RESUMO
ABSTRACT: Capnocytophaga canimorsus is a bacteria commonly found in the normal oral cavity of dogs that can cause bacteremia in immunocompromised patients following a dog bite. This case describes sepsis and disseminated intravascular coagulation associated with C. canimorsus in a patient with a history of alcohol abuse. Clinicians must be alert to the risk factors for this infection and provide appropriate prophylaxis following dog bites.
Assuntos
Antibacterianos/administração & dosagem , Bacteriemia/microbiologia , Bacteriemia/terapia , Mordeduras e Picadas/microbiologia , Mordeduras e Picadas/terapia , Capnocytophaga/patogenicidade , Coagulação Intravascular Disseminada/microbiologia , Coagulação Intravascular Disseminada/terapia , Cães/microbiologia , Infecções por Bactérias Gram-Negativas , Hospedeiro Imunocomprometido , Meningite/microbiologia , Meningite/terapia , Sepse/microbiologia , Sepse/terapia , Alcoolismo , Amputação Cirúrgica , Animais , Gangrena/microbiologia , Gangrena/cirurgia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Contributions of mechanical signals to airway remodeling during asthma are poorly understood. Transient receptor potential vanilloid 4 (TRPV4), a mechanosensitive ion channel, has been implicated in cardiac and pulmonary fibrosis; however, its role in asthma remains elusive. Employing a Dermatophagoides farinae-induced asthma model, we report here that TRPV4-knockout mice were protected from D. farinae-induced airway remodeling. Furthermore, lung fibroblasts that were isolated from TRPV4-knockout mice showed diminished differentiation potential compared with wild-type mice. Fibroblasts from asthmatic lung exhibited increased TRPV4 activity and enhanced differentiation potential compared with normal human lung fibroblasts. Of interest, TGF-ß1 treatment enhanced TRPV4 activation in a PI3K-dependent manner in normal human lung fibroblasts in vitro Mechanistically, TRPV4 modulated matrix remodeling in the lung via 2 distinct but dependent pathways: one enhances matrix deposition by fibrotic gene activation, whereas the other slows down matrix degradation by increased plasminogen activator inhibitor 1. Of importance, both pathways are regulated by Rho/myocardin-related transcription factor-A and contribute to fibroblast differentiation and matrix remodeling in the lung. Thus, our results support a unique role for TRPV4 in D. farinae-induced airway remodeling and warrant further studies in humans for it to be used as a novel therapeutic target in the treatment of asthma.-Gombedza, F., Kondeti, V., Al-Azzam, N., Koppes, S., Duah, E., Patil, P., Hexter, M., Phillips, D., Thodeti, C. K., Paruchuri, S. Mechanosensitive transient receptor potential vanilloid 4 regulates Dermatophagoides farinae-induced airway remodeling via 2 distinct pathways modulating matrix synthesis and degradation.