Search Results (27)

The present study was designed to establish the distribution pattern and immunohistochemical characteristics of phoenixin-immunoreactive (PNX-IR) urinary bladder afferent neurons (UB-ANs) of dorsal root ganglia (DRG) in female pigs. The sensory neurons investigated were visualized with a retrograde tracing method using Fast Blue (FB), while their chemical profile(s) were identified using double-labelling immunohistochemistry with antibodies against PNX, calcitonin gene-related peptide (CGRP), calretinin (CRT), galanin (GAL), neuronal nitric oxide synthase (nNOS), pituitary adenylate cyclase-activating polypeptide (PACAP), somatostatin (SOM) and substance P (SP). Nearly half of UB-ANs contained PNX (45%), and the majority of such encoded sensory neurons were small in size (66%). The most numerous subpopulation of FB/PNX-positive neurons were those containing SP (71%). CGRP, GAL or PACAP were observed in a smaller number of PNX-containing UB-ANs (50%, 30% or 25%, respectively), while PNX-positive sensory neurons simultaneously immunostained with nNOS, CRT or SOM constituted a small fraction of all retrogradely-traced DRG neurons (DRGs; 15%, 6.5% or 1.6%, respectively). Furthermore, the numerical analysis of neurons expressing individual antigens, performed on 10 μm-thick consecutive sections, allows us to state that studied sensory neurons can be classified as neurons “coded” either by the simultaneous presence of SP/CGRP/PACAP/GAL, SP/CGRP/PACAP/NOS, SP/CGRP/PACAP/NOS/CRT and/or SP/CGRP/GAL/PACAP, or, as a separate population, those capable of SOM synthesis (SP/CGRP/SOM/PACAP/GAL-positive neurons). The present study reveals the extensive expression of PNX in the DRGs supplying to the urinary bladder, indicating an important regulatory role of this neuropeptide in the control of physiological function(s) of this organ. Full article

Lower urinary tract dysfunction, such as incontinence or urinary retention, is one of the leading consequences of neurological diseases. This significantly impacts the quality of life for those affected, with implications extending not only to humans but also to clinical veterinary care. Having motor and sensory fibers, the pudendal nerve is an optimal candidate for neuromodulation therapies using bidirectional intraneural prostheses, paving the way towards the restoration of a more physiological urination cycle: bladder state can be detected from recorded neural signals, then an electrical current can be injected to the nerve based on the real-time need of the bladder. To develop such prostheses and investigate this novel approach, animal studies are still required since the morphology of the target nerve is fundamental to optimizing the prosthesis design. This study aims to describe the porcine pudendal nerve as a model for neuromodulation studies aiming at restoring lower urinary tract dysfunction. Five male farm pigs were involved in the study. First, a surgical procedure to access the porcine pudendal nerve without muscle resection was developed. Then, an intraneural interface was implanted to confirm the presence of fibers innervating the external urethral sphincter by measuring its electromyographic activity. Finally, the morphophysiology of the porcine pudendal nerve at the level of surgical exposure was described by using histological and immunohistochemical characterization. This analysis confirmed the fasciculate nature of the nerve and the presence of mixed fibers with a spatial and functional organization. These achievements pave the way for further pudendal neuromodulation studies by using a clinically relevant animal model with the potential for translating the findings into clinical applications. Full article

This paper describes cases of urolithiasis in fattening pigs on two farms (A and B). Bladder rupture due to urethral obstruction with calculi was the principal finding during the necropsy of the pigs. An in-depth diagnostic examination was performed to elucidate possible pathophysiological mechanisms, namely Fourier-transform infrared spectrophotometry (FT-IR) analysis of the uroliths, blood analysis (farm A: 5 samples, farm B: 10 samples) for assessing concentrations of minerals, the bone resorption marker cross-linked C-telopeptide of type 1 collagen (CTX), parathyroid hormone (PTH), and vitamin D components, biochemical urinalysis (farm A: 5 samples, farm B: 7 samples), microscopic examination of urinary sediment (Farms A and B: 7 samples each), mineral composition of the feed, and analysis of the drinking water. Calcium carbonate was the main component found in stones from both farms, and calcium carbonate and struvite were the main components found in crystals from farms A and B, respectively. On farm A, urinary calcium excretion and urinary pH were high; on farm B, urinary phosphorus was high and urinary calcium was low with a normal urinary pH. The mineral compositions of the feed and drinking water were similar on both farms and could therefore not explain the difference between the two farms. Disturbances in calcium and phosphorus absorption and homeostasis might have been involved in these problems. Further research should focus on the calcium, phosphorus, and vitamin D levels in the feed and take into account other factors, such as the absorption and excretion of minerals due to gut and urinary microbiota. Full article

Bisphenol A (BPA), a substance globally used to produce plastics, is part of many everyday items, including bottles, food containers, electronic elements, and others. It may penetrate the environment and living organisms, negatively affecting, among others, the nervous, immune, endocrine, and cardiovascular systems. Knowledge of the impact of BPA on the urinary bladder is extremely scarce. This study investigated the influence of two doses of BPA (0.05 mg/kg body weight (b.w.)/day and 0.5 mg/kg b.w./day) given orally for 28 days on the neurons situated in the ganglia located in the urinary bladder trigone using the typical double immunofluorescence method. In the study, an increase in the percentage of neurons containing substance P (SP), galanin (GAL), a neuronal isoform of nitric oxide synthase (nNOS—used as the marker of nitrergic neurons), and/or cocaine- and amphetamine-regulated transcript (CART) peptide was noted after BPA administration. The severity of these changes depended on the dose of BPA and the type of neuronal factors studied. The most visible changes were noted in the cases of SP- and/or GAL-positive neurons after administering a higher dose of BPA. The results have shown that oral exposure to BPA, lasting even for a short time, affects the intramural neurons in the urinary bladder wall, and changes in the neurochemical characterisation of these neurons may be the first signs of BPA-induced pathological processes in this organ. Full article

Introduction: Intra-abdominal pressure (IAP) monitoring is crucial for the detection and prevention of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS). In the 1970s, air-filled catheters (AFCs) for urodynamic studies were introduced as a solution to overcome the limitations of water-perfused catheters. Recent studies have shown that for correct IAP measurement with traditional AFC, the bladder needs to be primed with 25 mL of saline solution to allow pressure wave transmission to the transducer outside of the body, which limits continuous IAP monitoring. Methods: In this study, a novel triple balloon, air-filled TraumaGuard (TG) catheter system from Sentinel Medical Technologies (Jacksonville, FL, USA) with a unique balloon-in-balloon design was evaluated in a porcine and cadaver model of IAH via laparoscopy (IAP_gold). Results: In total, 27 and 86 paired IAP measurements were performed in two pigs and one human cadaver, respectively. The mean IAP_TG was 20.7 ± 10.7 mmHg compared to IAP_gold of 20.3 ± 10.3 mmHg in the porcine study. In the cadaver investigation, the mean IAP_TG was 15.6 ± 10.8 mmHg compared to IAP_gold of 14.4 ± 10.4 mmHg. The correlation, concordance, bias, precision, limits of agreement, and percentage error were all in accordance with the WSACS (Abdominal Compartment Society) recommendations and guidelines for research. Conclusions: These findings support the use of the TG catheter for continuous IAP monitoring, providing early detection of elevated IAP, thus enabling the potential for prevention of IAH and ACS. Confirmation studies with the TraumaGuard system in critically ill patients are warranted to further validate these findings. Full article

Neurogenic bladder dysfunction is a condition that affects both bladder storage and voiding function and remains one of the leading causes of morbidity after spinal cord injury (SCI). The vast majority of individuals with severe SCI develop neurogenic lower urinary tract dysfunction (NLUTD), with symptoms ranging from neurogenic detrusor overactivity, detrusor sphincter dyssynergia, or sphincter underactivity depending on the location and extent of the spinal lesion. Animal models are critical to our fundamental understanding of lower urinary tract function and its dysfunction after SCI, in addition to providing a platform for the assessment of potential therapies. Given the need to develop and evaluate novel assessment tools, as well as therapeutic approaches in animal models of SCI prior to human translation, urodynamics assessment techniques have been implemented to measure NLUTD function in a variety of animals, including rats, mice, cats, dogs and pigs. In this narrative review, we summarize the literature on the use of animal models for cystometry testing in the assessment of SCI-related NLUTD. We also discuss the advantages and disadvantages of various animal models, and opportunities for future research. Full article

The purpose of this study was to explore the relationship between bladder urothelial cancer (BLCA) and immunity, to screen prognosis-related immune genes (PIGs), and to construct an immune-related prognosis model (IRPM). We processed the relevant data of The Cancer Genome Atlas (TCGA-BLCA) and GSE13507 using R software and Perl. We divided BLCA into high-immunity and low-immunity subtypes. There were significant differences in the two subtypes. In addition, we identified 13 PIGs of BLCA by jointly analyzing the gene expression data and survival information of GSE13507 and TCGA-BLCA, and constructed IRPM through nine of them. The low-risk group had better survival outcome than the high-risk group. We also constructed a nomogram based on clinicopathological information and risk scores of the patients. Moreover, the prognosis of BLCA patients was significantly impacted by the expression of almost every gene used to calculate the risk score. The result of real-time fluorescence quantitative polymerase chain reaction revealed that all the genes used to calculate the risk score were differentially expressed between BLCA and adjacent normal tissues, except PDGFRA. Our research provided potential targets for the treatment of BLCA and a reference for judging the prognosis of BLCA. Full article

To explore the effect of different sources of iron on growth performance and intestinal health, 24 weaned pigs were randomly allocated to three groups and fed with a basal diet (BD) or BD containing 100 mg/kg ferrous sulfate (FS) or ferrous glycine (FG). The trial lasted for 21 d, and blood and tissue were collected for analysis. Results showed that FG significantly decreased the feed-to-gain ratio and increased the iron content in the liver and tibia (p < 0.05). Both FS and FG elevated bladder and fecal iron content and significantly elevated the contents of red blood cells, hemoglobin (HGB), and ferritin in the blood (p < 0.05). FG supplementation increased the serum concentrations of immunoglobulin (Ig) G and IgM, but decreased the concentrations of D-lactate and endotoxin (p < 0.05). Interestingly, FG significantly increased the villus height and the ratio of villus height to crypt depth (V/C) in the duodenum and ileum (p < 0.05). FG supplementation also increased the abundance of tight-junction protein ZO-1 but significantly decreased the rate of apoptosis in the jejunum (p < 0.05). Moreover, the activities of jejunal sucrase, maltase, and catalase (CAT) in the FG group were higher than that in other groups (p < 0.05). Importantly, FG not only elevated the expression levels of cationic amino acid transporter-1 (CAT1) in the duodenal and jejunum but also elevated the expression levels of glucose transporter-2 (GLUT2) and sodium/glucose co-transporter 1 (SGLT1) in the ileum (p < 0.05). These results indicated that appropriate iron supplementation is beneficial to piglet intestinal health by enhancing immunity and improving antioxidant capacity, and FG may serve as an efficient substitute for conventionally used iron sources. Full article

(1) Aims: To test a newly designed helical-wire hook electrode implanted in the bladder wall to induce contraction and promote voiding. (2) Methods: In three minipigs with a created lesion of the sacral spinal cord, four electrodes were implanted in the bladder wall, ventral to the trigone. Stimulation tests were conducted initially in conscious pigs, and later after general anesthesia. (3) Results: Electrical stimulation in the conscious animals on postoperative days 4 and 7 at 40 Hz was limited to 10 mA, because of abdominal, leg, and anal contractions with animal discomfort; bladder contractions were not induced. Electrical stimulation on postoperative days 9 and 28 at 60 mA under anesthesia induced sustained vesical wall contractions with bladder pressure variations, but without voiding. Simultaneous abdominal contractions occurred, with strong leg and anal contractions. Subsequent stimulation with a single set of electrodes or at 20 Hz induced less vesical pressure response. At autopsy, the electrodes had not migrated, and extraction forces were high, at 7.9 ± 0.9 Newtons (n = 12). (4) Conclusions: Our 28-day study has confirmed the utility of the new electrode design, preventing migration from the bladder wall and making it suitable for long-term electrode implants. Full article

Although guanethidine (GUA) was used in the past as a drug to suppress hyperactivity of the sympathetic nerve fibers, there are no available data concerning the possible action of this substance on the sensory component of the peripheral nervous system supplying the urinary bladder. Thus, the present study was aimed at disclosing the influence of intravesically instilled GUA on the distribution, relative frequency, and chemical coding of dorsal root ganglion neurons associated with the porcine urinary bladder. The investigated sensory neurons were visualized with a retrograde tracing method using Fast Blue (FB), while their chemical profile was disclosed with single-labeling immunohistochemistry using antibodies against substance P (SP), calcitonin gene-related peptide (CGRP), pituitary adenylate cyclase activating polypeptide (PACAP), galanin (GAL), neuronal nitric oxide synthase (nNOS), somatostatin (SOM), and calbindin (CB). After GUA treatment, a slight decrease in the number of FB⁺ neurons containing SP was observed when compared with untreated animals (34.6 ± 6.5% vs. 45.6 ± 1.3%), while the number of retrogradely traced cells immunolabeled for GAL, nNOS, and CB distinctly increased (12.3 ± 1.0% vs. 7.4 ± 0.6%, 11.9 ± 0.6% vs. 5.4 ± 0.5% and 8.6 ± 0.5% vs. 2.7 ± 0.4%, respectively). However, administration of GUA did not change the number of FB⁺ neurons containing CGRP, PACAP, or SOM. The present study provides evidence that GUA significantly modifies the sensory innervation of the porcine urinary bladder wall and thus may be considered a potential tool for studying the plasticity of this subdivision of the bladder innervation. Full article

The urinary bladder (UB) serves as a storage and elimination organ for urine. UB dysfunction can cause multiple symptoms of failure to store urine or empty the bladder, e.g., incontinence, frequent urination, and urinary retention. Treatment of these symptoms requires knowledge on bladder function, which involves physiology, pathology, and even psychology. There is no ideal animal model for the study of UB function to understand and treat associated disorders, as the complexity in humans differs from that of other species. However, several animal models are available to study a variety of other bladder disorders. Such models include animals from rodents to nonhuman primates, such as mice, rats, rabbits, felines, canines, pigs, and mini pigs. For incontinence, vaginal distention might mimic birth trauma and can be measured based on leak point pressure. Using peripheral and central models, inflammation, bladder outlet obstruction, and genetic models facilitated the study of overactive bladder. However, the larger the animal model, the more difficult the study is, due to the associated animal ethics issues, laboratory facility, and budget. This review aims at facilitating adapted animal models to study bladder function according to facility, priority, and disease. Full article

Accurate measurement of bladder volume is an important tool for evaluating bladder function. In this study, we propose a wearable bladder scanner system that can continuously measure bladder volume in daily life for urinary patients who need urodynamic studies. The system consisted of a 2-D array, which included integrated forward-looking piezoelectric transducers with thin substrates. This study aims to estimate the volume of the bladder using a small number of piezoelectric transducers. A least-squares method was implemented to optimize an ellipsoid in a quadratic surface equation for bladder volume estimation. Ex-vivo experiments of a pig bladder were conducted to validate the proposed system. This work presents the potential of the approach for wearable bladder monitoring, which has similar measurement accuracy compared to the commercial bladder imaging system. The wearable bladder scanner can be improved further as electronic voiding diaries by adding a few more features to the current function. Full article

This review paper deals with the influence of androgens (testosterone) on pelvic autonomic pathways in male mammals. The vast majority of the relevant information has been gained in experiments involving castration (testosterone deprivation) performed in male rats, and recently, in male pigs. In both species, testosterone significantly affects the biology of the pathway components, including the pelvic neurons. However, there are great differences between rats and pigs in this respect. The most significant alteration is that testosterone deprivation accomplished a few days after birth results some months later in the excessive loss (approximately 90%) of pelvic and urinary bladder trigone intramural neurons in the male pig, while no changes in the number of pelvic neurons are observed in male rats (rats do not have the intramural ganglia). In the castrated pigs, much greater numbers of pelvic neurons than in the non-castrated animals express CGRP, GAL, VIP (peptides known to have neuroprotective properties), and caspase 3, suggesting that neurons die due to apoptosis triggered by androgen deprivation. In contrast, only some morpho-electrophysiological changes affecting neurons following castration are found in male rats. Certain clinicopathological consequences of testosterone deprivation for the functioning of urogenital organs are also discussed. Full article

Background: The interleukin-1-receptor antagonist IL1RA (encoded by the IL1RN gene) is a potent competitive antagonist to interleukin-1 (IL1) and thereby is mainly involved in the regulation of inflammation. Previous data indicated a role of IL1RA in muscle-invasive urothelial carcinoma of the bladder (UCB) as well as an IL1-dependent decrease in tissue barrier function, potentially contributing to cancer cell invasion. Objective: Based on these observations, here we investigated the potential roles of IL1RA, IL1A, and IL1B in bladder cancer cell invasion in vitro. Methods: Cell culture, real-time impedance sensing, invasion assays (Boyden chamber, pig bladder model), qPCR, Western blot, ELISA, gene overexpression. Results: We observed a loss of IL1RA expression in invasive, high-grade bladder cancer cell lines T24, UMUC-3, and HT1197 while IL1RA expression was readily detectable in the immortalized UROtsa cells, the non-invasive bladder cancer cell line RT4, and in benign patient urothelium. Thus, we modified the invasive human bladder cancer cell line T24 to ectopically express IL1RA, and measured changes in cell migration/invasion using the xCELLigence Real-Time-Cell-Analysis (RTCA) system and the Boyden chamber assay. The real-time observation data showed a significant decrease of cell migration and invasion in T24 cells overexpressing IL1RA (T24-IL1RA), compared to cells harboring an empty vector (T24-EV). Concurrently, tumor cytokines, e.g., IL1B, attenuated the vascular endothelial barrier, which resulted in a reduction of the Cell Index (CI), an impedance-based dimensionless unit. This reduction could be reverted by the simultaneous incubation with IL1RA. Moreover, we used an ex vivo porcine organ culture system to evaluate cell invasion capacity and showed that T24-IL1RA cells showed significantly less invasive capacity compared to parental T24 cells or T24-EV. Conclusions: Taken together, our results indicate an inverse correlation between IL1RA expression and tumor cell invasive capacity and migration, suggesting that IL1RA plays a role in bladder carcinogenesis, while the exact mechanisms by which IL1RA influences tumor cells migration/invasion remain to be clarified in future studies. Furthermore, we confirmed that real-time impedance sensing and the porcine ex vivo organ culture methods are powerful tools to discover differences in cancer cell migration and invasion. Full article

This study was aimed at disclosing the influence of intravesically instilled guanethidine (GUA) on the distribution, relative frequency and chemical coding of both the urinary bladder intramural sympathetic nerve fibers and their parent cell bodies in the caudal mesenteric ganglion (CaMG) in juvenile female pigs. GUA instillation led to a profound decrease in the number of perivascular nerve terminals. Furthermore, the chemical profile of the perivascular innervation within the treated bladder also distinctly changed, as most of axons became somatostatin-immunoreactive (SOM-IR), while in the control animals they were found to be neuropeptide Y (NPY)-positive. Intravesical treatment with GUA led not only to a significant decrease in the number of bladder-projecting tyrosine hydroxylase (TH) CaMG somata (94.3 ± 1.8% vs. 73.3 ± 1.4%; control vs. GUA-treated pigs), but simultaneously resulted in the rearrangement of their co-transmitters repertoire, causing a distinct decrease in the number of TH⁺/NPY⁺ (89.6 ± 0.7% vs. 27.8 ± 0.9%) cell bodies and an increase in the number of SOM-(3.6 ± 0.4% vs. 68.7 ± 1.9%), calbindin-(CB; 2.06 ± 0.2% vs. 9.1 ± 1.2%) or galanin-containing (GAL; 1.6 ± 0.3% vs. 28.2 ± 1.3%) somata. The present study provides evidence that GUA significantly modifies the sympathetic innervation of the porcine urinary bladder wall, and thus may be considered a potential tool for studying the plasticity of this subdivision of the bladder innervation. Full article