Controlling the Magnetic Responsiveness of Cellulose Nanofiber Particles Embedded with Iron Oxide Nanoparticles.

2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-oxidized cellulose nanofiber (TOCN) particles, an innovative biobased material derived from wood biomass, have garnered significant interest, particularly in the biomedical field, for their distinctive properties as biocompatible particle adsorbents. However, their microscopic size complicates their separation in liquid media, thereby impeding their application in various domains. In this study, superparamagnetic magnetite nanoparticles (NPs), specifically iron oxide Fe3O4 NPs with an average size of 15 nm, were used to enhance the collection efficiency of TOCN-Fe3O4 composite particles synthesized through spray drying. These composite particles exhibited a remarkable ζ-potential (approximately -50 mV), indicating their high stability in water, as well as impressive magnetization properties (up to 47 emu/g), and rapid magnetic responsiveness within 60 s in water (3 wt % Fe3O4 to TOCN, 1 T magnet). Furthermore, the influence of Fe3O4 NP concentrations on the measurement of the speed of magnetic separation was quantitatively discussed. Additionally, the binding affinity of the synthesized particles for proteins was assessed on a streptavidin-biotin binding system, offering crucial insights into their binding capabilities with specific proteins and underscoring their significant potential as functionalized biomedical materials.

Endoscopic Features of Gastric Mucosa-Associated Lymphoid Tissue Lymphoma without Helicobacter pylori.

Although gastric mucosa-associated lymphoid tissue (MALT) lymphoma without Helicobacter pylori (HP) has increased recently, a specific endoscopic classification has not been established; its endoscopic characteristics have not been investigated. In this study, we retrospectively investigated gastric MALT lymphoma without HP in our hospital and assessed differences in the endoscopic findings according to HP infection status. Fifty-seven patients with gastric MALT lymphoma Lugano stage I, diagnosed between January 2013 and March 2023, were divided into three groups (currently HP infected, previously infected, and uninfected), wherein their endoscopic findings were evaluated. Furthermore, the superficial type, as per the classification of Sano et al., was independently subdivided based on the endoscopic differential diagnoses, as follows: atrophic gastritis-like, angiodysplasia-like, superficial gastritis-like, and undifferentiated carcinoma-like. Compared with the currently infected group, the HP-uninfected group tended to have more small lesions without erosion and more discolored, undifferentiated carcinoma-like depressed lesions. In addition, the positive rate of the tree-like appearance (TLA) and ballooning characteristics of gastric MALT lymphoma in magnified findings was lower in the HP-uninfected group. In patients without HP infection, MALT lymphoma should be excluded, even in the absence of suspicious magnifying findings such as TLA or ballooning.

Investigation of the 1-week effect of traffic light nutrition labeling on diet selection among Japanese university students: a randomized controlled trial.

BACKGROUND: The method of displaying nutrition information labels on the front of food packaging (FOP: Front of Pack) has been implemented worldwide to prevent lifestyle-related diseases. This study aimed to investigate whether the use of the UK's Traffic Light Food (TLF) label, known as the FOP label, influences the dietary choices of Japanese youth and promotes healthy dietary choices. METHODS: Diet selection was performed for one week each during the baseline and intervention periods. During the intervention period, TLF labels were displayed on meal images of the intervention group. Participants chose what they would like to have for dinner of the day from 15 images. Each meal was scored based on the color of the nutrition label, and a comparison between groups was made to determine whether TLF labeling influenced meal selection for dinner. The psychological stress caused by the presence or absence of nutrition labels and nutritional components when choosing meals was also evaluated. RESULTS: A total of 69 participants were randomly assigned to two groups. Dietary choice scores indicated that the TLF-labeled group made significantly healthier dietary choices than the unlabeled group. Additionally, the TLF-labeled group showed a significant increase in the percentage of people conscious of nutritional components when choosing meals. Furthermore, a significant increase in the number of people conscious of protein, a nutritional ingredient not indicated on the TLF label, was observed. During the test period, no difference in psychological stress caused by the presence and absence of the TLF labels was observed. CONCLUSIONS: The use of TLF labels also encouraged healthy dietary choices among Japanese university students. The use of FOP nutrition labels should be considered in Japan to prevent lifestyle-related diseases through healthy dietary choices. TRIAL REGISTRATION: UMIN Clinical Trials Registry Number: UMIN000047268. Registered March 23, 2022.

Relieving psychological stress and improving sleep quality by bergamot essential oil use before bedtime and upon awakening: A randomized crossover trial.

OBJECTIVES: The COVID-19 pandemic increased psychological stress and decreased sleep quality, especially among young people. Aromatherapy alleviates psychological stress, and bergamot essential oil helps improve depression. This study aimed to verify whether bergamot essential oil use alleviates psychological stress due to the COVID-19 pandemic and improves sleep quality and morning wakefulness. DESIGN: A placebo-controlled, randomized, open-label, two-arm, two-period crossover trial. INTERVENTIONS: Each intervention period was 1 week, with a 1-week washout period between the two periods. Participants used a bergamot or placebo spray before bedtime and upon awakening in each period. MAIN OUTCOME MEASURES: The primary outcome measures were sleep quality and morning wakefulness, assessed using the Ogri-Shirakawa-Azumi sleep inventory MA version (OSA-MA). The secondary outcome measures were depression, anxiety, and stress, assessed using the Depression Anxiety Stress Scales-21 (DASS-21). RESULTS: A total of 48 university students participated in the study. A significant improvement was observed in "sleepiness on rising," "refreshing on rising," and "sleep length" in the bergamot group. Additionally, a significant improvement was observed in depression, anxiety, and stress. CONCLUSION: Using bergamot essential oil before bedtime helps relax the mind and body and provides sound sleep. It also improves mood and wakefulness when used upon awakening. Using aromatic essential oils is expected to relieve psychological stress and improve sleep quality and morning wakefulness.

Comparison of the Ability of Artificial-Intelligence-Based Computer-Aided Detection (CAD) Systems and Endoscopists to Detect Colorectal Neoplastic Lesions on Endoscopy Video.

Artificial-intelligence-based computer-aided diagnosis (CAD) systems have developed remarkably in recent years. These systems can help increase the adenoma detection rate (ADR), an important quality indicator in colonoscopies. While there have been many still-image-based studies on the usefulness of CAD, few have reported on its usefulness using actual clinical videos. However, no studies have compared the CAD group and control groups using the exact same case videos. This study aimed to determine whether CAD or endoscopists were superior in identifying colorectal neoplastic lesions in videos. In this study, we examined 34 lesions from 21 cases. CAD performed better than four of the six endoscopists (three experts and three beginners), including all the beginners. The time to lesion detection with beginners and experts was 2.147 ± 1.118 s and 1.394 ± 0.805 s, respectively, with significant differences between beginners and experts (p < 0.001) and between beginners and CAD (both p < 0.001). The time to lesion detection was significantly shorter for experts and CAD than for beginners. No significant difference was found between experts and CAD (p = 1.000). CAD could be useful as a diagnostic support tool for beginners to bridge the experience gap with experts.

Effectiveness of Displaying Traffic Light Food Labels on the Front of Food Packages in Japanese University Students: A Randomized Controlled Trial.

Nutrition labeling on the front of food packages has been implemented worldwide to help improve public health awareness. In this randomized double-blind controlled trial, we used a Google Forms questionnaire to evaluate the effectiveness of nutrition labeling on food packages in university students. The questionnaire, ultimately completed by 247 students, included 15 dietary images from which they were asked to choose what they wanted to eat for breakfast, lunch, and dinner the following day. For the interventional (traffic light food [TLF]) group only, TLF labels were displayed on dietary images. This group had a significantly higher proportion of people conscious of healthy eating during all meals than the control group, and the effect of TLF labeling on choosing meals was the highest for lunch. In addition to the indicated nutritional components, the TLF group had a significantly higher proportion of people who were conscious of the ones of protein and dietary fiber that were not indicated on the label. The use of TLF labels resulted in an increase in the proportion of people choosing a healthy diet as well as being conscious of their nutritional components. Therefore, the use of TLF labels may help promote healthy dietary choices in Japan.

Antidepressants in the post-ketamine Era: Pharmacological approaches targeting the glutamatergic system.

The efficacy of currently available medications for depression is unsatisfactory, and that has spurred the development of novel antidepressants based on a hypothesis other than the monoamine hypothesis. Recent studies have revealed the importance of the glutamatergic system as a drug target for depression, and the validity of this hypothesis has been underpinned by the discovery of the antidepressant effects of ketamine, leading to the market launch of Spravato® nasal spray which delivers (S)-ketamine (esketamine). However, both ketamine and esketamine have unwanted adverse effects that hinder their routine use in daily practice. Extensive studies have elucidated the mechanisms underlying the antidepressant effects of ketamine, and that has encouraged numerous drug discovery activities to search for agents that retain a ketamine-like antidepressant profile but with lesser adverse effect liabilities. The discovery activities have included attempts to identify 1) the active substance(s) in the circulation after ketamine administration and 2) agents that act on the proposed mechanisms of action of ketamine. Clinical trials of agents discovered in the course of these activities are underway, and in 2022, AUVELITY™ (AXS-05; dextromethorphan with bupropion) was approved by the United States Food and Drug Administration. Drug development of post-ketamine agents should provide novel antidepressants that are safer, but as potent and rapidly acting as ketamine.

Esm1 and Stc1 as Angiogenic Factors Responsible for Protective Actions of Adipose-Derived Stem Cell Sheets on Chronic Heart Failure After Rat Myocardial Infarction.

BACKGROUND: Although adipose-derived stem cell (ADSC) sheets improve the cardiac function after myocardial infarction (MI), underlying mechanisms remain to be elucidated. The aim of this study was to determine the fate of transplanted ADSC sheets and candidate angiogenic factors released from ADSCs for their cardiac protective actions.Methods and Results:MI was induced by ligation of the left anterior descending coronary artery. Sheets of transgenic (Tg)-ADSCs expressing green fluorescence protein (GFP) and luciferase or wild-type (WT)-ADSCs were transplanted 1 week after MI. Both WT- and Tg-ADSC sheets improved cardiac functions evaluated by echocardiography at 3 and 5 weeks after MI. Histological examination at 5 weeks after MI demonstrated that either sheet suppressed fibrosis and increased vasculogenesis. Luciferase signals from Tg-ADSC sheets were detected at 1 and 2 weeks, but not at 4 weeks, after transplantation. RNA sequencing of PKH (yellow-orange fluorescent dye with long aliphatic tails)-labeled Tg-ADSCs identified mRNAs of 4 molecules related to angiogenesis, including those of Esm1 and Stc1 that increased under hypoxia. Administration of Esm1 or Stc1 promoted tube formation by human umbilical vein endothelial cells. CONCLUSIONS: ADSC sheets improved cardiac contractile functions after MI by suppressing cardiac fibrosis and enhancing neovascularization. Transplanted ADSCs existed for >2 weeks on MI hearts and produced the angiogenic factors Esm1 and Stc1, which may improve cardiac functions after MI.

Differences among hemoglobin thresholds for red blood cell transfusions in patients with hematological diseases in teaching hospitals: a real world data in Japan.

A hemoglobin (Hb) threshold level of 7 g/dL has been proposed for red blood cell (RBC) transfusion in patients with chronic anemia in the Japanese guideline since 2005. However, Hb thresholds for hematological diseases in clinical practice and factors responsible for higher Hb thresholds remain unclear. Hb thresholds were collected for patients with hematological diseases from 32 Japanese teaching hospitals. Uni- and multivariate analyses were used to analyze relationships between Hb threshold level and various patient and hospital factors. In total, 4996 units of RBC were transfused to 1054 patients with hematological diseases in 2421 transfusions. Median age was 68 years. Myelodysplastic syndrome was the most frequent diagnosis. Overall median Hb threshold level was 6.9 g/dL. Multivariate linear regression analysis detected the following variables associated with Hb threshold level: hospital; cardiovascular disease; symptomatic anemia; and hematopoietic stem cell transplantation. Hospital was the most significant factor. Collectively, median Hb threshold level in clinical practice in Japan was similar to the guidelines. Higher Hb threshold level depended on the hospitals at which the transfusions were performed as well as patient condition. Educational approaches directed toward hospitals may be useful to promote transfusion guidelines.

ß-Adrenergic Blocker, Carvedilol, Abolishes Ameliorating Actions of Adipose-Derived Stem Cell Sheets on Cardiac Dysfunction and Remodeling After Myocardial Infarction.

BACKGROUND: Treatment of myocardial infarction (MI) includes inhibition of the sympathetic nervous system (SNS). Cell-based therapy using adipose-derived stem cells (ASCs) has emerged as a novel therapeutic approach to treat heart failure in MI. The purpose of this study was to determine whether a combination of ASC transplantation and SNS inhibition synergistically improves cardiac functions after MI.Methods and Results:ASCs were isolated from fat tissues of Lewis rats. In in vitro studies using cultured ASC cells, mRNA levels of angiogenic factors under normoxia or hypoxia, and the effects of norepinephrine and a ß-blocker, carvedilol, on the mRNA levels were determined. Hypoxia increased vascular endothelial growth factor (VEGF) mRNA in ASCs. Norepinephrine further increased VEGF mRNA; this effect was unaffected by carvedilol. VEGF promoted VEGF receptor phosphorylation and tube formation of human umbilical vein endothelial cells, which were inhibited by carvedilol. In in vivo studies using a rat MI model, transplanted ASC sheets improved contractile functions of MI hearts; they also facilitated neovascularization and suppressed fibrosis after MI. These beneficial effects of ASC sheets were abolished by carvedilol. The effects of ASC sheets and carvedilol on MI heart functions were confirmed by Langendorff perfusion experiments using isolated hearts. CONCLUSIONS: ASC sheets prevented cardiac dysfunctions and remodeling after MI in a rat model via VEGF secretion. Inhibition of VEGF effects by carvedilol abolished their beneficial effects.

Endosomal escape by photo-activated fusion of liposomes containing a malachite green derivative: a novel class of photoresponsive liposomes for drug delivery vehicles.

We conducted photo-activated delivery of drugs based on the fusion of liposomes with endocytic membranes, thus allowing the direct release of encapsulated drugs inside the cytoplasm. As described in our earlier works, liposomes can be photoresponsive and fusogenic following the incorporation of a malachite green derivative carrying a long alkyl chain (MGL) into the lipid membrane. We prepared MGL liposomes using 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine and encapsulated doxorubicin (DOX). Though the shape of MGL liposomes became elliptical after encapsulating DOX, UV irradiation did not enhance DOX leakage from MGL liposomes. We demonstrated the cellular uptake of MGL liposomes into murine cells derived from colon cancer (Colon 26 cells) using flow cytometry, and we found that the uptake was governed by a clathrin-dependent endocytosis pathway. Confocal fluorescence microscopic observations of Colon 26 cells treated with MGL liposomes encapsulating DOX revealed that DOX was localized in endosomes under dark conditions, while DOX was observed in the cytosol and nucleus after UV irradiation. The viability of Colon 26 cells treated with MGL liposomes encapsulating DOX was reduced by UV irradiation, indicating photo-induced enhancement of anti-cancer efficacy.

Solar-panel and parasol strategies shape the proteorhodopsin distribution pattern in marine Flavobacteriia.

Proteorhodopsin (PR) is a light-driven proton pump that is found in diverse bacteria and archaea species, and is widespread in marine microbial ecosystems. To date, many studies have suggested the advantage of PR for microorganisms in sunlit environments. The ecophysiological significance of PR is still not fully understood however, including the drivers of PR gene gain, retention, and loss in different marine microbial species. To explore this question we sequenced 21 marine Flavobacteriia genomes of polyphyletic origin, which encompassed both PR-possessing as well as PR-lacking strains. Here, we show that the possession or alternatively the lack of PR genes reflects one of two fundamental adaptive strategies in marine bacteria. Specifically, while PR-possessing bacteria utilize light energy ("solar-panel strategy"), PR-lacking bacteria exclusively possess UV-screening pigment synthesis genes to avoid UV damage and would adapt to microaerobic environment ("parasol strategy"), which also helps explain why PR-possessing bacteria have smaller genomes than those of PR-lacking bacteria. Collectively, our results highlight the different strategies of dealing with light, DNA repair, and oxygen availability that relate to the presence or absence of PR phototrophy.

The Non-Mendelian Green Cotyledon Gene in Soybean Encodes a Small Subunit of Photosystem II.

Chlorophyll degradation plays important roles in leaf senescence including regulation of degradation of chlorophyll-binding proteins. Although most genes encoding enzymes of the chlorophyll degradation pathway have been identified, the regulation of their activity has not been fully understood. Green cotyledon mutants in legume are stay-green mutants, in which chlorophyll degradation is impaired during leaf senescence and seed maturation. Among them, the soybean (Glycine max) green cotyledon gene cytG is unique because it is maternally inherited. To isolate cytG, we extensively sequenced the soybean chloroplast genome, and detected a 5-bp insertion causing a frame-shift in psbM, which encodes one of the small subunits of photosystem II. Mutant tobacco plants (Nicotiana tabacum) with a disrupted psbM generated using a chloroplast transformation technique had green senescent leaves, confirming that cytG encodes PsbM. The phenotype of cytG was very similar to that of mutant of chlorophyll b reductase catalyzing the first step of chlorophyll b degradation. In fact, chlorophyll b-degrading activity in dark-grown cytG and psbM-knockout seedlings was significantly lower than that of wild-type plants. Our results suggest that PsbM is a unique protein linking photosynthesis in presenescent leaves with chlorophyll degradation during leaf senescence and seed maturation. Additionally, we discuss the origin of cytG, which may have been selected during domestication of soybean.

Case of pleomorphic rhabdomyosarcoma arising on subcutaneous tissue in an adult patient: Review of the published works of 13 cases arising on cutaneous or subcutaneous tissue.

Rhabdomyosarcoma (RMS) is a malignant mesenchymal tumor usually occurring in children, young adults, and predominantly arising in the head and neck or deep soft tissue of the extremities. Pleomorphic RMS (PRMS) arising on subcutaneous tissue in an adult patient's trunk is extremely rare. We present a case of primary PRMS occurring on the back of a 50-year-old man. The tumor was diagnosed by histological and immunohistochemical findings of the resected specimen. One month after the surgery, axillary lymph node metastases were found. Subsequently, the patient received three cycles of combined chemotherapy. The rest of those axillary lymph nodes were reduced in size and there was no local recurrence 6 months postoperatively. PRMS is a very rare but aggressive tumor. Thus, it is important to confirm the diagnosis and provide adequate treatments.

Protective Effect of Hydrogen Gas Inhalation on Muscular Damage Using a Mouse Hindlimb Ischemia-Reperfusion Injury Model.

BACKGROUND: Ischemia-reperfusion injury is one of the leading causes of tissue damage and dysfunction, in particular, free tissue transfer, traumatically amputated extremity, and prolonged tourniquet application during extremity surgery. In this study, the authors investigated the therapeutic effects of hydrogen gas on skeletal muscle ischemia-reperfusion injury. METHODS: The authors compared the concentration of hydrogen in a muscle on intraperitoneal administration of hydrogen-rich saline and on inhalation of hydrogen gas. Animals were subjected to ischemia-reperfusion. Mice were treated with inhalation of hydrogen gas, and the hind gastrocnemius muscle was collected. Muscle morphology and inflammatory change were evaluated after ischemia-reperfusion. Moreover, a footprint test was performed to assess the functional effect of hydrogen. RESULTS: Hydrogen concentration of tissue was significantly higher, and the elevated level was maintained longer by hydrogen gas inhalation than by intraperitoneal administration of hydrogen-rich saline. Infarct zone and area with loss of tissue structure and marked cellular infiltration were significantly decreased in groups treated by hydrogen gas inhalation during ischemia-reperfusion; however, these effects were not observed by posttreatment of hydrogen. One week after ischemia-reperfusion, mice that had been pretreated with hydrogen gas recovered faster and achieved smoother walking in appearance compared with mice in the other groups as assessed by the footprint test. CONCLUSIONS: Inhalation of hydrogen gas attenuates muscle damage, inhibits inflammatory response, and enhances functional recovery. These findings suggest that the optimal route for hydrogen delivery is continuous inhalation of hydrogen gas, which could be a novel clinical mode of treatment in ischemia-reperfusion injury.

Primary bone marrow lymphoma presenting with cold-type autoimmune hemolytic anemia.

We report a rare case of primary bone marrow lymphoma with cold-type autoimmune hemolytic anemia (AIHA). A 70-year-old Japanese woman with suspected liver disorder presented to our hospital with palpitation. On physical examination, she had jaundice and signs of anemia. No lymphadenopathy or hepatosplenomegaly was noted. A direct antiglobulin test was positive for complement C3b and C3d. Anti-IgG testing was negative. Cold agglutinin was positive with a titer of 1:≥8,192, and haptoglobin was absent. A diagnosis of cold-type AIHA was made. Bone marrow biopsy revealed involvement with a population of lymphocytes that were positive for CD20 (L-26), CD79a, and Bcl-2. No lymphoma lesion was detected on computerized tomography or on upper and lower endoscopy. The patient was diagnosed with diffuse large B cell lymphoma (DLBCL) presenting with cold-type AIHA. She was treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone, resulting in complete remission after six cycles. As of 22 months after presentation, no signs of cold-type AIHA or lymphoma were present.

Pharmacological profile of the selective ß3-adrenoceptor agonist mirabegron in cynomolgus monkeys.

Mirabegron is a novel ß3-adrenoceptor agonist developed for the treatment of overactive bladder. To clarify the relationship between the pharmacological effects of mirabegron in monkeys and the clinical efficacy in patients with overactive bladder, the effect of mirabegron on bladder function was evaluated using cynomolgus monkeys. Quantitative PCR revealed that mRNA expression of ß3-adrenoceptors was most abundant (98 %) among ß-adrenoceptor subtypes in the bladder of cynomolgus monkeys. Mirabegron, which showed selective and potent agonistic activity on monkey ß3-adrenoceptors expressed in Chinese hamster ovary cells with EC50 value of 32 nmol/L and intrinsic activity of 0.8, induced concentration-dependent relaxation of bladder smooth muscle strips isolated from cynomolgus monkeys with EC50 values of 120 nmol/L in 20 mmol/L KCl stimulation and 43 nmol/L under 9.81 mN resting tension. In conscious cynomolgus monkeys, mirabegron decreased micturition frequency at oral doses of 1 and 3 mg/kg and increased mean volume voided per micturition at an oral dose of 3 mg/kg. Plasma concentration at which bladder function improved in the cynomolgus monkeys was similar to that at the clinically effective dose in patients with overactive bladder. These data suggest that the relaxant function in monkey bladder is mainly mediated by ß3-adrenoceptors similar to that in the human bladder and mirabegron showed efficacy on the bladder functions of the same parameters in clinical evaluation endpoints.

Effect of mirabegron, a novel ß3-adrenoceptor agonist, on bladder function during storage phase in rats.

Mirabegron, a selective ß(3)-adrenoceptor agonist, facilitates urine storage function by exerting a relaxing effect on bladder smooth muscle. Here, we investigated the effect of mirabegron on bladder function during the storage phase. We assessed the effect of mirabegron on the resting intravesical pressure in anesthetized rats and also tested antimuscarinics (oxybutynin and tolterodine) under the same experimental conditions. Mirabegron dose-dependently decreased the resting intravesical pressure, while oxybutynin and tolterodine showed no statistically significant effects on resting intravesical pressure. We also investigated the effect of mirabegron on bladder function using cystometry technique in conscious rats with bladder outlet obstruction. While mirabegron dose-dependently decreased the frequency of nonvoiding contractions, considered an index of abnormal response in bladder storage, no significant effects were noted on the amplitude of nonvoiding contractions, micturition pressure, threshold pressure, voided volume, residual volume, or bladder capacity. Neither oxybutynin nor tolterodine affected the frequency of nonvoiding contractions; however, oxybutynin increased residual volume and tended to decrease voided volume in a dose-dependent manner, and tolterodine dose-dependently decreased voided volume. Taken together, these results shed light on the suggestion of mirabegron as a therapeutic agent, compared with antimuscarinics, with its most prominent effect being the facilitation of bladder storage.

In vitro and in vivo pharmacological profile of the selective ß3-adrenoceptor agonist mirabegron in rats.

To investigate the pharmacological properties of mirabegron in in vitro and in vivo, the effects on cAMP accumulation in Chinese hamster ovary (CHO) cells expressing rat ß-adrenoceptors, the relaxant activity in isolated rat bladder smooth muscle, and the voiding effects in cerebral infarcted rats were evaluated. Mirabegron increased cAMP accumulation with EC(50) value and intrinsic activity of 19 nmol/L and 1.0, respectively, in CHO cells expressing rat ß(3)-adrenoceptors. The EC(50) values and the intrinsic activities of mirabegron were 610 nmol/L and 0.6 for rat ß(1)-adrenoceptors and were sumless and 0.1 for ß(2)-adrenoceptors, respectively. Mirabegron showed concentration-dependent relaxant and full agonistic effects in rat bladder strips under passive tension with EC(50) value of 290 nmol/L. The concentration-response curve of mirabegron was affected neither by the ß(1)-adrenoceptor selective antagonist CGP-20712A nor by the ß(2)-adrenoceptor selective antagonist ICI-118,551. In in vivo studies with cerebral infarcted rats, a significant decrease in the volume voided per micturition compared with sham-operated rats was observed. Mirabegron dose-dependently increased the volume voided per micturition. In conclusion, we have extended the selectivity profile of mirabegron to rats and demonstrated that it is effective via stimulation of ß(3)-adrenoceptors in a rat cerebral infarction model of detrusor overactivity.