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Reports on the developments in the clinical and pathophysiological aspects of urticaria. Understanding of the heterogeneity of mast cells; Importance of neuropeptides in the pathogenesis of urticaria; Role of adhesion molecules in the development of urticarial weal.

Corticosteroids may mediate some of their anti-inflammatory effects via induction of a specific 38 kDa protein, lipocortin-I. Anti-lipocortin-I antibodies (ALA) were measured by enzyme-linked immunosorbent assay (ELISA) in 23 patients with plaque-type psoriasis alone (NAP), in 21 patients with psoriasis and arthritis (PA), and in 67 healthy controls. Only two of 23 NAP patients had elevated ALA, whereas six of 21 PA patients had raised levels of ALA (P = 0.2). Sero-negative polyarthritis was the most common pattern of joint disease in those PA patients with elevated ALA (4/6). ALA levels did not correlate with the extent or severity of cutaneous involvement, and are unlikely to be involved in the pathogenesis of cutaneous psoriasis. [ABSTRACT FROM AUTHOR]

The role of locally released cytokines in inducing lymphocyte activation and infiltration in the skin lesions of mycosis fungoides has been investigated. The levels of selected cytokines were measured in chamber fluid samples from lesional and control skin. Biologically active interleukin 6 was significantly elevated in lesional samples and a recombinant form of this cytokine was shown to induce lymphocyte migration in an in vitro assays Biologically active interleukin i was detected in all control chamber fluid samples. Significantly reduced levels of this cytokine were present in lesional samples, which may be the result of the release of preformed material Interleukin 2 and tumour necrosis factor activity, and 7 interferon and granulocyte macrophage colony-stimulating factor immunoreactivity, were not detectable in any of the samples. Interleukins 1 and 6 may play a role in the pathogenesis of the lesional lymphocyte infiltrates in mycosis fungoides. [ABSTRACT FROM AUTHOR]

Patients with the idiopathic hypereosinophilic syndrome (HES) may develop associated skin disorders. We describe a patient who had xerosis since birth, but who first developed symptoms of aquagenic pruritus soon after he presented with HES. Photochemotherapy with psoralen and UVA treatment reduced his peripheral blood eosinophil count. The good response to treatment suggests that there was a close relationship between the dermatosis and the blood disorder. [ABSTRACT FROM AUTHOR]

Out of 98 female referrals with acne vulgaris it was possible to define ovarian morphology by high resolution ultrasound imaging of the pelvis in 82 (84%). Sixty-eight (83%) were shown to have polycystic ovaries, compared with 19% in a control group without acne. The presence of polycystic ovaries in the acne patients did not correlate with acne severity, infertility, menstrual disturbance, hirsutes, or biochemical endocrinological abnormalities. [ABSTRACT FROM AUTHOR]

Clobetasol propionate 0.05% ointment and an otherwise identical steroid-free base were applied topically to a 10 cm² area on the anterior thighs of six patients with symptomatic dermographism for 6 weeks. Four patients showed a significantly decreased wealing response to stroking of steroid pretreated skin compared to that of control sites. There was a parallel decrease in mast cell numbers and histamine levels in skin biopsies taken from the steroid treated areas. At 6 weeks two patients demonstrated a decrease in flare areas following the intradermal injection of compound 48/80 in steroid pretreated skin compared to base treated sites. Flare areas following intradermal injection of histamine in these two patients were equivalent in base and steroid treated skin. [ABSTRACT FROM AUTHOR]

A randomized double-blind placebo controlled trial of colchicine in the treatment of 13 patients with delayed pressure urticaria enabled us to assess some of the variables in this disorder. We have modified a previously described method of pressure testing using a calibrated dermographometer and shown a pressure induced papular dose response curve. Assessment of disease activity was based on the number of pressure weals which occurred, the size of delayed pressure induced papules using a dermographometer calibrated at 9.75 × 105 pascals for five separate time periods on the back and estimations of erythrocyte sedimentation rate and the acute phase protein levels. We have been unable to show a therapeutic effect using coichicine 0.5 mg bd for I week. [ABSTRACT FROM AUTHOR]

In two patients with painful cutaneous leiomyomata, induction of pain by the application of an ice cube allowed assessment of a number of topical and systemic treatments aimed at reducing or preventing the pain. In one patient the alpha-adrenoceptor blocker, phenoxybenzamine alleviated cold-induced pain. In the second patient, topical 9",, hyoscine hydrobromide (an anticholinergic agent) decreased pain induced by the ice cube, but was not helpful in reducing lesional pain due to cold weather. [ABSTRACT FROM AUTHOR]

A study of dithranol ointment in the mouse-tail test showed that 0.2% dithranol ointment induced a granular layer and orthokeratosis in mouse-tail epidermis. This provides further evidence of the value of the mouse-tail test in evaluating anti-psoriatic activity of topical preparations. [ABSTRACT FROM AUTHOR]

One hundred and twenty patients with chronic idiopathic urticaria, who entered a study at five centres (Sheffield, London, Bristol, Cardiff and Leeds) were treated with therapeutic doses of the H1 antagonist chlorpheniramine for 6 weeks. Histamine H1 non-responders (40 patients) were entered into a double-blind study and received chlorpheniramine plus cimetidine 400 mg q.d.s. (21 patients) or chlorpheniramine plus placebo (19 patients) for a further 8 weeks. The most important response measure was the change from baseline of the total symptom score: an assessment of the number and duration of new weals and degree of itching. There was a statistically significant difference between the average response in the two treatment groups in favour of chlorpheniramine plus cimetidine after 4 and 8 weeks' treatment (P<0.05 and P<0.01, respectively). No significant side-effects related to treatment were noted. [ABSTRACT FROM AUTHOR]

Passive transfer experiments were carried out on three species of monkey, Macaca mulatta, Macaca nemestrina and Macaca fascicularis, using human serum from patients affected with severe symptomatic dermographism (factitious urticaria), cholinergic urticaria, chronic idiopathic urticaria and normal subjects. The monkeys were tested for dermographism by means of a calibrated dermographometer 24 h after intradermal injection of the serum, using Evans blue as a marker. Positive responses were seen initially in the M. nemestrina. Four sites injected with serum from patients with severe symptomatic dermographism gave positive responses, one site injected with serum from a normal subject produced a faint response. One of the four responses was reproduced one month later in M. fascicularis. These results indicate that passive transfer of dermographism is possible from human to monkey. [ABSTRACT FROM AUTHOR]

A case of localized heat urticaria in a 70-year-old woman is reported. Increased plasma levels of prostaglandin D2 and blood histamine after heat challenge indicate a role for mast cell degranulation in the pathophysiology of the syndrome. Treatment with astemizole increased the temperature threshold to wealing, but not to itch or erythema. The patient was partially desensitized by repeated exposure to heat and this was further improved by indomethacin. After treatment there was no increase in plasma prostaglandin D2 on challenge. No evidence was found for the activation of the alternative complement pathway. [ABSTRACT FROM AUTHOR]

We report a patient with cholinergic urticaria in whom stroking the skin produced a band of erythema studded with the small weals characteristics of cholinergic urticaria. This response was suppressed by pre-treatment with topical scopolamine. Light and electron microscopy of the weal showed mast cell degranulation and a moderate mononuclear cell infiltrate. [ABSTRACT FROM AUTHOR]

The article examines the role of acidic lipid neutrophil chemo-attractant in the pathogenesis of the inflammatory changes in chronic plaque psoriasis. The evidence obtained to date is presented here in six sections, according to the above criteria. The article informs about the process to recover lipoxygenase products from psoriatic lesions. In order to recover such compounds, a skin chamber sampling technique has been developed. It also states that psoriasisis not a multifactorial disease. LTB4-like material and 12-HETE have been recovered from psoriatic lesions and from calcium ionophore stimulated human epidermal cell suspensions. These two compounds, applied topically, have also been shown to reproduce some features of the psoriatic lesion.

A case of eosinophilic cellulitis is described. Tests of eosinophil function were normal. Radioimmunoassay identification of inflammatory mediators showed greatly increased concentrations of leukotrienes LTC4/D4 (components of slow-reacting substance of anaphylaxis) in affected skin. These mediators may play a causal role in the inflammation seen with eosinophilic cellulitis. [ABSTRACT FROM AUTHOR]

Autonomic function in patients with cholinergic urticaria and atopic eczema was compared with that in patients with chronic idiopathic urticaria and non- atopic allergic contact dermatitis, respectively. Forty-nine patients were studied. The following specific tests of sympathetic and parasympathetic function were used to assess the integrity of autonomic control: pupillary reflex amplitude in response to pulsed light stimulation and response to topical arecoline hydrobromide (parasympathetic); the speed of pupillary dilatation following a large light reflex (sympathetic); pupillary resting diameter (sympathetic and parasympathetic); sweat gland response to forearm intradermal injection of acetylcholine chloride; and the effect of postural change and deep breathing on blood pressure and heart rate (sinus arrhythmia indicating parasympathetic function). No significant difference in autonomic function was found between the four groups of patients. [ABSTRACT FROM AUTHOR]

The role of histamine in urticaria is reviewed with particular reference to experiments on cold contact urticaria. In this model, histamine release clearly has a central role, but the failure of drugs which suppress histamine release to alleviate symptoms, other than itching, suggests that other pharmacological agents must be involved. Evidence is presented that prostaglandin E may play a role in some of these patients. The discovery that human blood vessels possess H2 receptors as well as Hi receptors is discussed with particular reference to the role of combined H1 and H2 pharmacological blockade. [ABSTRACT FROM AUTHOR]

Focuses on the role of the neutrophil polymorphonuclear leukocyte in the pathogenesis of the psoriatic lesion. Debate regarding the relationship of neutrophils to the histogenesis of psoriasis; Involvement of neutrophil invasion of epidermis in psoriasis; Need for fully controlled therapeutic studies of lipoxygenase inhibitors in psoriasis.

Use of differential effects of agonists and antagonists has provided an experimental basis for subdivision of histamine receptors into H1 and H2. This has enabled classification of the responses to histamine in a wide range of organs and tissues. In human skin the vascular and sensory effects of histamine have been studied, and the influence of histamine on epidermal cell growth has been evaluated in vitro. The direct vasodilator and vascular permeability actions of histamine appear to involve both H1 and H2 receptors. However, the axon reflex flare due to histamine appears to be predominantly an H1 effect. Histamine itch involves HI receptors. These findings have prompted clinical evaluation of combined therapy with H1 and H2 antagonists in patients with urticaria. Initial results have been encouraging in patients with factitious urticaria. Histamine exerts an inhibitory action on epidermopoiesis in vitro in a number of mammalian epidermal cell outgrowth systems including human explants. The pathophysiological relevance of this effect, which involves epidermal H2 receptors and which may be cyclic AMP dependent, is unknown. [ABSTRACT FROM AUTHOR]

Comments on the applicability of ultraviolet-A (UV-A) radiation for treatment of cutaneous disorders. Questions on the capacity of long-continued irradiation of skin by UV-A to evoke skin cancer; Concerns on the marketing of sunbeds for home use; Caution for the use of UV-A for cosmetic purposes.

Two patients with urticaria evoked at the site of contact of skin with water have been studied. Protection of the skin from contact with water by prior application of petrolatum ointment prevented wealing, but removal of the stratum corneum enhanced wealing. Organic solvents did not themselves evoke wealing, but they enhanced the reaction to subsequent challenge by water. That the release of acetylcholine is an essential step in the pharmacogenesis of wealing in aquagenic urticaria is indicated by the suppressive effect of locally-applied scopolamine on water-evoked wealing. Aquagenic urticaria is also associated with elevated blood histamine levels and degranulation of mast cells in the water-challenged skin. The relationship of acetylcholine and histamine to each other and to contact of water with the skin remains uncertain. [ABSTRACT FROM AUTHOR]

Determines the potential involvement of histamine receptors in the physiological and pathological events of the human skin. Role played by histamine in delayed hypersensitivity skin reactions, including contact allergic dermatitis; Effects of histamine on epidermal growth; Function of histamine as a mediator of pruritis.

The antagonistic activity of oxatomide, and its effects on evoked histamine release and histamine-N-methyl transferase activity in skin, have been studied. Oxatomide antagonizes H1 activity in a dose-dependent but non-competitive manner. It also shows same atropine-like activity. Oxatomide did not cause detectable inhibition of antigen-stimulated histamine release from skin slices of sensitized guinea-pigs although the possibility that oxatomide may cause weak inhibition could not be excluded. In the presence of low concentrations of histamine, oxatomide suppressed human skin histamine-N-methyl transferase, but in the presence of higher substrate concentrations it enhanced activity of this enzyme. These observations, which Were limited by the poor solubility of oxatomide in aqueous media, should encourage further in vivo studies of oxatomide's histamine-suppressing properties in the human subject. [ABSTRACT FROM AUTHOR]

Plasma levels of six protease inhibitors have been measured in patients with chronic urticaria, chronic urticaria with angio-ocdema, cold and cholinergic urticaria. In chronic urticaria C1 esterase inhibitor activity was increased compared with a reference control population but there was no detectable abnormality of any other protease inhibitor. Patients with chronic urticaria/angio-oedema showed a reduction in inter-α trypsin inhibitor. They also manifested a rise in C1 esterase inhibitor. In cold urticaria there was a significant lowering of α1 antichymotrypsin. The reduction in α1 antitrypsin in this group probably reflects a genetic difference compared with the control population. Patients with cholinergic urticaria also showed a reduction of α1 antichymotrypsin. The elevated levels of α2 macroglobulin in the three groups are probably due to differences in the mean age of these groups compared with the reference population. Comparison of levels in subgroups of patients with and without active lesions suggest that a consumptive effect may contribute to the reduced values, although it seems unlikely to account for them entirely. The results suggest that involvement of pharmacologically active products of protein digestion may be involved in the pathogenesis of urticaria and should prompt attempts to identify these agents and encourage trial of medications which lead to inhibition of proteolytic activity in urticaria. [ABSTRACT FROM AUTHOR]

Irradiation of human blood platelets with UV-A in vitro impairs their ability to aggregate after challenge with collagen. There also appears to be mild and transient inhibition of platelet aggregability in psoriatics during the fourth week of photochemotherapy. [ABSTRACT FROM AUTHOR]

Mast cell population density was determined in normal skin from two regions of the arm of several healthy men and compared with blood vessel density and histamine concentration in the same sites, Mast cell and blood vessel counts were made in 1-1.5 μm thick plastic sections, by light microscopy and tissue-histamine concentrations were determined by automated fluorinietric analysis. Statistically significant correlations were found between mast cell counts, blood vessel counts and histamine content in skin from the upper arm but no similar correlations were obtained in the forearm. Anatomical differences between the two sites may have been the cause of this discrepancy. Wide variations in mast cell counts and blood vessel density were found in different sections from the same biopsy samples which confirms the notion that dermal mast cells are unevenly distributed. Analysis of variance of the mast cell counts showed that the variance between sections from different blocks from the same biopsy samples was greater than the variance between adjacent biopsies. There was also a marked variation in the histamine content between biopsy samples from sites only 2 cm apart in the same subject. [ABSTRACT FROM AUTHOR]

This article presents information on study related to Cimetidine in chronic idiopathic urticaria. Patients with chronic idiopathic urticaria are usually treated with conventional Hr antihistamines, but the response is good in no more than about 1/3 of patients. Furthermore, the use of higher doses of antihistamines is limited by troublesome atropine and hyoscine-like side effects. The study has explored the possibility that combination therapy with a conventional Hr antihistamine (chiorpheniramine) and the specific H2 antihistamine cimetidine might be more effective than chiorpheniramine alone in the treatment of chronic urticaria. Existing medication, including antihistamines, was withdrawn for one week prior to the study.

Methods for establishing the diagnosis in cholinergic urticaria are reviewed and compared. Provocation by exercise or hot bath is more effective than local provocation by intradermal tests. Of the intradermal tests, responses to nicotine acid tartrate and acetyl β methylcholine chloride are positive only in patients with the more severe, readily induced eruptions. Furthermore, intradermal testing is not always reproducible in the same patient. In our patients, exercise proved the simplest, most effective diagnostic test. [ABSTRACT FROM AUTHOR]

This paper reports chemotactic studies on human polymorphonuclear leukocytes using prostaglandins, prostaglandin precursors and prostaglandin metabolites in vitro. Chemotaxis could not be demonstrated when arachidonic acid, prostaglandins D2, E1, E2, F2α, and the prostaglandin metabolites 15 keto E2, 15 keto F2α were incubated with polymorphonuclear leukocytes using the Boyden millipore technique. [ABSTRACT FROM AUTHOR]

We have demonstrated the release in vitro by normal human skin of a factor which possesses IL-1-like activity in the mouse thymocyte amplification assay. Quantitatively similar amounts of this factor were released from involved and uninvolved skin of patients with cutaneous T cell lymphoma. The IL-l-like factor was associated with inhibitory activity in the mouse thymocyte amplification assay. High performance liquid chromatographic analysis showed that this inhibitory activity co-chromatographed with prostaglandin E2. These results provide further evidence for the role of the skin as an immunologically active organ and suggest that PGE2 may have an immunomodulatory role in human skin. [ABSTRACT FROM AUTHOR]

Incubation of histamine with guinea-pig skin or with a particle-free supernatant fraction of homogenized skin caused progressive temperature dependent decay of histamine activity. The loss of histamine activity was due to enzymic degradation of histamine by diamine oxidase since it was reversed by aminoguanidine. Burimamide caused a .similar though less marked reversal of histamine degradation. Studies using S-adenosylmethionine, an essential cofactor of histamine-N-methyl transferase suggested the presence in a latent form in guinea-pig skin of a second pathway for enzymic degradation of histamine involving N-methylation. Pretreatment of guinea-pigs with aminoguanidine caused marked potentiation of the 72 hr homologous PCA reaction which suggests that histamine degradation is an important modulating factor in immediate allergic reaction in this species. [ABSTRACT FROM AUTHOR]

Presents various letters to the editor. Information on lymphocytic leukaemia; Discussion on Dermatosis mimicking granuloma annulare developed in the region of healed varicella-zoster; Information on plasma levels of immunoreactive platelet activating factor in patients with psoriasis.

We report three cases of Wegener's granulomatosis presenting with cutaneous ulceration resembling pyoderma gangrenosum. Wegener's granulomatosis classically affects the upper and lower respiratory tracts and the kidneys. Skin involvement occurs in up to 50% of patients.[sup1] In creased awareness that cutaneous involvement can take the form of pyoderma gangrenosum and that it can be a presenting sing may lead to more rapid diagnosis of Wegener's granulomatosis. [ABSTRACT FROM AUTHOR]

Most women with acne are found to have polycystic ovaries on high resolution pelvic ultrasonography, but most of these women do not manifest the other classical clinical characteristics of the polycystic ovary syndrome[sup1]. We have compared the endocrinological profile of women with acne who were found to have polycystic ovaries with that of women with polycystic ovaries who presented to an endocrine clinic with hirsutes or non-dermatological manifestations of the polycystic-ovary syndrome. The group of women with acne had normal serum hormonal concentrations. Unlike other women with polycystic ovaries, they did not have significantly elevated serum concentrations of luteinizing hormone or testosterone. By clinical and endocrinological criteria, patients with acne who have polycystic ovaries appear to be a distinct sub-population of women with polycystic ovaries. [ABSTRACT FROM AUTHOR]

The histological features of follicular mucinosis are known to occur in association with mycosis fungoides and may also be found in a variety of inflammatory, hamarto-matous, hyperplastic or neoplastic conditions. We report follicular mucinosis occurring in a patient with Sézary syndrome, to our knowledge a previously unreported association. [ABSTRACT FROM AUTHOR]

Twenty-seven biopsy specimens from II patients with pressure urticaria were studied. Sixteen of the specimens were from spontaneous lesions, of which five were pairs of early and late lesions. Some early lesions showed neutrophilia and eosinophilia in the deep tissue, and Late lesions showed significant perivascular lymphocytosis with cosinophilia. Eleven dermographometer-induced lesions showed neutrophilia in the superficial localized dermal tissue and progressive eosinophilia in the superficial localized dermal tissue; the deep vascular and dermal tissues were occasionally involved. The level of Cl-esterase inhibitor was elevated in eight of the nine cases studied. We believe that pressure urticaria may be similar to other whealing diseases, with an early neutrophilic phase of inflammation and a late phase of lymphocytosis and eosinophilia. [ABSTRACT FROM AUTHOR]

Fifty patients with a history of symptomatic dermographism were investigated. The mean age of onset was 25.75 years (range: 'from birth' to 52 years) and the peak age of onset was in the second and third decades. The mean duration at last follow-up was 5.1 years (range: 3 months to 47 years). The duration was longer than 5 years in 22% and longer than 10 years in 10% of the patients. Ninety-two percent of patients, but not a single member of an age-matched group of sixty control subjects, produced measurable wealing at a pressure of 3.5 × 10[SUP5] Pa or less applied with a calibrated dermographometer. The incidence of the atopic diathesis was not increased in patients with symptomatic dermographism, and no associations with systemic diseases, food allergens or medications were established. Routine haematological, biochemical, microbiological and intradermal screening tests were not found to be helpful in the management of this condition. Protease inhibitor profiles revealed a significant reduction in the level of circulating α 1-antitrypsin inhibitor which was not the result of a genetic difference between the patient and control groups. In a double-blind randomized controlled trial of eight different antihistamine regimes in twelve patients, a combination of hydroxyzine (10 mg qds) and cimetidine (400 mg qds) proved significantly superior to all other treatments in reducing dermographometer-induced wealing, and was associated with fewest side-effects. [ABSTRACT FROM AUTHOR]

Radioimmunoassay is a rapid, convenient, specific and sensitive method of measuring methotrexate (MTX) levels in plasma and skin exudate. Chronic users have a delayed peak level compared to recently treated patients. MTX levels in skin exudate approximate to those in plasma. Only 50% of plasma MTX is free, whereas almost all is free in skin exudate. [ABSTRACT FROM AUTHOR]

Cutis verticis gyrata is a rare disorder of the scalp characterized by permanent folds and furrows. If these are parallel then the appearance is of corrugations usually running in an antero-posterior direction. If the folds run in diverse directions, then the gyrate appearance is similar to cerebral sulci. The folds vary in width whilst the furrows are narrower, often trapping hairs in tufted rows. The pathogenesis of the folding is not known. There is an increase in skin area relative to the underlying tissues which could be a result of either local overgrowth of the skin or contraction of subcutaneous tissues.

The results of a double-blind study of zinc sulphate treatment in patients with venous leg ulceration are reported. No significantly increased rate of healing occurred in the zinc treated group. The serum zinc concentration at the onset of treatment did not significantly influence the rate of healing in zinc-treated patients, but patients with an initial low serum zinc showed a more rapid rate of healing than those with a high zinc level irrespective of treatment. This finding could be accounted for by a defect of distribution of zinc in patients with venous leg ulceration. [ABSTRACT FROM AUTHOR]

The magnitude of a histamine-mediated inflammatory reaction in skin depends on the local concentrations of histamine achieved in response to the evoking stimulus. These concentrations in turn depend upon the amount and rate of histamine secreted or released, and upon the rate of decay of histamine activity in the injured skin. Decay of histamine activity in part depends on passive diffusion within the interstitial fluid. Histamine also finds its way into the lymphatic and blood circulations. Active uptake mechanisms for histamine are known to exist in myocardial muscle cells and neoplastic mast cells and active histamine uptake by skin cells cannot be excluded.

This article focuses on immunopharmacology of the immediate allergic response in skin. Corticosteroids may have a more complex effect on whealing responses in human skin than is generally realized. In addition to the welt-known inhibitory affect on vasodilatation and increased vascular permeability, glucocorticoids may act early on in the reaction by reducing histamine secretion by skin mast cells. Disodium cromoglycate's inhibitory action on histamine release from the lung cannot be reliably reproduced in skin in vitro.

The effect of cytochalasin B (which selectively inhibits the function of cytoplasmic contractile microfilaments) on IgE-mediated hypersensitivity in human skin was studied. Cytochalasin B inhibited the antigen-induced histamine release from human skin slices sensitized passively in vitro with human reaginic serum. The magnitude of inhibition of histamine release was related to the duration of preincubation of sensitized skin slices with cytochatasin B. The effect of cytochalasin B on antigen-induced histamine release from sensitized skin was reversible, indicating that the inhibition of histamine release may be due to the inhibition of contraction of cytoplasmic microfilaments in sensitized target cells by cytochalasin B. [ABSTRACT FROM AUTHOR]

The effect of drugs that increase the cellular concentration of cyclic AMP on antigen-evoked histamine release from IgE sensitized human skin was studied. Using a new in vitro model consisting of human skin slices passively sensitized by antigen-specific IgE antibody, histamine release following challenge of skin by antigen was consistently inhibited by adrenalin and theophylline in a dose-related manner. That the inhibitory effect of adrenalin is due to β-adrenergic stimulation was established using the specific β-adrenergic antagonist propranolol. When adrenalin and theophylline were combined marked synergism was demonstrated. Further confirmation of these results was obtained using dibutyryl cyclic AMP which produced dose-related inhibition of antigen-evoked histamine release from human skin. These results demonstrate that drugs that increase cellular cyclic AMP consistently inhibit human cutaneous anaphylaxis and raise the possibility that cyclic AMP exerts a regulatory effect on IgE-mediated hypersensitivity in human skin. [ABSTRACT FROM AUTHOR]

A method has been devised for obtaining from rabbit blood suspensions of leucocytes rich in basophils but depleted of platelets. The preparation contains histamine equivalent to 0.2 µg/ml of blood or 1.3 pg/basophil. In vitro anaphylactic histamine release by suspensions obtained from actively sensitized rabbits has been demonstrated and some properties of this new system have been described. [ABSTRACT FROM AUTHOR]

Histamine release from rabbit leucocytes is temperature-dependent and requires the presence of calcium but not magnesium. It is inhibited by agents which reduce disulphide linkages, and by sulphydryl-blocking agents, but potentiated by certain dicarboxylic acids. [ABSTRACT FROM AUTHOR]

THE problem of pharmacological mediators of inflammation still remains unsolved despite the isolation and characterization of an increasingly wide range of naturally occurring vasoactive substances. This subject has recently been reviewed by Spector and Willoughby (1968). We have developed a continuous skin perfusion method for use in human subjects which enables direct recovery of pharmacological substances from inflamed skin. In this communication we report results obtained in 2 types of inflammation-immediate and delayed. The possible applications of this technique to evaluation of the mode of action of anti-inflammatory drugs are also considered. [ABSTRACT FROM AUTHOR]

The responses to topical application of tetrahydrofurfuryl nicotinate (Trafuril) cream were studied using a continuous skin perfusion method in clinically uninvolved skin of patients with chronic urticaria and in control patients. Trafuril causes inflammation but also renders the skin susceptible to dermographism. In non eurticarial subjects little pharmacological activity was detected during Trafuril inflammation or after stroking the skin to induce dermographism. This suggests that Trafuril causes inflammation by a direct effect on the cutaneous vasculature. By contrast in urticarial patients histamine was recovered more frequently than in non-urticarial patients during Trafuril inflammation, both before and after the skin was stroked. Perfusates from urticarial subjects also contained unidentified smooth muscle contracting activity which was not due to histamine, kinins, serotonin or acetyl choline. These results suggest that the skin of patients with chronic urticaria releases histamine and some other pharmacological agents more readily than that of normal subjects in response to inflammation producing stimuli. [ABSTRACT FROM AUTHOR]