Sustained Release of Phenytoin Following the Oral Administration of Phenytoin Sodium/Ethylcellulose Microcapsules in Human Subjects and Rabbits.

The present study analysed the effects of the flavanol ( − )-epicatechin in rats after chronic inhibition of NO synthesis with NG-nitro-l-arginine methyl ester (l-NAME), at doses equivalent to those achieved in the studies involving human subjects. Wistar rats were randomly divided into four groups: (1) control-vehicle, (2) l-NAME, (3) l-NAME-epicatechin 2 (l-NAME-Epi 2) and (4) l-NAME-epicatechin 10 (l-NAME-Epi 10). Rats were daily given by oral administration for 4 weeks: vehicle, ( − )-epicatechin 2 or 10 mg/kg. Animals in the l-NAME groups daily received l-NAME 75 mg/100 ml in drinking-water. The evolution in systolic blood pressure and heart rate, and morphological and plasma variables, proteinuria, vascular superoxide, reactivity and protein expression at the end of the experiment were analysed. Chronic ( − )-epicatechin treatment did not modify the development of hypertension and only weakly affected the endothelial dysfunction induced by l-NAME but prevented the cardiac hypertrophy, the renal parenchyma and vascular lesions and proteinuria, and blunted the prostanoid-mediated enhanced endothelium-dependent vasoconstrictor responses and the cyclo-oxygenase-2 and endothelial NO synthase (eNOS) up-regulation. Furthermore, ( − )-epicatechin also increased Akt and eNOS phosphorylation and prevented the l-NAME-induced increase in systemic (plasma malonyldialdehyde and urinary 8-iso-PGF2α) and vascular (dihydroethidium staining, NADPH oxidase activity and p22phox up-regulation) oxidative stress, proinflammatory status (intercellular adhesion molecule-1, IL-1β and TNFα up-regulation) and extracellular-signal-regulated kinase 1/2 phosphorylation. The present study shows for the first time that chronic oral administration of ( − )-epicatechin does not improve hypertension but reduced pro-atherogenic pathways such as oxidative stress and proinflammatory status of the vascular wall induced by blockade of NO production.

Download Full-text

Oral administration of radioactive sulfate to measure extracellular fluid space in man

Journal of Applied Physiology ◽

10.1152/jappl.1976.40.4.648 ◽

1976 ◽

Vol 40 (4) ◽

pp. 648-650 ◽

Cited By ~ 29

Author(s):

J. H. Bauer

Keyword(s):

Oral Administration ◽

Human Subjects ◽

Extracellular Fluid ◽

Mean Difference ◽

Routes Of Administration ◽

Extracellular Fluid Space ◽

The Mean ◽

Kinetics Of ◽

Plasma Activity

Radioactive sulfate-35 (35S) was administered to eight human subjects intravenously and orally, to compare respective kinetics of distribution. Intravenously administered 35S attained equilibration within 60–90 min. Orally administered 35S attained equilibration within 60–105 min and thereafter achieved plasma activity equivalent to the intravenously administered tracer. Eighty percent or greater of the 35S dose was recovered in the 24-h urine, following either intravenous or oral administration. The mean extracellular fluid space demonstrated less than 9% mean difference between routes of administration. It is concluded that 35S is completely absorbed at tracer doses, and may be administered orally as a reliable substitute for intravenously administered 35S for measuring extracellular fluid space.

Download Full-text