Assuntos
Líquen Plano , Alopecia , Humanos , Líquen Plano/radioterapia , Projetos Piloto , Estudos Prospectivos , Couro CabeludoRESUMO
Cell therapy has the potential to drastically improve clinical outcomes for the 1.45 million patients suffering from a myocardial infarction (MI) each year in the U.S. However, the limitations associated with this treatment - including poor engraftment, significant cell death and poor differentiation potential - have prevented its widespread application clinically. To optimize functional improvements provided by transplanted cells, there is a need to develop methods that increase cellular retention and viability, while supporting differentiation and promoting paracrine signaling. Current in vivo models are expensive, difficult to access and manipulate and are time consuming. We have developed an in vitro model of MI which allows for a straightforward, consistent and relatively accurate prediction of cell fate following injection in vivo. The model demonstrated how the infarct environment impairs cellular engraftment and differentiation, but identified an implantation strategy which enhanced cell fate in vitro. Multivariate linear regression identified variables within the model that regulated vascular differentiation potential including oxygen tension, stiffness and cytokine presence, while cardiac differentiation was more accurately predicted by Isl-1 expression in the original cell isolate than any other variable present within the model system. The model highlighted how the cells' sensitivity to the infarct variables varied from line to line, which emphasizes the importance of the model system for the prediction of cell fate on a patient specific basis. Further development of this model system could help predict the clinical efficacy of cardiac progenitor cell therapy at the patient level as well as identify the optimal strategy for cell delivery.
Assuntos
Proteínas com Homeodomínio LIM/genética , Modelos Cardiovasculares , Infarto do Miocárdio/terapia , Miócitos Cardíacos/metabolismo , Transplante de Células-Tronco , Células-Tronco/citologia , Fatores de Transcrição/genética , Animais , Biomarcadores/metabolismo , Diferenciação Celular , Rastreamento de Células , Citocinas/metabolismo , Modelos Animais de Doenças , Matriz Extracelular/metabolismo , Expressão Gênica , Dureza , Proteínas com Homeodomínio LIM/metabolismo , Modelos Lineares , Masculino , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Miócitos Cardíacos/patologia , Oxigênio/metabolismo , Comunicação Parácrina , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/metabolismo , Ratos , Ratos Sprague-Dawley , Células-Tronco/metabolismo , Fatores de Transcrição/metabolismoAssuntos
Alopecia/tratamento farmacológico , Espironolactona/administração & dosagem , Adulto , Idoso , Alopecia/diagnóstico , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Espironolactona/efeitos adversos , Resultado do Tratamento , Adulto JovemAssuntos
Alérgenos/imunologia , Alopecia/diagnóstico , Cosméticos/efeitos adversos , Dermatite Alérgica de Contato/diagnóstico , Líquen Plano/diagnóstico , Monoterpenos Acíclicos/administração & dosagem , Monoterpenos Acíclicos/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Alérgenos/administração & dosagem , Alopecia/imunologia , Alopecia/patologia , Alopecia/prevenção & controle , Biópsia , Estudos de Coortes , Cosméticos/administração & dosagem , Cosméticos/química , Dermatite Alérgica de Contato/complicações , Dermatite Alérgica de Contato/imunologia , Dermatite Alérgica de Contato/prevenção & controle , Feminino , Fibrose , Ácido Gálico/administração & dosagem , Ácido Gálico/imunologia , Folículo Piloso/imunologia , Folículo Piloso/patologia , Humanos , Líquen Plano/imunologia , Líquen Plano/patologia , Líquen Plano/prevenção & controle , Masculino , Pessoa de Meia-Idade , Odorantes , Testes do Emplastro/estatística & dados numéricosRESUMO
Alopecia neoplastica (AN) is caused by neoplastic cells damaging hair follicles, resulting in patchy hair loss like cicatricial alopecia and alopecia areata. AN has predominantly described cutaneous metastasis to the scalp from primary visceral malignant tumors. Less frequently, AN results from a primary scalp neoplasm. Compared to "secondary AN," there is a paucity of literature on "primary AN." Herein, we present a comprehensive literature review of primary AN and introduce a unique case of amelanotic melanoma causing primary AN. Including our presented case, 11 cases of primary AN have been reported with causative scalp neoplasms including angiosarcoma, hemangioendothelioma, syringomatous carcinoma, ectopic extramammary Paget's disease, and primary desmoplastic melanoma. 27.3% (3 of 11) of cases were misdiagnosed and treated for a primary alopecia, and 36.4% (4 of 11) of lesions were present for multiple years or an unknown amount of time, likely due to difficulty in recognizing scalp lesion or misdiagnosis. All patients required surgical excision with 36.4% (4 of 11) requiring chemotherapy, radiation, or photodynamic therapy. Two patients with scalp angiosarcoma died from their aggressive disease. Due to the risks of malignant primary AN if allowed to progress, primary AN should be considered in patients presenting with scarring alopecia.
RESUMO
Androgenetic alopecia (AGA) and acne vulgaris are two conditions commonly seen by dermatologists. Androgens and the androgen receptors play an essential role in the manifestation of both conditions, and some systemic therapies function by interfering in this pathway. The use of topical antiandrogen therapies has gained traction in recent years due to their potential efficacy in treating AGA and acne vulgaris, as well as their reduced adverse effects compared with systemic drugs. This review discusses the role of androgens in skin physiology and pathology and assesses the potential efficacy and safety of three topical antiandrogen therapies in the treatment of AGA and acne vulgaris. A literature review utilizing the PubMed, US Clinical Trials, and SCOPUS databases was conducted to search for randomized clinical trials, systematic reviews, cohort studies, case reports, and other relevant published studies on the pathogenesis and treatment of each condition with topical finasteride, ketoconazole shampoo, and cortexolone 17α-propionate (C17P). The results demonstrated that topical formulations of finasteride, ketoconazole, and C17P are promising treatments for male pattern hair loss, especially topical finasteride in combination with topical minoxidil. Limited studies have shown C17P to have potential in treating acne vulgaris in both males and females. Minimal adverse effects have been reported in clinical trials for all topical therapies, although topical finasteride is still contraindicated in pregnancy. Recognizing the preliminary evidence, more peer-reviewed studies on topical antiandrogen treatments for AGA and acne vulgaris are necessary before definitive recommendations can be made regarding efficacy and safety. There is also a critical need to include more women in study populations for these treatments.
Assuntos
Acne Vulgar/tratamento farmacológico , Alopecia/tratamento farmacológico , Antagonistas de Androgênios/uso terapêutico , Administração Tópica , HumanosRESUMO
Alopecia areata (AA), an unpredictable, nonscarring hair loss, is commonly perceived as a cosmetic, rather than medical, concern. However, substantial evidence exists describing the negative impact on quality of life, as the disease affects patients personally, socially, financially, and physically. Over time, the cumulative disability may perpetuate poor confidence, social disconnection, negative coping strategies, and failure to achieve a full life potential. Here, we describe the cumulative life course impairment (CLCI) of AA by examining the complex interaction of (1) stigmatization, (2) physical and psychiatric comorbidities, and (3) coping strategies. The model aggregates existing cross-sectional data, which have previously captured disease burden only as snapshots in time. Thus, by examining cumulative effects, the CLCI model serves as a proxy for longitudinal data to better describe life course epidemiology of the disease.
RESUMO
BACKGROUND: Fecal microbiota transplantation is an effective treatment for recurrent Clostridium difficile infection and is being investigated as a treatment for other microbiota-associated diseases. To facilitate these activities, an international public stool bank has been created, which screens donors and processes stools in a standardized manner. The goal of this research is to use mathematical modeling and analysis to optimize screening and donor management at the stool bank. RESULTS: Compared to the current policy of screening active donors every 60 days before releasing their quarantined stools for sale, costs can be reduced by 10.3 % by increasing the screening frequency to every 36 days. In addition, the stool production rate varies widely across donors, and using donor-specific screening, where higher producers are screened more frequently, also reduces costs, as does introducing an interim (i.e., between consecutive regular tests) stool test for just rotavirus and C. difficile. We also derive a donor release (i.e., into the system) policy that allows the supply to approximately match an exponentially increasing deterministic demand. CONCLUSIONS: More frequent screening, interim screening for rotavirus and C. difficile, and donor-specific screening, where higher stool producers are screened more frequently, are all cost-reducing measures. If screening costs decrease in the future (e.g., as a result of bringing screening in house), a bottleneck for implementing some of these recommendations may be the reluctance of donors to undergo serum screening more frequently than monthly.