Creatine and guanidinoacetate reference values in a French population.

Creatine and guanidinoacetate are biomarkers of creatine metabolism. Their assays in body fluids may be used for detecting patients with primary creatine deficiency disorders (PCDD), a class of inherited diseases. Their laboratory values in blood and urine may vary with age, requiring that reference normal values are given within the age range.

Screening for primary creatine deficiencies in French patients with unexplained neurological symptoms.

A population of patients with unexplained neurological symptoms from six major French university hospitals was screened over a 28-month period for primary creatine disorder (PCD). Urine guanidinoacetate (GAA) and creatine:creatinine ratios were measured in a cohort of 6,353 subjects to identify PCD patients and compile their clinical, 1H-MRS, biochemical and molecular data. Six GAMT [N-guanidinoacetatemethyltransferase (EC 2.

Effects of hydrogen sulfide on hemodynamics, inflammatory response and oxidative stress during resuscitated hemorrhagic shock in rats.

Introduction: Hydrogen sulfide (H2S) has been shown to improve survival in rodent models of lethal hemorrhage. Conversely, other authors have reported that inhibition of endogenous H2S production improves hemodynamics and reduces organ injury after hemorrhagic shock. Since all of these data originate from unresuscitated models and/or the use of a pre-treatment design, we therefore tested the hypothesis that the H2S donor, sodium hydrosulfide (NaHS), may improve hemodynamics in resuscitated hemorrhagic shock and attenuate oxidative and nitrosative stresses.

Mitochondrial bioenergetic background confers a survival advantage to HepG2 cells in response to chemotherapy.

Cancer cells mainly rely on glycolysis for energetic needs, and mitochondrial ATP production is almost inactive. However, cancer cells require the integrity of mitochondrial functions for their survival, such as the maintenance of the internal membrane potential gradient (DeltaPsim). It thus may be predicted that DeltaPsim regeneration should depend on cellular capability to produce sufficient ATP by upregulating glycolysis or recruiting oxidative phosphorylation (OXPHOS).

Gastric bypass is not associated with protein malnutrition in morbidly obese patients.

Background: Patients undergoing bariatric surgery with a gastric bypass lose about 66% of excess weight. Although this procedure induces weight loss, it is unknown whether it leads to protein malnutrition, which is studied here.

Methods: One hundred ten obese patients (body mass index, 47.

High birth weight and early postnatal weight gain protect obese children and adolescents from truncal adiposity and insulin resistance: metabolically healthy but obese subjects?

Objective: Low birth weight (LBW), no early catch-up weight, and subsequent fat accumulation have been associated with increased risks of insulin resistance from childhood onward and later cardiovascular disease. We sought to clarify the effects of high birth weight (HBW) and postnatal weight gain on insulin resistance.

Research Design And Methods: A total of 117 obese children aged 10.

Hemodynamic and antifibrotic effects of a selective liver nitric oxide donor V-PYRRO/NO in bile duct ligated rats.

Aim: To assess whether a liver specific nitric oxide (NO) donor (V-PYRRO/NO) would prevent the development of portal hypertension and liver fibrosis in rats with bile duct ligation (BDL).

Methods: Treatment (placebo or V-PYRRO/NO 0.53 micromol/kg per hour) was administered i.

Maternal and cord blood ghrelin in the pregnancies of smoking mothers: possible markers of nutrient availability for the fetus.

Aims: To investigate the role of ghrelin in maternal and fetal metabolism, we determined its value in maternal smoking, a specific cause of reduced placenta function and fetal growth.

Methods: In 85 normal term pregnancies, 42 in smoking and 43 in non-smoking mothers, we measured ghrelin in the maternal blood at the onset of labor and in the cord blood of their 85 singletons immediately after birth. We determined the relationships between ghrelin and placental GH (PGH), pituitary GH (pitGH), and IGF-I.

Influence of intensity of food restriction on skeletal muscle mitochondrial energy metabolism in rats.

Variable durations of food restriction (FR; lasting weeks to years) and variable FR intensities are applied to animals in life span-prolonging studies. A reduction in mitochondrial proton leak is suggested as a putative mechanism linking such diet interventions and aging retardation. Early mechanisms of mitochondrial metabolic adaptation induced by FR remain unclear.

Dinitrophenol-induced mitochondrial uncoupling in vivo triggers respiratory adaptation in HepG2 cells.

Here, we show that 3 days of mitochondrial uncoupling, induced by low concentrations of dinitrophenol (10 and 50 microM) in cultured human HepG2 cells, triggers cellular metabolic adaptation towards oxidative metabolism. Chronic respiratory uncoupling of HepG2 cells induced an increase in cellular oxygen consumption, oxidative capacity and cytochrome c oxidase activity. This was associated with an upregulation of COXIV and ANT3 gene expression, two nuclear genes that encode mitochondrial proteins involved in oxidative phosphorylation.

ANT2 isoform required for cancer cell glycolysis.

The three adenine nucleotide translocator (ANT1 to ANT3) isoforms, differentially expressed in human cells, play a crucial role in cell bioenergetics by catalyzing ADP and ATP exchange across the mitochondrial inner membrane. In contrast to differentiated tissue cells, transformed cells, and their rho(0) derivatives, i.e.

Maternal smoking is associated with mitochondrial DNA depletion and respiratory chain complex III deficiency in placenta.

Maternal smoking during pregnancy is often associated with a decrease in placental function, which might lead to intrauterine growth retardation. Because tobacco is known to alter the mitochondrial respiratory function in cardiomyocytes and lung tissue, we hypothesized that placental mitochondrial function could be altered by maternal smoking. Placental mitochondria from 9 smoking and 19 nonsmoking mothers were isolated by differential centrifugation.

Divergent effect of endogenous and exogenous sex steroids on the insulin-like growth factor I response to growth hormone in short normal adolescents.

The lower responsiveness to GH in women than in men is probably due to a divergent effect of gonadal steroids. It is unknown, however, how the progressive increase in sex steroid production that occurs during puberty affects this responsiveness. To compare the effects of puberty and sex steroid administration on responsiveness to GH, we used the IGF-I generation test, in which the peak IGF-I level 24 h after a single injection of GH (2 mg/m2) was studied in 117 healthy short subjects (56 females and 61 males).

Food restriction affects energy metabolism in rat liver mitochondria.

To examine the effect of 50% food restriction over a period of 3 days on mitochondrial energy metabolism, liver mitochondria were isolated from ad libitum and food-restricted rats. Mitochondrial enzyme activities and oxygen consumption were assessed spectrophotometrically and polarographically. With regard to body weight loss (-5%), food restriction decreased the liver to body mass ratio by 7%.

Mitochondrial energy metabolism in a model of undernutrition induced by dexamethasone.

The present investigation was undertaken to evaluate whether mitochondrial energy metabolism is altered in a model of malnutrition induced by dexamethasone (DEX) treatment (1.5 mg/kg per d for 5 d). The gastrocnemius and liver mitochondria were isolated from DEX-treated, pair-fed (PF) and control (CON) rats.

Dexamethasone treatment specifically increases the basal proton conductance of rat liver mitochondria.

We investigated the role that mitochondrial proton leak may play in the glucocorticoid-induced hypermetabolic state. Sprague-Dawley rats were injected with dexamethasone over a period of 5 days. Liver mitochondria and gastrocnemius subsarcolemmal and intermyofibrillar mitochondria were isolated from dexamethasone-treated, pair-fed and control rats.

Low-dose terlipressin improves systemic and splanchnic hemodynamics in fluid-challenged endotoxic rats.

Objective: Vasopressin has been used to treat arterial hypotension associated with hyperdynamic vasoplegic states, but detrimental effects on splanchnic circulation have been reported. We tested the effects of a low-dose vasopressin analogue, terlipressin (6 microg/kg), on systemic and splanchnic hemodynamics in fluid-challenged endotoxic rats (lipopolysaccharide, 30 mg/kg in 1 hr).

Design: Prospective, randomized, controlled experimental study with repeated measures.

Hemodynamic and antifibrotic effects of losartan in rats with liver fibrosis and/or portal hypertension.

Background/aims: To assess the effects of the early and chronic administration of losartan--a specific angiotensin II receptor antagonist--in the prevention of hepatic fibrosis and portal hypertension.

Methods/results: (1) In CCl(4) rats, losartan at 5 and 10 mg/kg per day significantly decreased portal pressure (-11, -18%, respectively), splenorenal shunt blood flow (-60, -80%) and liver fibrosis (liver hydroxyproline and area of fibrosis) without significant changes in mortality and mean arterial pressure (MAP). (2) In bile duct ligated (BDL) rats, losartan at 5 mg/kg per day significantly decreased portal pressure (-14%), splenorenal shunt blood flow (-70%) and liver fibrosis.

Oxygen consumption and expression of the adenine nucleotide translocator in cells lacking mitochondrial DNA.

It has been shown previously that human rho degrees cells, deprived of mitochondrial DNA and consequently of functional oxidative phosphorylation, maintain a mitochondrial membrane potential, which is necessary for their growth. The goal of our study was to determine the precise origin of this membrane potential in three rho degrees cell lines originating from the human HepG2, 143B, and HeLa S3 cell lines. Residual cyanide-sensitive oxygen consumption suggests the persistence of residual mitochondrial respiratory chain activity, about 8% of that of the corresponding parental cells.