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Biomedical subjects

W Dorsch

Publications and source records attributed to W Dorsch.

At least 19 recordsLinked to original sources

[Clinical application of extracts of Echinacea purpurea or Echinacea pallida. Critical evaluation of controlled clinical studies].

The phytotherapy should be understood as being integrated into the rational pharmacotherapy. The modern phytotherapy tries hard to proof effects with pharmacological and clinical studies. The task force E of the federal bureau of health of Germany has made a statement regarding this problem. This article reviews only controlled clinical trials about the application of extracts of echinacea purpura or echinacea pallida.

Adjuvants, Immunologic

Determinants of cord-blood IgE concentrations in 6401 German neonates.

For screening atopy risk in 6401 (84%) of all infants born during the year 1990 in six obstetric departments of five German cities, cord-blood IgE values were determined with CAP-RAST-FEIA. After cases with elevated IgA values had been excluded, 25% of the values were above the detection limit of 0.35 kU/l, and 8.5% were above 0.9 kU/l. Boys had significantly higher values than girls (P < 0.001). The distribution of values was significantly different for different nationalities of mothers (P < 0.001). The percentage of elevated values (> 0.9 kU/l) increased significantly with the number of close family members with atopic history (P < 0.001). Regarding the atopic history of the father, siblings, and mother separately, only the mother's history had a significant association with the cord-blood IgE class (P < 0.001). The IgE values of 81 twin pairs correlated significantly with a coefficient of r = 0.4909 (P < 0.001). The smoking history of the parents during pregnancy showed an association with cord-blood IgE values (P < 0.02). No significant association could be shown between cord-blood IgE distribution and other variables, i.e., gestational age, birth size, birth modus, Apgar score, cord-blood pH value, neonatal problems, parity, age of the mother, medication during pregnancy, educational level of mother or father, time of year, or obstetric department. It is hypothesized that, in addition to some postpartum contamination or placental transfer of maternal IgE, cord-blood IgE values are also determined by the fetal immunologic reaction to intrauterine exposure to allergens and trigger factors, and by genetic influences.

Adrenal Cortex Hormones

[Bronchial asthma].

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Anti-Inflammatory Agents

[Immunostimulation].

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Anti-Inflammatory Agents, Non-Steroidal

Tetragalloylquinic acid, the major antiasthmatic principle of Galphimia glauca.

In the search for antiasthmatic principles in plant drugs, a bioguided fractionation of an alcoholic extract of Galphimia glauca was performed using a plethysmographic in vivo model. Tetragalloylquinic acid (G1), which was found together with other compounds (gallic acid, methyl gallate, ellagic acid, and flavonoid acylglycosides), showed the highest activity against bronchial hyperreactivity and allergic reactions. Using mass and NMR spectroscopy in combination with energy calculations, the structure G1 was elucidated as tetra-O-galloylquinic acid. Depending on the solvent used, the quinic acid skeleton can occupy a fixed conformation or several interconverting ones on the NMR time scale.

Animals

Antiasthmatic effects of Galphimia glauca, gallic acid, and related compounds prevent allergen- and platelet-activating factor-induced bronchial obstruction as well as bronchial hyperreactivity in guinea pigs.

A methanolic extract from Galphimia glauca (320 mg/kg, orally) inhibited acute bronchial reactions to allergen (ovalbumin, 10 mg/ml) and platelet-activating factor (PAF, 1 microgram/ml) inhalation challenges, but not to histamine or acetylcholine in spontaneously breathing guinea pigs. Furthermore, the PAF-induced bronchial hyperreactivity was markedly reduced. Gallic acid and related compounds as well as the flavonoid, quercetin, were identified as active compounds. Gallic acid, methyl gallate and quercetin showed significant effects after a single oral dose of 45 mg/kg, tetragalloyl quinic acid after 5 mg/kg. Continuous treatment of the animals with one certain fraction (GG II, 3 days, 3 x 2 mg/kg) containing all active compounds reduced allergen- and PAF-induced bronchial reactions by more than 70%.

Animals

In vitro IgE eluation and histamine releasability from peripheral leukocytes of atopics and normals.

The relation between the amount of cell-bound IgE and the histamine 'releasability' of peripheral leukocytes was studied in 28 patients with atopic diseases and 26 non-atopic controls after in vitro stimulation with anti-IgE. Cell-bound IgE was eluted in acid buffer (pH 3.7) and the amount of histamine released (HR) into supernatant at this pH was measured. Incubation with acetate buffer (pH 3.7) induced significantly higher spontaneous HR (32 net percent) in atopics compared to 18% in controls. The amount of IgE eluted was significantly higher in atopics: The calculated number of IgE molecules/basophil was 332,000 in atopics compared to 177,000 in controls. There was a significant positive correlation between plasma IgE and in vitro elutable IgE in atopics (r = 0.73) compared to controls (r = 0.24). After a careful washing procedure attempts were made to 'resensitize' the basophils through incubation with autologous plasma or standard IgE solutions. When resensitization was possible, there was no correlation between histamine releasability after resensitization and original IgE content of basophils. It is concluded that the increased histamine releasability from leukocytes of atopic individuals after stimulation with anti-IgE is only in part due to an increased number of IgE molecules per basophil surface. A non-specific increased releasability was demonstrated by increased spontaneous HR rates in acid buffer (pH 3.7). A resensitization with autologous plasma-IgE was possible only in half of the subjects investigated, most of them being atopic. The data support the concept of an altered releasability both towards IgE-dependent and independent stimuli being one possible factor in the pathogenesis of atopic eczema.

Adolescent

New antiasthmatic drugs from traditional medicine?

Several plants are used in traditional medicine for the treatment of bronchial asthma. We are trying to identify the active compound(s) and their mode of action. For the isolation and identification of the active principles, different chromatographic methods, HPLC, MPLC, elementary analysis, UV, mass, 1H- and 13C-NMR spectroscopy are used. Whole plant extracts, fractionated extracts and pure compounds are tested in the following pharmacological systems: cyclooxygenase and lipoxygenase pathway of arachidonic acid metabolism, bronchial obstruction of guinea pigs after inhalation of allergens, platelet-activating factor (PAF), histamine or acetylcholine, PAF-induced bronchial hyperreactivity of guinea pigs, histamine release, chemoluminescence and chemotaxis of human polymorphonuclear leukocytes as well as thromboxane biosynthesis of human platelets. As active compounds in onion extracts, thiosulfinates and cepaenes could be identified. They exert a wide spectrum of pharmacologic activities, both in vitro and in vivo. Tetragalloyl quinic acid from Galphimia glauca, suppressed allergen- and PAF-induced bronchial obstruction, PAF-induced bronchial hyperreactivity (5 mg/kg orally) in vivo and thromboxane biosynthesis in vitro. Hitherto unknown alkaloids from Adhatoda vasica showed pronounced protection against allergen-induced bronchial obstruction in guinea pigs (10 mg/ml aerosol). Androsin from Picrorhiza kurroa prevented allergen- and PAF-induced bronchial obstruction (10 mg/kg orally; 0.5 mg inhalative). Histamine release in vitro was inhibited by other compounds of the plant extract yet to be identified. Pharmacological effects of plant extracts and pure compounds in man are under investigation.

Allium

Antiasthmatic effects of Picrorhiza kurroa: androsin prevents allergen- and PAF-induced bronchial obstruction in guinea pigs.

In the Ayurvedic medicine, Picrorhiza kurroa Royle ex Benth. is used for the treatment of liver and lung diseases. Using different chemical and pharmacological methods, we could identify the phenol glycoside androsin as active compound preventing allergen and platelet-activating factor induced bronchial obstruction in guinea pigs in vivo (10 mg/kg p.o.; 1 h prior to the inhalation challenge). Histamine release from human polymorphonuclear leukocytes in vitro was inhibited by other compounds yet to be identified.

Acetates

Antiasthmatic effects of onions: inhibition of 5-lipoxygenase and cyclooxygenase in vitro by thiosulfinates and "Cepaenes".

Nine thiosulfinates (TS) and four "Cepaenes" (CS) isolated from onions and/or synthetized by us showed dose dependent (0.25 to 100 microM) marked inhibitory effects on both cyclooxygenase (CA, tested on sheep seminal vesicle microsomes) and 5-lipoxygenase activity (LO, tested on porcine leukocytes). The following rank order of activity was observed: saturated aliphatic TS less than aromatic TS approximately alpha, beta-unsaturated TS less than CS. CS inhibited both CA and LO by more than 75% at 10 and 1 microM concentrations respectively. Most likely, these in vitro effects are responsible for antiinflammatory and antiasthmatic properties of onion extracts observed in vivo, at least in part.

Allium

Anti-inflammatory effects of onions: inhibition of chemotaxis of human polymorphonuclear leukocytes by thiosulfinates and cepaenes.

Seven different synthetic thiosulfinates, and cepaene- and/or thiosulfinate-rich onion extracts were found to inhibit in vitro the chemotaxis of human granulocytes induced by formyl-methionine-leucine-phenylalanine in a dose-dependent manner and at a concentration range of 0.1-100 microM. Diphenylthiosulfinate showed the highest activity and was found to be more active than prednisolone. The anti-inflammatory properties of onion extracts are related, at least in part, to the inhibition of inflammatory cell influx by thiosulfinates and cepaenes.

Adult

[Bronchial asthma: allergy and inflammation. Principles of rational asthma therapy].

Improved concepts concerning the pathogenesis of chronic bronchial asthma, the role of air pollutants, infections, and allergic reactions are the basis of established therapeutic principles and the development of new drugs: Allergens initiate long lasting inflammatory processes ("late phase reactions") in the bronchial system. This inflammation causes bronchial hyperreactivity and altered lung function. A large number of inflammatory cells and mediators are involved. Air pollutants and infections can act in the same way. Asthma treatment should focus in the inflammatory process, start early and prevent and treat both chronic inflammation and acute bronchospasm.

Asthma

Antiasthmatic effects of onions. Prevention of platelet-activating factor induced bronchial hyperreactivity to histamine in guinea pigs by diphenylthiosulfinate.

Thiosulfinates are responsible for antiasthmatic and anti-inflammatory properties of onions. We tested the effect of diphenylthiosulfinate on platelet-activating factor (PAF)-induced bronchial hyperreactivity to histamine: According to a randomized crossover protocol, groups of 14 guinea pigs inhaled histamine, were then treated orally with either vehicle or with 10-100 mg/kg diphenylthiosulfinate, inhaled 1 microgram PAF, and thereafter the same histamine dose given prior to PAF. In the control group the histamine response increased threefold; in the treated group the histamine response decreased. The effect of 100 mg diphenylthiosulfinate lasted 12 h. Antihistamine effects were not demonstrable in this test system. We conclude that thiosulfinates inhibit PAF-induced hyperreactivity.

Allium

Anti-asthmatic effects of onions. Alk(en)ylsulfinothioic acid alk(en)yl-esters inhibit histamine release, leukotriene and thromboxane biosynthesis in vitro and counteract PAF and allergen-induced bronchial obstruction in vivo.

Five alk(en)ylsulfinothioic acid alk(en)yl-esters isolated from onions and four synthetic thiosulfinates inhibited 5-lipoxygenase of porcine leucocytes, histamine release and leukotriene B4 and C4 biosynthesis of human polymorphonuclear leucocytes, thromboxane B2 biosynthesis by human platelets and allergen- and PAF-induced bronchial obstruction of guinea-pigs. The anti-asthmatic and anti-inflammatory effects of onions depend in part on the thiosulfinate moiety: (Formula: see text).

Allergens

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