1.The Effects of a Red-Light Controllable Nitric Oxide Donor, NORD-1, on Erectile Dysfunction in Rats with Streptozotocin Induced Diabetes Mellitus
Yuji HOTTA ; Kyoya OYAMA ; Takuma YOSHIDA ; Naoya IEDA ; Taiki MORI ; Yasuhiro HORITA ; Tomoya KATAOKA ; Yoko FURUKAWA-HIBI ; Susumu OHYA ; Hidehiko NAKAGAWA ; Kazunori KIMURA
The World Journal of Men's Health 2025;43(1):197-204
Purpose:
Patients with diabetes mellitus (DM) often exhibit refractory erectile dysfunction (ED). Red-light-controllable nitric oxide donor (NORD-1) and red-light irradiation have successfully enhanced erectile function in intact rats. In this study, we investigated whether the combination of NORD-1 and red-light irradiation effectively treated ED in streptozotocin (STZ)-treated rats with DM.
Materials and Methods:
Seven-week-old male Sprague-Dawley rats were used in this study. Rats in the DM and sham groups received intravenous STZ (50 mg/kg) and saline, respectively. One week after treatment, the blood glucose level of rats in the DM group was >250 mg/dL. Five weeks after the treatment, we performed a functional study by measuring intracavernous pressure (ICP) under cavernous nerve stimulation before and after NORD-1 treatment with and without light irradiation. Additionally, we performed an isometric tension study using the corpus cavernosum of rats treated with NORD-1 or the control compound, SiR650.
Results:
The ICP/mean arterial pressure (MAP) ratio was significantly lower in the DM group than in the sham group before and after NORD-1 treatment without light irradiation (both p<0.05). After NORD-1 treatment with light irradiation, the ICP/MAP ratio in the sham and DM groups was significantly enhanced than before and after NORD-1 treatment without light irradiation (all p<0.05). The ICP/MAP ratio in the DM group after NORD-1 with light irradiation was similar to that in the sham group under normal conditions before NORD-1 treatment. Moreover, the systemic blood pressure was not affected by NORD-1 or light irradiation. In the tension study, the corpus cavernosum of rats treated with SiR650 was not changed by red light in the sham or DM groups. However, the rats treated with NORD-1 were strongly relaxed by red light in both groups.
Conclusions
NORD-1 and red-light irradiation could improve ED in the presence of DM without lowering blood pressure.
2.The Effects of a Red-Light Controllable Nitric Oxide Donor, NORD-1, on Erectile Dysfunction in Rats with Streptozotocin Induced Diabetes Mellitus
Yuji HOTTA ; Kyoya OYAMA ; Takuma YOSHIDA ; Naoya IEDA ; Taiki MORI ; Yasuhiro HORITA ; Tomoya KATAOKA ; Yoko FURUKAWA-HIBI ; Susumu OHYA ; Hidehiko NAKAGAWA ; Kazunori KIMURA
The World Journal of Men's Health 2025;43(1):197-204
Purpose:
Patients with diabetes mellitus (DM) often exhibit refractory erectile dysfunction (ED). Red-light-controllable nitric oxide donor (NORD-1) and red-light irradiation have successfully enhanced erectile function in intact rats. In this study, we investigated whether the combination of NORD-1 and red-light irradiation effectively treated ED in streptozotocin (STZ)-treated rats with DM.
Materials and Methods:
Seven-week-old male Sprague-Dawley rats were used in this study. Rats in the DM and sham groups received intravenous STZ (50 mg/kg) and saline, respectively. One week after treatment, the blood glucose level of rats in the DM group was >250 mg/dL. Five weeks after the treatment, we performed a functional study by measuring intracavernous pressure (ICP) under cavernous nerve stimulation before and after NORD-1 treatment with and without light irradiation. Additionally, we performed an isometric tension study using the corpus cavernosum of rats treated with NORD-1 or the control compound, SiR650.
Results:
The ICP/mean arterial pressure (MAP) ratio was significantly lower in the DM group than in the sham group before and after NORD-1 treatment without light irradiation (both p<0.05). After NORD-1 treatment with light irradiation, the ICP/MAP ratio in the sham and DM groups was significantly enhanced than before and after NORD-1 treatment without light irradiation (all p<0.05). The ICP/MAP ratio in the DM group after NORD-1 with light irradiation was similar to that in the sham group under normal conditions before NORD-1 treatment. Moreover, the systemic blood pressure was not affected by NORD-1 or light irradiation. In the tension study, the corpus cavernosum of rats treated with SiR650 was not changed by red light in the sham or DM groups. However, the rats treated with NORD-1 were strongly relaxed by red light in both groups.
Conclusions
NORD-1 and red-light irradiation could improve ED in the presence of DM without lowering blood pressure.
3.The Effects of a Red-Light Controllable Nitric Oxide Donor, NORD-1, on Erectile Dysfunction in Rats with Streptozotocin Induced Diabetes Mellitus
Yuji HOTTA ; Kyoya OYAMA ; Takuma YOSHIDA ; Naoya IEDA ; Taiki MORI ; Yasuhiro HORITA ; Tomoya KATAOKA ; Yoko FURUKAWA-HIBI ; Susumu OHYA ; Hidehiko NAKAGAWA ; Kazunori KIMURA
The World Journal of Men's Health 2025;43(1):197-204
Purpose:
Patients with diabetes mellitus (DM) often exhibit refractory erectile dysfunction (ED). Red-light-controllable nitric oxide donor (NORD-1) and red-light irradiation have successfully enhanced erectile function in intact rats. In this study, we investigated whether the combination of NORD-1 and red-light irradiation effectively treated ED in streptozotocin (STZ)-treated rats with DM.
Materials and Methods:
Seven-week-old male Sprague-Dawley rats were used in this study. Rats in the DM and sham groups received intravenous STZ (50 mg/kg) and saline, respectively. One week after treatment, the blood glucose level of rats in the DM group was >250 mg/dL. Five weeks after the treatment, we performed a functional study by measuring intracavernous pressure (ICP) under cavernous nerve stimulation before and after NORD-1 treatment with and without light irradiation. Additionally, we performed an isometric tension study using the corpus cavernosum of rats treated with NORD-1 or the control compound, SiR650.
Results:
The ICP/mean arterial pressure (MAP) ratio was significantly lower in the DM group than in the sham group before and after NORD-1 treatment without light irradiation (both p<0.05). After NORD-1 treatment with light irradiation, the ICP/MAP ratio in the sham and DM groups was significantly enhanced than before and after NORD-1 treatment without light irradiation (all p<0.05). The ICP/MAP ratio in the DM group after NORD-1 with light irradiation was similar to that in the sham group under normal conditions before NORD-1 treatment. Moreover, the systemic blood pressure was not affected by NORD-1 or light irradiation. In the tension study, the corpus cavernosum of rats treated with SiR650 was not changed by red light in the sham or DM groups. However, the rats treated with NORD-1 were strongly relaxed by red light in both groups.
Conclusions
NORD-1 and red-light irradiation could improve ED in the presence of DM without lowering blood pressure.
4.The Effects of a Red-Light Controllable Nitric Oxide Donor, NORD-1, on Erectile Dysfunction in Rats with Streptozotocin Induced Diabetes Mellitus
Yuji HOTTA ; Kyoya OYAMA ; Takuma YOSHIDA ; Naoya IEDA ; Taiki MORI ; Yasuhiro HORITA ; Tomoya KATAOKA ; Yoko FURUKAWA-HIBI ; Susumu OHYA ; Hidehiko NAKAGAWA ; Kazunori KIMURA
The World Journal of Men's Health 2025;43(1):197-204
Purpose:
Patients with diabetes mellitus (DM) often exhibit refractory erectile dysfunction (ED). Red-light-controllable nitric oxide donor (NORD-1) and red-light irradiation have successfully enhanced erectile function in intact rats. In this study, we investigated whether the combination of NORD-1 and red-light irradiation effectively treated ED in streptozotocin (STZ)-treated rats with DM.
Materials and Methods:
Seven-week-old male Sprague-Dawley rats were used in this study. Rats in the DM and sham groups received intravenous STZ (50 mg/kg) and saline, respectively. One week after treatment, the blood glucose level of rats in the DM group was >250 mg/dL. Five weeks after the treatment, we performed a functional study by measuring intracavernous pressure (ICP) under cavernous nerve stimulation before and after NORD-1 treatment with and without light irradiation. Additionally, we performed an isometric tension study using the corpus cavernosum of rats treated with NORD-1 or the control compound, SiR650.
Results:
The ICP/mean arterial pressure (MAP) ratio was significantly lower in the DM group than in the sham group before and after NORD-1 treatment without light irradiation (both p<0.05). After NORD-1 treatment with light irradiation, the ICP/MAP ratio in the sham and DM groups was significantly enhanced than before and after NORD-1 treatment without light irradiation (all p<0.05). The ICP/MAP ratio in the DM group after NORD-1 with light irradiation was similar to that in the sham group under normal conditions before NORD-1 treatment. Moreover, the systemic blood pressure was not affected by NORD-1 or light irradiation. In the tension study, the corpus cavernosum of rats treated with SiR650 was not changed by red light in the sham or DM groups. However, the rats treated with NORD-1 were strongly relaxed by red light in both groups.
Conclusions
NORD-1 and red-light irradiation could improve ED in the presence of DM without lowering blood pressure.
5.The Effects of a Red-Light Controllable Nitric Oxide Donor, NORD-1, on Erectile Dysfunction in Rats with Streptozotocin Induced Diabetes Mellitus
Yuji HOTTA ; Kyoya OYAMA ; Takuma YOSHIDA ; Naoya IEDA ; Taiki MORI ; Yasuhiro HORITA ; Tomoya KATAOKA ; Yoko FURUKAWA-HIBI ; Susumu OHYA ; Hidehiko NAKAGAWA ; Kazunori KIMURA
The World Journal of Men's Health 2025;43(1):197-204
Purpose:
Patients with diabetes mellitus (DM) often exhibit refractory erectile dysfunction (ED). Red-light-controllable nitric oxide donor (NORD-1) and red-light irradiation have successfully enhanced erectile function in intact rats. In this study, we investigated whether the combination of NORD-1 and red-light irradiation effectively treated ED in streptozotocin (STZ)-treated rats with DM.
Materials and Methods:
Seven-week-old male Sprague-Dawley rats were used in this study. Rats in the DM and sham groups received intravenous STZ (50 mg/kg) and saline, respectively. One week after treatment, the blood glucose level of rats in the DM group was >250 mg/dL. Five weeks after the treatment, we performed a functional study by measuring intracavernous pressure (ICP) under cavernous nerve stimulation before and after NORD-1 treatment with and without light irradiation. Additionally, we performed an isometric tension study using the corpus cavernosum of rats treated with NORD-1 or the control compound, SiR650.
Results:
The ICP/mean arterial pressure (MAP) ratio was significantly lower in the DM group than in the sham group before and after NORD-1 treatment without light irradiation (both p<0.05). After NORD-1 treatment with light irradiation, the ICP/MAP ratio in the sham and DM groups was significantly enhanced than before and after NORD-1 treatment without light irradiation (all p<0.05). The ICP/MAP ratio in the DM group after NORD-1 with light irradiation was similar to that in the sham group under normal conditions before NORD-1 treatment. Moreover, the systemic blood pressure was not affected by NORD-1 or light irradiation. In the tension study, the corpus cavernosum of rats treated with SiR650 was not changed by red light in the sham or DM groups. However, the rats treated with NORD-1 were strongly relaxed by red light in both groups.
Conclusions
NORD-1 and red-light irradiation could improve ED in the presence of DM without lowering blood pressure.
6.Efficacy of a Red-Light Controllable Nitric Oxide Releaser for Neurogenic Erectile Dysfunction: A Study Using a Rat Model of Cavernous Nerve Injury
Taiki MORI ; Yuji HOTTA ; Naoya IEDA ; Tomoya KATAOKA ; Hidehiko NAKAGAWA ; Kazunori KIMURA
The World Journal of Men's Health 2023;41(4):909-919
Purpose:
Neurogenic erectile dysfunction (ED) is a common side effect of radical prostatectomy (RP) because of cavernous nerve damage. In these patients, the production of nitric oxide (NO), which is important for erection, is decreased in the corpus cavernosum. Therefore, NO donors are useful for post-RP ED. However, short half-life and systemic side effects are problems of NO application in ED therapy. To avert these problems, we developed a red-light controllable NO releaser, NORD-1. This study aimed to investigate the effect of NORD-1 and red-light irradiation on neurogenic ED using a rat model of bilateral cavernous nerve injury (BCNI).
Materials and Methods:
BCNI and sham operations were conducted on 8-week-old rats. After 4 weeks, erectile function was evaluated using changes in intracavernous pressure (ICP) during electrostimulation of the cavernous nerve. ICP was measured under three conditions; without NORD-1 and red-light irradiation, with NORD-1 and without red-light irradiation, and with NORD-1 and red-light irradiation. SiR650 which absorbs red-light but does not release NO was used for the negative control. After the experiment, localization of NORD-1 was observed using a microscope.
Results:
Erectile function in a BCNI rat model was significantly decreased compared to sham-operated rats (p<0.05). After injecting NORD-1 into the penis, erectile function did not change without red-light irradiation. However, the combination of NORD-1 and red-light irradiation significantly improved erectile function (p<0.05) without affecting systemic arterial pressure. In contrast, when SiR650 was used, erectile function did not change in all three conditions. NORD-1 was detected only in the corpus cavernosum and not in the urethra and dorsal vein.
Conclusions
NORD-1 combined with red-light irradiation is effective for ED induced by cavernous nerve injury. This treatment may have low risks of hypotension and urinary incontinence, and it can replace the current treatment for post-RP ED.
7.Mode of Imaging Study and Endovascular Therapy for a Large Ischemic Core: Insights From the RESCUE-Japan LIMIT
Fumihiro SAKAKIBARA ; Kazutaka UCHIDA ; Shinichi YOSHIMURA ; Nobuyuki SAKAI ; Hiroshi YAMAGAMI ; Kazunori TOYODA ; Yuji MATSUMARU ; Yasushi MATSUMOTO ; Kazumi KIMURA ; Reiichi ISHIKURA ; Manabu INOUE ; Kumiko ANDO ; Atsushi YOSHIDA ; Kanta TANAKA ; Takeshi YOSHIMOTO ; Junpei KOGE ; Mikiya BEPPU ; Manabu SHIRAKAWA ; Takeshi MORIMOTO ;
Journal of Stroke 2023;25(3):388-398
Background:
and Purpose Differences in measurement of the extent of acute ischemic stroke using the Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) by non-contrast computed tomography (CT-ASPECTS stratum) and diffusion-weighted imaging (DWI-ASPECTS stratum) may impact the efficacy of endovascular therapy (EVT) in patients with a large ischemic core.
Methods:
The RESCUE-Japan LIMIT (Recovery by Endovascular Salvage for Cerebral Ultra-acute Embolism Japan–Large IscheMIc core Trial) was a multicenter, open-label, randomized clinical trial that evaluated the efficacy and safety of EVT in patients with ASPECTS of 3–5. CT-ASPECTS was prioritized when both CT-ASPECTS and DWI-ASPECTS were measured. The effects of EVT on the modified Rankin Scale (mRS) score at 90 days were assessed separately for each stratum.
Results:
Among 183 patients, 112 (EVT group, 53; No-EVT group, 59) were in the CT-ASPECTS stratum and 71 (EVT group, 40; No-EVT group, 31) in the DWI-ASPECTS stratum. The common odds ratio (OR) (95% confidence interval) of the EVT group for one scale shift of the mRS score toward 0 was 1.29 (0.65–2.54) compared to the No-EVT group in CT-ASPECTS stratum, and 6.15 (2.46–16.3) in DWI-ASPECTS stratum with significant interaction between treatment assignment and mode of imaging study (P=0.002). There were significant interactions in the improvement of the National Institutes of Health Stroke Scale score at 48 hours (CT-ASPECTS stratum: OR, 1.95; DWIASPECTS stratum: OR, 14.5; interaction P=0.035) and mortality at 90 days (CT-ASPECTS stratum: OR, 2.07; DWI-ASPECTS stratum: OR, 0.23; interaction P=0.008).
Conclusion
Patients with ASPECTS of 3–5 on MRI benefitted more from EVT than those with ASPECTS of 3–5 on CT.
8.Successful High-Dose Radiation Treatment for Chemo-Resistant Oral Squamous Cell Carcinoma in a Kindler’s Syndrome Patient
Yuka KIMURA ; Atsushi TANEMURA ; Yuma HANAOKA ; Eiji KIYOHARA ; Mari WATAYA-KANEDA ; Manabu FUJIMOTO ; Katsuto TAMAI ; Keisuke TAMARI ; Yuji SEO ; Kazuhiko OGAWA
Annals of Dermatology 2021;33(4):382-384
9.Successful High-Dose Radiation Treatment for Chemo-Resistant Oral Squamous Cell Carcinoma in a Kindler’s Syndrome Patient
Yuka KIMURA ; Atsushi TANEMURA ; Yuma HANAOKA ; Eiji KIYOHARA ; Mari WATAYA-KANEDA ; Manabu FUJIMOTO ; Katsuto TAMAI ; Keisuke TAMARI ; Yuji SEO ; Kazuhiko OGAWA
Annals of Dermatology 2021;33(4):382-384
10.Associations between thyroid-stimulating hormone and hypertension according to thyroid cyst status in the general population: a cross-sectional study.
Yuji SHIMIZU ; Yuko NABESHIMA-KIMURA ; Shin-Ya KAWASHIRI ; Yuko NOGUCHI ; Yasuhiro NAGATA ; Takahiro MAEDA ; Naomi HAYASHIDA
Environmental Health and Preventive Medicine 2020;25(1):69-69
BACKGROUND:
The absence of thyroid cysts may indicate latent thyroid damage, as demonstrated in our previous study. However, the association between the absence of thyroid cysts and latent functional damage of the thyroid is unknown. At low thyroid hormone productivity, which may be associated with latent functional damage of the thyroid, the association between thyroid-stimulating hormone (TSH) and hypertension might be enhanced. Therefore, we evaluated the association between TSH level and hypertension stratified by thyroid cyst status.
METHODS:
We conducted a cross-sectional study of 1724 euthyroid Japanese individuals aged 40-74 years who participated in an annual health checkup in 2014.
RESULTS:
In the study population, 564 and 686 participants had thyroid cysts and hypertension, respectively. A significant positive association was observed between TSH and hypertension in subjects without a thyroid cyst but not in subjects with thyroid cysts. There was a significant positive association between hypertension and TSH in subjects without a thyroid cyst (odds ratio [OR] 1.27; 95% confidence intervals [CI] 1.01, 1.61) but not in subjects with thyroid cysts (OR 0.79; CI 0.57, 1.09) in the model fully adjusted for known confounding factors. The correlation between the TSH and free triiodothyronine (fee T3) levels (simple correlation coefficient [r] = - 0.13, p < 0.01) was stronger in the subjects without thyroid cysts than in those with thyroid cysts (r = - 0.03, p = 0.525).
CONCLUSIONS
TSH is positively associated with hypertension only in individuals without thyroid cysts. The correlation between the TSH and free T3 levels was stronger in the subjects without thyroid cysts than in those with thyroid cysts. Therefore, the absence of thyroid cysts could be related to the association between TSH level and hypertension, possibly by indicating that the subjects without thyroid cysts had limited thyroid hormone reserves. Therefore, the absence of thyroid cysts could indicate the latent functional damage of the thyroid.
Aged
;
Cross-Sectional Studies
;
Cysts/etiology*
;
Female
;
Humans
;
Hypertension/metabolism*
;
Japan
;
Male
;
Middle Aged
;
Thyroid Diseases/etiology*
;
Thyroid Gland/pathology*
;
Thyrotropin/metabolism*

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