Diprolene
Chondroprotective effect of betamethasone in lapine pyogenic arthritis.

Stricker SJ, Lozman PR, Makowski AL, Gunja-Smith Z.

Department of Orthopaedic Surgery, University of Miami School of Medicine, Florida, U.S.A.

The chondroprotective effect of betamethasone was examined to determine if corticosteroids can decrease articular cartilage injury caused by inflammatory exudate in Staphylococcus aureus gonarthritis in rabbits. Three experimental groups of antibiotic-treated rabbits were created, comparing parenteral versus low-dose intraarticular routes of betamethasone administration. Rabbits that received ceftriaxone plus supplemental parenteral betamethasone (group 2) demonstrated significantly less articular cartilage proteoglycan loss than did rabbits treated with antibiotics alone (group 1). Supplemental intraarticular betamethasone (group 3) was somewhat less effective in this regard, possibly reflecting the smaller steroid dosage. This animal study introduces histologic and biochemical evidence that betamethasone, administered early and in conjunction with appropriate systemic antibiotics, may help protect infected articular cartilage from proteolytic degradation. Further study is needed to prove safety and efficacy of corticosteroids before recommending their clinical use in the treatment of septic arthritis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8742291&dopt=Abstract betamethasone Diprolene AF



Diprolene
Simultaneous diffusion and metabolism of betamethasone 17-valerate in the living skin equivalent.

Kubota K, Ademola J, Maibach HI.

Department of Dermatology, University of California, San Francisco, School of Medicine 94143-0989, USA.

Simultaneous diffusion and metabolism of betamethasone 17-valerate was studied using betamethasone 17-valerate, betamethasone 21-valerate, and betamethasone as permeants. These corticosteroids were suspended in silicone adhesive and applied to an artificial living skin equivalent (LSE) for 72 h. When betamethasone was applied, no metabolites were detected in the receptor medium. Conversely, with betamethasone 21-valerate application, only betamethasone but no betamethasone 21-valerate was detected in the receptor medium indicating the metabolism of the latter by skin esterases. When tested with the theory for simultaneous diffusion and metabolism, the result is consistent with the enzyme rate constant in the LSE homogenate measured in a previous study. When betamethasone 17-valerate was applied to the LSE, more than half of the total amount of corticosteroids detected in the receptor medium was unchanged, consistent with the previously reported chemical (as opposed to enzymatic) degradation half-life of about 8 h. This result also indicated that very little metabolism of betamethasone 17-valerate occurred in the skin.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8748331&dopt=Abstract betamethasone Diprolene AF



Diprolene
Developmental regulation of corticosteroid-binding globulin biosynthesis in the baboon fetus.

Pepe GJ, Jury HH, Hammond GL, Albrecht ED.

Department of Physiology, Eastern Virginia Medical School, Norfolk, Virginia 23501, USA.

The present study determined the roles of estrogen and cortisol in maternal and fetal corticosteroid-binding globulin (CBG) levels and fetal hepatic messenger RNA (mRNA) expression in the baboon. Samples of fetal liver, kidney, and brain were obtained from untreated control animals at early (day 60; n = 4), mid (day 100; n = 8), and late (day 165; n = 5) gestation (term = day 184). Maternal and umbilical blood samples were collected on day 100 from baboons in which betamethasone was administered sc to the mother (n = 6) on days 60-99 of gestation and on day 165 from animals (n = 4) in which the fetus was administered betamethasone on days 150-164 of gestation. Maternal serum cortisol concentrations were similar at mid (43 +/- 2 micrograms/dl) and late (42 +/- 3 micrograms/dl) gestation and decreased (P < 0.05) at midgestation (1 +/- 1 micrograms/dl) and term (31 +/- 4 micrograms/dl) after betamethasone treatment. Umbilical serum cortisol levels were also reduced (P < 0.05) at both mid (1 +/- 1 micrograms/dl) and late (14 +/- 5 micrograms/dl) gestation by betamethasone treatment. Fetal serum CBG levels in untreated animals were lower (P < 0.05) on day 165 (444 +/- 29 pmol/ml) than on day 100 (844 +/- 35 pmol/ml) and increased (P < 0.05) at midgestation (1098 +/- 64 pmol/ml), but not at term (551 +/- 24 pmol/ml), after betamethasone treatment. In contrast, maternal serum CBG levels (range, 528-770 pmol/ml) were not altered by gestational age or betamethasone. The human CBG complementary DNA hybridized to a single mRNA species of 1.8 kilobases in baboon fetal liver; however, CBG was not expressed in fetal kidney and was detectable in fetal brain and pancreas only by reverse transcription-PCR. In untreated baboon fetuses, the mRNA levels of hepatic CBG, expressed as a ratio of 18S RNA, progressively decreased (P < 0.05) in early (1.83 +/- 0.17), mid (0.97 +/- 0.12), and late (0.51 +/- 0.04) gestation. These results demonstrate that fetal hepatic CBG mRNA expression and serum CBG concentrations were elevated early in baboon gestation and exhibited a progressive decline during the course of advancing pregnancy. We suggest that the increased levels of fetal CBG in the early stages of gestation reflect stimulation of hepatic CBG synthesis by maternal cortisol, which we previously demonstrated to occur in the fetus as a result of preferential 11 beta-hydroxysteroid dehydrogenase-catalyzed glucocorticoid reduction across the placenta. The decline in fetal CBG may reflect the developmental increase in catabolism of cortisol to bioinactive cortisone in target tissues of the fetus such as the liver.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8754758&dopt=Abstract betamethasone Diprolene AF



Diprolene
Betamethasone modulation of sphingomyelin hydrolysis up-regulates CTP:cholinephosphate cytidylyltransferase activity in adult rat lung.

Mallampalli RK, Mathur SN, Warnock LJ, Salome RG, Hunninghake GW, Field FJ.

Pulmonary Division, Department of Veterans Affairs Medical Center, Iowa City, IA, USA.

Glucocorticoids appear to play an integral role in stimulating surfactant synthesis by activating the rate-regulatory enzyme for phosphatidylcholine synthesis, CTP:cholinephosphate cytidylyltransferase (CT). The activity of liver CT, in vitro, has been shown to be inhibited by the sphingomyelin hydrolysis product, sphingosine. In order to investigate the mechanisms by which glucocorticoids alter CT activity, in vivo, we administered betamethasone (1 mg/kg intraperitoneally) sequentially to adult male rats for 5 days. Betamethasone increased CT activity 2-fold relative to control in whole lung. The hormone also increased membrane-bound activity, but did not affect cytosolic enzyme activity. Betamethasone modestly increased CT mRNA as determined by the reverse-transcription PCR and Southern analysis of PCR products, but did not alter the levels of immunoreactive enzyme in lung membranes as demonstrated by Western blotting. The hormone did, however, produce a nearly 3-fold increase in membrane-associated sphingomyelin, and co-ordinately a substantial decrease in the levels of sphingosine in lung membranes. Sphingosine, but not sphinganine, was a competitive, reversible inhibitor of lung CT with respect to the enzyme activator, phosphatidylglycerol. Betamethasone decreased the activities of the sphingomyelin hydrolases: acid sphingomyelinase by 33% and of alkaline ceramidase by 21%. The hormone also inhibited the generation of sphingosine from lysosphingomyelin in lung membranes. There was no significant effect of the hormone on serine palmitoyltransferase activity, the first committed enzyme for sphingolipid biosynthesis. Further, administration of L-cycloserine, an inhibitor of sphingosine formation, was shown to stimulate CT activity by 74% and increase disaturated phosphatidylcholine in alveolar lavage by 52% relative to control. These observations suggest that glucocorticoids up-regulate surfactant synthesis at the level of a key regulatory enzyme by significantly altering the availability of inhibitory metabolites resulting from sphingomyelin hydrolysis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8761490&dopt=Abstract betamethasone Diprolene AF



Diprolene
Antenatal betamethasone therapy potentiates nitric oxide-mediated relaxation of preterm ovine coronary arteries.

Gao Y, Zhou H, Raj JU.

Department of Pediatrics, Harbor-UCLA Medical Center, University of California-Los Angeles School of Medicine, Torrance 90509, USA.

The present study was designed to test the hypothesis that betamethasone may potentiate nitric oxide-mediated relaxation of coronary arteries of preterm lambs. Isolated coronary arteries were obtained from lambs delivered at 128 days gestation. The lambs were treated intramuscularly with a single dose of betamethasone or saline 48 h before delivery and were killed after 3 h of ventilation after delivery. Vessel rings were suspended in organ chambers filled with modified Krebs-Ringer solution (95% O2-5% CO2, 37 degrees C), and their isometric tension was recorded. The endothelium-dependent relaxation induced by bradykinin and calcium ionophore A23187 was greater in arteries from antenatal betamethasone-treated lambs than in arteries from control lambs. The relaxation was abolished by N omega-nitro-L-arginine. Nitric oxide induced a greater relaxation in vessels from antenatal betamethasone-treated lambs and in vessels preincubated with betamethasone than in vessels from controls. Coronary arteries from control and antenatal betamethasone-treated lambs relaxed similarly to 8-bromoguanosine 3',5'-cyclic monophosphate. Nitric oxide induced a greater increase in guanosine 3',5'-cyclic monophosphate content in coronary arteries from antenatal betamethasone-treated lambs than in arteries from control lambs. Our data suggest that antenatal betamethasone therapy potentiates nitric oxide-mediated relaxation in coronary arteries from preterm lambs, probably by affecting the activity of soluble guanylate cyclase of vascular smooth muscle cells.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8779828&dopt=Abstract betamethasone Diprolene AF