[Time of appearance of cutaneous radioactivity after administration of oleic acid labeled with I131].
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Administration, Cutaneous↗
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Persistent immune tolerance to nickel and chromium by oral administration prior to cutaneous sensitization.
Oral administration of allergens, foreign proteins, or cell-bound antigens may induce systemic suppression of subsequent humoral and cell-mediated immune responses ("oral tolerance"). The induction of specific immune tolerance provides a potential strategy for treatment of T-cell-dependent immune diseases. Therefore, in depth studies into preconditions for optimal and persistent tolerance induction are mandatory. Here we report on such studies in a guinea pig model using the non-cross-reactive contact allergens nickel and chromium. Feeding per os of nickel sulfate or potassium dichromate did not trigger systemic TDTH-effector functions. Instead, short feeding periods led to a dose-dependent, and metal-specific, suppression of subsequently induced allergic contact hypersensitivity. Administration of the allergens onto the oral mucosa was most effective in the induction of immune tolerance. When first sensitizing attempts were delayed until 1 year after feeding, the degree of unresponsiveness was reduced. In contrast, with cutaneous contacts starting shortly after the feeding period, tolerance was fully stable and undiminished for at least 2 years. Thus, in orally treated guinea pigs cutaneous contacts provide boosting tolerogenic signals, supporting the view that oral tolerance does not result from clonal deletion but from active antigen-specific immunosuppression. Indeed, unresponsiveness to cutaneous immunization could be transferred by lymphoid cells from fed guinea pigs in a metal-specific way.
Administration, Oral↗
[Cutaneous complications in oral administration of sulfapyridine].
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Administration, Cutaneous↗
Distribution and excretion of a new insect repellent, 14C-DEM, in the mouse after intravenous, cutaneous, and oral administration.
The distribution of 14C after administration of 14C-DEM was qualitatively similar irrespective of the administration route (intravenous, cutaneous or oral). The major accumulation sites were lacrimal and nasal glands, parotis, liver, and kidney. The main excretion was through the urine and only minor quantities through the faeces and the expired gases. It could be confirmed that the new repellent had a low skin uptake.
Acetamides↗
Cutaneous toxicity following the administration of dactinomycin.
Dactinomycin (AMD) is an effective drug in the management of several malignant disorders and has been used for almost 40 years. Skin and subcutaneous toxicities following extravasation are well known and can be harmful. Similarly radiation-recall is a well established phenomenon following the administration of AMD. We report a patient who developed a localized brawny erythema in the crural folds and the axillae, likely due to AMD. This rare skin complication of AMD seems to benefit from topical corticosteroid treatment, although postinflammatory hyperpigmentation may take months to disappear.
Administration, Cutaneous↗
Clinical pharmacokinetics of organic nitrates.
Plasma concentrations of glyceryl trinitrate (nitroglycerin), isosorbide dinitrate and isosorbide 2- and 5-mononitrates in man have been measured after administration via different routes. Appropriate precautions have to be taken in the administration of these agents (to avoid loss during intravenous infusion), and in their sampling and assay. Pharmacokinetic calculations based on plasma concentrations should be viewed with caution, as the data on which these calculations are based are often very limited, and the very rapid disappearance of for example glyceryl trinitrate from plasma makes the choice of an appropriate kinetic model and exact calculations difficult. Glyceryl trinitrate disappears from plasma within a few minutes, and a high apparent volume of distribution and a very high systemic clearance are found. After oral administration, plasma concentrations are very low; with sublingual or cutaneous administration, higher plasma concentrations can be obtained, suggesting a high first-pass extraction after oral administration, but quantitative data on bioavailability are lacking. For isosorbide dinitrate the systemic clearance, although high, is lower than for glyceryl trinitrate; disappearance from the plasma is slower and plasma concentrations after different routes of administration are much higher. Here too, quantitative data on bioavailability are lacking. High plasma concentrations of isosorbide 2-mononitrate and isosorbide 5-mononitrate are found in plasma after administration of isosorbide dinitrate. These metabolites have a good bioavailability, and half-lives of around 2.5 hours for isosorbide 2-mononitrate and 5 hours for isosorbide 5-mononitrate. Only very limited data are available about the influence of disease states and interactions with food and other drugs on the kinetics of the organic nitrates. It is very difficult to correlate the effects of the nitrates to their plasma concentrations; counter-regulation, development of tolerance, and the presence of metabolites could disturb the interpretation of such a relationship. It is at present impossible to predict the pharmacological effects or the efficacy of organic nitrates on the basis of their plasma concentrations.
Administration, Oral↗
Assessment and management of cutaneous reactions with amifostine administration: findings of the ethyol (amifostine) cutaneous treatment advisory panel (ECTAP).
PURPOSE: To review reports of severe skin reactions during amifostine treatment. METHODS AND MATERIAL: The expert panel reviewed postmarketing reports of skin reactions and discussed strategies for evaluation and management. RESULTS: Between 1994 and April 2002, 35 events were classified as severe skin reactions worldwide: erythema multiforme (8), Stevens-Johnson syndrome (10), toxic epidermal necrolysis (11), toxicoderma (3), and bullae (3). Unadjusted incidences were 6-9 per 10,000 radiotherapy patients and 0.8-1 per 10,000 chemotherapy patients. In 10 patients (29%) amifostine was continued after cutaneous signs and symptoms appeared. CONCLUSIONS: Practical recommendations for practicing clinicians were developed. Cutaneous evaluation for rash, ulceration, or lesions-particularly on lips/mucosa, palmar/plantar surfaces, and the trunk-should be performed before amifostine administration. Reactions can be classified as local injection site/radiation port reactions or non-injection site reactions; and non-injection site reactions with associated fever or constitutional symptoms must be differentiated from radiation-induced dermatitis or cutaneous reaction with another etiology. Amifostine should be permanently discontinued for severe skin reactions or reactions associated with constitutional symptoms not known to be due to any other etiology. Increased physician awareness, proper patient management, monitoring before administration, and early intervention/discontinuation for non-injection site reactions may reduce the incidence of cutaneous reactions and enhance amifostine safety.
Adolescent↗
[Pharmacology and toxicology of etofenamate. 2].
1. Since the anti-inflammatory effect of 2-(2-hydroxyethoxy)-ethyl-N-(a,a,a-trifluoro-m-tolyl)anthranilate (etofenamate, TVX 485, Rheumon Gel) is occasionally stronger than that of flufenamic acid and as its toxicity is in the same range as that of the latter, a wider therapeutic margin may be expected for etofenamate in therapeutic use of Rheumon gel. 2. In subchronic oral administration, rats tolerated 22 mg/kg and dogs 100 mg/kg without any signs of toxicity. Sub-chronic cutaneous administration of Rheumon gel in pigs (2 g/kg) likewise showed no signs of toxicity. Thus, an adequate safety factor would seem to exist, bearing in mind the comparative daily dose in man of approx. 0.3 g gel/kg body weight. In histological tests oedema of kidney papillas or degeneration of papillas, respectively, could not be seen. 3. In the dose range tested, etofenamate shows no signs of teratogenic or fetotoxic effects in either rats or rabbits. 4. The evidence of the cutaneous absorption of etofenamate from Rheumon gel could be demonstrated by the biological effect in animal experiments.
Animals↗
Pharmacological study of cantharidin-induced ear inflammation in mice.
Cantharidin applied to the Swiss mouse ear induced a clearly observable inflammatory reaction after 6 hr, maximal after 24 hr, and persisting several days. Desonide and hydrocortisone strongly inhibited the acute (6 hr) and delayed (24 hr) phases after their local application, while, after oral treatment, a reduction in the acute edema was obtained only when using high doses. The cutaneous application of high doses of mepyramine, disodium cromoglycate, methysergide, and (at a quite lower level) cimetidine reduced the 6-hr inflammation. Phenylbutazone and acetylsalicylic acid showed little activity on the same phase after their cutaneous administration. All the nonsteroid compounds produced little or no effect on the 24-hr inflammation after their cutaneous application and were quite inactive on both phases after their systemic treatment. The cantharidin-induced inflammatory reaction in Swiss mouse seems thus to be characterized by two phases. The chronic delayed phase is an example of chronic inflammation without the involvement of immunological processes. Histamine and serotonin might be involved in the acute inflammation.
Administration, Oral↗
Cutaneous blood flow and local sweating after systemic atropine administration.
Localized cutaneous vasodilation (flush) is seen following systemic atropine administration. To verify calculated enhanced dry heat loss with actual changes in cutaneous blood flow, four men were studied in both control and atropine (0.025 mg.kg-1; im) experiments (Ta = 30 degrees C, Tdp = 7 degrees C) during moderate exercise (55% VO2 peak). Esophageal temperature (Tes) and arm sweating (ms) by local dewpoint were measured continously. Skin (forearm) blood flow (FBF) was measured twice each minute by venous occlusion plethysmography. Injection of atropine (2 mg) caused an increased sensitivity (+85%, p less than 0.01) in FBF to Tes with no change in the vasodilator threshold. An elevated Tes onset (0.3 degrees C, p less than 0.05) for sweating occurred with no change in the sensitivity of ms to Tes (-27%, p less than 0.20). No elevation in either forearm or Tsk occurred before the onset of vasodilation, however, both mean skin (Tsk) and local arm temperatures were higher in the atropine experiments after 15 min of exercise. Systemic atropine resulted in higher cutaneous vasodilation at the same core temperature with the local skin temperature following passively. The effect of systemic atropine in stimulation of increased cutaneous vasodilation is suggested to result by a combination of central and local responses which may be mediated through the release of vasoactive sustances.
Adult↗
In regard to Boccia et al.: assessment and management of cutaneous reactions with amifostine administration: findings of the ethyol (amifostine) cutaneous treatment advisory panel (ECTAP) (INT J RADIAT ONCOL BIOL PHYS 2004;60:302-309).
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Amifostine↗
Effect of a PAF antagonist, BN52063, on antigen-induced, acute, and late-onset cutaneous responses in atopic subjects.
Platelet-activating factor (PAF) is a potent phospholipid that has been implicated as a mediator of allergic inflammatory responses, since it may induce a biphasic response and eosinophil infiltration in the skin that is reminiscent of antigen-induced reactions after cutaneous administration in man. We have studied the effect of a PAF antagonist, the ginkgolide mixture, BN52063, to determine the role of PAF in antigen-induced cutaneous responses in a double-blind, placebo-controlled, crossover study in 10 atopic subjects. Two hours after ingestion of BN52063 (120 mg), the wheal-and-flare response to intradermal PAF (200 ng), but not to histamine (1 micrograms), was inhibited, as previously described in nonatopic subjects. The late-onset component of the response to allergen (8 hours after injection) was significantly attenuated from 2.89 +/- 0.76 cm3 to 1.41 +/- 0.58 cm3 (p less than 0.05). Although the early wheal response was reduced in 50% of subjects, it was not significant overall, nor was there any significant reduction in the flare response. These observations suggest that PAF contributes to the late inflammatory response to allergen that is known to be associated with an inflammatory cell (predominantly eosinophil) infiltrate. This lends support to the idea that PAF is a mediator of allergic inflammation and that PAF antagonists may have a therapeutic role in allergic diseases.
Acute Disease↗
Glutathione metabolism in mice is enhanced more with hapten-induced allergic contact dermatitis than with irritant contact dermatitis.
Cutaneous inflammation induced by electrophilic compounds involves irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD). Reduced glutathione (GSH) and related thiols have been postulated to play important roles in detoxification of electrophilic xenobiotics, protection of tissues against reactive oxygen species, and modulation of immunologic functions in normal and diseased subjects. The dynamic aspects of GSH metabolism, however, and its significance in patients with ICD and ACD remain to be clarified. The current study was carried out to elucidate the pathogenesis and possible involvement of GSH in both types of inflammation. Normal mice and mice sensitized with dinitrochlorobenzene (DNCB) were challenged by cutaneous administration of DNCB, and changes in GSH metabolism in skin and liver were determined. Kinetic analysis revealed that 24 h after challenge with DNCB, levels of hepatic glutathione and its secretion increased more markedly in the sensitized mice than in the unsensitized animals. Administration of buthionine-L-sulfoximine (BSO), a specific inhibitor of GSH synthesis, inhibited the increase in glutathione levels in the liver and the skin of both groups. Histologic examination revealed that cutaneous inflammation was enhanced by BSO more significantly in mice with ACD than with ICD. These results suggest that GSH might play an important role in the suppression of the immune reaction in mice with ACD.
Animals↗
Undesirable side effects of isoniazid and rifampin in largely twice-weekly short-course chemotherapy for tuberculosis.
Between January 1976 and June 1981, 814 patients with pulmonary tuberculosis were treated for 9 months with isoniazid (INH) and rifampin (RIF), daily for 1 month and twice weekly for the other 8 months. Overall success was achieved in 95% of the 586 patients who completed therapy: in 15 patients (2.9%), sputum cultures failed to convert to negative during therapy, and 10 patients (1.7%) have relapsed since stopping the chemotherapy. Major toxic effects occurred in 22 patients; in 14 during the daily phase and in 8 during the twice-weekly phase. Hepatic toxicity occurred in 13 patients during daily and in 5 during twice-weekly treatment, and it was caused by RIF in 5, INH in 10, and was undetermined in 3. Hematologic abnormalities developed in 4 patients: in 1 during the daily and in 3 during the twice-weekly phase. Minor side effects, which were not life threatening, were encountered in 62 patients: in 35 during the daily and in 27 during the twice-weekly therapy. These were gastrointestinal intolerance in 18, drug fever in 27 (including 11 with "flu-syndrome" during twice-weekly administration), cutaneous rashes in 14, and headache, general malaise, and weakness in 3. These side effects were produced by RIF in 43, by INH in 18, and the responsible drug was not identified in 1. Hypersensitivity reactions to twice-weekly administration of RIF were infrequent. Clinical surveillance for toxicity is preferred over routine and regular biochemical monitoring.
Adolescent↗
Onychomycosis. Agents of choice.
The management of onychomycosis has changed considerably in the past few years. The main trends have been improvement in the choice of evidence and cover of infections other than dermatophytosis, shortening of periods of oral therapy, and introduction of topical agents designed to treat nail disease. At present there have been almost no comparative studies of these different approaches, and choice is therefore largely based on enlightened guesswork coupled with personal experience. It is hoped that within the next few years such studies will be carried out to allow dermatologists to make an accurate choice based on appropriate scientific data.
Administration, Cutaneous↗
Peripheral NMDA and non-NMDA glutamate receptors contribute to nociceptive behaviors in the rat formalin test.
The present study demonstrates that local cutaneous administration of either the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist MK-801 or the non-NMDA glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) significantly attenuates formalin-induced nociceptive behaviors. Specifically, pretreatment with either drug reduced the magnitude and time course of lifting and licking behavior in the late phase of formalin pain; however, flinching behavior was not affected. In contrast, post-treatment of formalin pain with either antagonist did not affect lifting and licking behavior, although flinching behavior was mildly attenuated. We hypothesize that these actions result from blocking of peripheral glutamate receptors located on unmyelinated axons at the dermal-epidermal junction. These data suggest that peripheral glutamate receptors on cutaneous axons can be manipulated to reduce certain aspects of pain of peripheral origin. This route of administration offers the advantage of avoiding the side effects of systemic administration.
6-Cyano-7-nitroquinoxaline-2,3-dione↗
Atopic dermatitis with mononuclear phagocytic activity deficiency.
Five patients with atopic dermatitis, three males and two females, aged 2 to 17 years, had positive reactions to air allergens (Dermatophagoides pteronyssinus and/or farinae). All the patients suffered from severe recurrent dermatophytosis that responded poorly to antifungal treatment. The results of immunologic evaluation by laboratory tests were normal, except for a decrease in the ingestion phase by mononuclear phagocytes. After diagnosis of immunodeficiency, ketoconazole shampoo was used prophylactically and at the very first signs of recurrence of dermatophytosis, systemic antifungal treatment was started, without concurrent use of macrolides and with monitoring of hepatic function. The fungal infections responded well to this treatment and the patients' quality of life markedly improved.
Administration, Cutaneous↗
The role of gustatory flushing in Frey's syndrome and its treatment with botulinum toxin type A.
After parotid surgery, gustatory sweating and flushing occur more frequently, the former reportedly in 15-100% of cases, while no reliable data are available for the latter. Although botulinum toxin (BoNT) is effective in controlling sweating, little is known about its effect on flushing. In 17 patients suffering from Frey's syndrome after parotid surgery, we studied the gustatory flushing phenomenon as compared to gustatory sweating, analyzing their frequency, area, type of stimulus and response to BoNT administration. Cutaneous blood flow (CBF) was monitored by laser Doppler flowmetry (LDF) on affected and unaffected areas of the cheek in basal conditions and after meals, before and then 1 month after starting the BoNT injections. The Minor test was used to identify the sweating area. Flushing was observed in 7 of 17 patients after masticatory activity, spicy meals or citrus fruits. No clinical data correlated with any presence of flushing. Flushing regressed completely after BoNT administration and CBF reached similar values in the affected and unaffected sites. No adverse effects were observed. BoNT administration proved an effective and safe treatment for gustatory sweating and flushing in patients with Frey's syndrome.
Adult↗