Higher platelet cytochrome oxidase specific activity in surviving than in non-surviving septic patients.

Introduction: In a previous study with 96 septic patients, we found that circulating platelets in 6-months surviving septic patients showed higher activity and quantity of cytochrome c oxidase (COX) normalized by citrate synthase (CS) activity at moment of severe sepsis diagnosis than non-surviving septic patients. The objective of this study was to estimate whether COX specific activity during the first week predicts 1-month sepsis survival in a larger cohort of patients.

Methods: Using a prospective, multicenter, observational study carried out in six Spanish intensive care units with 198 severe septic patients, we determined COX activity per proteins (COXact/Prot) in circulating platelets at day 1, 4 and 8 of the severe sepsis diagnosis.

Severe septic patients with mitochondrial DNA haplogroup JT show higher survival rates: a prospective, multicenter, observational study.

Objective: In a previous cohort study (n=96), we found an association between mitochondrial (mt) DNA haplogroup JT and increased survival of severe septic patients, after controlling for age and serum lactic acid levels. The aim of this research was to increase the predictive accuracy and to control for more confounder variables in a larger cohort (n=196) of severe septic patients, to confirm whether mtDNA haplogroup JT influences short and medium-term survival in these patients.

Methods: We conducted a prospective, multicenter, observational study in six Spanish Intensive Care Units.

Stressed cybrids model demyelinated axons in multiple sclerosis.

Multiple sclerosis is likely caused by a complex interaction of multiple genes and environmental factors. The contribution of mitochondrial DNA genetic backgrounds has been frequently reported. To evaluate the effect of mitochondrial DNA haplogroups in the same genetic and environmental circumstances, we have built human transmitochondrial cell lines and simulated the effect of axon demyelination, one of the hallmarks of multiple sclerosis pathology, by altering the ionic gradients through the plasmalemma and increasing ATP consumption.

Survival and mitochondrial function in septic patients according to mitochondrial DNA haplogroup.

Introduction: We recently found that platelet cytochrome c oxidase (COX) activities and quantities in 6-month-survival septic patients are significantly higher than those of patients who died before 6 months. Other studies suggested that the mitochondrial DNA (mtDNA) genotype could play a major role in sepsis survival. Given that COX catalytic subunits are encoded by mtDNA, the objective of the present study was to explore whether mtDNA population genetic variation could affect COX activity and quantity and favors sepsis survival.

OXPHOS toxicogenomics and Parkinson's disease.

Activities and quantities of several oxidative phosphorylation (OXPHOS) system complexes are decreased in many Parkinson's disease (PD) patients. Mutations in PD-associated nuclear genes affect OXPHOS function. Moreover, the inactivation of other nuclear genes related to mitochondrial DNA (mtDNA) replication and expression also leads to Parkinsonism.

Platelet cytochrome c oxidase activity and quantity in septic patients.

Objective: The cytopathic hypoxia theory proposes that there is an impaired cellular oxygen utilization during sepsis. Respiratory complex IV, or cytochrome c oxidase, was only previously studied in muscle biopsies of 16 surviving and 12 nonsurviving septic patients. We hypothesized that higher activities and quantities of this enzyme complex could be associated with septic patient survival.

Melatonin inhibits serotonin transporter activity in intestinal epithelial cells.

Gastrointestinal serotonin (5-HT) and melatonin are two closely related neuromodulators which are synthesised in the enterochromaffin cells of the intestinal epithelium and which have been shown to be involved in the physiopathology of the gastrointestinal tract. The effects of 5-HT depend on 5-HT availability which is, in part, modulated by the serotonin transporter (SERT). This transporter provides an efficient 5-HT uptake after release and is expressed in the membrane of the enterocytes.

Lipopolysaccharide induces alteration of serotonin transporter in human intestinal epithelial cells.

Intestinal serotoninergic activity and serotonin transporter (SERT) function have been shown to be altered in intestinal inflammatory diseases. Serotonin (5-HT) plays a critical role in the regulation of gastrointestinal physiology. Activity of 5-HT depends on its extracellular availability, partly modulated by SERT that transports 5-HT into the cell.

Effect of long-term fluoxetine treatment on the human serotonin transporter in Caco-2 cells.

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) broadly used in the treatment of human mood disorders and gastrointestinal diseases involving the serotoninergic system. The effectiveness of this therapy depends on repeated long-term treatment. Most of the long-term studies in vivo of SSRI effects on serotoninergic activity have focused on their effects on autoreceptors or postsynaptic receptors.