ABSTRACT
Collection of an adequate amount of autologous haematopoietic stem progenitor cells (HSPC) is required for ex vivo manipulation and successful engraftment for certain inherited disorders. Fifty-seven paediatric patients (age 0.5-11.4 years) underwent a bone marrow harvest for the purpose of HSPC gene therapy (GT), including adenosine deaminase-severe combined immunodeficiency (ADA-SCID), Wiskott-Aldrich syndrome (WAS) and metachromatic leukodystrophy (MLD) patients. Total nucleated cells and the percentage and absolute counts of CD34+ cells were calculated at defined steps of the procedure (harvest, CD34+ cell purification, transduction with the gene transfer vector and infusion of the medicinal product). A minimum CD34+ cell dose for infusion was 2 × 106/kg, with an optimal target at 5-10 × 106/kg. Median volume of bone marrow harvested was 34.2 ml/kg (range 14.2-56.6). The number of CD34+ cells collected correlated inversely with weight and age in all patients and particularly in the MLD children group. All patients reached the minimum target dose for infusion: median dose of CD34+ cells/kg infused was 10.3 × 106/kg (3.7-25.9), with no difference among the three groups. Bone marrow harvest of volumes > 30 ml/kg in infants and children with ADA-SCID, WAS and MLD is well tolerated and allows obtaining an adequate dose of a medicinal product for HSPC-GT.
Subject(s)
Bone Marrow/metabolism , Genetic Therapy/methods , Hematopoietic Stem Cell Transplantation/methods , Transplantation Conditioning/methods , Female , Humans , MaleABSTRACT
Ethanolic crude extract (ECE) of leaves from Syzygium cumini (L.) Skeels, Myrtaceae was screened for its hypoglycemic and hypolipidemic activity (125, 250 and 500 mg/kg v.o.). Rats were divided into three groups for the evaluation of the hypoglycemic effect: normal rats, rats with alloxan-induced diabetes and hyperglycemic normal rats. Hypolipidemia was evaluated in rats with alloxan-induced diabetes. The antihyperglycemic activity was compared to treatment with glibenclamide, an oral hypoglycemic agent. The acute treatment with S. cumini ECE caused a significant decrease in the blood glucose in hyperglycemic normal rats (250 mg/kg), and in glucose (125 and 250 mg/kg), triglyceride (125 and 500 mg/kg) and cholesterol (125 mg/kg) levels of diabetic rats, but no effect was observed in the normal treated rats. Syzygium cumini leaves are a good candidate for alternative and/or complementary medicine in the management of diabetes mellitus, since they showed hypoglycemic activity in addition to a hypolipidemic action in diabetic animals.
Na região de Criciúma-SC, as folhas de Syzygium cumini (L.) Skeels, Myrtaceae, conhecida popularmente como jambolão, são utilizadas para diminuir níveis de glicose plasmática em pessoas diabéticas. Dentro deste contexto o presente trabalho teve o interesse de avaliar o efeito hipoglicêmico e hipolipidêmico do extrato bruto hidroalcoólico (EBH) das folhas de S. cumini (125, 250 e 500 mg/kg). Para tal os animais foram divididos em três grupos para o efeito hipoglicêmico: ratos normais, ratos normais submetidos a curva de glicose (hiperglicêmicos) e ratos diabéticos induzidos com aloxana. O efeito hipolipidêmico foi avaliado em animais diabéticos induzidos por aloxana. O efeito hipoglicêmico foi comparado com glibenclamida. O tratamento agudo com EBH de S. cumini causou uma diminuição estatisticamente significativa na glicose sanguínea em animais normais que foram submetidos à cura de glicose (250 mg/kg), e sobre os níveis de glicose (125 e 250 mg/kg), triglicerídeo (125 e 500 mg/kg) e colesterol (125 mg/kg) em animais diabéticos. Nenhuma das doses testadas apresentou efeito em animais normais. Dentro deste contexto pode-se sugerir que o EBH das folhas de S. cumini pode ser uma alternativa terapêutica no tratamento alternativo ou complementar na diabete, uma vez que apresentou atividade hipoglicêmica e hipolipidêmica em animais diabéticos.
