Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 45
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Viruses ; 13(8)2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34452412

RESUMO

Acyclovir, valacyclovir, and famciclovir are used for the treatment of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections. Helicase-primase inhibitors (HPIs) inhibit replication fork progression that separates double DNA strands into two single strands during DNA synthesis. The HPIs amenamevir and pritelivir have novel mechanisms of anti-herpetic action, and their once-daily administration has clinical efficacy for genital herpes. Among HPIs, amenamevir has anti-VZV activity. The concentrations of HSV-1 and VZV required for the 50% plaque reduction of amenamevir were 0.036 and 0.047 µM, respectively. We characterized the features of amenamevir regarding its mechanism, resistance, and synergism with acyclovir. Its antiviral activity was not influenced by the viral replication cycle, in contrast to acyclovir. A clinical trial of amenamevir for herpes zoster demonstrated its non-inferiority to valacyclovir. To date, amenamevir has been successfully used in over 1,240,000 patients with herpes zoster in Japan. Post-marketing surveillance of amenamevir in Japan reported side effects with significant potential risk identified by the Japanese Risk Management Plan, including thrombocytopenia, gingival bleeding, and palpitations, although none of these were serious. The clinical efficacy and safety profiles of amenamevir were established in patients with herpes zoster. Therefore, amenamevir as an HPI opens a new era of anti-herpes therapy.


Assuntos
Antivirais/uso terapêutico , DNA Helicases/antagonistas & inibidores , DNA Primase/antagonistas & inibidores , Herpes Zoster/tratamento farmacológico , Herpesvirus Humano 1/efeitos dos fármacos , Oxidiazóis/uso terapêutico , Animais , Ensaios Clínicos como Assunto , Herpes Genital/tratamento farmacológico , Humanos , Camundongos
2.
Dermatol Res Pract ; 2018: 4127303, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30057596

RESUMO

Several traditional Japanese medicines including Keigairengyoto (KRT) are used to treat acne vulgaris, but there is no robust evidence of their effectiveness. In this study, we examined the effectiveness and safety of KRT in treating acne vulgaris. An open-label, randomized, parallel control group comparison was conducted with a conventional treatment group (adapalene and topical antibiotics; control group) and a KRT group (control treatment plus KRT). The test drugs were administered for 12 weeks to patients (15 to 64 years, outpatient) with inflammatory acne on their face, and the amount of acne at 2, 4, 8, and 12 weeks was measured. Sixty-four patients were enrolled; 29 patients in each group were included in the analysis. Twenty-eight patients in the control group and 24 patients in the KRT group were included in the efficacy analysis. The number of inflammatory skin rashes at 4 and 8 weeks in the KRT group was significantly decreased compared with the control group. There was no significant difference between the two groups in noninflammatory eruptions and general rashes. There were no serious adverse events in both groups. KRT may be a useful agent in patients with inflammatory acne in combination with conventional treatments. This trial is registered with UMIN 000014831.

3.
Int J Oncol ; 45(3): 1200-8, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24970722

RESUMO

The characteristic histopathological feature of mycosis fungoides (MF) and adult T-cell leukemia/lymphoma (ATLL) is epidermotropism. To identify the mechanism for epidermotropism of lymphoma cells, total RNAs were obtained from skin biopsies of epidermis and dermis of MF and ATLL patients by means of laser capture microdissection, and used for subsequent complementary DNA (cDNA) microarray experiments. This procedure has made it possible for us to observe and evaluate the regional environment of MF and ATLL. Hierarchical cluster analysis revealed that the cDNAs could be clearly differentiated into MF and ATLL. CCL27 was expressed in the dermis generated from keratinocytes, CCR4/CCR6/CCR7/CCR10/cutaneous lymphocyte-associated antigen (CLA) lymphoma cells in the dermis, and CCL21 in the extracellular matrix (stroma). Lymphotoxin (LT) ß and CCL21 expression was significantly higher and that of CCR10 relatively for MF, while CCR4 and CLA expression was relatively higher for ATLL. In the epithelium, keratinocytes expressed CCL20/CCL27, and lymphoma cells CCR4/CCR6/CCR10, while CCR4, CCR6, CCL20 and CCL27 expression was relatively higher for ATLL than MF. The dermis of MF, but not that of ATLL, showed correlation between CCR7 and CCL21. These findings support the suggestion that chemokines and chemokine receptors are involved in the pathogenesis of MF and ATLL, indicate that cutaneous homing seems to be different for MF and ATLL, and point to the possibility that cutaneous T-cell lymphomas originate in regulatory T cells, especially in the case of ATLL.


Assuntos
Quimiocina CCL27/genética , Microdissecção e Captura a Laser/métodos , Leucemia-Linfoma de Células T do Adulto/genética , Micose Fungoide/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Receptores CCR10/genética , Neoplasias Cutâneas/genética , Adulto , Idoso , Quimiocina CCL27/metabolismo , Derme/metabolismo , Derme/patologia , Epiderme/metabolismo , Epiderme/patologia , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Queratinócitos/metabolismo , Leucemia-Linfoma de Células T do Adulto/patologia , Masculino , Pessoa de Meia-Idade , Micose Fungoide/patologia , Receptores CCR10/metabolismo , Neoplasias Cutâneas/patologia , Adulto Jovem
4.
J Dermatol ; 40(12): 962-7, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24147543

RESUMO

We treated 12, 15 and 13 Japanese actinic keratosis (AK) lesions with 5-aminolevulinic acid photodynamic therapy (PDT), 5% imiquimod cream and combination of both therapies, respectively, and compared the effects. Patients underwent the second course, when AK lesions remained after the first course. Efficacy was evaluated 1 month after each treatment. Combination therapy cleared all AK lesions only after the first course, while PDT and imiquimod therapy cleared 41.7% and 66.7% of AK lesions after the first course, respectively. All residual AK lesions after the first course were cleared by the second courses of PDT or imiquimod therapy. During the course, erosion and crust developed significantly more frequently in combination therapy (P < 0.001). Most Japanese AK lesions can be satisfactorily treated with either PDT or imiquimod monotherapy. However, only severe cases may better be treated with combination therapy, which show higher efficacy even though adverse events occur frequently.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Aminoquinolinas/uso terapêutico , Ceratose Actínica/tratamento farmacológico , Fotoquimioterapia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imiquimode , Japão , Masculino , Pessoa de Meia-Idade , Fotoquimioterapia/efeitos adversos , Resultado do Tratamento
7.
Dermatol Ther ; 25(4): 382-5, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22950566

RESUMO

We evaluated the effectiveness of mizoribine, a newly developed immunosuppressive agent, as an adjuvant therapy in the treatment of both pemphigus vulgaris and pemphigus foliaceus. Eleven pemphigus patients (eight pemphigus vulgaris and three pemphigus foliaceus) received the combination therapy of prednisolone and mizoribine. Complete remission was observed in three of the eight patients with pemphigus vulgaris and in one of the three patients with pemphigus foliaceus. The four patients with complete remission had a rapid clinical response and achieved remission at a median of 11.8 months. Partial remission was achieved in two of the three patients with pemphigus foliaceus. The median time to achieve partial remission was 16.0 months. Six (55.6%) of the 11 patients with pemphigus had complete or partial remission and were able to taper their prednisolone. The cumulative probability of having a complete remission was 64.3% at 19 months of follow-up using Kaplan-Meier analysis. The effectiveness of the additional mizoribine therapy could be attributed to its corticosteroid-sparing properties as well as its immunosuppressive effects. The serum concentration titer of mizoribine was around 1.0 µg/mL 2 hours after administration. Patients who were not improved by the additional mizoribine might require a continuously higher dose of mizoribine to achieve effective therapy.


Assuntos
Imunossupressores/uso terapêutico , Pênfigo/tratamento farmacológico , Ribonucleosídeos/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/sangue , Imunossupressores/farmacocinética , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prednisolona/uso terapêutico , Estudos Retrospectivos , Ribonucleosídeos/sangue , Ribonucleosídeos/farmacocinética , Resultado do Tratamento
8.
Australas J Dermatol ; 53(3): 202-6, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22881466

RESUMO

Psoriasis greatly impacts the health-related quality of life of patients, including any dermatological conditions that are listed in the dermatology life quality index (DLQI). We investigated the relationships between DLQI and the degree of patient satisfaction using questionnaires among psoriasis patients treated only with topical corticosteroids. Patients who were dissatisfied with topical corticosteroids alone and agreed to receive cyclosporin were given low-dose oral cyclosporin. We assessed changes of the DLQI and the psoriasis area and severity index (PASI) scores in patients dissatisfied with treatment during the period of cyclosporin addition. Of 32 enrolled patients, 17 reported dissatisfaction with the current treatment of topical corticosteroids alone. There was a significantly positive correlation between the degree of patient satisfaction questionnaires and the DLQI of these 32 patients. Among the 17 dissatisfied patients, 12 patients agreed to receive additional cyclosporin therapy and five did not. The 12 patients who started on cyclosporin had a significantly lower PASI after 12 weeks than they did at baseline. The DLQI improved significantly after 12 weeks in the cyclosporin-treated patients. The 12 patients who agreed to receive cyclosporin showed a significantly lower DLQI at 12 weeks compared to the five patients who declined the addition of cyclosporin to their treatment. Assessing the degree of patient satisfaction with therapy using a questionnaire could be useful for improving clinical interventions in psoriasis patients. Low-dose oral cyclosporin could be effective in patients who are dissatisfied with topical corticosteroid treatment alone.


Assuntos
Ciclosporina/administração & dosagem , Imunossupressores/administração & dosagem , Satisfação do Paciente , Psoríase/tratamento farmacológico , Qualidade de Vida , Corticosteroides/uso terapêutico , Adulto , Idoso , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença
9.
J Dermatol ; 39(11): 902-8, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22670895

RESUMO

Famciclovir is a guanine analog antiviral drug used commonly for herpes zoster. Efficacy of famciclovir treatment has been reported to be comparable to valacyclovir treatment. Both of these medications reduce the time to complete cessation of zoster-associated pain including post-herpetic neuralgia, as compared to acyclovir. We conducted a multicenter, randomized, open clinical trial in order to evaluate the extent of pain relief afforded by these two antiviral drugs during the acute disease phase of herpes zoster. The study group comprised 86 immunocompetent adult patients suffering from herpes zoster, who were treated with either famciclovir or valacyclovir for 7 days. Of these, 55 patients enrolled in this study within 72 h of the onset of the rash and 31 patients after 72 h of the onset. There was a significant reduction in acute herpes zoster pain with famciclovir on day 7 and at 2-3 weeks in both of these patient groups, while with valacyclovir, there was not significant reduction in pain on day 7. Of patients aged 50 years or older, there was a significantly earlier reduction in pain with famciclovir than with valacyclovir. In addition, a significant reduction in the number of patients with pain was observed as early as days 3-4 with famciclovir treatment as compared with valacyclovir treatment. We conclude that famciclovir was superior to valacyclovir in the relief of acute pain of herpes zoster. Accordingly, famciclovir is recommended for herpes zoster patients with moderate symptoms and a visual analog scale score of under 50 mm.


Assuntos
2-Aminopurina/análogos & derivados , Dor Aguda/tratamento farmacológico , Aciclovir/análogos & derivados , Herpes Zoster/tratamento farmacológico , Valina/análogos & derivados , 2-Aminopurina/uso terapêutico , Dor Aguda/fisiopatologia , Aciclovir/uso terapêutico , Adulto , Idoso , Anti-Inflamatórios não Esteroides/uso terapêutico , Antivirais/uso terapêutico , Povo Asiático , Famciclovir , Feminino , Herpes Zoster/fisiopatologia , Humanos , Imunocompetência , Japão , Masculino , Pessoa de Meia-Idade , Medição da Dor , Valaciclovir , Valina/uso terapêutico
12.
J Am Acad Dermatol ; 66(2): 278-91, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21835496

RESUMO

BACKGROUND: Blastic plasmacytoid dendritic cell neoplasm (BPDC) is a rare hematologic neoplasm, which almost always involves the skin and shows poor prognosis. OBJECTIVE: The aim of our study was to enhance BPDC diagnosis and indications for prognosis. METHODS: This study involved 26 patients with BPDC. To investigate the histogenesis of BPDC, we reviewed the clinical features and stained markers of various hematopoietic lineages, chemokines, and their receptors. RESULTS: Bone-marrow infiltration was detected in 13 of the 19 cases examined and leukemic changes in 18. Complete remission was achieved in 14 cases, but more than half of the patients showed recurrence within a short time, and 14 patients died of the disease after 1 to 25 months (mean 8.5 months). Positivity for CD123 was detected in 18 of 24 cases and for T-cell leukemia 1 in 18 of 22 cases. Of the chemokines and their receptors, 8 of 15 skin biopsy specimens proved to be positive for CXCL12. Leukemic change subsequent to skin lesions occurred in 7 of 8 CXCL12-positive cases (87.5%) and in 3 of 6 CXCL12-negative cases (50%). Seven of the 8 CXCL12-positive patients (87.5%) and two of the 6 CXCL12-negative patients (33.3%) have died, whereas one of 8 CXCL12-positive patients (12.5%) and 4 of 6 CXCL12-negative patients (66.7%) remain alive. LIMITATIONS: The number of patients was limited. CONCLUSIONS: We speculate that the presence of CXCL12-positive cells in the skin may be associated with leukemic change and a poor prognosis.


Assuntos
Quimiocina CXCL12/análise , Células Dendríticas/patologia , Linfoma Cutâneo de Células T/patologia , Neoplasias Cutâneas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Pré-Escolar , Células Dendríticas/imunologia , Feminino , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/patologia , Humanos , Japão/epidemiologia , Linfoma Cutâneo de Células T/mortalidade , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/mortalidade , Transtornos Mieloproliferativos/patologia , Prognóstico , Pele/patologia , Neoplasias Cutâneas/mortalidade
14.
Exp Dermatol ; 20(12): 1022-4, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22017210

RESUMO

Th17 cells play crucial roles in the pathogenesis of autoimmune diseases. We previously reported that Th17 cells are recruited to the lesional skin in pemphigus vulgaris (PV) and pemphigus foliaceus (PF). The aim of this study was to evaluate lesional Th17 cells and Treg cells in bullous pemphigoid (BP). Correlations between these cells and disease severity of BP were also evaluated. Immunohistochemical studies showed that both IL-17+ and Foxp3+ cells were present in higher numbers in BP lesions, compared with control skin. IL-17/CD4 ratio in BP was significantly higher than that in PF. Foxp3/CD4 ratio in BP was significantly less than that in either PV or PF. There were no obvious correlations between these cells and disease severity of BP. This study suggests that, compared with pemphigus, BP shows more Th17 cell-related inflammation and less Treg-related regulation.


Assuntos
Vesícula/imunologia , Penfigoide Bolhoso/imunologia , Penfigoide Bolhoso/patologia , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Vesícula/patologia , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Interleucina-17/sangue , Interleucina-17/metabolismo , Masculino , Pessoa de Meia-Idade , Penfigoide Bolhoso/sangue , Pênfigo/imunologia , Pênfigo/patologia , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/patologia , Células Th17/metabolismo , Células Th17/patologia
15.
Biochem Biophys Res Commun ; 412(4): 626-32, 2011 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-21864505

RESUMO

CADM2, a candidate gene for psoriasis, was identified by a genome-wide association study using microsatellites in the Japanese population (561 cases and 561 controls). Moreover, haplotype analysis included an additional 68 SNPs and indicated that a 110-kb haplotype block was detected for the protective risk haplotype of psoriasis. We also identified an initial exon of novel splicing variants in this haplotype block. A functional analysis by qRT-PCR using RNAs from the blood of 56 cases and 64 controls significantly demonstrated an inverse correlation between expression frequencies in a novel splicing variant and the number of alleles associated with psoriasis. To confirm these results, we must perform replication studies using other ethnic groups and more functional analysis particularly for skin tissues.


Assuntos
Processamento Alternativo , Moléculas de Adesão Celular/genética , Predisposição Genética para Doença , Psoríase/genética , Alelos , Sequência de Aminoácidos , Cromossomos Humanos Par 3/genética , Estudo de Associação Genômica Ampla , Humanos , Dados de Sequência Molecular
17.
Artigo em Inglês | MEDLINE | ID: mdl-20886023

RESUMO

Effects of olopatadine hydrochloride, a histamine H(1) receptor antagonist, on histamine-induced skin responses were evaluated in 10 healthy subjects in comparison with placebo, fexofenadine hydrochloride, and bepotastine besilate. Olopatadine significantly suppressed histamine-induced wheal, flare, and itch, starting 30 minutes after oral administration. Olopatadine was more effective than fexofenadine and bepotastine. None of the drugs studied impaired performance of word processing tasks. These results suggest that olopatadine can suppress skin symptoms caused by histamine soon after administration.

18.
J Dermatol ; 37(3): 220-30, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20507385

RESUMO

Type VII collagen is an adhesion molecule of the extracellular matrix in epithelial basement membranes, and the main constituent of anchoring fibrils at the dermal-epidermal junction (DEJ). Autoimmunity against this protein is causing the rare organ-specific epidermolysis bullosa acquisita (EBA). EBA is a rare acquired, heterogeneous, chronic blistering disease of skin disease of skin and mucous membranes characterized by subepidermal blisters and tissue-bound as well as circulating autoantibodies to the DEJ. EBA has several distinct clinical presentations with other subepidermal bullous diseases, such as mainly dystrophic epidermolysis bullosa or bullous pemphigoid. The circulating immunoglobulin G autoantibodies for EBA react with a 290-kDa dermal protein, type VII collagen, as detected by immunoblot analysis using dermal extracts. The pathogenicity of these autoantibodies has been demonstrated by experimental animal models, in which anti-type VII collagen antibodies injected into a mouse produced an EBA-like blistering disease in the animal. EBA cases often require high doses of systemic corticosteroids and a variety of immunosuppressants. Although treatment for EBA is frequently difficult and unsatisfactory, some therapeutic success has been reported with colchicine, dapsone, infliximab and i.v. immunoglobulin. In this review, we will focus on recent progress in our understanding of the clinical manifestations, the etiopathogenesis as well as the management of EBA.


Assuntos
Autoanticorpos/imunologia , Doenças Autoimunes , Vesícula , Epidermólise Bolhosa Adquirida , Corticosteroides/uso terapêutico , Adulto , Animais , Anticorpos Monoclonais/uso terapêutico , Autoantígenos/imunologia , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Membrana Basal/imunologia , Membrana Basal/patologia , Vesícula/tratamento farmacológico , Vesícula/imunologia , Vesícula/patologia , Colchicina/uso terapêutico , Colágeno Tipo VII/imunologia , Dapsona/uso terapêutico , Epidermólise Bolhosa Adquirida/tratamento farmacológico , Epidermólise Bolhosa Adquirida/imunologia , Epidermólise Bolhosa Adquirida/patologia , Matriz Extracelular/imunologia , Feminino , Humanos , Imunização Passiva , Imunoglobulina G/imunologia , Imunossupressores/uso terapêutico , Infliximab , Masculino , Camundongos , Pele/imunologia , Pele/patologia
19.
J Dermatol ; 37(3): 231-8, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20507386

RESUMO

Anti-laminin gamma1 pemphigoid is an autoimmune subepidermal bullous disease first described in 1996, and has been distinct from previously known subepidermal blistering diseases, such as bullous pemphigoid and epidermolysis bullosa acquisita. Circulating autoantibodies of the patients do not react to any known autoantigen of the skin, but react to a 200-kDa molecule (p200) from dermal extracts. The identity of p200 was unmasked as laminin gamma1, an extracellular matrix glycoprotein composing several forms of laminin heterotrimers. We renamed this disease from the previously used anti-p200 pemphigoid to anti-laminin gamma1 pemphigoid, a new entity of an autoimmune bullous disease. In this decade, we have experienced over 70 cases of this disease. Although the number of the cases of anti-laminin gamma1 pemphigoid is half as many as the number of definitely diagnosed cases of epidermolysis bullosa acquisita in the same duration, a considerable number of the cases could be clinically misdiagnosed as epidermolysis bullosa acquisita. Unveiling the pathogenicity and development of a useful diagnostic method is necessary for appropriate management of this new disease.


Assuntos
Laminina/imunologia , Penfigoide Bolhoso/imunologia , Idoso , Autoanticorpos/sangue , Autoanticorpos/imunologia , Autoantígenos/imunologia , Autoantígenos/isolamento & purificação , Membrana Basal/imunologia , Vesícula/imunologia , Vesícula/patologia , Humanos , Pessoa de Meia-Idade , Infiltração de Neutrófilos , Penfigoide Bolhoso/patologia
20.
Eur J Dermatol ; 20(4): 472-5, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20406724

RESUMO

Mycophenolate mofetil has been used as an immunosuppressive agent to prevent acute rejection in kidney transplantation since the early 1990s. There are several reports that mycophenolate mofetil is effective in autoimmune bullous diseases including pemphigus vulgaris in combination with high doses of systemic corticosteroids or as a monotherapy. In Japan, however, there are few reports of pemphigus vulgaris treated with mycophenolate mofetil. The present study showed that mycophenolate mofetil treatment combined with systemic corticosteroid was successful in four Japanese patients with pemphigus vulgaris who were refractory to therapies including systemic corticosteroids, plasmapheresis, and oral immunosuppressives. For Japanese and European patients, mycophenolate mofetil may be an excellent therapy in a combination with systemic corticosteroid for refractory patients with pemphigus vulgaris.


Assuntos
Imunossupressores/uso terapêutico , Ácido Micofenólico/análogos & derivados , Pênfigo/tratamento farmacológico , Corticosteroides/uso terapêutico , Adulto , Quimioterapia Combinada , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...