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Background. Drug-metabolizing capacity is generally reduced in the elderly. The purpose of this investigation was to study antipyrine clearance and metabolite excretion in old subjects of both sexes. Methods. Saliva clearance of antipyrine and the production clearances of antipyrine metabolites were studied in young and elderly volunteers of both sexes. Seventy-six elderly subjects (mean age 81 years) were compared with a group of 24 young subjects (mean age 29 years). Results. After oral administration, salivary antipyrine clearance declined with age in both males and females, whether or not this variable was corrected for weight, and antipyrine half-life was significantly prolonged in elderly groups of either sex. The percentage urinary excretion of the antipyrine metabolites (hydroxymethylantipyrine, HMA; norantipyrine, NORA; and 4-hydroxyantipyrine, OHA) was reduced at 48 h in the elderly compared to young subjects by 23%, 31%, and 10%, respectively, in males, and by 41%, 41%, and 24%, respectively, in females. The formation clearance of HMA was reduced by 47% in males and by 52% in females. NORA clearance declined by 42 and 56%, respectively, in males and females. A decrease of 30% in males and 44% in females was observed in OHA clearance. Conclusions. The findings suggest that aging leads to altered disposition of antipyrine in both males and females and that the main metabolic pathways of the compound are not different in the elderly.

This study aimed to investigate the effect of eccentric exercise on the expression of the different nitric oxide synthase (NOS) isoforms in rat deep vastus lateralis muscle. Twenty-four rats were allocated to four experimental groups: rested control group, acutely exercised group after an intermittent downhill protocol for 90 mm, acutely exercised group treated with pyrrolidine dithiocarbamate (100 mg/kg ip) for 24 and 1 h before the acute exercise bout, and acutely exercised group with a previous submaximal eccentric training of 8 wk. Acutely exercised rats showed increased levels of protein tyrosine nitration, NF-KB binding, and phospho-IKBα content. A significant increase was observed in mRNA level and protein content of neuronal NOS, inducible NOS, and endothelial NOS. The binding of NF-KB to the NOS isoform promoters, measured by a chromatin immunoprecipitation assay, was undetectable in rested rats, whereas it was evident in acutely exercised animals. All of these effects were partially abolished by pyrrolidine dithiocarbamate treatment and by training. In summary, our findings provide a direct link between the NF-KB signaling cascade and NOS expression in skeletal muscle following eccentric exercise and suggest a modulation of the expression of the three NOS isoforms by this transcription factor. [ABSTRACT FROM AUTHOR]

Objective: The effects of exercise intensity and age on oxidative stress induced by isometric exercise were investigated. Methods: Sixteen women (8 old: O, and 8 young: Y) performed two isometric protocols (30% and 50% maximal voluntary isometric contraction, MVIC). Results: Blood lactate changed significantly from immediately after to 10-min post-exercise in group Y at both intensities. Values differed significantly between Y and O groups only at 1-min post-exercise at 30% and 50% MVIC. No significant changes occurred in thiobarbituric reactants or reduced ascorbic acid. The oxidised/reduced glutathione ratio increased significantly from 1-min to 10-min post-exercise in both groups at 50% MVIC, and at 30% MVIC in group Y. Values increased significantly from 3-min to 10-min post-exercise in group O at 30% MVIC. Conclusions: Exercise intensity and age had no significant effect on oxidative stress response after wrist-flexor isometric exercise, and the glutathione system could provide a sufficient defence against oxidative damage. [ABSTRACT FROM AUTHOR]

The present study was aimed to investigate in elderly humans changes in NF-kappaB activation and in the expression of the inflammation-related genes inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6) induced in peripheral blood mononuclear cells (PBMC) by acute eccentric exercise and by submaximal eccentric training. Eleven subjects, aged 66-75 years, carried out 2 bouts of eccentric exercise separated by 8 weeks of training. Following the first bout, NF-kappaB activation, and protein level of p50/p65 subunits, phospho-IkappaBalpha and phospho-IKKalpha increased, while IkappaBalpha protein level was significantly reduced. This was accompanied by a significant increase in iNOS, COX-2 and IL-6 mRNA protein level and protein content. Changes were significantly attenuated following the second exercise bout. In conclusion, acute eccentric exercise increases NF-kappaB activation and the expression of several inflammation-related genes in PBMC from elderly individuals. Regular eccentric training might be an effective method of preventing undesirable inflammatory responses induced by eccentric exercise.

This study was aimed to investigate changes in blood markers of oxidative damage induced by short-term supramaximal anaerobic exercise and to determine whether oxidative stress was associated to activation of the redox-sensitive transcription factor nuclear factor-kappaB (NF-kappaB). Both a single Wingate test (WAnT) test and series of four WAnTs separated by 60 min rest intervals were carried out by eight professional cyclists. Leukocyte 8-OH-2-deoxyguanosine levels were significantly elevated 24 h after both exercise protocols. A significant decrease in blood reduced glutathione (GSH) concentration was observed immediately after and at 15, 60 and 120 min of the single WAnT, followed by a return to basal value after 24 h. This decrease was parallel to a significant increase of the oxidised/reduced glutathione (GSSG/GSH) ratio, to an activation of NF-kappaB and to a significant decrease in the protein level of its inhibitor IkappaB. GSH concentration and the GSSG/GSH ratio changed significantly for the first three of the WAnTs series and normalised thereafter. A significant activation of NF-kappaB and a decrease in the IkappaB protein level were also detected. We conclude that short-term supramaximal anaerobic exercise induces oxidative stress, as evidenced by non cumulative damage to macromolecules and changes in the glutathione status. Our data also indicate that high intensity anaerobic work gives rise to an activation of the transcription factor NF-kappaB accompanied by a degradation of IkappaB.