Abstract. Simvastatin, a cholesterol synthesis inhibitor, enhances BMP2 expression in osteoblasts. The purpose of the present study was to examine whether simvastatin stimulates bone regeneration when combined with calcium sulfate as a carrier. Critical-sized bone defects in rat calvaria were treated with calcium sulfate or with combination of 1 mg simvastatin and calcium sulfate. In the combination group, although the least amount of bone formation with intense soft tissue inflammation was observed at 2 and 4 weeks, remarkable bone formation was evident at 8 weeks. Conclusively, the combination of simvastatin and calcium sulfate stimulated bone regeneration in spite of the inflammatory response.

When combined with alpha-TCP particles, 0.1 mg simvastatin is the optimal dose for stimulation of the maximum bone regeneration in rat calvarial defects without inducing inflammation and it could be applied as an effective bone graft material.

Although RF did not correlate with histological implant-bone contact, the present results demonstrated that a connection between the implant and bone at the neck region of the implant affects RF the most effectively, further suggesting the superiority of RFA in the process of implant treatment and the follow-up. The present results could explain the discrepancy between RFA and other parameters of implant stability.

Chronic injection of an anti-c-KIT receptor tyrosine kinase monoclonal antibody (ACK2) results in the disruption of the normal motility patterns of young BALB/c mice intestine. This effect is accompanied by a drastic decrease in the number of intestinal c-kit-expressing (c-kit+) cells when studied immunohistochemically with the fluorescence-labelled antibody. In order to clarify the mechanism underlying the ACK2 action and the physiological roles of intestinal c-kit+ cells, we studied the excitability of intestinal c-kit+ cells in primary culture by use of the nystatin perforated-patch-clamp technique. Under voltage-clamp at -40 mV, the majority of c-kit+ cells tested (59/70) elicited rhythmic current waves with an amplitude and frequency of 263 +/- 24 pA and 2.30 +/- 0.25 cycles/min (mean +/- SEM), respectively. Intracellular perfusion of the c-kit+ cells with ethylenebis (okonitrilo) tetraacetate (EGTA) as well as a nominally Ca(2+)-free external solution or low holding voltage (< -60 mV) prevented the rhythmic current. The reversal potential of the rhythmic current was close to the equilibrium potential for Cl-(ECl). Moreover the rhythmic current was depressed by a Cl- channel blocker, 4-acetoamido-4-isothiocyanat-ostilbene-2,2'-disulphoni c acid (SITS). The smooth muscle cells freshly dissociated from the same intestinal specimen revealed a Ca(2+)-activated K+ current, as has been described in a variety of smooth muscle cells. Cultured smooth muscle cells from the ileum preparation lacked neither the Ca(2+)-activated K+ nor rhythmic Cl- currents. Smooth muscle cells freshly dissociated from the same ileum preparation and those in culture showed no immunoreactivity with the labelled ACK2, which was consistent with our previous in situ study. Results provided direct evidence that the intestinal c-kit+ cells, but not the smooth muscle cells, possess a rhythmic Cl- current oscillation, suggesting their participation in pacemaker activity for the peristaltic gut movement.

The aim of this study is to estimate the increase of bone-inductive potency by human demineralized dentin matrix (DDM) with recombinant human bone morphogenetic protein-2 (BMP-2). Human teeth were crushed, completely demineralized in 0.6M HCl, and freeze-dried. The tooth-derived material is called DDM. The shape of DDM was a particle type and its size varied from 0.4 to 0.8 mm. The BMP-2 dose-dependent study in the rat subcutaneous tissues demonstrated that the volume of induced bone and marrow increased at a dose-dependent manner. The time-course study of bone induction by the BMP-2 (5.0 μg)/DDM (70 mg) was estimated histologically and biochemically. Histological findings showed that the BMP-2/DDM increased bone and marrow sequentially between the DDM particles. Calcium content in the BMP-2/DDM-induced tissue was compatible to the histological findings. ALP activity in the BMP-2/DDM showed a maximal value at 1 week and gradually decreased. The morphometric analysis demonstrated that the BMP-2/DDM showed 66.9%, 79.0% in the volume of bone and marrow, and 32.4%, 21.0% in that of DDM at 8, 32 weeks, respectively. We confirmed that BMP-2 significantly accelerated bone formation in the acid-insoluble human-dentin carriers. These results indicate that human DDM should be an effective carrier for delivering BMP-2 and superior scaffold for bone-forming cells.

ABSTRACT:In the proximal tubules of rat (r) kidney, the polyspecific organic cation transporters (OCTs), rOCT1 and rOCT2, mediate the basolateral uptake of various organic cations, including many drugs, toxins, and endogenous compounds, and the apical type of H ؉ / organic cation antiporter, rat multidrug and toxin extrusion 1 (rMATE1), mediate the efflux of organic cations. Renal clearances of H 2 receptor antagonists, including famotidine, were reported to be decreased in patients with kidney disease. Therefore, acute kidney injury (AKI) could influence renal excretion and disposition of organic cations accompanied by the regulation of organic cation transporters. The aim of this study was to investigate the pharmacokinetic alteration of cationic drugs and the expression of tubular organic cation transporters, rOCT1, rOCT2, and rMATE1, in ischemia/reperfusion (I/R)-induced AKI rats. I/R-induced AKI increased the plasma concentration of i.v. administrated famotidine, a substrate for rOCT1 and rOCT2, or tetraethylammonium (TEA), a substrate for rOCT1, rOCT2, and rMATE1. The areas under the plasma concentration curves for famotidine and TEA were 2-and 6-fold higher in I/R rats than in sham-operated rats, respectively. The accumulation of TEA into renal slices was significantly decreased, suggesting that organic cation transport activity at the basolateral membranes was reduced in I/R rat kidney. The protein expressions of basolateral rOCT2 and luminal rMATE1 were down-regulated in I/R rat kidneys. These data suggest that the urinary secretion of cationic drugs via epithelial organic cation transporters is decreased in AKI.

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The purpose of this study was to determine whether bone augmentation could be obtained by the composite of recombinant human bone morphogenetic protein-2 (rhBMP-2) and bioabsorbable atelocollagen when the periosteum was resected, and to compare the efficacy of the rhBMP-2/collagen implant and the collagen alone implant. The onlay implant was inserted into the space between the elevated galea aponeurotica and the skull without the periosteum of 10-month-old rats. The rhBMP-2/collagen implant resulted in osteoblasts differentiation under the galea at 1 week and active bone formation without a prior formation of cartilage. At 4 weeks, the bony trabeculae were interconnected and connected directly with the compact bone of the skull. Histomorphometric analysis at 4 weeks demonstrated that the rhBMP-2/collagen implant showed 92.5% in the volume of bone tissue, whereas the collagen alone showed 0%. The implanted collagen was gradually replaced by bone tissue in the presence of rhBMP-2. Our present results indicate that rhBMP-2 stimulates undifferentiated mesenchymal cells in the galea overlying the implant to proliferate and differentiate directly into osteoblasts on the carrier collagen fibers. The collagen matrix was stably placed on the skull and suitable as a substitute for rhBMP-2. The rhBMP-2/collagen onlay implant might be clinically applicable for bone augmentation even under the condition without the periosteum.