RESUMO
Cardiac fibroblasts (CF) are key cells for maintaining extracellular matrix (ECM) protein homeostasis in the heart, and for cardiac repair through CF-to-cardiac myofibroblast (CMF) differentiation. Additionally, CF play an important role in the inflammatory process after cardiac injury, and they express Toll like receptor 4 (TLR4), B1 and B2 bradykinin receptors (B1R and B2R) which are important in the inflammatory response. B1R and B2R are induced by proinflammatory cytokines and their activation by bradykinin (BK: B2R agonist) or des-arg-kallidin (DAKD: B1R agonist), induces NO and PGI2 production which is key for reducing collagen I levels. However, whether TLR4 activation regulates bradykinin receptor expression remains unknown. CF were isolated from human, neonatal rat and adult mouse heart. B1R mRNA expression was evaluated by qRT-PCR, whereas B1R, collagen, COX-2 and iNOS protein levels were evaluated by Western Blot. NO and PGI2 were evaluated by commercial kits. We report here that in CF, TLR4 activation increased B1R mRNA and protein levels, as well as COX-2 and iNOS levels. B1R mRNA levels were also induced by interleukin-1α via its cognate receptor IL-1R1. In LPS-pretreated CF the DAKD treatment induced higher responses with respect to those observed in non LPS-pretreated CF, increasing PGI2 secretion and NO production; and reducing collagen I protein levels in CF. In conclusion, no significant response to DAKD was observed (due to very low expression of B1R in CF) - but pre-activation of TLR4 in CF, conditions that significantly enhanced B1R expression, led to an additional response of DAKD.
Assuntos
Fibroblastos/metabolismo , Miócitos Cardíacos/metabolismo , Receptor B1 da Bradicinina/biossíntese , Receptor 4 Toll-Like/biossíntese , Animais , Células Cultivadas , Fibroblastos/efeitos dos fármacos , Expressão Gênica , Humanos , Lipopolissacarídeos/toxicidade , Camundongos , Camundongos Knockout , Miócitos Cardíacos/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Receptor B1 da Bradicinina/agonistas , Receptor B1 da Bradicinina/genética , Receptor 4 Toll-Like/agonistas , Receptor 4 Toll-Like/genéticaRESUMO
BACKGROUND: Medical treatment of disabling intermittent claudication or critical limb-threatening ischemia causing rest pain often fails or has partial response. METHODS: In this pilot study, 36 patients (12 females) affected by disabling intermittent claudication or rest pain of the lower extremities were exposed to a daily 3-L water intake for up to 6 weeks. Cutaneous foot temperature, ankle/brachial index, time and distance of claudication, and pain intensity were recorded before and at the completion of the hydration period. RESULTS: Patients with a mean ± SE age of 71 ± 2 years (range, 40-86) had disabling claudication (less than 100 meters) for more than 5 months while 11% reported pain at rest. A 6-week water intake of more than 2,500 mL/24 hr was achieved in 35 of the 36 patients enrolled in the study. Increased water intake was associated with significant improvements in median ankle/brachial index (from 0.60 to 0.76; P < 0.0001) and skin temperature (first dorsal right toe, from 29.95°C to 30.0°C, P < 0.001). Time and distance to report claudication of supervised treadmill exercise improved from 1.25 to 6.25 min (P < 0.0001) and from 100 meters to 535 meters (P < 0.0001), respectively. CONCLUSIONS: This study suggests that hydration attained by daily water consumption of more than 2.5 L has a robust impact on reducing the symptoms of disabling claudication and rest pain caused by peripheral vascular disease.
Assuntos
Ingestão de Líquidos , Hidratação/métodos , Claudicação Intermitente/terapia , Extremidade Inferior/irrigação sanguínea , Doenças Vasculares Periféricas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice Tornozelo-Braço , Argentina , Avaliação da Deficiência , Tolerância ao Exercício , Feminino , Humanos , Claudicação Intermitente/diagnóstico , Claudicação Intermitente/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estado de Hidratação do Organismo , Medição da Dor , Doenças Vasculares Periféricas/diagnóstico , Doenças Vasculares Periféricas/fisiopatologia , Projetos Piloto , Estudos Prospectivos , Recuperação de Função Fisiológica , Temperatura Cutânea , Fatores de Tempo , Resultado do Tratamento , Equilíbrio HidroeletrolíticoRESUMO
Bacterial lipopolysaccharide (LPS) is a known ligand of Toll-like receptor 4 (TLR4) which is expressed in cardiac fibroblasts (CF). Differentiation of CF to cardiac myofibroblasts (CMF) is induced by transforming growth factor-ß1 (TGF-ß1), increasing alpha-smooth muscle actin (α-SMA) expression. In endothelial cells, an antagonist effect between LPS-induced signaling and canonical TGF-ß1 signaling was described; however, it has not been studied whether in CF and CMF the expression of α-SMA induced by TGF-ß1 is antagonized by LPS and the mechanism involved. In adult rat CF and CMF, α-SMA, ERK1/2, Akt, NF-κß, Smad3, and Smad7 protein levels were determined by western blot, TGF-ß isoforms by ELISA, and α-SMA stress fibers by immunocytochemistry. CF and CMF secrete the three TGF-ß isoforms, and the secretion levels of TGF-ß2 was affected by LPS treatment. In CF, LPS treatment decreased the protein levels of α-SMA, and this effect was prevented by TAK-242 (TLR4 inhibitor) and LY294002 (Akt inhibitor), but not by BAY 11-7082 (NF-κß inhibitor) and PD98059 (ERK1/2 inhibitor). TGF-ß1 increased α-SMA protein levels in CF, and LPS prevented partially this effect. In addition, in CMF α-SMA protein levels were decreased by LPS treatment, which was abolished by TAK-242. Finally, in CF LPS decreased the p-Smad3 phosphorylation and increased the Smad7 protein levels. LPS treatment prevents the CF-to-CMF differentiation and reverses the CMF phenotype induced by TGF-ß1, through decreasing p-Smad3 and increasing Smad7 protein levels.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Miócitos Cardíacos/efeitos dos fármacos , Miofibroblastos/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Animais , Diferenciação Celular/fisiologia , Células Cultivadas , Fibroblastos/efeitos dos fármacos , Fibroblastos/fisiologia , Masculino , Miócitos Cardíacos/fisiologia , Miofibroblastos/fisiologia , Ratos , Ratos Sprague-Dawley , Receptor 4 Toll-Like/agonistasRESUMO
BACKGROUND: Carotid angioplasty and stenting can be used in stroke prevention in high-risk patients. As embolic complications can occur during carotid angioplasty and stenting, a device was developed to protect from cerebral embolization. METHODS: Between September 1999 and May 2002, carotid angioplasty and stenting was performed in 100 patients (84 men; mean age, 69.2 years) with symptomatic (26%) or asymptomatic (74%) severe carotid artery stenosis. Wallstents were used in all cases with selective pre-dilatation. Cerebral protection devices (Parodi Anti-Emboli System [PAES], ArteriA, San Francisco, Calif) were used in all patients. All patients were evaluated by a neurologist, both before and after the procedure. According to the criteria set forth by the large trials, the occurrence of minor, major or fatal stroke and myocardial infarction (end points) within 30 days and follow-up were determined as end points. Data were collected prospectively. RESULTS: The overall perioperative stroke and death rate was 3% (1 noncorresponding minor stroke, 1 hemorrhagic stroke, and 1 cardiac event). Four patients developed postoperative transient neurologic events (three related to hemodynamic instability and the fourth due to postoperative embolization). The overall technical success rate for carotid angioplasty (protection device placed in position percutaneously) was 99%. CONCLUSION: The efficacy and safety of carotid angioplasty and stenting with PAES are confirmed. This innovative protection device may prevent the debris released by angioplasty from entering the cerebral circulation. Further investigation is warranted.
Assuntos
Angioplastia com Balão , Estenose das Carótidas/terapia , Embolia Intracraniana/prevenção & controle , Próteses e Implantes , Stents , Idoso , Idoso de 80 Anos ou mais , Artéria Carótida Interna/fisiopatologia , Estenose das Carótidas/epidemiologia , Circulação Cerebrovascular , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fluxo Sanguíneo Regional , Fatores de Risco , Acidente Vascular Cerebral/prevenção & controleRESUMO
La mano zamba congénita es una de las afecciones ortopédicas de más difícil tratamiento. Procederemos a presentar el caso de un paciente portador de esta entidad por agenesia del radio, que fue tratado con el minifijador externo modelo RALCA. Se obtienen resultados satisfactorios, y se muestran las bondades de este sistema de fijación externa.
Assuntos
Humanos , Masculino , Criança , Contenções , Fixadores Externos , Deformidades Congênitas da Mão/diagnóstico , Deformidades Congênitas da Mão/terapia , Aparelhos OrtopédicosRESUMO
En este trabajo se realiza una revisión de 31 pacientes con enfermedad luxante de la cadera, atendidos y tratados en el Servicio de Ortopedia y Traumatología del Hospital Pediátrico Provincial Docente "José Luis Miranda" de Santa Clara, en el periodo comprendido entre enero de 1989 y junio de 1991. Se realiza un Análisis de variables importantes como edad, sexo, elementos clínicos que propiciaron el diagnóstico, clasificación, tratamiento empleado y periodo de sanidad. Se hace especial énfasis en las ventajas que reportaron el arnés de Pavlik y la órtesis de Ponseti, así como los efectos favorables que nos brindaron su colocación precoz. Se muestran los resultados finales obtenidos al tratar esta patología que continúa siendo un problema difícil que debe enfrentar el cirujano ortopédico. Se recomienda nuestro esquema de tratamiento por considerar que favorece la curación y porque acorta el periodo de rehabilitación.
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Luxação Congênita de Quadril/cirurgia , Luxação Congênita de Quadril/fisiopatologia , Luxação Congênita de Quadril/terapia , Aparelhos OrtopédicosRESUMO
La mano zamba congénita es una de las afecciones ortopédicas de más difícil tratamiento, Se presentó un caso de un paciente portador de esta entidad, por agenesia del radio; quien fue tratado con el minifijador externo modelo RALCA. Se obtuvieron resultados satisfactorios, que muestran las "bondades" de este sistema de fijación externa
Assuntos
Deformidades Congênitas da Mão/cirurgia , Fixadores Externos , Rádio (Anatomia)/anormalidades , Procedimentos Ortopédicos/métodosRESUMO
La literatura reporta una aparente disminución en la incidencia de defectos del tubo neural a través del mundo. Una evaluación de 9 años de certificados de natimuertos y de reportes quirúrgicos de procedimientos de cierre de los defectos, arroja la evidencia de que Puerto Rico probablemente posee la más alta incidencia de todos los territorios de Estados Unidos y que esta tendencia no está disminuyendo