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1.
J Inherit Metab Dis ; 47(2): 302-316, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38131282

RESUMEN

Mevalonate kinase deficiency (MKD) is an autoinflammatory metabolic disorder caused by bi-allelic loss-of-function variants in the MVK gene, resulting in decreased activity of the encoded mevalonate kinase (MK). Clinical presentation ranges from the severe early-lethal mevalonic aciduria to the milder hyper-IgD syndrome (MKD-HIDS), and is in the majority of patients associated with recurrent inflammatory episodes with often unclear cause. Previous studies with MKD-HIDS patient cells indicated that increased temperature, as caused by fever during an inflammatory episode, lowers the residual MK activity, which causes a temporary shortage of non-sterol isoprenoids that promotes the further development of inflammation. Because an increase of the residual MK activity is expected to make MKD-HIDS patients less sensitive to developing inflammatory episodes, we established a cell-based screen that can be used to identify compounds and/or therapeutic targets that promote this increase. Using a reporter HeLa cell line that stably expresses the most common MKD-HIDS variant, MK-V377I, C-terminally tagged with bioluminescent NanoLuc luciferase (nLuc), we screened the Prestwick Chemical Library®, which includes 1280 FDA-approved compounds. Multiple compounds increased MK-V377I-nLuc bioluminescence, including steroids (i.e., glucocorticoids, estrogens, and progestogens), statins and antineoplastic drugs. The glucocorticoids increased MK-V377I-nLuc bioluminescence through glucocorticoid receptor signaling. Subsequent studies in MKD-HIDS patient cells showed that the potent glucocorticoid clobetasol propionate increases gene transcription of MVK and other genes regulated by the transcription factor sterol regulatory element-binding protein 2 (SREBP-2). Our results suggest that increasing the flux through the isoprenoid biosynthesis pathway by targeting the glucocorticoid receptor or SREBP-2 could be a potential therapeutic strategy in MKD-HIDS.


Asunto(s)
Deficiencia de Mevalonato Quinasa , Humanos , Deficiencia de Mevalonato Quinasa/tratamiento farmacológico , Deficiencia de Mevalonato Quinasa/genética , Células HeLa , Receptores de Glucocorticoides/uso terapéutico , Proteína 1 de Unión a los Elementos Reguladores de Esteroles , Fosfotransferasas (Aceptor de Grupo Alcohol)
2.
BJOG ; 131(6): 740-749, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38149520

RESUMEN

OBJECTIVE: To evaluate the efficacy and safety of a novel non-ablative Nd:YAG/Er:YAG dual laser treatment for vulvar lichen sclerosus (LS) in comparison with the recommended first-line therapy with topical steroid. DESIGN: A randomised investigator-initiated active-controlled trial. SETTING: Single tertiary referral centre. POPULATION: Women with vulvar LS. METHODS: Randomisation (2:1) to Nd:YAG/Er:YAG laser therapy or topical clobetasol proprionate therapy. Four laser treatments at 0, 1, 2 and 4 months or decreasing doses of steroid for 6 months. MAIN OUTCOME MEASURES: The primary outcome was the change in objective validated clinical LS score in the laser arm between baseline and 6 months. Secondary outcomes were laser tolerability/safety, symptom scores and patient satisfaction. RESULTS: Sixty-six women were included, 44 in the laser group and 22 in the steroid group. The total LS score decreased by -2.34 ± 1.20 (95% CI -2.71 to -1.98) in women treated with laser compared with a decrease of -0.95 ± 0.90 (95% CI -1.35 to -0.56) in those receiving steroid applications (p < 0.001). Laser treatment was safe and well tolerated. Subjective severity scores (on visual analogue scale) and vulvovaginal symptoms questionnaire scores improved similarly for the laser and steroid arms without significant differences between the two treatments. Patient satisfaction was higher in the laser arm than in the steroid arm (p = 0.035). CONCLUSIONS: Non-ablative dual Nd:YAG/Er:YAG laser therapy was safe and significantly improved clinical outcome and subjective symptoms at the 6-month follow up. This suggests that laser may be a promising alternative to corticosteroid therapy. However, the authors caution regular follow ups because of the premalignant nature of the disease.


Asunto(s)
Láseres de Estado Sólido , Liquen Escleroso Vulvar , Femenino , Humanos , Glucocorticoides , Clobetasol/uso terapéutico , Clobetasol/efectos adversos , Láseres de Estado Sólido/uso terapéutico , Esteroides/uso terapéutico , Resultado del Tratamiento
3.
Acta Pharmacol Sin ; 45(7): 1506-1519, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38480835

RESUMEN

Combining radiotherapy with Nrf-2 inhibitor holds promise as a potential therapeutic strategy for radioresistant lung cancer. Here, the radiosensitizing efficacy of a synthetic glucocorticoid clobetasol propionate (CP) in A549 human lung cancer cells was evaluated. CP exhibited potent radiosensitization in lung cancer cells via inhibition of Nrf-2 pathway, leading to elevation of oxidative stress. Transcriptomic studies revealed significant modulation of pathways related to ferroptosis, fatty acid and glutathione metabolism. Consistent with these findings, CP treatment followed by radiation exposure showed characteristic features of ferroptosis in terms of mitochondrial swelling, rupture and loss of cristae. Ferroptosis is a form of regulated cell death triggered by iron-dependent ROS accumulation and lipid peroxidation. In combination with radiation, CP showed enhanced iron release, mitochondrial ROS, and lipid peroxidation, indicating ferroptosis induction. Further, iron chelation, inhibition of lipid peroxidation or scavenging mitochondrial ROS prevented CP-mediated radiosensitization. Nrf-2 negatively regulates ferroptosis through upregulation of antioxidant defense and iron homeostasis. Interestingly, Nrf-2 overexpressing A549 cells were refractory to CP-mediated ferroptosis induction and radiosensitization. Thus, this study identified anti-psoriatic drug clobetasol propionate can be repurposed as a promising radiosensitizer for Keap-1 mutant lung cancers.


Asunto(s)
Clobetasol , Ferroptosis , Neoplasias Pulmonares , Mitocondrias , Factor 2 Relacionado con NF-E2 , Especies Reactivas de Oxígeno , Humanos , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/antagonistas & inhibidores , Ferroptosis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/efectos de la radiación , Clobetasol/farmacología , Fármacos Sensibilizantes a Radiaciones/farmacología , Células A549 , Peroxidación de Lípido/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos
4.
Contact Dermatitis ; 91(3): 228-236, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38965446

RESUMEN

BACKGROUND: Budesonide and tixocortol pivalate as markers of contact allergy to corticosteroids have been questioned, as they are not able to detect a significant percentage of allergic patients. OBJECTIVES: To investigate the potential role of clobetasol propionate in enhancing corticosteroid sensitisation detection. METHODS: Between January 2022 and December 2023, patients who attended centres involved in the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy were tested with an extended baseline series that included budesonide, tixocortol pivalate, clobetasol propionate 0.1% in ethanol and 1% in petrolatum. RESULTS: A total of 4338 patients were tested. Twenty-four patients were allergic to budesonide (0.55%, 95% CI: 0.37-0.82); nine patients were allergic to tixocortol pivalate (0.21%, 95% CI: 0.11-0.39); and 23 patients were allergic to clobetasol (0.53%, 95% CI: 0.35-0.79). Only four of those patients allergic to clobetasol were detected by budesonide and one by tixocortol pivalate. No significant differences in the number of positive tests were found between clobetasol in petrolatum or ethanol. CONCLUSIONS: In Spain budesonide remains the main corticosteroid allergy marker whereas the role of tixocortol pivalate is questionable. The addition of clobetasol propionate to the Spanish baseline series would improve the ability to detect patients allergic to corticosteroids.


Asunto(s)
Budesonida , Clobetasol , Dermatitis Alérgica por Contacto , Humanos , Clobetasol/efectos adversos , Dermatitis Alérgica por Contacto/etiología , Dermatitis Alérgica por Contacto/diagnóstico , Budesonida/efectos adversos , España , Femenino , Masculino , Pruebas del Parche , Adulto , Persona de Mediana Edad , Glucocorticoides/efectos adversos , Hidrocortisona/análogos & derivados
5.
Oral Dis ; 29(3): 1250-1258, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34817126

RESUMEN

OBJECTIVES: To evaluate the serum and salivary levels of IL-1ß, IL-6, IL-17A, TNF-α, IL-4, and IL-10 in patients with oral lichen planus (OLP) treated with Photobiomodulation (PBM) and clobetasol propionate 0.05%. MATERIAL AND METHODS: Thirty-four OLP patients were randomized into two groups: Control (clobetasol propionate 0.05%) and PBM (660 nm, 100 mW, 177 J/cm2 , 5 s, 0.5 J per point). Serum and saliva were collected at baseline and at the end of treatment (after 30 days) and evaluated using ELISA. The cytokine results were correlated with pain, clinical subtypes, and clinical scores of OLP. RESULTS: IL-1ß, IL-6, IL-17A, TNF-α, and IL-4 levels were higher in saliva in relation to serum. IL-1ß was the most concentrated cytokine in saliva, and a positive correlation with the severity of OLP was noticed. After treatment with corticosteroid, IL-1ß in saliva decreased significantly. No modulation of all cytokines was observed after PBM. CONCLUSION: IL-1ß appears to be an important cytokine involved in OLP pathogenesis. In addition, the mechanisms of action of PBM do not seem to be linked to the modulation of pro or anti-inflammatory cytokines at the end of treatment. It is possible that this events occurred early during treatment.


Asunto(s)
Citocinas , Liquen Plano Oral , Humanos , Citocinas/análisis , Interleucina-6/análisis , Interleucina-17 , Factor de Necrosis Tumoral alfa , Clobetasol/uso terapéutico , Liquen Plano Oral/tratamiento farmacológico , Liquen Plano Oral/radioterapia , Interleucina-4 , Saliva/química
6.
Wound Repair Regen ; 30(4): 491-497, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35589608

RESUMEN

The present study designed to evaluate the healing power of platelet-rich fibrin (PRF) in terms of pain control and mucosal repair. A randomised, controlled, pilot clinical trial was conducted on 16 patients randomly distributed with 1:1 allocation ratio into two groups. The treatment group received PRF minced and mixed with orabase and the control group received clobetasol propionate 0.05% mixed with orabase. Pain reduction was evaluated as primary outcome along with mucositis healing as secondary outcome. A statistically significant difference in pain reduction was observed between the two groups (p ≤ 0.05). The clinical results at Day 7 has shown that PRF group had 100% pain reduction while, CP group had 32.5% reduction from base line. PRF offered superior clinical results providing rapid pain alleviation and accelerated ulcer healing compared to corticosteroids.


Asunto(s)
Úlceras Bucales , Fibrina Rica en Plaquetas , Enfermedades de la Piel , Humanos , Dolor , Cicatrización de Heridas
7.
Dermatol Ther ; 34(2): e14855, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33559259

RESUMEN

Prurigo nodularis (PN) is a chronic, benign neurodermatitis of unclear etiology characterized by excoriated, intensely pruritic nodules secondary to an intense itch-scratch cycle. PN treatment is still a challenge, and it is frustrating for both dermatologists and patients. The evidence for the effectiveness of a readily available treatment like cryotherapy is limited. To compare the efficacy of cryotherapy vs 0.05% clobetasol propionate in PN patients attending the RDTC, Northern Tanzania, from October 2018 to July 2019. Based on previous year data, it was expected to enroll nine patients. Assent and consent were obtained. Fourteen patients were enrolled, 11 analyzed; intra-subject control done each one-half of the body received either intervention randomly. The cryotherapy was given in two cycles from 5 to 10 s in one session and clobetasol propionate was applied twice daily for 4 weeks. The patients were followed-up weekly by telephone reminded them to apply clobetasol. Data entry and analysis was done in SPSS version 20. Ethical considerations were observed. Eleven patients were analyzed; four (36%) males and seven (64%) females. Cryotherapy had nodule clearance in the 11 patients of 75% to 100% in 11 (100%) and clobetasol propionate only in three of the patients. Seven patients (63.6%) preferred cryotherapy. Cryotherapy preferred above clobetasol propionate.


Asunto(s)
Neurodermatitis , Prurigo , Clobetasol/uso terapéutico , Femenino , Humanos , Masculino , Prurigo/diagnóstico , Prurigo/terapia , Tanzanía , Centros de Atención Terciaria , Resultado del Tratamiento
8.
Australas J Dermatol ; 62(2): e262-e264, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33393075

RESUMEN

Topical corticosteroids are known to be effective in the treatment of alopecia areata, but the potential effects on intraocular pressure are a concern. The purpose of this retrospective study is to evaluate the effect of clobetasol propionate 0.05% under occlusion on patients with active phase alopecia areata and to examine the effects on intraocular pressure. We also wished to see if reducing the frequency of application of clobetasol increased the safety with respect to intraocular pressure. Elevation of intraocular pressure due to topical corticosteroids is unlikely to occur at the dose of 9.8 g or less per week used in this study; however, ophthalmologic examination at the start of treatment was thought to be worthwhile in identifying patients with latent glaucoma.


Asunto(s)
Alopecia Areata/tratamiento farmacológico , Clobetasol/administración & dosificación , Glucocorticoides/administración & dosificación , Presión Intraocular/efectos de los fármacos , Apósitos Oclusivos , Administración Tópica , Adolescente , Adulto , Clobetasol/efectos adversos , Femenino , Glucocorticoides/efectos adversos , Humanos , Masculino , Estudios Retrospectivos
9.
Australas J Dermatol ; 61(2): 140-146, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-31944270

RESUMEN

BACKGROUND/OBJECTIVES: Palmoplantar psoriasis is a localised variant of psoriasis. Topical therapy is the preferred treatment modality, but in severe and recalcitrant cases, systemic drugs like methotrexate are prescribed, with potential for significant adverse effects. Iontophoresis is gaining popularity in enhancing the transdermal delivery of drugs in ionic state. This study was undertaken to evaluate and compare the efficacy of topical methotrexate by iontophoresis technique with clobetasol propionate 0.05% ointment in the treatment of palmar psoriasis. METHODS: This was a prospective randomised controlled study conducted on patients with palmar psoriasis. Group 1 patients (n = 31) were treated with once weekly iontophoretic delivery of methotrexate over 6 sittings, and group 2 patients (n = 31) were treated with clobetasol propionate 0.05% ointment, twice daily for 6 weeks. Severity of palmar psoriasis was assessed by modified Palmoplantar Pustular Psoriasis Area and Severity Index (m-PPPASI), and treatment was considered as satisfactory when there was >50% improvement. RESULTS: Sixty two patients were recruited, of which 50 completed the study. Eight out of 25 (32%) patients in group 1 and 12 out of 25 (48%) patients in group 2 showed satisfactory improvement at the end of 6 weeks. However, this difference was statistically not significant (P = 0.25). Burn injury was noted in 12 (48%) group 1 patients with no adverse effects in group 2. CONCLUSION: Iontophoretic delivery of methotrexate is a promising therapeutic modality, the efficacy of which is comparable to that of clobetasol propionate ointment in the treatment of palmar psoriasis.


Asunto(s)
Antiinflamatorios/uso terapéutico , Queratolíticos/uso terapéutico , Metotrexato/uso terapéutico , Psoriasis/tratamiento farmacológico , Administración Cutánea , Adulto , Calcitriol/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
10.
Postepy Dermatol Alergol ; 36(6): 722-726, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31998001

RESUMEN

INTRODUCTION: The effectiveness of topical tacrolimus in the treatment of oral and genital lichen planus has been verified in many randomized studies; however, there are only few case reports in treatment of cutaneous lichen planus (CLP). AIM: We sought to compare the safety and efficacy of topical clobetasol propionate and tacrolimus ointment in the treatment of CLP. MATERIAL AND METHODS: Retrospective analysis of patient files was performed. We enrolled patients who were diagnosed with CLP and treated with topical tacrolimus 0.1% or topical clobetasol propionate 0.05%. Visual Analogue Scale (VAS) scores of pigmentation and pruritus, clinical response, laboratory data and adverse effects were obtained from medical records. RESULTS: A total of 27 patients were included in the clobetasol group and 23 patients in the tacrolimus group. Both groups showed an improvement in VAS scores regarding pruritus and pigmentation but a statistically significant difference was observed in the clobetasol group (p< 0.05). At week 12, a complete response was observed in 63% (n = 17) of the clobetasol and 26% (n = 6) of the tacrolimus group. CONCLUSIONS: In our study, both treatments were found effective in the treatment of CLP but clobetasol propionate was more effective. However tacrolimus may be preferred before topical corticosteroids for lesions on the face, neck, and intertriginous regions of the body, which are sensitive to the cutaneous adverse effects of topical corticosteroids. Our study may be one of the first studies to compare the effects of topical clobetasol and tacrolimus ointment in the management of CLP.

11.
Dermatol Ther ; 31(5): e12632, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30253049

RESUMEN

To assess the efficacy, safety, and cost-effectiveness of all-trans retinoic acid/Clobetasol Propionate Compound Ointment and calcipotriol/betamethasone dipropionate ointment in the treatment of mild-to-moderate patients with psoriasis vulgaris. This was a randomized, single-blind, multicenter clinical trial. A total of 240 patients were randomized to receive twice-daily all-trans retinoic acid/Clobetasol Propionate Compound Ointment (treatment group) or once-daily calcipotriol/betamethasone dipropionate ointment (control group) for 4 weeks. The efficacy, safety, and cost-effectiveness were assessed at Weeks 2 and 4. After 4 weeks, both groups showed a significant clinical improvement compared to baseline (88.33% vs. 89.83%, respectively, p = .7112). But PASI 75 response in the treatment group was superior to the control group (44.12% vs. 28.57%, respectively, p = .0200), at Week 4. SSRI improvement rate in the treatment group was also superior to control group (67.11% vs. 59.43%, respectively, p = .0119) at Week 4. All-trans retinoic acid/Clobetasol Propionate Compound Ointment showed a significant clinical improvement in erythema, infiltration, and scales of skin lesions and PASI score compared to baseline. 1.67% of patients (treatment group) reported adverse reactions compared to 2.50% (control group) with no statistical significance. In addition, the cost-effectiveness assessment showed a higher cost-effectiveness of the treatment group compared to the control group in 4 weeks (199.25 vs. 801.51). All-trans retinoic acid/Clobetasol Propionate Compound Ointment was effective and safe in the treatment of psoriasis vulgaris with similar efficacy as calcipotriol/betamethasone dipropionate ointment and lower treatment costs.


Asunto(s)
Antiinflamatorios/uso terapéutico , Betametasona/análogos & derivados , Calcitriol/análogos & derivados , Clobetasol/uso terapéutico , Queratolíticos/uso terapéutico , Psoriasis/tratamiento farmacológico , Tretinoina/uso terapéutico , Adolescente , Adulto , Anciano , Antiinflamatorios/efectos adversos , Antiinflamatorios/economía , Betametasona/efectos adversos , Betametasona/economía , Betametasona/uso terapéutico , Calcitriol/efectos adversos , Calcitriol/economía , Calcitriol/uso terapéutico , Clobetasol/efectos adversos , Clobetasol/economía , Análisis Costo-Beneficio , Fármacos Dermatológicos/economía , Fármacos Dermatológicos/uso terapéutico , Combinación de Medicamentos , Femenino , Humanos , Queratolíticos/efectos adversos , Queratolíticos/economía , Masculino , Persona de Mediana Edad , Pomadas , Índice de Severidad de la Enfermedad , Método Simple Ciego , Tretinoina/efectos adversos , Tretinoina/economía , Adulto Joven
12.
Photodermatol Photoimmunol Photomed ; 34(4): 249-256, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29419896

RESUMEN

BACKGROUND: Very few studies have assessed the efficacy of excimer in the treatment of palmoplantar psoriasis (PPP), and none has compared the excimer with calcipotriol-clobetasol propionate combination. PURPOSE: To compare the effectiveness and safety of excimer lamp vs topical ointment containing calcipotriol (0.005% w/w) and clobetasol propionate (0.05% w/w) combination in PPP. METHODS: This right-left randomization trial included 36 patients with PPP, who received treatment with excimer lamp (twice weekly) on one side and calcipotriol-clobetasol combination (once daily) on another side for 12 weeks, followed by 8 weeks of follow-up. Recruitment and response assessment was done by 2 experienced dermatologists (SD and TN) using modified palmoplantar pustular psoriasis area and severity index score (mPPPASI, originally devised for palmoplantar pustulosis, suitably modified to assess response in PPP). Primary outcome measure was percentage improvement in mPPPASI at 12 weeks, which was classified as minimal (≤25%), mild (>25%-50%), moderate (>50%-75%), and marked (>75%). Secondary outcome measures were the proportion of patients achieving >75% reduction in mPPPASI and the time taken to achieve it. RESULTS: Of 36 recruited patients, 33 completed treatment and 21 adhered to 8-weeks follow-up. The mean mPPPASI on the excimer-treated sides reduced significantly from 7.75 ± 4.62 to 4.01 ± 4.07 (P < .001) at 12th week (end of the treatment) and 2.66 ± 3.97 at 20th week (at 8 weeks follow-up). The mean mPPPASI on the calcipotriol-clobetasol combination treated sides reduced significantly from 7.36 ± 4.46 to 3.55 ± 3.77 (P < .001) and 2.70 ± 3.97 at 12th week and 20th week, respectively. The reduction was significant for both treatment and the difference between the two was not statistically significant. Minimal, mild, moderate, and marked improvement was seen in 5/33 (15.2%) and 1/33 (3.0%), 6/33 (18.2%) and 8/33 (24.2%), 12/33 (36.4%) and 13/33 (39.4%), and 8/33 (24.2%) and 8/33 (24.2%) sides in the excimer and calcipotriol-clobetasol combination, respectively. A total of 8 patients in each group achieved mPPPASI 75 at 12 weeks. The mPPPASI 75 was achieved at 2, 4, and 8 weeks in 1, 2, and 8 patients, respectively, using either modalities. The adverse effects (most commonly hyperpigmentation) were noted more frequently on the excimer-treated sides; however, they were well tolerated. CONCLUSION: Both excimer lamp and calcipotriol-clobetasol propionate combination are equally effective in the treatment of PPP.


Asunto(s)
Calcitriol/análogos & derivados , Clobetasol/administración & dosificación , Fotoquimioterapia/instrumentación , Fotoquimioterapia/métodos , Psoriasis/tratamiento farmacológico , Adulto , Anciano , Calcitriol/administración & dosificación , Calcitriol/efectos adversos , Clobetasol/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Psoriasis/patología , Índice de Severidad de la Enfermedad
13.
Oral Dis ; 24(4): 573-579, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29121431

RESUMEN

OBJECTIVE: To determine corticosteroid treatment effectiveness in patients with oral lichen planus/oral lichenoid lesions (OLP/OLL). MATERIAL AND METHODS: Twenty-one patients with OLP and eighty-one patients with OLL received 0.05% clobetasol propionate (CP) or 0.05% triamcinolone acetonide (TA) in aqueous solution (AS) or orabase (OB), evaluating responses to treatment and follow-up compliance. RESULTS: Lesions were atrophic (72 of 102; 70.6%), extensive (58 of 100; 58%), producing eating difficulties (62 of 102; 60.8%), and spontaneous pain (30 of 102; 29.4%); 50 patients (49%) received CP-AS. The mean ± SD percentage of follow-ups attended was 43 ± 32%. Symptom remission was achieved in 46% of patients receiving CP-AS, 36.36% of those receiving TA-AS, 20% of those receiving CP-OB, and 25% of those receiving TA-OB. Follow-up compliance was poor in 66.7% of patients. Among 51 patients with continuous symptoms, 64.7% evidenced total remission at treatment completion; among 33 with intermittent symptoms, 73.1% had outbreaks 2-3 times/year and 51.5% controlled outbreaks with <6 corticosteroid applications. Adverse effects were observed in seven patients (6.8%) (moon face, hirsutism, capillary fragility) in induction stage, subsiding with dose; among 15 patients under maintenance treatment for >6 months, one showed hypothalamic-pituitary-adrenal (HPA) axis inhibition but not adrenal insufficiency. CONCLUSIONS: Our treatment proved highly effective and safe. Recall programs are desirable to enhance follow-up compliance.


Asunto(s)
Antiinflamatorios/uso terapéutico , Carboximetilcelulosa de Sodio/análogos & derivados , Clobetasol/uso terapéutico , Liquen Plano Oral/tratamiento farmacológico , Triamcinolona Acetonida/uso terapéutico , Administración Tópica , Adulto , Anciano , Anciano de 80 o más Años , Antiinflamatorios/efectos adversos , Carboximetilcelulosa de Sodio/efectos adversos , Carboximetilcelulosa de Sodio/uso terapéutico , Clobetasol/efectos adversos , Combinación de Medicamentos , Femenino , Humanos , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Resultado del Tratamiento , Triamcinolona Acetonida/efectos adversos
14.
Ann Dermatol Venereol ; 145(2): 83-88, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29150154

RESUMEN

BACKGROUND: The cosmetic use of bleaching products is common among women from sub-Saharan Africa. The most frequently used products are highly potent corticosteroids (clobetasol propionate) and hydroquinone. Herein, we report 8 cases of SCC in women using skin bleaching products for cosmetic purposes. Our aim is to describe the epidemiological, clinical and pathological aspects of the carcinomas observed during the course of skin lightening. METHODS: We conducted a descriptive multicentre study from August 2005 to January 2016 in three dermatology units in Senegal. We included all patients consulting for cutaneous squamous cell carcinoma associated with skin bleaching. Sociodemographic, clinical, paraclinical and therapeutic data were recorded. RESULTS: A total of 8 female patients were included. The mean age was 48.1 years (37-63 years). Topical hydroquinone and highly potent corticosteroids were the main products used over the whole body, for an average duration of 20.3 years. No pre-neoplastic skin disease was found in our patients. The clinical aspects of tumours were as follows: cauliflower-like (n=4), ulcerated (n=3) and nodular (n=1). The average development time before consultation was 6.75 months. All the cutaneous squamous cell carcinomas were localized to lichenoid lesions or exogenous ochronotic lesions on photo-exposed areas: face (n=1), neck (n=3) or upper back (n=4). The most common histopathological type was the infiltrating form and there was one case of in situ carcinoma. The outcome was favourable in six of eight patients after surgical resection. Two deaths occurred: one through tumour recurrence and the other through haemorrhagic shock. CONCLUSIONS: From 2005 to 2016, eight cases of cutaneous squamous cell carcinomas associated with cosmetic use of bleaching products were reported in Senegal. The mechanism was not fully elucidated and further studies are necessary. These observations provide an additional argument for combating this practice and including skin bleaching among known risk factors for squamous cell carcinoma.


Asunto(s)
Carcinoma de Células Escamosas/inducido químicamente , Preparaciones para Aclaramiento de la Piel/efectos adversos , Neoplasias Cutáneas/inducido químicamente , Adulto , Dorso , Carcinoma in Situ/inducido químicamente , Carcinoma in Situ/patología , Carcinoma de Células Escamosas/patología , Clobetasol/efectos adversos , Cara , Femenino , Humanos , Hidroquinonas/efectos adversos , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Senegal , Choque Hemorrágico/etiología , Neoplasias Cutáneas/patología
15.
Biomed Chromatogr ; 31(2)2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27502902

RESUMEN

Clobetasol propionate (CLO) is a potent steroid used for the treatment of several dermatological diseases. Recent studies suggest its additional use in alopecia topical treatment, generating a demand for novel formulations with specific delivery into hair follicles. Hence, a selective analytical method for drug quantification in follicular structures and skin layers is required. For this, a simple HPLC-UV method was developed. Quantification was performed using a RP-C18 column (4.6 mm × 15 cm, 5 µm), with a mixture of methanol-acetonitrile-water (50:15:35 v/v) as mobile phase, a flow rate of 1.2 mL/min, oven temperature of 30°C, injection volume of 50 µL and detection at 240 nm. The optimized conditions enabled a 12 min running with CLO elution at 10.1 min and resolution of 2.424 from skin matrix interferences. Validation was performed in accordance with International Conference on Harmonization guidelines and fulfilled the criteria of selectivity, linearity (0.5-15.0 µg/mL), robustness, precision, accuracy and limits of detection and quantification (0.02 and 0.07 µg/mL, respectively). The validated method was successfully applied for CLO quantification following in vitro skin permeation experiments and differential tape-stripping for hair follicle deposition determination, demonstrating its suitability.


Asunto(s)
Antiinflamatorios/farmacocinética , Cromatografía Líquida de Alta Presión/métodos , Clobetasol/farmacocinética , Glucocorticoides/farmacocinética , Folículo Piloso/metabolismo , Absorción Cutánea , Piel/metabolismo , Cromatografía de Fase Inversa/métodos , Humanos , Límite de Detección
16.
Molecules ; 22(11)2017 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-29099755

RESUMEN

A rapid, simple to use and low-cost thin-layer chromatographic procedure in normal phase system with densitometric detection at 246 nm was carefully validated according to the International Conference on Harmonisation (ICH) guidelines for assay of clobetasol propionate in topical solution containing clobetasol propionate in quantity 0.50 mg/mL. The adopted thin-layer chromatographic (TLC)-densitometric procedure could effectively separate clobetasol propionate from its related compound, namely clobetasol. It is linear for clobetasol propionate in the range of 0.188 ÷ 5 µg/spot. The limit of detection (LOD) and limit of quantification (LOQ) value is 0.061 and 0.186 µg/spot, respectively. Accuracy of proposed procedure was evaluated by recovery test. The mean recovery of studied clobetasol propionate ranges from 98.7 to 101.0%. The coefficient of variation (CV, %) obtained during intra-day and inter-day studies, which was less than 2% (0.40 ÷ 1.17%), confirms the precision of described method. The assay value of clobetasol propionate is consistent with the pharmacopoeial requirements. In conclusion, it can be suitable as a simple and economic procedure for routine quality control laboratories of clobetasol propionate in topical solution.


Asunto(s)
Antiinflamatorios/análisis , Cromatografía en Capa Delgada/métodos , Clobetasol/análisis , Densitometría/métodos , Bioensayo/métodos , Límite de Detección , Reproducibilidad de los Resultados
17.
Zhonghua Nan Ke Xue ; 23(7): 635-638, 2017 Jul.
Artículo en Zh | MEDLINE | ID: mdl-29723458

RESUMEN

OBJECTIVE: To investigate the clinical effect of 0.02% clobetasol propionate cream (CPC) on phimosis in prepubertal children. METHODS: We retrospectively analyzed the clinical data about 237 prepubertal children with phimosis present at the Outpatient Department from June 2012 to December 2015. The patients were aged 2-14 (mean 8.6) years, all treated by topical application of 0.02% CPC to the narrowed opening and adhered part of the foreskin twice a day, in the morning and evening respectively. At the time of CPC application, the foreskin was slightly retracted. We evaluated the therapeutic effect every week from the end of the first week of treatment. RESULTS: Totally, 233 of the patients completed the 8-week treatment, of whom 181 (77.68%) showed full retraction of the foreskin, 28 (12.01%) experienced improvement (disappearance of the phimotic ring), and 24 (10.30%) failed to respond, with a total effectiveness rate of 89.70%. No significant local or systemic adverse reactions were observed during the treatment. CONCLUSIONS: Topical application of 0.02% Clobetasol Propionate Cream is a safe, effective, painless, and inexpensive option for the treatment of phimosis in prepubertal chilodren.


Asunto(s)
Antiinflamatorios/administración & dosificación , Clobetasol/administración & dosificación , Fimosis/tratamiento farmacológico , Administración Tópica , Adolescente , Niño , Preescolar , Prepucio , Geles , Humanos , Masculino , Pacientes Ambulatorios , Estudios Retrospectivos , Resultado del Tratamiento
18.
Environ Res ; 150: 403-410, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27372064

RESUMEN

Skin lightening products are types of cosmetics (creams, gels, lotions and soaps) applied voluntarily on skin. Several of these products contain a variety of active ingredients that are highly toxic. Among those toxic agents, the present study focuses on mercury, hydroquinone, and clobetasol propionate. Out of the 93 lightening soaps and 98 creams purchased in large city markets in sub-Saharan West Africa and in small ethnic shops in Canada, 68-84% of all creams and 7.5-65% of all soaps exceeded regulatory guidelines for at least one active ingredient when considering different regulations. Mercury was found in high concentrations mainly in soaps, while hydroquinone and clobetasol propionate concentrations exceeded US FDA standards in some creams for all countries included in our study. Concentrations of the three compounds declared on labels of soaps and creams usually did not correspond to concentrations actually measured, particularly for mercury and hydroquinone. Overall, our results indicate that most studied skin-lightening products are potentially toxic and that product labels are frequently inaccurate with respect to the presence of toxic agents.


Asunto(s)
Clobetasol/análisis , Hidroquinonas/análisis , Mercurio/análisis , Preparaciones para Aclaramiento de la Piel/análisis , África Occidental , Monitoreo del Ambiente , Quebec
19.
Int J Mol Sci ; 18(1)2016 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-28035957

RESUMEN

The aim of this work was to assess in vivo the anti-inflammatory efficacy and tolerability of clobetasol propionate (CP) loaded lecithin/chitosan nanoparticles incorporated into chitosan gel for topical application (CP 0.005%). As a comparison, a commercial cream (CP 0.05% w/w), and a sodium deoxycholate gel (CP 0.05% w/w) were also evaluated. Lecithin/chitosan nanoparticles were prepared by self-assembling of the components obtained by direct injection of soybean lecithin alcoholic solution containing CP into chitosan aqueous solution. Nanoparticles obtained had a particle size around 250 nm, narrow distribution (polydispersity index below 0.2) and positive surface charge, provided by a superficial layer of the cationic polymer. The nanoparticle suspension was then loaded into a chitosan gel, to obtain a final CP concentration of 0.005%. The anti-inflammatory activity was evaluated using carrageenan-induced hind paw edema test on Wistar rats, the effect of formulations on the barrier property of the stratum corneum were determined using transepidermal water loss measurements (TEWL) and histological analysis was performed to evaluate the possible presence of morphological changes. The results obtained indicate that nanoparticle-in-gel formulation produced significantly higher edema inhibition compared to other formulations tested, although it contained ten times less CP. TEWL measurements also revealed that all formulations have no significant disturbance on the barrier function of skin. Furthermore, histological analysis of rat abdominal skin did not show morphological tissue changes nor cell infiltration signs after application of the formulations. Taken together, the present data show that the use of lecithin/chitosan nanoparticles in chitosan gel as a drug carrier significantly improves the risk-benefit ratio as compared with sodium-deoxycholate gel and commercial cream formulations of CP.


Asunto(s)
Antiinflamatorios/administración & dosificación , Clobetasol/administración & dosificación , Glucocorticoides/administración & dosificación , Nanopartículas/efectos adversos , Piel/efectos de los fármacos , Animales , Antiinflamatorios/farmacología , Quitosano/química , Clobetasol/farmacología , Glucocorticoides/farmacología , Lecitinas/química , Masculino , Nanopartículas/química , Ratas , Ratas Wistar
20.
Acta Paediatr ; 104(2): 174-7, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25297721

RESUMEN

AIM: There is a lack of evidence on the best treatment option for umbilical granuloma. The primary aim of this study was to compare three treatments for umbilical granuloma: standard treatment with topical silver nitrate, clobetasol propionate cream (0.05%) and ethanol wipes. The secondary aim was to evaluate whether the treatment could be successfully administered by a parent at home, rather than in the outpatient clinic. METHODS: A total of 109 infants were randomised to one of three groups and 94 infants completed the assigned treatment: 30 infants received standard treatment with silver nitrate (99%) in the outpatient clinic, 30 infants had topical clobetasol propionate cream (0.05%) applied at home, and 34 infants received cleansing with ethanol wipes (82%) at home. RESULTS: Silver nitrate and clobetasol propionate cream (0.05%) were significantly superior to ethanol wipes, with shorter healing times and higher resolution rates (p = 0.0001). Healing time and resolution rates were identical for silver nitrate and clobetasol propionate cream (0.05%). Mild side effects were occasionally reported, all of which were self-limiting. CONCLUSION: Treating umbilical granuloma with topical clobetasol propionate cream (0.05%) at home is as effective as treating it with topical silver nitrate (99%) in the clinic.


Asunto(s)
Granuloma/tratamiento farmacológico , Enfermedades de la Piel/tratamiento farmacológico , Cordón Umbilical , Administración Tópica , Antiinfecciosos Locales/uso terapéutico , Clobetasol/uso terapéutico , Etanol/uso terapéutico , Femenino , Glucocorticoides/uso terapéutico , Humanos , Lactante , Masculino , Nitrato de Plata/uso terapéutico
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