Effects of glycemic control on glucose utilization and mitochondrial respiration during resuscitated murine septic shock.

Background: This study aims to test the hypothesis whether lowering glycemia improves mitochondrial function and thereby attenuates apoptotic cell death during resuscitated murine septic shock.

Methods: Immediately and 6 h after cecal ligation and puncture (CLP), mice randomly received either vehicle or the anti-diabetic drug EMD008 (100 μg · g(-1)). At 15 h post CLP, mice were anesthetized, mechanically ventilated, instrumented and rendered normo- or hyperglycemic (target glycemia 100 ± 20 and 180 ± 50 mg · dL(-1), respectively) by infusing stable, non-radioactive isotope-labeled (13)C6-glucose.

Early resuscitation of dengue shock syndrome in children with hyperosmolar sodium-lactate: a randomized single-blind clinical trial of efficacy and safety.

Introduction: Dengue shock syndrome (DSS) fluid resuscitation by following the World Health Organization (WHO) guideline usually required large volumes of Ringer lactate (RL) that might induce secondary fluid overload. Our objective was to compare the effectiveness of the recommended volume of RL versus a smaller volume of a hypertonic sodium lactate solution (HSL) in children with DSS. The primary end point was to evaluate the effect of HSL on endothelial cell inflammation, assessed by soluble vascular cell adhesion molecule-1 (sVCAM-1) measurements.

Half-molar sodium lactate infusion to prevent intracranial hypertensive episodes in severe traumatic brain injured patients: a randomized controlled trial.

Purpose: Preventive treatments of traumatic intracranial hypertension are not yet established. We aimed to compare the efficiency of half-molar sodium lactate (SL) versus saline serum solutions in preventing episodes of raised intracranial pressure (ICP) in patients with severe traumatic brain injury (TBI).

Methods: This was a double-blind, randomized controlled trial including 60 patients with severe TBI requiring ICP monitoring.

Reactive oxygen species are produced at low glucose and contribute to the activation of AMPK in insulin-secreting cells.

Excess reactive oxygen species (ROS) production is thought to play a key role in the loss of pancreatic β-cell number and/or function, in response to high glucose and/or fatty acids. However, contradictory findings have been reported showing that in pancreatic β cells or insulin-secreting cell lines, ROS are produced under conditions of either high or low glucose. Superoxide production was measured in attached INS1E cells as a function of glucose concentration, by following in real time the oxidation of dihydroethidine.

Effects of a high-fat diet on energy metabolism and ROS production in rat liver.

Background & Aims: A high-fat diet affects liver metabolism, leading to steatosis, a complex disorder related to insulin resistance and mitochondrial alterations. Steatosis is still poorly understood since diverse effects have been reported, depending on the different experimental models used.

Methods: We hereby report the effects of an 8 week high-fat diet on liver energy metabolism in a rat model, investigated in both isolated mitochondria and hepatocytes.

Liver mitochondria and insulin resistance.

With a steadily increasing prevalence, insulin resistance (IR) is a major public health issue. This syndrome is defined as a set of metabolic dysfunctions associated with, or contributing to, a range of serious health problems. These disorders include type 2 diabetes, metabolic syndrome, obesity, and non-alcoholic steatohepatitis (NASH).

High expression of thyroid hormone receptors and mitochondrial glycerol-3-phosphate dehydrogenase in the liver is linked to enhanced fatty acid oxidation in Lou/C, a rat strain resistant to obesity.

Besides its well recognized role in lipid and carbohydrate metabolisms, glycerol is involved in the regulation of cellular energy homeostasis via glycerol-3-phosphate, a key metabolite in the translocation of reducing power across the mitochondrial inner membrane with mitochondrial glycerol-3-phosphate dehydrogenase. Here, we report a high rate of gluconeogenesis from glycerol and fatty acid oxidation in hepatocytes from Lou/C, a peculiar rat strain derived from Wistar, which is resistant to age- and diet-related obesity. This feature, associated with elevated cellular respiration and cytosolic ATP/ADP and NAD(+)/NADH ratios, was linked to a high expression and activity of mitochondrial glycerol-3-phosphate dehydrogenase.

Half-molar sodium-lactate solution has a beneficial effect in patients after coronary artery bypass grafting.

Objective: To compare two solutions for fluid resuscitation in post-coronary artery bypass grafting (CABG) surgery patients: Ringer's lactate (RL) versus a new solution containing half-molar sodium-lactate (HL).

Design: Prospective randomized open label study.

Setting: The first 12 h post-CABG surgery in an intensive care unit (ICU).

Intradialytic nutritional support.

Purpose Of Review: Intradialytic nutritional support has been used for more than 30 years both in critically ill patients with acute renal failure and during maintenance hemodialysis. Present knowledge allows better estimation of its metabolic and nutritional efficacy, as well its effect on patient outcome.

Recent Findings: Recent data showed that intradialytic nutritional support is able to counteract these effects of dialysis on protein metabolism and to improve both nitrogen and energy balance.

The flavonoid silibinin decreases glucose-6-phosphate hydrolysis in perfused rat hepatocytes by an inhibitory effect on glucose-6-phosphatase.

Background/aims: The flavonoid silibinin has been reported to be beneficial in several hepatic disorders. Recent evidence also suggests that silibinin could be beneficial in the treatment of type 2 diabetes, owing to its anti-hyperglycemic properties. However, the mechanism(s) underlying these metabolic effects remains unknown.

Mitochondrial function and substrate availability.

Carbohydrates and lipid oxidations support energy metabolism by distinct pathways exhibiting similarities and differences. Alterations of energy metabolism during sepsis are well recognized; however, failure of oxygen or substrate supply is not a prominent cause. The occurrence of a "mitochondrial cytopathy" induced by sepsis explains some of these abnormalities, which may represent a "metabolic hibernation," a potential strategy of defense during the very acute phase of the illness.

Intradialytic parenteral nutrition does not improve survival in malnourished hemodialysis patients: a 2-year multicenter, prospective, randomized study.

Although intradialytic parenteral nutrition (IDPN) is a method used widely to combat protein-calorie malnutrition in hemodialysis patients, its effect on survival has not been thoroughly studied. We conducted a prospective, randomized trial in which 186 malnourished hemodialysis patients received oral nutritional supplements with or without 1 year of IDPN. IDPN did not improve 2-year mortality (primary end point), hospitalization rate, Karnofsky score, body mass index, or laboratory markers of nutritional status.

Nutritional management in acute illness and acute kidney insufficiency.

There are now powerful compensatory therapies to counteract kidney deficiency and the prognosis of patients with acute renal failure is mainly related to the severity of the initial disease. Renal failure is accompanied by an increase in both severity and duration of the catabolic phase leading to stronger catabolic consequences. The specificity of the metabolic and nutritional disorders in the most severely ill patients is the consequence of three additive phenomena: (1) the metabolic response to stress and to organ dysfunction, (2) the lack of normal kidney function and (3) the interference with the renal treatment (hemodialysis, hemofiltration or both, continuous or intermittent, lactate or bicarbonate buffer, etc.

The effect of iNOS deletion on hepatic gluconeogenesis in hyperdynamic murine septic shock.

Objective: To investigate the role of the inducible nitric oxide synthase activation-induced excess nitric oxide formation on the rate of hepatic glucose production during fully resuscitated murine septic shock.

Design: Prospective, controlled, randomized animal study.

Setting: University animal research laboratory.

Effects of a cantaloupe melon extract/wheat gliadin biopolymer during aortic cross-clamping.

Objective: We previously reported in healthy volunteers that a cantaloupe melon extract chemically combined with wheat gliadin (melon extract/gliadin) and containing SOD, catalase and residual glutathione peroxidase (GPx), protected against DNA strand-break damage induced by hyperbaric oxygen (HBO), a well-established model of DNA damage resulting from oxidative stress. Aortic cross-clamping is a typical example of ischemia/reperfusion injury-related oxidative stress, and therefore we investigated whether this melon extract/gliadin would also reduce DNA damage after aortic cross-clamping and reperfusion.

Design: Prospective, randomized, controlled experimental study.

The ROS production induced by a reverse-electron flux at respiratory-chain complex 1 is hampered by metformin.

Mitochondrial reactive oxygen species (ROS) production was investigated in mitochondria extracted from liver of rats treated with or without metformin, a mild inhibitor of respiratory chain complex 1 used in type 2 diabetes. A high rate of ROS production, fully suppressed by rotenone, was evidenced in non-phosphorylating mitochondria in the presence of succinate as a single complex 2 substrate. This ROS production was substantially lowered by metformin pretreatment and by any decrease in membrane potential (Delta Phi(m)), redox potential (NADH/NAD), or phosphate potential, as induced by malonate, 2,4-dinitrophenol, or ATP synthesis, respectively.

Intradialytic parenteral nutrition: comparison of olive oil versus soybean oil-based lipid emulsions.

Lipid, oxidative and inflammatory parameters are frequently altered in dialysis patients and may be worsened by intravenous lipid emulsions (ILE). We assessed the efficacy and tolerance of olive as compared with standard soybean oil-based ILE during intradialytic parenteral nutrition (IDPN). IDPN mixtures containing amino acids, glucose, and either olive oil (OO group, n 17) or soybean oil-based ILE (SO group, n 18) were administered in a 5-week randomized, double-blind study.

Application of branched-chain amino acids in human pathological states: renal failure.

During renal failure, abnormalities of BCAA and branched-chain keto acid (BCKA) metabolism are due to both the lack of renal contribution to amino acid metabolism and the impact of renal failure and acidosis on whole-body nitrogen metabolism. Abnormal BCAA and BCKA metabolism result in BCAA depletion as reflected by low plasma BCAAs and cellular valine. BCAA metabolic disturbances can alter tissue activities, particularly brain function, and nutritional status.

Lactate in the intensive care unit: pyromaniac, sentinel or fireman?

Lactate, indispensable substrate of mammalian intermediary metabolism, allows shuttling of carbons and reducing power between cells and organs at a high turnover rate. Lactate is, therefore, not deleterious, although an increase in its concentration is often a sensitive sign of alteration in energy homeostasis, a rise in it being frequently related to poor prognosis. Such an increase, however, actually signifies an attempt by the body to cope with a new energy status.

Polyunsaturated fatty acid deficiency reverses effects of alcohol on mitochondrial energy metabolism.

Background/aims: Polyunsaturated fatty acids (PUFA) deficiency is common in patients with alcoholic liver disease. The suitability of reversing such deficiency remains controversial. The aim was to investigate the role played by PUFA deficiency in the occurrence of alcohol-related mitochondrial dysfunction.

HMR1402, a potassium ATP channel blocker during hyperdynamic porcine endotoxemia: effects on hepato-splanchnic oxygen exchange and metabolism.

Objective: To assess the effects of the potassium ATP (KATP) channel blocker HMR1402 (HMR) on systemic and hepato-splanchnic hemodynamics, oxygen exchange and metabolism during hyperdynamic porcine endotoxemia.

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

Effect of cardiopulmonary bypass on lactate metabolism.

Objective: We have investigated the role of cardiopulmonary bypass on lactate metabolism in patients undergoing uncomplicated surgery for elective coronary artery bypass grafting (CABG).

Design: Prospective non-randomized observational study.

Settings: National Cardiovascular Center.

Adenosine triphosphate-magnesium chloride: relevance for intensive care.

Background: Despite aggressive resuscitation shock often results in multiple-organ failure characterized by increased energy demands of organs and decreased ability of effective energy production. The administration of ATP-MgCl(2) as a supportive measure has been investigated in various animal models of ischemia/reperfusion injury and hemorrhagic, endotoxic, and septic shock.

Investigations: These studies showed improvement in organ blood flow, microcirculation, energy balance, cellular and mitochondrial, functions and restoration of immune competence, ultimately leading to increased survival.