High-speed impact test using an inertial mass and an optical interferometer.

A high-speed impact testing method for evaluating mechanical properties of materials is proposed using an inertial mass and a dual beat-frequencies laser Doppler interferometer (DB-LDI). In this method, an inertial mass levitated using an aerostatic linear bearing is made to collide with the material being tested at a high initial velocity. During the collision, the velocity of the mass, which is even higher than the critical velocity (±0.56 m/s) defined by the frequency difference of the Zeeman laser, is accurately measured using the DB-LDI. The position, acceleration, and impact force of the mass are calculated from the measured velocity. Using the proposed method, the mechanical properties of a visco-elastic material under a high-speed impact loading condition can be accurately evaluated.

Oral mucosal bioadhesive tablets of pectin and HPMC: in vitro and in vivo evaluation.

The potential of tablets containing 1:4, 1:1 and 4:1 weight ratios of pectin and hydroxypropyl methylcellulose (HPMC) for the sustained release of diltiazem by sublingual administration has been investigated. Measurements of maximum adhesive force to rat peritoneal membrane indicated a satisfactory bioadhesive strength. An in vitro sustained release of diltiazem over 5 h was achieved with bilayer tablets composed of a drug-free ethylcellulose layer in addition to the pectin/HPMC layer containing drug. Plasma concentration-time curves obtained following sublingual administration to rabbits of single and bilayer tablets with 1:1 weight ratios of pectin and HPMC showed evidence of sustained release of diltiazem. Bioavailability of diltiazem was 2.5 times that achieved by oral administration for single layer tablets and 1.8 times for the bilayered tablets.

A tightly associated serine/threonine protein kinase regulates phosphoinositide 3-kinase activity.

We identified a serine/threonine protein kinase that is associated with and phosphorylates phosphoinositide 3-kinase (PtdIns 3-kinase). The serine kinase phosphorylates both the 85- and 110-kDa subunits of PtdIns 3-kinase and purifies with it from rat liver and immunoprecipitates with antibodies raised to the 85-kDa subunit. Tryptic phosphopeptide maps indicate that p85 from polyomavirus middle T-transformed cells is phosphorylated in vivo at three sites phosphorylated in vitro by the associated serine kinase. The 85-kDa subunit of PtdIns 3-kinase is phosphorylated in vitro on serine at a stoichiometry of approximately 1 mol of phosphate per mol of p85. This phosphorylation results in a three- to sevenfold decrease in PtdIns 3-kinase activity. Dephosphorylation with protein phosphatase 2A reverses the inhibition. This suggests that the association of protein phosphatase 2A with middle T antigen may function to activate PtdIns 3-kinase.

Pharmaceutical application of biomedical polymers. XXIX. Preliminary study on film dosage form prepared from chitosan for oral drug delivery.

The potential of chitosan films containing diazepam as an oral drug delivery was investigated in rabbits. The results indicated that a film composed of a 1:0.5 drug-chitosan mixture might be an effective dosage form that is equivalent to the commercial tablet dosage forms. The ability of chitosan to form films may permit its use in the formulation of film dosage forms, as an alternative to pharmaceutical tablets.

Sustained release of indomethacin from chitosan granules in beagle dogs.

The potential of chitosan granules as an oral sustained-release dosage form of indomethacin has been compared with conventional capsules in beagle dogs. When a commercial capsule was administered orally, the plasma concentrations reached the maximum level in 30 min. The granules did not give a sharp peak to the plasma concentration, but produced a sustained plateau of the drug. This may be due to the slow rate of release and a longer residence time in the stomach. Thus, in terms of reducing the peak in plasma concentration and maintenance of drug concentration in plasma, the chitosan granules were superior to conventional capsules.

Purification and characterization of phosphatidylinositol kinase from porcine liver microsomes.

Phosphatidylinositol kinase was solubilized and purified from porcine liver microsomes to apparent homogeneity. The purification procedure includes: solubilization of microsomes by 2% Triton X-100, ammonium sulfate precipitation (20-35% saturation), Reactive blue agarose chromatography, DEAE-Sephacel chromatography and two consecutive hydroxyapatite chromatographies. A total of 4900-fold purification with 8% recovery of enzyme activity was achieved. The molecular weight of the enzyme as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis was 55000. The enzyme is stimulated in a decreasing order by Mg2+, Fe2+, Mn2+, Fe3+ and Co2+. Ca2+ inhibited Mg2+-stimulated activity with an I50 of 0.4 mM. Apparent Km values for phosphatidylinositol and ATP are 120 and 60 microM, respectively. The enzyme is inhibited by adenosine (I50 = 70 microM), ADP (I50 = 120 microM) and quercetin (I50 = 100 microM). The enzyme is also sensitive to sulfhydryl inhibitors. Using the purified enzyme as an immunogen, we have successfully prepared antibodies for phosphatidylinositol kinase in rabbits. The antibodies appear to recognize an antigen of Mr 55000 on SDS-polyacrylamide gel electrophoresis from various porcine tissues in Western blot analysis.

Antitumour effect of fibrinogen microspheres containing doxorubicin on Ehrlich ascites carcinoma.

The antitumour activity of fibrinogen microspheres containing doxorubicin has been evaluated against Ehrlich ascites carcinoma in mice in terms of changes in body weight and survival. Tumour cell injections were made on day 0 and microsphere injections on day 1, both intraperitoneally. The suppressive effect of the drug-containing microspheres on increase in body weight was higher than that of the free drug, and tumour-bearing mice given the microspheres lived longer than those given the free drug.