Parkin cooperates with GDNF/RET signaling to prevent dopaminergic neuron degeneration.

Parkin and the glial cell line-derived neurotrophic factor (GDNF) receptor RET have both been independently linked to the dopaminergic neuron degeneration that underlies Parkinson's disease (PD). In the present study, we demonstrate that there is genetic crosstalk between parkin and the receptor tyrosine kinase RET in two different mouse models of PD. Mice lacking both parkin and RET exhibited accelerated dopaminergic cell and axonal loss compared with parkin-deficient animals, which showed none, and RET-deficient mice, in which we found moderate degeneration.

The influence of serotonin on fear learning.

Learning of associations between aversive stimuli and predictive cues is the basis of Pavlovian fear conditioning and is driven by a mismatch between expectation and outcome. To investigate whether serotonin modulates the formation of such aversive cue-outcome associations, we used functional magnetic resonance imaging (fMRI) and dietary tryptophan depletion to reduce brain serotonin (5-HT) levels in healthy human subjects. In a Pavlovian fear conditioning paradigm, 5-HT depleted subjects compared to a non-depleted control group exhibited attenuated autonomic responses to cues indicating the upcoming of an aversive event.

Complications of non-compaction of the left ventricular myocardium in a paediatric population: a prospective study.

Aims: Non-compaction of the left ventricular myocardium (NCVM) is reportedly exceedingly rare and associated with a high morbidity and mortality. A different genetic background has been suggested for NCVM with [non-isolated NCVM (ni-NCVM)] and without [isolated NCVM (i-NCVM)] other congenital heart defects. We prospectively evaluated both the NCVM subgroups regarding frequency of occurrence and cardiovascular complications in a paediatric population.

Electroencephalographic changes after pediatric cardiac surgery with cardiopulmonary bypass: is slow wave activity unfavorable?

Pediatric cardiac surgery with cardiopulmonary bypass (CPB) is frequently associated with neurologic deficits. We describe the postoperative EEG changes, assess their possible causes, and evaluate their relevance to neurologic outcome. Thirty-one children and five neonates with congenital heart disease were included.

Oxidative stress precedes peak systemic inflammatory response in pediatric patients undergoing cardiopulmonary bypass operation.

Oxidative stress seems to contribute to cardiopulmonary bypass (CPB)-related postoperative complications. Pediatric patients are particularly prone to these complications. With this in mind, we measured oxidative stress markers in blood plasma of 20 children undergoing elective heart surgery before, during, and up to 48 h after cessation of CPB, along with inflammatory parameters and full analysis of iron status.

Localization of alpha-tocopherol transfer protein in trophoblast, fetal capillaries' endothelium and amnion epithelium of human term placenta.

Vitamin E has been linked to fertility since its discovery in 1922. However, the exact mechanism by which alpha-tocopherol allows pregnancy to continue until term has remained puzzling over the last 80 years. Alpha-tocopherol transfer protein (TTPA) is expressed in liver and in Purkinje cells of the cerebellum.

Evidence for increased oxidative stress in peroxisomal D-bifunctional protein deficiency.

Peroxisome biogenesis disorders (PBDs) and D-bifunctional protein (D-BP) deficiency are two types of inherited peroxisomal disorders. Patients with a PBD lack functional peroxisomes and patients with D-BP deficiency lack the enzyme, which is responsible for the second and third step of the peroxisomal beta-oxidation. The clinical presentation of these peroxisomal disorders is severe and includes several neurological abnormalities.

Membrane oxidation assay--a novel lipoxygenase-based evaluation of membrane oxidizability.

A membrane oxidation assay is presented which uses isolated erythrocyte membranes ("ghosts") alipoxygenase as a selective catalyst for the transfer of oxygen to cis-cis-1,4-pentadiene-moieties. The latter are, for instance, present in linoleic and arachidonic acids, both of which are integral parts of membranes. These non-conjugated double bonds represent energetically favorable sites for oxidative attack and therefore, may be rearranged and partially consumed during oxidative stress.

Neonatal blood plasma is less susceptible to oxidation than adult plasma owing to its higher content of bilirubin and lower content of oxidizable Fatty acids.

Newborn infants are susceptible to a range of problems attributed to excessive production of free radicals. Because of a higher content of antioxidants, above all bilirubin, and a lower content of oxidizable lipids, newborn plasma should be better protected against oxidation than adult plasma. To test this hypothesis, we measured the susceptibility of plasma to in vitro oxidation in microsamples (7 microL) from 57 healthy newborns and 18 adults.

Influence of diagnostic categories, age, and gender on antioxidative defense and lipid peroxidation in skeletal muscle of patients with neuromuscular diseases.

The influence of diagnostic categories, age, and gender on parameters of oxidative stress measured in 102 patients with neuromuscular diseases and 11 control subjects was assessed using a stepwise multiple linear regression model. Antioxidative enzyme activities, lipophilic antioxidants, and lipid peroxidation were analyzed in muscle biopsies. Mitochondrial myopathies and amyotrophic lateral sclerosis (ALS) are thought to be particularly susceptible to increased oxidative stress.

Radical trapping in glycogen storage disease 1a.

Unlabelled: Oxidative mechanisms involving lipid peroxidation in the subendothelium of the arterial vessel wall play a key role in atherogenesis. Despite severe hyperlipidaemia, patients with glycogen storage disease type 1a (GSD1a) do not develop premature atherosclerosis. Therefore, we analysed parameters of antioxidative defence and oxidative stress in plasma and serum of patients with GSD1a ( n=17) and compared them with those of patients with type 1 diabetes mellitus ( n=17), familial hypercholesterolaemia ( n=18) and healthy controls ( n=20).

Plasma antioxidants in pediatric patients with glycogen storage disease, diabetes mellitus, and hypercholesterolemia.

Oxidative modification of lipoproteins in vessel walls plays a key role in atherogenesis. Patients with glycogen storage disease type Ia (GSD Ia) do not develop premature atherosclerosis despite severe hyperlipidemia. We analyzed antioxidative defense and oxidative stress in plasma and serum of patients with GSD Ia (n = 17) compared to patients with type I diabetes mellitus (DMI, n = 17), familial hypercholesterolemia (FH, n = 18), and healthy controls (n = 20).

Septo-optic dysplasia associated with a new mitochondrial cytochrome b mutation.

We report on a 25-year-old patient with isolated mitochondrial complex III deficiency and a new heteroplasmic mutation (T14849C) in the cytochrome b gene. He suffered from septo-optic dysplasia, retinitis pigmentosa, exercise intolerance, hypertrophic cardiomyopathy, and rhabdomyolysis. A HESX1 mutation was excluded as a cause of his septo-optic dysplasia.