Insights into intestinal regeneration signaling mechanisms.

The cellular mechanisms underlying the amazing ability of sea cucumbers to regenerate their autotomized intestines have been widely described by us and others. However, the signaling pathways that control these mechanisms are unknown. Previous studies have shown that Wnt homologs are upregulated during early intestinal regenerative stages, suggesting that the Wnt/ß-catenin pathway is active during this process. Here, we used small molecules, putative disruptors of the Wnt pathway, to determine the potential role of the canonical Wnt pathway on intestine regeneration in the sea cucumber Holothuria glaberrima. We evaluated their effects in vivo by using histological analyses for cell dedifferentiation, cell proliferation and apoptosis. We found that iCRT14, an alleged Wnt pathway inhibitor, decreased the size of the regenerating intestine, while LiCl, a presumed Wnt pathway activator, increased its size. The possible cellular mechanisms by which signaling pathway disruptors affect the gut rudiment size were further studied in vitro, using cultures of tissue explants and additional pharmacological agents. Among the tested signaling activators, those that act through GSK-3 inhibition, LiCl, 1-Azakenpaullone, and CHIR99021 were found to increase muscle cell dedifferentiation, while the inhibitor iCRT14 blocked cell dedifferentiation. Differently, cell proliferation was reduced by all GSK-3 inhibitors, as well as by iCRT14 and C59, which interferes with Wnt ligand secretion. The in vivo temporal and spatial pattern of ß-catenin activity was determined using an antibody against phosphorylated ß-catenin and shown to correlate with cell proliferative activity. In vitro treatment using C59 decreased the number of cells immunostained for nuclear phosphorylated ß-catenin. Our results showed that the cell dedifferentiation observed during intestinal regeneration can be decoupled from the cell proliferation event and that these cellular processes can be modulated by particular signaling pathway inhibitors and activators. These results open the door for future studies where the cellular signaling pathways involved at each regeneration stage can be determined.

[Relationship between C-reactive protein level and early recurrence of atrial fibrillation after electrical cardioversion]. / Relación entre concentraciones de proteína C reactiva y recurrencia precoz de la fibrilación auricular tras cardioversión eléctrica.

INTRODUCTION AND OBJECTIVES: Atrial remodeling is responsible for the early recurrence of atrial fibrillation (AF) after cardioversion. Recently, it has been shown that the C-reactive protein (CRP) level is elevated in patients with AF, indicating that inflammation may play a role in the pathogenesis of this arrhythmia. We postulated that a high CRP level would predict early recurrence of AF after electrical cardioversion. PATIENTS AND METHOD: Forty-two patients with persistent AF, but without known heart disease, who underwent elective electrical cardioversion were investigated. The CRP level was measured immediately before cardioversion. The study population comprised the 37 patients in whom sinus rhythm was restored. RESULTS: After a follow-up period of 30 days, 16 patients (43%) had recurrence of AF; the other 21 (57%) remained in sinus rhythm. The mean CRP level was significantly higher in patients with AF recurrence (6.3 [3.3] mg/L vs 2.4 [2.1] mg/L, P=.0001). On dividing patients according to whether their CRP level was < or =3 mg/L or >3 mg/L, it was observed that only 33% of those in sinus rhythm had a level >3 mg/L compared with 81% of those with AF recurrence (P=.004). Patients with a CRP level >3 mg/L had a significant increase in the 1-month risk of AF recurrence (RR=3.7; 95% CI, 1.3-10.8). There was no association between CRP level and left atrial diameter (P =.50) or AF duration (P=.458). CONCLUSIONS: A high CRP level is associated with early recurrence of AF after electrical cardioversion, suggesting that inflammation could play a role in atrial remodeling.

Relación entre concentraciones de proteína C reactiva y recurrencia precoz de la fibrilación auricular tras cardioversión eléctrica / Relationship between C-reactive protein level and early recurrence of atrial fibrillation after electrical cardioversion

Introducción y objetivos. El remodelado auricular es la causa principal de recurrencia de la fibrilación auricular (FA) tras la cardioversión. Se han observado concentraciones elevadas de proteína C reactiva (PCR) en pacientes con FA, lo que sugiere que la inflamación puede participar en la patogenia de esta arritmia. Nosotros planteamos que las concentraciones elevadas de PCR podrían estar asociadas con la recurrencia de la FA tras cardioversión eléctrica. Pacientes y método. Se analizó a 42 pacientes con FA persistente remitidos para cardioversión eléctrica electiva, sin cardiopatía ni proceso intercurrente conocido. La PCR se obtuvo inmediatamente antes de la cardioversión. Se restauró ritmo sinusal (RS) en 37 pacientes. Resultados. A los 30 días, 16 pacientes estaban de nuevo en FA (43%) y los restantes 21 permanecían en RS (57%). La PCR media fue significativamente mayor en los pacientes con recurrencia de la FA (6,3 ± 3,3 frente a 2,4 ± 2,1 mg/l; p = 0,0001). Al dividir a los pacientes de acuerdo con los valores de PCR ≤ 3 y > 3 mg/l, sólo el 33% de los que estaban en RS tenía valores > 3 mg/l, frente al 81% de los pacientes con recurrencia de la FA (p = 0,004). Los individuos con PCR > 3 mg/l tenían más riesgo de estar en FA al mes (riesgo relativo [RR] = 3,7; intervalo de confianza [IC] del 95%, 1,3-10,8). La PCR no se asoció con el tamaño de aurícula izquierda (p = 0,50) ni con el tiempo de evolución de la FA (p = 0,458). Conclusiones. Los valores elevados de PCR están asociados con la recurrencia precoz de la FA tras cardioversión eléctrica, lo que sugiere que la inflamación podría participar en el remodelado auricular

Introduction and objectives. Atrial remodeling is responsible for the early recurrence of atrial fibrillation (AF) after cardioversion. Recently, it has been shown that the C-reactive protein (CRP) level is elevated in patients with AF, indicating that inflammation may play a role in the pathogenesis of this arrhythmia. We postulated that a high CRP level would predict early recurrence of AF after electrical cardioversion. Patients and method. Forty-two patients with persistent AF, but without known heart disease, who underwent elective electrical cardioversion were investigated. The CRP level was measured immediately before cardioversion. The study population comprised the 37 patients in whom sinus rhythm was restored. Results. After a follow-up period of 30 days, 16 patients (43%) had recurrence of AF; the other 21 (57%) remained in sinus rhythm. The mean CRP level was significantly higher in patients with AF recurrence (6.3 [3.3] mg/L vs 2.4 [2.1] mg/L, P=.0001). On dividing patients according to whether their CRP level was ≤3 mg/L or >3 mg/L, it was observed that only 33% of those in sinus rhythm had a level >3 mg/L compared with 81% of those with AF recurrence (P=.004). Patients with a CRP level >3 mg/L had a significant increase in the 1-month risk of AF recurrence (RR=3.7; 95% CI, 1.3-10.8). There was no association between CRP level and left atrial diameter (P =.50) or AF duration (P=.458). Conclusions. A high CRP level is associated with early recurrence of AF after electrical cardioversion, suggesting that inflammation could play a role in atrial remodeling

[Aspergillus fumigatus endocarditis in a patient with a biventricular pacemaker]. / Endocarditis por Aspergillus fumigatus en un marcapasos bicameral.

Aspergillus fumigatus endocarditis is one of the rarest and severest complications in cardiological patients. We describe a patient with an intracardial pacemaker who was diagnosed as having Aspergillus fumigatus endocarditis. Postmortem examination showed a large, Aspergillus-infected thrombus encased in the right ventricle, pulmonary trunk and main pulmonary branches.

Endocarditis por Aspergillus fumigatus en un marcapasos bicameral / Aspergillus fumigatus endocarditis in a patient with a biventricular pacemaker

La endocarditis por Aspergillus fumigatus es una de las complicaciones más raras y severas que puede presentar un paciente cardiológico. Presentamos el caso de una paciente portadora de marcapasos endocavitario diagnosticada de endocarditis por Aspergillus. El estudio postmortem mostró un trombo infectado por Aspergillus que ocupaba el ventrículo derecho, así como la arteria y las ramas de la arteria pulmonar (AU)

Aspergillus fumigatus endocarditis is one of the rare stand severest complications in cardiological patients. We describe a patient with an intracardial pacemaker who was diagnosed as having Aspergillus fumigatus endocarditis .Postmortem examination showed a large, Aspergillus-infected thrombus encased in the right ventricle, pulmonary trunk and main pulmonary branches (AU)