Proper activation of phosphoinositide 3-kinase-Akt pathway is critical for the prevention of tumorigenesis. Recent data have characterized a negative feedback loop, wherein mammalian target of rapamycin (mTOR) blocks additional activation of the Akt/mTOR pathway through inhibition insulin receptor substrate 1 (IRS-1) function. However, the potential of IRS-1 inhibition during rapamycin treatment has not been examined. Herein, we show that IRS-1 antisense oligonucleotide and rapamycin synergistically antagonize the activation of mTOR in vivo and induced tumor suppression, through inhibition of proliferation and induction of apoptosis, in prostate cancer cell xenografts. These data demonstrate that the addition of agents that blocks IRS-1 potentiate the effect of mTOR inhibition in the growth of prostate cancer cell xenografts.
RESUMOo atraso no crescimento é freqüente e grave em crianças com doença renal crônica (drc). vários fatores contribuem para o comprometimento do crescimento nestas crianças, incluindo as alterações no eixo hormônio de crescimento (gH) -insulin-like growth factor 1 (igF-1), desnutrição, acidose, doença renal óssea e uso de corticóides. em crianças com drc, o tratamento do atraso no crescimento é difícil em virtude da presença de doenças associadas que necessitem de adequado tratamento médico. Apesar de as evidên-cias a respeito da segurança e de a eficácia do gH nesta população, este tratamento ainda é pouco utilizado. esta revisão mostra o impacto, as causas e o tratamento do atraso no crescimento em crianças com drc. H istoricamente, o termo insuficiência renal crônica (IRC) tem sido usado para descrever pacientes com ritmo de filtração glomerular (RFG) menor que 75 mL/min/1,73 m 2 de área corporal (1). Mais recentemente, a National Kidney Foundation (NKF) introduziu o termo doença renal crônica (DRC), bem como a classificação do quadro, a fim de propiciar a detecção precoce, retardar a progressão e prevenir complicações relacionadas. Essa classificação descreve cinco estágios da DRC considerando a presença de lesão
RESUMOAtualmente, é grande o impacto psicossocial da baixa estatura nas crianças e adolescentes com insuficiência renal crônica (IRC), sendo o hormônio de crescimento recombinante humano (rhGH) uma alternativa terapêutica. Avaliamos o crescimento e a composição corporal (CC) em 11 crianças pré-púberes (9M/2F; 3,5-12,8a) com IRC e baixa estatura e/ou baixa velocidade de crescimento, tratadas com rhGH (0,7-1,0UI/Kg/semana) por 18 meses. Avaliamos antropometria e CC por impedância bioelétrica tetrapolar antes e 6, 12 e 18 meses após o início do rhGH; maturação esquelética e função renal foram avaliadas antes e após 6 e 12 meses. Houve aumento significativo do peso, da altura, da VC e da massa magra (MM), com diminuição significativa da massa gorda (MG) no período de 0 a 6 meses de tratamento. Entre 0 e 12 meses houve apenas aumento significativo da altura. Entre 6 e 12 meses houve inversão da CC, com diminuição significativa da MM e aumento da MG. Entre 12 e 18 meses houve restabelecimento da CC inicial, com diminuição significativa da MG e aumento da MM. Não se observaram alterações na função renal, nem avanço exagerado da maturação esquelética. Em conclusão, o rhGH em doses de reposição por 18 meses promoveu melhora do crescimento com mudança da CC neste grupo de crianças com IRC, especialmente nos primeiros 12 meses de tratamento, sem efeitos colaterais. At present, the impairment of linear growth remains one of the major obstacles to successful social adaptation of children and adolescents with chronic renal insufficiency (CRI), being the recombinant human growth hormone (rhGH) a therapeutic option. We evaluated growth and body composition (BC) in 11 prepubertal patients (9M/2F; 3.5-12.8y) with CRI and short stature and/or slow growth velocity treated with rhGh (0.7-1.0IU/Kg/week) for 18 months. Anthropometry and BC, examined by a tetrapolar bioeletrical impedance, were evaluated before, 6, 12 and 18 months after rhGH treatment; biochemical examinations and bone age were assessed before, and after 6 and 12 months. Six months after the onset of rhGH, there was a significant increment of weight, height, growth velocity and lean mass, with a significant decrease of fat mass; 12 months after, there was only a significant increment of height. Between 6 and 12 months, an inversion of BC was observed, with significant increment of fat mass and decrease of lean mass. Between 12 and 18 months, BC recovered, with a significant increment of lean mass and correspondent decrease of fat mass. The residual renal function was preserved, as well as the normal increment of bone age. In conclusion, rhGH administration for 18 months to children with CRI improved growth significantly and changed the BC, particularly in the first 12 months, with no side effects. (Arq Bras Endocrinol Metab 2002;46/6:661-667) artigo original
Abstract. Pastures are complex land covers with a variety of land use systems. This land cover occupies large areas in the globe and is mainly used for livestock production. Brazil is one of the largest livestock producers and has extensive pasture areas. We analyzed the pasture land cover change of the São Paulo State between the years 2000 to 2015. São Paulo was chosen as study case due to its large industrial and agricultural importance and its expressive land cover changes over past decades. It was analyzed land covers databases generated by the Brazilian Annual Land Use and Land Cover Mapping Project (MapBiomas Project) – Collection 4. Transition matrix was generated to analyze the land cover change during the period. Gain, loss, total change, net change and swap were calculated in terms of area. Total pasture area decreased but continues the largest land cover of the São Paulo State; with 79.5% of persistence in the area. Main changes were from losses of pastures and gains in agriculture. Most of the changes to pasture came from other non vegetated areas and grassland categories. These results demonstrated the relevance of pastures areas in land cover change dynamics to address land use policy and plan future land use scenarios.
The replacement doses of rhGH during 12 months in a selected group of CRF children determined an increment in IGF-1 and IGFBP-3, associated to normal serum leptin and insulin resistance.
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