Papers - HATTORI Hidemi
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Nambu M., Ishihara M., Nakamura S., Mizuno H., Yanagibayashi S., Kanatani Y., Hattori H., Takase B., Ishizuka T., Kishimoto S., Amano Y., Yamamoto N., Azuma R., Kiyosawa T.
Wound Repair and Regeneration 15 ( 4 ) 505 - 510 2007.7
Language：English Publishing type：Research paper (scientific journal) Publisher：Wound Repair and Regeneration
The aim of this study was to evaluate the potential accelerating effects of an adipose tissue-derived stromal cells (ATSC)-containing atelocollagen matrix with silicone membrane (ACMS) for repairing mitomycin C-treated healing-impaired wounds. Mitomycin C was applied to full-thickness skin incisions in this study to create a healing-impaired wound model in rat. After thoroughly washing out the mitomycin C from the wound, ACMS alone or ATSC-containing ACMS was applied to the wounds. Histological sections of the wounds were then prepared at indicated time periods after the treatments. These results indicated significantly advanced granulation tissue and capillary formations in the healing-impaired wounds treated with ATSC-containing ACMS compared with those treated with ACMS alone. Thus, this study suggested that transplantation of inbred ATSC-containing ACMS is effective for repairing healing-impaired wounds. © 2007 by the Wound Healing Society.
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異なった抗不整脈薬剤の心拍変動指標に及ぼす影響. Invited Reviewed
高瀬凡平, 野上弥志郎, 服部秀美, 石原雅之, 浜部晃, 原幹, 荒川宏, 楠原正俊, 大鈴文孝, 栗田明.
Therapeutic Research 28 ( 2 ) 208 - 10 2007.2
Language：Japanese Publishing type：Research paper (conference, symposium, etc.)
特発性心室性期外収縮患者14例(男9例・女5例)を無作為にdisopyramide投与7例(平均59歳:A群)とaprindine投与7例(平均61歳:B群)の2群に分け、24時間ホルター心電図により心拍変動(HRV)指標に及ぼす影響を比較した。HRV時系列解析指標としてmean間隔、SDANN、SD index、rMSSD、pNN50を、HRV周波数解析指標はtotal power、low frequency spectra(LF)、high frequency spectra(HF)、LF/HFを、また非線形HRV指標としてfractal component(β)(フラクタル成分)を求めた。両群とも4週間の投薬で心室性期外収縮頻度は有意に低下した。A群は時系列・周波数解析指標には有意な変化がなかったが、フラクタル成分は有意に減少した。B群では時系列解析指標のうちSD index、周波数解析指標ではtotal power、LFが有意に増加し、他の各指標も増加傾向を示した。フラクタル成分は有意な変化がなかった。HRV指標に対しaprindine投与は改善、disopyramide投与は悪化傾向を示すことが示唆された。
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Short QT症候群型心電図の頻度と予後に関する検討. Invited Reviewed
高瀬凡平, 服部秀美, 石原雅之, 浜部晃, 原幹, 荒川宏, 大鈴文孝, 永井知雄, 上畑昭実, 栗田明.
Therapeutic Research 28 ( 1 ) 91 - 4 2007.1
Language：Japanese Publishing type：Research paper (conference, symposium, etc.)
2002～2005年に防衛医大病院を受診し心電図がファイリングシステムに記録された55000例および1999～2000年に自衛隊仙台病院で行われた自衛隊循環器検診において記録された心電図4054例を対象に、Short QT症候群型心電図の頻度と同心電図を呈した症例の予後について検討した。心拍数が≦60bpmでQT<320msを「definite Short QT症候群型心電図」、心拍数にかかわらずQT<320msを「probable Short QT症候群型心電図」、心拍数にかかわらずQT>320msかつQT<350msを「possible Short QT症候群型心電図」と定義した。防衛医大病院においてdefinite Short QT症候群型心電図の頻度は0%、probable Short QT症候群型は0.01%、possible Short QT症候群型は0.24%であり、予後は2.5±1.3年の追跡調査で心臓性突然死は1例もなかった。自衛隊仙台病院においてdefinite Short QT症候群型は0%、probable Short QT症候群型は0.24%、possible Short QT症候群型は9.1%であり、4.2±0.8年の追跡調査で心臓性突然死はなかった。
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Effect of lateral body position on heart rate variability in patients with sleep apnea syndrome. Reviewed
Urabe T, Takase B, Tomiyama Y, Maeda Y, Ishikawa Y, Hattori H, Uehata A, Ishihara M.
Journal of Arrhythmia 23 ( 2 ) 140 - 5 2007
Language：English Publishing type：Research paper (scientific journal)
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Masuoka K., Asazuma T., Hattori H., Yoshihara Y., Sato M., Matsumura K., Matsui T., Takase B., Nemoto K., Ishihara M.
Journal of Biomedical Materials Research - Part B Applied Biomaterials 79 ( 1 ) 25 - 34 2006.10
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Biomedical Materials Research - Part B Applied Biomaterials
Adipose tissue derived stromal cells (ATSCs), which were isolated from adipose tissue of rabbit, have shown to possess multipotential, that is, they differentiate into osteoblasts and adipocytes in plate-culturing and into chondrocytes in an established aggregate culture using defined differentiation-inductive medium. The aim of this study was to evaluate the utility of ATSCs in tissue engineering procedures for repair of articular cartilage-defects using the atelocollagen honeycomb-shaped scaffold with a membrane sealing (ACHMS-scaffold). We intended to repair full-thickness articular cartilage defects in rabbit knees using autologously cultured ATSCs embedded in the ACHMS-scaffold. ATSCs were incubated within the ACHMS-scaffold to allow a high density and three-dimensional culture with control medium. An articular cartilage defect was created on the patellar groove of the femur, and the defect was filled with the ATSCs-containing ACHMS-scaffold, ACHMS-scaffold alone, or empty (control). Twelve weeks after the operation, the histological analyses showed that only the defects treated with the ATSCs-containing ACHMS-scaffold were filled with reparative hyaline cartilage, highly expressed Type II collagen. These results indicate that transplantation of autologous ATSCs-containing ACHMS-scaffold is effective in repairing articular cartilage defects. © 2006 Wiley Periodicals, Inc.
DOI： 10.1002/jbm.b.30507
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高血圧症例におけるアテノロールの運動負荷時の心拍変動指標および血圧反応に及ぼす影響 Reviewed
高瀬凡平, 阿部良行, 永田雅良, 服部秀美, 大鈴文孝, 栗田明, 石原雅之.
血圧 13 ( 10 ) 1137 - 42 2006.10
Language：Japanese Publishing type：Research paper (scientific journal)
血圧コントロールが不良な本態性高血圧症患者11例を対象にアテノール(25mg/日)投与を4週間行い、運動負荷中の血圧反応と心拍変動指数(HRV)を測定した。その結果、アテノールの4週間投与で、運動負荷時の血圧上昇は有意に抑制され、また、安静時および運動負荷時のHRVを有意に増加させることが確認された。
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Nakamura S., Ishihara M., Obara K., Masuoka K., Ishizuka T., Kanatani Y., Takase B., Matsui T., Hattori H., Sato T., Kariya Y., Maehara T.
Journal of Biomedical Materials Research - Part A 78 ( 2 ) 364 - 371 2006.8
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Biomedical Materials Research - Part A
We prepared a 6-O-desulfated (DS-) heparin (Hep) hydrogel as an excellent carrier for the controlled release of Hep-binding growth factors, such as fibroblast growth factor (FGF)-2. This material, which is partially derived from photoreactive groups, such as cinnamate, is easily crosslinked upon ultraviolet light (UV)-irradiation, resulting in a water-insoluble, viscous, and injectable hydrogel. In the present study, we examined the capacity of 6-O-DS-Hep hydrogel to immobilize FGF-2, as well as the controlled release of FGF-2 molecules from this hydrogel in vitro and in vivo. Only 10% of FGF-2 was gradually released from the FGF-2-containing 6-O-DS-Hep hydrogel (photocrosslinked 6-O-DS-Hep (4%; w/w) hydrogel containing 50 μg/mL FGF-2) into PBS (phosphate-buffered saline) within first 7 days. The 6-O-DS-Hep hydrogel in vitro maintained the original form through 1 weeks incubation in PBS, but it was gradually fragmented and could not maintain the original form by 2-3 week-washing. When the FGF-2-containing 6-O-DS-Hep hydrogel was subcutaneously injected into the back of rats, significant neovascularization and fibrous tissue formation were induced near the injected site from day 3 after the injection. And, the hydrogel had been biodegraded and completely disappeared from the injected sites in vivo within about 15-20 days after the injection. These findings indicate a controlled release of biologically active FGF-2 molecules together with fragmentation and biodegradation of 6-O-DS-Hep hydrogel and the subsequent induction of neovascularization in vivo. © 2006 Wiley Periodicals, Inc.
DOI： 10.1002/jbm.a.30688
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Noncontact vital sign monitoring system for isolation unit (casualty care system) Reviewed
Matsui T., Gotoh S., Arai I., Hattori H., Fujita M., Obara K., Masuoka K., Nakamura S., Takase B., Ishihara M., Kikuchi M.
Military Medicine 171 ( 7 ) 639 - 643 2006.7
Language：English Publishing type：Research paper (scientific journal) Publisher：Military Medicine
For measuring the vital signs of casualties inside an isolation unit, we developed a noncontact vital sign monitoring system using a microwave radar. The system was tested on eight healthy volunteers ranging in age from 30 to 48 years. The heart and respiratory rates derived by the microwave radar correlated with the heart and respiratory rates determined by electrocardiogram and respiratory sensor (r = 0.98, p < 0.0001 for heart rate; r = 0.84, p < 0.01 for respiratory rate). The exhaled CO and CO2, as a measure of trauma injury, were measured using an exhaled gas analyzer. The CO and CO 2 concentrations were found to average 3.8 ± 4.3 ppm and 2.9 ± 0.4%, respectively, The expired air temperature and body temperature, as indicators of hemorrhagic hypothermia, averaged 31.8 ± 1.7°C and 36.2 ± 0.4°C, respectively. The results show that our system is promising for future prehospital application in determining casualty conditions for fluid infusions by the Casualty Care System intravenous lines. Copyright © by Association of Military Surgeons of U.S., 2006.
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Hattori H., Ishihara M., Fukuda T., Suda T., Katagiri T.
Biochemical and Biophysical Research Communications 343 ( 4 ) 1118 - 1123 2006.5
Language：English Publishing type：Research paper (scientific journal) Publisher：Biochemical and Biophysical Research Communications
In the clinical field, cell-based therapies are used to treat bone defects. Adipose tissues contain many osteoblast progenitors, among other cell types. We separated mouse adipose tissue-derived stromal cells (ATSCs) according to their cell adhesive properties. Cells in a fraction adherent to the culture dishes 0.5 h after inoculation (AF-0.5) had a potent ability to differentiate into both osteoblasts and adipocytes in vitro. Their differentiation pathways depended on the culture conditions. In these cells, the expression of marker genes for osteoblast differentiation was induced in osteogenic medium. Moreover, the AF-0.5 cells, which were induced to differentiate into osteoblasts in vitro, formed abundant bone tissues in vivo. These results suggest that the AF-0.5 cells have been enriched with bi-potential progenitor cells destined for either osteoblasts or adipocytes. This simple and efficient method for preparing osteoblast progenitor cells from ATSCs may be utilized for bone defect treatment clinically. © 2006 Elsevier Inc. All rights reserved.
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2006239379 虚血性心疾患予後予測における上腕動脈内皮機能および頸動脈硬化指標の役割 運動負荷心電図との比較検討 Invited Reviewed
高瀬凡平, 松島吉宏, 上畑昭美, 浜部晃, 河野浩章, 服部秀美, 荒川宏, 大鈴文孝, 矢野捷介, 石原雅之, 栗田明.
心臓 38 ( Suppl.2 ) 3 - 6 2006.5
Language：Japanese Publishing type：Research paper (scientific journal)
冠動脈疾患の疑いで冠動脈造影を施行した患者103例(男79例・女24例,平均62歳)を対象に,症候限界性treadmill運動負荷試験,上腕動脈flow-mediated vasodilation(FMD),頸動脈超音波法による頸動脈内膜の肥厚(IMT)を測定し,これらの関係を検討した.患者の臨床的背景は,高血圧症64例,糖尿病38例,高脂血症71例,喫煙62例,冠動脈疾患有家族歴22例であった.冠動脈造影の結果,70%以上の有意狭窄を73例に認めた.動脈硬化指数(CSI)とIMT,FMDとの間には有意な相関を認めたが,nitroglycerin依存性内皮非依存性血管拡張能との間には認めなかった.平均49.8ヵ月間の追跡期間で,心事故は15例に認め,致死性心筋梗塞1例,非致死性心筋梗塞2例,不安定狭心症10例,急性左心不全2例であった.心事故発症と各測定値との関連をみると,虚血性運動負荷心電図変化およびFMDは心事故予測に有用であったが,IMTとは関連を認めなかった
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Yura H., Ishihara M., Kanatani Y., Takase B., Hattori H., Suzuki S., Kawakami M., Matsui T.
Journal of Biochemistry 139 ( 4 ) 637 - 643 2006.4
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Biochemistry
Flow cytometric analysis of synthetic galactosyl polymers, asialofetuin and LDL derivatives labeled with FITC (Fluorescein Isothiocyanate) was carried out to determine the phenotypes of endocytic receptors, such as asialoglycoprotein (ASPG) and the LDL receptor, on various types of cells. When FITC-labeled galactosyl polystyrene (GalCPS), being a synthetic ligand of ASPG, was applied to rat hepatocytes and human cancer cells (Hep G2 and Chang Liver), surface fluorescence intensities varied according to receptor expression on the cells. The fluorescence intensity originates from the calcium-dependent binding of the FITC-labeled GalCPS. Although unaltered by pre-treatment with glucosyl polystyrene (GluCPS), fetuin and LDL, the fluorescence intensity was suppressed by pre-treatment with (non-labeled) GalCPS and asialofetuin. Flow cytometry allowed us to demonstrate that the calcium-dependent binding of FITC-labeled LDL (prepared from rabbits) upon the addition of 17α-ethinyl estradiol enhances LDL receptor expression, and the expression is suppressed upon the addition of a monoclonal antibody to the LDL receptor. The binding efficiency based on the combination of FITC-labeled ligands suggests a possible application for the classification of cell types and conditions corresponding to endocytic receptor expression without the need for immuno-active antibodies or radiolabeled substances. Furthermore, the synthetic glycoconjugate (GalCPS) is shown to be a sensitive and useful marker for classification based on cell phenotype using flow cytometry. © 2006 The Japanese Biochemical Society.
DOI： 10.1093/jb/mvj077
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Matsui T., Hattori H., Takase B., Ishihara M.
Journal of Medical Engineering and Technology 30 ( 2 ) 97 - 101 2006.3
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Medical Engineering and Technology
In order to conduct non-contact estimation of arterial blood pH after massive haemorrhage, we calculated the arterial pH based on linear-regression analysis of exhaled gas concentrations (CO and CO2) and vital signs (heart rate, respiratory rate, and surface temperature) measured using non-contact methods in hypovolemic animals. © 2006 Taylor & Francis.
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Bone formation using human adipose tissue-derived stromal cells and a biodegradable scaffold Reviewed
Hattori H., Masuoka K., Sato M., Ishihara M., Asazuma T., Takase B., Kikuchi M., Nemoto K., Ishihara M.
Journal of Biomedical Materials Research - Part B Applied Biomaterials 76 ( 1 ) 230 - 239 2006.1
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Biomedical Materials Research - Part B Applied Biomaterials
Human adipose tissue, obtained by liposuction, was processed to obtain a fibroblast-like population of cells or adipose tissue-derived stromal cells (ATSCs). The ATSCs, as well as bone marrow-derived mesenchymal stem cells (BMSCs), have the capacity for renewal and the potential to differentiate into multiple lineages of mesenchymal tissues. These cells are capable of forming bone when implanted ectopically in an appropriate scaffold. The aim of this study was to evaluate a β-tricalcium phosphate (β-TCP) as a scaffold and to compare the potential of osteogenic differentiation of ATSCs with BMSCs. Both cell types were loaded into β-TCP disk and cultured in an osteogenic induction medium. Optimal osteogenic differentiation in ATSCs in vitro, as determined by secretion of osteocalcin, scanning electron microscope, and histology, were obtained in the culturing with the β-TCP disk. Furthermore, bone formation in vivo was examined by using the ATSC- or BMSC-loaded scaffolds in nude mice. The present results show that ATSCs have a similar ability to differentiate into osteoblasts and to synthesize bone in β-TCP disk as have BMSCs. © 2005 Wiley Periodicals, Inc.
DOI： 10.1002/jbm.b.30357
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Obara K., Ishihara M., Ozeki Y., Ishizuka T., Hayashi T., Nakamura S., Saito Y., Yura H., Matsui T., Hattori H., Takase B., Ishihara M., Kikuchi M., Kikuchi M., Maehara T.
Journal of Controlled Release 110 ( 1 ) 79 - 89 2005.12
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Controlled Release
A photocrosslinkable chitosan (Az-CH-LA) aqueous solution containing paclitaxel resulted in an insoluble hydrogel within 30 s of ultrtaviolet light (UV)-irradiation. About 35-40% of the paclitaxel was released from the paclitaxel-incorporated chitosan hydrogel into phosphate buffered saline (PBS) within 1 day, after which gradual release occurred during 3 days under in vitro non-degradation conditions of the hydrogel. The paclitaxel remaining in the chitosan hydrogel retained its biological activity in vitro for at least 21 days, and was released from the chitosan hydrogel in vivo upon degradation of the hydrogel. The paclitaxel-incorporated Az-CH-LA hydrogel inhibited the growth of subcutaneously induced tumors with Lewis lung cancer (3LL) cells more effectively than those treated with only Az-CH-LA, only paclitaxel, and a non-treated group (control) for at least 11 days. Furthermore, paclitaxel-incorporated chitosan hydrogel markedly reduced the number of CD34-positive vessels in subcutaneous 3LL tumors, indicating a strong inhibition of angiogenesis. These results suggested that application of paclitaxel-incorporated Az-CH-LA hydrogel has an inhibitory activity on angiogenesis and tumor growth. © 2005 Elsevier B.V. All rights reserved.
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Matsui T., Arai I., Gotoh S., Hattori H., Takase B., Kikuchi M., Ishihara M.
Biomedicine and Pharmacotherapy 59 ( SUPPL. 1 ) S188 - S191 2005.10
Language：English Publishing type：Research paper (scientific journal) Publisher：Biomedicine and Pharmacotherapy
Background. - The impaired balance of the low-frequency/high-frequency ratio obtained from spectral components of RR intervals can be a diagnostic test for sepsis. In addition, it is known that a reduction of heart rate variability (HRV) is useful in identifying septic patients at risk of the development of multiple organ dysfunction syndrome (MODS). We have reported a non-contact method using a microwave radar to monitor the heart and respiratory rates of a healthy person placed inside an isolator or of experimental animals exposed to toxic materials. Apparatus design and testing. - With the purpose of preventing secondary exposure of medical personnel to toxic materials under biochemical hazard conditions, we designed a novel apparatus for non-contact measurement of HRV using a 1215 MHz microwave radar, a high-pass filter, and a personal computer. The microwave radar monitors only the small reflected waves from the subject's chest wall, which are modulated by the cardiac and respiratory motion. The high-pass filter enhances the cardiac signal and attenuates the respiratory signal. In a human trial, RR intervals derived from the non-contact apparatus significantly correlated with those derived from ECG (r=0.98, P<0.0001). The non-contact apparatus showed a similar power spectrum of RR intervals to that of ECG. Conclusions. - Our non-contact HRV measurement apparatus appears promising for future pre-hospital monitoring of septic patients or for predicting MODS patients, inside isolators or in the field for mass casualties under biochemical hazard circumstances. © 2005 Elsevier SAS. All rights reserved.
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Nogami Y., Takase B., Matsui T., Hattori H., Hamabe A., Fujita M., Ohsuzu F., Ishihara M., Maekara T.
Biomedicine and Pharmacotherapy 59 ( SUPPL. 1 ) S169 - S173 2005.10
Language：English Publishing type：Research paper (scientific journal) Publisher：Biomedicine and Pharmacotherapy
The cardiac arrhythmic suppression trial (CAST) reported that antiarrhythmic treatments in post-myocardial infarction (MI) patients resulted in poor outcome and decreased in heart rate variability indices (HRV). The goal of the present study was to determine whether aprindine and procainamide, antiarrhythmic agents that increase HRV, result in beneficial effects in post-MI rabbits. Four weeks before experiment, MI was induced in four rabbits by ligating the major branch of left coronary artery. A total of eight rabbits (four post-MI and four normal rabbits) were randomly assigned to treatment with either intravenous aprindine (1 mg/kg) or intravenous procainamide (15 mg/kg). Frequency domain HRV (low frequency spectra, LF, 0.04-0.15 Hz; high frequency spectra, HF, 0.15-0.40 Hz) were assessed by MemCalc software. Aprindine significantly increased HF and LF in both MI and normal rabbits, whereas procainamide tended to decrease HF and LF in MI and normal rabbits (in total rabbits; aprindine, LF, from 6.3 ± 7.9 to 16.5 ± 15.0 ms 2/Hz, P < 0.05; HF, from 8.0 ± 11.7 to 17.5 ± 15.0 ms2/Hz, P < 0.05; procainamide, LF, from 4.9 ± 7.4 to 4.8 ± 8.5 ms2/Hz, NS; HF, from 11.1 ± 23.0 to 5.1 ± 10.6 ms2/Hz, NS). Under pharmacological denervation with propranolol (0.1 mg/kg) and atropine (0.04 mg/kg), aprindine increased LF and HF (LF, from 0.2 ± 0.2 to 0.8 ± 0.7 ms2/Hz, P < 0.05; HF, from 0.1 ± 0.0 to 0.2 ± 0.0 ms2/Hz, P < 0.05). These data suggest that aprindine can increase HRV in post-MI rabbits. Further experiments in human subjects would be of benefit. © 2005 Elsevier SAS. All rights reserved.
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Masuoka K., Asazuma T., Ishihara M., Sato M., Hattori H., Ishihara M., Yoshihara Y., Matsui T., Takase B., Kikuchi M., Nemoto K.
Journal of Biomedical Materials Research - Part B Applied Biomaterials 75 ( 1 ) 177 - 184 2005.10
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Biomedical Materials Research - Part B Applied Biomaterials
The aim of this study was to investigate with tissue engineering procedures the possibility of using atelocollagen honeycomb-shaped scaffolds sealed with a membrane (ACHMS scaffold) for the culturing of chondrocytes to repair articular cartilage defects. Chondrocytes from the articular cartilage of Japanese white rabbits were cultured in ACHMS scaffolds to allow a high-density, three-dimensional culturing for up to 21 days. Although the DNA content in the scaffold increased at a lower rate than monolayer culturing, scanning electron microscopy data showed that the scaffold was filled with grown chondrocytes and their produced extracellular matrix after 21 days. In addition, glycosaminoglycan (GAG) accumulation in the scaffold culture was at a higher level than the monolayer culture. Cultured cartilage in vitro for 14 days showed enough elasticity and stiffness to be handled in vivo. An articular cartilage defect was initiated in the patellar groove of the femur of rabbits and was subsequently filled with the chondrocyte-cultured ACHMS scaffold, ACHMS scaffold alone, or nonfilled (control). Three months after the operations, histological analysis showed that only defects inserted with chondrocytes being cultured in ACHMS scaffolds were filled with reparative hyaline cartilage, and thereby highly expressing type II collagen. These results indicate that implantation of allogenic chondrocytes cultured in ACHMS scaffolds may be effective in repairing articular cartilage defects. © 2005 Wiley Periodicals, Inc.
DOI： 10.1002/jbm.b.30284
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Takase B., Abe Y., Nagata M., Matsui T., Hattori H., Ohsuzu F., Ishihara M., Kurita A.
Biomedicine and Pharmacotherapy 59 ( SUPPL. 1 ) S158 - S162 2005.10
Language：English Publishing type：Research paper (scientific journal) Publisher：Biomedicine and Pharmacotherapy
Betaxolol hydrochloride is a β1-selective antagonist that produces vasodilation in patients with hypertension and ischemic heart disease. The goal of the present study was to characterize the effect of betaxolol on heart rate variability indices (HRV), a well-established prognostic marker. Symptom limited-treadmill exercise testing was performed in 17 hypertensive patients (60.9 ± 14.8 years-old) before and immediately a 3 weeks course of betaxolol hydrochloride (5 mg daily). Frequency domain HRV (high frequency spectra, HF; 0.15-0.40 Hz: low frequency spectra, LF; 0.04-0.15 Hz) was measured during exercise treadmill testing using MemCalc software. Betaxolol hydrochloride significantly decreased the maximal systolic blood pressure and heart rate (184 ± 29 vs. 156 ± 26 mmHg, P < 0.01; 132 ± 21 vs. 113 ± 15 bpm, P < 0.01) and significantly increased HF and LF during exercise treadmill testing (HF, 32 ± 36 vs. 56 ± 55 men/Hz, P < 0.01; LF, 64 ± 58 vs. 95 ± 86 men/Hz, P < 0.01). Thus, treatment with betaxolol hydrochloride resulted in a decrease in blood pressure during exercise treadmill testing and in an increase in HRV. This suggests that this agent could have beneficial effects on long-term prognosis in patients with hypertension. © 2005 Elsevier SAS. All rights reserved.
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Obara K., Ishihara M., Fujita M., Kanatani Y., Hattori H., Matsui T., Takase B., Ozeki Y., Nakamura S., Ishizuka T., Tominaga S., Hiroi S., Kawai T., Maehara T.
Wound Repair and Regeneration 13 ( 4 ) 390 - 397 2005.7
Language：English Publishing type：Research paper (scientific journal) Publisher：Wound Repair and Regeneration
Application of ultraviolet light irradiation to a photocrosslinkable chitosan (Az-CH-LA) aqueous solution including fibroblast growth factor-2 (FGF-2) results within 30 seconds in an insoluble, flexible hydrogel. The FGF-2 molecules retained in the chitosan hydrogel remain biologically active and are released from the chitosan hydrogel upon in vivo biodegradation of the hydrogel. To evaluate the accelerating effect on wound healing of this hydrogel, full-thickness skin incisions were made in the backs of healing-impaired diabetic (db/db) mice and their normal (db/+) littermates. The mice were later killed, and histological sections of the wound were prepared. The degree of wound healing was evaluated using several histological parameters such as the rate of contraction, epithelialization, and tissue filling. Application of the chitosan hydrogel significantly advanced the rate of contraction on Days 0 to 2 in db/db and db/+ mice, Although the addition of FGF-2 into the chitosan hydrogel in db/+ mice had little effect, application of the chitosan hydrogel-containing FGF-2 further accelerated the adjusted tissue filling rate (Days 2 to 4 and Days 4 to 8) in db/db mice. Furthermore, the chitosan hydrogel-containing FGF-2 markedly increased the number of CD-34-positive vessels in the wound areas of db/db mice on Day 4, Thus, the application of chitosan hydrogel-containing FGF-2 onto a healing-impaired wound induces significant wound contraction and accelerates wound closure and healing. Copyright © 2005 by the Wound Healing Society.
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Fujita M., Ishihara M., Morimoto Y., Simizu M., Saito Y., Yura H., Matsui T., Takase B., Hattori H., Kanatani Y., Kikuchi M., Maehara T.
Journal of Surgical Research 126 ( 1 ) 27 - 33 2005.6
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Surgical Research
Background. Therapeutic angiogenesis in ischemic myocardium has been shown to be an effective strategy to improve regional blood flow and myocardial function. However, no effective delivery system for growth factor administration is yet known to induce important therapeutic angiogenic responses in ischemic myocardium. Materials and methods. FGF-2-incorporated chitosan (FGF-2/chitosan) hydrogels were immobilized on the surface of ischemic myocardium of rabbit models of chronic myocardial infarction by UV-irradiation. After 4 weeks, cardiac functional analyses by noradrenalin challenge and histopathological analyses were performed to evaluate the efficacy of a controlled release of FGF-2 from FGF-2/chitosan hydrogel immobilized on the surface of ischemic myocardium. Results. Significant improvement by application of FGF-2/chitosan hydrogels was found in systolic pressure at the left ventricle, +dp/dt maximum, and -dp/dt maximum during noradrenalin challenge at a dose of 1 μg/kg/min. Histological observations showed that a significantly larger amount of viable myocardium and CD 31 immunostained blood vessels were found in the FGF-2/chitosan hydrogel-applied group than only the chitosan-applied and control groups. Conclusions. These preliminary results indicate that the controlled release of biologically active FGF-2 molecules from FGF-2/chitosan hydrogel induces angiogenesis and possibly collateral circulation in ischemic myocardium, thereby protecting the myocardium. © 2005 Elsevier Inc. All rights reserved.