RESUMO
BACKGROUND: Tapinarof cream is a topical aryl hydrocarbon receptor-modulating agent under investigation for the treatment of psoriasis. Tapinarof modulates the expression of interleukin-17 and the skin-barrier proteins filaggrin and loricrin. METHODS: We conducted two identical phase 3 randomized trials of tapinarof in patients with mild-to-severe plaque psoriasis. Adults with a baseline Physician's Global Assessment (PGA) score of 2 (mild) to 4 (severe) (on a scale from 0 to 4, with higher scores indicating more severe psoriasis) and a percent of total body-surface area affected of 3 to 20% were randomly assigned in a 2:1 ratio to use tapinarof 1% cream or vehicle cream once daily for 12 weeks. The primary end point, PGA response, was a PGA score of 0 (clear) or 1 (almost clear) and a decrease from baseline of at least 2 points at week 12. Secondary efficacy end points at week 12 were a reduction of at least 75% in the Psoriasis Area and Severity Index (PASI) score, a PGA score of 0 or 1, the mean change from baseline in the percent of body-surface area affected, and a reduction of at least 90% in the PASI score. Patient-reported outcomes were the mean changes from baseline to week 12 in the proportion of patients who had a decrease of at least 4 points in the Peak Pruritus Numeric Rating Scale (PP-NRS) score (range, 0 [no itch] to 10 [worst imaginable itch]), the PP-NRS total score, the Dermatology Life Quality Index total score, and the Psoriasis Symptom Diary score. RESULTS: In trials 1 and 2, a total of 692 and 674 patients, respectively, were screened, with 510 and 515 patients being enrolled. A PGA response occurred in 35.4% of the patients in the tapinarof group and in 6.0% of those in the vehicle group in trial 1 and in 40.2% and 6.3%, respectively, in trial 2 (P<0.001 for both comparisons). Results for secondary end points and patient-reported outcomes were generally in the same direction as those for the primary end point. Adverse events with tapinarof cream included folliculitis, nasopharyngitis, contact dermatitis, headache, upper respiratory tract infection, and pruritus. CONCLUSIONS: Tapinarof 1% cream once daily was superior to vehicle control in reducing the severity of plaque psoriasis over a period of 12 weeks but was associated with local adverse events and headache. Larger and longer trials are needed to evaluate the efficacy and safety of tapinarof cream as compared with existing treatments for psoriasis. (Funded by Dermavant Sciences; PSOARING 1 and 2 ClinicalTrials.gov numbers, NCT03956355 and NCT03983980, respectively.).
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Psoríase/tratamento farmacológico , Resorcinóis/administração & dosagem , Estilbenos/administração & dosagem , Adulto , Anti-Inflamatórios não Esteroides/efeitos adversos , Dermatite de Contato/etiologia , Método Duplo-Cego , Feminino , Cefaleia/induzido quimicamente , Humanos , Análise de Intenção de Tratamento , Interleucina-17/metabolismo , Masculino , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Psoríase/complicações , Receptores de Hidrocarboneto Arílico/efeitos dos fármacos , Receptores de Hidrocarboneto Arílico/metabolismo , Resorcinóis/efeitos adversos , Índice de Gravidade de Doença , Creme para a Pele/administração & dosagem , Estilbenos/efeitos adversosRESUMO
Tapinarof is an aryl hydrocarbon receptor (AHR) ligand which is used to treat plaque psoriasis in adults. However, the underlying mechanism is not yet fully understood. In this study, we applied two of the most studied psoriasis mouse models: topical application of imiquimod (IMQ) and subcutaneous injection of IL-23. Although both models successfully induced psoriasis-like lesions in mice, tapinarof had a completely opposite effect on the two models. Tapinarof decreased the expression of multiple essential cytokines involved in the pathological IL-23/IL-17/IL-22 axis and ameliorated IMQ-induced psoriatic dermatitis, inhibiting keratinocyte proliferation and abnormal differentiation. However, in the IL-23-injection-model, tapinarof instead aggravated the disease. Here, tapinarof increased epidermal thickness and differentiated epidermal dysplasia in mice. Our data suggest that tapinarof may have different effects on varied types of psoriasis.
Assuntos
Psoríase , Estilbenos , Animais , Camundongos , Imiquimode , Psoríase/metabolismo , Resorcinóis/efeitos adversos , Interleucina-23 , Modelos Animais de Doenças , Camundongos Endogâmicos BALB CRESUMO
BACKGROUND: Tapinarof cream 1% once daily, an aryl hydrocarbon receptor-modulating agent, was significantly more efficacious than vehicle and well tolerated in two 12-week phase 3 trials in adults with mild to severe plaque psoriasis. OBJECTIVE: To assess long-term safety, efficacy, remittive effect, durability of response, and tolerability of tapinarof. METHODS: Patients completing the 12-week trials were eligible for 40-weeks' open-label treatment and 4-weeks' follow-up. Treatment was based on the Physician Global Assessment (PGA) score. Patients entering with PGA≥1 received tapinarof until PGA = 0. Patients with PGA = 0 discontinued tapinarof and were monitored for remittive effect. Patients with PGA≥2 were re-treated until PGA = 0. RESULTS: Overall, 91.6% (n = 763) of eligible patients enrolled; 40.9% of patients achieved complete disease clearance (PGA = 0), and 58.2% entering with PGA≥2 achieved PGA = 0 or 1. Mean duration of off therapy remittive effect for patients achieving PGA = 0 was 130.1 days. No new safety signals were observed. Most frequent adverse events were folliculitis (22.7%), contact dermatitis (5.5%), and upper respiratory tract infection (4.7%). LIMITATIONS: Open-label; no control; may not be generalizable to all forms of psoriasis; remittive effect/response rate potentially underestimated. CONCLUSIONS: Efficacy improved beyond the 12-week trials, with a 40.9% complete disease clearance rate, â¼4-month off therapy remittive effect, durability on therapy, and consistent safety.
Assuntos
Psoríase , Receptores de Hidrocarboneto Arílico , Adulto , Humanos , Emolientes/uso terapêutico , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Resorcinóis/efeitos adversos , EstilbenosRESUMO
Topical and systemic antibiotic therapy remains the first-line treatment for mild-to-moderate hidradenitis suppurativa (HS). However, literature data on antibiotic resistance in HS are growing. A total of 134 patients with mild-to-moderate HS were retrospectively evaluated. Seventy-three patients (group A) received topical clindamycin 1% and 61 patients (group B) received topical resorcinol 15%. We evaluated the efficacy and tolerability of topical 15% resorcinol versus topical 1% clindamycin in mild-to-moderate HS, comparing the clinical response at 12 weeks of treatment. Patients treated with resorcinol 15% showed a significant improvement in Hidradenitis Suppurativa Clinical Response, International Hidradenitis Suppurativa Severity Score System, and Pain Visual Analogue Scale score from baseline compared to patients treated with clindamycin 1%. Topical resorcinol 15% could be a valid alternative to clindamycin in the management of acute and long-standing HS, limiting antibiotic use and antimicrobial resistance.
Assuntos
Clindamicina , Hidradenite Supurativa , Antibacterianos/efeitos adversos , Clindamicina/efeitos adversos , Hidradenite Supurativa/induzido quimicamente , Hidradenite Supurativa/diagnóstico , Hidradenite Supurativa/tratamento farmacológico , Humanos , Resorcinóis/efeitos adversos , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Tapinarof (VTAMA®; Dermavant Sciences, Inc.) is a novel, non-steroidal, topical, aryl hydrocarbon receptor agonist, FDA approved for psoriasis treatment and under investigation for atopic dermatitis treatment as a 1% cream formulation for once-daily (QD) application. OBJECTIVE: Evaluate cumulative skin irritation, sensitization, and photoallergic and phototoxic potential of tapinarof cream 1% across a range of dosing frequencies and conditions. METHODS: We conducted 4 randomized, controlled, phase 1 trials of topical tapinarof cream 1% vs vehicle or other appropriate controls in healthy adults. Cumulative skin irritation was assessed following QD application for 21 days under fully occlusive patch conditions. Contact sensitization, photoallergenicity, and phototoxicity were assessed under semi-occlusive patch conditions. The contact sensitization and photoallergenicity trials used an induction phase of repeated applications followed by a 2-week rest period and a 1-time challenge, with rechallenge if responses indicated sensitization/photosensitization; the phototoxicity trial comprised a single application. Ultraviolet A and B irradiation was used to assess photoallergenicity/toxicity. RESULTS: 376 participants were randomized across the 4 trials. In the cumulative irritation trial, tapinarof cream 1% QD was classified as having a slight potential for very mild cumulative irritation under the exaggerated test conditions of repeated dosing for 21 days. There was no evidence of sensitization, photosensitization, or phototoxicity. Tapinarof was well tolerated and there was a low discontinuation rate across all trials. CONCLUSIONS: Tapinarof cream 1% was well tolerated, non-sensitizing, non-phototoxic, and non-photoallergic, with no evidence of clinically meaningful cumulative skin irritation in 4 dermal safety trials in healthy adults. TRIAL REGISTRATION: IND 104601 J Drugs Dermatol. 2022;21(10):1084-1090. doi:10.36849/JDD.6627R1.
Assuntos
Resorcinóis , Creme para a Pele , Adulto , Dermatite Fotoalérgica/epidemiologia , Dermatite Fototóxica/epidemiologia , Humanos , Receptores de Hidrocarboneto Arílico/agonistas , Resorcinóis/efeitos adversos , Creme para a Pele/efeitos adversosRESUMO
BACKGROUND: Tapinarof cream is a topical therapeutic aryl hydrocarbon receptor modulating agent under investigation for treatment of psoriasis and atopic dermatitis. METHODS: In a phase 2b, double-blind, vehicle-controlled study, adults with plaque psoriasis were randomized to tapinarof cream 0.5% or 1% once or twice daily or vehicle once or twice daily for 12 weeks with 4-week follow-up. Efficacy outcomes included Physician Global Assessment (PGA) scores, change in PGA and total target lesion grading scores, and proportion of patients achieving ≥50%, ≥75%, and ≥90% reductions in the Psoriasis Area and Severity Index scores from baseline (PASI50, PASI75, and PASI90). RESULTS: At week 12, improvements were observed in all tapinarof groups vs vehicle in PGA response, change in PGA and total target lesion grading scores, PASI50 (71%-92% vs 10%-32%), PASI75 (46%-65% vs 5%-16%), and PASI90 (18%-40% vs 0%); all differences were statistically significant with tapinarof 1% once daily. Tapinarof responses were apparent from week 2, with significant efficacy at week 8 maintained through week 16. Most adverse events were mild or moderate. LIMITATIONS: The analyses reported require confirmation in larger prospective studies. CONCLUSIONS: Tapinarof may represent an important advance in the development of topical medicines for treatment of psoriasis.
Assuntos
Medidas de Resultados Relatados pelo Paciente , Psoríase/tratamento farmacológico , Resorcinóis/administração & dosagem , Creme para a Pele/administração & dosagem , Estilbenos/administração & dosagem , Adolescente , Adulto , Idoso , Canadá , Método Duplo-Cego , Esquema de Medicação , Feminino , Seguimentos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Psoríase/diagnóstico , Resorcinóis/efeitos adversos , Índice de Gravidade de Doença , Creme para a Pele/efeitos adversos , Estilbenos/efeitos adversos , Resultado do Tratamento , Estados Unidos , Adulto JovemRESUMO
BACKGROUND: Tapinarof is a topical therapeutic aryl hydrocarbon receptor modulating agent under investigation for atopic dermatitis (AD) and psoriasis treatment. METHODS: A phase 2b, double-blind, vehicle-controlled study randomly assigned adolescents and adults with AD to receive tapinarof cream 0.5%, 1%, or vehicle, once or twice daily, for 12 weeks with a 4-week follow-up. Outcomes included Investigator Global Assessment (IGA), Eczema Area and Severity Index (EASI), body surface area affected, pruritus numeric rating scale scores, patients' impressions of AD and pruritus symptom severity, and Patient-Oriented Eczema Measure (POEM) scores. RESULTS: Overall, 191 of 247 randomized patients completed the study. Week 12 IGA responses were higher in the tapinarof groups versus the vehicle group, reaching statistical significance with tapinarof 1% twice daily, ≥75%/90% improvement in EASI from baseline were significantly higher in the tapinarof groups (except 0.5% once daily and 0.5% twice daily), EASI scores were significantly improved in all tapinarof groups, and body surface area affected was significantly reduced in the tapinarof groups (except 0.5% twice daily). More patients reported AD and pruritus symptom severity as very/moderately improved in tapinarof groups, and POEM improvements were observed in all groups. Most adverse events were mild or moderate. LIMITATIONS: Larger prospective studies are required to confirm the reported analyses. CONCLUSIONS: Tapinarof is a potential important advance in topical medicine development for AD.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Dermatite Atópica/tratamento farmacológico , Resorcinóis/administração & dosagem , Creme para a Pele/administração & dosagem , Estilbenos/administração & dosagem , Adolescente , Adulto , Idoso , Anti-Inflamatórios não Esteroides/efeitos adversos , Criança , Dermatite Atópica/diagnóstico , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Resorcinóis/efeitos adversos , Índice de Gravidade de Doença , Creme para a Pele/efeitos adversos , Estilbenos/efeitos adversos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Melasma can be refractory to treatment, and relapses are frequent. Thiamidol is a new potent tyrosinase inhibitor that has been found effective as a cosmeceutical for the depigmenting of melasma. OBJECTIVE: This study compared the efficacy and tolerability of topical 0.2% Thiamidol vs. 4% hydroquinone for facial melasma. METHODS: Fifty women with facial melasma participated in a randomized, evaluator-blinded, controlled study from September through November 2020. Patients were randomly assigned to apply a double layer of 0.2% Thiamidol twice a day or 4% hydroquinone cream at bedtime, for 90 days. Both groups received tinted sunscreen (sun protection factor 60, PPD 20). The primary outcome was the change from the baseline Modified Melasma Area Seve:rity Index (mMASI) score. Secondary outcomes were improvements in the patients' quality of life [Melasma Quality of Life Index (MELASQoL)], colourimetry, and Global Aesthetic Improvement Scale (GAIS) evaluation. RESULTS: One participant, from the hydroquinone group, did not complete the study (unrelated to adverse effects). The mean (SD) age of the participants was 43 (6) years, and 86% were phototypes III-IV. Both groups exhibited a reduction in mMASI, MELASQoL, and colour contrast scores (P < 0.01). The mean [95% confidence interval (CI 95%)] reductions of the mMASI scores were 43% (35-50%) for Thiamidol and 33% (23-42%) for hydroquinone. There was no difference between the groups in the reductions in mMASI, MELASQoL, colourimetric contrast and GAIS scores (P ≥ 0.09). The GAIS analysis resulted in an improvement of 84% (CI: 95% 67-97%) for participants in the Thiamidol group and 74% (CI: 95% 61-93%) for those in the hydroquinone group. There were only mild adverse effects in the Thiamidol group, but allergic contact dermatitis was evidenced in two (8%) participants. CONCLUSION: The melasma improvement achieved using 0.2% Thiamidol did not differ from that of 4% hydroquinone cream. Thiamidol can be considered a suitable option for melasma patients with poor tolerability or treatment failure with hydroquinone.
Assuntos
Hidroquinonas , Melanose , Adulto , Feminino , Humanos , Hidroquinonas/efeitos adversos , Melanose/tratamento farmacológico , Recidiva Local de Neoplasia , Qualidade de Vida , Resorcinóis/efeitos adversos , Resultado do TratamentoRESUMO
Historically skin sensitisation risk assessment for cosmetic ingredients was based on animal models, however regulatory demands have led to Next Generation Risk Assessment (NGRA), using data from New Approach Methodologies (NAM) and Defined Approaches (DA). This case study was meant to investigate if the use of resorcinol at 0.2% in a face cream was safe and a maximum use concentration could be defined. The NAM data and DA predictions could not provide sufficient confidence to determine a point of departure (POD). Therefore, the application of read-across was explored to increase the level of confidence. Analogue searches in various tools and databases using "mode of action" and "chemical structural features" retrieved 535 analogues. After refinement by excluding analogues without a defined structure, similar reactivity profile and skin sensitisation data, 39 analogues remained. A final selection was made based on three approaches: expert judgment, chemical similarity or Local Lymph Node Assay data (LLNA). All read-across approaches supported a moderate potency. A POD derived from the LLNA EC3 of 3.6% was determined leading to a favourable NGRA conclusion and a maximum use concentration of 0.36%. This was supported by a traditional risk assessment based on the available animal data for resorcinol.
Assuntos
Cosméticos/efeitos adversos , Ensaio Local de Linfonodo , Resorcinóis/efeitos adversos , Creme para a Pele/efeitos adversos , Pele/efeitos dos fármacos , Animais , Cosméticos/administração & dosagem , Análise de Dados , Humanos , Resorcinóis/administração & dosagem , Medição de Risco , Pele/metabolismo , Pele/patologia , Creme para a Pele/administração & dosagemRESUMO
Mild to moderate atopic dermatitis (AD) occurs frequently in children and adults and is usually managed through the use of pharmacologic treatments, such as topical corticosteroids (TCS) and topical calcineurin inhibitors (TCIs), and good skin care practices. As chronic TCS or TCI can lead to the development of adverse effects, there is a need for safe, alternative treatments for patients with resistant AD. A systemic literature review was performed to examine the safety and efficacy of topical agents currently in phase II and phase III clinical trials for AD. Our team searched the databases, PubMed, Google Scholar, and ClinicalTrials.gov, on March 2020 for studies pertaining to the use of topical agents in AD. Key words included each drug (tapinarof, crisaborole, ARQ-151 cream, ruxolitinib) or "topical agents"; combined with "atopic dermatitis"; Articles published within the last 5 years were included as references. References within retrieved articles were also reviewed to identify potentially missed studies. A total of 24 articles were included in this review. Tapinarof, crisaborole, and ruxolitinib lead to statistically significant improvements in multiple disease severity scores. ARQ-151 cream achieved statistical significance in secondary endpoints, including vIGA-AD and EASI-75, but not in the primary endpoint of the study. All topical agents were well-tolerated by study participants. The findings demonstrate that tapinarof, crisaborole, ARQ-151 cream, and ruxolitinib are safe, effective treatment options for patients with mild to moderate AD. J Drugs Dermatol. 2020;19(10):956-959. doi: 10.36849/JDD.2020.5214.
Assuntos
Dermatite Atópica/tratamento farmacológico , Fármacos Dermatológicos/administração & dosagem , Creme para a Pele/administração & dosagem , Administração Cutânea , Aminopiridinas/administração & dosagem , Aminopiridinas/efeitos adversos , Benzamidas/administração & dosagem , Benzamidas/efeitos adversos , Compostos de Boro/administração & dosagem , Compostos de Boro/efeitos adversos , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Ciclopropanos/administração & dosagem , Ciclopropanos/efeitos adversos , Dermatite Atópica/diagnóstico , Fármacos Dermatológicos/efeitos adversos , Humanos , Nitrilas , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Pirimidinas , Resorcinóis/administração & dosagem , Resorcinóis/efeitos adversos , Índice de Gravidade de Doença , Creme para a Pele/efeitos adversos , Estilbenos/administração & dosagem , Estilbenos/efeitos adversos , Resultado do TratamentoRESUMO
Resorcinol is a frequently used hair dye, whose quantitative risk assessment (QRA) for hair color products is presented in this review as an example to assess its skin sensitization risk after topical application. Its purpose is to determine the maximum concentration that can be used without expecting skin sensitization to occur. The focus is to prevent the de novo development of a contact allergy. Epidemiological data which are provided via dermatological surveillance, e.g., by the IVDK (Information Network of Departments of Dermatology) in Germany, are an important source of information that help to assess the quality and the effectivity of the QRA.
Assuntos
Alérgenos , Dermatite Alérgica de Contato , Resorcinóis , Alérgenos/efeitos adversos , Dermatite Alérgica de Contato/etiologia , Dermatite Alérgica de Contato/prevenção & controle , Alemanha , Humanos , Testes do Emplastro , Resorcinóis/efeitos adversos , Medição de Risco , PeleRESUMO
The aim of this study was to apply the enzymatic treatment and fermentation by Pediococcus acidilactici BaltBio01 strain for industrial cereal by-products conversion to food/feed bioproducts with high amount of probiotic lactic acid bacteria (LAB). LAB propagated in potato media and spray-dried remained viable during 12 months (7.0 log10 cfu/g) of storage and was used as a starter for cereal by-products fermentation. The changes of microbial profile, biogenic amines (BAs), mycotoxins, lactic acid (L+/D-), lignans and alkylresorcinols (ARs) contents in fermented cereal by-product were analysed. Cereal by-products enzymatic hydrolysis before fermentation allows to obtain a higher count of LAB during fermentation. Fermentation with P. acidilactici reduce mycotoxins content in fermented cereal by-products. According to our results, P. acidilactici multiplied in potato juice could be used for cereal by-products fermentation, as a potential source to produce safer food/feed bioproduct with high amount of probiotic LAB for industrial production.
Assuntos
Ração Animal/microbiologia , Grão Comestível/metabolismo , Alimentos Fermentados/microbiologia , Aditivos Alimentares/metabolismo , Hidrolases/metabolismo , Pediococcus acidilactici/metabolismo , Probióticos/metabolismo , Alquilação , Ração Animal/efeitos adversos , Ração Animal/análise , Ração Animal/economia , Animais , Aminas Biogênicas/efeitos adversos , Aminas Biogênicas/análise , Aminas Biogênicas/metabolismo , Grão Comestível/efeitos adversos , Grão Comestível/química , Grão Comestível/economia , Fermentação , Alimentos Fermentados/efeitos adversos , Alimentos Fermentados/análise , Alimentos Fermentados/economia , Aditivos Alimentares/efeitos adversos , Aditivos Alimentares/química , Aditivos Alimentares/economia , Contaminação de Alimentos/prevenção & controle , Manipulação de Alimentos , Indústria de Processamento de Alimentos/economia , Humanos , Hidrolases/efeitos adversos , Hidrólise , Resíduos Industriais/economia , Letônia , Lignanas/efeitos adversos , Lignanas/análise , Lignanas/metabolismo , Viabilidade Microbiana , Micotoxinas/isolamento & purificação , Micotoxinas/metabolismo , Micotoxinas/toxicidade , Pediococcus acidilactici/crescimento & desenvolvimento , Probióticos/efeitos adversos , Resorcinóis/efeitos adversos , Resorcinóis/análise , Resorcinóis/metabolismoRESUMO
BACKGROUND: Melasma is a common challenging pigmentary skin disorder especially in dark-skinned females urging them to seek medical help. Many modalities of treatment are available, but none is satisfactory. OBJECTIVE: To compare safety and efficacy of combined trichloroacetic acid (TCA) (20%-25%) and Jessner's solution versus TCA (20%-25%) alone in dark patients with melasma. MATERIALS AND METHODS: The study design was a split face, right-left, assessor-blinded, randomized controlled study. Twenty-four adult female patients (skin phototypes IV-V) with bilateral melasma were treated for 6 sessions at 2 weeks intervals. Clinical assessment of the 2 sides of the face with Melasma Area and Severity Index (MASI) score was performed, and photographs were taken before and after the peeling course. RESULTS: Both therapeutic modalities showed significant decrease in MASI score, which was significantly lower on the side treated with both Jessner solution and TCA. There were significant negative correlations between the percentage of improvement of MASI score and both age of the patients and duration of the melasma. CONCLUSION: Dark skin melasma can be treated with both regimens safely and effectively; however, combined Jessner solution and TCA is more effective.
Assuntos
Abrasão Química/métodos , Etanol/uso terapêutico , Ácido Láctico/uso terapêutico , Melanose/terapia , Resorcinóis/uso terapêutico , Salicilatos/uso terapêutico , Ácido Tricloroacético/uso terapêutico , Adulto , Fatores Etários , Abrasão Química/efeitos adversos , Combinação de Medicamentos , Quimioterapia Combinada , Etanol/efeitos adversos , Feminino , Humanos , Ácido Láctico/efeitos adversos , Pessoa de Meia-Idade , Resorcinóis/efeitos adversos , Salicilatos/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Ácido Tricloroacético/efeitos adversos , Adulto JovemRESUMO
BACKGROUND: The high risk of occupational skin disease among hairdressers, caused by skin exposure to irritants and sensitizers, such as hair dye substances, is of great concern. OBJECTIVES: The aim of the present study was to assess how the various tasks involved in hair dyeing contribute to hairdressers' exposure to hair dye, in order to enable the formulation of well-founded recommendations on working routines that will reduce exposure and prevent occupational disease. METHODS: Skin exposure to hair dye was measured for 20 hairdressers applying highlights and all-over hair colour with the hand rinsing technique. Resorcinol was used as a proxy for hair dye exposure. RESULTS: Applying hair dye and cutting the newly dyed hair were the tasks that contributed most to exposure in treatments for highlights. After cutting all-over-coloured hair, all hairdressers had measurable amounts of hair dyes on both hands. CONCLUSIONS: Hairdressers are exposed to hair dye ingredients during all steps of the hair dyeing procedure. Cutting newly dyed hair contributes significantly to exposure. For the prevention of occupational disease resulting from hair dye exposure, we suggest cutting hair before dyeing it, and wearing gloves during all other work tasks.
Assuntos
Indústria da Beleza , Dermatite Alérgica de Contato/etiologia , Dermatite Ocupacional/etiologia , Tinturas para Cabelo/efeitos adversos , Exposição Ocupacional/efeitos adversos , Adulto , Dermatite Alérgica de Contato/prevenção & controle , Dermatite Ocupacional/prevenção & controle , Feminino , Luvas Protetoras , Humanos , Pessoa de Meia-Idade , Resorcinóis/efeitos adversos , Medição de Risco , Fatores de Risco , Suécia , Adulto JovemRESUMO
Chemical peeling is a common treatment in cosmetic dermatology. A peel that has been used for many years is trichloroacetic acid. Its adverse effects have for a long time been a major limitation. We present a practical review of the characteristics, mechanisms of action, indications, and complications of superficial chemical peels and of peeling with trichloroacetic acid.
Assuntos
Abrasão Química , Ácidos/efeitos adversos , Ácidos/uso terapêutico , Animais , Abrasão Química/efeitos adversos , Abrasão Química/métodos , Colágeno Tipo I/biossíntese , Combinação de Medicamentos , Elastina/biossíntese , Epiderme/efeitos dos fármacos , Epiderme/metabolismo , Etanol/efeitos adversos , Etanol/uso terapêutico , Dermatoses Faciais/terapia , Humanos , Hiperpigmentação/terapia , Ceratolíticos/efeitos adversos , Ceratolíticos/uso terapêutico , Ácido Láctico/efeitos adversos , Ácido Láctico/uso terapêutico , Camundongos , Transtornos da Pigmentação/induzido quimicamente , Lesões Pré-Cancerosas/terapia , Resorcinóis/efeitos adversos , Resorcinóis/uso terapêutico , Salicilatos/efeitos adversos , Salicilatos/uso terapêutico , Envelhecimento da Pele , Neoplasias Cutâneas/prevenção & controle , Ácido Tricloroacético/efeitos adversos , Ácido Tricloroacético/uso terapêuticoRESUMO
BACKGROUND: AUY922 is an inhibitor of heat shock protein 90 (Hsp90). Hsp90 inhibitors induce kit degradation in preclinical gastrointestinal stromal tumor (GIST) models. This trial was designed to determine the progression-free survival (PFS) of patients with GIST refractory to or intolerant of imatinib and sunitinib. METHODS: Eligible patients received AUY922 70 mg/mg(2) by intravenous (IV) infusion on days 1, 8, and 15 of 21-day cycles. Treatment continued until progression or unacceptable toxicity. RESULTS: Between December 2011 and January 2015, 25 patients were enrolled (median age, 63 years; 56% male) and received a median of 2 cycles (range: 1-12) of AUY922 treatment. Thirty-four patients were planned, but enrollment was stopped early due to slow accrual. Median PFS was 3.9 months (95% CI: 2.5, 5.3) and median OS was 8.5 months (95% CI: 5.2, 16.7). Radiographic response was evaluated in 21 patients; one patient achieved PR (4%) with another 15 having best response of stable disease (60%). The most common treatment-related adverse event was diarrhea (60% all grades). Reversible ocular toxicities that resulted in drug hold (24%) or reduction (8%) were also observed. CONCLUSION: AUY922 produced a median PFS which compares favorably to historical controls of placebo (6 weeks) for patients refractory to treatment with imatinib. While diarrhea and ocular toxicities were common, the majority of patients received treatment until disease progression.
Assuntos
Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Isoxazóis/uso terapêutico , Resorcinóis/uso terapêutico , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Terapia Combinada , Intervalo Livre de Doença , Feminino , Seguimentos , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/mortalidade , Tumores do Estroma Gastrointestinal/patologia , Humanos , Isoxazóis/administração & dosagem , Isoxazóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Mutação , Resorcinóis/administração & dosagem , Resorcinóis/efeitos adversos , Retratamento , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To investigate the time-dose-response relationship of benvitimod cream after topical administration in patients with mild and moderate psoriasis vulgaris for dosage regimen exploring. METHODS: 36 patients with mild and moderate psoriasis vulgaris were randomly assigned to receive 0.5%, 1.0%, 1.5%, and 0% (placebo) benvitimod cream of 30 g/1.7 m2 twice daily for 6 weeks. The primary efficacy outcome was the proportion of patients achieving more than 75% change of the psoriasis area and severity index (PASI 75) from baseline. A longitudinal Emax model was established using the NONMEM method, and then applied to try to find an appropriate dose for following trials. RESULTS: In the final time-dose-response model, the primary outcome at week 6 of PASI 75 of the 0.5%, 1.0%, and 1.5% benvitimod cream was 31%, 63%, and 75%, respectively, demonstrating that the 1.0% benvitimod cream was an appropriate dose for the next trial. The time parameters of ET50 and ET90 were 15 and 69 days for 1.0% benvitimod cream, indicating that the maximum efficacy of PASI change rate was obtained at approximately week 10. The accuracy of PASI change rate by extrapolation prediction was limited at week 10, so the treatment period should be longer in future trials. CONCLUSIONS: The established dose-response model could well describe the relationship between PASI change rate and doses of benvitimod cream in patients with mild and moderate psoriasis vulgaris. This modeling approach may help choose 1.0% benvitimod cream twice daily as a dosage regimen in following clinical trials.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Psoríase/tratamento farmacológico , Resorcinóis/administração & dosagem , Estilbenos/administração & dosagem , Adulto , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pomadas , Resorcinóis/efeitos adversos , Estilbenos/efeitos adversosRESUMO
BACKGROUND: This phase I study determined the maximum tolerated dose (MTD) of AUY922 with capecitabine in advanced solid tumors. METHODS: Capecitabine 1000 mg/m(2) PO BID was administered with escalating doses of AUY922 IV; the MTD of AUY922 was combined with capecitabine 1250 mg/m(2) (DL6). RESULTS: 23 patients were treated at 5 dose levels (22 mg/m(2)-70 mg/m(2)). No DLTs were observed until DL6 (grade 3 diarrhea). Reversible vision darkening was seen in 26%. Four patients had partial response; 2 previously progressed on fluorouracil. Eight patients had stable disease (median 25.5 weeks). CONCLUSION: AUY922 plus capecitabine was well-tolerated up to 70 mg/m(2) with encouraging preliminary efficacy.