Biomedical subjects

O Hägermark

Publications and source records attributed to O Hägermark.

At least 55 records · Page 3Linked to original sources

PubMed1981

Studies on pruritogenic and histamine-releasing effects of some putative peptide neurotransmitters.

Pruritus, whealing and axon-reflex erythema appeared in human skin after intradermal injection of (i) several peptides with a putative transmitter function, i.e. vasoactive intestinal polypeptide (VIP) (10(-7)--10(-4) M), [Gln4]-neurotensin (10(-7)--10(-4) M), neurotensin (10(-5)--10(-4) M) and secretin (10(-5)--10(-4) M), which were compared with substance P (10(-7)--10(-5) M) previously shown to be one of the most potent histamine liberators when administered intradermally in humans; (ii) the basic polypeptide protamine (10(-7)--10(-4) M); and (iii) histamine (0.3-10 micrograms/ml) and the histamine liberator compound 48/80 (0.3-10 micrograms/ml). The reactions were inhibited in a dose-related manner by the antihistamine mepyramine, indicating that the peptide-induced responses were mediated by released histamine. This was further confirmed by the histamine release observed when the peptides were incubated with rat peritoneal mast cells. In human skin, VIP was more potent than the other neuropeptides and had roughly the same potency as substance P. The two adjacent basic amino-acid residues and the amide substitution of the terminal C-group of VIP, in addition to its strong net basic charge, may explain its potency as a histamine releaser.

Adolescent↗

PubMed1980

Effect in man of oral terbutaline on cutaneous reactions induced by allergen and cold stimulation.

In eight atopic subjects wheal and flare responses to intradermally injected horse dander and histamine were determined after pretreatment with 5 mg oral terbutaline or placebo in a double-blind cross-over study. In each individual a dose of allergen was used that produced a flare reaction approximately the size of the ED50 for histamine. Pretreatment with terbutaline was found to attenuate both the wheal and the flare reactions to allergen throughout the observation period of 150 min but only the effect on the wheal response reached statistical significance (P less than 0.01). The responses to histamine were not influenced. In five subjects with cold urticaria, treatment with 2.5 mg terbutaline t.i.d. for a week had no effect on the time period of cold provocation needed to evoke an urticarial lesion. It is concluded that oral treatment with terbutaline may produce an inhibitory action on allergen induced reactions but that this effect is not strong enough to interfere with clinical skin testing and hence the drug need not to be withdrawn prior to such testing.

Administration, Oral↗

PubMed1980

Cutaneous responses to allergen after local pretreatment with beta-adrenoceptor stimulating and blocking agents.

beta-Adrenoceptor stimulating agents possess anti-allergic effects in vitro and in vivo. To study the mechanism of action further we compared in 10 atopic subjects the effects on allergen-induced cutaneous reactions of intradermally (i.d.) injected prenalterol (1-10 microgram) terbutaline (2.5-250 ng) and KWD 2131 (100 ng-2.5 microgram), i.e. compounds with preferential actions on beta 1-, beta 2-adrenoceptors and on beta-adrenoceptors not fitting this classification. All injections were given according to a double-blind design. Terbutaline and KWD 2131 produced a dose-dependent inhibition of the skin reactions induced by injecting horse dander allergen 5 min later. Terbutaline was about 20 times as potent as KWD 2131 whereas prenalterol was inactive. Propranolol fully blocked the anti-allergic effect produced by terbutaline. The results suggest that the cutaneous anti-allergic effect of beta-adrenoceptor-stimulating drugs is mediated via activation of beta 2-adrenoceptors, possibly on the mast cell, resulting in inhibition of mediator release.

Adrenergic beta-Agonists↗

PubMed1979

Effect of terbutaline, a beta 2-adrenergic receptor stimulating compound, on cutaneous reponses to histamine, allergen, compound 48/80, and trypsin.

The beta-adrenoceptor stimulating agent terbutaline (2 ng-2 microgram) injected intradermally in eight atopic subjects produced a dose-dependent inhibition of the skin reactions induced by subsequently injected allergen. After injection of 0.5 microgram terbutaline inhibition of the flare and weal responses was demonstrable throughout the observation period of 90 min. The flare response induced by histamine, the histamine liberator compound 48/80 and the proteolytic enzyme trypsin was not inhibited by terbutaline in the doses used, suggesting a selective action of terbutaline on the allergen-induced response. The weal response elicited by histamine and compound 48/80 was slightly reduced by 2 microgram terbutaline. It is suggested that pretreatment of the skin with terbutaline interferes with the ability of the cutaneous mast cells to respond to challenge with allergen and that terbutaline produces this effect in doses lower than those needed to counteract the permeability increasing effect of released mediator substances.

Adolescent↗

PubMed1979

Effects of histamine receptor antagonists on histamine-induced responses in human skin.

The effects of intradermally administered histamine H1- and H2-receptor antagonists on the cutaneous responses--redness, weal, flare and itch--induced by intradermal injection of histamine were studied in man. Weal and redness were studied after blockade of the axon reflex by local infiltration with lidocaine. All responses were significantly inhibited by the H1-receptor antagonist mepyramine. The H2-antagonists cimetidine and metiamide reduced flare and itch significantly but not to the same extenet as mepyramine and not in a clearly dose-related manner. The size of weal and redness was not significantly reduced by cimetidine. No further reduction of flare, itch or weal was obtained by adding metiamide or cimetidine to mepyramine. After blockade of the axon reflex with lidocaine the histamine-induced weals turned white at the centre. This blanching was more prominent when histamine was injected in combination with cimetidine. Substituting mepyramine for cimetidine resulted in small weals with an intense red colour. It is concluded that, apart from being engaged in the direct vasodilatory response to histamine, H2-receptors do not seem to be involved in the other cutaneous responses to histamine studied.

Adult↗

PubMed1978

Flare and itch induced by substance P in human skin.

Intradermal injection of synthetic substance P (10(-7)--10(-5) M in humans produced flare, wheal and itching. These responses were inhibited by oral pretreatment of the subjects with an antihistaminic drug (chlorcyclizine) or by local pretreatment with Compound 48/80 administered to deplete the local stores of mast-cell bound histamine. The findings indicate that the responses induced by substance P were mainly mediated by histamine released from the dermal mast cells. In contrast to previously studied histamine liberators, substance P was less potent when acting on rat mast cells in vitro than on human skin mast cells in vivo. When incubated with rat peritoneal mast cells, about 100 times higher concentrations (10(-5) M) were required to induce histamine release than in the in vivo studies on humans. It was concluded that substance P is a potent histamine liberator in human skin.

Adult↗

PubMed1978

Gaschromatography of clemastine. A study of plasma kinetics and biological effect.

A method for estimation of clemastine in human plasma has been developed. By chronic acid oxidation the drug is degradated to chlorobenzophenone, which can then be analysed by gas-liquid-chromatography using electron-capture detection. The plasma levels of clemastine after oral and i.v. administration have been studied. Using different methods for extraction of the drug from plasma a metabolic degradation of the pyrrolidine part of clemastine is demonstrated. The metabolite proposed may be biologically active. The plasma level of the drug was found to be directly related to its biologic effect, measured as inhibition of the histamine-induced flare in human skin.

Administration, Oral↗

PubMed1978

Transcutaneous nerve stimulation and itching.

The response to transcutaneous nerve stimulation (TNS)--a method used for treatment of chronic pain--was studied in 41 patients with itching of diverse etiology. At a first trial, 63% of the patients found that TNS ameliorated their itching, 20% reported complete relief. As a rule the effect lasted for many hours, although TNS was given only for 5-30 min. In 15 of the patients, having suffered from extensive pruritus for more than one year, TNS was given several times a day for 5-47 days. During this time the effect declined. Twelve patients were relieved initially, either partially or completely, but ultimately only 6 had a partial relief and in none had the itching disappeared completely. Only one patient wanted to continue the TNS therapy. The decreasing efficacy is discussed; probably there was an initial placebo effect which declined during the course of treatment. The results indicate that TNS is of limited value for treating chronic itching.

Adult↗

PubMed1977

Potentiation of itch and flare responses in human skin by prostaglandins E2 and H2 and a prostaglandin endoperoxide analog.

The itch and erythematous responses induced by intradermal injection of prostaglandin E2 (PGE2), the unstable prostaglandin endoperoxide PGH2 (t1/2 approximately 5 min at 37 degrees C) and the stable endoperoxide analog (15S)-hydroxy-9alpha, 11alpha-(epoxymethano)prosta-5,13-dienoic acid (EPA) were studied in volunteers. The compounds were given alone or in combination with histamine. All the compounds produced flare reaction in the skin; the order of potency was PGE2 greater than PGH2 greater than EPA. PGE2 and PGH2 evoked a sensation of itch in about half of the subjects whereas the same doses of EPA gave no itch response. In combination with histamine all compounds elicited itch of longer duration and flare of larger area than could be accounted for by simple additive effects of any released histamine. The results indicate that the PGs and PG intermediates formed in skin may potentiate the pruritogenic and flare-inducing effects of inflammagens in man.

Adolescent↗

PubMed1977

Prostaglandin E2 in blister fluid of bullous diseases and experimental suction blisters.

Prostaglandin(PG)-like activity in the fluid of spontaneous and suction blisters was measured by bioassay on isolated guinea-pig colon after acidic lipid extraction. The fluid from spontaneous blisters in 15 patients with various bullous dermatoses, such as pemphigoid, porphyria cutanea tarda, erythema multiforme, contact dermatitis, X-ray dermatitis, all contained measurable amounts of activity, varying from 0.4 to 54 ng/ml, expressed as PGE2-activity. From 4 patients with pemphigoid, samples of fluid were collected, adequate to permit of analysis regarding the identity of the spasmogenic material. In silicic acid column chromatography, thin-layer chromatography, and in reversed phase partition chromatography, the major part of the biological activity co-chromatographed with 3H-PGE2. In one patient part of the activity coincided with PGF2alpha. The PG-like activity of experimental suction blisters was found to be significantly higher in patients with dermatitis herpetiformis than in control and psoriasis patients. The appearance of PGs in blister fluid is compatible with a role as chemical mediator involved in blister formation.

Adult↗

PubMed1977

Pruritogenic activity of prostaglandin E2.

The itch and erythematous responses induced by intradermal injection of histamine and PGE2 were studied in human skin. Both compounds produced a sensation of itch. The histamine-elicited flare reached a maximum in 3 min and had disappeared after 1 hours. PGE2 induced a similar flare reaction initially, but it was gradually replaced by a smaller, dusky and well delimited erythema. The itch and the flare-like erythema induced by either histamine or PGE2 were alleviated when the subjects were pretreated with the antihistaminic drug chlorcyclizine, thus indicating that at least part of the PGE2 response may be mediated via histamine release. However, when given combined in a mixture, histamine and PGE2 elicited itch of longer duration and flare of larger area than could be accounted for by simple additive histamine effects. Thus, PGE2 seems to potentiate the itch and flare responses induced by histamine in human skin.

Adolescent↗

PubMed1976

Plasma concentrations of griseofulvin in healthy volunteers and out-patients treated for onychomycosis.

Therapeutic failure of griseofulvin therapy are fairly common, espcially when toe nail infections are treated. The reasons for the failures remain largely unknown. The aim of the present investigation was to study whether pharmacokinetic factors may be responsible. At first, single-dose and steady-state pharmacokinetics of griseofulvin were analysed in volunteers by means of a gas-chromatographic technique. It was found that there was no difference in plasma levels of the three brands of griseofulvin commercially available in Sweden, whereas there was a singificant difference of absorption between individuals. The plasma half-life varied considerably from day to day in the same individual. In the second part of the investigation griseofulvin plasma concentrations were determined in 27 patients treated with griseofulvin for onychomycosis and related to the therapeutic result. All patients but one were initially improved but the therapeutic effect faded in 15 patients after 5-20 months of treatment ("partially healed" patients). In 11 patients the nail infections were clinically healed after 6-24 months. However, no statistically significant difference of the plasma griseofilvin levels could be demonstrated between the healed and partially healed groups. Some possible reasons for the therapeutic failure are discussed.

Adolescent↗

PubMed1974