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These studies explored the effects of oral pharmacological doses of glucocorticoids on the normal small intestine of the adult rat. Short-term (7 days) prednisolone had little effect on mucosal structure or cell kinetics but enhanced the maximum absorptive capacities of the jejunum and ileum for galactose. This was due to an increase in carrier-mediated transport in the individual enterocytes and not to a change in the cell population. Activities of brush border enzymes were elevated and turnover studies indicated an increased rate of synthesis of brush border proteins associated with an enhanced glycoprotein content of the microvillus membrane. Subcellular fractionation studies demonstrated a large increase in the membrane-bound ribosomal RNA content of the enterocytes consistent with an enhanced synthesis of membrane proteins. These findings implicate a direct action of prednisolone on the enterocytes to increase their absorptive and digestive capacities by the induction of specific functional proteins. These effects on the absorptive and digestive functions of the small intestine were sustained with long-term (28 days) prednisolone feeding. An equivalent long-term oral dose of betamethasone-17-valerate, a locally rather than a systemically active glucocorticoid, had a similar effect on the enterocytes. However, an inhibition of crypt cell turnover resulted in a marked hypoplasia and hence no net change in the functional capacity of the mucosa. These findings emphasise the separate and opposing actions of glucocorticoids on the adult mucosa, on the one hand to stimulate enterocyte function, but on the other to reduce the enterocyte population. The predominant activity appears to be a function of each individual steroid. The predominant stimulatory action of prednisolone was further emphasised by investigating the effects of this glucocorticoid on the adapted ileum following jejunal resection. Indeed, short-term prednisolone enhanced the adaptive hyperplasia in the ideal remnant by increasing the functional capacity of the expanded population of enterocytes.
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It was observed that the permeation of BM across ASC from all the formulations tested was higher by factors 9.7-27.7 than that from the same formulations permeating through SC, while the permeation sequence of the tested formulations was almost the same for SC and ASC. Afterwards the effect of the dilution of the semisolid formulations containing BM-17-V 0.1% weight on their permeation through SC was examined by mixing them with different ointments and a cream base. The permeation rate of BM from the dilution of Soderm ointment with WO and from WO diluted with different formulations from the German Pharmacopoeia were very similar.
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Mean reduction of the Modified Psoriasis Area and Severity Index (M-PASI) score after 28 days of treatment was considered the primary outcome measure, which was analyzed on an intention-to-treat basis. The secondary outcome was a visual analog scale score for itching.
The objective was to compare the in vivo distribution profiles of betamethasone 17-valerate (BMV) across the stratum corneum (SC) following (a) delivery from gelled and un-gelled formulations, and (b) two different skin cleaning procedures at the end of the application period. BMV was dissolved in gelled and un-gelled vehicles comprising either medium chain triglycerides (MCT) or a brand microemulsion (ME). The BMV concentration was adjusted to 80% of saturation and applied to the forearms of healthy volunteers. After 2 h, the treated skin site was cleaned either with a dry paper towel or with an isopropyl alcohol swab, and the SC was then progressively removed by repeated adhesive tape-stripping. BMV distribution profiles across the SC showed reasonable reproducibility, and that delivery from the ME was significantly superior to that from MCT. Gelled vehicles were less efficiently removed from the skin surface by dry wiping than un-gelled formulations. Removing excess formulation more aggressively with isopropyl alcohol resulted in a lower apparent uptake of drug into the SC. Excess gelled formulation may be trapped in the skin 'furrows', and requires an efficient skin cleaning procedure to ensure its complete removal.
Progressive pigmented purpura (Schamberg's disease), a form of purpura pigmentosa chronica, is a lymphocytic capillaritis of unknown etiology and obscure pathogenesis. Our purpose was to assess the expression of cell membrane antigens (CD3, CD4, CD1a, CD36), of adhesion receptors (leukocyte function adhesion 1, LFA-1, endothelial leukocyte adhesion molecule 1, ELAM-1) intercellular adhesion molecule 1, ICAM-1), and the intercellular relationships in the early phase of the disease.
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To compare hair regrowth and side effects of topical betamethasone valerate foam, intralesional triamcinolone acetonide and tacrolimus ointment in management of localized AA.
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The cosmetic properties of topical formulations are important parameters for the adherence to treatment, where modern oil-in-water emulsions are considered more acceptable compared with ointments. After application of an emulsion to the skin, the concentration of active ingredients in the formulation residue on the skin will increase, due to evaporation of volatile ingredients.
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Test areas treated with indomethacin 60 min and 5 min before irradiation showed the significantly lowest visual erythema scores and no significant changes in skin mechanical parameters. At all other test sites, a significant decrease in elasticity parameters (Ue, Ur, Ua/Uf, Ur/Uf) and an increase in viscoelasticity parameters (Uv, Uv/Ue) of the skin were observed. No significant changes of epidermal hydration were found at any of the test sites.
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Eosin has a short-term effect similar to topical steroids. The low cost of eosin treatment and its limited collateral effects suggest that eosin could be an effective steroid-sparing agent in the initial phase of psoriasis treatment.
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In a double-blind study, topically applied caffeine 30%-hydrocortisone 0.5% in hydrophilic ointment was compared to betamethasone valerate 0.1% cream and to hydrocortisone 0.5% in hydrophilic ointment. Eighty-three patients were evaluated over a three-week period for pruritus, erythema, scaling, lichenification, excoriation, oozing, and global impression. The betamethasone and caffeine-hydrocortisone groups performed significantly better than the hydrocortisone group on three of the seven scales: lichenification, excoriation, and global impression. Also, the betamethasone group differed significantly from the hydrocortisone group on six of the seven scales, but did not differ significantly from the caffeine-hydrocortisone group on any scale. It is suggested that caffeine is effective because it elevates local levels of cyclic adenosine-3',5'-monophosphate by inhibiting phosphodiesterase.
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Post-occlusive reactive hyperaemia is the temporary increase of blood flow in a tissue following transient vascular obstruction, and has recently been proposed as an in vivo method for ranking topical corticosteroid potency. We investigated in vivo vascular reactions before and during post-occlusive hyperaemia using laser-Doppler flowmetry and reflectance spectroscopy (RS). RS enables resolution of in vivo erythema into deoxygenated (venous) [DOH] and oxygenated (arterial) haemoglobin (OH) components (expressed in arbitrary units, AU). Using a randomized 24-h occlusive exposure in 10 healthy volunteers the effects of a corticosteroid (betamethasone-17-valerate), a non-steroidal anti-inflammatory drug (NSAID) [indomethacin], an antihistamine (diphenhydramine), or vehicle, were studied before and during post-occlusive hyperaemia. The 24-h vehicle exposure decreased total haemoglobin (composed of a small increase in OH [P < 0.001] and a greater decrease in DOH [P < 0.005], [OH, 0.23 +/- 0.18 AU; DOH, 0.28 +/- 0.12 AU]). The blood flow increased 7.1% to 28 +/- 8 AU (P > 0.05). Betamethasone-17-valerate exposure decreased total haemoglobin further (OH, 0.10 +/- 0.09 AU [P < 0.005]; DOH, 0.18 +/- 0.08 AU [P < 0.05]), which corresponded to a 15% blood flow decrease (P < 0.05). Indomethacin reduced OH to 0.18 +/- 0.12 AU (P < 0.02) and increased DOH slightly, with a trend towards decreased blood flow (P > 0.05). Diphenhydramine caused no significant changes in RS or laser-Doppler flowmetry readings before post-occlusive hyperaemia. Post-occlusive hyperaemia increased total haemoglobin maximally at the first observation time (OH, 0.63 +/- 0.13 AU; DOH, 0.31 +/- 0.11 AU [P < 0.001]).(ABSTRACT TRUNCATED AT 250 WORDS)
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We reported previously that the betamethasone derivative betamethasone dipropionate behaves as an anti-glucocorticoid in rat endotoxin-induced uveitis (EIU). In the present study, we produced EIU in guinea pigs and investigated the effects of betamethasone dipropionate on the EIU.
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The effects of topical application of glucocorticoids on the epidermal beta-adrenergic adenylate cyclase response were investigated. A significant increase in this receptor response was observed 24 h following topical application of potent glucocorticoid ointments (0.12% betamethasone-17-valerate, 0.05% clobetasol-17-propionate). The application of a relatively weak glucocorticoid, hydrocortisone-17-butyrate, revealed no augmentation effect. There was no significant difference in other adenylate cyclase responses (adenosine-, and histamine-) between control and glucocorticoid-treated epidermis. UVB irradiation is known to augment the beta-adrenergic response of epidermis. Comparison of the effects revealed that topical glucocorticoid treatment had less effect than UVB irradiation, and when the UVB irradiation was combined with glucocorticoid treatment, the beta-adrenergic augmentation effect was not enhanced. Cyclic AMP phosphodiesterase activities were not significantly altered by the glucocorticoid-, UVB-, or combined treatments. Our data indicate that epidermal beta-adrenergic adenylate cyclase response is affected by topical application of 'potent' glucocorticoids in vivo. Although the effect is weaker than that induced by UVB irradiation, we believe the system might be a useful tool for dissecting the glucocorticoidal potency of topical preparations using the epidermal keratinocyte response in vivo.
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Ninety-nine patients with secondarily infected eczema were allocated at random to receive 10-days' treatment with either 2% fusidic acid plus 0.1% betamethasone cream or 0.1% gentamicin plus 0.1% betamethasone cream. Both preparations were applied to the lesions twice daily and assessment of the signs and symptoms was carried out before, after 2 to 4 days, and after 7 to 12 days of treatment, severity being rated on a 4-point scale. Bacteriological tests were carried out before and after treatment. The results showed that the combination with fusidic acid was marginally superior in clinical effect. Staphylococcus aureus was the most commonly isolated pathogen from eczematous lesions (86%) and fusidic acid showed the lowest resistance rate (9%), followed by gentamicin (21%). Chloramphenicol, neomycin and tetracycline showed resistance rates from 48% to 59%.
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Topical calcipotriol is a vitamin D3 analogue which influences keratinocyte proliferation and differentiation. Its efficacy in cutaneous lichen planus has not been well evaluated.
To evaluate the efficacy, tolerability and safety of BVF treatment in patients with mild-to-moderate AA.
Plasminogen activation is a widely documented physiological phenomenon in which plasminogen activators (mainly urokinase and tissue type plasminogen activator) transform the zymogen plasminogen into the wide-spectrum proteinase plasmin. We show here that psoriatic epidermis is provided with abnormal plasminogen activator activity, mainly dependent on the activity of tissue type plasminogen activator and that this abnormal activity can be reversed with common topical treatments (i.e. anthralin, and 0.1% betamethasone valerate cream). We also report abnormal immunohistochemical localization of plasminogen, urokinase and tissue type plasminogen activator in psoriatic epidermis which returned to normal after the topical treatments. These data suggest a major role of plasminogen activation in the pathogenesis of psoriasis.
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Both topical pimecrolimus and topical tacrolimus are more effective than placebo treatments for atopic dermatitis, but in the absence of studies that show long term safety gains, any advantage over topical corticosteroids is unclear. Topical tacrolimus is similar to potent topical corticosteroids and may have a place for long term use in patients with resistant atopic dermatitis on sites where side effects from topical corticosteroids might develop quickly. In the absence of key comparisons with mild corticosteroids, the clinical need for topical pimecrolimus is unclear. The usefulness of either treatment in patients who have failed to respond adequately to topical corticosteroids is also unclear.
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A 4 week study was undertaken of patients with at least moderately severe dermatoses as judged by scoring of a target lesion. Weekly global improvement was assessed, as well as change in target lesion scores. Local side effects were noted including observation of atrophy.
The present clinical study demonstrates for the first time that the effective and well tolerated therapeutic efficacy of glycolic acid scalp lotions is enhanced when used in conjunction with a 0.1% betamethasone scalp application against scalp psoriasis. This potential offers the practising dermatologist with novel treatment modes against severe skin conditions by combining topical corticosteroid with exfoliative agent therapy.
Female NC/Nga mice in which dermatitis had been induced with Dermatophagoides farinae were divided into six groups: 1) a betamethasone group (betamethasone ointment, six times a week), 2) an FTY720 group (FTY720, orally, three times a week), 3) an FTY720 plus betamethasone ointment group, 4) an ointment base group (ointment base, six times a week), 5) an FTY720 plus ointment base group and 6) a placebo group (vehicle alone). The therapeutic efficacy was evaluated in terms of the severity of dermatitis and histochemical observations after two weeks of treatment.
The theraprutic efficacy of inhaled beclomethasone dipropionate and inhaled betamethasone valerate in chronic asthma has been studied in 14 treatment centres in 158 patients who had previously been taking prednisone tablets regularly. Doses of 400 mug daily of beclomethasone dipropionate and a dose of 800 mug daily of betamethasone valerate allowed approximately 80% of patients to discontinue prednisone initially and 60% to remain off daily prednisone for 24 weeks. A mean reduction in daily prednisone dose of 8 mg was achieved by patients inhaling corticosteroids whilst placebo inhaler permitted a 5 mg reduction. The three inhaled corticosteroid preparations were equally effective in facilitating prednisone reduction and provided equally good control of asthma, alone or as an ancillary to prednisone. The higher dose of beclomethasone dipropionate was superior to the lower in permitting more patients to remain off daily prednisone for the period of the trial. Although 82% of patients recovered a normal adrenal response to tetracosactrin 24 weeks after prednisone was discontinued and inhaled corticosteroids subsituted, 18% still showed some suppression of adrenal function. There was no significant difference between the treatment groups in this.