Фармакокинетика теофиллина в ночное время при однократном приеме: сравнение трех препаратов в одинаковых условиях

We have carried out a stead y state pharmacokynetic comparison of three different theophylline preparations in nine healthy volunteers using a once a day dosage schedule of 600 mg theophylline given before bedtime for four days. The preparations tested were Retafyllin 200 mg depot tablet (R), Theo-Dur 200 mg depot tablet (T) and Uniphyllin 200 mg tablet (U). All preparations in steady state reached the serum level of 8.9— 10.2 microg/ml after a single evening dose of theophylline 600 mg. The pharmacokinetic profile of these slow release theophylline preparations was such that there is no risk of exceeding the therapeutic range even after a rather high evening dose. Individual variation was also observed in the present study but nobody exceeded the therapeutic range. The pharmacokinetic profiles of R and U were quite similar and they seemed to have suitable pharmacokinetic properties for once a day dosage, and they showed a more sustained action than T. Only minimal gastrointestinal side effects were reported during this study.

Ecological and genetic analysis of copper and streptomycin resistance in Pseudomonas syringae pv. syringae

Strains of Pseudomonas syringae pv. syringae resistant to copper, streptomycin, or both compounds were recovered from symptomless and diseased tissue of four woody hosts in three nurseries in Oklahoma. In strains resistant to copper and streptomycin (Cu^r Sm^r), resistance to both compounds was cotransferred with a single plasmid which was either 68, 190, or 220 kilobase pairs (kb). All Cu^s Sm^r strains contained a 68-kb conjugative plasmid. Cu^r Sm^s, strains contained one plasmid which varied in size from 60 to 73 kb. All conjugative plasmids which transferred streptomycin resistance contained sequences homologous to the strA and strB Sm^r genes from the broad-host-range plasmid RSF1010. The Sm^r determinant was subsequently cloned from a 68-kb Cu^r Sm^r plasmid designated pPSR1. A restriction map detailing the organization of the homologous Sm^r genes from pPSR1 and RSF1010 and cloned Sm^r genes from P. syringae pv. papulans and Xanthomonas campestris pv. vesicatoria revealed the conservation of all sites studied. The Cu^r genes cloned from P. syringae pv. tomato PT23 and X. campestris pv. vesicatoria XV10 did not hybridize to the Cu^r plasmids identified in the present study, indicating that copper resistance in these P. syringae pv. syringae strains may be conferred by a distinct genetic determinant.Peer reviewedPlant Patholog

ATP release from human airway epithelial cells studied using a capillary cell culture system

Epithelial release of adenosine triphosphate (ATP), an important autocrine and paracrine signalling molecule, is acutely mechanosensitive and therefore difficult to study. We describe here a novel preparation that minimizes mechanical and metabolic perturbations, and use it to examine ATP secretion by epithelial cells. The Calu-3 cell line derived from human airway sub-mucosal glands was cultured in a hollow fibre bioreactor on porous capillaries that were perfused by a re-circulating medium pump. Cells became polarized and cultures were stable for > 5 months, as evidenced by microscopy and lactate production (≈250 μg (108 cells)−1 day−1). Elevating apical flow rate 5-fold increased ATP secretion from ≈200 to 6618 fmol min−1. Reducing apical osmolarity by 25–43 % also increased ATP secretion, which then declined spontaneously to a plateau rate that persisted as long as hypotonic perfusion was maintained. Release deactivated rapidly after shear and osmotic stresses were terminated, and was not associated with detectable cell lysis. Lowering apical [Ca2+] to increase connexin hemichannel permeability also stimulated ATP release and increased secretion during both hyposmotic and shear stress; however, the connexin 43 blocker flufenamic acid inhibited shear-induced ATP release only in low-Ca2+ solution, and therefore another secretory pathway may operate with physiological (i.e. mm) calcium. Regardless of the mechanism, the present results quantify ATP responses to mechanical and osmotic stimuli and demonstrate the usefulness of capillary cultures for studying epithelial secretion