The pharmacokinetics of multiple-dose linezolid were determined following administration of five 600-mg oral doses given every 12 h to each of six healthy male volunteers. Concentrations of the drug were determined in plasma and inflammatory blister fluid using high-pressure liquid chromatography. A mean peak concentration in plasma of 18.3 g/ml (standard deviation [SD], 6.0) was attained at a mean time of 0.7 h (SD, 0.3) after the final dose. The penetration into the inflammatory fluid was 104% (SD, 20.7). A mean peak concentration of 16.4 g/ml (SD, 10.6) was attained in the inflammatory fluid at 3 h (SD, 0.6) after the final dose. The elimination half-life from serum and inflammatory fluid was 4.9 (SD, 1.8) and 5.7 (SD, 1.7) h, respectively. The area under the concentration-time curve in plasma and blister fluid was 140.3 (SD, 73.1) and 155.3 (SD, 80.1) g ⅐ h/ml, respectively. These data suggest that linezolid has good tissue penetration, and we can predict that it will be successful in the treatment of a variety of gram-positive infections.Linezolid belongs to a new class of antibiotics, the oxazolidinones. It acts by selectively inhibiting the initiation of bacterial protein synthesis and has been shown to possess in vitro and in vivo activity against gram-positive organisms, including Streptococcus pneumoniae strains that are resistant to penicillin, methicillin-resistant Staphylococcus aureus, Enterococcus faecalis, and Enterococcus faecium with phenotypes Van A, B, and C (2,6,9,11,13). The aim of this study was to assess the pharmacokinetics and tissue penetration of linezolid following multiple oral doses of 600 mg. A blister technique was used to assess tissue penetration since blister fluid mimics inflammatory exudate and hence is a model of likely pharmacokinetics at the site of infection (10). MATERIALS AND METHODSSubjects. Eight healthy volunteers, with a mean age of 29.6 years (standard deviation [SD], 8.7), a mean weight of 78.6 kg (SD, 7.1), and a mean height of 180.4 cm (SD, 14.1), gave written informed consent to participate in this study. One volunteer was unable to attend the actual study day due to febrile illness; therefore, only seven participants were studied. Exclusion criteria for the trial included any history of significant illness or atopy, recent participation in another drug trial, and use of prescription or nonprescription drugs (particularly monoamine oxidase inhibitors) within 14 or 7 days of the study, respectively. All volunteers underwent a full medical history, an examination and a full blood count, clotting, renal, and liver function tests, and urinalysis and a urine drugsof-abuse screen, all of which were normal. The hospital's ethics committee granted approval for this study.Drug administration. The volunteers were given one 600-mg linezolid tablet every 12 h for 2.5 days (a total of five doses). The first dose was given in the hospital with the physician present for the first hour. Doses two and three were self-administered by the volunteer at home. This was confirmed b...

Oxidative stress is an important element in the etiology of ischemic stroke. Lowbush blueberries (Vaccinium angustifolium Aiton) have a high antioxidant capacity and thus we determined whether consumption of lowbush blueberries would protect neurons from stroke-induced damage. Rats were fed AIN-93G diets containing 0 or 14.3% blueberries (g fresh weight/100 g feed) for 6 weeks. Stroke was then simulated by ligation of the left common carotid artery (ischemia), followed by hypoxia. One week later, plasma and urine were collected, and neuronal damage in the hippocampus was determined histologically. In control rats, hypoxia-ischemia resulted in 40 +/- 2% loss of neurons in the hippocampus of the left cerebral hemisphere, as compared to the right hemisphere. Rats on blueberry-supplemented diets lost only 17 +/- 2% of neurons in the ischemic hippocampus. Neuroprotection was observed in the CA1 and CA2 regions, but not CA3 region, of the hippocampus. The blueberry diet had no detectable effects on the plasma or urine oxygen radical absorbance capacity (ORAC) or plasma lipids. We conclude that consumption of lowbush blueberries by rats confers protection to the brain against damage from ischemia, suggesting that inclusion of blueberries in the diet may improve ischemic stroke outcomes.

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Twelve patients with vertebral fracture osteoporosis were recruited into a trial of treatment with hPTH 1-34 by daily injection for 1 year combined (from the 5th month) with an anti-resorptive agent (oestrogen, n = 9; nandrolone, n = 3). Treatment outcomes were monitored by biochemical and radiotracer measurements together with histomorphometry of transiliac biopsies before and at the end of treatment following double in vivo pre-labelling with demethylchlortetracycline. Indices of whole body bone formation, obtained from the analysis of 85Sr data, showed substantial increases (P less than 0.005) for all three indices measured) while biochemical (hydroxyproline) and kinetic measurements of bone resorption showed modest and equivocal changes only. As a result calcium balance improved. Gastrointestinal calcium absorption showed a tendency to improve, while urine calcium decreased; but these changes were statistically not significant except for radiocalcium absorption in the oestrogen treated subgroup. Histomorphometry revealed substantial increases in cancellous bone volume as reported previously with hPTH 1-34 given alone. However, iliac (as distinct from whole body) indices related to bone formation and resorption appeared to have returned towards pre-treatment values by the time of the second biopsy under the influence of the anti-resorptive agent given with the hPTH 1-34. It is confirmed that hPTH 1-34 therapy can increase iliac cancellous bone mass (as well as spinal cancellous bone mass as reported earlier) without a long-term increment in whole body bone resorption, providing the hPTH is combined with an anti-resorptive agent.