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Purpose: Patients with diabetes mellitus (DM) often exhibit refractory erectile dysfunction (ED). Red-light-controllable nitric oxide donor (NORD-1) and red-light irradiation have successfully enhanced erectile function in intact rats. In this study, we investigated whether the combination of NORD-1 and red-light irradiation effectively treated ED in streptozotocin (STZ)- treated rats with DM. Materials and Methods: Seven-week-old male Sprague-Dawley rats were used in this study. Rats in the DM and sham groups received intravenous STZ (50 mg/kg) and saline, respectively. One week after treatment, the blood glucose level of rats in the DM group was >250 mg/dL. Five weeks after the treatment, we performed a functional study by measuring intracavernous pressure (ICP) under cavernous nerve stimulation before and after NORD-1 treatment with and without light irradiation. Additionally, we performed an isometric tension study using the corpus cavernosum of rats treated with NORD-1 or the control compound, SiR650. Results: The ICP/mean arterial pressure (MAP) ratio was significantly lower in the DM group than in the sham group before and after NORD-1 treatment without light irradiation (both p

Quantifying the transport of floating macroplastic debris (FMPD) in waterways is essential for understanding the plastic emission from land. However, no robust tool has been developed to monitor FMPD. Here, to detect FMPD on river surfaces, we developed five instance segmentation models based on state-of-the-art You Only Look Once (YOLOv8) architecture using 7,356 training images collected via fixed-camera monitoring of seven rivers. Our models could detect FMPD using object detection and image segmentation approaches with accuracies similar to those of the pretrained YOLOv8 model. Our model performances were tested using 3,802 images generated from 107 frames obtained by a novel camera system embedded in an ultrasonic water level gauge (WLGCAM) installed in three rivers. Interestingly, the model with intermediate weight parameters most accurately detected FMPD, whereas the model with the most parameters exhibited poor performance due to overfitting. Additionally, we assessed the dependence of the detection performance on the ground sampling distance (GSD) and found that a smaller GSD for image segmentation approach and larger GSD for object detection approach are capable of accurately detecting FMPD. Based on the results from our study, more appropriate category selections need to be determined to improve the model performance and reduce the number of false positives. Our study can aid in the development of guidelines for monitoring FMPD and the establishment of an algorithm for quantifying the transport of FMPD.

Catheterization is commonly performed in pelvic surgery to manage postoperative urinary dysfunction. However, little is known about the effects of catheterization on bladder function, although catheterization can drain urine from the bladder. In the present study, we evaluated the short-term effects of catheterization on detrusor muscle contraction in a rat model of postoperative urinary dysfunction due to bilateral accessory nerve injury (BACNI). Ten-week-old male Wistar/ST rats were divided into sham, sham＋catheterization (sham＋C), BACNI, and BACNI＋catherterization (BACNI＋C) groups. The sham＋C and BACNI＋C groups underwent catheter placement in the bladder dome prior to sham or BACNI surgery and intermittent bladder drainage during the observation period. Four hours after surgery, the bladders were excised and subjected to isometric tension study and immunofluorescence staining. Bladder overdistension and overflow urinary incontinence were observed in the BACNI group, not the BACNI＋C group. The contractile responses of the detrusor muscle to 80 mM KCl, carbachol, and electrical field stimulation (EFS) were enhanced in the BACNI group compared to the sham group; the enhanced contractile responses to EFS were improved in the BACNI＋C group. The ratio of the detrusor muscle layer area to the total bladder area increased with increasing interstitial area ratio in the BACNI and BACNI＋C groups, while the total bladder area increased in the sham＋C and BACNI＋C groups. These results suggest that catheterization does not improve the augmentation of detrusor muscle contraction and increase in the detrusor muscle layer area ratio immediately after BACNI and that catheterization causes bladder hypertrophy.

Purpose: Neurogenic erectile dysfunction (ED) is a common side effect of radical prostatectomy (RP) because of cavernous nerve damage. In these patients, the production of nitric oxide (NO), which is important for erection, is decreased in the corpus cavernosum. Therefore, NO donors are useful for post-RP ED. However, short half-life and systemic side effects are problems of NO application in ED therapy. To avert these problems, we developed a red-light controllable NO releaser, NORD-1. This study aimed to investigate the effect of NORD-1 and red-light irradiation on neurogenic ED using a rat model of bilateral cavernous nerve injury (BCNI). Materials and Methods: BCNI and sham operations were conducted on 8-week-old rats. After 4 weeks, erectile function was evaluated using changes in intracavernous pressure (ICP) during electrostimulation of the cavernous nerve. ICP was measured under three conditions; without NORD-1 and red-light irradiation, with NORD-1 and without red-light irradiation, and with NORD-1 and red-light irradiation. SiR650 which absorbs red-light but does not release NO was used for the negative control. After the experiment, localization of NORD-1 was observed using a microscope. Results: Erectile function in a BCNI rat model was significantly decreased compared to sham-operated rats (p

Podocyte injury is responsible for nephrotic syndrome. Previously, we found that tadalafil, a phosphodiesterase 5 inhibitor, might have protective effects on podocytes. Here, we investigated the effects of tadalafil in a nephrotic syndrome model and human podocyte cells.We divided adriamycin (ADR)-induced nephrotic syndrome model rats into the following groups: control + vehicle, control + tadalafil, ADR + vehicle, and ADR + tadalafil. The tadalafil-treated groups were orally administered 10 mg/kg tadalafil for 2 weeks. Renal parameters were measured. Immunohistology and immunofluorescence assays of glomerular injury were performed. Human primary podocytes were treated with or without tadalafil, and ADR. Cell viability and permeability assays were performed.ADR + vehicle exhibited severe proteinuria compared with control + vehicle and control + tadalafil. ADR + tadalafil attenuated proteinuria compared with ADR + vehicle. Wilms’ tumor 1 (WT1) immunostaining revealed that the number of WT1-positive cells was decreased by ADR; however, this decrease was prevented by ADR + tadalafil. In human podocytes, tadalafil increased the viability of ADR-treated cells, which was abrogated by KT5823, a cGMP-dependent protein kinase (PKG) inhibitor. Moreover, tadalafil prevented albumin permeability in ADR-treated cells. ADR treatment alone increased the permeability of albumin compared with the control.Tadalafil might inhibit kidney injury progression by preventing damage to podocytes and dysfunction of the glomerular filtration barrier.

Cisplatin (CDDP) is a widely used anticancer drug, but acute kidney injury (AKI) is one of the most important dose-limiting factors. Trace metal elements are present in various concentrations in the body and play an important role in maintaining normal vital functions. However, the relationship between CDDP-induced AKI and trace metal elements is unknown. In this study, we cultured human renal proximal tubular epithelial cells in the presence of CDDP (0, 12.5, 25, 50 μM) and analyzed the concentration of trace elements in medium after 24 h. We found that CDDP significantly increased the concentrations of zinc (Zn) and manganese (Mn) in medium and significantly decreased them in lysate. Therefore, we examined the effects of CDDP (3 mg/kg, i.p.) administration on serum and urinary Zn and Mn concentrations in rats. The results showed that urinary excretion of Zn and Mn increased in CDDP-treated rats 5 days after administration. Also, 5 days after administration, pyknosis, nuclear loss, loss of the brush border membrane, and DNA fragmentation were observed, and serum creatinine and blood urea nitrogen levels were found to be significantly increased. These data suggested that 24-h excretion of Zn and Mn might reflect on CDDP induced nephropathy. Monitoring urinary Zn and Mn excretion may be beneficial in detecting AKI, but further studies are needed for clinical application.

Abstract Background Erectile dysfunction (ED) is one of the causes of male infertility and is a disease that requires treatment. The first‐line drugs for ED are phosphodiesterase 5 (PDE‐5) inhibitors, and further treatment options are currently limited. Medical technologies, such as genetic control and regenerative medicine, are developing rapidly. Research on erectile function is progressing rapidly, coupled with technological innovations in other areas. Methods A PubMed search using the keywords “animal (rat, mouse, rabbit, dog, and monkey)” and “erectile” was conducted, and all relevant peer‐reviewed English results were evaluated. Main findings The methods for evaluating erectile function include intracavernous pressure (ICP) measurements, isometric tension studies, and dynamic infusion cavernosometry. Papers also reported various disease model animals for the study of diabetes mellitus, cavernous nerve injury, and drug‐induced ED. Conclusion Basic research on ED treatment has progressed rapidly over the past 20 years. In particular, research on the mechanism of ED has been accelerated by the publication of a study on the evaluation of erectile function using ICP measurements in rats. In addition, molecular biological experimental methods such as polymerase chain reaction (PCR) and western blotting have become relatively easy to perform due to technological progress, thus advancing research development.

ABSTRACT: Background: Testosterone is an important hormone for the physical and mental health of men; however testosterone administration has also been suggested to adversely affect the cardiovascular system. Aim: To investigate the effects of excessive testosterone administration on vascular endothelial and erectile function in rats. Methods: A total of seventy-five 12-week-old rats were divided into the following groups: Sham, castrated (Cast), castrated with subcutaneous administration of 100 mg/kg/month testosterone (Cast + T1), and castrated with subcutaneous administration of 100 mg/kg/week testosterone (Cast + T4). To observe the changes in testosterone level after the administration, rats were further divided into the following groups: control; T(6.25), wherein the rats were subcutaneously injected with 6.25 mg/kg testosterone; T(25) per week, wherein the rats were subcutaneously injected with 25 mg/kg testosterone per week; and T(100), wherein the rats were subcutaneously injected with 100 mg/kg testosterone per week. The relaxation responses of aorta were measured in these rats using standardized methods, and their erectile function was also evaluated. Statistical analysis of the obtained data was performed using two-way analysis of variance (ANOVA), Tukey-Kramer's multiple comparison test, or Student's t-test. Outcomes: At the end of the study period, endothelial function was evaluated through measurement of isometric tension, while erectile function was assessed using intracavernosal pressure (ICP), mean arterial pressure (MAP), and the expression of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), sirtuin 1 (Sirt1) and vascular endothelial growth factor A. Results: The ICP/MAP ratio in the Cast group (0.42 ± 0.04) was significantly lower than that in the Sham group (0.79 ± 0.07). The ICP/MAP ratio in the Cast + T1 group (0.73 ± 0.06) was significantly higher than that in the Cast group (P < .01) and that of the Cast + T4 (0.38 ± 0.01) group was unchanged (P > .05). The T(25) and T(100) groups exhibited significantly lower responses to ACh than the control group at 4 weeks (P < .01). Meanwhile, the ICP/MAP ratios in the T(25) group (0.44 ± 0.07) and T(100) group (0.47 ± 0.03) were significantly lower than that in the control group (0.67 ± 0.05) at stimulation frequencies of 16 Hz (P < .05). The expression of androgen receptor, Sirt1, and eNOS were significantly lower while that of iNOS was higher in the T(25) group compared with the control group (P < .05). Clinical Translation: The results based on this animal model indicate that extremely high testosterone levels may affect endothelial and erectile function. Strengths and Limitations: We found that high-dose testosterone administration decreased endothelial function in aorta and erectile function in rats. A major limitation of this study is that the blood concentration may not be representative of that in humans, and further research is needed. Conclusion: The findings suggest that high doses of testosterone may cause endothelial dysfunction in the aorta and erectile dysfunction in rats and that the blood concentration should be monitored after testosterone administration.Kataoka T, Fukamoto A, Hotta Y, et al. Effect of High Testosterone Levels on Endothelial Function in Aorta and Erectile Function in Rats. Sex Med 2022;10:100550.

Background: The number of patients with cancer and end-stage renal disease is increasing because of the success of hemodialysis treatment. However, methods for monitoring opioids to control severe pain induced by cancer remain unsatisfactory. Case Presentation: A 72-year-old male, with a history of hemodialysis induced by diabetic nephropathy for 16 years and prostate cancer for three years, was diagnosed with metastasis in his 12th thoracic and 2nd lumbar vertebrae, and treated with analgesic pain management (oxycodone, acetaminophen, and pregabalin) and radiotherapy. Case management and outcome: Concern about poor pain control induced by the instability of blood opioid levels caused by hemodialysis meant the serum concentration of oxycodone was measured pre- and post-dialysis. Since the impact of pain on daily life cannot be fully assessed by pain score questionnaires, we also monitored patient activity using a wrist band-type activity tracker. A pain numeric rating score was used. Inter-day variations in the number of steps per day were observed. The relationship between pain score and blood concentrations of oxycodone pre- and post-dialysis was analyzed. The serum concentration of oxycodone was stable, even after hemodialysis, and the patient's pain gradually decreased. Conclusion: By monitoring the serum concentration of oxycodone, we obtained good pain control for bone metastasis in a patient with prostate cancer undergoing dialysis. We also monitored physical activity using an activity tracker. These findings might be useful in the selection of analgesics during the control of cancer pain in dialysis patients and allow for the objective management of opioid dosage.

We aimed to control the relaxation of rat bladder neck specimens by using NORD-1, a red light-reactive nitric oxide (NO) releaser. Female and male 10–11-week-old Wistar/ST rats were divided into three groups: NORD-1, vehicle, and NORD-1+[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; a soluble guanylyl cyclase inhibitor). We infused 10−4 M NORD-1 into the bladders of NORD-1 and NORD-1+ODQ group rats and the vehicle into those of vehicle group rats. Isometric tension was analyzed using circular bladder neck specimens with 10−5 M NG-nitro-l-arginine methyl ester, an NO synthase inhibitor. Moreover, 10−5 M ODQ was added into the NORD-1+ODQ group bath. After precontraction with 10−5 M carbachol, the specimens were irradiated with red light and their relaxation responses were measured. We evaluated NORD-1 tissue permeability by observing the sliced bladder neck specimens. The NORD-1 group specimens relaxed during red light irradiation; the relaxation response increased with the increase in light intensity. The vehicle and NORD-1+ODQ group specimens did not respond to irradiation. Sex-related differences in responsiveness were not noted. NORD-1 permeated into the urothelium of NORD-1 group specimens. Rat bladder neck relaxation was controlled by NORD-1 and light irradiation in vitro. NORD-1 might be a novel therapeutic agent for voiding dysfunction.

We aimed to investigate detrusor function in a previously developed rat neurogenic voiding dysfunction model that we have developed previously. We performed sham or bilateral accessory nerve injury (BACNI) surgeries on ten-week-old male Wistar/ST rats. One week after surgery, we evaluated detrusor contractility in the bladder using isometric tension and mRNA expression assays. Cholinergic contraction was attenuated in the injury model, whereas carbachol-evoked contraction was enhanced, and mRNA expression of the cholinergic receptor increased. These findings suggest that there was a reduction in neurotransmitter release causing detrusor underactivity.

Abstract Purpose Erectile dysfunction (ED) is one of the increasing diseases with aging society. The basis of ED derived from local penile abnormality is poorly understood because of the complex three‐dimensional (3D) distribution of sinusoids in corpus cavernosum (CC). Understanding the 3D histological structure of penis is thus necessary. Analyses on the status of regulatory signals for such abnormality are also performed. Methods To analyze the 3D structure of sinusoid, 3D reconstruction from serial sections of murine CC were performed. Histological analyses between young (2 months old) and aged (14 months old) CC were performed. As for chondrogenic signaling status of aged CC, SOX9 and RBPJK staining was examined. Results Sinusoids prominently developed in the outer regions of CC adjacent to tunica albuginea. Aged CC samples contained ectopic chondrocytes in such regions. Associating with the appearance of chondrocytes, the expression of SOX9, chondrogenic regulator, was upregulated. The expression of RBPJK, one of the Notch signal regulators, was downregulated in the aged CC. Conclusions Prominent sinusoids distribute in the outer region of CC which may possess important roles for erection. A possibility of ectopic chondrogenesis induced by alteration of SOX9/Notch signaling with aging is indicated.

Androgens are essential for male physical activity. Age-related androgen deficiency, known as late-onset hypogonadism (LOH), is considered a risk factor for several diseases. There are many men’s health supplements on the market. Therefore, the purpose of this review is to summarize the food ingredients that have been suggested in published literature to increase testosterone levels. A review of previously reported animal studies suggested that 5 representative nutritional components, 7 food ingredients, and 25 supplements were associated with testosterone. Some food and supplements influence testosterone levels in various animals by directly increasing testosterone or suppressing the decrease in testosterone production due to testicular toxicity. There are three mechanisms by which foods or supplements increase testosterone production: 1) regulating luteinizing hormone, the hormone that stimulates testosterone production, 2) regulating testosterone synthase in the testis, and 3) regulating testosterone-degrading enzymes. In contrast, suppressing the decrease in testosterone depends on the antioxidant effect of the foods. Although detailed mechanistic studies and clinical trials are required to validate these findings, the use of food to regulate testosterone levels is a promising therapeutic option.

ABSTRACT: Background: A platinum-containing anti-cancer agent, oxaliplatin (L-OHP), is known to induce peripheral neuropathy, including erectile dysfunction (ED) as a side effect, while Gosha-jinki-gan (GJG) is a traditional Japanese herbal medicine mainly used for peripheral neuropathy. Aim: To investigate the effect of GJG on L-OHP-induced ED in rats. Methods: Twelve-week-old male Wister/ST rats were categorized into the following groups: Sham, Sham+GJG, L-OHP, and L-OHP+GJG (each n = 10). The L-OHP and L-OHP+GJG groups were injected intravenously with L-OHP (4 mg/kg) for 2 consecutive days in the first week. Statistical significance was determined using Bonferroni's multiple comparison test. Outcomes: At the end of the study period, erectile function was evaluated by measuring intracavernosal pressure (ICP) and mean arterial pressure (MAP) after cavernous nerve stimulation. Western blot analysis was used to assess the neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) levels, and quantitative polymerase chain reaction was used to assess the expression of phosphodiesterase-5 (PDE-5) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-1. Results: The ICP/MAP ratio of L-OHP rats (0.34 ± 0.06) was significantly lower than that of Sham rats (0.67 ± 0.03, P < .01), however, the ICP/MAP ratio of L-OHP+GJG rats (0.55 ± 0.01) was significantly higher than that of L-OHP rats (P < .01). There were no significant differences in the nNOS and eNOS protein expression between both groups (P > .05). GJG administration significantly decreased PDE-5 and NADPH oxidase-1 messenger RNA expressions in the L-OHP+GJG group. Clinical Translation: This animal model study suggests that GJG might be effective for erectile function in cancer survivors. Strengths & limitations: Our study identified that GJG had no notable side effects in the treated group. Further investigation of the cavernous nerve would also help elucidate the mechanism of GJG effect, which is a limitation of this study. Conclusion: We found that GJG administration improved L-OHP-induced ED by improving transcriptional PDE-5 expression.Kataoka T, Kawaki Y, Kito Y, et al. Gosha-Jinki-Gan Improved Erectile Dysfunction Caused by Anti-Cancer Agent Oxaliplatin by Decreasing Transcriptional Expression of Phosphodiesterase-5 in Rats. Sex Med 2022;10:100484.

ABSTRACT: Introduction: Carbohydrate restriction in diet is becoming a popular means of losing weight nowadays, although it has been reported that excessive intake of low-carbohydrate and high-protein (LCHP) diet causes an adverse effect on cardiovascular function. Aim: To investigate the influence of LCHP on erectile function in rats. Methods: A total of 48, 12-week-old rats were divided into 2 groups and either fed a LCHP diet (LCHP group) or a normal diet (Control group). Hematological examination, blood pressure evaluation, erectile function assessments as well as evaluations of the relaxation and contractile responses of corpus cavernosum were carried out in these rats by using standardized methods. Statistical analysis using 2-way ANOVA and Welch's t-test was conducted to examine the obtained data. Main Outcome Measure: At the end of the study period, the evaluated outcomes to assess erectile function were intracavernosal pressure , mean arterial pressure , endothelial functions, nitric oxide (NO)-operated nerve functions and the expressions of endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), and sphingosine-1-phosphate receptor 1 (S1P1). Results: The intracavernosal pressure / mean arterial pressure ratio was significantly lower in the LCHP group (P < .05) at 4 weeks. Compared to the Control group, the LCHP group exhibited significantly lower responses to ACh and EFS and a decreased nNOS mRNA expression. The results based on this animal model indicate that extreme carbohydrate restricted diet may affect erectile function. Our study identified that LCHP decreased erectile function in rats. A major limitation of this study is, due to the extreme condition of completely replacing carbohydrates with protein, that carbohydrate intake will be gradually increased in the future. Conclusion: Extreme carbohydrate restriction and high protein in diet may cause ED with vascular endothelial dysfunction and a decrease in the relaxation response of the corpus cavernosum smooth muscle via NO-operated nerves.Kataoka T, Hidaka J, Suzuki J, et al. Evaluating the Effects of Low Carbohydrate and High Protein Diet on Erectile Function in Rats. Sex Med 2021;10:100500.

Abstract Purpose Penile research is expected to reveal new targets for treatment and prevention of the complex mechanisms of its disorder including erectile dysfunction (ED). Thus, analyses of the molecular processes of penile ED and continuous erection as priapism are essential issues of reproductive medicine. Methods By performing mouse N‐ethyl‐N‐nitrosourea mutagenesis and exome sequencing, we established a novel mouse line displaying protruded genitalia phenotype (PGP; priapism‐like phenotype) and identified a novel Pitpna gene mutation for PGP. Extensive histological analyses on the Pitpna mutant and intracavernous pressure measurement (ICP) and liquid chromatography–electrospray ionization tandem mass spectrometry (LC–ESI/MS)/MS analyses were performed. Results We evaluated the role of phospholipids during erection for the first time and showed the mutants of inducible phenotypes of priapism. Moreover, quantitative analysis using LC–ESI/MS/MS revealed that the level of phosphatidylinositol (PI) was significantly lower in the mutant penile samples. These results imply that PI may contribute to penile erection by PITPα. Conclusions Our findings suggest that the current mutant is a mouse model for priapism and abnormalities in PI signaling pathways through PITPα may lead to priapism providing an attractive novel therapeutic target in its treatment.

Monitoring marine contamination by floating litter can be particularly challenging since debris are continuously moving over a large spatial extent pushed by currents, waves, and winds. Floating litter contamination have mostly relied on opportunistic surveys from vessels, modeling and, more recently, remote sensing with spectral analysis. This study explores how a low-cost commercial unmanned aircraft system equipped with a high-resolution RGB camera can be used as an alternative to conduct floating litter surveys in coastal waters or from vessels. The study compares different processing and analytical strategies and discusses operational constraints. Collected UAS images were analyzed using three different approaches: (i) manual counting (MC), using visual inspection and image annotation with object counts as a baseline; (ii) pixel-based detection, an automated color analysis process to assess overall contamination; and (iii) machine learning (ML), automated object detection and identification using state-of-the-art convolutional neural network (CNNs). Our findings illustrate that MC still remains the most precise method for classifying different floating objects. ML still has a heterogeneous performance in correctly identifying different classes of floating litter; however, it demonstrates promising results in detecting floating items, which can be leveraged to scale up monitoring efforts and be used in automated analysis of large sets of imagery to assess relative floating litter contamination.

Abstract Stress is a risk factor for erectile dysfunction (ED); however, the pathology of stress‐induced ED remains unclear. Accordingly, in this study, we investigated the mechanisms of stress‐induced ED using a rat model. Ten‐week‐old male Wistar/ST rats were maintained in a cage filled with water to a height of 2 cm (stress group) or a normal cage (control group). We found that water immersion stress significantly enhanced the contractile response to noradrenaline in the corpus cavernosum (CC) (p

Background: Because androgen replacement therapy (ART) is not performed immediately after the onset of androgen deficiency, the treatment is considered to be late. Aim: To investigate the effects of late ART, starting 4 weeks after castration of rats, on erectile function and structural changes in the corpus cavernosum. Methods: Rats were subjected to ART for 4 (Late-ART [4w]) or 8 (Late-ART [8w]) weeks. In either case, rats were assigned to the following groups: castrated (Cast), castrated with subcutaneous administration of testosterone (3 mg/kg/day; Cast+T), and sham (Sham). Cast + T rats received daily subcutaneous doses of testosterone starting 4 weeks after castration for 4 or 8 weeks whereas Sham and Cast rats received only the vehicle. Outcomes: Erectile function was assessed by evaluating intracavernosal pressure (ICP) and mean arterial pressure (MAP) after electrical stimulation of the cavernous nerve, corporal veno-occlusive function using dynamic infusion cavernosometry, and histology using Masson's trichrome staining. Results: No increase in the ICP was observed in Cast+T rats in the Late-ART (4w) group (0.47 ± 0.02, P > .05), whereas, in Cast+T rats in the Late-ART (8w) group, there was a significant increase in the ICP/MAP ratio (0.60 ± 0.02, P < .05), drop rate, and smooth muscle/collagen ratio. Clinical Translation: The present study provides scientific evidence for the effect of late ART on erectile function. Strengths and Limitations: This study provides insights into the influence of late ART on erectile function through improvements in the structure of corpus cavernosum. The major limitation of this study is the difference in the time required for healing between the humans and rats, which might have a bearing on the translational relevenace of the results. Conclusions: Late ART could improve erectile function. However, as improvement requires a considerable time period, it is necessary to persist with therapy patiently for optimal results.Kataoka T, Hotta Y, Yamamoto Y, et al. Effect of Late Androgen Replacement Therapy on Erectile Function Through Structural Changes in Castrated Rats. Sex Med 2021;XX:XX–XXX.

The photochemically-induced thrombosis (photothrombosis) method can create focal cerebral infarcts anywhere in the relatively superficial layers of the cerebrum; it is easy to implement and minimally invasive. Taking advantage of this versatility, we aimed to establish a new rat model of urinary frequency with focal cerebral infarction, which was characterized by its simplicity, nonlethal nature, and high reproducibility. The prefrontal cortex and the anterior cingulate cortex, which are involved in lower urinary tract control, were targeted for focal cerebral infarction, and urinary parameters were measured by cystometrogram. Cystometric analysis indicated that micturition intervals significantly shortened in photothrombosis-treated rats compared with those in the sham operative group on Days 1 and 7 (P < 0.01), but prolonged after 14 days, with no difference between the two groups. Immunopathological evaluation showed an accumulation of activated microglia, followed by an increase in reactive astrocytes at the peri-infarct zone after photothrombotic stroke. Throughout this study, all postphotothrombosis rats showed cerebral infarction in the prefrontal cortex and anterior cingulate cortex; there were no cases of rats with fatal cerebral infarction. This model corresponded to the clinical presentation, in that the micturition status changed after stroke. In conclusion, this novel model combining nonlethality and high reproducibility may be a suitable model of urinary frequency after focal cerebral infarction.

Abstract Phosphodiesterase 5 inhibitors are widely used to treat erectile dysfunction and lower urinary tract symptoms with benign prostatic hyperplasia. Recent studies have indicated the renoprotective effects of this class of compounds. Whether renoprotection depends on blood pressure reduction remains controversial. In this study, we investigated the renoprotective effects of the phosphodiesterase 5 inhibitor, tadalafil, in a rat model of high‐salt induced kidney injury with hypertension. Dahl salt‐sensitive rats were fed a normal diet, high‐salt (8% sodium chloride) diet, or high‐salt diet with oral administration of either low‐ or high‐dose tadalafil (1 and 10 mg kg−1 day−1, respectively). Serum creatinine, urinary protein, and blood pressure were measured at baseline and after 8 weeks, at which point the rats were examined for glomerular injury and fibrosis. PAI1 mRNA levels were also evaluated. After 8 weeks, blood pressure, serum creatinine, and urinary protein levels were significantly higher in the high‐salt group than those in the normal‐salt group. Serum creatinine and urinary protein were significantly lower in both tadalafil groups than those in the high‐salt group, while only high‐dose tadalafil affected blood pressure. In addition, glomerulosclerosis and α‐smooth muscle actin expression significantly decreased in both tadalafil treatment groups. PAI1 mRNA increased significantly in the high‐salt group but decreased in both tadalafil‐treated groups. Our results indicated that both low‐ and high‐dose tadalafil prevented fibrosis and glomerular injury in a chronic kidney disease rat model. Mechanistically, these effects may be associated with PAI1 expression and glomerular structure protection.

We aimed to investigate whether high salt intake affects bladder function via epithelial sodium channel (ENaC) by using Dahl salt-resistant (DR) and salt-sensitive (DS) rats. Bladder weight of DR + high-salt diet (HS, 8% NaCl) and DS + HS groups were significantly higher than those of DR + normal-salt diet (NS, 0.3% NaCl) and DS + NS groups after one week treatment. We thereafter used only DR + HS and DS + HS group. Systolic and diastolic blood pressures were significantly higher in DS + HS group than in DR + HS group after the treatment period. Cystometrogram showed the intercontraction intervals (ICI) were significantly shorter in DS + HS group than in DR + HS group during infusion of saline. Subsequent infusion of amiloride significantly prolonged ICI in DS + HS group, while no intra-group difference in ICI was observed in DR + HS group. No intra- or inter-group differences in maximum intravesical pressure were observed. Protein expression levels of ENaCα in the bladder were significantly higher in DS + HS group than in DR + HS group. ENaCα protein was localized at bladder epithelium in both groups. In conclusion, high salt intake is considered to cause urinary storage dysfunction via upregulation of ENaC in the bladder epithelium with salt-sensitive hypertension, suggesting that ENaC might be a candidate for therapeutic target for urinary storage dysfunction.

Background: It is difficult to objectively evaluate chemotherapy-related adverse events early in elderly patients with urothelial carcinoma. A delayed response causes a reduction in quality of life (QoL). Wearable activity systems that objectively record life logs have recently been used. Objectives: This study was undertaken to verify the reliability and effectiveness of a wearable activity system (Fitbit) to monitor subjective symptoms in an objective manner during chemotherapy for elderly patients with urothelial cancer (UC). Materials and Methods: This was a cohort prospective study. Elderly patients with UC were enrolled who received short hydration gemcitabine and cisplatin (shGC) combination therapy at Nagoya City University Hospital from January 2018 to March 2020. A Fitbit was used to monitor heart rate, distance moved, and cardio zone time. Heart rate was also monitored by an oscillometric method. The relationship between Fitbit recordings and perceived adverse events, such as fatigue, constipation and nausea, observed during chemotherapy was investigated using a general linear mixed effects model. Results: Twenty-one of 28 inpatients were enrolled and observed for a total of 824 days. A significant, moderately strong correlation was found between two measurements of heart rate (Pearson's r = 0.65, p < 0.05). The measurement of fatigue using Fitbit was effective (p = 0.03). Conclusion: Fitbit monitoring can measure the QoL of a patient and was useful for monitoring elderly patients with UC undergoing shGC therapy in an outpatient setting. Fitbit may be useful for monitoring outpatients and their QoL during chemotherapy.

Purpose: To investigate whether relaxation of the rat penile corpus cavernosum could be controlled with NOBL-1, a novel, lightcontrollable nitric oxide (NO) releaser. Materials and Methods: Fifteen-week-old male Wistar-ST rats were used. The penile corpus cavernosum was prepared and used in an isometric tension study. After noradrenaline (10−5 M) achieved precontraction, the penile corpus cavernosum was irradiated by light (470–500 nm) with and without NOBL-1 (10−6 M). In addition, we noted rats’ responses to light with vardenafil (10−6 M), a phosphodiesterase-5 (PDE-5) inhibitor. Next, responses to light in the presence of a guanylate cyclase inhibitor, ODQ (1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one) (10−5 M), were measured. All measurements were performed in pretreated L-NAME (10−4 M) conditions to inhibit endogenous NO production. Results: Corpus cavernosal smooth muscle, precontracted with noradrenaline, was unchanged by light irradiation in the absence of NOBL-1. However, in the presence of NOBL-1, corpus cavernosal smooth muscle, precontracted with noradrenaline, relaxed in response to light irradiation. After blue light irradiation ceased, tension returned. In addition, the light response was obviously enhanced in the presence of a PDE-5 inhibitor. Conclusions: This study showed that rat corpus cavernosal smooth muscle relaxation can be light-controlled using NOBL-1, a novel, light sensitive NO releaser. Though further in vivo studies are needed to investigate possible usefulness, NOBL-1 may be prove to be a useful tool for erectile dysfunction therapy, specifically in the field of penile rehabilitation.

We aimed to evaluate mineralocorticoid receptor (MR) expression in rat bladder and the physiological role of the MR-epithelial sodium channel (ENaC) pathway in controlling bladder function in 10–12-week-old, male Sprague–Dawley rats. First, we examined the mRNA expression of MR and localization of MR and ENaC-α proteins in the urinary bladder. MR mRNA expression was observed in untreated-rat urinary bladders, and MR and ENaC-α proteins were localized in the epithelium. Next, rats were treated with vehicle (controls) or fludrocortisone (an MR agonist) for 3 days, and ENaC-α protein expression levels and bladder function were evaluated on day 4. ENaC-α protein expression was significantly higher in fludrocortisone-treated rats than in controls. In addition, cystometry was performed during intravesical infusion of saline and amiloride (an ENaC inhibitor). While intercontraction intervals (ICIs) during saline infusion were significantly shorter in the fludrocortisone group than in the controls, infusion of amiloride normalized the ICIs in the fludrocortisone group. However, no intra- or inter-group differences in maximum intravesical pressure were observed. Taken together, MR protein is localized in the rat urinary bladder epithelium, and may regulate ENaC expression and bladder afferent input. The MR-ENaC pathway may be a therapeutic target for ameliorating storage symptoms.

There is no established chemotherapy regimen in metastatic primary urethral cancer (mPUC). The efficacy of a cisplatin (CDDP)-based regimen has been reported, however, when the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) occurs, the chemotherapy regimen should be changed to another platinum compound. In this report, we describe a 66-year-old woman who was diagnosed as mPUC with, CDDP-induced SIADH. After switching her to CBDCA and careful managing her sodium balance, three courses of the chemotherapy regimen were completed.

We aimed to elucidate the changes in the relaxation function of corpus cavernosal smooth muscle (CCSM) and erectile function using acute penile ischemic rabbits. Relaxation response to acetylcholine (Ach) was unchanged at 3 days after ischemia. The response to ACh had significantly decreased at 1 week, but had recovered completely at 4 weeks. The reaction to sodium nitroprusside and electrical field stimulation was unchanged by ischemia at all time points. Erectile function was changed in the same manner as the response of ACh. The endothelium-dependent relaxing responses of CCSM and erectile function were found to be initially decreased, but subsequently improved completely. Keywords:: arteriogenic erectile dysfunction, corpus cavernosal smooth muscle, endothelium