our own patient population with primary colorectal cancer (n = 1352, 1971-1984) we analyzed the frequency, characteristics and prognosis of multiple carcinomas. The overall incidence was 7.3% (4.5% synchronous and 2.8% metachronous carcinomas). Compared to single cancer synchronous tumors had a worse and metachronous tumors had a better 5 year-prognosis (58%, 43% and 86% respectively). This suggests that synchronous and metachronous colorectal carcinomas may be two biologically separate entities. Conclusions from our observations are discussed in regard to diagnosis, therapy and follow-up.

Colonic Neoplasms↗
PubMed1986

[A food-borne infection caused by Campylobacter jejuni serotype Lauwers 19].

Report on a outbreak due to contaminated food involving 556 schoolchildren who got their lunch from a school kitchen. The outbreak occurred abruptly without any secondary infectious. Examinations for Salmonellae, Shigellae, Enteritis-coli, Yersiniae and Rotaviruses were negative. However, Campylobacter jejuni were isolated from 105 specimens of faeces in Rostock. Sixty of these strains and another 2 that had been isolated at the same time but had no relation to the outbreak in Rostock, were further differentiated in Berlin-Buch. All of them proved to be Campylobacter jejuni biotype 2. Serotyping according to Lauwers revealed that 58 out of the 60 strains isolated belong to serotype 19. One of the two remaining strains could not be typed, the other was identified as serotype 1. One of the two cultivated strains that were not related to the outbreak in Rostock, was untypable, the other being of serotype 2. Therefore it can be assumed that the outbreak came from the same source of infection. Epidemiological investigations pointed to some food which had been served 6 days prior to the outbreak. The meal had consisted of white cabbage stew with beef. The kitchen supplies the cooked food to several institutions; 3 different dishes being prepared each day, referred to as dish, A, B and C. The institutions receiving dish A - which on November 1, 1985 was the above-mentioned white cabbage stew - actually included several classes of a school as well as a kindergarten. On that particular day however the kindergarten had not been supplied with dish A but, as an exception, with dish B.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗