Papers - HATTORI Hidemi
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Effects of Excessive High-fructose Corn Syrup Drink Intake in Middle-aged Mice. Reviewed
Hidaka M, Oshima Y, Hanai Y, Kataoka H, Hattori H
In vivo 38 ( 3 ) 1152 - 1161 2024.5
Authorship：Last author, Corresponding author Language：English Publishing type：Research paper (scientific journal)
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Excessive intake of high-fructose corn syrup drinks induces impaired glucose tolerance Reviewed
Hattori H., Hanai Y., Oshima Y., Kataoka H., Eto N.
Biomedicines 9 ( 5 ) 512 2021.5
Authorship：Lead author, Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Biomedicines
The number of patients with diabetes was approximately 463 million worldwide in 2019, with almost 57.6% of this population concentrated in Asia. Asians often develop type 2 diabetes (T2D), even if they are underweight and consume a smaller amount of food. Soft drinks contain large amounts of sweeteners, such as high-fructose corn syrup (HFCS). Excessive intake of HFCS drinks is considered to be one of the causes of T2D. In the present study, we investigated the effect of excessive consumption of HFCS–water on glucose tolerance and obesity under conditions of controlled caloric intake using a mouse model. Three-week-old male ICR mice were divided into two groups and given free access to 10% HFCS–water or deionized water. The caloric intake was ad-justed to be the same in both groups using a standard rodent diet. The excess HFCS–water intake did not lead to obesity, but led to impaired glucose tolerance (IGT) due to insulin-secretion defect. It affected glucose and fructose metabolism; for example, it decreased the expression of glucoki-nases, ketohexokinase, and glucose transporter 2 in the pancreas. These results suggest that excessive consumption of HFCS drinks, such as soft drinks, without a proper diet, induces nonobese IGT due to insulin-secretion defect.
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Hattori H, Ishihara M.
Cell Biology International 44 ( 5 ) 1124 - 1132 2020.5
Language：English Publishing type：Research paper (scientific journal) Publisher：Cell Biology International
The relationships between eosinophils and adipose tissues are involved in metabolic homeostasis. Eotaxin is a chemokine with potent effects on eosinophil migration. To clarify the mechanisms of eotaxin expression in adipose tissues, we examined the effects of fibroblast growth factor-2 (FGF-2) and interleukin-4 (IL-4) stimulation on eotaxin expression in adipose tissue-derived stromal cells (ASCs), a type of adipocyte progenitor, in vitro. ASCs expressed eotaxin-1 and did not express eotaxin-2 or -3. Eotaxin-1 expression was increased in a concentration-dependent manner following FGF-2 treatment. Additionally, ASCs expressed FGF receptor-1 (FGFR-1) and did not express FGFR-2, -3, or -4. Eotaxin-1 expression was inhibited in cells treated with the FGFR tyrosine kinase inhibitor and extracellular signal-regulated kinase (ERK) inhibitor U0126, even in the presence of FGF-2. Moreover, eotaxin-1 expression was synergistically enhanced by combined treatment with FGF-2 and IL-4 and inhibited in the presence of U0126. Eotaxin-1 expression induced by FGF-2 and IL-4 was involved in ERK activation via FGFR-1 in ASCs. Upregulation of eotaxin expression in adipose tissues could increase eosinophil migration, thereby inducing IL-4 secretion and activation of alternative macrophages and improving glucose homeostasis. These findings provide insights into the mechanisms through which eotaxin mediates metabolic homeostasis in adipose tissues and eosinophils.
DOI： 10.1002/cbin.11309
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Immunostimulatory effect of kumquat (Fortunella crassifolia) and its constituents, β-cryptoxanthin and R-limonene. Reviewed
Terao R, Murata A, Sugamoto K, Watanabe T, Nagahama K, Nakahara K, Kondo T, Murakami N, Fukui K, Hattori H, Eto N
Food & function 10 ( 1 ) 38 - 48 2019.1
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Stability of Weakly Acidic Hypochlorous Acid Solution with Microbicidal Activity. Reviewed
Ishihara M, Murakami K, Fukuda K, Nakamura S, Kuwabara M, Hattori H, Fujita M, Kiyosawa T, Yokoe H.
Biocontrol Science 22 ( 4 ) 223 - 227 2017.11
Language：English Publishing type：Research paper (scientific journal)
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Hattori H., Tsujimoto H., Hase K., Ishihara M.
Carbohydrate Polymers 175 592 - 600 2017.11
Language：English Publishing type：Research paper (scientific journal) Publisher：Carbohydrate Polymers
© 2017 Elsevier Ltd To examine the potential of chitosan-based agents for submucosal injection in endoscopic techniques, a chitosan derivative was prepared with lactose moieties linked to the amino groups of its glucosamine units (CH-LA). After dissolving CH-LA in neutral pH solutions, including physiological saline (CH-LA-S), its response to different concentrations of anionic glycosaminoglycans and proteins in the surrounding environment was examined. The CH-LA-S form changed in the presence of sulfated glycosaminoglycans (heparin, chondroitin sulfate, and mucin) and protein (fibrinogen). High concentrations of sulfated substrates in the solution caused the formation of larger structures. In contrast, in the presence of hyaluronan, 30 mg/mL CH-LA-S did not form any large structures. Submucosal injection of 30 mg/mL CH-LA-S into extracted swine stomachs showed a strong lifting effect of the gastric mucosa. These results indicate the potential utility of CH-LA-S as a submucosal injection for endoscopic techniques such as endoscopic submucosal dissection and mucosal resection of tumors.
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Takabayashi Y., Ishihara M., Kuwabara M., Takikawa M., Nakamura S., Hattori H., Kiyosawa T.
Annals of Plastic Surgery 78 ( 5 ) 562 - 568 2017.5
Language：English Publishing type：Research paper (scientific journal) Publisher：Annals of Plastic Surgery
Activated platelet-rich plasma secrets many growth factors (GFs), and low-molecular weight heparin-protamine micro/nanoparticles (LMWH-P M/NPs) significantly interact with, enhance, and stabilize the secreted GFs. Objective: The purpose of this study was to evaluate the effects of LMWH-P M/NPs and GFs (from platelet-rich plasma) on full-thickness skin graft (FTSG). Methods: A total of 96 inbred male rats were anesthetized and 4-cm2 fullthickness skin wound were created on dorsal skin of rats. LMWH-P M/NPs and GFs, LMWH-P M/NPs, GFs and saline (control) were then injected evenly into cutaneous muscles at the wound. The next day, the rats underwent FTSG. On the indicated days after FTSG, blood flow of FTSG site (wound bed and FTSG) was examined by 2-dimensional laser Doppler blood flowmeter. On 10 days, pictures of FTSG site were taken and FTSG survival rate was evaluated. Histologic analyses of skin samples were performed on 4, 7, and 10 days. Results: Treatment of full-thickness skin wound with LMWH-P M/NPs and GFs effectively promoted survival rate of FTSG and blood flow of FTSG site compared with those treated with GFs, LMWH-P M/NPs, and control. LMWH-P M/NPs and GFs also promoted new vessel formation at FTSG site. Conclusions: The prior injection of LMWH-P M/NPs and GFs into wound bed increases FTSG survival rate, and promotes blood flow and angiogenesis at FTSG site.
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Feasibility of improving platelet-rich plasma therapy by using chitosan with high platelet activation ability. Reviewed
Hattori H, Ishihara M
Experimental and therapeutic medicine 13 ( 3 ) 1176 - 1180 2017.3
Language：English Publishing type：Research paper (scientific journal)
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Cytotoxicity of Silver Nanoparticle and Chitin-Nanofiber Sheet Composites Caused by Oxidative Stress. Reviewed
Kinoda J, Ishihara M, Hattori H, Nakamura S, Fukuda K, Yokoe H
Nanomaterials (Basel, Switzerland) 6 ( 10 ) 2016.10
Language：English Publishing type：Research paper (scientific journal)
DOI： 10.3390/nano6100189
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Kishimoto S., Inoue K., Nakamura S., Hattori H., Ishihara M., Sakuma M., Toyoda S., Iwaguro H., Taguchi I., Inoue T., Yoshida K.
Atherosclerosis 249 132 - 139 2016.6
Language：English Publishing type：Research paper (scientific journal) Publisher：Atherosclerosis
Heparin/protamine micro/nanoparticles (LH/P-MPs) were recently developed as low-molecular weight, biodegradable carriers for adipose-derived stromal cells (ADSCs). These particles can be used for a locally delivered stem cell therapy that promotes angiogenesis. LH/P-MPs bind to the cell surface of ADSCs and promote cell-to-cell interaction and aggregation of ADSCs. Cultured ADSC/LH/P-MP aggregates remain viable. Here, we examined the ability of these aggregates to rescue limb loss in a mouse model of hindlimb ischemia. Methods: Unilateral hindlimb ischemia was induced in adult male BALB/c mice by ligation of the iliac artery and hindlimb vein. For allotransplantation of ADSCs from the same inbred strain, we injected ADSC alone or ADSC/LH/P-MP aggregates or control medium (sham-treated) directly into the ischemic muscles. Ischemic limb blood perfusion, vessel density, and vessel area were recorded. The extent of ischemic limb necrosis or limb loss was assessed on postoperative days 2, 7, and 14. Results: Compared with the sham-treatment control, treatment with ADSCs alone showed modest effects on blood perfusion recovery and increased the number of α-SMA-positive vessels. Response to ADSC/LH/P-MP aggregates was significantly greater than ADSCs alone for every endpoint. ADSC/LH/P-MP aggregates more effectively prevented the loss of ischemic hindlimbs than ADSCs alone or the sham-treatment. Conclusion: The LH/P-MPs augmented the effects of ADSCs on angiogenesis and reversal of limb ischemia. Use of ADSC/LH/P-MP aggregates offers a novel and convenient treatment method and potentially represents a promising new therapeutic approach to inducing angiogenesis in ischemic diseases.
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Takabayashi Y., Nambu M., Ishihara M., Kuwabara M., Fukuda K., Nakamura S., Hattori H., Kiyosawa T.
Clinical, Cosmetic and Investigational Dermatology 9 127 - 134 2016.5
Language：English Publishing type：Research paper (scientific journal) Publisher：Clinical, Cosmetic and Investigational Dermatology
Purpose: Although treatments for alopecia are in high demand, not all treatments are safe and reliable. Dalteparin/protamine nanoparticles (D/P NPs) can effectively carry growth factors (GFs) such as fibroblast GF (FGF)-2. The purpose of this study was to identify the effects of FGF-2-containing D/P NPs (FGF-2&D/P NPs) on hair growth. Patients and methods: In this study, the participants were 12 volunteers with thin hair. One milliliter of FGF-2 (100 ng/mL) and D/P NPs (56 μg/mL) was applied and massaged on the skin of the scalp by the participants twice a day. They were evaluated for 6 months. Participants were photographed using a digital camera for general observation and a hair diagnosis system for measuring hair diameter. Results: The mean diameter of the hairs was significantly higher following the application of FGF-2&D/P NPs for 6 months. Objective improvements in thin hair were observed in two cases. Nine participants experienced greater bounce and hair resilience. Conclusion: The transdermal application of FGF-2&D/P NPs to the scalp can be used as a new treatment for alopecia.
DOI： 10.2147/CCID.S108187
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Takikawa M., Ishihara M., Takabayashi Y., Sumi Y., Takikawa M., Yoshida R., Nakamura S., Hattori H., Yanagibayashi S., Yamamoto N., Kiyosawa T.
Journal of Plastic Surgery and Hand Surgery 49 ( 5 ) 268 - 274 2015.9
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Plastic Surgery and Hand Surgery
Purpose: The purpose of this study was to evaluate the accelerating effects of platelet-rich plasma-containing (PRP&) fragmin/protamine microparticles (F/P MPs) for repairing mitomycin C-treated healing-impaired wounds. Staining with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL-staining) showed that apoptosis of dermal fibroblast cells (DFCs) and epidermal keratinocyte cells (EKCs) were significantly induced in the skin of the mitomycin C-treated rats. Method: Full-thickness skin defects were made on the back of rats and mitomycin C was applied on the wounds to prepare a healing-impaired wound. After washing out the mitomycin C, saline (control), F/P MPs alone, PRP alone, and PRP&F/P MPs were injected around the wounds. The rats were later euthanised and histological sections of the wounds were then prepared at indicated time periods after the treatment. Results and conclusion: These results indicated the numbers of large, medium, and small capillary lumens 7 days after injection of PRP&F/P MPs were significantly higher than those after injection of PRP or F/P MPs alone. Furthermore, epithelium and granulation tissue formations were significantly stimulated in the healing-impaired wounds treated with PRP&F/P MPs 3, 7 and 14 days after injection of PRP&F/P MPs.
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Takikawa M., Nakamura S., Ishihara M., Takabayashi Y., Fujita M., Fujita M., Hattori H., Kushibiki T., Ishihara M.
Journal of Surgical Research 196 ( 2 ) 247 - 257 2015.6
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Surgical Research
We produced fibroblast growth factor (FGF)-2-containing low-molecular-weight heparin (Fragmin)/protamine nanoparticles (FGF-2 + F/P NPs). The purpose of this study was to evaluate the effectiveness of the local administration of FGF-2 + F/P NPs on repairing crush syndrome (CS)-injured lesions after compression release using a nonlethal and reproducible CS injury rat model. Materials and methods The hind limbs of the anesthetized rats were compressed for 6 h using 3.6 kg blocks, as previously described. The effects of administering FGF-2 + F/P NPs (group A), F/P NPs alone (group B), FGF-2 alone (group C), and saline (control; group D) were examined. Motor function, surface blood flow in the hind limbs, and the wet/dry weight ratio in the tibialis anterior muscle were examined for 1-28 d after the compression release. Histologic analyses were also performed. Results At the middle and late stages (3-28 d after the compression release), group A had higher scores in the motor function, improved blood flow, increased number of blood vessels, and faster recovered muscle tissue, compared with the other groups. There was no significant difference in enhanced edema in the tibialis anterior muscle among all groups. Conclusions The local administration of FGF-2 + F/P NPs to a CS-injured lesion was effective in repairing damaged muscle tissue after compression release.
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Hattori H., Ishihara M.
Stem Cell Research and Therapy 6 ( 1 ) 70 2015.4
Language：English Publishing type：Research paper (scientific journal) Publisher：Stem Cell Research and Therapy
Introduction: Paracrine effects can be exploited in cell-based therapies that secrete factors, such as chemokines and cytokines, and can recruit inflammatory cells to transplants. In this study, mouse adipose tissue-derived stromal cells (ASCs) and bone marrow-derived stromal cells (ST2 cells) were used to examine changes in paracrine interactions with inflammation cells. Methods: Green fluorescent protein positive (GFP<sup>+</sup>) bone marrow cells (BMCs) were injected into an irradiated mouse via the femoral vein, and ASCs and ST2 cells were transplanted intradermally. Subsequently, an in vivo imaging system was used to observe behaviors of GFP<sup>+</sup> BMCs. To detect bone marrow-derived inflammatory cells which migrated to the ASC and ST2 cell transplantation area, the sections were immunostained using antibodies against Gr1, CD11c, and F4/80, and secretory proteins were detected in culture medium using enzyme-linked immunosorbent assay. Results: Many bone marrow-derived inflammatory cells migrated to ASC and ST2 cell transplantation sites. Among these, neutrophils were detected during the early period and macrophages were predominantly detected at a later point in time. Many chemokines, cytokines, growth factors, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) were secreted in abundance from ASCs, and the secretion increased by co-culturing with inflammatory cells, except for secretions of insulin-like growth factor-1, MMP-9 and MMP-13. Although secretions from ST2 cells were less than those from ASCs, co-culture with inflammatory cells increased these secretions to levels similar to those of ASCs. However, unlike ASCs, the ST2 cells did not secrete angiostatin, MMP-2, or MMP-3. Finally, ASCs secreted not only proinflammatory cytokines, angiogenic factors and MMPs but also anti-inflammatory cytokines, anti-angiogenesis factors, and TIMPs. Conclusions: The effects of cell-based therapies using ASCs and ST2 cells are depended on paracrine effects that are mediated by chemokines, cytokines, growth factors, MMPs, and TIMPs, which comprise responses to interactions between transplanted cells and inflammatory cells. Moreover, paracrine effects of transplanted cells are influenced by inflammatory cells, and are moderated by a balance of secreted inhibitors.
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Hattori H., Ishihara M.
Biomedical Materials (Bristol) 10 ( 1 ) 015014 2015.2
Language：English Publishing type：Research paper (scientific journal) Publisher：Biomedical Materials (Bristol)
Because the molecular weight (Mw) and degree of deacetylation (DDA) of chitosan can vary depending on the purification method, the identification of appropriate chitosan structures is important for developing more effective hemostatic agents. In this study, the influence of varying Mw and DDA of chitosan on blood aggregation was characterized by 10 types of chitosan with different Mw and DDA, including oligomers. The highest aggregation of whole blood, washed erythrocytes and platelets in platelet-rich plasma (PRP) were observed in chitosan with Mw of 8.6 kDa or more and with DDA of 75 to 88%. However, chitosan with too high Mw (247 kDa) inhibited the aggregation of whole blood, washed erythrocytes and PRP at high chitosan concentration. At certain concentrations, chitosan with 75-85% DDA and 50-190 kDa and chitosan with 87.6% DDA and 247 kDa both aggregated proteins in PRP. Chitosan oligomer did not affect blood aggregation. The results suggested that the aggregation by chitosan depended on the interaction of positively charged chitosan with negatively charged erythrocytes, platelets and plasma protein. It seemed that a suitable balance of positive charge in chitosan and negative charge in hemocytes and some kinds of proteins was important. To develop a hemostatic with effective blood aggregation, the chitosan should not be limited to a single Mw and a single DDA but may be a mixed chitosan with wide range of Mw (8.6-247 kDa) and DDA of 75 to 88%.
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Nguyen V., Ishihara M., Kinoda J., Hattori H., Nakamura S., Ono T., Miyahira Y., Matsui T.
Journal of Nanobiotechnology 12 ( 1 ) 49 2014.12
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Nanobiotechnology
Background: Chitin nanofibers sheets (CNFSs) with nanoscale fiber-like surface structures are nontoxic and biodegradable biomaterials with large surface-to-mass ratio. CNFSs are widely applied as biomedical materials such as a functional wound dressing. This study aimed to develop antimicrobial biomaterials made up of CNFS-immobilized silver nanoparticles (CNFS/Ag NPs). Materials and methods: CNFSs were immersed in suspensions of Ag NPs (5.17 ± 1.9 nm in diameter; mean ± SD) for 30 min at room temperature to produce CNFS/Ag NPs. CNFS/Ag NPs were characterized by transmission electron microscopy (TEM) and then tested for antimicrobial activities against Escherichia (E.) coli, Pseudomonas (P.) aeruginosa, and H1N1 influenza A virus, three pathogens that represent the most widespread infectious bacteria and viruses. Ultrathin sectioning of bacterial cells also was carried out to observe the bactericidal mechanism of Ag NPs. Results: The TEM images indicated that the Ag NPs are dispersed and tightly adsorbed onto CNFSs. Although CNFSs alone have only weak antimicrobial activity, CNFS/Ag NPs showed much stronger antimicrobial properties against E. coli, P. aeruginosa, and influenza A virus, with the amount of immobilized Ag NPs onto CNFSs. Conclusions: Our results suggest that CNFS/Ag NPs interacting with those microbes exhibit stronger antimicrobial activities, and that it is possible to apply CNFS/Ag NPs as anti-virus sheets as well as anti-infectious wound dressings.
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Takase B., Hattori H., Tanaka Y., Nagata M., Ishihara M.
International Angiology 33 ( 1 ) 27 - 34 2014.2
Language：English Publishing type：Research paper (scientific journal) Publisher：International Angiology
Aim. Assessment of flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) in the brachial artery by a new device (UNEXEF18G) has been reported to be excellent for evaluating endothelial function, and sympathetic overdrive can accelerate the atherosclerotic process. The purpose of this study was to investigate and confirm whether anti-sympathetic beta-blocking action can enhance the pleiotropic effects of statins. Methods. FMD and NMD were measured using the UNEXEF18G before and after 4-week treatment of rosuvastatin (5 mg/day) with or without atenolol (25 mg/day) in 44 hypercholesterolemic patients (70±8 years old, LDL-C >140 mg/dL) with hypertension. Patients were randomly allocated to two treatment arms: rosuvastatin alone (R-group, N.=22) and rosuvastatin with atenolol (RA-group, N.=22). Results. Baseline FMD was not different between the two treatment arms, and both groups showed improvement in FMD (R-group, 3.48±1.9% to 4.65±2.41%, P<0.05; RAgroup, 3.42±1.48% to 5.46±1.79%, P<0.05), while there were no differences in NMD. The effects on lipid profiles were identical in the two groups. In addition, FMD improvement was greater in the RA-group than in the R-group (Δchange 2.15±1.29% vs. 1.16±1.15%, P<0.05). Conclusion. Beta-blockade enhances the pleiotropic effects of statins on endothelial function. The mechanism should be confirmed by further studies.
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Sumi Y., Ishihara M., Kishimoto S., Takikawa M., Hattori H., Takikawa M., Azuma R., Nakamura S., Fujita M., Kiyosawa T.
Annals of Plastic Surgery 72 ( 1 ) 113 - 120 2014
Language：English Publishing type：Research paper (scientific journal) Publisher：Annals of Plastic Surgery
We investigated the effectiveness of the application of inbred adipose-derived stromal cells (IR-ASCs) in high inbred rat plasma (IRP) (6%)-Dulbecco modified Eagle medium (DMEM) gel with fragmin/protamine microparticles (F/P MPs) (IR-ASCs + IRP-DMEM gel + F/P MPs) on wound healing in streptozotocin-induced diabetic rats. F/P MPs have previously been used as a cell carrier for IR-ASCs in inbred Fisher 344 rats and for preservation and controlled release of various cytokines in IRP-DMEM gel. We applied IR-ASCs + IRP-DMEM gel + F/P MPs to full-thickness skin excisions on the backs of the diabetic rats. The statistical significance of wound closure was evaluated on postwounding days 3, 7, 10, and 14, and the skin area surrounding the wound was removed for histological examination on days 7 and 14. The wound closure rate and histological examination of wounds treated with IR-ASCs + IRP-DMEM gel + F/P MPs demonstrated significantly advanced epithelialization, capillary formation, and granulation tissue formation. When DiI-labeled IR-ASCs + IRP-DMEM gel + F/P MPs were applied to full-thickness skin wounds on the backs of the diabetic rats, histological observation at 2 weeks showed appearances of both DiI-labeled granulation tissue and CD31-immunostained microvessels in the transplant areas. A portion of the transplanted IR-ASCs + IRP-DMEM gel + F/P MPs had been taken up into the granulation tissues to promote wound healing. Thus, IR-ASCs + IRP-DMEM gel + F/P MPs were effective for repairing healing-impaired wounds such as those arising in the diabetic rats. Copyright © 2013 Lippincott Williams & Wilkins.
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Hattori H., Amano Y., Habu-Ogawa Y., Ando T., Takase B., Ishihara M.
Cell Transplantation 22 ( 12 ) 2381 - 2392 2013.12
Language：English Publishing type：Research paper (scientific journal) Publisher：Cell Transplantation
The aim of this study was to identify novel angiogenic mechanisms underlying the regenerative process. To that end, interactions between adipose tissue-derived stromal cells (ASCs) and bone marrow cells (BMCs) were initially investigated using real-time fluorescence optical imaging. To monitor cell behavior in mice, we injected green fluorescent protein-positive (GFP+) BMCs into the tail vein and injected PKH26-labeled ASCs behind the ears. Angiogenesis and inflammation were observed at these sites via an optical imaging probe. Injected GFP+ BMCs migrated from the blood vessels into the tissues surrounding the ASC injection sites. Many of the migrating GFP+ BMCs discovered at the ASC injection sites were inflammatory cells, including Gr-1+, CD11b+, and F4/80+ cells. ASCs cocultured with inflammatory cells secreted increased levels of chemokines such as macrophage inflammatory protein (MIP)-1α, MIP-1β, keratinocyte-derived chemokines, and monocyte chemotactic protein 1. Similarly, these ASCs secreted increased levels of angiogenic growth factors such as hepatocyte growth factor and vascular endothelial growth factor. However, when anti-CXC chemokine receptor type 4 antibody was injected at regular intervals, the migration of GFP+ BMCs (especially Gr-1+ and CD11b+ cells) to ASC injection sites was inhibited, as was angiogenesis. The collective influence of the injected ASCs and BMC-derived inflammatory cells promoted acute inflammation and angiogenesis. Together, the results suggest that the outcome of cell-based angiogenic therapy is influenced not only by the injected cells but also by the effect of intrinsic inflammatory cells. © 2013 Cognizant Comm. Corp.
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Takase B., Nagata M., Hattori H., Tanaka Y., Ishihara M.
Medical Principles and Practice 23 ( 1 ) 59 - 65 2013.12
Language：English Publishing type：Research paper (scientific journal) Publisher：Medical Principles and Practice
Objective: This study evaluated the efficacy of combined therapy with probucol and cilostazol on endothelial function in silent lacunar cerebral infarcts (SLCI) and mild hypercholesterolemia. Subjects and Methods: Flow-mediated vasodilatation (FMD) and nitroglycerin-induced vasodilatation (NMD) were measured before and after 4 weeks of combined therapy with probucol (500 mg/day) and cilostazol (200 mg/day) in 34 patients with a mean age of 72 ± 7 years (range 57-80 years) with SLCI, mild hypercholesterolemia (low-density lipoprotein cholesterol >100 mg/dl) and impaired endothelial function (FMD <6%). Patients were randomly allocated to one of the following two treatment groups: (1) aspirin (100 mg/day) with behavioral modifications, such as diet and/or exercise therapy (A group or control group, n = 17), and (2) probucol and cilostazol treatment (PC group, n = 17), also with behavioral modifications. Results: Although the baseline FMD was not different between the two treatment arms (2.7 ± 1.5 vs. 2.6 ± 1.5%, n.s.), the posttreatment FMD was significantly improved in the PC group (from 2.7 ± 1.5 to 3.5 ± 1.7%, p < 0.05) but not in the A group (from 2.6 ± 1.5 to 2.9 ± 1.4%, n.s.). No differences were observed between baseline and posttreatment NMD in either group. The effects of treatments on lipid profiles were more profound in the PC group. Conclusion: Combined treatment with probucol and cilostazol resulted in subacute improvement in FMD/endothelial function in patients with SLCI with mild hypercholesterolemia. This combination therapy has the potential to reduce the risk of cardiovascular events via improvements in endothelial function and lipid profiles. © 2013 S. Karger AG, Basel.
DOI： 10.1159/000355825