No abstract

No abstract

Oxidative damage is greater in brain tissue from patients with Alzheimer's disease (AD) than age-matched controls. The timing of this damage in relation to other pathogenic processes in AD remains unclear. We have examined the relationship of lipid peroxidation (thiobarbituric acid-reactive substances; TBARS) and antioxidant capacity (Trolox-equivalent) to APOE status, Braak tangle stage, amyloid-β (Aβ) plaque load, and the concentration of soluble and insoluble forms of Aβ, post-synaptic and dendritic spine proteins PSD95 and drebrin, β-secretase and Aβ-degrading enzymes neprilysin (NEP), insulin-degrading enzyme (IDE), and angiotensin-converting enzyme (ACE), in frontal, temporal, and parietal cortex from AD and control brains. Antioxidant capacity was significantly elevated in AD and directly related to disease severity as indicated by Braak tangle stage and the amount of insoluble Aβ. APOE ε4 was associated with increased antioxidant capacity in AD but not controls. In contrast, apart from a reduction in TBARS in Braak stages III-IV in frontal cortex, this measure of oxidative damage did not change significantly with any indicator of disease severity. It was, however, higher in APOE ε4-positive than ε4-negative AD patients and correlated with β-secretase activity. Neither antioxidant capacity nor oxidative damage was related to the level of PSD95 or drebin or the activity of NEP, IDE, or ACE. Antioxidant capacity in AD is closely related to the level of insoluble Aβ and increases with pathological progression of the disease. Increased β-secretase activity associated with oxidative stress is likely to contribute to the accumulation of Aβ and this, in turn, to induce antioxidant capacity.

No abstract

The synthesis of lipid from ~4C-glucose and aH-Manine was measured from rat liver slices using a micro-superfusion technique that allows continuous monitoring of the perifusate output. Increase in substrate glucose results in prompt elevation of fatty acid synthesis. Insulin addition also produced an increased 14C incorporation into lipid. The effects were independent. Both these factors may be active in the hypertriglyceridaemia of high carbohydrate intake or diabetes. Augmentation de la synth~se des ~ipides par des coupes de foie dans un syst~me de superfusion apr~s dldvation de la concentration de glucose ou d'insuline Rdsumd. La synth@se des lipides ~ partir du ~aC-glucose et de la 3H-alanine fur mesur6e dans des tranehes de foie de rat, en utilisant une technique de microsuperfusion qui permettait l'enregistrement eontinu du ddbit du pdrifusat. L'addition de glucose amena une hausse immddiate de la synthbse d'acide gras. L'addition d'insuline provoqua de m6me une augmentation de l'incorporation de laC dans les lipides. Les effets dtaient inddpendants. Ces deux facteurs pourraient 6tre actifs dans l'hypertriglycdriddmie aprbs l'absorption importante d'hydrates de earbone ou dans l'6tat diab6tique. Erh6hte .Lipidsynthese von Leberschnitte~ in einem Superfusionssystem naeh erhOhten Konzentrationen von Glucose und Insulin Zusammenfassung. An Rattenleberschnitten wurde mit einer Mikrosuperfusionstechnik, die eine dauernde Kontrolle des Perfusatflusses erlaubt, die Lipidsynthese aus l~C-Glucose und SH-Alanin gemessen. Eine Erh6hung des Glucosesubstrats fiihrte zu einer sofortigen Steigerung der Fetts/iuresynthese. Zugegebenes Insulin erzeugte ebenfalls einen erhShten laC-Einbau in die Lipide. Beide Effekte waren unabh~ngig.-Diese beiden Faktoren kSnnen in der I-Iypertriglyeerin/~mie naeh hoher Kohlenhydrataufnahme oder beim Diabetes wirksam sein.