A new physiological phenomenon of mammalian body for organ and tissue neo-regeneration in vivo: adult stem cell technology in the perspective of literature

A new phenomenon by which adult developed mammalian and human body, can neo-regenerate its own tissue/organ in vivo, is recognized as "Desired Metaplasia". Reserve stem cells present in the tissues of adult developed body, are responsible for repair and replacement of lost tissues and cells during life, is plasia. Chronic tissue damage, due to long-standing causative factor, is taken care of and protected by forming resistant tissues, is metaplasia. Both these changes take place at the anatomical abode of the tissues. When stem cells of one tissue are colonized with another tissue/organ system, away from its anatomical abode, the neo-organo-histogenesis takes place by a phenomenon of desired metaplasia. This being new is critically, analytically and scientifically studied and discussed with reference to the available literature. An attempt has been made to establish the scientific account of the phenomenon. The laws of nature and embryology, as well as the basic philosophy responsible for neo-regeneration of tissues and organs in vivo, are discussed. In conclusion, the mammalian and human bodies can neo-regenerate their tissues and organs in vivo by desired metaplasia, provided certain criteria of embryological organogenesis are strictly observed.     

Surface morphology of kidney, ureters and urinary bladder models based on data from the visible human male

The aim of the present work was to create a simplified high-resolution three-dimensional model of kidneys, ureters and urinary bladder in a data form suitable for finite element/volume based numerical simulations. The exterior morphology of the organs was based on images from the Visible Human Male data set. In both the right and left kidney, there were defined their topographic relations to the neighbouring anatomical structures. This model of kidneys, ureters and urinary bladder will be incorporated into the model of The Visible Human Male abdomen and pelvis and it is ready to be used for numerical simulations in urinary system biomechanics.     

Adrenergic innervation of the ureters, urinary bladder, and urethra in pigs

Studies were conducted on 4 sexually mature and 4 immature pigs. Scraps of the ureters, urinary bladder, and urethra were cut with a freezing microtome. Fluorescence method of Torre and Surgeon (1976) was used to reveal the adrenergic innervation. It was found that the ureters were weakly supplied with the adrenergic nerves; most of the nerves were located in the muscular and submucosal membranes. Apex of the urinary bladder possessed the weakest innervation. More nerves were found in particular layers of the bladder corpus whereas bladder trigonum and cervix possessed numerous nerves. Adrenergic innervation of the urethra was similar to that of the urinary bladder's cervix. Adrenergic nerves were present in the serous and muscular membranes of both the urinary bladder and the urethra. Part of the nerve fibres was connected with blood vessels of the organs under study.     

Adrenergic innervation of the lower urinary tract in cattle

Studies were carried out on 8 sexually immature male calves. Sections of the ureters, urinary bladder, and urethra were cut with a freezing microtome and the method of Ky?s?la et al. (1980) was used to visualize the adrenergic nerve fibres. It was found that bovine ureters possessed weak innervation; most of the nerves was located in the muscular membrane, and only in the paravesical part, sparse nerve fibres were found in the submucosa of this one. Apex of the urinary bladder was more weakly supplied with the adrenergic nerves than the corpus, whereas bladder's trigonum and cervix possessed numerous nerve fibres in both muscular and submucosal membranes. The distribution pattern of adrenergic nerves in the urethra was similar to that of urinary bladder's cervix. The presence of adregeneric nerve fibres was found in submucosal layer of both the urinary bladder and the urethra. Part of the nerves was connected with blood vessels of the organs under study.     

Endoscopic Management of Bladder Diverticula

A 50-year-old man with benign prostatic hyperplasia and urinary retention had a very large diverticulum on the posterior wall of the bladder. The patient was managed with transurethral resection of the prostate and endoscopic fulguration of the bladder diverticulum mucosa using the Orandi technique. There was near-complete resolution of the bladder diverticulum following endoscopic management, obviating the need for bladder diverticulectomy. The patient now empties his bladder, with a postvoid residual < 50 mL and the absence of urinary tract infection after 6-month follow-up. We report the successful treatment of a large bladder diverticulum with endoscopic fulguration to near-complete resolution. This minimally invasive technique is a useful alternative in patients unfit for a more extensive surgical approach.     

The development of the bladder trigone, the center of the anti-reflux mechanism

The urinary tract is an outflow system that conducts urine from the kidneys to the bladder via the ureters that propel urine to the bladder via peristalsis. Once in the bladder, the ureteral valve, a mechanism that is not well understood, prevents backflow of urine to the kidney that can cause severe damage and induce end-stage renal disease. The upper and lower urinary tract compartments form independently, connecting at mid-gestation when the ureters move from their primary insertion site in the Wolffian ducts to the trigone, a muscular structure comprising the bladder floor just above the urethra. Precise connections between the ureters and the trigone are crucial for proper function of the ureteral valve mechanism; however, the developmental events underlying these connections and trigone formation are not well understood. According to established models, the trigone develops independently of the bladder, from the ureters, Wolffian ducts or a combination of both; however, these models have not been tested experimentally. Using the Cre-lox recombination system in lineage studies in mice, we find, unexpectedly, that the trigone is formed mostly from bladder smooth muscle with a more minor contribution from the ureter, and that trigone formation depends at least in part on intercalation of ureteral and bladder muscle. These studies suggest that urinary tract development occurs differently than previously thought, providing new insights into the mechanisms underlying normal and abnormal development.     

Alterations in cytokeratin expression precede histological changes in epithelia of vitamin A-deficient rats

Summary Normal epithelial cell differentiation is charactezied by the production of distinct cytokeratin proteins. It is well known that epithelia of several organs show squamous metaplasia in a vitamin A-deficient status. It is not yet known whether these histological changes are concomitant with a change in cytokeratin expression. Therefore, 3-week-old female rats (BN/BiRij) were fed a vitamin A-deficient diet for 8 weeks. The cytokcratin expression in epithelia of various organs was monitored immunohistochemically during the induction of vitamin A deficiency. Therefore, monoclonal antibodies specific for human cytokeratin 4, 5, 5+8, 7, 10, 14, 18 and 19 were used. In a normal vitamin A status, the distributional pattern for the different cytokeratins in rats was similar to that reported for human tissue. No change in cytokeratin expression was seen in trachea, skin, liver and colon at any time point studied. Squamous metaplasia in urinary bladder and salivary glands was observed after six weeks on the vitamin A-deficient diet. This was concomitant with a substitution of cytokeratins 4, 5+8, 7, 18 and 19 by cytokeratin 10. The latter cytokeratin is specific for keratinzed squamous epithelium. A change in cytokeratin expression was observed in bladder, ureter, kidney, salivary glands, uterus and conjunctiva before histological alterations appeared. In conclusion, the changes in cytokeratin expression observed under vitamin A deficiency in epithelia in vivo are in agreement with those described in other studies for epithelial cells in vitro. The changes in cytokeratin expression and the subsequent differentiation into squamous cells occurs in basal cells of the bladder but not in transitional cells. Furthermore, histological alterations are preceded by changes in cytokeratin expression indicating that vitamin A status controls cytokeratin expression in vivo.     

Mechanisms of synergism of the autonomic nervous system compartments

The realization mechanisms of phenomena of sympathetic nerve potentiation of vagal stimulation of motor activity of duodenal and jejunal intestine, urinary bladder and ureters, uterus and tubes, vas deference and mechanism of sympathetic nerve potentiation of vagal cardioinhibitory action were studied. There were demonstrated that these phenomena were realized with participation of preganglionic serotoninergic nerve fibers transmitting an excitation on ganglionary serotoninergic neurons. It was found an existence of increasing cranio-caudal and decreasing ventro-dorsal gradients of serotoninergic innervation of visceral organs.     

Synthesis and antimuscarinic activity of a series of 4-(1-Imidazolyl)-2,2-diphenylbutyramides: discovery of potent and subtype-selective antimuscarinic agents.

In a study directed toward the development of new, selective agents with potential utility in the treatment of altered smooth muscle contractility and tone, for example, as seen in urinary incontinence associated with bladder muscle instability, a series of 4-(1-imidazolyl)-2,2-diphenylbutyramide derivatives was prepared. These compounds were examined for M1, M2, and M3 muscarinic receptor subtype selectivity in isolated tissue assays. The compounds that showed potency and/or selectivity in these tests were further evaluated for in vivo anticholinergic effects on various organs and tissues, including urinary bladder, salivary gland, and eye in rats. The structure activity relationships for the series of 4-(1-imidazolyl)-2,2-diphenylbutyramide derivatives are also discussed. This study led to the identification of 4-(2-methyl-1-imidazolyl)-2,2-diphenylbutyramide (KRP-197) as a candidate drug for the treatment of urinary bladder dysfunction.     

Some Coelozoic Myxosporida From New Zealand Fishes: Family Sphaerosporidae1

SYNOPSIS. The trophic stages and spores of Sphaerospora undulans n. sp. from the urinary bladder, and ureters, and oviducts of Caulopsetta scapha, and the urinary bladder and ureters of Peltorhamphus novaezelandiae are described. An undescribed species from Genypterus blacodes is also mentioned. The host fishes were taken in New Zealand.     

A biomechanical model to assess the contribution of pelvic musculature weakness to the development of stress urinary incontinence

A biomechanical model of the female pelvic support system was developed to explore the contribution of pelvic floor muscle defect to the development of stress urinary incontinence (SUI). From a pool of 135 patients, clinical data of 26 patients with pelvic muscular defect were used in modelling. The model was employed to estimate the parameters that describe the stiffness properties of the vaginal wall and ligament tissues for individual patients. The parameters were then implemented into the model to evaluate for each patient the impact of pelvic muscular defect on the vaginal apex support and the bladder neck support, a factor that relates to the onset of SUI. For the modelling analysis, the compromise of pelvic muscular support was demonstrated to contribute to vaginal apex prolapse and bladder neck prolapse, a condition commonly seen in SUI patients, while simulated conditions of restored muscular support were shown to help re-establish both vaginal apex and bladder neck supports. The findings illustrate the significance of pelvic muscle strength to vaginal support and urinary continence; therefore, the clinical recommendation of pelvic muscle strengthening, such as Kegel exercises, has been shown to be an effective treatment for patients with SUI symptoms.     

Luteinizing hormone and follicle-stimulating hormone receptors and their transcribed genes (mRNA) are present in the lower urinary tract of intact male and female dogs

In dogs, one of the side effects of neutering is the development of urinary incontinence. The relationship between neutering and urinary incontinence caused by acquired urethral sphincter mechanism incompetence (USMI) has been reported. Recently, GnRH analogue treatment that suppresses elevated plasma gonadotrophin concentrations post-spaying has been successfully used in incontinent bitches. These data and the fact that non-gonadal tissues may contain receptors for LH (LHR) and FSH (FSHR) suggest that there might be a functional relationship between gonadotrophins and the lower urinary tract in dogs. This study aimed to investigate the presence of LHR and FSHR in the lower urinary tract of intact male and female dogs. Four regions of the lower urinary tract, i.e. (i) body of the bladder, (ii) neck of the bladder, (iii) proximal urethra and (iv) distal urethra were collected from 10 healthy dogs (5 males and 5 anoestrous females). In situ hybridization and immunohistochemistry were performed to characterise the presence of receptor mRNA and receptor protein. Staining was rated semi-quantitatively, incorporating both the distribution and intensity of specific staining. The distribution of receptor expression in different tissue layers (epithelium, subepithelial stroma and muscle) in each region was statistically analyzed. Luteinizing hormone receptor and FSHR mRNA and protein were present in all four regions and in three tissue layers of males and females. Irrespective of region and layer, female dogs expressed significantly higher expression for LHR mRNA (P<0.001), LHR protein (P<0.05) and FSHR protein (P<0.001). The expression of LHR and FSHR mRNA and protein was not uniform and depended on region, tissue layer and gender. The expression of LHR mRNA was higher in the bladder, compared to the urethra (P<0.05). The FSHR mRNA significantly increased from the bladder to the urethra. Protein expression for LHR and FSHR was highest in the proximal urethra (P<0.05). The overall expression for LHR and FSHR at both mRNA and protein levels was highest in the epithelium, intermediate to low in the subepithelial stroma and muscle. A significant interaction between region and tissue layer showed that mRNA and protein expression for LHR and FSHR decreased from the bladder to the urethra in the epithelium and subepithelial stroma. In contrast, it gradually increased from the bladder to the urethra in the muscle. In conclusion, the present study showed that both mRNA and protein for LHR and FSHR were expressed in the canine lower urinary tract, and the expression levels varied between genders and among regions and tissue layers. The presence of these receptors suggests that gonadotrophins have a role in the physiology and/or pathology of the lower urinary tract function in the dog.     

Update on vesicoureteral reflux: pathogenesis, nephropathy, and management

Clinical reflux was first visualized over 100 years ago. In the 1950s and early 1960s, the assumption was that surgery to relieve bladder neck obstruction would have a positive effect on bladder function and reflux. By the early 1970s it was understood that the underlying structural problems leading to primary reflux were congenitally abnormal distal ureters and orifices. Researchers in the 1960s and 1970s demonstrated the connection between reflux and renal scarring. More recently, reflux nephropathy in the absence of urinary tract infections has been observed, leading researchers to investigate an association between bladder dysfunction and reflux with resulting nephropathy. The cornerstone of management of the child with vesicoureteral reflux is antibiotic prophylaxis; treatment regimens for various grades of reflux are reviewed. Indications for surgical treatment of reflux are also discussed. Controversies regarding vesicoureteral reflux, including duration of prophylactic treatment, remain to be resolved.     

New Amniotic Membrane Based Biocomposite for Future Application in Reconstructive Urology

Objective

Due to the capacity of the amniotic membrane (Am) to support re-epithelisation and inhibit scar formation, Am has a potential to become a considerable asset for reconstructive urology i.e., reconstruction of ureters and urethrae. The application of Am in reconstructive urology is limited due to a poor mechanical characteristic. Am reinforcement with electrospun nanofibers offers a new strategy to improve Am mechanical resistance, without affecting its unique bioactivity profile. This study evaluated biocomposite material composed of Am and nanofibers as a graft for urinary bladder augmentation in a rat model.

Material and Methods

Sandwich-structured biocomposite material was constructed from frozen Am and covered on both sides with two-layered membranes prepared from electrospun poly-(L-lactide-co-E-caprolactone) (PLCL). Wistar rats underwent hemicystectomy and bladder augmentation with the biocomposite material.

Results

Immunohistohemical analysis (hematoxylin and eosin [H&E], anti-smoothelin and Masson’s trichrome staining [TRI]) revealed effective regeneration of the urothelial and smooth muscle layers. Anti-smoothelin staining confirmed the presence of contractile smooth muscle within a new bladder wall. Sandwich-structured biocomposite graft material was designed to regenerate the urinary bladder wall, fulfilling the requirements for normal bladder tension, contraction, elasticity and compliance. Mechanical evaluation of regenerated bladder wall conducted based on Young’s elastic modulus reflected changes in the histological remodeling of the augmented part of the bladder. The structure of the biocomposite material made it possible to deliver an intact Am to the area for regeneration. An unmodified Am surface supported regeneration of the urinary bladder wall and the PLCL membranes did not disturb the regeneration process.

Conclusions

Am reinforcement with electrospun nanofibers offers a new strategy to improve Am mechanical resistance without affecting its unique bioactivity profile.     

Intramural neurons in the urinary bladder of the guinea-pig

Summary The urinary bladder of adult female guinea-pigs was stained histochemically to detect the presence of intramural ganglion neurons. Counts on wholemount preparations of entire bladders revealed the presence of 2000–2500 neurons per bladder, either as individual nerve cells or, more often, as ganglia containing up to 40 neurons. Both ganglia and single neurons lie along nerve trunks and are interconnected to form a plexus. Ganglia occur in every part of the bladder; they are more numerous on the dorsal than on the ventral wall, and they are especially abundant in an area within a radius of 800 m from the point of entry into the bladder wall of ureters and urinary arteries. The ganglia are located inside the muscle coat and close to muscle bundles; they usually lie nearer the mucosa than the serosa. Ultrastructurally, each ganglion is surrounded by a capsule; in addition to neurons and glial cells, the ganglia contain capillaries, collagen fibrils and fibroblasts; ganglion neurons are individually wrapped by glial cells and are separated from one another by connective tissue.     

Suppression of the PI3K Pathway In Vivo Reduces Cystitis-Induced Bladder Hypertrophy and Restores Bladder Capacity Examined by Magnetic Resonance Imaging

This study utilized magnetic resonance imaging (MRI) to monitor the real-time status of the urinary bladder in normal and diseased states following cyclophosphamide (CYP)-induced cystitis, and also examined the role of the phosphoinositide 3-kinase (PI3K) pathway in the regulation of urinary bladder hypertrophy in vivo. Our results showed that under MRI visualization the urinary bladder wall was significantly thickened at 8 h and 48 h post CYP injection. The intravesical volume of the urinary bladder was also markedly reduced. Treatment of the cystitis animals with a specific PI3K inhibitor {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002 reduced cystitis-induced bladder wall thickening and enlarged the intravesical volumes. To confirm the MRI results, we performed H&E stain postmortem and examined the levels of type I collagen by real-time PCR and western blot. Inhibition of the PI3K in vivo reduced the levels of type I collagen mRNA and protein in the urinary bladder ultimately attenuating cystitis-induced bladder hypertrophy. The bladder mass calculated according to MRI data was consistent to the bladder weight measured ex vivo under each drug treatment. MRI results also showed that the urinary bladder from animals with cystitis demonstrated high magnetic signal intensity indicating considerable inflammation of the urinary bladder when compared to normal animals. This was confirmed by examination of the pro-inflammatory factors showing that interleukin (IL)-1α, IL-6 and tumor necrosis factor (TNF)α levels in the urinary bladder were increased with cystitis. Our results suggest that MRI can be a useful technique in tracing bladder anatomy and examining bladder hypertrophy in vivo during disease development and the PI3K pathway has a critical role in regulating bladder hypertrophy during cystitis.     

Wild Cane Toads (Rhinella marina) Expel Foreign Matter from the Coelom via the Urinary Bladder in Response to Internal Injury,Endoparasites and Disease

Dissections of >1,200 wild-caught cane toads (Rhinella marina) in tropical Australia confirm a laboratory report that anurans can expel foreign objects from the coelom by incorporating them into the urinary bladder. The foreign objects that we found inside bladders included a diverse array of items (e.g., grass seeds, twigs, insect prey, parasites), many of which may have entered the coelom via rupture of the gut wall. In some cases, the urinary bladder was fused to other organs including liver, fat bodies, ovaries, Bidder’s organs, lungs, mesentery, stomach wall, gall bladder, and the abdominal wall. Acanthocephalan parasites (of a range of developmental stages) were identified from the walls of the urinary bladders of three cane toads. This organ may play a significant role in destroying or excreting metazoan parasites, as well as inanimate objects.     

Immunologic determination of an epidermal G2-chalone-like factor as a marker of squamous cell structures in the urinary bladder and urine in rats

The epidermal G2 chalone-like substance of the rat skin may be determined by immunochemical methods only in squamous epithelia and it is revealed neither in mucosa of the urinary bladder, nor in urine of control rats. The antigenic activity of the chalone was revealed in 37 extracts of 56 tumors of the rat bladder. All antigen-containing tumors were found to be squamous cell carcinomas, transitional cell carcinomas with squamous cell metaplasia or possessed ultramicroscopic signs of squamous cell metaplasia appearing as "pure" transitional cell carcinomas under light microscope. The epidermal G2 chalone-like substance was present in urine of 7 out of 10 rats bearing the antigen-positive tumors of the urinary bladder.