研究者詳細 - 小川　恵美悠

Efficacy of interstitial photodynamic therapy using talaporfin sodium and a semiconductor laser for a mouse allograft glioma model

Nagai K., Akimoto J., Fukami S., Saito Y., Ogawa E., Takanashi M., Kuroda M., Kohno M.

Scientific Reports （Scientific Reports） 14 （ 1 ） 2024年12月

　概要を見る

To investigate the therapeutic potential of photodynamic therapy (PDT) for malignant gliomas arising in unresectable sites, we investigated the effect of tumor tissue damage by interstitial PDT (i-PDT) using talaporfin sodium (TPS) in a mouse glioma model in which C6 glioma cells were implanted subcutaneously. A kinetic study of TPS demonstrated that a dose of 10 mg/kg and 90 min after administration was appropriate dose and timing for i-PDT. Performing i-PDT using a small-diameter plastic optical fiber demonstrated that an irradiation energy density of 100 J/cm2 or higher was required to achieve therapeutic effects over the entire tumor tissue. The tissue damage induced apoptosis in the area close to the light source, whereas vascular effects, such as fibrin thrombus formation occurred in the area slightly distant from the light source. Furthermore, when irradiating at the same energy density, irradiation at a lower power density for a longer period of time was more effective than irradiation at a higher power density for a shorter time. When performing i-PDT, it is important to consider the rate of delivery of the irradiation light into the tumor tissue and to set irradiation conditions that achieve an optimal balance between cytotoxic and vascular effects.
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Near-Infrared II Photobiomodulation Preconditioning Ameliorates Stroke Injury via Phosphorylation of eNOS

Yokomizo S., Kopp T., Roessing M., Morita A., Lee S., Cho S., Ogawa E., Komai E., Inoue K., Fukushi M., Feil S., Kim H.H., Bragin D.E., Gerashchenko D., Huang P.L., Kashiwagi S., Atochin D.N.

Stroke （Stroke） 55 （ 6 ） 1641 - 1649 2024年06月

ISSN 00392499

　概要を見る

BACKGROUND: The current management of patients with stroke with intravenous thrombolysis and endovascular thrombectomy is effective only when it is timely performed on an appropriately selected but minor fraction of patients. The development of novel adjunctive therapy is highly desired to reduce morbidity and mortality with stroke. Since endothelial dysfunction is implicated in the pathogenesis of stroke and is featured with suppressed endothelial nitric oxide synthase (eNOS) with concomitant nitric oxide deficiency, restoring endothelial nitric oxide represents a promising approach to treating stroke injury. METHODS: This is a preclinical proof-of-concept study to determine the therapeutic effect of transcranial treatment with a low-power near-infrared laser in a mouse model of ischemic stroke. The laser treatment was performed before the middle cerebral artery occlusion with a filament. To determine the involvement of eNOS phosphorylation, unphosphorylatable eNOS S1176A knock-in mice were used. Each measurement was analyzed by a 2-way ANOVA to assess the effect of the treatment on cerebral blood flow with laser Doppler flowmetry, eNOS phosphorylation by immunoblot analysis, and stroke outcomes by infarct volumes and neurological deficits. RESULTS: Pretreatment with a 1064-nm laser at an irradiance of 50 mW/cm2improved cerebral blood flow, eNOS phosphorylation, and stroke outcomes. CONCLUSIONS: Near-infrared II photobiomodulation could offer a noninvasive and low-risk adjunctive therapy for stroke injury. This new modality using a physical parameter merits further consideration to develop innovative therapies to prevent and treat a wide array of cardiovascular diseases.
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“Honey pot”-like lesion formation: Impact of catheter contact angle on lesion formation by novel diamond-embedded temperature-controlled ablation catheter in a porcine experimental model

Ogiso S., Fukaya H., Ogawa E., Mori H., Masuda Y., Yazaki Y., Murayama Y., Saito D., Kobayashi S., Nakamura H., Ishizue N., Kishihara J., Niwano S., Oikawa J., Ako J.

Heart Rhythm （Heart Rhythm） 2024年

ISSN 15475271

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Background: Novel diamond-embedded catheter enables precise temperature-controlled ablation. However, the effects of contact angle on lesion formation of this catheter are poorly understood. Objective: The purpose of this study was to evaluate lesion formation using the temperature-controlled ablation catheter embedded with diamond at different angles in a porcine experimental model. Methods: Freshly sacrificed porcine hearts were used. Radiofrequency catheter ablation was performed at 50 W for 15 seconds at an upper temperature setting of 60°C. The contact force (5g, 10g, 30g) and catheter contact angles (30°, 45°, 90°) were changed in each set (n = 13 each). Surface width, maximum lesion width, lesion depth, surface area, distance from the distal edge to the widest area, and impedance drop were evaluated. Results: Surface width and maximum lesion width were longer at 30° than at 90° (P <.05). There were no significant differences in the lesion depth by catheter angle except at 30g. Surface area was larger at 30° than at 90° (P <.05). Distance from the distal edge to the widest area was longer at 30° than at 90° (P <.05). There were no significant differences in impedance drop according to catheter angle. Conclusion: With diamond-embedded temperature-controlled ablation catheters, lesion width increased at a shallower contact angle, whereas lesion depth did not. Surface area also increased at a shallower contact angle. This catheter created a large ablation lesion on the proximal side of the catheter, which looked like a “honey pot.”
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Photobiomodulation and nitric oxide signaling

Kashiwagi S., Morita A., Yokomizo S., Ogawa E., Komai E., Huang P.L., Bragin D.E., Atochin D.N.

Nitric Oxide - Biology and Chemistry （Nitric Oxide - Biology and Chemistry） 130 58 - 68 2023年01月

ISSN 10898603

　概要を見る

Nitric oxide (NO) is a well-known gaseous mediator that maintains vascular homeostasis. Extensive evidence supports that a hallmark of endothelial dysfunction, which leads to cardiovascular diseases, is endothelial NO deficiency. Thus, restoring endothelial NO represents a promising approach to treating cardiovascular complications. Despite many therapeutic agents having been shown to augment NO bioavailability under various pathological conditions, success in resulting clinical trials has remained elusive. There is solid evidence of diverse beneficial effects of the treatment with low-power near-infrared (NIR) light, defined as photobiomodulation (PBM). Although the precise mechanisms of action of PBM are still elusive, recent studies consistently report that PBM improves endothelial dysfunction via increasing bioavailable NO in a dose-dependent manner and open a feasible path to the use of PBM for treating cardiovascular diseases via augmenting NO bioavailability. In particular, the use of NIR light in the NIR-II window (1000–1700 nm) for PBM, which has reduced scattering and minimal tissue absorption with the largest penetration depth, is emerging as a promising therapy. In this review, we update recent findings on PBM and NO.
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Consideration of Laser Speckle Contrast Analysis for Shunt Management

Kumagai H., Nakatake H., Ogawa E., Takeda S., Kosuge T., Inaoka S.

IEEJ Transactions on Electronics, Information and Systems （IEEJ Transactions on Electronics, Information and Systems） 143 （ 4 ） 471 - 472 2023年

ISSN 03854221

　概要を見る

In hemodialysis, normal venipuncture cannot deliver large amounts of blood, so about 90% of patients make an arteriovenous anastomosis called an internal shunt. In addition, since dialysis is performed multiple times a week, frequent puncture and pressure hemostasis are required. As a result, blood vessels are stressed, resulting in stenosis and occlusion. In order to detect and treat such shunt troubles at an early stage, daily shunt management is important. Laser speckle contrast analysis is of interest in the field of visualization of the hemodynamics of living tissues. In this study, the relationship between the flow rate and the contrast value was investigated by a technique for quantifying the amount of change in the dynamic speckle pattern.
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