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1.
Cureus ; 16(2): e55094, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38558602

RESUMO

Atypical fibroxanthoma (AFX) is a rare spindle cell proliferation arising from significant sun exposure. AFX often appears as a red papule, typically found in the head and neck region of elderly patients. Since there is no specificity in immunohistology, various stains differentiate AFX from other skin cancers. The stains include cluster of differentiation 68 (CD68), cluster of differentiation 163 (CD163), vimentin, cytokeratin epithelial (CKAE), and melanin. While local recurrence is common, AFX rarely metastasizes. Thus, the treatment options are complete surgical excision or micrographically oriented histographic surgery.

2.
JMIR Res Protoc ; 9(8): e18706, 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32851981

RESUMO

BACKGROUND: Outcomes after peripheral nerve injuries are poor despite current nerve repair techniques. Currently, there is no conclusive evidence that mammalian axons are capable of spontaneous fusion after transection. Notably, certain invertebrate species are able to auto-fuse after transection. Although mammalian axonal auto-fusion has not been observed experimentally, no mammalian study to date has demonstrated regenerating axolemmal membranes contacting intact distal segment axolemmal membranes to determine whether mammalian peripheral nerve axons have the intrinsic mechanisms necessary to auto-fuse after transection. OBJECTIVE: This study aims to assess fusion competence between regenerating axons and intact distal segment axons by enhancing axon regeneration, delaying Wallerian degeneration, limiting the immune response, and preventing myelin obstruction. METHODS: This study will use a rat sciatic nerve model to evaluate the effects of a novel peripheral nerve repair protocol on behavioral, electrophysiologic, and morphologic parameters. This protocol consists of a variety of preoperative, intraoperative, and postoperative interventions. Fusion will be assessed with electrophysiological conduction of action potentials across the repaired transection site. Axon-axon contact will be assessed with transmission electron microscopy. Behavioral recovery will be analyzed with the sciatic functional index. A total of 36 rats will be used for this study. The experimental group will use 24 rats and the negative control group will use 12 rats. For both the experimental and negative control groups, there will be both a behavior group and another group that will undergo electrophysiological and morphological analysis. The primary end point will be the presence or absence of action potentials across the lesion site. Secondary end points will include behavioral recovery with the sciatic functional index and morphological analysis of axon-axon contact between regenerating axons and intact distal segment axons. RESULTS: The author is in the process of grant funding and institutional review board approval as of March 2020. The final follow-up will be completed by December 2021. CONCLUSIONS: In this study, the efficacy of the proposed novel peripheral nerve repair protocol will be evaluated using behavioral and electrophysiologic parameters. The author believes this study will provide information regarding whether spontaneous axon fusion is possible in mammals under the proper conditions. This information could potentially be translated to clinical trials if successful to improve outcomes after peripheral nerve injury. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/18706.

3.
J Immunol ; 198(10): 3809-3814, 2017 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-28389592

RESUMO

Targeted inhibition of Rho-associated kinase (ROCK)2 downregulates the proinflammatory T cell response while increasing the regulatory arm of the immune response in animals models of autoimmunity and Th17-skewing human cell culture in vitro. In this study, we report that oral administration of a selective ROCK2 inhibitor, KD025, reduces psoriasis area and severity index scores by 50% from baseline in 46% of patients with psoriasis vulgaris, and it decreases epidermal thickness as well as T cell infiltration in the skin. We observed significant reductions of IL-17 and IL-23, but not IL-6 and TNF-α, whereas IL-10 levels were increased in peripheral blood of clinical responders after 12 wk of treatment with KD025. Collectively, these data demonstrate that an orally available selective ROCK2 inhibitor downregulates the Th17-driven autoimmune response and improved clinical symptoms in psoriatic patients via a defined molecular mechanism that involves concurrent modulation of cytokines without deleterious impact on the rest of the immune system.


Assuntos
Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Interleucina-10/sangue , Interleucina-17/sangue , Psoríase/tratamento farmacológico , Pele/efeitos dos fármacos , Pele/imunologia , Quinases Associadas a rho/antagonistas & inibidores , Administração Oral , Adolescente , Adulto , Idoso , Autoimunidade/efeitos dos fármacos , Citocinas/biossíntese , Citocinas/genética , Citocinas/imunologia , Regulação para Baixo , Feminino , Regulação da Expressão Gênica , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Humanos , Interleucina-10/genética , Interleucina-10/imunologia , Interleucina-17/genética , Interleucina-17/imunologia , Queratinócitos/imunologia , Masculino , Pessoa de Meia-Idade , Psoríase/imunologia , Psoríase/patologia , Índice de Gravidade de Doença , Pele/patologia , Células Th17/imunologia , Adulto Jovem
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