Unique and reliable rat model for the assessment of cell therapy: bone union in the rat mandibular symphysis using bone marrow stromal cells

Many kinds of bone graft materials have been developed and reported to repair various bone defects. The defects are usually created by surgical resection of pre‐existing bone tissue. However, spontaneous healing of bone defects without implantation of materials could be seen, because bone tissue possesses inherent repairing property. The central portion of the lower jaw bone in many animals consists of fibrous tissue and is called the mandibular symphysis. It persists even in old animals and thus can be interpreted as a physiological bone gap or a non‐healing bone defect. We implanted calcium phosphate porous ceramics alone or composites of the ceramics and bone marrow stromal cells (BMSCs) into the bone defect (mandibular symphysis) to examine whether it could be filled with new bone tissue, resulting in bone union. Eight weeks after implantation, micro‐computed tomography (micro‐CT) and histological and biomechanical analyses demonstrated that bone union of the mandibles occurred in all rats with composites but in none of those with ceramics alone. These results showed that the rat mandibular symphysis is a unique bone defect site for the evaluation of bone graft materials. These analyses demonstrated that ceramics alone could not contribute to bone healing in the defect; however, supplementation with BMSCs drastically changed the properties of the ceramics (turning them into osteogenic ceramics), which completely healed the defect. As BMSCs can be culture‐expanded using small amounts of bone marrow, the use of the composites might have clinical significance for the reconstruction of various bone tissues, including facial bone. Copyright © 2012 John Wiley & Sons, Ltd.     

Three methods for evaluation of left atrial volume.

AIM: To compare and contrast 3 different echocardiographic methods used to measure left atrial (LA) volume: biplane area length (AL), biplane modified Simpson (SIMP), and prolate ellipse (PE) methods. METHODS AND RESULTS: A review of consecutive patients who presented to our outpatient echocardiography laboratory for a resting transthoracic study between April 2006 and May 2006 was performed. Echocardiograms were reexamined and LA volume measured using the AL, SIMP, and PE methods. Of 102 consecutive patients evaluated, 97 had a measure of LA volume using all 3 methods. A significant difference in the measurement of mean +/- SD LA volume was noted among the 3 different methods: 37 +/- 16 mL/m(2) for AL, 34 +/- 14 mL/m(2) for SIMP, and 27 +/- 12 mL/m(2) for PE. The PE method yielded routinely smaller values compared with either the AL or SIMP method (P < 0.001). Differences increased with increased LA volume. The SIMP method derived consistently smaller (<5 mL/m(2)) values than those of the AL method, consistent across the full range of LA volumes. CONCLUSION: Significant differences exist among these 3 commonly used methods for measuring LA volume. Standardization of the measurement of LA volume is recommended.     

The renin-angiotensin system is involved in the production of plasminogen activator inhibitor type 1 by cultured endothelial cells in response to chylomicron remnants.

Triglyceride-rich lipoproteins have been suggested to promote atherosclerosis. Plasminogen activator inhibitor type 1 (PAI-1) plays an important role in the events of cardiovascular pathophysiology. The renin-angiotensin system influences various vascular functions, including PAI-1 production. We examined whether or not chylomicron remnants increased PAI-1 mRNA and protein production in endothelial cells and whether or not an inhibition of the renin-angiotensin system interfered with this effect. Chylomicron remnants were isolated from functionally hepatectomized rats injected with chylomicrons. Human umbilical vein endothelial cell cultures (HUVECs) were incubated with chylomicron remnants with or without an angiotensin-converting enzyme inhibitor (temocaprilat), an angiotensin II receptor type 1 antagonist (RNH-6270), or an angiotensin II receptor type 2 antagonist (PD123319). Chylomicron remnants increased PAI-1 secretion in HUVECs (0.5 microg/ml; 128.3 +/- 6.1%, the mean +/- SEM) as well as angiotensin II (10 nmol/l; 130.7 +/- 9.5%) in 18 h, as compared with the controls, as well as stimulated PAI-1 mRNA expression to a maximum level at 4 h. Temocaprilat and RNH-6270, but not PD123319, attenuated all of these effects. Chylomicron remnants enhanced nuclear extract binding to a very low-density lipoprotein response element in the PAI-1 promoter region and activated nuclear factor-kappaB. Extracellular signal-regulated kinase (ERK 1/2) was phosphorylated in response to chylomicron remnants. These effects were inhibited by temocaprilat or RNH-6270. In conclusion, chylomicron remnants increased protein secretion and mRNA expression of PAI-1 in HUVECs. Inhibition of the renin-angiotensin system reduced this stimulation.     

Influence of bone parameters on peri-implant bone strain distribution in the posterior mandible

Objectives: The success rate of dental implants depends on the type of bone at the implant site. The purpose of the present study was to investigate the effects of the bone parameters at the implant-placement site on peri-implant bone strain distributions. Study Design: The morphologies and bone densities of seventy-five potential implant sites in the posterior mandible were measured using computed tomography (CT). Based on the CT data, we defined bone parameters (low and high in terms of cancellous-bone density and crestal-cortical bone density, and thin and thick in terms of crestal-cortical bone thickness), and we constructed finite-element models simulating the various bone types. A buccolingual oblique load of 200 N was applied to the top of the abutment. The von Mises equivalent (EQV) strains in the crestal-cortical bone and in the cancellous bone around the implant were calculated. Results: Cancellous-bone density greatly affected the maximum EQV strain regardless of the density and thickness of the crestal cortical-bone. The maximum EQV strains in the crestal cortical-bone and the cancellous bone in the low-density cancellous-bone models (of 150 Hounsfield units (HU) were 1.56 to 2.62-fold and 3.49 to 5.31-fold higher than those in the high-density cancellous-bone models (of 850 HU), respectively. The crestal cortical-bone density affected the maximum EQV strains in the crestal cortical-bone and in the cancellous bone in the low-density cancellous-bone models. The crestal cortical-bone thickness affected the maximum EQV strains in the cancellous bone and in the crestal cortical-bone in the low-density cancellous-bone models. Conclusions: Our results confirm the importance of bone types for the peri-implant bone strain distribution. Cancellous-bone density may be a critical factor for peri-implant bone strain. Key words:Dental implant, bone density, finite-element analysis.     

R-wave amplitude response to myocardial ischemia in hypertrophic cardiomyopathy

Background and Purpose

R-wave amplitude change during exercise has been reported to enhance diagnostic value for myocardial ischemia in coronary heart disease.

Methods

We summed up R-wave amplitude in all the 12 leads during exercise testing and correlated the results with regional myocardial ischemia or diffuse subendocardial ischemia as detected by scintigraphy in 49 patients with hypertrophic cardiomyopathy (HCM) and 16 controls.

Results

The sum of R-wave amplitude decreased during exercise in patients with HCM (mean, 12.4 mV to 11.7 mV, P < .01) as well as in controls (8.0 mV to 7.7 mV, P < .05). Percent changes in the sum of R-wave amplitude did not differ between 4 subgroups of patients with HCM: one having both regional and subendocardial ischemia, one only the former, one only the latter, and one neither of them (mean, 6.5%, 7.7%, 4.6%, and 5.1%; P = .79).

Conclusions

R-wave amplitude response to exercise failed to demonstrate myocardial ischemia in our patients with HCM.     

Improved survival rate by temperature control at compression sites in rat model of crush syndrome

Background

Crush syndrome (CS) has been reported in disasters, terrorist incidents, and accidents, and the clinical and pathologic picture has gradually been clarified. Few lethal and reproducible animal models of CS with use of a quantitative load are available. A new model is needed to investigate pathologic and therapeutic aspects of this injury.

Materials and methods

Using a device built from commercially available components, both hindlimbs of anesthetized rats were respectively compressed for 6 h using 3.6-kg blocks. The effects of trunk warming alone without compressed hindlimbs (Group A), non-warming at room temperature (Group B), whole-body warming including compressed hindlimbs (Group C), or warming of compressed hindlimbs alone (Group D) during compression were examined. Survival rates were compared and hematological and histologic analyses were performed at specific time points after compression release.

Results

Limb or whole-body warming significantly worsened the survival of rats. We found a much lower survival rate of 0%–10% in animals, in which the hindlimbs were warmed during compression (Groups C and D) at 12 h after compression release, compared with 90%–100% in animals without warming of the hindlimbs (Groups A and B). Groups C and D showed significantly enhanced hyperkalemia at ≥4 h after compression release and all blood samples from dead cases showed hyperkalemia (>10 mEq/L).

Conclusions

We developed a new lethal and reproducible rat CS model with a quantitative load. This study found that warming of compressed limbs worsened the survival rate and significantly enhanced hyperkalemia, apparently leading to cardiac arrest.