X-linked hypophosphatemic rickets with advanced bone age treated with aromatase inhibitor

We present an adolescent with X-linked hypophosphatemic rickets (XLH) with bone age advancement and its response to aromatase inhibitors (AIs). A male with XLH, confirmed with a deletion on the PHEX gene, received regular treatment since the first year of life with average growth velocity and height. He had bone age compatible with chronological age until 13 when he had a bone age advancement and a decrease in the predicted final height thought to be due to initiation of oral isotretinoin, which has been previously reported. Then, anastrozole was initiated and maintained concomitant to the rickets treatment for 2 years with bone age stabilization. He had no adverse effects or worsening of bone health markers. As a result, he maintained his height gain and improved his final height Z score compared with the predicted final height at initiating anastrozole. In conclusion, although AIs was a reasonable strategy to stabilize bone age and minimize height impairment, careful monitoring is mandatory to understand its benefits and effects on XLH patients

Pré-condicionamento precoce da medula espinal isquêmica: pesquisa em coelhos

Investigou-se a possibilidade de desencadear o fenômeno do pré-condicionamento, imediatamente antes da esquemia de 30 minutos, como meio adicional de proteção medular nos casos de pinçamento aórtico prolongado. Oitenta e sete coelhos da raça Nova Zelândia, distribuídos em 6 grupos, foram estudados. A isquemia medular resultou do pinçamento (P) da aorta abdominal, imediatamente após a origem da artéria renal esquerda. Estimulou-se o pré-condicionamento por curtos e repetidos períodos de isquemia, assinalados no texto por grifo, seguidos por variáveis tempos de reperfusão. Grupo I - Controle: 20 animais tiveram a aorta pinçada por 30 min. Dois (10%) recuperaram integralmente a motricidade e a sensibilidade das patas posteriores e cauda; 18 (90%) tornaram-se paraplégicos. Grupo II - Operação simulada: 10 (100%) animais operados como os do grupo anterior, exceto pelo não pinçamento da aorta, recuperaram plenamente as funções sensitivo-motoras. Grupo III - Pré-condicionamento: 10 animais - (P) 1 min ®15 min ®(P) 30 min® reperfusão final. Todos (100%) tornaram-se paraplégicos. Grupo IV - Pré-condicionamento: 6 animais - (P) 1 min ®5 min ®(P) 2 min ®5 min ®(P) 2 min ®5 min (P) 30 min ®reperfusão final. Cinco (83,33%) coelhos ficaram paraplégicos e 1 (16,66%) ficou monoplégico. Grupo V - Clorpromazina: 20 animais receberam clorpromazina por via endovenosa, na dose de 2 mg/kg peso, 10 min antes do pinçamento aórtico. Onze (55%) tiveram recuperação sensitivo-motora integral e 9(45%), ficaram paraplégicos. Grupo VI - Clorpromazina + pré-condicionamento: 21 animais receberam a clorpromazina como os do grupo anterior, sendo pré-condicionados da forma (P) 1 min ® 5 min ®(P) 1 min ® 5 min ®(P) 30 min ® reperfusão final. Nove 42,8%) tiveram recuperação sensitivo-motora integral e 2 (9,52%), recuperação parcial. Os demais (47,68%) ficaram paraplégicos. A análise estatística demonstrou não haver diferença significativa entre os resultados dos grupos III e IV, e quando ambos foram comparados com o grupo I. Não foi significativa a diferença entre os grupos V e VI, mas foi significativa quando ambos foram comparados com o grupo I (p<0,05). Estudo histológico - Outros 12 animais foram usados exclusivamente para o estudo histológico sob microscopia óptica: 6 do grupo controle e 6 com pré-condicionamento do tipo (P) 1 min ® 5 min ®(P) 1 min ® 5 min ® (P) 30 min ® reperfusão de 5 h. Os resultados, avaliados pelo percentual de neurônios isquêmicos, evidenciaram importante dispersão dos valores, sem diferença significativa entre os grupos, considerando-se a mediana desses números (p < 0,05)

Impact of hypoxia on IGF-I, IGF-II, IGFBP-3, ALS and IGFBP-1 regulation and on IGF1R gene expression in children

Hypoxia is one of many factors involved in the regulation of the IGF system. However, no information is available regarding the regulation of the IGF system by acute hypoxia in humans. Objective: The aim of this study was to evaluate the effect of acute hypoxia on the IGF system of children. Design: Twenty-seven previously health children (14 boys and 13 girls) aged 15 days to 9.5 years were studied in two different situations: during a hypoxemic state (HS) due to acute respiratory distress and after full recovery to a normoxemic state (NS). In these two situations oxygen saturation was assessed with a pulse-oximeter and blood samples were collected for serum IGF-I, IGF-II, IGFBP-1, IGFBP-3, ALS and insulin determination by ELISA; fluoroimmunometric assay determination for GH and also for IGF1R gene expression analysis in peripheral lymphocytes by quantitative real-time PCR. Data were paired and analyzed by the Wilcoxon non-parametric test. Results: Oxygen saturation was significantly lower during HS than in NS (P<0.0001). IGF-I and IGF-II levels were lower during HS than in NS (P<0.0001 and P=0.0004. respectively). IGFBP-3 levels were also lower in HS than in NS (P=0.0002) while ALS and basal GH levels were higher during HS (P=0.0015 and P=0.014, respectively). Moreover, IGFBP-1 levels were higher during HS than in NS (P=0.004). No difference was found regarding insulin levels. The expression of IGF1R mRNA as 2(-Delta Delta CT) was higher during HS than in NS (P=0.03). Conclusion: The above results confirm a role of hypoxia in the regulation of the IGF system also in humans. This effect could be direct on the liver and/or mediated by GH and it is not restricted to the hepatocytes but involves other cell lines. During acute hypoxia a combination of alterations usually associated with reduced IGF action was observed. The higher expression of IGF1R mRNA may reflect an up-regulation of the transcriptional process. (C) 2012 Elsevier Ltd. All rights reserved.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Conselho Nacional de Desenvolvimento Cientifico e TecnologicoConselho Nacional de Desenvolvimento Cientifico e Tecnologic