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Maruhashi T.,Hiroshima University | Soga J.,Hiroshima University | Fujimura N.,Hiroshima University | Idei N.,Hiroshima University | And 12 more authors.
Circulation | Year: 2012

Background-Patients with Gilbert syndrome have mild unconjugated hyperbilirubinemia. It has been shown that bilirubin is an endogenous antioxidant. We evaluated the role of oxidative stress in endothelial function in patients with Gilbert syndrome under normal conditions without cardiovascular risk factors. Methods and Results-A total of 108 young men with Gilbert syndrome without cardiovascular risk factors and 108 age-matched healthy men (normal controls) were enrolled in this study. Serum concentrations of bilirubin were higher in patients with Gilbert syndrome than in control subjects (29.2±11.6 versus 9.4±2.7 μmol/L; P<0.001). Serum concentrations of malondialdehyde-modified low-density lipoprotein and urinary excretion of 8-hydroxy-2′-deoxyguanosine (8-OHdG), as indices of oxidative stress, were lower in patients with Gilbert syndrome than in control subjects (61.8±24.5 versus 72.5±21.8 U/L, P=0.034; 7.8±2.4 versus 10.4±3.2 ng/mg creatinine, P=0.001, respectively). Flow-mediated vasodilation was greater in patients with Gilbert syndrome than in normal control subjects (7.2±2.2% versus 5.9±1.7%; P<0.001). Vascular responses to nitroglycerine were not significantly different between the 2 groups. Flow-mediated vasodilation correlated with serum concentration of bilirubin (r=0.44, P<0.001), malondialdehyde-modified low-density lipoprotein (r=-0.25, P=0.01), and urinary excretion of 8-OHdG (r=-0.27, P=0.004) in patients with Gilbert syndrome but not in control subjects. In addition, serum concentration of bilirubin correlated with malondialdehyde-modified low-density lipoprotein (r=-0.20, P=0.04) and 8-OHdG (r=-0.21, P=0.02) in patients with Gilbert syndrome but not in control subjects. Conclusions-Patients with Gilbert syndrome had low levels of oxidative stress associated with hyperbilirubinemia and enhancement of endothelium-dependent vasodilation. Clinical Trial Registration-URL: http://www.umin.ac.jp. Unique identifier: UMIN000003409. © 2012 American Heart Association, Inc.

Iba T.,Juntendo University | Saito D.,National Defense Medical College Research Institute | Wada H.,Mie University | Asakura H.,Kanazawa University
Thrombosis Research | Year: 2012

Introduction: Although supplementation with antithrombin (AT) concentrates has been widely accepted for the treatment of disseminated intravascular coagulation (DIC) in Japan, the effects and adverse effects have not been investigated. Materials and Methods: We conducted a nonrandomized multi-institutional survey. A total of 729 septic DIC patients with AT activity levels of 70% or lower, who had undergone AT substitution at either 1500 IU/day or 3000 IU/day for consecutive 3 days were analyzed. Of these, 650 and 79 patients had received 1500 IU/day (AT1500 group) and 3000 IU/day (AT3000 group), respectively. Results: Bleeding events were observed in 6.52% of patients (severe bleeding, 1.71%). A significant decrease in initial AT level (below 50%) was observed in 69.6% of patients in AT3000 group and 48.2% in AT1500 group, and this difference was significant (P < 0.01). A logistic-regression analysis conducted using age, gender, body weight, initial AT activity, and supplemented AT dose, revealed that higher initial AT activity (odds ratio (OR), 1.032; P < 0.001), AT dose of 3000 IU/day (OR, 1.912; P = 0.026), and age (OR, 0.985; P = 0.023) were significant factors for improved survival. Conclusion: The risk of severe bleeding is less than 2%, and concomitant administration of heparin did not increase the risk. The survival in AT1500 group was 65.2%, while that in AT3000 group was 74.7%. © 2012 Elsevier Ltd.

Sato S.,National Defense Medical College Research Institute | Ando T.,Keio University | Obara M.,Keio University
Optics Letters | Year: 2011

We developed an optical-fiber-based photomechanical gene transfer system for endoscopic or catheter-based application. A fiber tip with a laser-absorbing film covered with a transparent plastic disk for plasma confinement was attached to a quartz fiber; the film was irradiated with nanosecond laser pulses transmitted through the fiber to generate photomechanical waves (PMWs). Characteristics of PMWs emitted from the fiber tip were examined to confirm the necessary conditions for gene transfer. We then attempted to transfer reporter genes to the rat skin as a test tissue in vivo with the fiber system, and the results showed significantly high protein levels and spatially selective pinpoint gene expressions in the tissue. © 2011 Optical Society of America.

Takahashi Y.,National Defense Medical College Research Institute
Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica | Year: 2012

In 1996, the United Nations (UN) and the World Health Organization (WHO) published guidelines for developing suicide prevention measures at national level. In Japan, the Basic Act on Suicide Prevention was promulgated in June 2006 and a Comprehensive Suicide Measures Framework was formulated in June 2007, which announced that suicide prevention is an official concern and that entire societies should be engaged in such suicide prevention efforts. One of the fundamental principles moving forward is to place emphasis on coordination between medical and community models of care. The medical model is based on the notion that mental disorders that could lead to suicide should be diagnosed at earlier stages and addressed through appropriate psychiatric treatment. The community model, which concerns awareness activities that emphasize earlier detection and attentive social support, is also important. Implementing policies with a long-term perspective that maintain close linkages between these models is a critical strategy for suicide prevention. This presentation investigates the current conditions and issues around Japanese suicide prevention with reference to the UN/WHO guidelines for suicide prevention, and compares the situation to that in other countries.

Terakawa M.,Keio University | Tsuda H.,National Defense Medical College | Ashida H.,National Defense Medical College Research Institute | Sato S.,National Defense Medical College Research Institute
Lasers in Surgery and Medicine | Year: 2010

Background and Objective: We previously delivered a therapeutic gene to skin grafts of rats by using photomechanical waves (PMWs), also called laser-induced stress waves (LISWs), with the objective of enhancing adhesion of grafted tissue. The objective of this study was to evaluate tissue alterations that are possibly caused by PMWs used for gene delivery on the basis of immunohistochemistry and electron microscopy. Materials and Methods: PMWs were generated by irradiating an elastic laser target (rubber disk) with 532nm nanosecond laser pulses from a (of) Q-switched Nd:YAG laser. Tissue alterations were evaluated by histological analysis using hematoxylin and eosin (H&E) staining and immunohistochemical stainings, including anti-rat CD68 antibody staining to identify macrophages for detection of inflammation and terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining for assessment of apoptosis. Morphological changes of cell membranes and organelles were evaluated by transmission electron microscopy. Results: Skin exposed to PMWs that were generated at a laser fluence of 1.2 J/cm2 (42MPa in peak pressure), which is the optimum laser fluence (pressure) for therapeutic gene delivery to skin graft, showed no noticeable damage. At fluences higher than 1.8 J/cm2 (>51 MPa), fragmentation of nuclei was observed and the number of CD68-positive cells increased remarkably. No significant increases in the numbers of TUNEL-positive keratinocytes and fibroblasts were observed at 1.2 J/cm2. At fluences higher than 1.8 J/cm2, the averaged ratio of TUNELpositive cells also increased. The results of electron microscopy revealed that PMWs generated at 1.2 J/cm2 caused neither damage to the cell membrane, nuclear membrane, or organelles. Conclusion: We observed no noticeable tissue alteration under the optimum laser irradiation conditions used for therapeutic gene delivery to a skin graft, demonstrating low invasiveness of our PMW-based gene transfection. © 2010 Wiley-Liss, Inc.

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