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Evaluation of topical antipsoriatic treatment by chromametry, visiometry and 20-MHz ultrasound in the psoriasis plaque test.

The antipsoriatic effects of two topical antipsoriatic agents, betamethasone valerate (Betnovate) and calcipotriol (Daivonex), and a pure nanocolloid gel were assessed in 10 patients with chronic plaque-type psoriasis in a modified psoriasis plaque test. Three noninvasive bioengineering methods were applied to measure antipsoriatic effects: chromametry for objective evaluation of erythema; visiometry, a method for profilometry, and 20-MHz skin ultrasound for the measurement of skin thickness as a parameter of inflammatory infiltration and psoriatic hyperproliferation of the epidermis. Regarding inflammation parameters such as skin thickness (infiltration) and erythema (dilatation of vessels and hyperperfusion), the steroid preparation Betnovate proved to be significantly most effective in our study. Daivonex showed significant decreases in the skin roughness parameters, underlining its antiproliferative effect. The nanocolloid carrier was significantly effective in thickness reduction, this effect being most probably due to occlusion. 20-MHz ultrasound, chromametry and visiometry proved to provide multiparameter assessment of treated and untreated psoriatic skin and can be recommended as objective and reproducible measurements for further studies.

Administration, Topical↗

Effects of widespread dermatitis and topical steroid therapy on thyroid function tests.

Five patients with extensive dermatitis and 5 normal subjects were treated with topical betamethasone valerate 0.1% (Betnovate, Glaxo) 19-34 g daily for 4 days. Thyroid functions tests were not affected by the treatment but some patients with widespread inflamed skin demonstrated altered serum thyroid hormone levels as a result of the euthyroid sick syndrome.

Administration, Cutaneous↗

Influence of the base on the results of clinical trials with topical corticosteroids.

A comparative trial between betamethasone valerate and halcinonide has shown the former to be superior, thus contradicting the results from other trials. It is thought that the discrepancy is due to differences in the nature of the preparations used in the various studies. It is suggested that note is made of the base used in trials before final conclusions about the efficicacy of steroids are made.

Administration, Topical↗

Treatment of melasma (chloasma) by local application of a steroid cream.

15 patients with melasma were treated with betamethasone 17-valerate in a cream base containing DMSO. One patient with secondary pigmentation was also entered in the trial. In nine patients results were favourable and in three results were moderate. This effect could be ascribed to the steroid.

Administration, Topical↗

Methods for the assessment of skin atrophogenicity of topical corticosteroids.

A review is given of the methods used to estimate the atrophogenicity of corticosteroids after topical use. An experiment was performed in human volunteers in which measurement of mean epidermal thickness showed that the adverse effect of betamethasone 17-valerate exceeded that of placebo, hydrocortisone 17-butyrate ranking in between. To evaluate the atrophy caused by corticosteroid on dermis the radiological technique of Black was further modified and adapted. With this method clobetasol proprionate proved to give significantly more atrophy compared with a placebo. The atrophy disappeared 2 months after treatment was stopped.

Administration, Topical↗

Comparative study of triamcinolone acetonide and hydrocortisone 17-butyrate in rosacea with special regard to the rebound phenomenon.

The clinical efficacy and the rebound phenomenon were studied in a left-right double-blind trial comparing triamcinolone acetonide (TA) and hydrocortisone 17-butyrate (HC 17-B, Locoid). The trial comprised 19 patients with rosacea-like dermatitis of whom 7 did not receive treatment and 12 were pretreated with betamethasone valerate (BMV). Tetracyclince was given all the time as additional treatment. Clinically there was no significant difference between TA and HC 17-B. No rebound phenomenon was observed. If corticosteroids are to be used at all in rosacea or resoacea-like dermatitis, preference is given to HC 17-B.

Administration, Topical↗

Hyperlipoproteinemia, atherosclerosis and gemfibrozil.

Elevated levels of serum cholesterol have long been associated with an increased risk of both the occurrence and the progression of coronary atherosclerosis. The use of dietary therapy to reduce elevated lipid labels has received widespread attention, but like other therapy requiring behavioral modification has met with only partial success in most patients. Little wonder that drugs which lower lipids have been utilized to supplement the effect of diet in hyperlipidemia subjects. Currently available hypolipidemic agents are far from ideal in their effectiveness and lack of side effects, so the search for more potent, safer drugs has been intense. This paper reports on the use of one such agent, gemfibrozil; and its comparison with clofibrate and placebo. Gemfibrozil (CL719, 2,2-dimethyle-5-(2,5 xylyloxy) valeric acid is a substituted phenoxy alkyl acid which has been shown to decrease lipids in hyperlipidemia subjects. A short term study using 1200 mg of gemfibrozil daily demonstrated reduction in total serum cholesterol, triglyceride and apo B levels, and a concomitant rise in HDL cholesterol levels. A long term study of the effect so gemfibrozil showed that the drug had a more pronounced effect on triglyceride then cholesterol, that it had few side effects and the effect was sustained. A recent study from New Zealand demonstrated that gemfibrozil, compared to placebo, lowered plasma cholesterol, triglyceride and VLDL levels and raised HDL levels.

Adult↗

Comparative merits of two topical corticosteroid antimicrobial drugs.

The anti-inflammatory and antimicrobial activities of two topical creams, one containing halcinonide, neomycin and nystatin (HNN), and the other betamethasone valerate, gentamicin, iodochlorhydroxyquin and tolnaftate (BGI), were compared in a randomized, parallel study of 154 patients (eighty-seven secondarily infected eczematous dermatoses; sixty-seven cutaneous candidiasis). Repeated clinical assessments showed that the two creams produced equivalent therapeutic responses both in patients with infected eczematous lesions and candidiasis. HNN and BGI creams eradicated the bacterial pathogens isolated prior to treatment in 80% and 76%, respectively, of the patients with eczematous dermatoses. The organism most frequently isolated in these patients was S. aureus. Local irritation prompting discontinuance of therapy occurred in just one patient receiving HNN, and two patients receiving BGI.

Administration, Topical↗

Halomethasone (C 48.401-Ba) for the topical treatment of common dermatoses.

C 48.401-Ba cream, containing 0.05% halomethasone was compared in a double-blind between-patients trial with a cream containing 0.1% betamethasone valerate in forty-eight patients suffering from atopic dermatitis and in thirty-nine patients suffering from seborrhoeic dermatitis. A similar comparison was made with ointments containing the same concentration of active ingredient in forty-six patients suffering from atopic dermatitis. Both ointments were also compared in a within-patient double-blind trial in thirty patients suffering from psoriasis. The analysis of the results showed that for the treatment of the above-mentioned dermatoses, both drugs, the cream as well as the ointment, are equally effective and well tolerated.

Administration, Topical↗

Steroid-induced vasoconstriction: glucocorticoid antagonist studies.

Two currently used steroids (clobetasone butyrate and betamethasone valerate) reproducibly cause vasoconstriction on topical application to human forearm skin. Progesterone, deoxycorticosterone, testosterone, and estradiol, even at 100- to 200-fold higher concentrations, cause no vasoconstriction when applied alone. Applied with clobestasone butyrate, testosterone and estradiol are without antagonist effect; in contrast, both progesterone and deoxycorticosterone antagonize the vasoconstrictor response in a dose-related fashion, with a half-maximal effect at 20-30 times the concentration of clobetasone. Neither progesterone nor deoxycorticosterone affects the vasoconstriction produced by the intradermal injection of epinephrine. In most glucocorticoid-responsive systems, progesterone and deoxycorticosterone are glucocorticoid antagonists, and estradiol and testosterone are inactive. We interpret these studies as evidence that the vasoconstrictor effects of topical steroids are mediated by occupancy of classical glucocorticoid receptors, rather than by nonspecific pharmacological mechanisms.

Adult↗

Studies on topical antiinflammatory agents. I. Synthesis and vasoconstrictive activity of corticosteroid 17-succinyl esters.

A series of 17-succinyl derivatives of four corticosteroids was prepared. They were tested for vasoconstrictive activity in humans, using 9 alpha-fluoro-11 beta, 21-dihydroxy-16 beta-methyl-17 alpha-valeryloxy-1,4-pregnadiene-3,20-dione (betamethasone 17-valerate, BV) as a standard. The activities of the 21-chloro 17-methylsuccinate compounds (6A, 6C and 6D) were greater than that of BV. A structure-activity relationship study showed that the activities of the 21-chloro 17-methylsuccinates were more potent than those of the corresponding 21-esters.

Administration, Topical↗

[Pharmacological study on hydrocortisone 17-butyrate 21-propionate (author's transl)].

The topical and systemic anti-inflammatory activities of hydrocortisone 17-butyrate 21-propionate (HBP) were studied. The systemic anti-inflammatory activities of HBP and reference steroids were examined for their effects on dinitrochlorobenzene dermatitis, carrageenin edema, cotton pellet granuloma and adjuvant arthritis in rats and by the delayed allergic edema test in mice. The topical anti-inflammatory activities of these steroids were examined for their effects on croton oil dermatitis, croton oil ear edema, carrageenin edema and cotton pellet granuloma in rats. Furthermore, effects of these steroids on liver glycogen deposition in mice, thymolysis, and decrease of serum corticosterone level in rats were examined. Systemically administered HBP was less potent than betamethasone 17-valerate (BV), but was almost equal to hydrocortisone 17-butyrate (HB) in anti-inflammatory activity, and its effects on liver glycogen deposition, thymolysis, and the decrease of serum corticosterone level. However, the topical anti-inflammatory activity of HBP was more potent than that of BV and HB, although in the same experiment, thymolytic activity of HBP was less potent than that of BV, but was almost equal to HB. The inhibitory effect of HBP on hypotonic induced hemolysis was weaker than that of BV, but was stronger than that of HB in vitro. The affinity of HBP was higher than that of BV and HB to polymorphonuclear leucocytes used as the inflammatory cells in vitro. On the other hand no marked difference was observed in the affinity to erythrocytes used as the non-inflammatory cells in vitro. These results suggest that HBP is a useful drug which has superior topical anti-inflammatory activity, but has a weak systemic effect.

Animals↗

The combined effect of topical CX-659S, a novel diaminouracil derivative, with topical corticosteroid on the three types of allergic responses in mice or guinea pigs.

CX-659S ((S)-6-amino-5-(6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxamido)-3-methyl-1-phenyl-2,4(1H,3H)-pyrimidinedione), a newly discovered anti-inflammatory compound, exerts inhibitory effects against picryl chloride-, oxazolone-, and dinitrochlorobenzene-induced acute contact hypersensitivity responses (CHRs) characterized by Th1-type reactions. Furthermore, this compound suppressed chronic CHRs characterized by Th2-type reactions, which is well known to mimic many, if not all, events occurring within the lesional skin of patients with atopic dermatitis (AD). The present study was conducted to determine the combined effect of topical CX-659S with topical corticosteroid on immediate type (ITR), late type (LTR), and delayed type hypersensitivity (DTHR) allergic reactions that are involved in AD. An ineffective dose of CX-659S (0.03 mg/ear) combined with betamethasone valerate (BV) significantly potentiated inhibitory activity of BV alone (0.1 micro g/ear and 0.3Shizuokag/ear) on both the ITR and the LTR in mice with the ovalbumin (OVA)-induced biphasic cutaneous reaction. Furthermore, the combined effect of CX-659S with BV was also observed on dinitrochlorobenzene (DNCB)-induced DTHR in guinea pigs. These results indicate that CX-659S has a combined effect with corticosteroids on every ITR, LTR, and DTHR. Proper treatment with corticosteroids for a safe and effective treatment of AD is needed. Thus, the combination therapy of topical CX-659S with topical corticosteroid would be one of the potential approaches for devising a proper treatment with corticosteroids.

Administration, Topical↗

[Studies on antigenicity, phototoxicity and other specific toxicities of hydrocortisone 17-butyrate 21-propionate (HBP) (author's transl)].

The present experiments were undertaken to determine the antigenicity and other toxicities of HBP; such as phototoxicity, photosensitivity, ulcerogenicity, adrogenic-myotropic, estrogenic and progestational activities, and mutagenicity. No antibody formation and delayed type skin reaction of HBP were seen in rabbits. Active systemic anaphylaxis was not observed in guinea pigs challenged by HBP. In the phototoxicity and photosensitivity test, 0.1% HBP ointment, 0.1% HBP cream and 10% HBP acetone solution did not show any skin reaction with or without irradiation of ultraviolet light. Repeated subcutaneous administration of HBP irritated the gastric and intestinal mucosa dose dependently in rats as hydrocortisone 17-butyrate and betamethasone 17-valerate (BV). HBP had neither androgenic-myotropic nor estrogenic activity, but antiestrogenic activity was observed. The progestational activity of HBP in immature rabbit pretreated with estrone was less potent than BV. In the mutagenicity test os HBP investigated by the reverse mutation according to the method by Ames, no significant increase in the number of revertants was observed in the presence or absence of S9 mixture.

Administration, Topical↗

[Studies on toxicity of hydrocortisone 17-butyrate 21-propionate -2. Subacute toxicity in rats by subcutaneous administration (author's transl)].

Subacute toxicity of hydrocortisone 17-butyrate 21-propionate (HBP), a new synthetic corticosteroid, was studied in rats, using betamethasone 17-valerate (BV) and hydrocortisone 17-butyrate (HB) as the reference drugs. HBP was subcutaneously injected to rats at the daily doses of 0.08, 0.4, 2.0, 10 and 50 mg/kg for 30 days. BV and HB were also administered at the daily doses of 0.08, 0.4 and 2.0 mg/kg. The recovery test was performed for 4 weeks after administration of HBP, BV and HB. The suppression of body weight gain by HBP was observed at the doses more than 0.08 mg/kg in male and more than 2.0 mg/kg in female rats. In addition, at the doses more than 0.4 mg/kg of HBP induced the dose-dependent symptoms such as decrease in the number of circulating white blood cells, lymphocyte counts and S-ALP level, increase in total cholesterol, GOT and GPT level of serum, and regressive changes in adrenals, lymphatic and hematopoietic tissues. There were fatal cases in rats given 50 mg/kg of HBP. These changes are considered to be common phenomena to other corticosteroids, and less toxic in female than male rats. Changes of symptoms caused by the administration of HBP 2.0 mg/kg were almost recovered after withdrawal. The toxicities of three corticosteroids were in the order of BV greater than HB greater than or equal to HBP in strength. As the result, maximum non-toxic dose of HBP was estimated to be 0.08 mg/kg in female and lower than that in male rats.

Administration, Topical↗

[Studies of toxicity of hydrocortisone 17-butyrate 21-propionate -5. Chronic toxicity in rats by percutaneous administration (author's transl)].

Chronic toxicity of a new synthetic corticosteroid, hydrocortisone 17-butyrate 21-propionate (HBP), was investigated in rats of both sexes. HBP was percutaneously given to rats with 0.1%, 0.5% cream and ointment at the daily dose level of 150 mg per 100 g body weight for 6 months. For the comparison, the percutaneous toxicity with 0.12% betamethasone 17-valerate (BV) cream and ointment, and 0.1% hydrocortisone 17-butyrate (HB) cream and ointment at the daily dose level of 150 mg per 100 g body weight were studied. Rats receiving HBP showed the dose-dependent changes such as the suppression of body weight gain and food intake, emaciation, decrease in the number of white blood cells and lymphocytes, total protein, increase in the number of red cells, hematocrit, hemoglobin, blood sugar and total cholesterol, regressive changes in adrenal cortex, lymphatic and hematopoietic tissues and skin, and gastric erosion, which have been well known as toxic effects of synthetic corticosteroids. These findings were comparatively high toxic in male, and almost disappeared in rats elapsed recovery time of month after withdrawal of HBP. The toxicities of HBP, BV and HB were qualitatively same. However, the grade of effects of HBP toxicity was similar to that of HB, weaker than of BV.

Administration, Topical↗

The role of poly-hydroxy-alkanoate form in determining the response of enhanced biological phosphorus removal biomass to volatile fatty acids.

Anaerobic-aerobic batch experiments indicated that poly-hydroxy-alkanoate (PHA) form was important in determining the net phosphorus removal resulting from different volatile fatty acids (VFAs). Poly-3-hydroxy-butyrate (3HB) content was found to correlate fairly well with higher observed aerobic phosphorus uptake per unit PHA carbon degraded. Poly-3-hydroxy-valerate (3HV) correlated with lower aerobic phosphorus uptakes per unit PHA carbon degraded. These experiments, conducted with synthetic wastewater, imply that VFA speciation might have a significant effect on aerobic phosphorus uptakes and net phosphorus removal. In addition, the model parameter fP.UPT (Barker and Dold, 1997) could vary with the proportion of acetic to propionic acid received (i.e., the acetic/propionic acid ratio may be an important parameter for these systems). Carbohydrate data implied that the lower aerobic phosphorus uptake resulting from 3HV might have been caused by a greater fraction of PHA carbon shunting to carbohydrate biosynthesis during aerobiosis.

Acetic Acid↗

Ultrastructure of murine epidermis treated with the vitamin D3 analogue KH-1060.

A new highly potent analogue (KH-1060) of vitamin D3 has been recently shown to stimulate the growth and differentiation of keratinocytes. This study was intended to determine the effects of this new analogue on epidermis at the ultrastructural level. KH-1060 was applied topically on the backs of hairless mice for 4 weeks; the skin was then studied by routine electron microscopy. The effects were compared with those of betamethasone-17-valerate and with concomitant treatment of KH-1060 following betamethasone. KH-1060 stimulated normal function of keratinocytes and formed a thick epidermis. The ultrastructure of the thick epidermis represents an enhanced normal process of keratinization and proliferation. Moreover, KH-1060 diminished the atrophogenic effects of betamethasone.

Administration, Cutaneous↗