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Biomedical subjects

W Dorsch

Publications and source records attributed to W Dorsch.

At least 37 records · Page 2Linked to original sources
PubMed1988

Pancreatic and gastric responses to gastric versus jejunal beer in humans.

To investigate the influence of beer on gastric and pancreatic secretion, 14 fasted volunteers were studied on two different days. A multilumen intestinal tube allowed measurement of intraluminal pressures and collection of gastric and duodenal juices. Seven subjects received in random order 250 ml of either beer or glucose (5.6%, w/v) intragastrically; seven other subjects received these intrajejunally. After 15 min, 48 +/- 8% of beer and 47 +/- 6% of glucose were emptied into the duodenum. Intragastric beer induced a nearly sevenfold increase in gastric acid output as compared with glucose (16.3 +/- 2.9 mmol/h versus 2.5 +/- 0.6 mmol/h; p less than 0.05), intrajejunal beer induced a nearly threefold increase (5.1 +/- 0.8 mmol/h versus 1.7 +/- 0.3 mmol/h). The stimulated gastric acid output was threefold higher after intragastric than after intrajejunal beer. Trypsin output was slightly but significantly (p less than 0.05) stimulated by intragastric beer as compared with glucose (4,639 +/- 460 U/h versus 3,628 +/- 399 U/h) and nearly threefold by intrajejunal beer (2,579 +/- 455 U/h versus 849 +/- 181 U/h) (p less than 0.05). Trypsin response to intragastric beer was 1.8 times higher than after intrajejunal beer (p less than 0.05). Intragastric beer induced a nearly ninefold increase of the 1 h integrated plasma gastrin response as compared with glucose (998 +/- 347 pM min vs 115 +/- 70 pM min) (p less than 0.05). Intrajejunal beer and glucose did not release gastrin. We conclude that both intragastric and intrajejunal beer stimulate gastric acid and pancreatic enzyme secretion; intragastric beer being a more potent stimulant. Gastrin might partially mediate the responses to intragastric but not to intrajejunal beer.

Adult↗
PubMed1987

Comparison of histamine release and prostaglandin E2 production of human basophils in atopic and normal individuals.

The influence of arachidonic acid (AA) metabolism upon histamine release (HR) from human basophils after stimulation with anti-IgE was studied in 23 atopic and 11 normal individuals. HR occurred significantly faster in atopics than in normals; the total amount of HR after a 40 min incubation period was not significantly different between the two groups. Indomethacin and acetylsalicylic acid (ASA) increased the quantity of HR significantly both in atopics and normals without influencing the time course. Addition of exogenous PGE2 decreased HR; here atopics were more affected than normals 5 and 10 min after challenge with anti-IgE. Production of PGE2 after stimulation with anti-IgE was very low in both groups (in the range of 30-50 pg/10(6) cells) and often below detection limit (10-20 pg/ml). Addition of glutathione (GSH), a coenzyme of PGE2-isomerase, increased PGE2 production 2 to 5-fold during stimulation with anti-IgE. These data support the idea that arachidonic acid metabolites play an important role in modulating the "releasability" of human basophils. It is suggested that the basophils of atopic individuals may release their histamine faster than normals - perhaps on the basis of a more slowly acting endogenous feedback mechanism by PGE2. Both phenomena support the idea of an altered "releasability" of basophils from atopics compared to normals.

Adolescent↗
PubMed1987

Adverse effects of acetylcysteine on human and guinea pig bronchial asthma in vivo and on human fibroblasts and leukocytes in vitro.

The term 'allergen tachyphylaxis' denotes decreasing bronchial reactivity to allergen after repeated allergen inhalation challenges. In guinea pig bronchial asthma this self-protecting mechanism depends on endogenous prostaglandin E biosynthesis and can be inhibited by certain thiols. Therefore, we tested the effect of acetylcysteine (AC), a secretolytic thiol, on allergen tachyphylaxis in 25 guinea pigs. We observed inhibition of allergen tachyphylaxis and prolongation of each single asthmatic reaction. A possible clinical relevance of this observation was tested by the following experiments: Human lung fibroblasts (Wi-38) were stimulated with arachidonic acid and calcium ionophore and exposed to increasing amounts of AC. PgE biosynthesis was reduced from 2,408 pg/ml (control) to 84.2 pg/ml (0.6% AC) and 18.6 pg/ml (6% AC). Histamine release (HR) from human peripheral leukocytes was induced by anti-IgE. AC (0.016, 0.16, 1.6%) augmented both spontaneous HR (0-51.8%) and anti IgE induced HR (23.5-57.9%, p less than 0.001). Patients with isolated immediate bronchial reactions after allergen challenge inhaled 3 times a constant allergen dose. In few cases the reaction decreased from one test to another. This 'allergen tachyphylaxis' was inhibited by AC. We conclude that AC should be used with caution in patients suffering from bronchial asthma.

Acetylcysteine↗
PubMed1987

Antiasthmatic effects of onions. Inhibition of platelet-activating factor-induced bronchial obstruction by onion oils.

Lyophilized onion extract and ether extracts of onions were separated by chromatographic methods into several subfractions and tested for their effects on asthmatic reactions of guinea pigs to allergen, histamine, acetylcholine and platelet-activating factor (PAF) inhalation as well as on thromboxane biosynthesis of human platelets and lung fibroblasts. Onion oils are counteracting the bronchial obstruction due to PAF inhalation.

Allium↗
PubMed1985

Altered releasability of vasoactive mediator secreting cells in atopic eczema.

A summarizing survey of different studies in atopic eczema involving three types of cells (platelets, neutrophils, basophils) and their mediators is given. Platelets were found to release normal amounts of serotonin upon stimulation with epinephrine, thrombin and slightly reduced amounts after aggregated IgG stimulation. Serotonin uptake by washed platelets was found to be slower in atopics than in normals. Neutrophils showed a decreased release of beta-glucuronidase to stimuli like zymosan or aggregated IgG in atopics compared to controls. This might be regarded as a contributory factor to the well-known decreased resistance to infections observed in atopic eczema. Basophils in most studies released increased amounts of histamine in the atopic population compared to controls, especially after stimulation with anti-IgE. Concomitantly to the histamine release there was a slight increase in prostaglandin E2 production both in atopics and normals, which was increased by preincubation with reduced glutathion-a coenzyme of PGE2 isomerase. Histamine release tended to occur faster in atopics. Two possible factors influencing releasability characteristics were studied, namely the cyclic nucleotide system and arachidonic acid (AA) dependent mechanisms. Leucocytes of atopics showed a decreased response of cAMP to beta-adrenergic and an increased response of cGMP to cholinergic stimulation. Significant augmentation of anti-IgE-induced histamine release was observed after cholinergic stimulation. AA metabolites obviously play a regulating role in mediator release. PGE2 inhibited histamine release to various stimuli both in atopics and in normals. Indomethacin enhanced histamine release, especially after anti-IgE stimulation in atopics, while it inhibited complement-dependent release reactions both in atopics and in normals. The exogenous inhibitors of lipoxygenase eicosatetraynoic acid (ETYA) and nordihydroguaretic acid (NDGA) inhibited histamine release equally in atopics and normals. The endogenous lipoxygenase inhibitor 15-HETE showed no inhibitory but rather a slight enhancing effect upon histamine release. It is concluded that patients with atopic eczema often exhibit altered releasability patterns to a variety of stimuli. On the basis of our findings we describe "altered releasability" as one factor of a vicious cycle between increased IgE-production, mediator secretion and T cell regulatory disturbances in the pathogenesis of atopic eczema.

Animals↗
PubMed1984

Antiasthmatic effects of onion extracts--detection of benzyl- and other isothiocyanates (mustard oils) as antiasthmatic compounds of plant origin.

Previous studies showed the inhibitory effects of crude ethanolic onion extracts (COE) on allergic skin reactions in man as well as on allergen-induced bronchial asthma in man and guinea-pigs. Work is in progress in order to identify both the mode of action of COE and the active substance(s). The present study describes asthma-protective effects of isothiocyanates. Groups of at least 5 guinea-pigs sensitized to ovalbumin were challenged twice (time 0 and 10 min) by the inhalation of ovalbumin 30 min after oral treatment with increasing doses of the agent tested or control solutions. Bronchial obstruction (BO) was measured by whole body plethysmography. Chloroform extracts of onions showed similar protective effects on BO as COE. The water-soluble fraction of COE was inactive. Benzyl-isothiocyanate (BITC) was identified as one component of onion lipids by combined gas chromatography/mass spectrometry. BITC inhibited BO in a dose-dependent fashion: 150 mg/kg: 89%; 75 mg/kg: 76%; 30 mg/kg: 66%; 15 mg/kg: 49%. Ethyl-isothiocyanate and allyl-isothiocyanate showed similar effects; p-hydroxy-benzyl-isothiocyanate, a very unstable mustard oil, was ineffective. Additional experiments showed no antagonistic effects of COE on histamine- or acetylcholine-induced BO. The antiasthmatic effects of onions and - perhaps - other plants may be mediated at least in part by isothiocyanates.

Administration, Oral↗
PubMed1984

[The effect pf antacids on the tissue histamine and prostaglandin (PGE2) content of the gastric mucosa].

Stimulation tests (pentagastrin) induced significant changes in tissue histamine levels in the gastric mucosa within 30 minutes. Acid secretion and a decrease of histamine after application of antacids containing calcium could not be observed in our study; neither was application of antacids over a period of eight days followed by a change in gastric mucosal tissue histamine concentrations. Patients under non-steroidal antiphlogistic medication showed diminished histamine levels. Administration of antacids did not produce changes in histamine levels, but induced a rise of PGE2 levels in the fundal and corpus area of the stomach. This may be due to a cytoprotective effect of antacids containing calcium on the gastric mucosa.

Adult↗
PubMed1984

In vivo allergen tachyphylaxis in guinea pig lung is mediated by endogenous prostaglandin E biosynthesis.

The term "allergen tachyphylaxis" (AT) describes a progressively decreased bronchial reactivity to allergen exposition after repeated allergen challenge [in our test system measured by sequential inhalative antigen challenge of sensitized guinea pigs (GP)]. The hypothesis that AT is mediated by endogenous prostaglandin E (PGE) biosynthesis was tested in vivo on GP sensitized to ovalbumin (OA). Different groups of animals were challenged with simultaneous inhalation of OA (repeatedly at time 0, 10, 20, 60 and 70 min) together with inhibitors of PGE-biosynthesis ( parachloromercurobenzoic acid = PCMB, copper sulfate = Cu, copper dithiotreitol complex = CuDTT , dithiotreitol = DTT and dimercaptopropanol = DMP) or agents increasing PGE production (aurothioglucose = Au, zinc dithiotreitol complex = ZnDTT and reduced glutathion = GSH). Bronchial obstruction was measured by whole body plethysmography . PCMB, Cu, CuDTT , DTT and DMP inhibited AT, whereas Au and ZnDTT enhanced AT. Acetylsalicylic acid (ASA) treatment prevented AT. Aerosols of PGE2, but not of prostacyclin or prostaglandin D2 restored AT in ASA treated animals. In addition to these in vivo experiments in vitro investigations showed that PCMB, Cu and DTT decreased while ZnDTT increased PGE biosynthesis of allergen challenged GP lungs. It is concluded that AT, an important self-protecting mechanism of GP bronchial asthma, is mediated at least in part via endogenous PGE.

Allergens↗
PubMed1984

Sequential histamine inhalations cause increased bronchial histamine reactivity in guinea pigs: role of platelets, thromboxanes and prostacyclin.

Groups of 6-15 guinea pigs sensitized to ovalbumin were challenged by repeated inhalations of a constant histamine dose at time 0, 10, 20, 60 and 70 min. Bronchial obstruction was measured by whole body plethysmography. The degree of bronchial obstruction increased from one challenge to the other reaching maximal values after 70 min. This increase of bronchial responsiveness to histamine after repeated histamine challenges was reduced by pretreatment with clemastine (histamine H1-receptor antagonist, 0.12 mg/kg i.p., n = 7, P less than 0.05) and more effectively by combined clemastine/cimetidine pretreatment (combined H1-H2-receptor antagonists, 0.12 resp. 10 mg/kg, n = 7, P less than 0.001); pretreatment with acetylsalicylic acid (10 mg/kg orally) accelerated the increase of bronchial responsiveness to histamine (n = 9, P less than 0.01 at the second challenge), inhalation of prostacyclin (1 microgram) prior to each histamine inhalation prevented the increase of bronchial histamine sensitivity totally (n = 10, P less than 0.001), whereas inhibition of thromboxane biosynthesis (imidazol, 10 mg/kg i.p., n = 6; 4-[2-(1H-imidazol-1-yl)ethoxy]benzoic acid, 10 mg/kg i.p., n = 9; imidazo(1,5-a)pyridine-5-hexanoic acid, 1 mg/kg i.p., n = 8) as well as immunologic platelet depletion were ineffective in our test system. We conclude that prostacyclin inhibits the increase of bronchial responsiveness to histamine after sequential histamine inhalation challenges by a platelet independent mechanism. 1-(3-phenyl-2-propenyl)-1H-imidazol, the fourth type of thromboxane synthetase inhibitor tested (10 mg/kg i.p., n = 15) showed specific effects which may be attributed to antihistamine functions.

Animals↗
PubMed1984

Prevention of allergen-induced bronchial obstruction in sensitized guinea pigs by crude alcoholic onion extract.

Thirteen guinea pigs, sensitized to ovalbumin, were pretreated with either 1 ml alcoholic onion extract (= 12% v/v ethanol) or 1 ml 12% ethanol solution (control) according to a randomized crossover protocol. Thirty minutes later the animals were challenged twice for 30 sec (n = 5), respectively 60 sec (n = 8), by the inhalation of ovalbumin (1 ml 1% ovalbumin solution nebulized in 10 l air). The intensity of bronchial obstruction was measured by whole body plethysmography using as parameter the amount of 'compressed air'. Oral pretreatment of guinea pigs with onion extract markedly reduced the asthmatic response (p less than 0.02). After onion pretreatment near normal values were obtained after 30 sec challenge (0.04 +/- 0.06 ml compared to 0.24 +/- 0.15 ml in the control) and only slightly increased values after 60 sec challenge (0.16 +/- 0.07 ml compared to 0.33 +/- 0.25 ml in the control).

Airway Obstruction↗
PubMed1984

Suppression of immediate and late anti-IgE-induced skin reactions by topically applied alcohol/onion extract.

In a double blind study, alcohol/onion extract (5% ethanol) was injected simultaneously with 20 IU and 200 IU rabbit anti-human-IgE intradermally in 12 adult volunteers (6 atopics, 6 non-atopics). Diameters of wheals and flares were measured 10 min after and compared with control sites challenged with 20 IU and 200 IU anti-IgE in a 5% ethanol solution. The skin sites were then treated epidermally with 45% alcohol/onion extract and 45% ethanol under occlusion. Diameters of late cutaneous reactions were measured hourly. Oedema formation was clinically estimated according to an arbitrary scale and skin thickness measured with a calliper. In the onion-treated skin sites the wheal areas were significantly reduced (20 IU: control: 108 +/- 53 mm2; onion 69 +/- 42 mm2, P less than 0.05; 200 IU anti-IgE: control: 152 +/- 25 mm2, onion: 138 +/- 26 mm2, P less than 0.02). The oedema formation during the late phase skin reaction was markedly depressed (P less than 0.005 at 2 h, P less than 0.01 at 4 and 6 h, P less than 0.02 at 8 h). The extent of late skin reactions was slightly, but not significantly reduced. Obviously, onions contain pharmacologically active substances with anti-inflammatory and/or allergic properties.

Anaphylaxis↗
PubMed1984

Effect of 15-hydroxyeicosatetraenoic acid (15-HETE) on anti-immunoglobulin E- and calcium ionophore-induced histamine release from human leukocytes. Comparison with the effects of eicosatetraynoic acid and nordihydroguaiaretic acid.

15-Hydroxyeicosatetraenoic acid (15-HETE) was prepared by soybean lipoxygenase-mediated oxygenation of arachidonic acid to 15-hydroperoxyeicosatetraenoic acid (15-HETE) and subsequent reduction by NaBH4. 15-HETE was identified, purified and proved as biologically active by thin layer chromatography, high pressure liquid chromatography, gas chromatography/mass spectrometry and biological experiments on horse thrombocytes and rabbit peritoneal leukocytes. 15-HETE (0.1-40 microM) was added to peripheral leukocytes of 48 human donors (33 atopics, 15 nonatopics) which were challenged with rabbit anti-human-IgE or calcium ionophore A 23187. Its effect was compared with the effects of nordihydroguaiaretic acid (NDGA) and eicosatetraynoic acid (ETYA). NDGA and ETYA markedly inhibited histamine release (17 microM: 74 +/- 11 and 39 +/- 14,3%, respectively), whereas 15-HETE neither stimulated nor inhibited spontaneous anti-IgE- or calcium ionophore A 23187-induced histamine release.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1983

A selective inhibitor of thromboxane biosynthesis enhances immediate and inhibits late cutaneous allergic reactions in man.

Thromboxanes may be involved in late cutaneous reactions (LCRs). A new selective inhibitor of thromboxane biosynthesis was studied for its effect on immediate skin test reactions (WFRs) and LCRs in nine adult nonatopic volunteers (open study) and eight adult atopic patients (double-blind study vs. placebo). WFRs and LCRs were elicited by intradermal injections of 25 micrograms of compound 48/80 and 200 IU of rabbit anti-human IgE antibodies, and the patients' receiving injections of 0.32, 1.6, 8, 40, and 200 IU of anti-IgE antibodies. Dazoxiben (100 mg orally three times once every 4 hr) increased the diameter of wheals (p less than 0.005 in volunteers; p less than 0.05 in six patients receiving no additional drug treatment), favored their dispersion (lymphangitis/pseudopodia), and caused systemic reactions (headache, chills) in at least two out of eight patients. Edema formation during LCRs was markedly depressed in 13 out of 16 persons. Flare diameter and erythemata during LCRs were not altered. These data suggest a role of thromboxanes and their natural antagonists (e.g., prostacyclin) in the regulation of allergic inflammatory processes.

Adult↗
PubMed1982

Histamine1--histamine2 antagonism: effect of combined clemastine and cimetidine pretreatment on allergen and histamine-induced reactions of the guinea pig lung in vivo and in vitro.

In a preliminary study high doses of the H1-antagonist clemastine (clem) and the H2-antagonist cimetidine (cim) were used in order to detect the side effects of both drugs on allergic reactions. After pretreatment with clem or clem/cim different guinea pigs were challenged with either OA or histamine. Bronchial obstruction was measured by body plethysmography using a new parameter ('compressed air'). Pretreatment with clem/cim in high doses protected guinea pigs against OA-induced bronchial obstruction much more effectively than H1-receptor antagonism alone; lower cim doses produced insignificant effects. In histamine-challenged animals cim showed no protective effects. In vitro clem/cim caused a marked reduction of histamine release measured in perfused lungs from 16.9 +/- 4.2 ng/ml (eight control cases) to 2.8 +/- 1.7 ng/ml (n = 8). Our preliminary data suggest that high doses of clem/cim can protect sensitized guinea pigs against allergen-induced bronchial obstruction by inhibiting histamine release.

Allergens↗
PubMed1982

Mediator studies in skin blister fluid from patients with dual skin reactions after intradermal allergen injection.

Skin blister fluid (SBF) samples obtained after allergen skin testing in a total of 26 patients with late cutaneous reactions (LCRs) were examined for the presence of various vasoactive mediators. Histamine was predominant during the early phase of the wheal and flare reaction(206 +/- 40 ng/ml) and decreased with the development of the LCR toward normal SBF levels (around 20 ng/ml). Kallikrein activity was measurable in low amounts (around 5 ng/ml) in three out of 13 SBF samples taken 30 min after skin testing and in five of 13 SBF samples taken 6 hr after allergen testing. The thromboxane B2 content of SBF showed an increase with the development of LCR (control skin 976 +/- 483 ng/ml; allergen-tested skin 30 min after allergen injection, 1465 +/- 1566 ng/ml; allergen-tested skin 6 hr after antigen injection, 1775 +/- 731 ng/ml). SBF obtained from normal skin as well as from allergen-tested skin showed significant platelet-activating property as measured in an in vitro serotonin-release assay from washed human platelets. It is concluded that during the development of late-phase reactions a complex interaction of various mediator systems takes place.

Adolescent↗
PubMed1981

Allergen tachyphylaxis of guinea pigs in vivo; a prostaglandin E mediated phenomenon?

Ovalbumin (OA) sensitized guinea pigs were repeatedly challenged with 1% OA in saline nebulized ultrasonically at the 0, 10, 20, 60 and 70th min. The intensity of bronchial obstruction was measured by body plethysmography. The first three challenges (0. 10, 20 min) caused strong asthmatic reactions in all animals, the last two (60, 70 min) only mild one in 10 out of 15 animals. The development of this "tachyphylaxis" was markedly reduced by pretreatment of the animals with cyclooxygenase inhibitors (indomethacin 10 mg/kg intraperitoneally resp, acetylsalicylic acid 10 mg/kg orally 2 h before tests). The effect of both inhibitors (i.e. inhibition of tachyphylaxis) was abolished by supplementing prostaglandin E2 as aerosol simultaneously to the allergen (100-200 ng per inhalation). The results suggest that allergen tachyphylaxis we have observed in vivo might be due to synthesis of cyclooxygenase products, e.g. prostaglandin E.

Aerosols↗