Cardiomyocyte Specific Ablation of p53 Is Not Sufficient to Block Doxorubicin Induced Cardiac Fibrosis and Associated Cytoskeletal Changes

Doxorubicin (Dox) is an anthracycline used to effectively treat several forms of cancer. Unfortunately, the use of Dox is limited due to its association with cardiovascular complications which are manifested as acute and chronic cardiotoxicity. The pathophysiological mechanism of Dox induced cardiotoxicity appears to involve increased expression of the tumor suppressor protein p53 in cardiomyocytes, followed by cellular apoptosis. It is not known whether downregulation of p53 expression in cardiomyocytes would result in decreased rates of myocardial fibrosis which occurs in response to cardiomyocyte loss. Further, it is not known whether Dox can induce perivascular necrosis and associated fibrosis in the heart. In this study we measured the effects of acute Dox treatment on myocardial and perivascular apoptosis and fibrosis in a conditional knockout (CKO) mouse model system which harbours inactive p53 alleles specifically in cardiomyocytes. CKO mice treated with a single dose of Dox (20 mg/kg), did not display lower levels of myocardial apoptosis or reactive oxygen and nitrogen species (ROS/RNS) compared to control mice with intact p53 alleles. Interestingly, CKO mice also displayed higher levels of interstitial and perivascular fibrosis compared to controls 3 or 7 days after Dox treatment. Additionally, the decrease in levels of the microtubule protein α-tubulin, which occurs in response to Dox treatment, was not prevented in CKO mice. Overall, these results indicate that selective loss of p53 in cardiomyocytes is not sufficient to prevent Dox induced myocardial ROS/RNS generation, apoptosis, interstitial fibrosis and perivascular fibrosis. Further, these results support a role for p53 independent apoptotic pathways leading to Dox induced myocardial damage and highlight the importance of vascular lesions in Dox induced cardiotoxicity

Crescimento de plantas de mirtilo a partir de mudas micropropagadas Growth of blueberry from micropropagation plant

Mudas de mirtilo apresentam crescimento inicial lento e baixo índice de sobrevivência. Dentre os fatores envolvidos na produção de mudas, a qualidade do substrato é um fator de grande importância. O trabalho foi realizado com o objetivo de avaliar o desenvolvimento de mudas de mirtilo, em diferentes composições de substrato, durante os meses de dezembro de 2005 a março de 2006. Foram utilizadas mudas da cultivar Georgiagem, do grupo highbush, oriundas de multiplicação in vitro. Foram utilizados sete diferentes substratos para a formação das mudas: T1 - Plantmax® (100%); T2 - Plantmax® + perlita (1:1); T3 - solo + composto industrial + perlita (1:1:1); T4 - solo + casca de arroz + terra (1:1:2); T5 - solo + composto industrial + vermiculita (1:1:1); T6 - casca de acácia + terra (1:2); T7 - acícula de pínus + terra - (1:2). Foram avaliados: altura das plantas; acúmulo de matéria seca da parte aérea e raiz, e análise química dos substratos. A composição do substrato influenciou no desenvolvimento das mudas de mirtilo. Os melhores resultados foram observados em substratos com pH ácido. Conclui-se que os substratos acícula de pínus + terra, Plantmax®, Plantmax® + perlita e casca de arroz + terra apresentaram melhores resultados.<br>The blueberry presents slow development and low index of survival of the seedlings. Among the factors involved in the production of seedlings, the quality of the substrate is a factor of great importance. The work had as objective evaluates the development of blueberry seedlings in different substrate compositions, during the months of December 2005 to March 2006. It was used seedlings of the cultivar Georgiagem of the highbush group, originated from of multiplication in vitro. Seven different substrates were used for the formation of the seedlings: T1 - Plantmax® (100%); T2 - Plantmax® + Perlita (1: 1); T3 - Soil + industrial compost + Perlita (1: 1 :1); T4 - Soil + rice husks + Soil (1 : 1: 2); T5 - Soil + industrial compost + Vermiculite (1: 1: 1); T6 - Acacia bark + soil (1: 2); T7 - pine needle mulch + soil (1: 2). They were evaluated: height of the plants, accumulation of dried matter of the aerial part and root and chemical analysis of the substrate. The composition of the substrate influenced in the development of the blueberry seedlings. The best results were observed in substrates with acid pH. The substrate pine needle mulch + soil, Plantmax®, Plantmax® + perlita and rice bark + soil presented better results