Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 207
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
J Eur Acad Dermatol Venereol ; 38(3): 583-593, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38391212

RESUMO

BACKGROUND: Efficacy of the Janus kinase (JAK) inhibitor baricitinib for severe alopecia areata (AA) continuously increased over 52 weeks in two Phase 3 trials. There are limited long-term data on JAK inhibitors in AA. OBJECTIVES: To evaluate efficacy and safety of baricitinib for severe AA through 104 weeks of continuous therapy. METHODS: Integrated data from the BRAVE-AA1 and BRAVE-AA2 Phase 3 trials included adults with Severity of Alopecia Tool (SALT) scores ≥50 (≥50% scalp hair loss) randomized to and continuously treated with 2-mg or 4-mg baricitinib through Week 104. Patients who qualified to remain on continuous treatment included subjects who achieved SALT score ≤20 at Week 52 (Week-52 responders; 2-mg: N = 65; 4-mg: N = 129) and baricitinib 4-mg-treated patients who had SALT score >20 at Week 52 but achieved SALT score ≤20 at prior visit(s) and/or had significant improvement in eyebrow or eyelash hair growth relative to baseline by Week 52 (Week-52 mixed responders; N = 110). Week-104 outcomes included the proportion of patients achieving SALT score ≤20 (≤20% scalp hair loss). Data were censored after treatment discontinuation. RESULTS: Among baricitinib 4-mg-treated and baricitinib 2-mg-treated Week-52 responders, 90.7% and 89.2%, respectively, maintained SALT score ≤20 at Week 104. Among Week-52 mixed responders, 39.1% reached SALT score ≤20 by Week 104. Continued improvement in eyebrow and eyelash regrowth was observed across groups. The most frequent treatment-emergent adverse events were COVID-19, upper respiratory tract infection, headache, nasopharyngitis, acne, urinary tract infection and creatine phosphokinase increase. CONCLUSIONS: Baricitinib demonstrated a high level of maintenance of efficacy over 104 weeks in patients with severe AA. Efficacy increased in Week-52 mixed responders, illustrating that long-term treatment is necessary to observe maximum benefit in some patients. No new safety signals were observed.


Assuntos
Alopecia em Áreas , Azetidinas , Inibidores de Janus Quinases , Purinas , Sulfonamidas , Adulto , Humanos , Alopecia/tratamento farmacológico , Alopecia em Áreas/tratamento farmacológico , Azetidinas/efeitos adversos , Inibidores de Janus Quinases/efeitos adversos , Pirazóis/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Ensaios Clínicos Fase III como Assunto
2.
Br J Dermatol ; 176(1): 138-144, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27375176

RESUMO

BACKGROUND: Autosomal recessive woolly hair/hypotrichosis (ARWH/H) is caused by mutations in LIPH. Homozygotes for the LIPH c.736T>A (p.C246S) mutation, the most prevalent genotype in Japanese patients, present varying degrees of hair loss; however, determinants of this phenotypic diversity remain elusive. OBJECTIVES: To establish methodologies for quantitative assessment of clinical severity and provide a detailed characterization to elucidate the factors contributing to phenotypic divergence. METHODS: Digital image analyses were conducted to convert clinical severities into numerical values. Eight patients with ARWH/H were classified into three groups (mild, severe, very severe), based on severity scores. Dermoscopic images were collected and assessed for total hair numbers and hair thickness for intergroup comparisons. RESULTS: The image analysis detected a difference in hair thickness but not in total hair numbers, between mild and severe cases. A marked decrease in total hair number was noted in an atypical very severe case. Histopathologically, a patient with a mild case demonstrated hair miniaturization and a high telogen/anagen ratio without a decrease in total hair count, endorsing dermoscopic observations. Two children demonstrated spontaneous improvement without an increase in total hair numbers, and two adults responded well to topical minoxidil with increased total hair numbers and hair thickness. CONCLUSIONS: The difference in the frequency of underdeveloped hairs may be a major factor contributing to the clinical diversity of hair sparseness in LIPH c.736T>A homozygotes with ARWH/H. Hence, pharmacological modification to thicken existing fine hairs may provide a therapeutic strategy.


Assuntos
Doenças do Cabelo/genética , Cabelo/anormalidades , Cabelo/patologia , Hipotricose/genética , Lipase/genética , Adulto , Criança , Pré-Escolar , Dermoscopia/métodos , Feminino , Doenças do Cabelo/tratamento farmacológico , Doenças do Cabelo/patologia , Preparações para Cabelo/uso terapêutico , Homozigoto , Humanos , Hipotricose/tratamento farmacológico , Hipotricose/patologia , Masculino , Minoxidil/uso terapêutico , Mutação/genética , Fenótipo
7.
Br J Dermatol ; 179(5): 1023-1024, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30387508
8.
J Eur Acad Dermatol Venereol ; 27(1): 86-91, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22122058

RESUMO

BACKGROUND: Pemphigus vulgaris (PV) patients may develop scalp erosions, however, the development of alopecia has been reported to be extremely rare. OBJECTIVE: To delineate the clinicopathological features of alopecia in PV and provide insight into the pathogenesis of this rarely observed manifestation. METHODS: A retrospective case note review was performed on five PV patients presenting with progressive hair loss and alopecic patches. Data were collected on demographics and clinical findings. Results for hair pull tests, direct immunofluorescence study of plucked hairs, established laboratory tests to detect anti-desmoglein 1 and 3 autoantibodies and scalp swab culture were recorded. A combination of vertical and horizontal sectioning technique enabled detailed histopathological analysis of alopecic patches. Clinical course was monitored. RESULTS: Anagen hair follicles with the outer root sheath structure were easily pulled from perilesional scalp, with intercellular IgG deposition on the outer root sheath keratinocytes. Acantholysis between outer root sheath keratinocytes extending from the infundibulum to suprabalbar level was evident in anagen hair follicles of affected lesions. Perifollicular cell infiltration was observed in the lesions where scalp swabs detected micro-organisms. The bulge stem cell area was mostly intact. Alopecia was non-scarring and following 4 weeks of therapy hair re-growth was seen in all patients. CONCLUSION: In PV, the combination of anti-desmoglein autoantibody-mediated acantholysis in conjunction with secondary factors, such as inflammatory changes due to infection, may cause weakening of hair follicle anchorage resulting in hair loss and alopecic patches. This unusual clinical phenotype should alert physicians to PV as a potential diagnosis.


Assuntos
Alopecia/tratamento farmacológico , Alopecia/etiologia , Pênfigo/complicações , Corticosteroides/uso terapêutico , Adulto , Idoso , Alopecia/patologia , Biópsia por Agulha , Estudos de Coortes , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Imunossupressores/uso terapêutico , Japão , Masculino , Pessoa de Meia-Idade , Pênfigo/diagnóstico , Pênfigo/tratamento farmacológico , Doenças Raras , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Resultado do Tratamento
9.
Br J Dermatol ; 175(1): 12, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27484265
10.
Br J Dermatol ; 174(4): 710-1, 2016 04.
Artigo em Inglês | MEDLINE | ID: mdl-27115578

Assuntos
Pestanas
11.
J Eur Acad Dermatol Venereol ; 25(11): 1346-50, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21981340

RESUMO

BACKGROUND: Alopecia areata (AA) is a common hair loss disorder characterized by cellular autoimmune reaction predominantly involving the bulbar portion of anagen hair follicles. In most cases of AA, the bulge stem cell area remains intact. Recently, a couple of molecules, such as keratin15 (K15) and CD200, have been identified as biomarkers of human bulge cells. Of note, an immunosuppressive molecule, CD200 is speculated to provide an immune privilege for bulge stem cells. OBJECTIVE: To investigate expression levels of stem cell markers, especially CD200, in two senile female cases of AA with unusual lymphocytic cell infiltrates surrounding both the bulge and the bulbar regions. Then, compare them with those in common AA cases without the bulge involvement. METHODS: Transverse sections containing the bulge levels were prepared from unaffected and affected lesions, respectively, from each AA group and immunohistochemical investigation using anti-K15 and CD200 antibodies was performed. Importantly, an approach to detect CD200 in paraffin sections was newly developed. Immunoreactivities of individual antibodies were compared between corresponding lesions in each patient group. RESULTS: In unaffected bulge lesions, K15 immunoreactivity was not different between bulge-involving AA and common AA groups, whilst that of CD200 was decreased in the former group. Both K15 and CD200 immunoreactivities were decreased in affected bulge lesions of bulge-involving AA compared to the bulge of common AA cases. CONCLUSION: Selective downregulation of CD200 in the bulge area could contribute to the collapse of immune privilege with resultant unusual bulge involvement in a subset of AA.


Assuntos
Alopecia em Áreas/metabolismo , Biomarcadores/metabolismo , Cabelo/patologia , Células-Tronco/patologia , Idoso , Feminino , Humanos , Imuno-Histoquímica
17.
Clin Exp Dermatol ; 34(8): e712-5, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19663856

RESUMO

An extremely rare case of intractable ulcer caused by Mycobacterium shinshuense is described. A 59-year-old Japanese woman developed an ulcerated subcutaneous induration on the upper arm. Ziehl-Neelsen staining revealed positive bacilli. Tissue culture isolated Mycobacterium species, but standard identification techniques (including molecular biological approaches such as DNA-DNA hybridization) could not distinguish the precise causative pathogen, although it was narrowed down to three possibilities: Mycobacterium marinum, Mycobacterium ulcerans and M. shinshuense. Finally, a novel 16S rRNA sequencing method enabled the diagnosis of M. shinshuense infection. The epidemiology of the cutaneous infection caused by this mycobacterium has yet to be elucidated, but a review of reported cases indicated that ulcers having some resemblance to those caused by M. ulcerans infection were found in nonendemic areas and that M. shinshuense could be considered as the cause. The approach introduced in this report could provide a powerful tool for the identification of this organism.


Assuntos
Infecções por Mycobacterium/microbiologia , Micobactérias não Tuberculosas/classificação , RNA Bacteriano/genética , RNA Ribossômico 16S/genética , Úlcera/microbiologia , Feminino , Humanos , Pessoa de Meia-Idade , Dados de Sequência Molecular , Micobactérias não Tuberculosas/genética
18.
Inhal Toxicol ; 19 Suppl 1: 157-60, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17886063

RESUMO

Oxidative stress has emerged as a pivotal mechanism that underlies the toxic pulmonary effects of suspended particulate matter (SPM). Experimental evidence shows that redox-active transition metals, redox-cycling quinoids, and polycyclic aromatic hydrocarbons (PAHs) contained in SPM act synergistically, producing reactive oxygen species (ROS). The direct production of superoxide anion and the damaging hydroxyl radical has been studied in aqueous and dimethyl sulfoxide (DMSO) suspensions of SPM both with and without H2O2; however, no study has reported on the release of ROS from ingesting macrophages with SPM. We investigated the time course of the ability to induce lucigenin-dependent chemiluminescence (CL) from human monocyte-derived macrophages exposed to SPM, carbon black particles, and diesel exhaust particles (DEP). We also examined hydroxyl radical generation from the same experimental system using the 2-deoxy-d-robse method. We found an increase of CL for SPM, but not for carbon black particles or for DEP. Hydroxyl radical generation was observed in both SPM and DEP, but the release from DEP was more frequent than that from SPM. These results suggest that certain components of SPM are important in the response of ROS from ingesting macrophages with SPM, and that those components are discharged from SPM into the atmosphere.


Assuntos
Macrófagos/metabolismo , Material Particulado/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Emissões de Veículos , Células Cultivadas , Humanos , Macrófagos/efeitos dos fármacos
19.
Neuropharmacology ; 37(9): 1169-76, 1998 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9833647

RESUMO

The potential antidepressant properties of indeloxazine hydrochloride were examined in vitro and in vivo. Indeloxazine showed preferential affinity for both [3H] citalopram (Ki: 22.1 nM) and [3H]nisoxetine binding sites (Ki: 18.9 nM) in membranes of the rat cerebral cortex. In microdialysis studies, intraperitoneal injection of indeloxazine (3 and 10 mg/kg) dose-dependently increased the extracellular level of both serotonin and norepinephrine in rat frontal cortex of freely moving rats. Amitriptyline was almost equivalent to indeloxazine in these two assays with the exception of a much weaker effect on extracellular serotonin levels. Spontaneous [3H]serotonin release from rat cortical synaptosomes was significantly enhanced by indeloxazine (10-1000 nM). In behavioral studies, indeloxazine increased the number of wheel rotations in forced swimming tests in both ICR mice (50 mg/kg, p.o.) and SAMP8//YAN, a substrain of senescence-accelerated mouse (20 and 30 mg/kg, p.o.). Indeloxazine (3-10 mg/kg p.o.) also inhibited the incidence of muricide in raphe-lesioned rats. These results suggest that indeloxazine is an inhibitor of serotonin and norepinephrine uptake and has potential antidepressant properties. In addition, the drug-induced enhancement of serotonin release may contribute to its potent effects on the serotonergic system in vivo.


Assuntos
Antidepressivos/farmacologia , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Morfolinas/farmacologia , Amitriptilina/metabolismo , Amitriptilina/farmacologia , Animais , Antidepressivos/metabolismo , Ligação Competitiva , Encéfalo/metabolismo , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Relação Dose-Resposta a Droga , Masculino , Camundongos , Camundongos Endogâmicos ICR , Morfolinas/metabolismo , Atividade Motora/efeitos dos fármacos , Norepinefrina/metabolismo , Ensaio Radioligante , Ratos , Ratos Wistar , Serotonina/metabolismo , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/metabolismo
20.
J Med Chem ; 44(11): 1833-6, 2001 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-11356117

RESUMO

We previously reported the presence of cytotoxic substances in extracts of the Danaid butterfly, Ideopsis similis. In the present study, we isolated cytotoxic substances against a human gastric cancer cell line, TMK-1, in I. similis pupae, with an activity similar to that of the adult butterfly. The basic fraction, prepared from a methanol extract, accounted for 83% of the cytotoxic activity. Two major cytotoxic substances were purified by HPLC, and one was determined to be a new phenanthroindolizidine alkaloid, trans-(+)-3,14alpha-dihydroxy-6,7-dimethoxyphenanthroindolizidine (1), and the other a known compound, trans-(+)-3,14alpha-dihydroxy-4,6,7-trimethoxyphenanthroindolizidine (2). The IC(50) values for TMK-1 cells were 0.5 ng/mL and 0.7 ng/mL, respectively. These two compounds showed similar cytotoxic potential with four other cancer cell lines including cervical, lung, and colon carcinomas and leukemia. Quantitative analyses indicated the presence of each of the two phenanthroindolizidine alkaloids at levels of 11-74 microg in each larva, pupa, or adult of I. similis. However, 1 was not detected in the leaves of Tylophora tanakae, a host plant for larvae of I. similis, and the level of 2 (2 microg per gram of leaves) was far less than that in the larvae. Since the leaves of T. tanakae are known to contain various phenanthroindolizidines, compounds 1 and 2 are presumably metabolically converted from such alkaloids in larvae of I. similis.


Assuntos
Alcaloides/farmacologia , Antineoplásicos/farmacologia , Borboletas/química , Indolizinas/farmacologia , Fenantrenos/farmacologia , Alcaloides/química , Alcaloides/isolamento & purificação , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Indolizinas/química , Indolizinas/isolamento & purificação , Espectroscopia de Ressonância Magnética , Fenantrenos/química , Fenantrenos/isolamento & purificação , Folhas de Planta/química , Células Tumorais Cultivadas
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA