Diprolene
Combined effects of fetal beta agonist stimulation and glucocorticoids on lung function of preterm lambs.

Jobe AH, Ikegami M, Padbury J, Polk DH, Korirnilli A, Gonzales LW, Ballard PL.

Department of Pediatrics, UCLA School of Medicine, Harbor-UCLA Medical Center, Torrance, USA.

We asked whether a single-dose fetal treatment strategy using betamethasone plus either a long-acting beta 2 agonist (formoterol) or betamethasone plus agents that elevate intracellular cyclic adenosine monophosphate (isobutyl methylxanthine and dibutyryl-cyclic adenosine monophosphate) would augment the effects of prenatal betamethasone on postnatal lung function. Preterm lambs were treated with 0.5 mg/kg beta-methasone or betamethasone plus the other agents and delivered 48 h after treatment. The postnatal lung function as assessed by compliance, ventilatory efficiency, and lung volumes at 40 min of age was improved by prenatal betamethasone and improved further by combination treatment, although the augmented responses were not significantly greater than with betamethasone alone. Fatty acid synthase protein and enzymatic activity were not increased by betamethasone or combined treatments, in contrast to responses reported for other animal models. There were no effects of glucocorticoids or the combined treatments on surfactant. Stimulation of the beta 2 agonist system did not augment postnatal lung function significantly above that noted for betamethasone alone with the agents, doses, and duration of exposures tested.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9395841&dopt=Abstract betamethasone Diprolene AF



Diprolene
Impact of multiple antenatal doses of betamethasone on growth and development of mice offspring.

Stewart JD, Gonzalez CL, Christensen HD, Rayburn WF.

Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.

OBJECTIVE: Our purpose was to determine in a randomized, placebo-controlled manner whether multiple antenatal doses of betamethasone affect long-term growth and development of exposed mouse offspring. STUDY DESIGN: Sixty pregnant CD-1 mice received either two, four, or eight antepartum doses of 0.1 mg betamethasone or placebo. Perinatal outcomes, growth, and development of the offspring were compared in a blinded manner. Variables were compared by analysis of variance or chi 2 testing. RESULTS: Betamethasone-exposed subjects gained less weight during pregnancy and were delivered of fewer live pups, with fewer male survivors and lower birth weights. These trends were dose related. Growth measurements were similar after the neonatal period. No differences in functional development and physical maturation in the offspring were noted. The reproductive capability, perinatal outcomes, and growth and development of the second-generation offspring were unaffected by betamethasone exposure. CONCLUSION: Multiple antenatal dosings of betamethasone, reaching toxic levels, did not have an impact on the long-term growth and development of the surviving mouse offspring.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9396909&dopt=Abstract betamethasone Diprolene AF



Diprolene
The effect of topical diltiazem on the intraocular pressure in betamethasone-induced ocular hypertensive rabbits.

Melena J, Santafe J, Segarra J.

Departamento de Farmacologia, Facultad de Farmacia, Universidad del Pais Vasco, Vitoria, Spain.

The effect of calcium channel blockers (CCBs) on intraocular pressure (IOP) remains still controversial, although some preliminary reports suggest that these drugs may be effective in the management of ocular hypertension and low-tension glaucoma. The aim of the present work was to assess the effect of topical diltiazem on IOP in an animal model for glaucoma, the betamethasone-induced ocular hypertension in rabbits. IOP was measured with a manometrically calibrated applanation pneumatonograph. Ocular hypertension was produced in 120 rabbits by weekly subconjunctival injection of a betamethasone suspension into the left eye. The experiments examining the ocular actions of diltiazem were carried out in two stages. In the first one, the ability of topical diltiazem to prevent the rise in IOP induced by betamethasone was studied. In a second phase, the effect of topical diltiazem on IOP in betamethasone-induced ocular hypertensive rabbits was assessed. Diltiazem was topically applied once daily for 5 days a week into the left eye. The effect of five different concentrations of diltiazem was evaluated to obtain dose-response curves. Topical diltiazem was found to prevent in a dose-related fashion the betamethasone-induced IOP rise as well as to reduce IOP in rabbits made ocular hypertensive by weekly subconjunctival injection of betamethasone. Unilateral topical administration did not produce a clear effect on IOP in the untreated eye. This is the first report describing the ocular hypotensive action CCBs in animal model for glaucoma. These findings are in agreement with preliminary evidence suggesting that CCBs may have a beneficial effect in human ocular hypertension.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9435188&dopt=Abstract betamethasone Diprolene AF



Diprolene
Betamethasone-induced ocular hypertension in rabbits.

Melena J, Santafe J, Segarra J.

Department of Pharmacology, Faculty of Pharmacy, Basque Country University, Vitoria, Spain.

The effect of subconjunctivally injected betamethasone on intraocular pressure (IOP) was studied in 85 albino New Zealand rabbits. IOP was measured with a Mentor Model 30 classic pneumatonograph that was manometrically calibrated to the rabbit eye. Ocular hypertension was induced by weekly subconjunctival injections of a betamethasone suspension into the left eye. In one experiment, 70 rabbits were given betamethasone for 4 weeks, while a second group of 10 rabbits received betamethasone for 11 weeks. The short-term effects of subconjunctival injections of betamethasone on IOP were also recorded in a third group of 5 rabbits. Weekly injections over 4 weeks resulted in an increase in IOP in the treated eye, which was prolonged to 11 weeks by repeated weekly injections. A sustained increase in IOP was observed in the treated eye for a period of 7 weeks. During the early hours after betamethasone injection, a transient decrease in IOP was registered in both eyes. The results show that weekly subconjunctival injections of betamethasone cause a predictable increase in IOP in the treated eye which may be suitable for testing the short- and long-term effects of antiglaucoma drugs. Evidence suggesting that endogenous glucocorticoids may play a role in the development of ocular hypertension in humans strengthens the potential value of this glaucoma model.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9442479&dopt=Abstract betamethasone Diprolene AF



Diprolene
The effects of betamethasone derivatives on endotoxin-induced uveitis in guinea pigs.

Tsuji F, Sawa K, Ikuse T, Shirasawa E.

Discovery Research Division, Santen Pharmaceutical Co. Ltd., Osaka, Japan.

OBJECTIVE AND DESIGN: 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. MATERIAL: Male Hartley guinea pigs were used. TREATMENT: Glucocorticoids were instilled into the eye. METHOD: To elicit EIU, lipopolysaccharide (LPS) was injected into the anterior chamber of the eye. Cell numbers in the aqueous humor after LPS injection were determined by flow cytometry. Prostaglandin E2 (PGE2) production after LPS injection into the anterior chamber was also examined. RESULTS: Intracameral injection of LPS (1 microgram/eye) induced cell infiltration into the anterior chamber and PGE2 production. Betamethasone dipropionate inhibited cell infiltration and PGE2 production more strongly than betamethasone. These results suggest that betamethasone dipropionate is a potent glucocorticoid in guinea pigs. CONCLUSIONS: Structure-activity relationships of glucocorticoids in the guinea pig EIL model may differ from those in the rat EIU model.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9459078&dopt=Abstract betamethasone Diprolene AF