Publications (52) View all
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Article: Novel Collagen/Gelatin Scaffold with Sustained Release of Basic Fibroblast Growth Factor: Clinical trial for chronic skin ulcers.
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ABSTRACT: Chronic skin ulcers such as diabetic ulcers and venous leg ulcers are increasing and are a costly problem in healthcare. We have developed a novel artificial dermis, collagen/gelatin sponge (CGS), which is capable of the sustained release of basic fibroblast growth factor (bFGF) for more than 10 days. The objective of this study was to investigate the safety and efficacy of CGS impregnated with bFGF in the treatment of chronic skin ulcers. Patients with chronic skin ulcers that had not healed in at least four weeks were treated with CGS impregnated with bFGF at 7 μg/cm2 or 14 μg/cm2 after debridement, and the wound bed improvement was assessed 14 days after application. Wound bed improvement was defined as a granulated and epithelialized area on Day 14 with a proportion to the baseline wound area after debridement of 50% or higher. The wound area, the wound area on Day 14, and the granulation area on Day 14 were independently measured by blinded reviewers in a central review using digital images of wounds taken with a calibrator. Patients were followed up until 28 days after application to observe the adverse reactions related to the application of CGS. From May 2010 to June 2011, 17 patients were enrolled and, in 16 patients, the wound bed improved. Among the randomized patients in step 2, no significant difference was seen between the low-dose group and the high-dose group. No serious adverse reactions were observed. Adverse reactions with a clear causal relationship to the study treatment were mild and recovered from quickly. This study is the first-in-man clinical trial of CGS and showed the safety and efficacy of CGS impregnated with bFGF in the treatment of chronic skin ulcers. This combination therapy could be a promising therapy for chronic skin ulcers.Tissue Engineering Part A 03/2013; · 4.64 Impact Factor -
Article: Ezetimibe ameliorates early diabetic nephropathy in db/db mice.
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ABSTRACT: Lipid-lowering medications have been suggested to have a potential benefit in the treatment of chronic kidney disease (CKD) such as diabetic nephropathy. Although ezetimibe has been widely used to lower serum cholesterol levels, the effect of this drug on diabetic nephropathy remains unclear. In the present study, therefore, we examined the protective effect of ezetimibe on diabetic nephropathy in db/db mice. Db/db mice were fed a standard diet with 0.01% (w/w) of ezetimibe for 8 weeks from 8 weeks of age. Treatment with ezetimibe did not affect food intake, body weight gain, adiposity, or blood pressure in db/db mice. Ezetimibe also had no effect on glucose metabolism such as fasting plasma glucose and insulin; however, it markedly reduced plasma lipid levels and hepatic lipid contents and reduced the urinary excretion of albumin by 50% in db/db mice, suggesting the effect of ezetimibe on diabetic nephropathy. Furthermore, ezetimibe improved glomerular hypertrophy. Although ezetimibe had no effect on oxidative stress measured by urinary 8-OHdG in db/db mice, the plasma adiponectin level was normalized, and the expression of adiponectin receptor 1 in the kidney was increased by ezetimibe treatment. Our data suggest that ezetimibe can improve early diabetic nephropathy through its hypolipidemic effect, and the amelioration of adiponectin resistance may also be responsible for the renoprotective effect of ezetimibe as its underlying mechanism.Journal of atherosclerosis and thrombosis 04/2012; 19(7):608-18. · 2.69 Impact Factor -
Article: An exploratory clinical trial for combination wound therapy with a novel medical matrix and fibroblast growth factor in patients with chronic skin ulcers: a study protocol.
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ABSTRACT: Chronic skin ulcers such as diabetic ulcers and venous leg ulcers are increasing and are a costly problem in health care. We have developed a novel artificial dermis, collagen/gelatin sponge (CGS), that is capable of the sustained release of basic fibroblast growth factor (bFGF) for more than 10 days. The objective of this study was to investigate the safety and efficacy of CGS impregnated with bFGF in the treatment of chronic skin ulcers. Methods/ Seventeen patients (≥ 20 years of age) with chronic skin ulcers that have not healed by conventional therapy for at least 4 weeks are being recruited. Patients will be applied with CGS impregnated with bFGF of 7 μg/cm(2) or 14 μg/cm(2) after debridement, and the wound bed improvement will be assessed 14 days after application. "Wound bed improvement" is defined as a granulated and epithelialized area on Day 14 in proportion to the baseline wound area after debridement of 50% or higher. Patients will be followed up until 28 days after application to observe the adverse events related to the application of CGS. This study has been designed to address the safety and efficacy of CGS impregnated with bFGF. If successful, this intervention may be an alternative to bioengineered skin substitutes and lead to substantial and important changes in the management of chronic skin ulcers such as diabetic ulcers and venous ulcers.American Journal of Translational Research 01/2012; 4(1):52-9. -
Article: Atherosclerotic plaques induced by marble-burying behavior are stabilized by exercise training in experimental atherosclerosis.
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ABSTRACT: We assessed the hypothesis whether behavioral stress may affect the development of atherosclerosis and whether regular exercise training may influence the composition of atherosclerotic plaques in apolipoprotein (apo) E-deficient mice. Atherosclerosis was induced in apo E-deficient mice fed a high fat diet. Exercise training (45 min swimming, 3 times/week) was conducted, and behavioral stress was provoked by glass marble-burying procedure. Mice were treated with marble-burying, marble-burying behavior plus swimming training, and swimming alone over 8 weeks. Exercise training decreased the atherosclerotic lesions, but marble-burying behavior increased the lesions. The plaques containing macrophage accumulation with intercellular adhesion molecule-1 (ICAM-1) expression associated with reduced collagen contents were induced in the mice treated with marble-burying. However, ICAM-1 expression was suppressed and collagen contents were reversed in the mice that received marble-burying behavior plus exercise training. In addition, exercise alone and concomitant exercise training reduced the superoxide production in aortic walls, shown by dihydroethidium staining, compared with that in mice with marble-burying behavior alone. There were no significant differences in the serum lipids profiles among the groups. Behavioral stress increased the atherosclerotic lesions and induced the adhesion molecule expression with superoxide production on the lesions in apo E-deficient mice. Exercise training may stabilize plaque lesions induced by marble-burying behavior in this animal model.International journal of cardiology 09/2011; 151(3):284-9. · 7.08 Impact Factor -
Article: Differential effect of statins on diabetic nephropathy in db/db mice.
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ABSTRACT: Recent studies suggest a potential benefit of the lipid-lowering medication in the treatment of chronic kidney disease (CKD) such as diabetic nephropathy. Although statins have been widely used to lower serum cholesterol levels, the effect of these drugs on diabetic nephropathy has not been fully elucidated. In the present study, therefore, we addressed the role of different kinds of statins on diabetic nephropathy in db/db mice. Mice were fed with a standard diet with 0.005% (w/w) of pitavastatin, rosuvastatin, and pravastatin for 8 weeks starting from 8 weeks of age. The treatment with statins did not affect the food intake, body weight gain, adiposity, or blood pressure in db/db mice. Treatment with statins also had no effect on plasma lipid levels. In terms of the effect on albuminuria, pitavastatin and rosuvastatin reduced the urinary excretion of albumin by 60 and 40%, respectively, but not pravastatin, suggesting the effect of these two drugs on diabetic nephropathy. Furthermore, pitavastatin and rosuvastatin improved glomerular hypertrophy. All statins treatment improved insulin resistance. In addition, rosuvastatin and pravastatin treatment reduced oxidative stress measured by urinary 8-OHdG level, whereas the statins had no effect on the inflammatory response in the kidney of db/db mice. These results are not consistent with the renoprotective effect of statins. In conclusion, our data suggest that pitavastatin and rosuvastatin can improve diabetic nephropathy through the suppression of glomerular hypertrophy, independent of lipid-lowering or anti-oxidative effects.International Journal of Molecular Medicine 08/2011; 28(5):683-7. · 1.98 Impact Factor
