Prior treatment with vitamin K(2) significantly improves the efficacy of risedronate.

UNLABELLED: Prior 8-week treatment with menatetrenone, MK-4, followed by 8-week risedronate prevented the shortcomings of individual drugs and significantly increased the strength of ovariectomized ICR mouse femur compared to the ovariectomized (OVX) controls. Neither MK-4 following risedronate nor the concomitant administration may be recommended because they brought the least beneficial effect. INTRODUCTION: The objective of this study was to determine the best combinatory administration of risedronate at 0.25 mg/kg/day (R) with vitamin K(2) at approximately 100 microg MK-4/kg/day (K) to improve strength of osteoporotic mouse bone. METHODS: Thirteen-week-old ICR mice, ovariectomized at 9-week, were treated for 8 weeks with R, K, or R plus K (R/K), and then, either the treatment was withdrawn (WO) or switched to K or R in the case of R and K. After another 8 weeks, the mice were killed, and mechanical tests and analyses of femur properties by peripheral quantitative computed tomography, microfocus X-ray tube computed tomography, and confocal laser Raman microspectroscopy were carried out. RESULTS: The K to R femur turned out superior in parameters tested such as material properties, bone mineral density, BMC, trabecular structure, and geometry of the cortex. The increased cross-sectional moment of inertia, which occurred after K withdrawal, was prevented by risedronate in K to R. In addition to K to R, some properties of R to WO diaphysis and K to WO epiphysis were significantly better than OVX controls. CONCLUSION: Prior treatment with MK-4 followed by risedronate significantly increased femur strength in comparison to the OVX controls.

Unconventional critical behaviour in a quasi-two-dimensional organic conductor.

Changing the interactions between particles in an ensemble--by varying the temperature or pressure, for example--can lead to phase transitions whose critical behaviour depends on the collective nature of the many-body system. Despite the diversity of ingredients, which include atoms, molecules, electrons and their spins, the collective behaviour can be grouped into several families (called 'universality classes') represented by canonical spin models. One kind of transition, the Mott transition, occurs when the repulsive Coulomb interaction between electrons is increased, causing wave-like electrons to behave as particles. In two dimensions, the attractive behaviour responsible for the superconductivity in high-transition temperature copper oxide and organic compounds appears near the Mott transition, but the universality class to which two-dimensional, repulsive electronic systems belongs remains unknown. Here we present an observation of the critical phenomena at the pressure-induced Mott transition in a quasi-two-dimensional organic conductor using conductance measurements as a probe. We find that the Mott transition in two dimensions is not consistent with known universality classes, as the observed collective behaviour has previously not been seen. This peculiarity must be involved in any emergent behaviour near the Mott transition in two dimensions.

Role of Ca2+-sensitive protein kinase C in phenylephrine enhancement of Ca2+ sensitivity in rat tail artery.

We investigated the role of protein kinase C (PKC) isoforms on changes in sensitivity of contractile mechanisms to intracellular Ca(2+) (force /[Ca(2+)]i) by phenylephrine (0.1-100 microM) in rat tail arterial helical strips using simultaneous measurements of force and [Ca(2+)]i. Force/[Ca(2+)]Ii induced by phenylephrine was greater than that induced by 80 mM K+. Force/[Ca(2+)]i induced by phenylephrine in physiologic saline solution or low Ca(2+) solution was dependent on the agonist concentration. Removal of Ca(2+) completely abolished the phenylephrine-induced contraction. The PKC inhibitors staurosporine and calphostin C inhibited the increase in force/[Ca(2+)]i induced by phenylephrine to a much greater extent than that induced by 80 mM K+. LY379196, a specific PKCbeta inhibitor, did not inhibit the increase of calcium sensitivity due to phenylephrine. The classic PKC isoforms, alpha, betaI, and II not gamma were demonstrated in the artery by immunohistochemistry. These results suggest that in rat tail arterial smooth muscle, PKCalpha, and not beta or gamma, mediates the increase of changes in sensitivity of contractile mechanisms to intracellular Ca(2+) to high dose of alpha1 receptor stimulation (phenylephrine 100 microM) on nonphysiologic conditions.

In vitro and in vivo antibacterial activities of TAK-083, an agent for treatment of Helicobacter pylori infection.

The antibacterial activity of TAK-083 was tested against 54 clinical isolates of Helicobacter pylori and was compared with those of amoxicillin, clarithromycin, and metronidazole. The growth-inhibitory activity of TAK-083 was more potent than that of amoxicillin, clarithromycin, or metronidazole (the MICs at which 90% of the strains are inhibited were 0.031, 0.125, 64, and 8 microg/ml, respectively). The antibacterial activity of TAK-083 was highly selective against H. pylori; there was a >30-fold difference between the concentration of TAK-083 required to inhibit the growth of H. pylori and that required to inhibit the growth of common aerobic and anaerobic bacteria. Exposure of H. pylori strains to TAK-083 at the MIC or at a greater concentration resulted in an extensive loss of viability. When four H. pylori strains were successively subcultured in the medium containing subinhibitory concentrations of TAK-083, no significant change in the MICs of this compound was observed. TAK-083 strongly inhibited the formation of tryptophanyl-tRNA in H. pylori while exhibiting little effect on the same system in eukaryotes. TAK-083 was efficacious in the treatment of gastric infection caused by H. pylori in Mongolian gerbils. The results presented here indicate that TAK-083 is a promising candidate for the treatment of H. pylori infection.

Acute antihypertensive effects of calcium channel blockers are not affected by calcium supplementation in patients with essential hypertension.

The study was designed to investigate whether the acute antihypertensive effects of calcium channel blockers are affected by calcium supplementation in patients with essential hypertension. The antihypertensive effects of calcium channel blockers (oral manidipine or intravenous nicardipine) were studied before and during calcium supplementation (1200 mg/day for 8 weeks) in 30 hospitalized patients with essential hypertension. The averages of systolic and diastolic blood pressure during a 24-hour period were not decreased by calcium supplementation. The acute antihypertensive effects of the calcium channel blockers nicardipine (0.25, 0.5, 1.5, 2.0 micrograms/kg/min, intravenous infusion) or manidipine (20 mg, once a day, orally) were not enhanced by calcium supplementation. Thus, calcium channel blockers can be safely combined with calcium supplementation in terms of blood pressure.