-
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 -
Archivum Immunologiae Et Therapiae... Dec 2022Hematopoietic stem cell (HSC) transplantation is crucial to cure hematologic malignancies. Umbilical cord blood (UCB) is a source of stem cells, but 90% of UCB units are...
Hematopoietic stem cell (HSC) transplantation is crucial to cure hematologic malignancies. Umbilical cord blood (UCB) is a source of stem cells, but 90% of UCB units are discarded due to low cellularity. Improving the engraftment capacities of CD34 stem cells would allow the use of UCB that were so far rejected. Betamethasone induces long-term transcriptomic and epigenomic changes in immune cells through glucocorticoid receptor. We hypothesize that discarded UCB could be used owing to improvements induced by betamethasone. Isolated CD34 HSC from UCB were exposed to the synthetic glucocorticoids betamethasone and fluticasone for 20 h, and cell phenotype was determined before transplantation. NSG mice were sub-lethally irradiated (1 Gy or 2 Gy) 6 h before intravenously transferring 2-5 × 10 CD34 HSC. The peripheral blood engraftment levels and the leukocyte subsets were followed up for 20 weeks using flow cytometry. At end point, the engraftment and leukocyte subsets were determined in the spleen and bone marrow. We demonstrated that betamethasone has surprising effects in recovering immune system homeostasis. Betamethasone and fluticasone increase CXCR4 and decrease HLA class II and CD54 expression in CD34 HSCs. Both glucocorticoids-exposed cells showed a similar engraftment in 2 Gy-irradiated NSG mice. Interestingly, betamethasone-exposed cells showed enhanced engraftment in 1 Gy-irradiated NSG mice, with a trend to increase regulatory T cell percentage when compared to control. Betamethasone induces alterations in CD34 HSCs and improve the engraftment, leading to a faster immune system recovery, which will contribute to engrafted cells survival.
Topics: Mice; Animals; Fetal Blood; Cord Blood Stem Cell Transplantation; Mice, SCID; Mice, Inbred NOD; Betamethasone; Glucocorticoids; Antigens, CD34; Hematopoietic Stem Cells; Hematopoietic Stem Cell Transplantation; Fluticasone
PubMed: 36528821
DOI: 10.1007/s00005-022-00666-5 -
Food Safety (Tokyo, Japan) Jun 2020The Food Safety Commission of Japan (FSCJ) conducted a risk assessment of betamethasone (CAS No. 37-44-9), a synthetic adrenocortical hormone, based on the documents...
The Food Safety Commission of Japan (FSCJ) conducted a risk assessment of betamethasone (CAS No. 37-44-9), a synthetic adrenocortical hormone, based on the documents including assessment reports from the European Medicines Evaluation Agency (EMEA). Among results of various studies, a no-observed-adverse-effect level (NOAEL) of betamethasone (as betamethasone dipropionate) was shown as 0.02 mg/kg bw per day in a fertility and early embryonic development study in rats. FSCJ concluded that it is appropriate to set an acceptable daily intake (ADI) of betamethasone by applying the same ADI as dexamethasone. The ADI for dexamethasone at 0.01 μg/kg bw per day (0.00001 mg/kg bw/day) was specified based on the NOAEL of 0.001 mg/kg bw per day of the endocrine toxicity study in rats. Consequently, FSCJ specified the ADI for betamethasone at 0.01 μg/kg bw per day.
PubMed: 32626636
DOI: 10.14252/foodsafetyfscj.D-20-00016 -
Pharmaceuticals (Basel, Switzerland) Sep 2023Alopecia areata is managed with oral corticosteroids, which has known side effects for patients. Given that a topical application of formulations containing a corticoid...
Alopecia areata is managed with oral corticosteroids, which has known side effects for patients. Given that a topical application of formulations containing a corticoid and a substance controlling hair loss progression could reduce or eliminate such adverse effects and increase the patient's adherence to the treatment, this study prepares polymeric and lipidic nanoparticles (PNPs and NLCs) to co-entrap minoxidil and betamethasone and compares the follicular drug delivery provided by topical application of these nanoparticles. The prepared PNPs loaded 99.1 ± 13.0% minoxidil and 70.2 ± 12.8% betamethasone, while the NLCs entrapped 99.4 ± 0.1 minoxidil and 80.7 ± 0.1% betamethasone. PNPs and NLCs presented diameters in the same range, varying from 414 ± 10 nm to 567 ± 30 nm. The thermal analysis revealed that the production conditions favor the solubilization of the drugs in the nanoparticles, preserving their stability. In in vitro permeation studies with porcine skin, PNPs provided a 2.6-fold increase in minoxidil penetration into the follicular casts compared to the control and no remarkable difference in terms of betamethasone; in contrast, NLCs provided a significant (specifically, a tenfold) increase in minoxidil penetration into the hair follicles compared to the control, and they delivered higher concentrations of betamethasone in hair follicles than both PNPs and the control. Neither PNPs nor NLCs promoted transdermal permeation of the drugs to the receptor solution, which should favor a topical therapy. Furthermore, both nanoparticles targeted approximately 50% of minoxidil delivery to the follicular casts and NLCs targeted 74% of betamethasone delivery to the hair follicles. In conclusion, PNPs and NLCs are promising drug delivery systems for enhancing follicular targeting of drugs, but NLCs showed superior performance for lipophilic drugs.
PubMed: 37765130
DOI: 10.3390/ph16091322 -
Dermatology Online Journal Aug 2019Topical corticosteroids are available in many vehicles. However, patients' preference for vehicles are variable and could be tailored to maximize patient adherence.... (Review)
Review
BACKGROUND
Topical corticosteroids are available in many vehicles. However, patients' preference for vehicles are variable and could be tailored to maximize patient adherence. Spray vehicles may offer, convenience, and strong efficacy.
METHODS
A literature review was conducted using keywords: clobetasol, desoximetasone, betamethasone, triamcinolone, corticosteroid, topical, spray, vehicles, treatment, and clinical trial.
RESULTS
For moderate-to-severe plaque psoriasis, 87% of subjects achieved an Overall Disease Severity (ODS) Score ≤2 at week two and 78% achieved an ODS ≤1 after four weeks with clobetasol propionate (CP) 0.05% spray compared to 17% and 3% in the control group, respectively (P<0.001). For desoximetasone 0.25% spray, 31%-53% with moderate-to-severe psoriasis achieve Physician's Global Assessment (PGA) score ≤1 at day 28 versus 5%-18% in the vehicle spray group (P<0.01). For betamethasone dipropionate 0.05% spray, 19% with mild-to-moderate plaque psoriasis achieved an Investigator's Global Assessment (IGA) score ≤1 or a 2-grade reduction in IGA versus 2.3% in vehicle group (P≤0.001). For mild-to-severe steroid responsive inflammatory dermatoses, 64% using triamcinolone acetonide 0.2% spray achieved clear or almost clear skin at day 14 (no P value reported). Adverse events including burning, irritation, and dryness were similar across all corticosteroids.
Topics: Administration, Cutaneous; Aerosols; Dermatitis; Glucocorticoids; Humans; Inflammation; Medication Adherence; Patient Preference; Psoriasis
PubMed: 31553858
DOI: No ID Found -
Anais Brasileiros de Dermatologia 2022A 73-year-old male patient developed a poorly differentiated squamous cell carcinoma in the anal canal nine months ago. He was treated with two cycles of 5-fluorouracil...
A 73-year-old male patient developed a poorly differentiated squamous cell carcinoma in the anal canal nine months ago. He was treated with two cycles of 5-fluorouracil and cisplatin and concomitant radiotherapy (6 MeV linear photon accelerator, total dose of 54 Gy), with complete remission. Since forty-five days he presentes a painful perianal and intergluteal erosion with circinate pustular borders. Light microscopy showed pseudoepitheliomatous hyperplasia of the epidermis with microabscesses of inflammatory cells (neutrophils and eosinophils) and acantholytic keratinocytes . Indirect immunofluorescence was positive for IgG, with an intercellular pattern, 1:80 titer. The diagnosis of radiotherapy-induced pemphigus vegetans was established and there was significant regression with oral prednisone (40 mg) and topical betamethasone.
Topics: Aged; Humans; Hyperplasia; Male; Pemphigus; Suppuration
PubMed: 35300903
DOI: 10.1016/j.abd.2021.09.005 -
International Journal of Biological... 2021Glucocorticoids are important steroid hormones. As an outstanding scientific discovery, the scientist who discovered glucocorticoids was awarded the Nobel Prize in... (Review)
Review
Glucocorticoids are important steroid hormones. As an outstanding scientific discovery, the scientist who discovered glucocorticoids was awarded the Nobel Prize in Physiology and Medicine in 1950. Cortisone (hydrocortisone) is a natural glucocorticoid, which is secreted with circadian rhythm by the cortical cells of adrenal glands. Physiologically, about 10-20 mg of hydrocortisone are secreted each day for maintaining homeostasis. Since the biological half-life of natural glucocorticoid is short, scientists developed various synthetic glucocorticoids including prednisone, prednisolone, methylprednisolone, triamcinolone, dexamethasone, betamethasone, and so on. These synthetic glucocorticoids are generated by modifying some structures based on the cortisone backbone, leading to extension of their biological half-life with stronger activities. In the face of severe infection, allergy, shock, trauma, pain, and other stresses, the demand for glucocorticoids increases dramatically. It is critical to supplement extra glucocorticoids to protect the biological functions of vital organs. However, the amount and duration of glucocorticoid administration need to be carefully adjusted, because a series of side effects may occur after long-term or high-dose usage of glucocorticoids. This review article will discuss the application of glucocorticoids in the treatment of patients with severe or critical COVID-19 and solid tumors of advanced stage. The controversy of using glucocorticoid in medical community will also be discussed. This review article will help doctors and basic researchers better understand the practical application of glucocorticoids.
Topics: COVID-19; Glucocorticoids; Humans; Neoplasms; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 33907516
DOI: 10.7150/ijbs.58695 -
Dermatology and Therapy Oct 2023Topical treatment plays a crucial role in psoriasis management, with non-adherence being a major barrier to treatment success. The fixed-dose combination of calcipotriol... (Review)
Review
Topical treatment plays a crucial role in psoriasis management, with non-adherence being a major barrier to treatment success. The fixed-dose combination of calcipotriol (CAL) and betamethasone dipropionate (BDP) represents the first-line choice in topical psoriasis treatment. A CAL/BDP cream based on polyaphron dispersion (PAD) Technology has emerged as a novel formulation for a more convenient topical treatment of psoriasis. This article aims to summarize the most relevant published evidence about CAL/BDP PAD-cream and its underlying PAD Technology. The PAD Technology enables CAL and BDP stability in an aqueous cream through a multimolecular shell structure, as well as it increases the penetration of both active ingredients into the epidermis and dermis. This technology also demonstrated to increase the cosmetic acceptability and to provide the desirable sensory properties for a topical psoriasis treatment. Two phase III clinical trials have been conducted so far with CAL/BDP PAD-cream. Findings from both trials revealed high efficacy with a fast onset of action, a favourable safety and tolerability profile and convenience for CAL/BDP PAD-cream compared to CAL/BDP gel. In the trial including patients with psoriasis affecting the scalp (MC2-01-C7), results support the use of CAL/BDP PAD-cream in scalp psoriasis. An anchored matching-adjusted indirect comparison (MAIC) was conducted to compare CAL/BDP PAD-cream and CAL/BDP foam, as both products had been previously compared to CAL/BDP gel. CAL/BDP PAD-cream and CAL/BDP foam showed equivalent efficacy and quality of life at their recommended treatment duration, whereas greater treatment satisfaction for CAL/BDP PAD-cream was found after one week of treatment. Overall, the high patient acceptability and treatment satisfaction observed with CAL/BDP PAD-cream in clinical trials may lead to improved adherence and hence higher efficacy in clinical practice.
PubMed: 37740858
DOI: 10.1007/s13555-023-01003-0 -
International Journal of Surgery... Jan 2024Postoperative pain after laminoplasty and laminectomy occurs partially from local trauma of the paraspinal tissue. Finding a multimodal analgesic cocktail to enhance the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Postoperative pain after laminoplasty and laminectomy occurs partially from local trauma of the paraspinal tissue. Finding a multimodal analgesic cocktail to enhance the duration and effect of local infiltration analgesia is crucial. Because of the rapid onset and long duration of action of betamethasone, the authors hypothesized that, a pre-emptive multimodal infiltration regimen of betamethasone and ropivacaine reduces pain scores and opioid demand, and improves patient satisfaction following laminoplasty and laminectomy.
MATERIALS AND METHODS
This prospective, randomized, open-label, blinded endpoint study was conducted between 1 September 2021 and 3 June 2022, and included patients between the ages of 18 and 64 scheduled for elective laminoplasty or laminectomy under general anesthesia, with American Society of Anesthesiologists classification I/II. One hundred sixteen patients were randomly assigned to either the BR (Betamethasone-Ropivacaine) group or the R (Ropivacaine) group in a 1:1 ratio. Each group received pre-emptive infiltration of a total of 10 ml study solution into each level. Every 30 ml of study solution composed of 0.5 ml of betamethasone plus 14.5 ml of saline and 15 ml of 1% ropivacaine for the BR group, and 15 ml of 1% ropivacaine added to 15 ml of saline for the R group. Infiltration of epidural space and intrathecal space were avoided and the spinous process, transverse process, facet joints, and lamina were injected, along with paravertebral muscles and subcutaneous tissue. Cumulative 48 h postoperative butorphanol consumption via PCA (Patient-controlled analgesia) was the primary outcome. Intention-to-treat (ITT) principle was used for primary analysis.
RESULTS
Baseline characteristics were identical in both groups ( P >0.05). The cumulative 48 h postoperative butorphanol consumption via PCA was 3.0±1.4 mg in the BR group ( n =58), and 7.1±1.2 mg in the R group ( n =58) ( P <0.001). Overall cumulative opioid demand was lower at different time intervals in the BR group ( P <0.001), along with the estimated median time of first analgesia demand via PCA (3.3 h in the BR group and 1.6 h in the R group). The visual analog scale (VAS) score at movement and rest were also significantly lower until 3 months and 6 weeks, respectively. No side effects or adverse events associated with the intervention were observed in this study.
CONCLUSIONS
Pre-emptive analgesia with betamethasone and ropivacaine provides better postoperative pain management following laminoplasty and laminectomy, compared to ropivacaine alone. This is an effective technique worthy of further evaluation.
Topics: Humans; Adolescent; Young Adult; Adult; Middle Aged; Ropivacaine; Anesthetics, Local; Analgesics, Opioid; Betamethasone; Laminectomy; Butorphanol; Laminoplasty; Prospective Studies; Pain, Postoperative; Analgesia, Patient-Controlled; Double-Blind Method; Amides
PubMed: 37800559
DOI: 10.1097/JS9.0000000000000821 -
Medical Hypothesis, Discovery &... 2020The purpose of this study was to compare the effects of propranolol, timolol and bevacizumab with betamethasone to prevent corneal neovascularization (CNV) in rabbits....
The purpose of this study was to compare the effects of propranolol, timolol and bevacizumab with betamethasone to prevent corneal neovascularization (CNV) in rabbits. This study was performed on 28 male rabbits. CNV was induced by three 7-0 silk sutures 2 mm long and 1 mm distal to the limbus. Animals were randomly divided into 4 groups of propranolol + betamethasone, timolol + betamethasone and bevacizumab + betamethasone and betamethasone alone. Eye drops were started from the first day of study. On 7, 14, 21, 28, 35 and 42 days, vascular progression, time of neovascularization and vascular area were evaluated and compared with the control group (betamethasone alone). There was a significant reduction in the area of neovascularization in the timolol and bevacizumab groups compared to the control group (P-value = 0.05, P=0.047, respectively). Also, regarding vascular progression, there was a significant decrease in the timolol and bevacizumab groups (P-value = 0.014, P=0.002, respectively). Regarding delayed onset of neovascularization, there was a significant difference in the timolol and bevacizumab group in rabbits (P-value = 0.04, P=0.00, respectively). In conclusion, the use of timolol and bevacizumab drops besides betamethasone can delay neovascularization and decrease the length of corneal vascularization in rabbits.
PubMed: 31976343
DOI: No ID Found