Diprolene
Swine as a model of skin inflammation. Phospholipase A2-induced inflammation.

Nair X, Nettleton D, Clever D, Tramposch KM, Ghosh S, Franson RC.

Bristol-Myers Squibb Co., Pharmaceutical Research Institute, Buffalo, New York 14213.

A predictive animal model of skin inflammation is needed for the development of potential therapeutic agents. The existing models of inflammation rely on animals whose skin physiology or biochemistry differs significantly from human. The objective of this investigation was to evaluate the swine as a potential model of inflammation, because its skin has been recognized to exhibit morphologic and functional similarities to human skin. In the swine, an inflammatory response was produced following intradermal injection of snake venom phospholipase A2 (PLA2). This response was characterized by transient erythema (2-3 h) and microscopic changes of cell infiltration, epidermal hyperplasia, and dermal damage, which were apparent two days after PLA2 and peaked by day 7. In general, these microscopic changes persisted up to 21 days. Treatment with the antiinflammatory steroid, betamethasone dipropionate (Diprolene), gave a significant reduction of the inflammatory responses. Heat-inactivated PLA2, ovalbumin, or saline did not provoke this reaction, although PLA2 inactivated by bromophenacyl bromide alkylation did produce an inflammatory response. The alkylated PLA2 was also able to provoke an inflammatory response in the mouse paw edema assay. These results demonstrate that PLA2 can stimulate an inflammatory response in the swine skin, but that phospholipid hydrolytic activity is not required.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8491515&dopt=Abstract betamethasone Diprolene AF



Diprolene
Comparison of the effect of hydrocortisone, hydrocortisone-17-butyrate and betamethasone on collagen synthesis in human skin in vivo.

Haapasaari KM, Risteli J, Koivukangas V, Oikarinen A.

Department of Dermatology, University of Oulu, Finland.

It has been shown previously that topical corticosteroid treatment decreases collagen synthesis in human skin in vivo and that the adverse effects are due to reduced collagen synthesis. The aim of the present study was to evaluate the effect of hydrocortisone, hydrocortisone-17-butyrate and betamethasone on collagen synthesis in human skin in vivo. Fourteen healthy male volunteers applied hydrocortisone, hydrocortisone-17-butyrate, betamethasone and vehicle twice a day for one week to four separate areas marked on their abdominal skin. The collagen synthesis rate in the skin was measured by assaying collagen propeptides from the suction blisters induced on the treated areas. Aminoterminal propeptide of type I procollagen (PINP) and aminoterminal propeptide of type III procollagen (PIIINP) were measured from skin blister fluid using radioimmunoassays. Skin thickness was measured with ultrasound. Hydrocortisone decreased the two propeptides studied in the suction blister fluids less than did hydrocortisone-17-butyrate and betamethasone, but the interindividual variation was great. Hydrocortisone-17-butyrate and betamethasone had almost similar decreasing effects on the propeptides in the suction blister fluid. Hydrocortisone decreased the concentrations of PINP and PIIINP by about 35%. In some subjects (4/14) the decline of the collagen propeptide levels was over 50%. The decline in the concentration of PINP was 63% by hydrocortisone-17-butyrate and 69% by betamethasone, while the decrease in PIIINP was 55% by hydrocortisone-17-butyrate and 62% by betamethasone. None of the treatments had any effect on skin thickness within one week. In conclusion, it seems that hydrocortisone is less atrophogenic than hydrocortisone-17-butyrate and betamethasone, as shown by radioimmunoassays for collagen propeptides. The order of inhibitory potency of the three glucocorticoids on collagen synthesis was hydrocortisone < hydrocortisone-17-butyrate < betamethasone. Thus, assay of collagen propeptides from suction blisters can be used to screen various steroids with respect to their action on collagen synthesis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8578945&dopt=Abstract betamethasone Diprolene AF



Diprolene
[Betamethasone valerate reference standard (Control 941) of the National Institute of Health Sciences]

[Article in Japanese]

Kitajima A, Tanimoto T, Okada S.

The raw material for betamethasone valerate was tested for preparation of the "Betamethasone Valerate Reference Standard (Control 941)". Analytical data obtained were as follows: melting point, 194.3 degrees C (decomposition); UV and infrared spectra, the same as those for JP Betamethasone Valerate Reference Standard (Control 844); optical rotation, [alpha]20D = +79.4 degrees; thin-layer chromatography and high-performance liquid chromatography (HPLC), no impurities were detected; assay, 100.0% by HPLC. Based on the above results, the candidate material was authorized as the JP Betamethasone Valerate Reference Standard (Control 941).

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8717241&dopt=Abstract betamethasone Diprolene AF



Diprolene
Do we use too much antenatal betamethasone?

Skoll A, Ferreira E, Pedneault L, Duchesne M, Letourneau G.

Ste-Justine Hospital, University of Montreal, Montreal, QC, Canada.

OBJECTIVE: To review and rationalize the liberal use of antenatal betamethasone in the setting of threatened preterm birth.STUDY DESIGN: A retrospective review was performed using the charts of all patients at Ste-Justine Hospital, Montreal QC, who received antenatal betamethasone between 01 April 1997 and 31 March 1998. Initial treatment consisted of 2 doses of 12 mg IM given 24 hours apart. Repeat doses of 12 mg weekly were administered at the discretion of the treating physician. Optimal antenatal betamethasone therapy was defined as delivery within 1 week of initial treatment, prior to 34 weeks. Aside from number and timing of doses, other factors analyzed included: gestational age at admission and delivery, diagnosis associated with threatened preterm birth (PTB), number of hospital admissions, and delay between re-admission and delivery.RESULTS: Of the 334 patients identified, 82 (25%) received optimal treatment. Of the remaining 252 patients, 204 (81%) received repeat doses. In the repeat dose group, 112 (55%) women delivered after 34 weeks, while 70 of the 92 remaining patients were hospitalized until delivery. The other 22 patients who received serial doses were discharged at least once prior to delivery; of these patients, 8 were re-admitted more than 24 hours pre-delivery (i.e., adequate time for re-treatment), while 14 were not, but only 6 of these were delivered urgently. Thus, a maximum of 60 patients (25% of repeat doses) could potentially have benefited from this approach. Of the 48 patients not receiving repeat doses, 37 (77%) delivered after 34 weeks. Five remained hospitalized, and 6 were discharged prior to delivery and re-admitted (2 patients > 24 hr and 4 patients < 24 hr from delivery). This represented a potential underutilization of betamethasone by 3% (11/334) of the patients, but only 1.8% (6/334) were of less than 32 weeks' gestation.CONCLUSION: This study demonstrated the difficulty in predicting which of the patients presenting with threatened preterm birth would actually go on to deliver during the window of benefit of antenatal betamethasone therapy. Our desire to permit all premature fetuses to profit from the positive effects of this therapy must be balanced by a reserve in exposing too many to too much. Use of antenatal betamethasone in our unit has significantly decreased since this review.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12196869&dopt=Abstract betamethasone Diprolene AF



Diprolene
Interaction between betamethasone and vecuronium.

Parr SM, Robinson BJ, Rees D, Galletly DC.

Section of Anaesthesia, Wellington School of Medicine, New Zealand.

A possible interaction between betamethasone and vecuronium was examined in 20 rat phrenic nerve-hemidiaphragm preparations. Ten preparations were bathed in a physiological solution with betamethasone 1 mumol litre-1 added and, after a 30-min period were exposed to vecuronium at concentrations of 4, 6, 8 and 10 mumol litre-1 with vecuronium free washings between each exposure. Ten control experiments were performed also using a betamethasone-free bathing solution. In comparison with control, the betamethasone group had significantly (P = 0.0008) less depression of muscle contraction (twitch) force at all concentrations of vecuronium. The calculated ED50 (50% depression of muscle contraction force) was 5.65 mumol litre-1 for controls and 7.39 mumol litre-1 for betamethasone-pretreated preparations. This study confirms our previous clinical observations that an interaction occurs between vecuronium and betamethasone which is characterized by resistance to neuromuscular block.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1681841&dopt=Abstract betamethasone Diprolene AF