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PubMed2000

Double-blind clinical study reveals synergistic action between alpha-hydroxy acid and betamethasone lotions towards topical treatment of scalp psoriasis.

OBJECTIVE: A double-blind, single-site, split-face clinical study was organized and carried out in order to evaluate the efficacy, tolerability, and safety of a glycolic acid containing scalp lotion in conjunction with a betamethasone (as the 17-valerate) scalp application against conditions of psoriasis. BACKGROUND: Alpha-hydroxy acids (AHA) have been proposed as therapeutic modalities against skin exfoliative conditions such as ichthyosis, xeroderma, and psoriasis. AHAs are hereby clinically investigated as therapeutic modalities adjuvant to corticosteroids in order to diminish systemic and topical adverse side-effects most frequently associated with use of the latter. METHODS: Twenty patients suffering from scalp psoriasis and other psoriatic conditions were included in a double-blind, split-face clinical study, using combinations of a 10% (w/w) glycolic acid scalp lotion, placebo lotion (excipients only), and a 0.1% (w/w) betamethasone scalp application, applied twice daily without any bandage for a period of 8 weeks. Clinical assessments were carried out by highly experienced physician evaluations based on a four-grade scale, prior to treatment and after 2, 4, 6 and 8 weeks. RESULTS: Improvement was observed in all cases included in the study following treatment with the 10% glycolic acid lotion. However, when equal parts of the 0.1% betamethasone lotion were combined, most of the treated sites were healed. Moreover, the duration of treatment required for healing was in this case reduced to approximately half of that needed when the glycolic acid or the betamethasone lotions were used separately for treatment. CONCLUSIONS: The present clinical study demonstrates for the first time that the effective and well tolerated therapeutic efficacy of glycolic acid scalp lotions is enhanced when used in conjunction with a 0.1% betamethasone scalp application against scalp psoriasis. This potential offers the practising dermatologist with novel treatment modes against severe skin conditions by combining topical corticosteroid with exfoliative agent therapy.

Administration, Topical↗

PubMed1984

[Preventive treatment of respiratory distress syndrome in newborn infants with antepartal glucocorticoid administration (betamethasone). Clinical results and changes in the lecithin/sphingomyelin ratio of the amniotic fluid].

Betamethason was administered to 105 patients with threatened premature labour at risk for respiratory distress syndrome (RDS) of the newborn. The most important indications were premature rupture of the membranes (30%) and premature labour (40%). The betamethason treatment was given between the 27. and 35. week of gestation. 79% of the patients delivered prior to 36 weeks of gestation, over 50% prior to 34 weeks gestation. The total incidence of RDS was 25%. Severe types of RDS (stage III and IV) were rare (7%). The mortality of RDS after betamethason treatment was 5.4%. After 32 weeks gestation the mortality from RDS was 0%. Severe types of RDS appear to occur more often in male than in female infants. The incidence of RDS was not lowered further by premature of the membranes. The lecithin/sphingomyelin(L/S)-ratio in the amniotic fluid following treatment with betamethason increased to over 2 in only 2/3 of the cases. The predictive value of the L/S ratio that respiratory distress syndrome of the newborn only occurs rarely with values over 2 was maintained after treatment with betamethason. Our rate in cases with an L/S ratio over 2 was 7.9%.

Amniotic Fluid↗

PubMed1981

[Plasma concentration and systemic effect of betamethasone after intra-articular injection (author's transl)].

Plasma concentrations of betamethasone, cortisol and corticosterone were measured before and after intraarticular injection of a betamethasone-depot preparation (Celestan-Depot) by radioimmuno-assay in 31 patients. Plasma concentration of betamethasone reached its maximum of between of 10 and 17 microgram/dl 30 min after injection. It had fallen to half after 2 hours, and practically to nil from the eighth day onwards. Lowest plasma levels of cortisol and corticosterone occurred after 6--24 hours, returning to the normal range after four days. In nine patients with knee-joint effusion and synovitis the plasma concentration of betamethasone was significantly higher after 24 hours, and cortisol and corticosterone values after 48 hours significantly more suppressed, than in patients without joint effusions and signs of inflammation. The results indicate that plasma concentration of betamethasone and the suppressant effect on the adrenal cortex after intra-articular injection is similar to that after intramuscular applications. Correspondingly, systemic application of the cortisol derivatives can cause significant side effects and be contra-indicated also after intra-articular injection.

Adolescent↗

PubMed2000

Neonatal sepsis and death after multiple courses of antenatal betamethasone therapy.

OBJECTIVE: This study was undertaken to compare the effects of single versus multiple courses of betamethasone therapy on the frequencies of neonatal outcomes and perinatal infectious morbidity among singleton pregnancies complicated by preterm delivery. STUDY DESIGN: We performed a nonconcurrent prospective analysis of singleton pregnancies delivered between 24 and 34 weeks' gestation after antenatal betamethasone exposure. Patients were categorized into two groups according to betamethasone exposure: (1) two 12-mg doses in a 24-hour interval on admission (single-course group) and (2) repeated dosing after the initial single course (multiple-course group). All patients received prophylactic antibiotics for group B streptococci. Any patients with ruptured membranes for >24 hours before delivery were excluded. Data were analyzed with the Student t test, the chi(2) test, and the Fisher exact test. Multiple logistic regression analyses were performed to examine the effect of each steroid dosing regimen on early-onset neonatal sepsis and neonatal death. P <.05 was considered significant for all 2-tailed tests. RESULTS: A total of 453 patients were included, with 267 in the single-course group and 186 in the multiple-course group. The two groups were similar with respect to maternal demographic characteristics, gestational age at delivery, mode of delivery, birth weight, and maternal group B streptococcal colonization. Multiple courses were significantly associated with early-onset neonatal sepsis (odds ratio, 5.00; 95% confidence interval, 1.3-23. 2), chorioamnionitis (odds ratio, 9.96; 95% confidence interval, 2. 1-64.6), endometritis (odds ratio, 3.61; 95% confidence interval, 1. 7-8.1), and neonatal death (odds ratio, 2.92; 95% confidence interval, 1.3-6.9). The frequencies of the other neonatal outcomes analyzed, including respiratory distress syndrome and grade III or IV intraventricular hemorrhage, were similar between the 2 groups. Multiple logistic regression analyses confirmed that multiple courses of antenatal betamethasone were independently associated with early-onset neonatal sepsis (odds ratio, 1.25; 95% confidence interval, 1.1-1.9) and neonatal death (odds ratio, 1.70; 95% confidence interval, 1.1-1.9). CONCLUSIONS: Multiple courses of antenatal betamethasone are associated with increased risks of perinatal infectious morbidity and neonatal death.

Adult↗

PubMed2001

The effect of multidose antenatal betamethasone on maternal and infant outcomes.

OBJECTIVE: This study was undertaken to determine whether prolonged betamethasone therapy is, as has been suggested, associated with adverse maternal or neonatal outcomes. STUDY DESIGN: A secondary multivariate analysis of a randomized controlled trial was performed to determine whether duration of betamethasone therapy was associated with adverse maternal or neonatal outcomes. RESULTS: There were 414 fetuses whose mothers were randomly assigned to trial groups. Final models included only valid cases without missing or averaged data (N = 367 to N = 412, depending on the model). Three or more sets of weekly betamethasone injections were given in 21.3% of cases and > or =4 sets were given in 12.3% of cases. Prolonged antenatal betamethasone therapy was not associated with increases in incidences of antenatal fever, chorioamnionitis, reduced birth weight, suppressed neonatal adrenal function, neonatal sepsis, or neonatal death. It was associated with larger birth weights (P <.05). CONCLUSION: Prolonged antenatal betamethasone therapy was not associated with higher risks of antenatal maternal fever, chorioamnionitis, reduced birth weight, neonatal adrenal suppression, neonatal sepsis, and neonatal death.

Adrenal Insufficiency↗

PubMed2001

Effectiveness of a rescue dose of antenatal betamethasone after an initial single course.

OBJECTIVE: To evaluate the effects of a single rescue dose of antenatal betamethasone after an initial single course on the frequency of neonatal respiratory distress syndrome and perinatal infectious morbidity in pregnancies complicated with preterm labor and delivery. STUDY DESIGN: We performed a cohort analysis of singleton pregnancies for which delivery occurred between 28 and 34 weeks' gestation after a single course of betamethasone administered before 28 weeks' gestation. Patients were then segregated into the following 2 groups on the basis of betamethasone exposure at the delivery admission: (1) a single 12-mg injection (rescue group) and (2) observation only (observation group). Patients who delivered infants within 24 hours of the rescue dose were excluded, as were those who had ruptured membranes for longer than 24 hours before delivery, those with diabetes that required insulin, and those with exposure to repeated doses of betamethasone before admission. Data were analyzed by use of the Student t test, chi2 test, and Fisher exact test. Multiple logistic regression was performed to examine the effect of each steroid dosing regimen on respiratory distress syndrome. Two-tailed P values <.05 were considered to be significant. RESULTS: A total of 152 patients were included, with 89 in the rescue group and 63 in the observation group. Both groups were similar with respect to maternal demographics, mean gestational age at the initial single course and at delivery, mode of delivery, and mean birth weights. Rescue administration was significantly associated with a reduction in the frequency of respiratory distress syndrome (odds ratio, 0.44; 95% confidence interval, 0.2 to 0.9) and mean ventilator days (odds ratio, 0.44; 95% confidence interval, 0.2 to 0.8) compared with observation alone. All other studied perinatal outcomes analyzed were similar between the groups. Multiple logistic regression confirmed an independent association between a single rescue dose and a reduction in the frequency of respiratory distress syndrome (odds ratio, 0.40; 95% confidence interval, 0.2 to 0.9). CONCLUSIONS: A single rescue dose of betamethasone is associated with a reduction in the frequency of respiratory distress syndrome without an apparent increase in perinatal infectious disease.

Adult↗

PubMed2002

The effect of betamethasone on salivary estriol.

OBJECTIVE: Study of the degree and pattern of salivary estriol suppression after administration of betamethasone. STUDY DESIGN: A total of 26 patients with singleton pregnancies (> 24 but < 35 weeks' gestation) in preterm labor with intact membranes had salivary estriol collected prior to betamethasone administration and then daily in late afternoon to evening. All patients were receiving magnesium sulfate. Five patients received a second dose of steroids 1 week after the first. Specimens were frozen and later batch analyzed. RESULTS: Betamethasone induced a mean 35.1 +/- 18.2% decrease in salivary estriol which reached its nadir in 1-6 days. By day 6, the salivary estriol in all patients remained suppressed. A second dose of betamethasone caused a further decrease in estriol. CONCLUSION: Betamethasone suppressed salivary estriol in all patients, consistent with the effect of glucocorticoids on fetal adrenal estriol precursors. The suppression persisted for at least 1 week.

Adolescent↗

PubMed2001

Placebo-controlled, blinded comparison of antenatal betamethasone on mouse liver development.

The objective of this investigation was to evaluate, in a placebo-controlled manner, the developing mouse liver after antenatal exposure either to a single dose or to a multidose of betamethasone. Ninety gravid CD-1 mice were randomly divided into three groups (n = 30/group) to receive either saline (0.25 mL s.c.) or betamethasone (0.10 mg s.c.) as a single dose on gestational day (GD) 14 of a 19-day gestation or as a 0.10 mg dose given twice daily on GD 14 and on GD 15 (4 doses). GD 0 is defined by the presence of a copulatory plug. These exposures of betamethasone cause fetal mouse lung maturation as would be observed in premature humans at 24-34 weeks of gestation. The livers were removed either from the fetuses on GD 16.5 or from the offspring on postnatal day 1, 3, 5, and 120. Special stains were used to evaluate hepatocyte architecture, glycoprotein and glycogen content, extramedullary hematopoiesis and iron storage. Hepatocyte intranuclear DNA content, cell size, and cell shape were measured by image analysis (CAS 200). At GD 16.5, betamethasone produced a significant decrease in the liver/body weight ratio that, when compared with the placebo group, was greater with the multidose (p < 0.01) than with the single dose (p < 0.05). 16.5 GD single dose hepatocytes were smaller in size as compared to placebo without impact on intranuclear DNA (p < 0.01). Single dose PND 1 hepatocytes demonstrated an increase in intranuclear DNA as compared to placebo but without change in cell size (p < 0.001). The prenatal reduced liver weight recovered in the newborn period. No difference in microscopic architecture of the hepatocytes or histologic differences between either of the three treatment groups was found in glycogen deposition, extramedullary hematopoiesis or iron metabolism at GD 16.5 and postnatally. It was concluded antenatal betamethasone can cause a decrease in the liver/body weight ratio in the fetal mouse that recovers eventually without any functional impact as assessed histologically.

Animals↗

PubMed2007

Intrathecal betamethasone for cancer pain in the lower half of the body: a study of its analgesic efficacy and safety.

BACKGROUND: Sufficient analgesia for cancer pain is sometimes difficult to achieve with conventional treatments. We aimed at investigating the analgesic efficacy and safety of intrathecal betamethasone in patients with uncontrollable cancer pain. METHODS: Betamethasone 1 mg mixed with saline was injected into the lumbar intrathecal space once a week in 10 patients with persistent cancer pain in the lower half of the body. During the 4-week study period, the analgesic efficacy and adverse effects related to intrathecal betamethasone were observed. RESULTS: Long-lasting analgesia (mean numerical pain score < or = 5) for 7 days, after immediate analgesia within 10 min, was obtained without the need to increase the morphine dose in 5 of 10 patients. In almost all of the patients, not only pain, but also uncomfortable symptoms were improved. Adverse effects related to neurotoxicity of intrathecal betamethasone, such as sensory and motor dysfunctions, were not observed in any patients. CONCLUSION: When conventional cancer pain treatments are not successful, intrathecal betamethasone may be useful, as it probably induces long-lasting analgesia without adverse effects and improves activities of daily living, especially in patients with vertebral bone metastases.

Aged↗

PubMed1996

Increased concentrations of endothelin-1 messenger RNA in tissues and endothelin-1 peptide in plasma in septic pigs: modulation by betamethasone.

OBJECTIVES: To study the expression of preproendothelin-1 messenger RNA (mRNA) in tissue after Escherichia coli lipopolysaccharide challenge and to evaluate the possible effects of betamethasone both regarding endothelin-1 production as well as hemodynamic and vascular effects during E. coli lipopolysaccharide infusion in pigs in vivo. DESIGN: Prospective trial. SETTING: Laboratory at a university medical center. SUBJECTS: Ten domestic pigs, weighing 18 to 25 kg. INTERVENTIONS: Anesthetized pigs were given continuous infusions of E. coli lipopolysaccharide (15 micrograms/kg/hr for 3 hrs), with or without prior treatment with betamethasone (0.5 mg/kg im 12 hrs before the start of the surgical preparation and 0.5/kg iv at the start of the preparation). MEASUREMENTS AND MAIN RESULTS: The E. coli lipopolysaccharide infusion evoked the characteristic cardiovascular changes observed in septic shock: decreased mean arterial pressure and cardiac output; increased heart rate and increased pulmonary vascular resistance. Large increases in both arterial plasma concentrations of endothelin-1-like immunoreactivity, as well as preproendothelin-1 mRNA concentrations in tissues, were also observed during the E. coli lipopolysaccharide infusion. Treatment with betamethasone significantly attenuated the E. coli lipopolysaccharide-induced increase in endothelin-1 plasma concentrations, whereas the increased mRNA concentrations were only slightly affected. Furthermore, betamethasone treatment also affected cardiovascular parameters, with significant attenuation of the E. coli lipopolysaccharide-induced increase in heart rate and a higher cardiac output after 60 mins of the E. coli lipopolysaccharide infusion. The urine production, which was markedly decreased during the E. coli lipopolysaccharide infusion, was significantly higher in the betamethasone-treated group compared with the control group. CONCLUSIONS: The present results indicate that the increased concentrations of endothelin-1-like immunoreactivity that are observed in septic shock may have negative effects on both cardiovascular parameters as well as renal function, which is in agreement with a possible role for endothelin-1 in the pathogenesis of septic shock.

Animals↗

PubMedDate not supplied

Chondroprotective effect of betamethasone in lapine pyogenic arthritis.

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.

Animals↗

PubMed1998

The effect of epidural injection of betamethasone or bupivacaine in a rat model of lumbar radiculopathy.

STUDY DESIGN: The effect of epidural injection of betamethasone or bupivacaine was investigated in an animal model of lumbar radiculopathy. OBJECTIVE: To investigate the effects of an epidural steroid (betamethasone) or a local anesthetic (bupivacaine) in an animal model of radiculopathy produced by nerve root irritation. SUMMARY OF BACKGROUND DATA: Epidural injections are commonly used for the treatment of low back pain and sciatica. However, efficacy remains controversial, and there is a paucity of basic information to support clinical use or the injections. METHODS: Fifty-one rats were used. The left L4 and L5 nerve roots were loosely ligated with chromic gut, and either betamethasone, bupivacaine, betamethasone in combination with bupivacaine, or saline was injected using an epidurally placed catheter. The effects of epidural injection were evaluated using response to noxious stimuli and immunohistochemical methods. RESULTS: In betamethasone-treated rats (either alone or in combination with bupivacaine), thermal hyperalgesia was significantly less (P < 0.010 after surgery than that in saline- or bupivacaine-treated groups, in which the hyperalgesia was maximum at 2-3 postoperative weeks before resolving 5 weeks after surgery. Immunohistochemical analysis did not correlate with these results. CONCLUSIONS: Epidural steroid injection has a significant effect on the thermal hyperalgesia produced in a model of radiculopathy, which may provide clinical support for advocates of epidural steroids.

Anesthetics, Local↗

PubMed1976

Percutaneous absorption of betamethasone 17-benzoate measured by radioimmunoassay.

Percutaneous absorption was studied in patients following topical application of betametahsone 17-benzoate cream and gel with occlusion by means of a sensitive and specific radioimmunoassay method. Concentrations of betamethasone 17-benzoate in plasma were between 0.3 and 5 ng/ml, indicating approximately 0.05 to 0.3% of the steroid applied to the skin was detected in plasma. Plasma betamethasone 17-benzoate levels increased in proportion to the amount of the steroid applied to the skin. High correlation between plasma betamethasone 17-benzoate levels and percent inhibition of plasma cortisol was also observed. Approximately 3 ng/ml levels of betamethasone 17-benzoate in plasma induced 90% inhibition of plasma cortisol. The data suggest that betamethasone 17-benzoate in gel base was more readily absorbed than in cream base.

Administration, Topical↗

PubMed1989

A double-blind comparison of the efficacy of betamethasone dipropionate cream twice daily versus once daily in the treatment of steroid responsive dermatoses.

A total of 97 out-patients with steroid responsive dermatoses (63 eczema, 34 psoriasis) were recruited from two centres. They were randomly allocated in a double-blind manner to receive either betamethasone dipropionate cream twice daily or betamethasone dipropionate cream in the morning and base cream in the evening. The treatment period was 3 weeks. Eighty-five patients completed the study. There were no statistical differences between once daily application and twice daily for all of the parameters studied in both the eczema and psoriasis patients. Analysis of the diary card records, however, showed that symptomatic relief occurred more quickly in eczema patients receiving twice daily application of betamethasone dipropionate cream (P = 0.03). The use of betamethasone dipropionate cream once daily in conjunction with an emollient provides a regime which is as effective as a twice daily application of betamethasone dipropionate.

Administration, Topical↗

PubMed2001

Effect of antenatal betamethasone treatment on microtubule-associated proteins MAP1B and MAP2 in fetal sheep.

Betamethasone has been used extensively to accelerate fetal lung maturation, yet little is known of its effects on neuronal morphogenesis in the developing fetus. Microtubule-associated proteins (MAPs) are a diverse family of cytoskeletal proteins that are important for brain development and the maintenance of neuroarchitecture. Vehicle (n = 7) or betamethasone (10 ug h-1, n = 7) was infused I.V. to fetal sheep over 48 h beginning at 0.87 of gestation (128 days of gestation), producing fetal plasma betamethasone concentrations resembling those to which the human fetus is exposed during antenatal glucocorticoid therapy. Paraffin sections of the left hemisphere were stained with monoclonal antibodies against MAP1B and the MAP2 isoforms MAP2a,b,c and MAP2a,b. The level of the juvenile isoform MAP2c was determined by comparison of the two MAP2 immunostainings. We were able to detect MAP1B and MAP2 immunoreactivity (IR) in the fetal sheep brain. MAP2c was the major MAP2, constituting 90.2 % of the total MAPBetamethasone exposure diminished MAP1B IR in the frontal cortex and caudate putamen (P < 0.05) but not in the hippocampus. A decrease of MAP2 IR was found in the frontal cortex, hippocampus and caudate putamen (P < 0.05). Loss of MAP2 IR was mainly due to the loss of MAP2c IR. Haematoxylin-eosin staining did not demonstrate irreversible neuronal damage. Regional cerebral blood flow determined using coloured microspheres was significantly decreased by 28 % in the frontal cortex and by 36 % in the caudate putamen but not in the hippocampus 24 h after the onset of betamethasone exposure (P < 0.05). The loss of MAP1B and MAP2a,b,c IR showed a significant correlation to the cerebral blood flow decrease only in the frontal cortex (P < 0.05). These data suggest that mechanisms other than metabolic insufficiency caused by the decreased cerebral blood flow may contribute to the loss of MAPs. The results suggest that clinical doses of betamethasone may have acute effects on cytoskeletal proteins in the fetal brain.

Animals↗

PubMed1995

The effects of maternal betamethasone administration on the fetus.

OBJECTIVE: To examine prospectively the effects of maternal betamethasone administration on fetal heart rate variation, body, breathing and eye movements and the rest-activity cycle. DESIGN: Thirty-one women on 38 occasions were at risk of premature delivery and received two doses of betamethasone 24 h apart. Gestational age ranged between 26 and 32 weeks. Fetal heart rate was monitored on each of five successive days (0-4) and fetal body, breathing and eye movements were recorded on days 0, 2 and 4. RESULTS: Compared with the control day before steroid administration (day 0), both long term and short term fetal heart rate variation were reduced on days 2 and 3 (P < 0.01). In one-third of the cases, fetal heart rate variation fell transiently below the lower normal range for gestational age. Body movements were reduced on day 2 by 50% (P < 0.01) due to prolonged periods of inactivity (P < 0.01). Breathing movements were largely absent on day 2 (P < 0.01), but the occurrence of eye movements remained unchanged after betamethasone administration. All values returned to baseline on day 4, indicating that no fetal deterioration had occurred during the course of the study period. Similar responses to betamethasone were observed in five fetuses when studied at re-presentation two weeks later. CONCLUSIONS: Maternal betamethasone administration causes a considerable but transient reduction in fetal body movements and activity periods, breathing and heart rate variation, without affecting fetal eye movements. Knowledge of this phenomenon is important when assessing the fetal condition. The effect may be due to a glucocorticoid receptor mediated process in the fetal brain.

Betamethasone↗

PubMed1998

Effect of dexamethasone and betamethasone on fetal heart rate variability in preterm labour: a randomised study.

OBJECTIVE: To compare the effects of betamethasone and dexamethasone on fetal heart rate in appropriately grown fetuses. METHODS: Eighty-two pregnant women (97 fetuses) with preterm labour were randomly allocated to receive betamethasone (n=42) or dexamethasone (n=40) for fetal lung maturation in a nonblinded fashion. Computerised cardiotocogram (CTG) parameters were compared before, during and after treatment. RESULTS: A decrease in fetal heart rate variability was found with betamethasone but no significant changes were found with dexamethasone. Fetal heart rate variability returned to pre-treatment values within a week after cessation of treatment with betamethasone. Neonatal outcome was similar in the two groups. CONCLUSIONS: These findings might prove useful in the management of compromised fetuses with decreased fetal heart rate variability in which the CTG should be used together with other parameters to assess fetal wellbeing during corticosteroid treatment. Dexamethasone may be preferable as the drug of choice since it was associated with significantly less alteration in fetal heart rate variability compared with betamethasone.

Betamethasone↗

PubMed1993

Investigations into the mechanism of vasoconstrictor action of the topical steroid betamethasone-17-valerate in the rat.

1. The effect of topical betamethasone upon skin blood flow was investigated in the rat. Two types of vasodilator stimuli were used; local heating to the surface of the skin and intradermal application of inflammatory agents. Blood flow was measured by laser doppler velocimetry. 2. Topical betamethasone-17-valerate (1 g with an 18 h pretreatment) significantly inhibited the heat-induced vasodilatation in the rat skin, as also did systemically administered betamethasone (1 mg kg-1, 3 h pretreatment). 3. Angiotensin converting enzyme (ACE) inhibitors (captopril, 5 mg kg-1 and enalapril, 1 mg kg-1, 30 min pretreatments) were the only drugs out of several different types of systemically administered inhibitors and antagonists that were tested which also inhibited the heat-induced vasodilatation. Aprotinin (100,000 KIU kg-1, 5 min pretreatment) a serine protease inhibitor, significantly potentiated the heat-induced response. 4. Bradykinin (50 nmol per site), des-Arg9-bradykinin (5 nmol per site), substance P (0.1 nmol per site) and capsaicin (1 mumol per site) induced an increase in skin blood flow. 5. Topical betamethasone treatment resulted in a significant inhibition of the vasodilator response to des-Arg9-bradykinin, whereas captopril treatment inhibited the responses to substance P, capsaicin, bradykinin and des-Arg9-bradykinin. 6. Intradermal application of captopril (10-100 micrograms) also caused a dose-dependent inhibition of the heat-induced vasodilatation. 7. These results suggest that topical betamethasone may be acting in a manner similar to that of the ACE inhibitors to produce an inhibition of the flow responses in the skin and that this effect may be brought about by interfering with the action of vasodilator peptide(s) or protein(s).

Administration, Cutaneous↗