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FASEB Journal : Official Publication of... Jun 2023Antenatal glucocorticoids accelerate fetal lung maturation and reduce mortality in preterm babies but can trigger adverse effects on the cardiovascular system. The...
Antenatal glucocorticoids accelerate fetal lung maturation and reduce mortality in preterm babies but can trigger adverse effects on the cardiovascular system. The mechanisms underlying off-target effects of the synthetic glucocorticoids mostly used, Dexamethasone (Dex) and Betamethasone (Beta), are unknown. We investigated effects of Dex and Beta on cardiovascular structure and function, and underlying molecular mechanism using the chicken embryo, an established model system to isolate effects of therapy on the developing heart and vasculature, independent of effects on the mother or placenta. Fertilized eggs were treated with Dex (0.1 mg kg ), Beta (0.1 mg kg ), or water vehicle (Control) on embryonic day 14 (E14, term = 21 days). At E19, biometry, cardiovascular function, stereological, and molecular analyses were determined. Both glucocorticoids promoted growth restriction, with Beta being more severe. Beta compared with Dex induced greater cardiac diastolic dysfunction and also impaired systolic function. While Dex triggered cardiomyocyte hypertrophy, Beta promoted a decrease in cardiomyocyte number. Molecular changes of Dex on the developing heart included oxidative stress, activation of p38, and cleaved caspase 3. In contrast, impaired GR downregulation, activation of p53, p16, and MKK3 coupled with CDK2 transcriptional repression linked the effects of Beta on cardiomyocyte senescence. Beta but not Dex impaired NO-dependent relaxation of peripheral resistance arteries. Beta diminished contractile responses to potassium and phenylephrine, but Dex enhanced peripheral constrictor reactivity to endothelin-1. We conclude that Dex and Beta have direct differential detrimental effects on the developing cardiovascular system.
Topics: Chick Embryo; Female; Pregnancy; Animals; Betamethasone; Glucocorticoids; Heart; Arteries; Dexamethasone
PubMed: 37132324
DOI: 10.1096/fj.202200676RR -
Skin Therapy Letter Jul 2018Most people with mild-to-moderate psoriasis manage their disease with topical therapies. However, adherence to topical treatment remains a challenge, as the daily... (Review)
Review
Most people with mild-to-moderate psoriasis manage their disease with topical therapies. However, adherence to topical treatment remains a challenge, as the daily application creates a significant treatment burden. New topical therapeutic options need to offer higher efficacy and better patient acceptability, including easier application, to reduce treatment burden and enhance patient adherence. Topical foam vehicles are innovative alternatives to creams and ointments, addressing many patient challenges with traditional vehicles. Well-designed foam vehicles are easily spread over large areas of the skin, while importantly not leaving a greasy or oily film on the skin after application. Calcipotriol/betamethasone diproprionate aerosol foam is a new psoriasis treatment option that is rapidly effective, offers greater efficacy versus ointment and gel formulations, and has been shown to increase patient treatment satisfaction. Hence, by addressing the several crucial unmet clinical needs in patients with mild-to-moderate psoriasis, this optimized foam formulation is poised to improve treatment follow-through.
Topics: Administration, Cutaneous; Aerosols; Betamethasone; Calcitriol; Dermatologic Agents; Drug Combinations; Humans; Psoriasis; Randomized Controlled Trials as Topic
PubMed: 30086183
DOI: No ID Found -
BMC Oral Health Oct 2023Recurrent Aphthous Stomatitis (RAS) is painful oral ulceration frequently treated with topical steroids. There is limited published evidence for the efficacy of any... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Recurrent Aphthous Stomatitis (RAS) is painful oral ulceration frequently treated with topical steroids. There is limited published evidence for the efficacy of any treatment for RAS and there remains a need for longitudinal randomised clinical trials to evaluate and compare the effectiveness of different therapies in the management of RAS. The aim of the current project was to assess the efficacy of betamethasone mouthwash and colchicine tablets, individually and combined, for the treatment of RAS, and to establish the optimum treatment period necessary for a significant reduction in the disease severity.
METHODOLOGY
A randomised, prospective, parallel-group clinical trial was conducted over one year, to compare the efficacy of three therapies in RAS. One hundred and six patients were randomized into three groups; 35 received betamethasone mouthwash, 35 had colchicine tablets and 36 received both therapies. The response was evaluated quantitatively every 3 months for 1 year, using the Ulcer Severity Score (USS).
RESULTS
For all three treatment regimes, the mean USS decreased by about 30% in the first 3 months (p < 0.001). Further improvement was noted for up to 9 months. At the end of the study, the mean USS had improved by 50% from 34.9 ± 7.2 before treatment to 17.5 ± 8.9 after treatment (p < 0.001). Of included participants, 86% showed significant clinical improvement by the end of the study. There were no significant differences in outcomes between the three regimes (p < 0.05).
CONCLUSIONS
This clinical trial has provided evidence for the efficacy of betamethasone mouthwash and for colchicine tablets in the treatment of RAS and has shown that at least six months of treatment may be required for optimum effect.
CLINICAL TRIAL REGISTRATION NUMBER
ISRCTN3267716. Date of clinical trial registration: 15/04/2018.
Topics: Humans; Stomatitis, Aphthous; Colchicine; Mouthwashes; Prospective Studies; Betamethasone
PubMed: 37789351
DOI: 10.1186/s12903-023-03335-x -
Journal of Pharmacokinetics and... Apr 2021Population analysis of pharmacokinetic data for five differing dosage forms and routes for dexamethasone and betamethasone in 48 healthy nonpregnant Indian women was... (Randomized Controlled Trial)
Randomized Controlled Trial
Population analysis of pharmacokinetic data for five differing dosage forms and routes for dexamethasone and betamethasone in 48 healthy nonpregnant Indian women was performed that accounted for a partial and complex cross-over design. Single doses of 6 mg dexamethasone phosphate (DEX-P), betamethasone phosphate (BET-P), or 1:1 mixture of betamethasone phosphate and acetate (BET-PA) were administered orally (PO) or intramuscularly (IM). Plasma concentrations collected for two periods over 96 h were described with a two-compartment model with differing PO and IM first-order absorption inputs. Clearances and volumes were divided by the IM bioavailability [Formula: see text]. The homogeneous ages, body weights, and ethnicity of the women obviated covariate analysis. Parameter estimates were obtained by the Laplace estimation method implemented in NONMEM 7.4. Typical values for dexamethasone were clearance ([Formula: see text] of 9.29 L/h, steady-state volume ([Formula: see text] of 56.4 L, IM absorption constant [Formula: see text] of 0.460 1/h and oral absorption constant ([Formula: see text] of 0.936 1/h. Betamethasone parameters were CL/F of 5.95 L/h, [Formula: see text] of 72.4 L, [Formula: see text] of 0.971 1/h, and [Formula: see text] of 1.21 1/h. The PO to IM F values were close to 1.0 for both drugs. The terminal half-lives averaged about 7.5 h for DEX, 17 h for BET, and 78 h for BET from BET-PA with the latter reflecting very slow release of BET from the acetate ester. Overall, BET exhibited slower clearance, larger volume of distribution, faster absorption, and longer persistence than DEX. These data may be useful in considering exposures when substituting one form of corticosteroid for another.
Topics: Adult; Female; Humans; Young Adult; Administration, Oral; Adrenal Cortex Hormones; Betamethasone; Biological Availability; Biological Variation, Population; Cross-Over Studies; Dexamethasone; Drug Substitution; Half-Life; Healthy Volunteers; India; Injections, Intramuscular
PubMed: 33389521
DOI: 10.1007/s10928-020-09730-z -
American Family Physician Jun 2000Lichen planus is an inflammatory mucocutaneous condition with characteristic violaceous polygonal flat-topped papules and plaques. Pruritus is often severe. Skin lesions... (Review)
Review
Lichen planus is an inflammatory mucocutaneous condition with characteristic violaceous polygonal flat-topped papules and plaques. Pruritus is often severe. Skin lesions may be disfiguring, and involvement of the oral mucosa or genital mucosa in severe cases may be debilitating. Oral lichen planus may predispose to the development of squamous cell carcinoma within lesions. Involvement of the scalp and the nails may also occur. While most cases of lichen planus are idiopathic, some may be caused by the ingestion of certain medications (e.g., gold, antimalarial agents, penicillamine, thiazide diuretics, beta blockers, nonsteroidal anti-inflammatory drugs, quinidine and angiotensin-converting enzyme inhibitors) or linked to hepatitis C virus infection. Patients with localized lichen planus are usually treated with potent topical steroids, while systemic steroids are used to treat patients with generalized lichen planus.
Topics: Acitretin; Anti-Inflammatory Agents; Betamethasone; Clobetasol; Diagnosis, Differential; Humans; Keratolytic Agents; Lichen Planus; PUVA Therapy; Patient Education as Topic; Prednisone; Risk Factors; Teaching Materials
PubMed: 10865927
DOI: No ID Found -
Clinical and Translational Science Mar 2020High-dose betamethasone and dexamethasone are standard of care treatments for women at risk of preterm delivery to improve neonatal respiratory and mortality outcomes.... (Randomized Controlled Trial)
Randomized Controlled Trial
High-dose betamethasone and dexamethasone are standard of care treatments for women at risk of preterm delivery to improve neonatal respiratory and mortality outcomes. The dose in current use has never been evaluated to minimize exposures while assuring efficacy. We report the pharmacokinetics and pharmacodynamics (PDs) of oral and intramuscular treatments with single 6 mg doses of dexamethasone phosphate, betamethasone phosphate, or a 1:1 mixture of betamethasone phosphate and betamethasone acetate in reproductive age South Asian women. Intramuscular or oral betamethasone has a terminal half-life of 11 hours, about twice as long as the 5.5 hours for oral and intramuscular dexamethasone. The 1:1 mixture of betamethasone phosphate and betamethasone acetate shows an immediate release of betamethasone followed by a slow release where plasma betamethasone can be measured out to 14 days after the single dose administration, likely from a depo formed at the injection site by the acetate. PD responses were: increased glucose, suppressed cortisol, increased neutrophils, and suppressed basophils, CD3CD4 and CD3CD8 lymphocytes. PD responses were comparable for betamethasone and dexamethasone, but with longer times to return to baseline for betamethasone. The 1:1 mixture of betamethasone phosphate and betamethasone acetate caused much longer adrenal suppression because of the slow release. These results will guide the development of better treatment strategies to minimize fetal and maternal drug exposures for women at risk of preterm delivery.
Topics: Administration, Oral; Adult; Betamethasone; Cross-Over Studies; Dexamethasone; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Glucocorticoids; Half-Life; Humans; India; Injections, Intramuscular; Premature Birth; Prenatal Care
PubMed: 31808984
DOI: 10.1111/cts.12724 -
The Journal of Dermatological Treatment Dec 2023Psoriasis is a chronic skin disease, and topical sequential therapy with a combination of calcipotriol and calcipotriol betamethasone is currently approved topical...
BACKGROUND
Psoriasis is a chronic skin disease, and topical sequential therapy with a combination of calcipotriol and calcipotriol betamethasone is currently approved topical treatment. However, the exact mechanism by which this treatment regimen relieves psoriasis is unknown.
METHOD
We assembled a cohort of 65 psoriasis patients and divided post-treatment cohort into responder group and non-responder group according to the Psoriasis Area Severity Index (PASI) score after 12-week treatment. We measured the expression levels of proteins in collected 130 serum samples using our in-depth proteomics platform with a data-independent acquisition mass spectrometer and antibody microarray. We performed bioinformatics analyses of the biologic processes and signaling pathways that were changed in the responder group and constructed a proteomics landscape of psoriasis pathogenesis response to treatment. We then validated the biomarkers of disease severity in an independent cohort of 88 samples using an enzyme-linked immunosorbent assay.
RESULTS
We first identified 174 differentially expressed proteins (DEPs) for comparative analysis of proteins between responders and non-responders at baseline ( < 0.05). Then pathway analysis showed that the responders focused more on signaling molecules and interaction, complement and coagulation cascades, whereas the non-responders more on signal transduction and IL-17 signaling pathways. We further identified four candidate biomarkers (COLEC11, C1QA, BNC2, ITIH4) response to treatment. We also found 125 DEPs ( < 0.05) after treatment compared with before treatment in responder group. Pathway analysis showed an enrichment in pathways related to complement and coagulation cascades, phagosome, ECM-receptor interaction, cholesterol metabolism, vitamin digestion and absorption. CD14 was validated as potential biomarkers for the disease severity of psoriasis and treatment targets.
CONCLUSION
In this work, we analyzed the response to topical sequential therapy and finally identified four biomarkers. Additionally, we found that topical sequential therapy may alleviate psoriasis by regulating lipid metabolism and modulating the immune response by affecting the complement activation process.
Topics: Humans; Proteomics; Psoriasis; Betamethasone; Biomarkers; Computational Biology
PubMed: 37621164
DOI: 10.1080/09546634.2023.2248318 -
CMAJ : Canadian Medical Association... Mar 2017
Topics: Administration, Cutaneous; Adult; Anti-Inflammatory Agents; Betamethasone; Dermatitis; Histamine Antagonists; Humans; Loratadine; Male; Raw Foods; Shiitake Mushrooms
PubMed: 28385716
DOI: 10.1503/cmaj.160644 -
Indian Journal of Dermatology,... 2016Topical calcipotriol/betamethasone dipropionate ointment/gel has been commonly used for the treatment of psoriasis vulgaris. However, the efficacy of this combination... (Review)
Review
Topical calcipotriol/betamethasone dipropionate ointment/gel has been commonly used for the treatment of psoriasis vulgaris. However, the efficacy of this combination needs to be consolidated. We aimed to assess the effects and safety profile of calcipotriol/betamethasone dipropionate for the treatment of psoriasis vulgaris, using evidence based approach. Randomized controlled trials on the treatment of psoriasis vulgaris with calcipotriol/betamethasone dipropionate were identified by searching PubMed, China National Knowledge Infrastructure and the Cochrane Library. The primary outcome measure was the Psoriasis Area and Severity Index (PASI) score. Ten randomized controlled trials involving 6590 participants were included. The methodologies of the studies were generally of moderate to high quality. These trials used topical calcipotriol/betamethasone dipropionate for 4 or 8 weeks, and were compared with topical calcipotriol or betamethasone. The results showed that calcipotriol/betamethasone dipropionate was more effective than controls. A four-week treatment with calcipotriol/betamethasone dipropionate did not show any significant difference between the once-daily or twice-daily regimen. The adverse events of calcipotriol/betamethasone dipropionate were tolerable and acceptable. The reports included in this review are heterogenous and have limitations. Topical application of calcipotriol/betamethasone dipropionate once daily is an efficacious treatment for psoriasis vulgaris and is associated with few side effects.
Topics: Animals; Betamethasone; Calcitriol; Dermatologic Agents; Drug Combinations; Humans; Psoriasis; Randomized Controlled Trials as Topic
PubMed: 26924402
DOI: 10.4103/0378-6323.175919 -
British Journal of Clinical Pharmacology Feb 2022No study has evaluated the betamethasone pharmacokinetics in twin pregnancies according to chorionicity. This study aimed to describe and compare the betamethasone...
AIM
No study has evaluated the betamethasone pharmacokinetics in twin pregnancies according to chorionicity. This study aimed to describe and compare the betamethasone pharmacokinetic parameters in singleton and dichorionic (DC) and monochorionic twin pregnancies in the third trimester of pregnancy.
METHODS
Twenty-six pregnant women received 2 intramuscular doses of 6 mg of betamethasone sodium phosphate plus 6 mg betamethasone acetate due to preterm labour. Serial blood samples were collected for 24 hours after the first intramuscular dose of betamethasone esters. Betamethasone plasma concentrations were quantified using a validated liquid chromatography-tandem mass spectrometry analytical method, and the pharmacokinetic parameters were obtained employing a noncompartmental model. Preliminary data on the betamethasone placental transfer are also presented.
RESULTS
The geometric mean (95% confidence interval) of AUC 645.1 (504.3-825.2) vs. 409.8 (311.2-539.6) ng.h/mL and CL/F 17.70 (13.84-22.65) vs. 27.87 (21.17-36.69) were significantly different, respectively, in singleton pregnancies when compared to DC twins.
CONCLUSION
Data from this study suggest that the presence of 2 foetoplacental units may increase the betamethasone metabolism by hepatic CYP3A4 and/or placental 11β-HSD2 enzymes. Pharmacokinetic-pharmacodynamic clinical studies are needed to investigate whether these betamethasone pharmacokinetic changes have clinical repercussions for the newborns and require dose adjustment in DC twin pregnancies.
Topics: Betamethasone; Chorion; Female; Humans; Infant, Newborn; Placenta; Pregnancy; Pregnancy Trimester, Third; Pregnancy, Twin
PubMed: 34665470
DOI: 10.1111/bcp.15111