RESUMO
RATIONALE: Pyrotinib is a novel dual pan-ErbB receptor tyrosine kinase inhibitor, approved for the treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). However, there was still limited information regarding specific effect of pyrotinib on HER2-positive MBC patients with phosphoinositol-3 kinase mutation. PATIENT CONCERNS: A 63-year-old woman accidentally discovered a left breast lesion. The breast cancer was diagnosed by biopsy of breast lesion and postoperative pathological examination in March, 2017. The patient was presented with HER2-positive (3+), invasive carcinoma of the left breast with lymph nodes and lung nodules metastasis, and the clinical stage was T4N2M1. However, the lesion continued to aggressive disease progression with the treatment of trastuzumab plus multiple chemotherapy regimens and traditional Chinese medicine. DIAGNOSES: The woman was diagnosed with invasive carcinoma of the left breast and lymph nodes and lung nodules metastasis. INTERVENTIONS: The patient received 6 cycles of pyrotinib in combination with capecitabine regularly. OUTCOMES: Progression free survival was more than 6 months, and the patient's efficacy evaluation was partial remission. LESSONS: Our clinical observations demonstrated that pyrotinib may be an effective treatment for patients with HER2-positive MBC.
Assuntos
Acrilamidas/uso terapêutico , Aminoquinolinas/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Receptor ErbB-2/antagonistas & inibidores , Acrilamidas/administração & dosagem , Aminoquinolinas/administração & dosagem , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Capecitabina/administração & dosagem , Capecitabina/uso terapêutico , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
A rapid increase in Candida albicans infection and drug resistance has caused an emergent need for new clinical strategies against this fungal pathogen. In this study, we evaluated the inhibitory activity of a series of 2-alkylaminoquinoline derivatives against C. albicans isolates. A total of 28 compounds were assessed for their efficacy in inhibiting the yeast-to-hypha transition, which is considered one of the key virulence factors in C. albicans Several compounds showed strong activity to decrease the morphological transition and virulence of C. albicans cells. The two leading compounds, compound 1 (2-[piperidin-1-yl]quinolone) and compound 12 (6-methyl-2-[piperidin-1-yl]quinoline), remarkably attenuated C. albicans hyphal formation and cytotoxicity in a dose-dependent manner, but they showed no toxicity to either C. albicans cells or human cells. Intriguingly, compound 12 showed an excellent ability to inhibit C. albicans infection in the mouse oral mucosal infection model. This leading compound also interfered with the expression levels of hypha-specific genes in the cyclic AMP-protein kinase A and mitogen-activated protein kinase signaling pathways. Our findings suggest that 2-alkylaminoquinoline derivatives could potentially be developed as novel therapeutic agents against C. albicans infection due to their interference with the yeast-to-hypha transition.
Assuntos
Aminoquinolinas/farmacologia , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candida albicans/patogenicidade , Células A549 , Aminoquinolinas/administração & dosagem , Aminoquinolinas/química , Animais , Antifúngicos/administração & dosagem , Antifúngicos/química , Candida albicans/fisiologia , Candidíase Bucal/tratamento farmacológico , Candidíase Bucal/microbiologia , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Humanos , Hifas/efeitos dos fármacos , Masculino , Camundongos Endogâmicos BALB C , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Virulência/efeitos dos fármacosRESUMO
Actinic keratosis (AK) is a clinical condition characterized by keratinocytic dysplastic lesions of the epidermis, affecting individuals chronically exposed to sunlight. Topical therapies allow the treatment of a whole area of affected skin and currently include diclofenac sodium gel, 5-fluorouracil cream, 5-fluorouracil and acetylsalicylic acid solution, imiquimod cream, and ingenol mebutate gel. Due to the comparable efficacy of 3% diclofenac, ingenol mebutate, and 3.75% imiquimod in treating AK multiple lesions, a pharmacoeconomic evaluation of cost-effectiveness of the three treatments was needed. A cost-efficacy analysis comparing 3% diclofenac sodium with ingenol mebutate and 3.75% imiquimod was performed. In this analysis, efficacy data were combined with quality-of-life measurement derived from previous studies as well as the costs associated with the management of these lesions in Italy. Patients' demographics and clinical characteristics were assumed to reflect those from the clinical studies considered.
Assuntos
Aminoquinolinas/economia , Análise Custo-Benefício/métodos , Diclofenaco/economia , Diterpenos/economia , Ceratose Actínica/tratamento farmacológico , Ceratose Actínica/economia , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/economia , Aminoquinolinas/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/economia , Ensaios Clínicos Fase III como Assunto/economia , Árvores de Decisões , Diclofenaco/administração & dosagem , Diterpenos/administração & dosagem , Composição de Medicamentos , Humanos , Imiquimode , Estudos Multicêntricos como Assunto/economia , Ensaios Clínicos Controlados Aleatórios como Assunto/economia , Resultado do TratamentoRESUMO
BACKGROUND: Chronic HSV infection is a cause of chronic perineal ulcerations. We report a case of a chronic and refractory HSV infection revealing chronic lymphoid leukaemia. PATIENTS AND METHODS: An 85-year-old woman with an 8-month history of chronic perineal ulcerations was referred to our dermatology department. She had no previous medical history of herpes infection. Skin biopsies ruled out carcinoma but were consistent with HSV infection. A local swab was positive for HSV2. Treatment with valaciclovir and intravenous acyclovir (ACV) at the recommended doses was ineffective. Laboratory tests revealed type-B chronic lymphoid leukaemia. Molecular biology studies confirmed the presence of ACV-resistant HSV via decreased thymidine kinase activity (stop codon: M183stop). Foscarnet was administered for a period of 3 weeks with almost complete healing of the ulcerations. Treatment was stopped prematurely due to acute renal insufficiency and the remaining lesions were treated using imiquimod cream. Valaciclovir was prescribed to prevent further episodes. The condition recurred a mere 11 months later. DISCUSSION: The prevalence of ACV-resistant HSV is 0.32 % in immunocompetent patients and 3.5 % in immunocompromised patients. Insufficient dosing regimens or prolonged treatment with TK inhibitors result in the local selection of pre-existing mutant HSV viruses. Foscarnet, a DNA polymerase inhibitor, is the treatment of choice in HSV-resistant infections. ACV-resistant HSV is less virulent and replicates less, with reactivations being mainly due to wild-type HSV latent in the neural ganglia. Valaciclovir can be used as a preventive treatment. To our knowledge, this is the first case of ACV-resistant HSV infection revealing chronic lymphoid leukaemia. CONCLUSION: Chronic perineal ulcerations can be the first manifestation of immunodeficiency seen for example with haematological diseases. In the event of clinical resistance of an HSV infection to recommended thymidine kinase inhibitor regimens, the use of foscarnet should be considered.
Assuntos
Aciclovir , Antivirais , Foscarnet/uso terapêutico , Herpes Simples/complicações , Hospedeiro Imunocomprometido , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Aciclovir/administração & dosagem , Adjuvantes Imunológicos/administração & dosagem , Administração Cutânea , Idoso de 80 Anos ou mais , Aminoquinolinas/administração & dosagem , Antivirais/administração & dosagem , Feminino , Herpes Simples/tratamento farmacológico , Humanos , Imiquimode , Períneo/patologia , Períneo/virologiaRESUMO
BACKGROUND: The most widely used topical agents for the field-based treatment of multiple actinic keratoses (AKs) are 5-fluorouracil and imiquimod, but their comparative effectiveness has not been assessed in a real-world setting. OBJECTIVE: We compared the effectiveness of 5-fluorouracil and imiquimod in reducing risk for subsequent AKs in a large, integrated health care delivery system in northern California. METHODS: In this cohort study, we identified adult health plan members who had an AK diagnosed in 2007 and who subsequently filled a prescription for 5-fluorouracil or imiquimod (N = 5700). We followed subjects for subsequent AKs identified by the International Classification of Diseases codes and estimated the 2-year (short-term) and 5-year (long-term) differences in cumulative risk while controlling for potential confounding by pretreatment variables. RESULTS: 5-Fluorouracil reduced the short-term incidence of subsequent AKs (cumulative risk difference -4.54% [95% confidence interval, -7.91% to -1.17%]), but there was no statistically significant evidence of a long-term decreased risk (cumulative risk difference -1.43% [95% confidence interval, -3.43% to 0.05%]) compared with that with imiquimod. LIMITATIONS: This is a retrospective study with limited ascertainment of all relevant potential confounding variables. CONCLUSION: We found that 5-fluorouracil appeared to be significantly more effective than imiquimod in the short-term, but not long-term, prevention of subsequent AKs.
Assuntos
Aminoquinolinas/administração & dosagem , Fluoruracila/administração & dosagem , Ceratose Actínica/tratamento farmacológico , Administração Tópica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Imiquimode , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Malaria remains a major disease in the developing world and globally is the most important parasitic disease causing significant morbidity and mortality. Because of widespread resistance to conventional antimalarials, including chloroquine (CQ), new drugs are urgently needed. Here we report on the antimalarial efficacy, both in vitro and in vivo, of a series of aminoquinoline derivatives with adamantane or benzothiophene as a carrier. In vitro efficacy was evaluated by a lactate dehydrogenase (LDH) assay in cultures of a CQ-sensitive (3D7) and CQ-resistant (Dd2) strain of Plasmodium falciparum. Of a series of 26 screened compounds, 12 that exerted a growth inhibition rate of ≥50% were further examined in vitro to determine the 50% inhibitory concentration (IC50) values. Nine compounds shown in preliminary experiments to be non-toxic in vivo were evaluated in C57BL/6 mice infected with Plasmodium berghei ANKA strain using a modified Thompson test. All nine compounds examined in vivo prolonged the survival of treated versus untreated mice, four of which afforded ≥60% survival. Most notably, two of these compounds, both with the adamantane carrier, afforded complete cure (100% survival and parasite clearance). Interestingly, one of these compounds had no in vitro effect against the CQ-resistant P. falciparum strain. Better in vivo compared with in vitro results suggest a role for compound metabolites rather than the compounds themselves. The results presented here point to adamantane as a carrier that enhances the antimalarial potential of aminoquinolines.
Assuntos
Aminoquinolinas/administração & dosagem , Aminoquinolinas/farmacologia , Antimaláricos/administração & dosagem , Antimaláricos/farmacologia , Avaliação Pré-Clínica de Medicamentos/métodos , Plasmodium berghei/efeitos dos fármacos , Plasmodium falciparum/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Concentração Inibidora 50 , L-Lactato Desidrogenase/análise , Malária/tratamento farmacológico , Camundongos Endogâmicos C57BL , Testes de Sensibilidade Parasitária , Análise de Sobrevida , Resultado do TratamentoRESUMO
This review about the proactive sequential therapy (PST) of external genital and perianal warts (EGW) is based on the most current available clinical literature and on the broad clinical experience of a group of international experts, physicians who are well versed in the treatment of human papillomavirus-associated diseases. It provides a practical guide for the treatment of EGW, including epidemiology, etiology, clinical appearance, and diagnostic procedures for these viral infections. Furthermore, the treatment goals and current treatment options, elucidating provider- and patient-applied therapies, and the parameters driving treatment decisions are summarized. Specifically, the mode of action of the topical treatments sinecatechins and imiquimod, as well as the PST for EGW to achieve rapid and sustained clearance is discussed. The group of experts has developed a treatment algorithm giving healthcare providers a practical tool for the treatment of EGW which is very valuable in the presence of many different treatment options.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Aminoquinolinas/administração & dosagem , Doenças do Ânus/tratamento farmacológico , Catequina/administração & dosagem , Condiloma Acuminado/tratamento farmacológico , Doenças dos Genitais Femininos/tratamento farmacológico , Doenças dos Genitais Masculinos/tratamento farmacológico , Adjuvantes Imunológicos/uso terapêutico , Administração Tópica , Aminoquinolinas/uso terapêutico , Antineoplásicos , Catequina/uso terapêutico , Condiloma Acuminado/virologia , Feminino , Humanos , Imiquimode , Masculino , Infecções por Papillomavirus/tratamento farmacológico , Infecções por Papillomavirus/virologia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêutico , Chá , Resultado do TratamentoRESUMO
BACKGROUND/PURPOSE: Psoriasis continues to be a debilitating skin disease affecting 1-3% of the United States population. Although the effectiveness of several current biologic therapies have described this pathology as a IL-23, TNF-a and Th17-mediated disease, less invasive approaches are still in use and in need of refinement. One of these is the usage of narrow band-UVB (NB-UVB) therapy to deplete specifically intra-epidermal CD3+, CD4+ and CD8+ cells to clear psoriatic plaques. AIMS/OBJECTIVES: In order to improve NB-UVB therapy, we sought to determine whether skin pre-treatment with the TLR7 agonist imiquimod (IMQ) would help increase the efficiency of the former at resolving psoriatic plaques. MATERIALS AND METHODS: Eucerin® Original Moisturizing Lotion (topical vehicle) or Aldara® (imiquimod 5% topical cream) were applied for 5 days once daily to a maximum contiguous area of 25 cm2 (5 cm × 5 cm area). Patients were provided with sachets containing 12.5 mg of imiquimod each and were instructed to apply imiquimod (I) to two psoriasis plaques (5 sachets of imiquimod allotted to each plaque). A PHAROS excimer Laser EX-308 (Ra Medical Systems, Inc. Carlsbad, CA, USA) with an output of monochromatic 308-nm light and pulse width of 20-50 ns was used for all patients. Punch biopsies of psoriatic lesions (6 mm) were taken at 4 and 48 h after final application of topical treatment with or without excimer laser treatment. Real-time quantitative RT-PCR was performed according to manufacturer's instructions and Inmunohistochemistry was used as described before. RESULTS: Our results suggests that although IMQ seemed to activate the type I interferon pathway as previously described, its concomitant usage with NB-UVB for clearing psoriatic skin was ineffective. Although upregulation of genes MxA, GRAMD1A and DMXL2 suggested that IMQ treatment did induce skin changes in psoriasis patients, more optimal dosing of IMQ and NB-UVB might be necessary to achieve desired treatment responses. CONCLUSION: The observation that psoriasis involvement was not aggravated by usage of topical IMQ was encouraging. Additional observational studies might be necessary to further tailor the combination of IMQ with NB-UVB therapy to reliably improve the psoriatic pathology.
Assuntos
Aminoquinolinas/administração & dosagem , Terapia a Laser/métodos , Psoríase/metabolismo , Psoríase/patologia , Psoríase/terapia , Administração Tópica , Adulto , Idoso , Feminino , Humanos , Imiquimode , Masculino , Pessoa de Meia-IdadeRESUMO
Isogarcinol (YDIS), a natural compound extracted from Garcinia mangostana L., has a significant immunosuppressive effect on systemic lupus erythematosus and rheumatoid arthritis. This paper reports that it reduced imiquimod-induced psoriasis-like skin lesions in mice. It strongly attenuated the aberrant proliferation and differentiation of keratinocytes. Moreover, the expression of genes involving the interleukin-23 (IL-23)/T-helper 17 (Th17) axis was significantly inhibited in the dorsal skin of the YDIS-treated mice, as was that of the other pro-inflammatory factors TNF-α, IL-2, and even interferon (IFN)-γ. Furthermore, YDIS prevented the abnormal distribution of T cell types and suppressed the differentiation of CD4+ T cells into Th17 cells in the spleens of mice exposed to imiquimod. Interestingly, it elevated numbers of regulatory T cells (Tregs) in the spleen and boosted IL-10 expression in the skin. In agreement with the above, YDIS increased serum IL-10 and reduced serum IL-17. It also caused less damage to the liver and, especially, kidneys of mice than cyclosporine A (CsA). In vitro, YDIS caused more death of HaCaT keratinocytes than CsA. It also strongly inhibited inflammatory factor expression in lipopolysaccharide (LPS)-stimulated HaCaT cells. These findings suggest that YDIS is a promising immunosuppressive agent for treating psoriasis.
Assuntos
Aminoquinolinas/administração & dosagem , Garcinia mangostana/química , Extratos Vegetais/administração & dosagem , Psoríase/tratamento farmacológico , Pele/imunologia , Animais , Modelos Animais de Doenças , Feminino , Humanos , Imiquimode , Interleucina-2/genética , Interleucina-2/imunologia , Interleucina-23/genética , Interleucina-23/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Psoríase/genética , Psoríase/imunologia , Pele/efeitos dos fármacos , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Células Th17/efeitos dos fármacos , Células Th17/imunologia , Fator de Necrose Tumoral alfaRESUMO
BACKGROUND: Conventional treatments for warts like cryotherapy are limited by the pain during procedures, especially in pediatric patients. Imiquimod is a topical immune response modifier, but the thick stratum corneum of common warts prevents drug permeation through skin. OBJECTIVE: To evaluate the efficacy and safety of fractional laser/topical 5% imiquimod cream for the treatment of warts in children. METHODS: Eleven pediatric patients with multiple recalcitrant common warts were included. Lesions were treated using an ablative fractional 2,940-nm Er:YAG laser at 1- or 2-week interval. After each laser treatment session, imiquimod 5% cream was self-applied once daily 5 days a week. Response and adverse effects were assessed 2 weekly until complete clearance or up to maximum of 48 weeks. Pain during fractional laser was assessed using a visual analogue scale (0-10). RESULTS: Eight of the 11 (72.7%) children experienced complete clearance. Mean duration was 29.7 (16-48) weeks, and the mean number of fractional laser was 17.5 (8-37). No significant adverse effect was observed. Pain visual analogue scale during fractional laser was 2.4 (1-4) compared to 6.2 (5-8) during cryotherapy. CONCLUSION: This pilot study indicates that fractional laser-assisted topical imiquimod may provide benefit for recalcitrant warts in children.
Assuntos
Aminoquinolinas/uso terapêutico , Indutores de Interferon/uso terapêutico , Lasers de Estado Sólido/uso terapêutico , Verrugas/tratamento farmacológico , Administração Tópica , Adolescente , Aminoquinolinas/administração & dosagem , Anestesia Local/métodos , Criança , Feminino , Humanos , Imiquimode , Indutores de Interferon/administração & dosagem , Masculino , Medição da Dor , Projetos Piloto , Resultado do TratamentoRESUMO
A wide range of treatments is now available for nonmelanoma skin cancer (NMSC), including 5-fluorouracil, ingenol mebutate, imiquimod, diclofenac, photodynamic therapy, methotrexate, cetuximab, vismodegib, and radiotherapy. All are associated with high clinical and histologic response rates. However, some tumors do not respond due to resistance, which may be primary or acquired. Study of the resistance processes is a broad area of research that aims to increase our understanding of the nature of each tumor and the biologic features that make it resistant, as well as to facilitate the design of new therapies directed against these tumors. In this article we review resistance to the authorized topical treatments for NMSC.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Neoplasias Cutâneas/tratamento farmacológico , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/uso terapêutico , Administração Cutânea , Aminoquinolinas/administração & dosagem , Aminoquinolinas/farmacologia , Aminoquinolinas/uso terapêutico , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Células Apresentadoras de Antígenos/efeitos dos fármacos , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/farmacologia , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Carcinoma/imunologia , Carcinoma/metabolismo , Ensaios Clínicos como Assunto , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/farmacologia , Fármacos Dermatológicos/uso terapêutico , Diclofenaco/administração & dosagem , Diclofenaco/farmacologia , Diclofenaco/uso terapêutico , Diterpenos/administração & dosagem , Diterpenos/farmacologia , Diterpenos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Resistencia a Medicamentos Antineoplásicos/fisiologia , Fluoruracila/administração & dosagem , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Humanos , Imiquimode , Metanálise como Assunto , Proteínas de Neoplasias/fisiologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/metabolismoRESUMO
Cutaneous granulomas caused by Candida guilliermondii are difficult to cure. In situ photoimmunotherapy (ISPI) is a novel method composed of local photothermal therapy and immunoadjuvant. In this study, ISPI was used the first time clinically for cutaneous granuloma caused by itraconazole-resistant C.guilliermondii. A 10-week cycle of ISPI was composed of (1) 5% imiquimod applied topically every other day and (2) irradiation of lesions with an 808-nm diode laser at Days 14, 28, 42, and 56. Here we report our first case. A patient was treated with ISPI for four cycles. After the treatment, the lesions were eliminated without recurrence during a 12-month follow-up. Our results demonstrate that ISPI can be used as an effective treatment modality for cutaneous fungal granuloma.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Aminoquinolinas/administração & dosagem , Antifúngicos/uso terapêutico , Candidíase Cutânea/terapia , Farmacorresistência Fúngica , Granuloma/terapia , Imunoterapia/métodos , Itraconazol/uso terapêutico , Lasers Semicondutores/uso terapêutico , Fototerapia/métodos , Idoso de 80 Anos ou mais , Biópsia , Candidíase Cutânea/diagnóstico , Candidíase Cutânea/imunologia , Candidíase Cutânea/microbiologia , Granuloma/diagnóstico , Granuloma/imunologia , Granuloma/microbiologia , Humanos , Imiquimode , Masculino , Resultado do TratamentoRESUMO
Since their earliest description, keloids and hypertrophic scars have beleaguered patients and clinicians alike. These scars can be aesthetically disfiguring, functionally debilitating, emotionally distressing, and psychologically damaging, culminating in a significant burden for patients. Our current understanding of keloid pathophysiology has grown and continues to advance while molecular biology, genetics, and technology provide ever-deepening insight into the nature of wound healing and the pathologic perturbations thereof. Greater understanding will lead to the development and application of refined therapeutic modalities. This article provides an overview of our current understanding of keloids, highlighting clinical characteristics and diagnostic criteria while providing a comprehensive summary of the many therapeutic modalities available. The proposed mechanism, application, adverse events, and reported efficacy of each modality is evaluated, and current recommendations are summarized.
Assuntos
Cicatriz Hipertrófica , Fibroblastos/fisiologia , Queloide , Cicatrização/fisiologia , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/efeitos adversos , Adjuvantes Imunológicos/uso terapêutico , Aminoquinolinas/administração & dosagem , Aminoquinolinas/efeitos adversos , Aminoquinolinas/uso terapêutico , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/uso terapêutico , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/efeitos adversos , Antibióticos Antineoplásicos/uso terapêutico , Antimetabólitos/administração & dosagem , Antimetabólitos/efeitos adversos , Antimetabólitos/uso terapêutico , Bleomicina/administração & dosagem , Bleomicina/efeitos adversos , Bleomicina/uso terapêutico , Proliferação de Células , Cicatriz Hipertrófica/etiologia , Cicatriz Hipertrófica/patologia , Cicatriz Hipertrófica/terapia , Ensaios Clínicos como Assunto , Colágeno/metabolismo , Terapia Combinada/métodos , Crioterapia/métodos , Matriz Extracelular/fisiologia , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Humanos , Imiquimode , Inflamação/metabolismo , Queloide/etiologia , Queloide/patologia , Queloide/terapia , Terapia a Laser/métodosRESUMO
BACKGROUND: Recently, the Aldara-induced psoriasis-like skin inflammation model in mice has attracted increased attention, due to its dependence on the same immunological pathways and cell types as in human psoriasis. OBJECTIVES: To study the impact of constitutive deficiency of tumour necrosis factor (TNF)-α and its upstream regulator mitogen-activated protein kinase-activated protein kinase 2 (MAPKAPK-2, herein MK2) in the Aldara-induced psoriasis-like skin inflammation model. METHODS: TNF-α knockout (KO), MK2 KO and wild-type (WT) mice divided into separate groups received either 45-mg Aldara cream or control cream for 5 consecutive days. The skin inflammation was evaluated clinically, histologically, and by quantitative reverse transcription-polymerase chain reaction. RESULTS: We found that TNF-α KO mice developed significantly less skin inflammation compared with WT mice, as evaluated clinically and histologically. At the molecular level, we demonstrated that the Aldara-induced mRNA expression of the psoriasis-related inflammatory markers interleukin (IL)-17C, IL-23p19, IL-12p40, IL-17A, IL-22 and S100A8 was significantly decreased in TNF-α KO mice compared with WT mice. No significant difference in the mRNA expression of these inflammatory markers between MK2 KO mice and WT mice was found, although Aldara-treated MK2 KO mice showed a tendency towards a lower mRNA expression of IL-17A and IL-22 compared with WT mice. CONCLUSIONS: We were able to demonstrate significantly lower levels of inflammation in TNF-α KO mice compared with WT mice, supporting the use of this model in future studies characterizing the role of TNF-α in psoriasis.
Assuntos
Adjuvantes Imunológicos/toxicidade , Aminoquinolinas/toxicidade , Psoríase/induzido quimicamente , Fator de Necrose Tumoral alfa/fisiologia , Adjuvantes Imunológicos/administração & dosagem , Administração Cutânea , Aminoquinolinas/administração & dosagem , Animais , Biomarcadores/metabolismo , Calgranulina A/metabolismo , Toxidermias/etiologia , Imiquimode , Interleucinas/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pomadas/administração & dosagem , Pomadas/toxicidade , Proteínas Serina-Treonina Quinases/metabolismo , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
It has been previously shown that the long-term inhibition of milking-induced prolactin (PRL) release by quinagolide (QN), a dopamine agonist, reduces milk yield in dairy cows. To further demonstrate that PRL is galactopoietic in cows, we performed a short-term experiment that used PRL injections to restore the release of PRL at milking in QN-treated cows. Nine Holstein cows were assigned to treatments during three 5-d periods in a 3×3 Latin square design: 1) QN: twice-daily i.m. injections of 1mg of QN; 2) QN-PRL: twice-daily i.m. injections of 1mg of QN and twice-daily (at milking time) i.v. injections of PRL (2µg/kg body weight); and 3) control: twice-daily injections of the vehicles. Mammary epithelial cells (MEC) were purified from milk so that their viability could be assessed, and mammary biopsies were harvested for immunohistological analyses of cell proliferation using PCNA and STAT5 staining. In both milk-purified MEC and mammary tissue, the mRNA levels of milk proteins and BAX were determined using real-time reverse-transcription PCR. Daily QN injections reduced milking-induced PRL release. The area under the PRL curve was similar in the control and PRL injection treatments, but the shape was different. The QN treatment decreased milk, lactose, protein, and casein production. Injections of PRL did not restore milk yield but tended to increase milk protein yield. In mammary tissue, the percentage of STAT5-positive cells was reduced during QN but not during QN-PRL in comparison with the control treatment. The percentage of PCNA-positive cells was greater during QN-PRL injections than during the control or QN treatment and tended to be lower during QN than during the control treatment. In milk-purified MEC, κ-casein and α-lactalbumin mRNA levels were lower during QN than during the control treatment, but during QN-PRL, they were not different from the control treatment. In mammary tissue, the BAX mRNA level was lower during QN-PRL than during QN. The number of MEC exfoliated into milk was increased by QN injections but tended to be decreased by PRL injections. Injections of PRL also increased the viability of MEC harvested from milk. Although PRL injections at milking could not reverse the effect of QN treatment on milk production, their effects on cell survival and exfoliation and on gene expression suggest that the effect of QN treatment on the mammary gland is due to QN's inhibition of PRL secretion.
Assuntos
Aminoquinolinas/administração & dosagem , Bovinos/metabolismo , Lactação/efeitos dos fármacos , Glândulas Mamárias Animais/efeitos dos fármacos , Prolactina/administração & dosagem , Prolactina/antagonistas & inibidores , Animais , Caseínas/metabolismo , Proliferação de Células/efeitos dos fármacos , Suplementos Nutricionais , Agonistas de Dopamina/farmacologia , Células Epiteliais/química , Células Epiteliais/citologia , Feminino , Lactalbumina/metabolismo , Lactose/análise , Glândulas Mamárias Animais/química , Glândulas Mamárias Animais/citologia , Leite/citologia , Proteínas do Leite/genética , Antígeno Nuclear de Célula em Proliferação/análise , RNA Mensageiro/análise , Fator de Transcrição STAT5/análiseRESUMO
BACKGROUND: Patients with cutaneous melanoma metastases have experienced excellent responses to intralesional interleukin (IL)-2. This has led to its recent inclusion into the US National Comprehensive Cancer Network guidelines for management of cutaneous melanoma metastases. Despite this, intralesional IL-2 has not been highlighted in the US literature nor have US physicians adopted it. OBJECTIVE: We sought to evaluate the effectiveness of intralesional IL-2 combined with topical imiquimod and retinoid for treatment of cutaneous metastatic melanoma. METHODS: A retrospective case series of 11 patients with cutaneous metastatic melanoma were treated with intralesional IL-2 combined with topical imiquimod and retinoid. RESULTS: A 100% complete local response rate with long-term follow-up (average of 24 months) was seen in all 11 patients treated with this proposed regimen. Biopsy specimens of treated sites confirmed absence of malignant cells. The most common treatment-related adverse event was rigors. LIMITATIONS: Small number of patients, retrospective review of charts, and lack of a comparison group were limitations. CONCLUSION: Intralesional IL-2 administered concomitantly with topical imiquimod and a retinoid cream is a promising therapeutic option for managing cutaneous melanoma metastases. The regimen was well tolerated and should be considered as a reasonable alternative to surgical excision.
Assuntos
Aminoquinolinas/administração & dosagem , Interleucina-2/administração & dosagem , Melanoma/tratamento farmacológico , Retinoides/administração & dosagem , Neoplasias Cutâneas/tratamento farmacológico , Administração Tópica , Estudos de Coortes , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Imiquimode , Injeções Intralesionais , Masculino , Melanoma/secundário , Invasividade Neoplásica/patologia , Metástase Neoplásica , Estadiamento de Neoplasias , Estudos Retrospectivos , Medição de Risco , Neoplasias Cutâneas/patologia , Resultado do Tratamento , Melanoma Maligno CutâneoAssuntos
Aminoquinolinas/administração & dosagem , Hipertermia Induzida , Indutores de Interferon/administração & dosagem , Dermatoses do Couro Cabeludo/terapia , Verrugas/terapia , Administração Cutânea , Adulto , Terapia Combinada/métodos , Humanos , Imiquimode , Retratamento , Dermatoses do Couro Cabeludo/virologiaRESUMO
Focal epithelial hyperplasia (FEH) or Heck's disease is a rare, benign and asymptomatic mucosal proliferation associated with human papillomavirus (HPV) infection, mainly with genotypes 13 and 32. We report a florid case of FEH in an 11-year-old Haitian girl with systemic lupus erythematosus receiving immunosuppressive therapy. Cryotherapy was previously performed on numerous occasions with no results. We decided to prescribe a non-invasive and more comfortable treatment. A combination of topical retinoid and imiquimod cream was well tolerated and led to an important improvement. The evidence of infection by HPV-16 detected by polymerase chain reaction (PCR) technique, prompted us to prescribe the quadrivalent HPV vaccine (types 6, 11,16 and 18). Subsequent PCR sequencing with generic primers GP5-GP6 and further BLAST comparative analysis confirmed that genomic viral sequence in our case truly corresponded with HPV-32. This molecular misdiagnosis can be explained by the similarity between genomic sequences of both HPV-16 and -32 genotypes. At the 1-year follow up, we observed total clinical improvement and no recurrences of the disease. Complete healing in this case may correspond to a potential action of topical retinoid, imiquimod and the cross-protection mechanism of the quadrivalent HPV vaccine.
Assuntos
Hiperplasia Epitelial Focal/diagnóstico , Papillomavirus Humano 16 , Papillomaviridae , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/terapia , Adjuvantes Imunológicos/administração & dosagem , Aminoquinolinas/administração & dosagem , Criança , Terapia Combinada , Erros de Diagnóstico , Feminino , Hiperplasia Epitelial Focal/terapia , Hiperplasia Epitelial Focal/virologia , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/administração & dosagem , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/isolamento & purificação , Humanos , Imiquimode , Papillomaviridae/classificação , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Retinoides/administração & dosagemRESUMO
AIM: Zinc sulfate is beneficial in the treatment of epithelial warts. We conducted this study to compare the efficacy of combination therapy of oral zinc sulfate with conventional treatments in the treatment of vulvar warts. MATERIAL AND METHODS: This study was a randomized controlled trial. The sample size was 42 in each group. Women aged 20-50 years were placed by the block randomized method into six groups: the podophyllin-, imiquimod- and cryotherapy-treated groups, and another three groups receiving 8-week combination therapy of 400 mg oral zinc sulfate with one of the above-mentioned treatments. Data were analyzed using anova and Fischer's exact test with spss16. RESULTS: A total of 228 patients were recruited and completed the study in six treatment groups. No significant difference was observed in the response to treatment among these groups. Relapse after 6 months was significantly higher in the podophyllin-, imiquimod- and cryotherapy-treated patients compared to patients receiving these treatments in combination with oral zinc sulfate (P<0.05). CONCLUSIONS: Combined therapy of oral zinc sulfate with conventional treatments of vulvar warts appears to reduce the relapse rate.