Induction of adiponectin in skeletal muscle by inflammatory cytokines: in vivo and in vitro studies

Adiponectin (ApN) is an adipocytokine that plays a fundamental role in energy homeostasis and counteracting inflammation. We examined whether ApN could be induced in a nonadipose tissue, the skeletal muscle, in vivo, and in cultured myotubes in response to lipopolysaccharides or proinflammatory cytokines. We next explored the underlying mechanisms. In vivo, injection of lipopolysaccharides to mice caused, after 24 h, an approximately 10-fold rise in ApN mRNA abundance and a concomitant 70% increase in ApN levels in tibialis anterior muscle. This ApN induction was reproduced in C2C12 myotubes cultured for 48 h with a proinflammatory cytokine combination, interferon-gamma + TNFalpha. This effect occurred in a time- and dose-dependent manner. Several pieces of evidence suggest that nitric oxide (NO) mediates this up-regulation by cytokines in myotubes or muscle. First, ApN was induced in vitro exclusively in the experimental conditions that stimulated NO production. Second, inducible NO synthase mRNA induction or NO production clearly preceded ApN mRNA induction. Third, preventing NO production by inhibitors of the NO synthases, nitro-L-arginine methyl ester or NG-methyl-L-arginine, suppressed the inductive effect of the cytokines in vitro and in vivo. Finally, ApN mRNA induction by cytokines was reproduced in cultured human myotubes. In conclusion, our data provide evidence that adiponectin is up-regulated in vivo and in vitro in human and rodent myotubes in response to inflammatory stimuli. The underlying mechanisms seem to involve a NO-dependent pathway. This overexpression may be viewed as a local antiinflammatory protection and a way to deliver extra energy supplies during inflammation.     

Effects of hypoxia on stress proteins in the piglet brain at birth

Newborn piglets were submitted to normobaric hypoxia (5% O2, 95% N2) for either 1 or 4 h. The effects of hypoxia on the neonatal brain were characterized through a time-course analysis of levels of various proteins such as heat shock proteins (HSP27, 70, and 90), hypoxia inducible factor-1alpha (HIF-1alpha), neuronal nitric oxide synthase (nNOS), hemeoxygenase-2 (HO-2), and caspase-3. The expression of these proteins was determined at different stages of recovery up to 72 h in cerebellum, cortex, and hippocampus by Western blot analysis in hypoxic maintained animals that were made hypoxic at either 20 or 37 degrees C. In all regions of the brain, HIF-1alpha and HSP27 expression were strongly increased until 22 h of recovery. No significant changes were observed for HSP70, HSP90, and HO-2. A small elevation of expression of nNOS was observed at early stages in the cerebellum and the cortex with no change in the hippocampus. Expression of caspase 3 was strongly increased in the cortex 24 and 48 h after hypoxia but unchanged in the hippocampus. These results are presented in terms of the porcine model of nonischemic hypoxia and its delayed neuronal effects on the cerebral outcome. Because of their recently established biochemical and functional interactions, the expression of the main HSPs, HIF-1alpha, nNOS, and caspase-3 after hypoxia are delineated.     

Surgical treatment in primary hyperaldosteronism

From 1994 to 2000, 32 patients (16 men, 16 women; mean age 53 years) underwent laparoscopic adrenalectomy at H?pital l'Antiquaille of Lyon. All but one had systemic arterial hypertension and hypokaliemia was noted in all patients. All patients had unilateral adrenalectomy, and only one required conversion to conventional laparotomy. There were no deaths and complications were rare.     

Longitudinal bone insufficiency fracture of the tibia in a renal transplant recipient

We report a case of longitudinal tibial fracture as the first manifestation of bone insufficiency in a 50-year-old patient who had received a renal transplant 12 years earlier. The epidemiological, clinical, and imaging features of these fractures are reviewed. Bone loss occurs in the long term in about half of renal transplant recipients. The main causes are preexisting renal osteodystrophy; glucocorticoid therapy; and hyperparathyroidism, whether residual or secondary to imperfect graft function. The effects of cyclosporine therapy on bone metabolism remain unclear. Identification of patients at very high risk of fracture and available options for early prophylaxis are discussed.     

One or two-stage hepatectomy combined with portal vein embolization for initially nonresectable colorectal liver metastases

BACKGROUND: Portal vein embolization (PVE), proposed to induce contralateral hepatic hypertrophy before major hepatectomy, carries some negative side effects since growth rate of metastases in the future remnant liver (RL) can be more rapid than that of nontumoral liver parenchyma. Therefore, metastases in the RL should be ideally resected before PVE, and a major hepatectomy can then be performed after PVE in patients with multiple bilobar colorectal liver metastases (MBLM). The aim of this study was to assess feasibility and outcome in patients with initially unresectable colorectal liver metastases treated by a one- or two-stage hepatectomy procedure (TSHP) combined with PVE. PATIENTS AND METHODS: From December 1996 to December 1999, 180 patients with colorectal liver metastases underwent hepatectomy. During the same period, 18 were initially considered as unresectable. TSHP combined with PVE was attempted for 7 patients (group A) among those with MBLM, and a one-stage hepatectomy after PVE was attempted in another group of 11 patients (group B) among those with non-MBLM. RESULTS: Nonanatomical resections for left liver metastases were performed as a first stage without any complications in group A. A right hepatectomy (RH) was performed in 5 patients in group A (feasibility = 71%). In group B, 7 of the 11 patients underwent a RH or an extended RH after PVE (feasibility = 64%). Postoperative complications rate did not differ between group A and B. Mortality was nil. Three-year survival rate was 53% in group A and 100% in group B. CONCLUSIONS: These results suggest that one- or two-stage hepatectomy combined with PVE can be applied safely to selected patients initially considered as unresectable. Three-year survival was similar to that observed in patients with initially resectable liver metastases.     

Acaricidal activity of tonka bean extracts. Synthesis and structure-activity relationships of bioactive derivatives

The acaricidal effects of tonka bean, Dipterix odorata, extracts were investigated on Dermatophagoides pteronyssinus, the European house dust mite, and compared with benzyl benzoate as a standard acaricidal compound. A cyclohexane extract was the most effective, with an EC(50) = 0.075 g/m(2) after a 24 h period, as compared with benzyl benzoate (0.025 g/m(2)). Bioassay-guided fractionation of this extract led to the isolation of coumarin (1). Pharmacomodulation of this compound led us to test 20 analogues (2-21), which were either synthesized or purchased.     

White matter damage and intraventricular hemorrhage in very preterm infants: the EPIPAGE study

OBJECTIVE: To evaluate the prevalence of cranial ultrasound abnormalities in very preterm infants as a function of gestational age, plurality, intrauterine growth restriction, and death before discharge. STUDY DESIGN: A prospective, population-based cohort of 2667 infants born between 22 and 32 weeks of gestation in 1997 in nine regions of France, transferred to a neonatal intensive care unit, for whom at least one cranial ultrasound scan was available. RESULTS: The frequencies of white matter damage (WMD), major WMD, cystic periventricular leukomalacia (PVL), periventricular parenchymal hemorrhagic involvement, and intraventricular hemorrhage with ventricular dilatation were 21%, 8%, 5%, 3%, and 3%, respectively. The risk of WMD increased with decreasing gestational age. Mean age at diagnosis of cystic PVL was older for the most premature infants. Intraventricular hemorrhage with ventricular dilatation was associated with a higher risk of cystic PVL. Intrauterine growth restriction was not associated with a lower prevalence of cystic PVL. CONCLUSION: The frequency of WMD is high in very preterm babies and is strongly related to gestational age. The incidence of cystic PVL did not differ between babies with intrauterine growth restriction and babies who were appropriate for gestational age.