RESUMO
The mammalian heart has a remarkable regenerative capacity for a short period of time after birth, after which the majority of cardiomyocytes permanently exit cell cycle. We sought to determine the primary postnatal event that results in cardiomyocyte cell-cycle arrest. We hypothesized that transition to the oxygen-rich postnatal environment is the upstream signal that results in cell-cycle arrest of cardiomyocytes. Here, we show that reactive oxygen species (ROS), oxidative DNA damage, and DNA damage response (DDR) markers significantly increase in the heart during the first postnatal week. Intriguingly, postnatal hypoxemia, ROS scavenging, or inhibition of DDR all prolong the postnatal proliferative window of cardiomyocytes, whereas hyperoxemia and ROS generators shorten it. These findings uncover a protective mechanism that mediates cardiomyocyte cell-cycle arrest in exchange for utilization of oxygen-dependent aerobic metabolism. Reduction of mitochondrial-dependent oxidative stress should be an important component of cardiomyocyte proliferation-based therapeutic approaches.
Assuntos
Pontos de Checagem do Ciclo Celular , Miócitos Cardíacos/citologia , Espécies Reativas de Oxigênio/metabolismo , Acetilcisteína/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Dano ao DNA , Sequestradores de Radicais Livres/farmacologia , Camundongos , Mitocôndrias/metabolismo , Miócitos Cardíacos/metabolismo , Peixe-ZebraRESUMO
Prematurity and low birthweight are associated with increased mortality in infants undergoing cardiac surgery. Pulmonary atresia with intact ventricular septum and right ventricle-dependent coronary circulation carries one of the highest risks of mortality. We present a patient who was born at 28 weeks of gestation at 1.2 kg, with pulmonary atresia intact ventricular septum, right ventricle-dependent coronary circulation, coronary artery atresia, and discontinuous pulmonary arteries, who successfully underwent palliation with a modified Blalock-Taussig shunt, pulmonary arterioplasty, and subsequently a bidirectional Glenn.
Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Hipertrofia Ventricular Esquerda/metabolismo , Mitocôndrias Cardíacas/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Miócitos Cardíacos/metabolismo , Disfunção Ventricular Esquerda/metabolismo , Animais , Sinalização do Cálcio , Proteínas de Ligação ao Cálcio/genética , Modelos Animais de Doenças , Feminino , Hipertrofia Ventricular Esquerda/genética , Hipertrofia Ventricular Esquerda/fisiopatologia , Preparação de Coração Isolado , Masculino , Camundongos Knockout , Proteínas de Transporte da Membrana Mitocondrial/genética , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/fisiopatologia , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Disfunção Ventricular Esquerda/genética , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda , Pressão VentricularRESUMO
Abstract:Background andObjectives: Immunosuppressed individuals are at particularly increased risk for human papilloma virus-related infections. The primary objective of our study is to determine if there are any adverse effects associated with high-dose cimetidine treatment. A secondary objective is to report our experience with cimetidine in the treatment of cutaneous warts in pediatric heart transplant recipients. Methods and Results: This was a retrospective observational study. A total of 8 pediatric heart transplant recipients diagnosed with multiple recalcitrant warts were the subject of the study. All patients were treated with cimetidine (30-40 mg/kg/day) in two divided doses for 3 to 6 month durations. All patients had complete resolution of their lesions except 1 patient who had no clinical improvement. Of these 8 patients, one had recurrence of warts at one year follow-up, which resolved with restarting cimetidine therapy. One patient who had only 3 months of cimetidine therapy had immediate relapse after cimetidine was stopped. None of them had significant change in their tacrolimus trough, serum creatinine, and alanine transaminase levels. No adverse events were reported except one patient experienced mild gynecomastia. Conclusion: Cimetidine can be a safe and alternative treatment option for multiple warts in pediatric heart transplant recipients.
RESUMO
INTRODUCTION: Assessment of specific mRNAs in human samples is useful in characterizing disease. However, mRNA in human stool has been understudied. RESULTS: Compared to controls, infected stools showed increased transcripts of IL-1ß, IL-8 and calprotectin. mRNA and protein concentrations correlated for IL-8, but not for calprotectin. DISCUSSION: Stool mRNA quantification offers a potentially useful, noninvasive way to assess inflammation in the gastrointestinal tract, and may be more sensitive than EIA. METHODS: We purified fecal RNA from 46 children infected with Campylobacter jejuni, Escherichia coli O157:H7, Salmonella spp. or Shigella sonnei and 26 controls and compared the proportions of IL-1ß, IL-8, osteoprotegerin and calprotectin mRNA between groups using qRT-PCR. We determined the concentrations of calprotectin, IL-8 and osteoprotegerin by enzyme immunoassays in cognate specimens.