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Comparison of 0.1% halcinonide with 0.05% betamethasone dipropionate in the treatment of acute and chronic dermatoses.

A 4-week, bilateral, controlled study was carried out in 53 patients with various acute and chronic dermatoses to compare the effectiveness of 0.1% halcinonide in a water-miscible base, applied once daily, with 0.05% betamethasone dipropionate cream applied twice daily. Patients' response to treatment was assessed at the end of each week. Halcinonide proved to be equally as effective as betamethasone dipropionate in most and superior in some patients with psoriasis, lichen chronicus simplex, and atopic and neurodermatitis. There was also a prompt response to once daily treatment with halcinonide in patients with contact dermatitis, eczema of the hands, and more serious cases of eczema nummulare and allergic skin reactions, many of whom had failed to respond to previous topical steroid therapy. Both preparations were well tolerated and side-effects were noted in only 1 patient with psoriasis whose condition was aggravated by halcinonide. Only 3 patients had a relapse during the 1-month follow-up period after treatment was stopped.

Acute Disease↗

Local treatment of psoriasis with desoxymethasone and betamethasone 17,21-dipropionate: a double-blind comparison.

A double-blind comparison of the effectiveness of 0.25% desoxymethasone and 0.05% betamethasone 17,21-dipropionate creams was carried out in 40 patients with symmetrical, chronic psoriatic lesions. The lesions were pre-treated for 1 week with an inactive cream base and then the trial preparations were applied, without occlusion, to one or other side at random twice daily for 21 days. Overall response to treatment and the effect of the two topical steroids on scaling, induration, erythema, and pruritus were assessed at the start of and 4, 7, 14, and 21 days after the start of active treatment. The results indicated a better but not statistically significant response to desoxy-methasone. By the end of the trial period, the desoxymethasone-treated side was better in 22.5% of cases compared with 10% of cases in the betamethasone dipropionate-treated side. No side-effects of treatment were observed.

Administration, Topical↗

Differential expression of myometrial oxytocin receptor and prostaglandin H synthase 2, but not estrogen receptor alpha and heat shock protein 90 messenger ribonucleic acid in the gravid horn and nongravid horn in sheep during betamethasone-induced labor.

In the present study, we characterized four myometrial contraction-associated proteins (mCAPs): oxytocin receptor (OTR), prostaglandin H synthase 2 (PGHS2), estrogen receptor alpha (ERalpha), and heat shock protein 90 (Hsp90) messenger RNA (mRNA) expression in the nongravid horn of pregnant sheep and compared them with their expression in the gravid horn that is exposed to a greater degree of stretch. We also examined the regulatory effects of estrogen and progesterone on OTR mRNA expression in ovariectomized nonpregnant sheep. In addition, we determined the ontogeny of mCAP expression in the gravid horn throughout late pregnancy and during spontaneous term labor. Gravid horn and nongravid horn myometria were removed under general anesthesia from control ewes not in labor at 130-140 days gestational age (dGA; n = 3) and during betamethasone-induced labor (n = 6) at the same gestational age. Gravid horn myometrium was also collected from ewes not in labor at 95 dGA (n = 3), 101-110 dGA (n = 3), 111-120 dGA (n = 3), 121-130 dGA (n = 3), 131-140 dGA (n = 3), and 141-145 dGA (n = 4) and from ewes in spontaneous term labor (n = 4). All ewes were carrying single fetuses. Myometrium was also collected from ovariectomized nonpregnant ewes treated with saline (n = 5), estradiol (50 microg/day; n = 5), progesterone (0.3 g, intravaginally; n = 5), and estradiol plus progesterone (n = 5). Myometrial RNA was extracted and analyzed by Northern blot for OTR, PGHS2, ERalpha, and Hsp90 mRNA, normalized for 18S ribosomal RNA or beta-actin. ERalpha, Hsp90, OTR, and PGHS2 mRNA were all significantly up-regulated during betamethasone-induced labor (P < 0.01) in gravid and nongravid horn myometrium. The level of gravid horn OTR mRNA during labor was 3 times the level of nongravid horn OTR mRNA (P < 0.0001). Gravid horn PGHS2 mRNA was also higher than nongravid horn PGHS2 (P < 0.02). In contrast, in spontaneous term labor nongravid horn, ERalpha and Hsp90 mRNA were similar to gravid horn. Myometrial ERalpha and Hsp90 mRNA remained unchanged throughout late pregnancy and increased at spontaneous term labor (P < 0.05). In contrast, myometrial OTR increased around 130 dGA (P < 0.01) and further increased at spontaneous term labor (P < 0.02). Progesterone significantly inhibited myometrial OTR mRNA expression in nonpregnant sheep and estradiol antagonized progesterone's inhibitory effect. Mechanical stretch differentially regulated mCAP mRNA expression in the ovine gravid horn and nongravid horn. Mechanical stretch appears largely responsible for increased OTR mRNA and to a lesser degree PGHS2 mRNA. In addition, endocrine factors may be required for full activation of OTR and PGHS2 mRNA associated with labor. ERalpha and Hsp90 mRNA are not under the control of uterine stretch in keeping with our previous results, indicating that systemic hormones such as estradiol, are prime regulators for these two mCAP mRNA expression during labor.

Animals↗

[Radioimmunoassay for plasma betamethasone and its application for clinical study (author's transl)].

A sensitive and specific radioimmunoassay for plasma betamethasone has been developed. The antiserum used was obtained by immunizing rabbits with betamethasone-3-oxime-human serum albumin (BM-3-oxime-HSA) conjugate. The sensitivity was 20 pg and a standard curve was established with a useful range from 20 pg to 4 ng. The cross reactivity of all tested endogenous steroids was less than 0.2%. Cortisol with a cross reactivity of 0.14% caused slight interference at very high concentrations, but this factor is negligible when plasma cortisol level is less than 30 microgram/dl. The calculated interference by cortisol was less than 10%, and plasma not receiving BM consistently gave blanks which were less than 20 pg/tube. Reliability criteria were satisfactory. By this method plasma BM could be measured directly in dichloromethane extract of plasma. The plasma concentrations of BM were measured in normal subjects and patients with liver diseases following oral administration of BM. The peaks of the plasma concentrations for 1.0 mg and 1.5 mg of BM were 345 +/- 40 (n = 3) and 710 +/- 200 ng/dl (n = 5) respectively within 2 hours after administration in normal subjects. After the peak level, plasma BM rapidly fell and disappeared 24 hours after administration in all examined normal subjects. In patients with chronic active hepatitis, the peak levels for 1.0 mg and 1.5 mg of BM were 428 +/- 48 (n = 4) and 837 +/- 83 ng/dl (n = 7) respectively within 2 hours after administration. However, the peak levels of plasma BM were higher than those of normal subjects, and the disappearance of BM from the blood was markedly delayed, reaching a level of 318 +/- 88 nad 622 +/- 148 ng/dl respectively for 1.0 mg and 1.5 mg of BM at 5 hours. The relatively high plasma concentration of BM, ranging from 135 to 170 ng/dl was maintained even 24 hours after administration in all patients with chronic active hepatitis. The disappearance of cortisol from the blood also rapidly fell in normal subjects, but was markedly delayed in patients with chronic active hepatitis. There was good correlation between the severity of the liver disease as measured by the ICG retention at fifteen minutes and removals of BM and cortisol from the blood.

Adult↗

The effect of betamethasone administration on uterine motility in pregnancy. A prospective study using four-channel tocography.

We monitored 30 patients before and after betamethasone prophylaxis using four-channel tocography to evaluate if betamethasone therapy in the case of imminent preterm delivery increases uterine activity. Frequency of contractions slightly increased but global uterine activity decreased. We conclude that the changed contraction pattern did not impair the benefits of RDS prophylaxis.

Betamethasone↗

Effects of betamethasone and ritodrine on the fetal secretion of lung surfactant.

Beta-sympathomimetic drugs and glucocorticoid agents are given in preterm labor to prevent severe consequences of prematurity. It is unclear whether beta-sympathomimetics accelerate lung maturation, or whether they only tend to delay preterm delivery. We have evaluated the effects of betamethasone and ritodrine in rabbits on alveolar lavage phospholipids in premature rabbits, a mean of 28.7 days from conception. Betamethasone given to 26-day-old fetuses increased the surfactant phospholipids, phosphatidylinositol and disaturated phosphatidylcholine; increased disaturated phosphatidylcholine/sphingomyelin ratio, and phosphatidylinositol (percent of phospholipids), as compared to untreated littermates, or to saline treated controls. A low dose of ritodrine given to the pregnant doe, and a high dose given at premature birth had no detectable effects on alveolar lavage phospholipids. However, a high dose of ritodrine given one day before the delivery to the fetus and at premature birth decreased the disaturated phosphatidylcholine/sphingomyelin ratio and phosphatidylinositol in alveolar lavage. While glucocorticoid administration increases the synthesis and secretion of surfactant phospholipids, a high dose of a betasympathomimetic drug may decrease the surfactant. However, spontaneous premature labor is associated with accelerated lung maturation, and accordingly the present results do not contradict the use of a low dosage of betasympathomimetic drug to delay preterm delivery.

Animals↗

Effects of betamethasone on maternal plasma corticotropin releasing factor, ACTH and cortisol during pregnancy.

Corticotropin releasing factor immunoactivity (CRFi) has been identified in the plasma of women in the second half of gestation. There are several lines of evidence supporting a placental source for this hormone. Regulation of placental CRFi is poorly understood. In this study, the effect of a long-acting glucorticoid on the release of placental CRFi was investigated. Eleven women in the third trimester of pregnancy had plasma samples measured for CRFi, ACTH and cortisol before and after receiving 12 mg betamethasone. There was a significant decrease in ACTH (p less than 0.05) and cortisol levels (p less than 0.01) but no change in CRFi. It is concluded that the secretion of CRFi by the placenta is not inhibited by the administration of betamethasone while maternal levels of cortisol and ACTH are lowered. These results suggest that the acute regulation of placental CRFi is distinct from the regulation of hypothalamic CRF.

Adrenocorticotropic Hormone↗

Comparison of the influence of cyclosporine and topical betamethasone-17,21-dipropionate treatment on quality of life in chronic hand eczema.

In a randomized, controlled parallel group study we have shown that cyclosporine at 3 mg/kg/day is as effective as topical betamethasone-17,21-dipropionate in the treatment of chronic hand eczema. In this study we compared the influence of these therapies on the quality of life. Forty-one patients were treated with either treatment for 6 weeks, after which patients with failure were switched to the other treatment for another 6 weeks. Quality of life was assessed with the Eczema Disability Index (EDI) at baseline and at the end of both treatment periods. The total EDI score decreased significantly and to the same degree in both groups, i.e. from the mean value of 30.5 to 20.9 in the cyclosporine group and from 27.2 to 18.9 in the betamethasone-17,21-dipropionate group. Irrespective of the dimension of the EDI (daily activity, school/work, personal relationship, leisure, treatment), the difference between the treatment groups at the end of the first treatment period was not significant. In the second part of the study a slight further decrease in total score was observed, but without any difference between the groups. There was a significant correlation between changes in the total EDI score and changes in all the clinical assessments, i.e. disease activity, extent of the disease, itch, sleep disturbances and use of emollients. Though the significant correlation between the total EDI and clinical assessments makes quality of life assessments in hand eczema questionable, the missing correlation between some clinical assessments and dimensions of the EDI suggests that EDI views aspects of the disease not covered by clinical measures.

Administration, Topical↗

Effects of betamethasone on plasma levels of estriol, cortisol and HCS in late pregnancy.

The effect of a single dose of betamethasone on the maternal plasma concentration of estriol and cortisol was studied. The concentration of estriol decreased rapidly. A maximal suppression of about 70 per cent was seen after 6-24 hours. A similar influence on the maternal plasma concentration of cortisol was observed. HCS (human chorionic somatomammotropin) was not influenced by betamethasone. These facts have to be taken into consideration after treatment with synthetic corticosteroids in high risk pregnancies.

Adult↗

Betamethasone effects on paraquat lung toxicity.

1. Betamethasone (1 mg/ml) was administered i.v. to adult Wistar rats 3 h before paraquat injection (30 mg/ml) and various parameters of lung function were studied to determine the effect of an anti-inflammatory drug in paraquat lung toxicity. 2. Rats treated with both drugs showed not only increases in spontaneous lung chemiluminescence (90%), malondialdehyde formation (40%), migration of PMN cells to the lungs (450%) and lung wet wt (20%), but also the survival times were decreased to 25% at day 7. 3. The data indicate that betamethasone exacerbates the toxic effects of paraquat. The mechanism can be explained in terms of inhibition of phospholipase A2 activity, which may increase the accumulation of hydroperoxide, produced by paraquat redox cycling upon lipid membranes.

Animals↗

A double-blind comparative trial of acyclovir and adenine arabinoside in combination with dilute betamethasone in the management of herpetic disciform keratitis.

A double-blind comparative trial of acyclovir (ACV) and adenine arabinoside (ARA-A) in combination with dilute betamethasone was carried out in 30 patients with herpetic disciform keratitis. Of those receiving ACV and betamethasone, 86.7% healed in a mean time of 22.5 days, while 76.9% of those receiving the Ara-A combination healed in a mean time of 26.7 days. There was no statistical difference between the two treatment groups for efficacy parameters. However, the proportion of patients developing superficial punctate keratopathy (SPK) was significantly greater in the Ara-A treatment group.

Acyclovir↗

Ophthalmic fluorometholone-gentamicin versus ophthalmic betamethasone-gentamicin following cataract surgery.

A prospective, randomised, investigator-masked, parallel-group study was performed to compare fluorometholone-gentamicin eye drops and ointment with betamethasone-gentamicin eyedrops and ointment in the control of ocular inflammation after cataract surgery. Seventy patients (35 in each treatment group) of both sexes undergoing cataract-lens implant surgery for visually disabling cataract were enrolled in the study. The demographic and baseline parameters on day I, the day after surgery, were similar in the two study groups. After treatment, on day 3 and day 6 post-operatively, the reduction in cells in the anterior chamber and conjunctival hyperaemia were similar in the two study groups. Both treatments were equally well-tolerated. Ophthalmic fluorometholone-gentamicin was as effective as ophthalmic betamethasone-gentamicin in the control of ocular inflammation after cataract surgery.

Aged↗

In vitro release of betamethasone dipropionate from petrolatum-based ointments.

The purpose of this research was to develop new in vitro methodology for measuring release from petrolatum-based semisolids and to determine whether two ointments, both of which contained betamethasone dipropionate, 0.05%, but with different formulations, could be distinguished by release measurements. Several receptor media were explored to optimize the procedure utilizing Franz-type cells. Analysis was by HPLC. The release slope was 1.5 to 6 times greater from the ointment than the "augmented" ointment (which had greater clinical potency). Release was highest with a receptor consisting of a 5% solution of hexane in acetonitrile. Even so, it was necessary to subject samples of receptor from the augmented ointment to evaporation followed by reconstitution with a smaller volume of mobile phase to bring corticosteroid concentrations up to quantifiable levels. In another series of experiments, the HPLC mobile phase was used as the receptor and a relatively large volume (100 microliters) was injected onto the column. With the second approach, measured concentrations were lower but more reproducible. Quantifiable levels of betamethasone dipropionate were obtained for both formulations beginning from the first data point (at 1 hr), with satisfactory linearity of plots of amount released per unit area of membrane versus the square root of time. Using this methodology, it was possible to distinguish the effect of formulation differences in two ointments containing the same drug in the same concentration.

Administration, Topical↗

Antiangiogenic effect of betamethasone on the chick cam stimulated by TA3 tumor supernatant.

Tumor growth is the result of combined cell proliferation overwhelming cell death and neoangiogenesis. This report shows CAM angiogenesis promoted by TA3 tumor supernatant with or without low dosis of betamethasone (Minimal antiangiogenic concentration: beta-MAAC). Methylcellulose discs instilled with 10 microliters of beta-MAAC (0.08 microgram/ml), 10 microliters of tumor supernatant (TA3ts), 5 microliters beta-MAAC + 5 microliters TA3ts, and 10 microliters of PBS as control were implanted in host chick eggs. On day 12, the grafts were removed, photographed and fixed. Sections were stained in parallel, one and three with hematoxylin-eosin, and section two by the Tunel method. The number of vessels was evaluated in a microscopic field of the CAM (2250 micron 2). The results show that beta-MAAC produced a significant inhibition of neovascularization in comparison to that observed in controls (P < 0.0025; Student t-Test). Discs instilled with TA3ts produced an intense stimulation of angiogenesis in contrast, when discs were instilled with 5 microliters of beta-MAAC + 5 microliters of TA3ts the angiogenesis was significantly inhibited (P < 0.001). The results show that effective antiangiogenic doses of betamethasone are in the range of 10(-7) M, (probably a genomic mediated action) and that this effect of low concentration may have clinical applications.

Allantois↗

[Comparative study of efficacy and effect on plasma cortisol levels of micronised desonide cream 0.1 p. 100 versus betamethasone dipropionate cream 0.05 p. 100 In the treatment of childhood atopic dermatitis].

OBJECTIVE: Systemic side effects of local corticosteroid therapy may occur when treating chronic inflammatory dermatoses in children. We compared the effect of micronized desonide cream 0.1 p.100 versus betamethasone dipropionate cream 0.5 p.100. PATIENTS AND METHODS: A randomized double-blind trial was conducted to assess the efficacy of micronized desonide cream 0.1 p.100 (group 1) versus bethamethasone cream dipropionate 0.05 p.100 (group 2) in children treated for atopic dermatitis and to compare their effects on serum cortisol levels 8 hours after administration. Twenty-nine patients, mean age 13.8 months were included (15 in group 1 and 14 in group 2). The creams were applied twice a day from day 1 to 5 then once a day from day 6 to 7 and finally once every two days to day 15. RESULTS: The two treatments were effective with a decrease in body surface area involved and an improvement in lesion score from day 5 to day 20. Cortisolemia fell off significantly for both treatments between day 0 and day 5 (group 1: Deltad5=-4.74 mg/ml, p=0.01; group 2: Deltad5=-13.06 mg/ml, p<0.0001), only for group 2 between day 0 and day 20 (Deltad20=-7.38 mg/ml, p=0.02) and to a lesser degree between day 0 and day 30 (Deltad30=-3.18 mg/ml, p=0.06). The decrease was greater in group 2 than in group 1 on day 5 (p=0.01) and to a lesser degree at day 20 (p=0.06). CONCLUSIONS: Micronized desonide cream 0.1 p.100 has less potential for suppressing the adrenal cortisol axis than betamethasone dipropionate cream 0.05 p.100 while the therapeutic effect on childhood atopic dermatitis is the same.

Administration, Topical↗

[Pharmacological study on 9 alpha-fluoro-11 beta, 17,21-trihydroxy-16 beta-methyl pregna-1, 4-diene-3,20-dione-17-benzoate(betamethasone-17-benzoate, MS-1112), a local anti-inflammatory agent. (2). Its action of delayed hypersensitivity dermatitis].

The anti-inflammatory activity of MS-1112, a new steroid compound, after topical application and systemical administration was examined by means of delayed-type hypersensitivity in mice and compared with other glucocorticoid analogues, betamethasone-17-valerate (Val), dexamethasone (Dexa) and betamethasone (Beta). In the case of pretreatment and therapeutic effect, topically applied MS-1112 was most active in inhibiting the delayed-type hypersensitivity induced by picryl chloride. The order of those inhibitory activities of MS-1112 and Val was ointment greater than cream greater than gel. In contrast to MS-1112 and Val, inhibitory action of Dexa was slow in onset after the topical application. It appears that esterification of the 17-hydroxyl group increases the anti-inflammatory activity after topical application. While systemically administered, MS-1112 was more potent than Val, and similarly potent to Beta, but less active than Dexa. From the above results, it may be considered that topically applied MS-1112 is superior to other glucocorticoids in the percutaneous penetration and retention in the skin. MS-1112 is thus considered to be a very potent agent as a dermatocorticoid.

Administration, Topical↗

[A case of steroid psychosis associated with betamethasone].

Psychotic side effects of steroids have been observed at relatively high frequency if mild cases, such as euphoria, are included, while it has been said that incidences differ among kinds of steroids. We reported a case developing severe schizophrenia-like symptoms following the treatment with betamethasone although this drug is believed to be rarely involved in steroid-induced psychosis, and its psychotic side effects have been rarely reported. When betamethasone was administered for progressive peripheral facial paralysis at a mean daily dose of 7mg, psychotic symptoms appeared from the 15th treatment day. Psychosis began with interrupted appearance of excitation, autism, and misanthropia. Although the steroid was gradually decreased in dose because of abatement of facial paralysis, not only psychotic symptoms were aggravated, but also appeared hallucination. Thus the steroid was withdrawn before the scheduled date while its dose was gradually decreased, and haloperidol was administered. Psychotic symptoms were gradually eliminated and completely disappeared about 40 days after onset.

Adult↗

Induction of generalized pustular psoriasis by topical use of betamethasone-dipropionate ointment in psoriasis.

Three patients with chronic discoid psoriasis are described as having a generalized pustular eruption provoked by the topical use of betamethasone-dipropionate ointment (0.05%) over extensive skin areas for two or three weeks. All the lesions were nearly healed when the rash erupted. It is suggested that the potent topical steroid was absorbed through the damaged psoriatic skin, resulting in a systemic effect and a generalized pustular psoriasis (GPP). It was estimated that the patients absorbed at least 1.5 mg betamethasone per day during the application period.(i.e. 3 tablets of CelestonaR 0.5 mg). Just as steroids systemically are contraindicated in chronic discoid psoriasis by the risk of GPP, potent topical steroids must be avoided over large psoriatic skin areas.

Aged↗