Relation between mean arterial pressure and renal function in the early phase of shock: a prospective, explorative cohort study

International audienceIntroduction: Because of disturbed renal autoregulation, patients experiencing hypotension-induced renal insult might need higher levels of mean arterial pressure (MAP) than the 65 mmHg recommended level in order to avoid the progression of acute kidney insufficiency (AKI)

Etude de la relation entre la pression artérielle et la fonction rénale au cours des trois premiers jours de l'insuffisance circulatoire aiguë en réanimation

TOURS-BU Médecine (372612103) / SudocSudocFranceF

CORLI : Un corpus ouvert du français -ou comment travailler à rassembler les briques existantes ?

International audienc

CORLI : Un corpus ouvert du français -ou comment travailler à rassembler les briques existantes ?

International audienc

CORLI : Un corpus ouvert du français -ou comment travailler à rassembler les briques existantes ?

International audienc

CORLI : Un corpus ouvert du français -ou comment travailler à rassembler les briques existantes ?

International audienc

Gene therapy for Parkinson’s disease: preclinical evaluation of optimally configured TH:CH1 fusion for maximal dopamine synthesis

International audienceA recent phase I-II, open-label trial of ProSavin, a lentiviral vector delivering the key enzymes in the dopamine biosynthetic pathway to non-dopaminergic striatal neurons, demonstrated safety and improved motor function in parkinsonian patients. However, the magnitude of the effect suggested that optimal levels of dopamine replacement may not have been achieved. OXB-102, a lentiviral vector with an optimized expression cassette for dopamine biosynthesis, has been shown to achieve a significantly higher dopamine yield than ProSavin. We assessed the efficacy of OXB-102 in the MPTP macaque model of Parkinson's disease (PD). At 6 months post-vector administration, all treated animals showed significant improvements in clinical scores and spontaneous locomotor activity compared to controls, with the highest recovery observed in the OXB-102 high-dose (HD) group. Positron emission tomography quantification of 6-[ 18 F]-fluoro-L-m-tyrosine uptake showed a significant increase in amino acid decarboxylase activity for all treated animals, compared with controls, where the OXB-102 HD group showed the highest level of dopaminergic activity. A toxicology study in macaques demonstrated that the vector was safe and well tolerated, with no associated clinical or behavioral abnormalities and no immune response mounted against any transgene products. Overall, these data support the further clinical development of OXB-102 for the treatment of PD

Placental restriction reduces insulin sensitivity and expression of insulin signaling and glucose transporter genes in skeletal muscle, but not liver, in young sheep

Poor growth before birth is associated with impaired insulin sensitivity later in life, increasing the risk of type 2 diabetes. The tissue sites at which insulin resistance first develops after intrauterine growth restriction (IUGR), and its molecular basis, are unclear. We have therefore characterized the effects of placental restriction (PR), a major cause of IUGR, on whole-body insulin sensitivity and expression of molecular determinants of insulin signaling and glucose uptake in skeletal muscle andliver ofyounglambs. Whole-body insulin sensitivitywasmeasured at 30dby hyperinsulinaemic euglycaemic clamp and expression of insulin signaling genes (receptors, pathways, and targets) at 43 d in muscle and liver of control (n = 15) and PR (n = 13) lambs. PR reduced size at birth and increased postnatal growth, fasting plasma glucose (+15%, P < 0.004), and insulin (+115%, P = 0.009). PR reduced whole-body insulin sensitivity (-43%, P_0.001) and skeletal muscle expression of INSR (- 36%), IRS1 (-28%), AKT2 (- 44%), GLUT4 (- 88%), GSK3 (-35%), and GYS1 (-31%) overall (each P < 0.05) and decreased AMPK3 expression in females (P = 0.030). PR did not alter hepatic expression of insulin signaling and related genes but increased GLUT2 expression (P = 0.047) in males. Whole-body insulin sensitivity correlated positively with skeletal muscle expression of IRS1,AKT2,HK,AMPK2, andAMPK3 in PR lambs only (each P<0.05) but not with hepatic gene expression in control or PR lambs. Onset of insulin resistance after PR and IUGR is accompanied by, and can be accounted for by, reduced expression of insulin signaling and metabolic genes in skeletal muscle but not liver.Miles J. De Blasio, Kathryn L. Gatford, M. Lyn Harland, Jeffrey S. Robinson and Julie A. Owen