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Icing interventions on the injured skeletal muscle affect the macrophage-related regenerative events and muscle repair. However, despite its importance for the practice in sport medicine, the influence of different icing protocols on muscle regeneration remains unclear. Here, using a rodent model of mild muscle injury with necrosis in a small fraction of myofibers, the injured animals were allocated to four groups: non-icing control (Con) and a single treatment (Ice-1), three treatments (Ice-3), or nine treatments (Ice-9) with a 30-min icing each time within two days following injury. Muscle regeneration was compared between the groups on post-injury days 1, 3, 5, and 7. The results showed that compared with the Con group, muscle regeneration was faster in the Ice-9 group (but not in the Ice-1 and Ice-3 groups), as indicated by more rapid accumulation of satellite cells within the regenerating area and enlarged size of regenerating myofibers ( p <0.05, respectively). There was also less macrophage accumulation ( p <0.05) and a trend toward early removal of necrotic myofibers in the damaged/regenerating area in the Ice-9 group ( p =0.0535). These results demonstrate that in the case of mild muscle damage, more frequent icing treatment is more effective to stimulate muscle regeneration.

Recent advances in bleaching technology, such as bleaching ingredients, have accelerated the development of tooth whitening materials to change the color of natural teeth toward a lighter or whiter shade. Some bleaching materials are used for patients in combination with auxiliary medical devices to activate the bleaching materials by a light or heat source. Bleaching ingredients can be a poisonous and deleterious substance. Some bleaching materials are used in dental offices and the others at home. In clinical development of bleaching materials, appropriate evaluation of safety and efficacy is required according to the intended use. For appropriate and swift approval of the emerging bleaching materials, guideline on evaluation of dental whitening materials was discussed in a commissioned project by the Ministry of Health, Labour and Welfare of Japan for FY2021. Here, we summarize the current principles of the premarketing evaluation of the safety and efficacy., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)

Purpose: Gadobutrol 1.0 M is macrocyclic gadolinium-based contrast agent for magnetic resonance imaging (MRI). This multicenter, open-label, phase 3 study aimed to investigate the efficacy and safety of gadobutrol-enhanced versus unenhanced MRI in the visualization and diagnosis of central nervous system (CNS) lesions in Japanese patients., Methods: A total of 223 patients referred for contrast-enhanced MRI of the CNS underwent unenhanced and gadobutrol-enhanced (0.1 mmol/kg body weight) MRI. The unenhanced and combined (unenhanced and enhanced) images were evaluated by three independent readers in a blinded manner for degree of contrast enhancement, border delineation, internal morphology, and number of detected lesions (primary variables), and for primary diagnosis and diagnostic confidence. Final clinical diagnoses were established by an independent truth committee consisting of two neurosurgeons. Sensitivity, specificity, and accuracy were calculated for the detection of malignancy and the preciseness of diagnoses (secondary variables) by comparing the results obtained by the blinded readers and the truth committee., Results: Gadobutrol enhancement significantly improved three visualization parameters in MR images: contrast enhancement, border delineation, and internal morphology (P < 0.0001). Non-inferiority was achieved for mean number of lesions detected. Gadobutrol-enhanced imaging provided significant improvements in sensitivity and accuracy for the detection of malignant disease with no loss in specificity, and also improvements in accuracy of exact match diagnosis and diagnostic confidence. Drug-related adverse events were reported in 6 out of 223 patients (2.7%); all were non-serious., Conclusion: Gadobutrol is an effective and well-tolerated contrast agent for MR imaging of the CNS.

The present study aimed to evaluate the interaction between wavelength of light in the range of ultra violet A-visible and concentration of H2O2 in the reaction of photolysis of H2O2 from the point of view of hydroxyl radical (·OH) generation and the bactericidal activity. Light emitting diodes (LEDs) emitting the light at wavelengths of 365, 385, 400 and 465 nm were used at an irradiance of 1000 mW/cm(2). H2O2 was used at the final concentrations of 0, 250, 500, and 1000 mM. Quantitative analysis of ·OH generated by the LED irradiation of H2O2 were performed using an electron spin resonance-spin trapping technique. In a bactericidal assay, a bacterial suspension of Staphylococcus aureus prepared in sterile physiological saline was irradiated with the LEDs. The bactericidal activity of each test condition was evaluated by viable counts. When H2O2 was irradiated with the LEDs, ·OH was generated and bacteria were killed dependently on the concentration of H2O2 and the wavelength of LED. The two-way analysis of variance revealed that the wavelength, the H2O2 concentration and their interaction significantly affected the yield of ·OH and the bactericidal activity of the photolysis of H2O2. Therefore, it is suggested that bactericidal activity of photolysis of H2O2 could be enhanced by controlling the wavelength and the concentration of H2O2, which may contributes to shortening the treatment time and/or to reducing the concentration of H2O2., (Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

Our previous study showed that exposing mouse fibroblasts to proanthocyanidin (PA) for only 1 min accelerated cell proliferation in a concentration-dependent manner. In this study, exposing human gingival fibroblasts (HGFs) to PA for 1 min similarly accelerated the proliferative response of the cells. Besides the accelerated proliferative response, PA showed a cytoprotective effect on HGFs exposed to harsh environmental conditions; short-term exposure of HGFs in the mitotic phase to pure water or physiological saline resulted in a lower recovery of viable cells. Pretreatment and concomitant treatment with PA improved the low recovery of cells exposed to pure water or physiological saline. In addition, HGFs exposed to PA for 1 min proliferated well even after being cultured in serum-free medium. In 100% confluent HGFs, being cultured in serum-free medium resulted in a high intracellular reactive oxygen species (ROS) level, but pretreatment with PA prevented the cells from increasing intracellular ROS. Thus, the results suggest that a short-term PA treatment exerts cytoprotective effects on HGFs exposed to harsh environmental conditions by improving the intracellular oxidative stress response.

Objectives: To prospectively evaluate the safety and efficacy of combined unenhanced and gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance (MR) imaging compared with unenhanced MR imaging and triphasic contrast-enhanced spiral computed tomography (CT) for the detection and characterization of focal liver lesions., Materials and Methods: The study was reviewed and approved by the institutional review board at each of the 15 centers involved in the study, and informed written consent was given by all patients. In total, 178 patients with suspected focal hepatic lesions (based, in most patients, on CT, tumor marker and ultrasound examinations) underwent combined MR imaging with a single, rapid injection of Gd-EOB-DTPA 0.025 mmol/kg, including T1-weighted dynamic and delayed MR images 20 to 40 minutes postinjection. Triphasic contrast-enhanced CT, the comparator examination, was performed within 4 weeks of MR imaging. Standard of references (SOR) were resection histopathology and intraoperative ultrasonography, or combined CT during arterial portography and CT hepatic arteriography; in cases where, although the major lesions were treated, some lesion(s) were not treated, follow-up superparamagnetic iron oxide-enhanced MR imaging was additionally performed. All images were assessed for differences in lesion detection and characterization (specific lesion type) by on-site readers and 3, blinded (off-site) reviewers. All adverse events (AEs) occurring within 72 hours after Gd-EOB-DTPA administration were reported., Results: Overall, 9.6% of patients who received Gd-EOB-DTPA reported 21 drug-related AEs. A total of 151 patients were included in the efficacy analysis. Combined MR imaging showed statistically higher sensitivity in lesion detection (67.5%-79.5%) than unenhanced MR imaging (46.5%-59.1%; P < 0.05 for all). Combined MR imaging also showed higher sensitivity in lesion detection than CT (61.1%-73.0%), with the results being statistically significant (P < 0.05) for on-site readers and 2 of 3 blinded readers. Higher sensitivity in lesion detection with combined MR imaging compared with CT was also clearly demonstrated in the following subgroups: lesions with a diameter

The acute toxicities of heavy metals and detergents have been well examined with respect to several endpoints, such as mortality, for application to toxicity tests for environmental assessments. However, chronic influences of these agents on multicellular organisms still need to be determined. Here we studied long-term effects on the lifespan of a free-living nematode, Caenorhabditis elegans, resulting from prolonged exposure to heavy metals or detergents, as well as short-term inhibitory effects on reproduction and growth. These agents inhibited growth of hatched larvae and reproductive capacity in a concentration-dependent manner. They also effectively shortened the lifespan of the adult nematode over the same concentration range. Since toxic effects on both growth and lifespan were observed over similar concentration ranges, where acute toxicities in various endpoints are detected, the shortening of the lifespan can be used as a new endpoint for the assessment of various ecotoxic agents.

A case with splenial astrocytoma that showed various neuropsychological symptoms after disappearance of tumor due to chemo- and radiation therapies. A 40-year-old right-handed truck driver visited the Neurosurgical Clinic with complaints of memory disturbance and loosing his way during truck driving. Under diagnosis of protoplasmic astrocytoma chemotherapy and radiation treatments were carried out. These treatments were satisfactorily effective, but the patient showed marked memory deficits and personality change. He was hospitalized, therefore, into the Neuropsychiatric Clinic 20 months after the above mentioned treatments. Aside personality changes such as lack of inhibition and shameless acts, the patient showed interhemispheric disconnection symptoms (dyslexia in the left visual hemifield), memory deficits, and visual perceptual disturbances. His memory deficits consisted of anterograde and retrograde amnesia and disorientation of time and place, indicating that he had typical amnesic syndrome. In other words he had so-called retrosplenial amnesia. His visual perceptual deficits were impaired performance on many tasks already described as tests of visual perception.

We present a rare case of primary intracranial melanoma in the right occipital region of a 76-year-old male. Magnetic resonance imaging showed an isointensity mass with shorter T1 and T2 relaxation times than those of the opposite hemisphere. A well-defined, dark black tumor was totally removed and histologically diagnosed as malignant melanoma. Eight months postoperatively, however, the tumor recurred and was excised again. He was doing well 1 year after the second operation without additional treatment. In our case, 1) no systemic melanomas were found in close clinical examinations; 2) there was a single nodular tumor attached to the leptomeninges; and 3) a favorable outcome was obtained by surgical treatment alone. These results are consistent with the diagnosis of primary intracranial melanoma.

A series of N-(P-substituted phosphinoyl)peptides were synthesized and their antihypertensive activities were tested in spontaneously hypertensive rats (SHR). Among them, N-(dibenzyloxyphosphinoyl)-L-Ala-L-Pro-L-Pro-OH showed the most potent and long-lasting antihypertensive activity in SHR when administered orally. Although the inhibitory activity of this peptide against the angiotensin-converting enzyme was about one-hundredth of that of Captopril, the antihypertensive activity in SHR was significantly higher and longer-lasting than that of Enalapril which has been reported to be the most potent agent among similar converting enzyme inhibitors.

The antihypertensive effects and mechanisms of a newly developed orally active tripeptide, N-(dibenzyloxyphosphinoyl)-L-alanyl-L-prolyl-L-proline (PAPP), were investigated. When PAPP (1-30 mg/kg orally) was administered to spontaneously hypertensive rats (SHR), systolic blood pressure (SBP) reached a maximum reduction after 8 h and this effect lasted over 24 h. In two-kidney, one clip hypertensive rats (2KIC rats) and DOCA-salt hypertensive rats, PAPP also reduced SBP. In normotensive Wistar rats, however, PAPP did not have a hypotensive effect. PAPP showed low toxicity in Sprague-Dawley rats. The depressor response to bradykinin (BK) was potentiated, but the pressor response to angiotensin I (ANG I) was not inhibited by PAPP. PAPP significantly relaxed isolated SHR aortic strips treated with KC or norepinephrine. Angiotensin converting enzyme (ACE) inhibition by PAPP was relatively low in vivo and in vitro.