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

Positive selection on the Plasmodium falciparum clag2 gene encoding a component of the erythrocyte-binding rhoptry protein complex

A protein complex of high-molecular-mass proteins (PfRhopH) of the human malaria parasite Plasmodium falciparum induces host protective immunity and therefore is a candidate for vaccine development. Clarification of the level of polymorphism and the evolutionary processes is important both for vaccine design and for a better understanding of the evolution of cell invasion in this parasite. In a previous study on 5 genes encoding RhopH1/Clag proteins, positive diversifying selection was detected in clag8 and clag9 but not in the paralogous clag2, clag3.1 and clag3.2. In this study, to extend the analysis of clag polymorphism, we obtained sequences surrounding the most polymorphic regions of clag2, clag8, and clag9 from parasites collected in Thailand. Using sequence data obtained newly in this study and reported previously, we classified clag2 sequences into 5 groups based on the similarity of the deduced amino acid sequences and number of insertions/deletions. By the sliding window method, an excess of nonsynonymous substitutions over synonymous substitutions was detected in the group 1 and group 2 clag2 and clag8 sequences. Population-based analyses also detected a significant departure from the neutral expectation for group 1 clag2 and clag8. Thus, two independent approaches suggest that clag2 is subject to a positive diversifying selection. The previously suggested positive selection on clag8 was also supported by population-based analyses. However, the positive selection on clag9, which was detected by comparing the 5 sequences, was not detected using the additional 34 sequences obtained in this study

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

Recovery of Cryo-injured Rabbit Urethras by Biofabricated C-shaped Adipose-derived Mesenchymal Cell Structures

Article信州医学雑誌 68(6): 357-370(2020)journal articl

Combined treatment with β3-adrenergic receptor agonist and a muscarinic receptor antagonist inhibits detrusor overactivity induced by cold stress in spontaneously hypertensive rats

AimsThis study determined if combined treatment with the muscarinic receptor (MR) antagonist solifenacin and the (3)-adrenergic receptor (AR) agonist mirabegron could inhibit detrusor overactivity induced by cold stress in spontaneously hypertensive rats (SHRs). MethodsThirty-two female 10-week-old SHRs were fed an 8% NaCl-supplemented diet for 4 weeks. Cystometric measurements of the unanesthetized, unrestricted rats were performed at room temperature (RT, 272 degrees C) for 20min. The rats were then intravenously administered vehicle, 0.1mg/kg solifenacin alone, 0.1mg/kg mirabegron alone, or the combination of 0.1mg/kg mirabegron and 0.1mg/kg solifenacin (n=8 each group). Five minutes later, the treated rats were exposed to low temperature (LT, 42 degrees C) for 40min. Finally, the rats were returned to RT. After the cystometric investigations, the (3)-ARs and M-3-MRs expressed within the urinary bladders were analyzed. ResultsJust after transfer from RT to LT, vehicle-, solifenacin-, and mirabegron-treated SHRs exhibited detrusor overactivity that significantly decreased voiding interval and bladder capacity. However, treatment with the combination of solifenacin and mirabegron partially inhibited the cold stress-induced detrusor overactivity patterns. The decreases of voiding interval and bladder capacity in the combination-treated rats were significantly inhibited compared to other groups. Within the urinary bladders, there were no differences between expression levels of M-3-MR and (3)-AR mRNA. The tissue distribution of M-3-MRs was similar to that of the (3)-ARs. ConclusionsThis study suggested that the combination of solifenacin and mirabegron act synergistically to inhibit the cold stress-induced detrusor overactivity in SHRs. Neurourol. Urodynam. 36:1026-1033, 2017. (c) 2016 The Authors. Neurourology and Urodynamics Published by Wiley Periodicals, Inc.ArticleNEUROUROLOGY AND URODYNAMICS.36(4):1026-1033(2016)journal articl

Foehnlike Wind with a Traditional Foehn Effect plus Dry-Diabatic Heating from the Ground Surface Contributing to High Temperatures at the End of a Leeward Area

A foehn wind is an important factor in the occurrence of many extreme high-temperature events in geographically complex regions. In this study, the authors verified the hypothesis that a foehnlike wind contributes to high temperatures at the end of the leeward (eastward) area using three difference approaches: field experiments, numerical experiments, and statistical analyses. According to the hypothesis, a foehnlike wind has the features of the sum of a traditional foehn effect with adiabatic heating, plus dry-diabatic heating from the ground surface along the fetch of the wind. Field experiments conducted at seven observational points on Nobi Plain, Japan, where a mesoscale westerly wind blew, revealed that the westerly wind clearly had the features of a traditional foehn effect in the western part of the Nobi Plain. In addition to field experiments, a simplified estimate using a simple mixed-layer model demonstrated that the wind was further heated by dry-diabatic heating (sensible heat supply) from the ground surface along the fetch (especially in urbanized areas in the eastern region of the Nobi Plain) of the wind. This diabatic heating effect along the fetch of the wind on the high temperature at the end of the leeward area was also supported by both additional numerical experiments and a statistical analysis. These results proved that the hypothesis is correct and indicated that ground conditions and the land use and land cover in the windward area were strongly related to air temperature at the end of the leeward area, where an extremely high temperature was observed