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[PMID]:28716436
[Au] Autor:Tolkachjov SN; Chaudhry HM; Camilleri MJ; Torgerson RR
[Ad] Endereço:Surgical Dermatology Group, Birmingham, Alabama. Electronic address: stan.tolkachjov@gmail.com.
[Ti] Título:Frontal fibrosing alopecia among men: A clinicopathologic study of 7 cases.
[So] Source:J Am Acad Dermatol;77(4):683-690.e2, 2017 Oct.
[Is] ISSN:1097-6787
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Frontal fibrosing alopecia (FFA) is a lichen planopilaris-variant scarring alopecia that has rarely been described in men. OBJECTIVE: To characterize the clinicopathologic findings of FFA in men by studying a series of 7 male patients. METHODS: We conducted a retrospective review of all cases of male patients with FFA at the Mayo Clinic from 1992 to 2016. RESULTS: Seven male patients with FFA were identified. The frontal scalp (in 6 of 7 patients), sideburns (in 4 of 7), and temporal scalp (in 4 of 7) were most frequently involved. Three patients had involvement of the eyebrows. One patient had hair loss of the upper cutaneous lip. All patients had biopsy evidence of lichen planopilaris. None of the patients had associated autoimmune or thyroid disease. Two patients had hypogonadism upon testosterone studies. LIMITATIONS: Limitations include small sample size and varied follow-up. CONCLUSIONS: Although most often reported among postmenopausal women, FFA also occurs among men. The clinical and histopathologic characteristics of FFA in men parallel those described in women with FFA. Unique areas of involvement in men include sideburns and facial hair. Concomitant mucocutaneous lichen planus, autoimmune disease, and thyroid disease are infrequent among men with FFA. Distribution of hair loss and associated hormonal abnormalities aid in the recognition of FFA in men.
[Mh] Termos MeSH primário: Alopecia/tratamento farmacológico
Líquen Plano/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Idoso
Alopecia/complicações
Alopecia/patologia
Anti-Inflamatórios/uso terapêutico
Bochecha
Cicatriz/etiologia
Clobetasol/uso terapêutico
Fármacos Dermatológicos/uso terapêutico
Sobrancelhas
Testa
Seres Humanos
Hidroxicloroquina/uso terapêutico
Líquen Plano/complicações
Líquen Plano/patologia
Masculino
Meia-Idade
Estudos Retrospectivos
Couro Cabeludo
Tacrolimo/análogos & derivados
Tacrolimo/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents); 0 (Dermatologic Agents); 4QWG6N8QKH (Hydroxychloroquine); 7KYV510875 (pimecrolimus); ADN79D536H (Clobetasol); WM0HAQ4WNM (Tacrolimus)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170927
[Lr] Data última revisão:
170927
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170719
[St] Status:MEDLINE


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[PMID]:28557781
[Au] Autor:Jones N; Carvalho M; Branvold-Herr A
[Ad] Endereço:Professional Compounding Centers of America (PCCA), Houston, Texas. njones@pccarx.com.
[Ti] Título:Management of Psoriasis with a XemaTop Topical Compounded Formula: A Case Report.
[So] Source:Int J Pharm Compd;21(3):205-211, 2017 May-Jun.
[Is] ISSN:1092-4221
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Skin conditions such as psoriasis and eczema negatively impact the patient's quality of life; the primary goal of topical treatments is to minimize the disease-specific symptoms. This case report discusses the management of two refractory psoriasis skin lesions in an adult male using a topical compounded formula. The psoriasis symptoms were assessed quantitatively using two validated research instruments, the Psoriasis Symptom Inventory, and an adapted Numeric Rating Scale. A qualitative assessment was also performed by evaluating the digital photographs taken by the patient during the course of treatment. The compounded formula containing zinc pyrithione, clobetasol propionate, and cyanocobalamin in the Professional Compounding Centers of America's proprietary base PCCA XemaTop, applied topically for three weeks, significantly reduced the patient's self-reported psoriasis symptoms and improved his overall condition by 81.2%. This successful case report is important evidence for healthcare professionals when considering new, innovative topical compounded formulas for managing skin conditions such as psoriasis and eczema.
[Mh] Termos MeSH primário: Clobetasol/administração & dosagem
Compostos Organometálicos/administração & dosagem
Psoríase/tratamento farmacológico
Piridinas/administração & dosagem
Vitamina B 12/administração & dosagem
[Mh] Termos MeSH secundário: Administração Tópica
Adulto
Quimioterapia Combinada
Seres Humanos
Masculino
Resultado do Tratamento
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Organometallic Compounds); 0 (Pyridines); ADN79D536H (Clobetasol); P6YC3EG204 (Vitamin B 12); R953O2RHZ5 (pyrithione zinc)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170713
[Lr] Data última revisão:
170713
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170531
[St] Status:MEDLINE


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[PMID]:28504720
[Au] Autor:Choi EJ; Jung BJ; Lee SH; Yoo HS; Shin EA; Ko HJ; Chang S; Kim SY; Jeon SM
[Ad] Endereço:College of Pharmacy, Ajou University, Suwon, Republic of Korea.
[Ti] Título:A clinical drug library screen identifies clobetasol propionate as an NRF2 inhibitor with potential therapeutic efficacy in KEAP1 mutant lung cancer.
[So] Source:Oncogene;36(37):5285-5295, 2017 Sep 14.
[Is] ISSN:1476-5594
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The Kelch-like ECH-associated protein 1 (KEAP1)-nuclear factor E2-related factor 2 (NRF2)pathway has a central role in cellular antioxidant defense. NRF2 activation due to KEAP1 or NRF2 mutations occurs frequently in many cancers, suggesting that NRF2 inhibition could be a promising therapeutic strategy. However, no potent NRF2 inhibitors are clinically available to date. To develop potent NRF2 inhibitors for therapeutic purpose, we screened ~4000 clinical compounds and determined clobetasol propionate (CP) as the most potent NRF2 inhibitor. Mechanistically, CP prevented nuclear accumulation and promoted ß-TrCP-dependent degradation of NRF2 in a glucocorticoid receptor- and a glycogen synthase kinase 3 (GSK3)-dependent manner. As a result, CP induced oxidative stress and strongly suppressed the anchorage-independent growth of tumors with KEAP1 mutation, but not with the wild-type KEAP1. Further, CP alone or in combination with rapamycin strongly inhibited the in vitro and in vivo growth of tumors harboring mutations in KEAP1 or both KEAP1 and LKB1 that are frequently observed in lung cancer. Thus, CP could be a repurposed therapeutic agent for cancers with high NRF2 activity. We also proposed that the use CP and rapamycin in combination could be a potential therapeutic strategy for tumors harboring both KEAP1 and LKB1 mutations.
[Mh] Termos MeSH primário: Anti-Inflamatórios/farmacologia
Clobetasol/farmacologia
Proteína 1 Associada a ECH Semelhante a Kelch/genética
Neoplasias Pulmonares/tratamento farmacológico
Fator 2 Relacionado a NF-E2/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Ensaios de Seleção de Medicamentos Antitumorais
Seres Humanos
Neoplasias Pulmonares/genética
Neoplasias Pulmonares/patologia
Camundongos Endogâmicos BALB C
Camundongos Nus
Distribuição Aleatória
Transdução de Sinais
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents); 0 (KEAP1 protein, human); 0 (Kelch-Like ECH-Associated Protein 1); 0 (NF-E2-Related Factor 2); 0 (NFE2L2 protein, human); ADN79D536H (Clobetasol)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171013
[Lr] Data última revisão:
171013
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170516
[St] Status:MEDLINE
[do] DOI:10.1038/onc.2017.153


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[PMID]:28301619
[Au] Autor:Pariser D; Bukhalo M; Guenthner S; Kempers S; Shideler S; Gold LS; Tschen E; Berg J; Ferdon MB; Dromgoole S
[Ti] Título:Two Multicenter, Randomized, Double-Blind, Parallel Group Comparison Studies of a Novel Enhanced Lotion Formulation of Halobetasol Propionate, 0.05% Versus Its Vehicle in Adult Subjects With Plaque Psoriasis.
[So] Source:J Drugs Dermatol;16(3):234-240, 2017 Mar 01.
[Is] ISSN:1545-9616
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:

BACKGROUND: A novel lotion formulation of halobetasol propionate, 0.05% (HBP Lotion) with enhanced vehicle characteristics of a cream while preserving the ease of use and cosmetic elegance of a lotion has been developed to treat plaque psoriasis. OBJECTIVE: Determine the safety and effectiveness of HBP Lotion in patients with plaque psoriasis. METHODS: Two prospective, randomized, vehicle-controlled clinical studies were conducted in 443 adult subjects with moderate-severe plaque psoriasis. Subjects applied the test article to psoriatic plaques within the treatment area twice daily for 14 days. Efficacy data are based upon treatment "success" defined as those subjects that achieved scores of 0=clear or 1=almost clear with at least a two-grade improvement relative to baseline for an Investigator's Global Assessment (IGA) and clinical signs (plaque elevation, erythema, scaling). Safety data are presented as adverse events and local skin reactions. RESULTS: After two weeks of treatment with HBP Lotion, 44.5% of the HBP Lotion treated subjects in each study achieved (a) treatment "success" (ie, an IGA score of 0=clear or 1=almost clear and >2 grade improvement compared to baseline) and (b) a notable reduction in plaque elevation, erythema, scaling, and pruritus. In contrast, only 6.3% and 7.1% of VEH subjects in Studies 1 and 2, respectively, achieved treatment success and the reduction of disease related signs was materially lower. Statistically, at day 15 in both Phase 3 studies, treatment success with HBP Lotion was superior to VEH (P less than 0.001). From a safety perspective the outcomes were in general unremarkable with similar findings in the HBP Lotion and VEH treatment groups. CONCLUSIONS: The results demonstrate the safety and effectiveness of HBP Lotion in the treatment of plaque psoriasis. Furthermore, this novel HBP lotion formulation is also distinguished by its moisturization qualities and ease of use.

J Drugs Dermatol. 2017;16(3):234-240.

.
[Mh] Termos MeSH primário: Clobetasol/análogos & derivados
Glucocorticoides/uso terapêutico
Psoríase/tratamento farmacológico
[Mh] Termos MeSH secundário: Administração Cutânea
Adulto
Clobetasol/administração & dosagem
Clobetasol/efeitos adversos
Clobetasol/uso terapêutico
Método Duplo-Cego
Feminino
Glucocorticoides/administração & dosagem
Glucocorticoides/efeitos adversos
Seres Humanos
Masculino
Veículos Farmacêuticos/administração & dosagem
Estudos Prospectivos
Índice de Gravidade de Doença
Creme para a Pele
Resultado do Tratamento
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE III; COMPARATIVE STUDY; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Glucocorticoids); 0 (Pharmaceutical Vehicles); 9P6159HM7T (halobetasol); ADN79D536H (Clobetasol)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170914
[Lr] Data última revisão:
170914
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170317
[St] Status:MEDLINE


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[PMID]:28301614
[Au] Autor:Sugarman JL; Gold LS; Lebwohl MG; Pariser DM; Alexander BJ; Pillai R
[Ti] Título:A Phase 2, Multicenter, Double-Blind, Randomized, Vehicle Controlled Clinical Study to Assess the Safety and Efficacy of a Halobetasol/Tazarotene Fixed Combination in the Treatment of Plaque Psoriasis.
[So] Source:J Drugs Dermatol;16(3):197-204, 2017 Mar 01.
[Is] ISSN:1545-9616
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:

BACKGROUND: Psoriasis is a chronic, immune-mediated disease that varies widely in its clinical expression. Treatment options focus on relieving symptoms, reducing inflammation, induration, and scaling, and controlling the extent of the disease. Topical corticosteroids are the mainstay of treatment, however long-term safety remains a concern, particularly with the more potent formulations. Combination therapy with a corticosteroid and tazarotene may improve psoriasis signs at a lower corticosteroid concentration providing a superior safety profile. OBJECTIVE: To investigate the efficacy and safety of a once-daily application of a fixed combination halobetasol propionate 0.01% and tazarotene 0.045% (HP/TAZ) lotion in comparison with its monads and vehicle in subjects with moderate-to-severe plaque psoriasis. METHODS: Multicenter, randomized, double-blind, vehicle-controlled Phase 2 study in moderate or severe psoriasis (N=212). Subjects randomized (2:2:2:1 ratio) to receive HP/TAZ, individual monads, or vehicle, once-daily for 8 weeks. Efficacy assessments included treatment success (defined as at least a 2-grade improvement from baseline in the IGA score and a score of 'Clear' or 'Almost Clear'), and impact on individual signs of psoriasis (erythema, plaque elevation, and scaling) at the target lesion. Safety and treatment emergent adverse events (TEAEs) were evaluated throughout. RESULTS: HP/TAZ lotion demonstrated statistically significant superiority over vehicle as early as 2 weeks. At week 8, 52.5% of subjects had treatment success compared with 33.3%, 18.6%, and 9.7% in the HP (P=0.033), TAZ (P less than 0.001), and vehicle (P less than 0.001) groups, respectively. HP/TAZ lotion was superior to its monads and vehicle in reducing the psoriasis signs of erythema, plaque elevation, and scaling at the target lesion. At week 8, a 2-grade improvement in IGA was achieved by 54.2% of subjects for erythema, 67.8% for plaque elevation, and 64.4% for scaling. Most frequently reported TEAEs were application site reactions, and were more likely associated with the tazarotene component. Side effects such as skin atrophy were rare. CONCLUSIONS: HP/TAZ lotion was consistently more effective than its monads or vehicle in achieving treatment success and reducing psoriasis signs of erythema, plaque elevation, and scaling at the target lesion. Safety data were consistent with the known safety profile of halobetasol propionate and tazarotene, and did not reveal any new safety concerns with the combination product.

J Drugs Dermatol. 2017;16(3):197-204.

.
[Mh] Termos MeSH primário: Clobetasol/análogos & derivados
Fármacos Dermatológicos/uso terapêutico
Glucocorticoides/uso terapêutico
Ácidos Nicotínicos/uso terapêutico
Psoríase/tratamento farmacológico
[Mh] Termos MeSH secundário: Administração Cutânea
Clobetasol/administração & dosagem
Clobetasol/efeitos adversos
Clobetasol/uso terapêutico
Fármacos Dermatológicos/administração & dosagem
Fármacos Dermatológicos/efeitos adversos
Método Duplo-Cego
Combinação de Medicamentos
Feminino
Glucocorticoides/administração & dosagem
Glucocorticoides/efeitos adversos
Seres Humanos
Masculino
Ácidos Nicotínicos/administração & dosagem
Ácidos Nicotínicos/efeitos adversos
Veículos Farmacêuticos/administração & dosagem
Índice de Gravidade de Doença
Creme para a Pele
Resultado do Tratamento
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE II; COMPARATIVE STUDY; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Dermatologic Agents); 0 (Drug Combinations); 0 (Glucocorticoids); 0 (Nicotinic Acids); 0 (Pharmaceutical Vehicles); 81BDR9Y8PS (tazarotene); 9P6159HM7T (halobetasol); ADN79D536H (Clobetasol)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170914
[Lr] Data última revisão:
170914
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170317
[St] Status:MEDLINE


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[PMID]:28259803
[Au] Autor:Kaur A; Katiyar SS; Kushwah V; Jain S
[Ad] Endereço:Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Sector 67, SAS Nagar, Punjab, India.
[Ti] Título:Nanoemulsion loaded gel for topical co-delivery of clobitasol propionate and calcipotriol in psoriasis.
[So] Source:Nanomedicine;13(4):1473-1482, 2017 May.
[Is] ISSN:1549-9642
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Current work reports the development and optimization of clobitasol propionate (CP) and calcipotriol (CT) loaded nanoemulsion based gel for topical treatment of psoriasis. Components of nanoemulsion viz., oil and surfactant/co-surfactant were selected depending upon solubility and emulsification potential respectively. The optimized ratio of 5:3:2 of Capmul MCM C8 EP, Cremophor RH 40 and Labrafil 1944 CS was selected. Carbopol 980 was used as gelling agent to achieve final drug concentration of 0.05% w/w and 0.005% w/w respectively for CP and CT. HaCaT cell lines showed higher uptake of drug from nanoemulsion in correlation with the enhancement in penetration of both drugs in stratum corneum (SC) and viable layer from nanoemulsion and gel as compared to free drugs. Imiquimod induced psoriatic BALB/c mice revealed significantly higher anti-psoriatic activity of nanoemulsion gel as compared to free drugs and marketed formulation. The developed formulation showed negligible skin irritation despite increased penetration into the skin.
[Mh] Termos MeSH primário: Anti-Inflamatórios/farmacologia
Calcitriol/análogos & derivados
Clobetasol/farmacologia
Fármacos Dermatológicos/farmacologia
Nanopartículas/química
Psoríase/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Anti-Inflamatórios/administração & dosagem
Calcitriol/administração & dosagem
Calcitriol/farmacologia
Linhagem Celular
Clobetasol/administração & dosagem
Fármacos Dermatológicos/administração & dosagem
Combinação de Medicamentos
Liberação Controlada de Fármacos
Emulsões/química
Géis/uso terapêutico
Seres Humanos
Interleucina-6/sangue
Camundongos Endogâmicos BALB C
Psoríase/induzido quimicamente
Absorção Cutânea
Suínos
Fator de Necrose Tumoral alfa/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents); 0 (Dermatologic Agents); 0 (Drug Combinations); 0 (Emulsions); 0 (Gels); 0 (Interleukin-6); 0 (Tumor Necrosis Factor-alpha); 0 (interleukin-6, mouse); 143NQ3779B (calcipotriene); ADN79D536H (Clobetasol); FXC9231JVH (Calcitriol)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171012
[Lr] Data última revisão:
171012
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170306
[St] Status:MEDLINE


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[PMID]:28238742
[Au] Autor:Guttman-Yassky E; Ungar B; Malik K; Dickstein D; Suprun M; Estrada YD; Xu H; Peng X; Oliva M; Todd D; Labuda T; Suarez-Farinas M; Bissonnette R
[Ad] Endereço:Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY; Laboratory for Investigative Dermatology, Rockefeller University, New York, NY; Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address: Emma.Guttman@mountsinai.org.
[Ti] Título:Molecular signatures order the potency of topically applied anti-inflammatory drugs in patients with atopic dermatitis.
[So] Source:J Allergy Clin Immunol;140(4):1032-1042.e13, 2017 Oct.
[Is] ISSN:1097-6825
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Atopic dermatitis (AD) presents a large unmet need for treatments with better safety and efficacy. To facilitate development of topical therapeutics, we need an efficient model for assessing different formulations and concentrations. The "plaque model" has been successfully implemented in patients with psoriasis, another common inflammatory disease, to assess the efficacy of topical treatments. This model has not been validated for AD, which has higher placebo responses and less stable lesions than psoriasis. OBJECTIVE: We aimed to assess changes in molecular signatures of intrapatient target lesions treated with topical therapeutics. METHODS: We enrolled 30 patients with mild-to-moderate AD in a randomized, double-blind, intraindividual comparison of 3 approved agents applied blindly at the investigator site daily for 14 days: pimecrolimus, betamethasone dipropionate, clobetasol propionate, and a vehicle/emollient control. Changes in total sign scores (TSSs), transepidermal water loss, and tissue biomarkers (determined by using RT-PCR and immunohistochemistry) were evaluated. RESULTS: TSSs showed improvements of 30%, 40%, 68%, and 76% at 2 weeks with vehicle, pimecrolimus, betamethasone, and clobetasol, respectively, with parallel changes in transepidermal water loss (P < .05). Significant differences versus vehicle values were limited to steroids (P < .0001). Steroids (particularly clobetasol) restored epidermal hyperplasia and terminal differentiation versus minimal changes with vehicle or pimecrolimus (P < .001). Levels of cellular infiltrates and cytokines (IL-13, IL-22, and S100As) were similarly reduced only by steroids (P < .001). TSS improvement correlated with changes in hyperplasia, infiltrates, and differentiation markers. CONCLUSION: We detected significant clinical and tissue differences between agents, providing a novel approach to study the differential effects of topical formulations using a limited sample size.
[Mh] Termos MeSH primário: Anti-Inflamatórios/uso terapêutico
Dermatite Atópica/tratamento farmacológico
Pele/efeitos dos fármacos
[Mh] Termos MeSH secundário: Administração Tópica
Adulto
Idoso
Betametasona/análogos & derivados
Betametasona/uso terapêutico
Biomarcadores/metabolismo
Diferenciação Celular
Clobetasol/uso terapêutico
Citocinas/metabolismo
Feminino
Seres Humanos
Hiperplasia
Masculino
Meia-Idade
Efeito Placebo
Psoríase/tratamento farmacológico
Pele/patologia
Tacrolimo/análogos & derivados
Tacrolimo/uso terapêutico
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents); 0 (Biomarkers); 0 (Cytokines); 7KYV510875 (pimecrolimus); 826Y60901U (betamethasone-17,21-dipropionate); 9842X06Q6M (Betamethasone); ADN79D536H (Clobetasol); WM0HAQ4WNM (Tacrolimus)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170228
[St] Status:MEDLINE


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[PMID]:28069324
[Au] Autor:Noguchi A; Tominaga M; Takahashi N; Matsuda H; Kamata Y; Umehara Y; Ko KC; Suga Y; Ogawa H; Takamori K
[Ad] Endereço:Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan; Department of Dermatology, Juntendo University Urayasu Hospital, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
[Ti] Título:Differences in therapeutic effects of topically applied corticosteroid and tacrolimus on atopic dermatitis-like symptoms in NC/Nga mice.
[So] Source:J Dermatol Sci;86(1):54-62, 2017 Apr.
[Is] ISSN:1873-569X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Topical corticosteroid and calcineurin inhibitor have similar therapeutic benefits in atopic dermatitis (AD), but the differences in therapeutic mechanisms of action of these agents against AD symptoms are not fully understood. OBJECTIVE: This study was performed to examine the different effects of topical betamethasone valerate (BMV), clobetasol propionate (CBP), and tacrolimus (TAC) on itch-related behavior and dermatitis in NC/Nga mice with AD-like symptoms. METHODS: AD-like dermatitis was induced in the dorsal skin of NC/Nga mice by repeated topical application of Dermatophagoides farinae body (Dfb) ointment twice weekly for three weeks. Mice with dermatitis scores over 5 were divided into five groups with equal dermatitis scores and treated with BMV, CBP, TAC, or Vaseline (Vas) once daily for two consecutive days, or were not treated (NT). Scratching behavior was analyzed using a SCLABA -Real system. Transepidermal water loss (TEWL) before and after treatment was measured using a Tewameter TM210. Skin collected from each group was analyzed histologically. RESULTS: After the second treatment, dermatitis showed significantly greater improvement in the CBP and TAC-treated groups than in the Vas-treated and NT groups. The numbers of scratching bouts were significantly lower in CBP and TAC-treated mice than in Vas-treated mice. TEWL was significantly lower in TAC-, but not in CBP-, treated mice than in Vas-treated mice. Immunohistochemical examination showed that BMV, CBP and TAC did not reduce the increased densities of epidermal protein gene product 9.5- and substance P-immunoreactive fibers. The numbers of dermal CD4-immunoreactive T cells were significantly lower in BMV and CBP-treated mice than in Vas-treated and NT mice. The numbers of dermal eosinophils were significantly lower in BMV, CBP and TAC-treated mice than in Vas-treated and NT mice, with CBP showing the strongest effect. CBP significantly reduced epidermal thickness compared with Vas and NT. There were no significant differences in the numbers of interleukin-31-immunoreactive cells and mast cells, or in expression of epidermal thymic stromal lymphopoietin among all five groups. CONCLUSION: The therapeutic potency of TAC against AD-like symptoms, including pruritus, is equal to that of the corticosteroid CBP. Epidermal innervation of sensory nerves itself might not be related to the therapeutic effects of topical tacrolimus and corticosteroids in its early phase.
[Mh] Termos MeSH primário: Corticosteroides/uso terapêutico
Dermatite Atópica/tratamento farmacológico
Imunossupressores/uso terapêutico
Prurido/tratamento farmacológico
Tacrolimo/uso terapêutico
[Mh] Termos MeSH secundário: Administração Tópica
Corticosteroides/administração & dosagem
Animais
Valerato de Betametasona/administração & dosagem
Valerato de Betametasona/uso terapêutico
Clobetasol/administração & dosagem
Clobetasol/uso terapêutico
Citocinas/metabolismo
Dermatite Atópica/etiologia
Dermatophagoides farinae/imunologia
Modelos Animais de Doenças
Emolientes/administração & dosagem
Emolientes/uso terapêutico
Epiderme/efeitos dos fármacos
Epiderme/metabolismo
Epiderme/patologia
Seres Humanos
Imunossupressores/administração & dosagem
Masculino
Mastócitos/metabolismo
Camundongos
Pomadas/administração & dosagem
Pomadas/uso terapêutico
Vaselina/administração & dosagem
Vaselina/uso terapêutico
Tacrolimo/administração & dosagem
Resultado do Tratamento
Ubiquitina Tiolesterase/metabolismo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adrenal Cortex Hormones); 0 (Cytokines); 0 (Emollients); 0 (Immunosuppressive Agents); 0 (Ointments); 0 (thymic stromal lymphopoietin); 8009-03-8 (Petrolatum); 9IFA5XM7R2 (Betamethasone Valerate); ADN79D536H (Clobetasol); EC 3.4.19.12 (Ubiquitin Thiolesterase); EC 3.4.19.12 (Uchl1 protein, mouse); WM0HAQ4WNM (Tacrolimus)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170717
[Lr] Data última revisão:
170717
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170111
[St] Status:MEDLINE


  9 / 1209 MEDLINE  
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[PMID]:27987419
[Au] Autor:Hidasi AO; Groh KJ; Suter MJ; Schirmer K
[Ad] Endereço:Eawag, Swiss Federal Institute of Aquatic Science and Technology, Department of Environmental Toxicology, Dübendorf 8600, Switzerland; EPFL, School of Architecture, Civil and Environmental Engineering, Lausanne 1015, Switzerland.
[Ti] Título:Clobetasol propionate causes immunosuppression in zebrafish (Danio rerio) at environmentally relevant concentrations.
[So] Source:Ecotoxicol Environ Saf;138:16-24, 2017 Apr.
[Is] ISSN:1090-2414
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Synthetic glucocorticoids (GCs) are potential endocrine disrupting compounds that have been detected in the aquatic environment around the world in the low ng/L (nanomolar) range. GCs are used as immunosuppressants in medicine. It is of high interest whether clobetasol propionate (CP), a highly potent GC, suppresses the inflammatory response in fish after exposure to environmentally relevant concentrations. Bacterial lipopolysaccharide (LPS) challenge was used to induce inflammation and thus mimic pathogen infection. Zebrafish embryos were exposed to ≤1000nM CP from ~1h post fertilization (hpf) to 96 hpf, and CP uptake, survival after LPS challenge, and expression of inflammation-related genes were examined. Our initial experiments were carried out using 0.001% DMSO as a solvent vehicle, but we observed that DMSO interfered with the LPS challenge assay, and thus masked the effects of CP. Therefore, DMSO was not used in the subsequent experiments. The internal CP concentration was quantifiable after exposure to ≥10nM CP for 96h. The bioconcentration factor (BCF) of CP was determined to be between 16 and 33 in zebrafish embryos. CP-exposed embryos showed a significantly higher survival rate in the LPS challenge assay after exposure to ≥0.1nM in a dose dependent manner. This effect is an indication of immunosuppression. Furthermore, the regulation pattern of several genes related to LPS challenge in mammals supported our results, providing evidence that LPS-mediated inflammatory pathways are conserved from mammals to teleost fish. Anxa1b, a GC-action related anti-inflammatory gene, was significantly down-regulated after exposure to ≥0.05nM CP. Our results show for the first time that synthetic GCs can suppress the innate immune system of fish at environmentally relevant concentrations. This may reduce the chances of fish to survive in the environment, as their defense against pathogens is weakened.
[Mh] Termos MeSH primário: Clobetasol/toxicidade
Disruptores Endócrinos/toxicidade
Imunidade Inata/efeitos dos fármacos
Imunossupressores/toxicidade
Poluentes Químicos da Água/toxicidade
Peixe-Zebra/imunologia
[Mh] Termos MeSH secundário: Animais
Biomarcadores/metabolismo
Clobetasol/metabolismo
Regulação da Expressão Gênica/efeitos dos fármacos
Peixe-Zebra/embriologia
Peixe-Zebra/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Endocrine Disruptors); 0 (Immunosuppressive Agents); 0 (Water Pollutants, Chemical); ADN79D536H (Clobetasol)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161218
[St] Status:MEDLINE


  10 / 1209 MEDLINE  
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[PMID]:27951742
[Au] Autor:Kviecinski MR; David IM; Fernandes FS; Correa MD; Clarinda MM; Freitas AF; Silva JD; Gava M; Müller SD; Florentino D; Petronilho F; Moterle D; Kanis LA; Pedrosa RC
[Ad] Endereço:a Post-Graduate Program in Health Sciences , Universidade do Sul de Santa Catarina , Palhoça , Brazil.
[Ti] Título:Healing effect of Dillenia indica fruit extracts standardized to betulinic acid on ultraviolet radiation-induced psoriasis-like wounds in rats.
[So] Source:Pharm Biol;55(1):641-648, 2017 Dec.
[Is] ISSN:1744-5116
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:CONTEXT: Dillenia indica Linn. (Dilleniaceae) is traditionally used to treat skin inflammation. OBJECTIVE: This study evaluated the healing effect of Dillenia indica fruit extracts on induced psoriasis-like wounds in Wistar rats. MATERIALS AND METHODS: Extracts were standardized to betulinic acid, including an aqueous ethanolic extract (AEE), ethyl acetate extract (EAE) and petroleum ether extract. Effects against lipid peroxidation were assessed in vitro. Wounds were created at rat tails (n = 12). Topical treatments were applied once daily for 7 days (1 mL of AEE or EAE at 5 or 50 mg/mL). Maximal dose was defined by the extract solubility. A 10-fold lower dose was also tested. Positive and negative controls were treated with clobetasol (0.5 mg/mL) or excipient. Half of each group was euthanized for histology. The remaining animals were observed for 20 days for wound measurements. RESULTS: Yields of AEE and EAE were 4.3 and 0.7%, respectively. Betulinic acid concentrations in AEE and EAE were 4.6 and 107.6 mg/g. Extracts neutralized lipid peroxidation in vitro at 0.02 µg/mL, accelerating healing at 50 mg/mL. Complete healing in mice treated with AEE occurred 16 days after wound induction. This time was 14 and 12 days in mice treated with EAE and clobetasol. Compared to orthokeratosis, parakeratosis was reduced by AEE (25%), EAE (45%) and clobetasol (55%). EAE caused superior protection against biomolecules oxidation of skin compared to AEE. DISCUSSION AND CONCLUSION: EAE exhibited activity closer to that of clobetasol. Betulinic acid may be an active constituent, which should be assessed in future studies.
[Mh] Termos MeSH primário: Anti-Inflamatórios/farmacologia
Antioxidantes/farmacologia
Fármacos Dermatológicos/farmacologia
Dilleniaceae/química
Frutas/química
Extratos Vegetais/farmacologia
Psoríase/tratamento farmacológico
Pele/efeitos dos fármacos
Triterpenos/farmacologia
Raios Ultravioleta
Cicatrização/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Anti-Inflamatórios/isolamento & purificação
Anti-Inflamatórios/normas
Antioxidantes/isolamento & purificação
Antioxidantes/normas
Biomarcadores/metabolismo
Clobetasol/farmacologia
Fármacos Dermatológicos/isolamento & purificação
Fármacos Dermatológicos/normas
Modelos Animais de Doenças
Peroxidação de Lipídeos/efeitos dos fármacos
Masculino
Malondialdeído/metabolismo
Estresse Oxidativo/efeitos dos fármacos
Fitoterapia
Extratos Vegetais/isolamento & purificação
Extratos Vegetais/normas
Plantas Medicinais
Carbonilação Proteica/efeitos dos fármacos
Psoríase/etiologia
Psoríase/metabolismo
Psoríase/patologia
Ratos Wistar
Pele/metabolismo
Pele/patologia
Solventes/química
Fatores de Tempo
Triterpenos/isolamento & purificação
Triterpenos/normas
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents); 0 (Antioxidants); 0 (Biomarkers); 0 (Dermatologic Agents); 0 (Plant Extracts); 0 (Solvents); 0 (Triterpenes); 4G6A18707N (betulinic acid); 4Y8F71G49Q (Malondialdehyde); ADN79D536H (Clobetasol)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170313
[Lr] Data última revisão:
170313
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161214
[St] Status:MEDLINE



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