腹腔鏡下副腎摘除術202例の検討

Article信州医学雑誌 61(4):225-232(2013)journal articl

Pathways Involving Beta-3 Adrenergic Receptors Modulate Cold Stress-Induced Detrusor Overactivity in Conscious Rats

ObjectiveTo investigate pathways involving beta-3 adrenergic receptors (ARs) in detrusor overactivity induced by cold stress, we determined if the beta-3 AR agonist CL316243 could modulate the cold stress-induced detrusor overactivity in normal rats. MethodsTwodays prior to cystometric investigations, the bladders of 10-week-old female Sprague-Dawley rats were cannulated. Cystometric measurements of the unanesthetized, unrestricted rats were taken to estimate baseline values at room temperature (RT, 272 degrees C) for 20min. They were then intravenously administered vehicle, 0.1, or 1.0mg/kg CL316243 (n=6 in each group). Fiveminutes after the treatments, they were gently and quickly transferred to the low temperature (LT, 42 degrees C) room for 40min where the cystometric measurements were again made. Afterward, the rats were returned to RT for final cystometric measurements. The cystometric effects of CL316243 were also measured at RT (n=6 in each group). ResultsAt RT, both low and high dose of CL316243 decreased basal and micturition pressure while the high dose (1.0mg/kg) significantly increased voiding interval and bladder capacity. During LT exposure, the high dose of CL316243 partially reduced cold stress-induced detrusor overactivity characterized by increased basal pressure and urinary frequency. The high drug dose also significantly inhibited the decreases of both voiding interval and bladder capacity compared to the vehicle- and low dose (0.1mg/kg)-treated rats. ConclusionA high dose of the beta-3 agonist CL316243 could modulate cold stress-induced detrusor overactivity. Therefore, one of the mechanisms in cold stress-induced detrusor overactivity includes a pathway involving beta-3 ARs.ArticleLUTS-LOWER URINARY TRACT SYMPTOMS.7(1):50-55(2014)journal articl

Expression of 5-Hydroxytryptamine Receptors in Human Urinary Bladders with Benign Prostatic Hyperplasia

Introduction: This study investigated the mRNA expression pattern and distribution of 5-hydroxytryptamine (5-HT) receptors 5-HT2A, 5-HT2B, 5-HT3A, 5-HT4, and 5-HT7 within the urothelium and detrusor of normal bladder tissue and in the urothelium of bladders from patients with benign prostatic hyperplasia (BPH). Methods: Normal urinary bladder specimens were obtained from 13 patients undergoing radical cystectomy due to bladder cancer (normal group) and BPH specimens were obtained from 27 benign prostatic obstruction patients receiving transurethral prostatectomy or retropubic prostatectomy. Receptor subtype mRNA expression was determined by real-time reverse transcription polymerase chain reaction on urothelium, detrusor, and whole mucosal preparations. Receptor distribution was determined by immunohistochemistry. Results: In normal tissues, expressions of 5-HT2B and 5-HT7 receptor mRNAs in the urothelium, detrusor, and whole mucosa were greater than the average expression for all receptor subtype mRNAs. 5-HT2B receptor protein was distributed in the apical urothelium and among the detrusor smooth muscle layers. In contrast, the 5-HT7 receptors were within the urothelium middle cell layers and detrusor smooth muscle cells. The expression pattern of each 5-HT receptor subtype mRNA within the BPH urothelium was similar to that in the normal urothelium. The expression level of 5-HT2A receptor mRNA in the BPH group was significantly lower than the normal group; however, the expressions of both 5-HT3A and 5-HT7 mRNAs were significantly higher. The expressions of both 5-HT2B and 5-HT4 mRNAs were not significantly different between the normal and BPH groups. Conclusion: In normal urinary bladders, the expressions of both 5-HT2B and 5-HT7 mRNAs were higher compared to the 5-HT2A, 5-HT3A, and 5-HT4 mRNAs. The distributions of 5-HT2B and 5-HT7 receptors were different in the urothelium and detrusor layers. The 5-HT3A and 5-HT7 receptor mRNAs in the BPH group were significantly higher compared to the normal urothelium, while the 5-HT2A mRNA was significantly lower.ArticleADVANCES IN THERAPY.32:S29-S37(2015)journal articl

The Relationship Between alpha 1-Adrenergic Receptors and TRPM8 Channels in Detrusor Overactivity Induced by Cold Stress in Ovariectomized Rats

Purpose: We studied whether cold stress induced detrusor overactivity in ovariectomized rats is associated with increased thermosensitive TRPM8 channel expression in the skin and whether the response could be inhibited by alpha 1-adrenergic receptor blockade. Materials and Methods: A total of 24 Sprague-Dawley (R) rats at postnatal week 30 were randomly selected for ovariectomy (16) or sham ovariectomy (8). Five weeks later cystometric measurements of conscious, freely moving rats were made at room temperature (mean +/- SEM 28C +/- 2C) for 20 minutes. Eight ovariectomized rats were intravenously administered 1.0 mg/kg naftopidil. The other 8 ovariectomized and 8 sham operated rats were given naftopidil-free vehicle. Five minutes later they were transferred to a low temperature environment (mean 4C +/- 2C) and micturition patterns were again recorded. TRPM8 channel expression in lumbar skin was estimated by real-time reverse-transcriptase polymerase chain reaction and immunohistochemistry. Results: TRPM8 channel mRNA and protein in the skin of ovariectomized rats were significantly higher than in sham operated rats. At room temperature micturition parameters were similar in sham operated and ovariectomized rats. At low temperature sham operated and ovariectomized rats showed cold stress induced detrusor overactivity but increased micturition frequency and decreased bladder capacity were significantly greater in ovariectomized rats. Treatment of ovariectomized rats with naftopidil inhibited cold stress induced detrusor overactivity. Conclusions: Cold stress induced detrusor overactivity in rats with decreased estrogen is associated with TRPM8 channel up-regulation in the skin and mediated by nerve pathways using alpha 1-adrenergic receptors.ArticleJOURNAL OF UROLOGY. 189(5):1975-1981 (2013)journal articl

A New Milky Way Satellite Discovered In The Subaru/Hyper Suprime-Cam Survey

We report the discovery of a new ultra-faint dwarf satellite companion of the Milky Way based on the early survey data from the Hyper Suprime-Cam Subaru Strategic Program. This new satellite, Virgo I, which is located in the constellation of Virgo, has been identified as a statistically significant (5.5 sigma) spatial overdensity of star-like objects with a well-defined main sequence and red giant branch in their color-magnitude diagram. The significance of this overdensity increases to 10.8 sigma when the relevant isochrone filter is adopted for the search. Based on the distribution of the stars around the likely main sequence turn-off at r ~ 24 mag, the distance to Virgo I is estimated as 87 kpc, and its most likely absolute magnitude calculated from a Monte Carlo analysis is M_V = -0.8 +/- 0.9 mag. This stellar system has an extended spatial distribution with a half-light radius of 38 +12/-11 pc, which clearly distinguishes it from a globular cluster with comparable luminosity. Thus, Virgo I is one of the faintest dwarf satellites known and is located beyond the reach of the Sloan Digital Sky Survey. This demonstrates the power of this survey program to identify very faint dwarf satellites. This discovery of VirgoI is based only on about 100 square degrees of data, thus a large number of faint dwarf satellites are likely to exist in the outer halo of the Milky Way.Comment: typos are corrected, 6 pages, 4 figures, accepted for publication in Ap

Saliva and Plasma Reflect Metabolism Altered by Diabetes and Periodontitis

Periodontitis is an inflammatory disorder caused by disintegration of the balance between the periodontal microbiome and host response. While growing evidence suggests links between periodontitis and various metabolic disorders including type 2 diabetes (T2D), non-alcoholic liver disease, and cardiovascular disease (CVD), which often coexist in individuals with abdominal obesity, factors linking periodontal inflammation to common metabolic alterations remain to be fully elucidated. More detailed characterization of metabolomic profiles associated with multiple oral and cardiometabolic traits may provide better understanding of the complexity of oral-systemic crosstalk and its underlying mechanism. We performed comprehensive profiling of plasma and salivary metabolomes using untargeted gas chromatography/mass spectrometry to investigate multivariate covariation with clinical markers of oral and systemic health in 31 T2D patients with metabolic comorbidities and 30 control subjects. Orthogonal partial least squares (OPLS) results enabled more accurate characterization of associations among 11 oral and 25 systemic clinical outcomes, and 143 salivary and 78 plasma metabolites. In particular, metabolites that reflect cardiometabolic changes were identified in both plasma and saliva, with plasma and salivary ratios of (mannose + allose):1,5-anhydroglucitol achieving areas under the curve of 0.99 and 0.92, respectively, for T2D diagnosis. Additionally, OPLS analysis of periodontal inflamed surface area (PISA) as the numerical response variable revealed shared and unique responses of metabolomic and clinical markers to PISA between healthy and T2D groups. When combined with linear regression models, we found a significant correlation between PISA and multiple metabolites in both groups, including threonate, cadaverine and hydrocinnamate in saliva, as well as lactate and pentadecanoic acid in plasma, of which plasma lactate showed a predominant trend in the healthy group. Unique metabolites associated with PISA in the T2D group included plasma phosphate and salivary malate, while those in the healthy group included plasma gluconate and salivary adenosine. Remarkably, higher PISA was correlated with altered hepatic lipid metabolism in both groups, including higher levels of triglycerides, aspartate aminotransferase and alanine aminotransferase, leading to increased risk of cardiometabolic disease based on a score summarizing levels of CVD-related biomarkers. These findings revealed the potential utility of saliva for evaluating the risk of metabolic disorders without need for a blood test, and provide evidence that disrupted liver lipid metabolism may underlie the link between periodontitis and cardiometabolic disease.Sakanaka A., Kuboniwa M., Katakami N., et al. Saliva and Plasma Reflect Metabolism Altered by Diabetes and Periodontitis. Frontiers in Molecular Biosciences, 8, , 742002. https://doi.org/https://doi.org/10.3389/fmolb.2021.742002