Cold stress induces lower urinary tract symptoms

Cold stress as a result of whole-body cooling at low environmental temperatures exacerbates lower urinary tract symptoms, such as urinary urgency, nocturia and residual urine. We established a model system using healthy conscious rats to explore the mechanisms of cold stress-induced detrusor overactivity. In this review, we summarize the basic findings shown by this model. Rats that were quickly transferred from room temperature (27 +/- 2 degrees C) to low temperature (4 +/- 2 degrees C) showed detrusor overactivity including increased basal pressure and decreased voiding interval, micturition volume, and bladder capacity. The cold stress-induced detrusor overactivity is mediated through a resiniferatoxin-sensitve C-fiber sensory nerve pathway involving 1-adrenergic receptors. Transient receptor potential melastatin8 channels, which are sensitive to thermal changes below 25-28 degrees C, also play an important role in mediating the cold stress responses. Additionally, the sympathetic nervous system is associated with transient hypertension and decreases of skin surface temperature that are closely correlated with the detrusor overactivity. With this cold stress model, we showed that 1-adrenergic receptor antagonists have the potential to treat cold stress-exacerbated lower urinary tract symptoms. In addition, we showed that traditional Japanese herbal mixtures composed of Hachimijiogan act, in part, by increasing skin temperature and reducing the number of cold sensitive transient receptor potential melastatin channels in the skin. The effects of herbal mixtures have the potential to treat and/or prevent the exacerbation of lower urinary tract symptoms by providing resistance to the cold stress responses. Our model provides new opportunities for utilizing animal disease models with altered lower urinary tract functions to explore the effects of novel therapeutic drugs.ArticleINTERNATIONAL JOURNAL OF UROLOGY. 20(7):661-669 (2013)journal articl

Expression of α1-Adrenergic Receptor Subtypes and Angiotensin II Type 1 Receptor in the Prostate of Spontaneously Hypertensive Rats

Background :To clarify the mechanisms of lower urinary tract symptoms (LUTS) associated with benign prostate hyperplasia (BPH), we investigated the expression of α1-adrenergic receptor (AR) subtypes and the angiotensin II type 1 receptor (AT1) within the prostate of spontaneously hypertensive rats (SHRs). Methods :Twelve male 25-week-old SHRs and Wistar Kyoto (WKY) rats were randomly separated into two groups (n =6 each). One group was given 20 ml 0.9% sodium chloride solution (saline) orally per kg-body weight daily for one week. The other group received no treatment. After 7 days of saline loading, systolic blood pressure (SBP) and prostate weight were measured. The prostates were immunohistochemically analyzed for α1-AR subtypes and AT1. Results :After 7 days, the SBP and prostate weight of saline-loaded SHRs tended to increase, but was not significantly different compared to the untreated rats.The expression ofα1-AR subtypes and AT1 within the prostates of saline-loaded SHRs was higher than in the untreated ones. In contrast, the expression in the saline-loaded WKY rat prostates did not increase compared to the untreated ones. Conclusion : Increased numbers of α1-AR subtypes and AT1 in saline-loaded SHR prostates might play important roles in the development of LUTS associated with BPH.Article信州医学雑誌. 58(3): 103-114 (2010)journal articl

Implantation of Autologous Bone Marrow-derived Cells Improves : Erectile Dysfunction in Spontaneously Hypertensive Rats

Article信州医学雑誌 65(1): 37-44(2017)journal articl

The Microenvironment of Freeze-Injured Mouse Urinary Bladders Enables Successful Tissue Engineering

Mouse bone marrow-derived cells implanted into freeze-injured bladder walls form smooth muscle layers, but not in intact walls. We determined if the microenvironment within injured urinary bladders was supportive of smooth muscle layer development. The urinary bladders of female nude mice were freeze-injured for 30 s. Three days later, the rate of blood flow in the wounded areas and in comparable areas of intact control urinary bladders was observed by charge-coupled device (CCD) video microscopy. Injured and control bladder walls were also analyzed histologically and cytologically. Growth factor mRNA expression was determined by real-time reverse transcription polymerase chain reaction arrays. The injured regions maintained a partial microcirculation in which blood flow velocity was significantly less than in controls. The injured bladder walls had few typical smooth muscle layers, and blood vessels in the walls had reduced smooth muscle content. The loss of smooth muscle cells in the bladder walls may have resulted in the formation of large porous spaces seen by scanning electron microscopy of the injured areas. The expression of nineteen growth-related mRNAs, including secreted phosphoprotein 1, inhibin beta-A, glial cell line-derived neurotrophic factor, and transforming growth factor beta 1, were significantly upregulated in the injured urinary bladders. In conclusion, the microenvironment in freeze-injured urinary bladders enables successful tissue engineering.ArticleTISSUE ENGINEERING PART A. 15(11):3367-3375 (2009)journal articl

Male lower urinary tract symptoms and a1D-adrenoceptors

Historically, a1-adrenoceptors have been classified into three subtypes (a1A, a1B and a1D) that are widely distributed in various organs. Research on the a1D-adrenoceptors in the bladder, urethra and prostate has focused on the relationship between expression levels and symptoms of bladder outlet obstruction, and the implications and functional roles of a1D-adrenoceptors subtypes in these organs. The a1D-adrenoceptor messenger ribonucleic acid and protein seem to be increased in obstructed bladders or small capacity bladders. In contrast, a1D-adrenoceptor subtype knock-out mice have been found to have a prolonged voiding interval. Interestingly, an a1D-adrenoceptor antagonist was found to inhibit the facilitation of afferent nerve activity for the micturition reflex induced by intravesical infusion of acetic acid. Clinically, patients who felt urgency at low filling volumes and had a small bladder capacity were found to have more a1D-adrenoceptor messenger ribonucleic acid in their bladder mucosa than patients who felt urgency at high filling volumes and had a large bladder capacity. An a1D-adrenoceptor antagonist was found to increase the first desired volume and the maximum desired volume while decreasing detrusor overactivity in pressure flow studies. Thus, a1D-adrenoceptors in the lower urinary tract might play an important role in the pathophysiology of lower urinary tract disorders.ArticleINTERNATIONAL JOURNAL OF UROLOGY. 20(1):73-78 (2013)journal articl

Differentiation of Smooth Muscle Cells from Human Amniotic Mesenchymal Cells Implanted in the Freeze-Injured Mouse Urinary Bladder

Background: The multipotency of human amniotic mesenchymal cells (HAMCs) has been reported, but the role of HAMCs in urinary tract regeneration is unknown. Objective: The aim of the study was to determine if cells derived from HAMCs support the structural and functional reconstruction of freeze-injured mouse bladders. Design, setting, and participants: HAMCs were harvested from an amnion membrane, and cells were cultured for 7 d prior to injection into the freeze-injured bladder walls of nude mice. Intervention: Three days prior to implantation, the posterior bladder walls were freeze injured for 30 s. The cultured HAMC-derived cells (0.5 x 10(5) cells per 50 mu l) were implanted into the injured regions. Control bladders received a cell-free injection. At 1, 2, 4, and 6 wk after the cell implantation, the experimental bladders were extirpated. Measurements: The bladder tissues were examined by immunohistochemistry for alpha-smooth muscle actin (SMA). The HAMC-derived cells were detected by antihuman nuclei antibody (HuNu). Separately, bladder muscle strips were examined for contractile responses to potassium. Results and limitations: At 1 wk after implantation, the HAMC-derived cells, which were detected by HuNu, differentiated into muscular layers composed of SMA-positive cells. From 2 to 6 wk after implantation, abundant layers of SMA-positive and HuNu-positive cells developed. In control bladders, few SMA-positive cells remained at the injured regions at 1 wk, but by 6 wk, more were present. At 1 wk, the contractile responses to potassium of the cell-implanted bladders were significantly higher than those of the control-injected ones. Control-injected bladders also recovered by 6 wk, but the rate of recovery was slower. Conclusions: Freeze-injured mouse bladders implanted with HAMC-derived cells recovered morphology and function faster than control-injected bladders.ArticleEUROPEAN UROLOGY. 58(2):299-306 (2010)journal articl

Implantation of Autologous Bone-Marrow-Derived Cells Reconstructs Functional Urethral Sphincters in Rabbits

The purpose of this study was to determine if implantation of autologous bone-marrow-derived cells has the potential to treat stress urinary incontinence caused by intrinsic sphincter deficiency. Bone marrow cells harvested from femurs of New Zealand White rabbits were cultured for 10 days. Seven days before implantation, the urethral sphincters located at the internal urethral orifice were cryo-injured by spraying liquid nitrogen for 15 s. The cultured autologous bone-marrow-derived cells were implanted 7 days after cryo-injury. For controls, cell-free solutions were injected. At 7 and 14 days after implantation, leak point pressures were determined and the urethral sphincters were examined by immunohistochemistry. At 7 and 14 days, the cell-implanted regions contained numerous striated and smooth muscle-like cells expressing myoglobin and smooth muscle actin, respectively. The proportions of myoglobin- and smooth muscle actin-expressing areas in both the 7- and 14-day cell-implanted regions were significantly higher than in controls. By 14 days, these differentiated cells formed contacts with similar cells, creating layered muscle structures. At that time, the leak point pressure of the cell-implanted rabbits was significantly higher than that of the controls. In conclusion, autologous bone-marrow-derived cells can reconstruct functional urethral sphincters.ArticleTISSUE ENGINEERING PART A. 17(41098):1069-1081 (2011)journal articl

A Design for the 178-MHz WXGA 30-fps Optical Flow Processor Based on the HOE Algorithm

We propose an optical flow processor, which allows real-Time processing of WXGA 30-fps at 178.3 MHz. By introducing the SOR method and a pipeline operation for the Gauss-Seidel method to the iterative flow calculation, computational complexity can be reduced to 14.5% when compared to the previous HOE processor. We decreased the area of the embedded memory by using the image division method, applying line memory, and optimizing the computation word length. The core size of the designed processor is 16.82 mm2 in 90 nm process technology, which is approximately 5% of the previous HOE processor. The processor can operate completely in parallel, which ensures high-resolution scalability. © 2015 IEEE.18th IEEE International Symposium on Design and Diagnostics of Electronic Circuits and Systems, DDECS 2015; Belgrade; Serbia; 22 April 2015 through 24 April 2015; Category numberE5519; Code 11688