Recovery of choline acetyltransferase activity in the rat urinary bladder deprived of half of its innervation

In the urinary bladder of the rat, partially denervated by unilateral removal of the pelvic ganglion 3 days in advance, the activity of the acetylcholine-forming enzyme, choline acetyltransferase, measured by a radiolabelling method, was reduced to 58% of the control. A gain in enzyme activity of 28% was found to have occurred when the bladders were examined 25 days postoperatively; the main part of this increase took place during the period 3 to 6 days after the operation and beyond 25 days no further gain in enzyme activity was found. The present findings are compared with previous observations of a transient supersensitivity and an increased motor response to electrical stimulation of the intact pelvic nerve of such a partially denervated bladder.     

Muscarinic supersensitivity in the rat urinary bladder after capsaicin pretreatment

The effects of capsaicin on urinary bladder function have been investigated in adult rats. Ten days after capsaicin treatment immunocytochemical investigations showed a nearly complete disappearance of substance P (SP) and calcitonin gene-related peptide (CGRP) in all parts of the bladder. Recordings of micturition patterns and cystometrical investigations in conscious animals revealed no functional effects of capsaicin treatment. In-vitro experiments showed that the contractile response to substance P was similar before and after capsaicin treatment and CGRP exerted no contractile effects on the urinary bladder in either group of rats. The concentration–response curve to carbachol as well as the frequency-response curve to electrical stimulation were significantly shifted to the left in bladder muscle after capsaicin treatment. However, the maximal responses were similar in control and capsaicin-treated bladders. In the presence of scopolamine the maximal response to electrical stimulation was clearly lower in bladders subjected to capsaicin treatment than in controls. In conclusion, depletion of substance P and CGRP in the rat urinary bladder by capsaicin induced no supersensitivity to these peptides. However, the increased sensitivity to carbachol and to electrical stimulation seen after capsaicin treatment indicates the development of a supersensitivity to muscarinic receptor stimulation. Despite this supersensitivity in vitro no functional effects of capsaicin treatment were found in vivo.     

Disuse as cause of supersensitivity in the rat urinary bladder*

Ureterostomia in situ was performed to reduce the nervous reflex activation of the bladders without concomitant hypertrophy. In muscle strips of these disused and non-hypertrophied bladders, supersensitivity to methacholine was demonstrated, which did not increase between 1 and 3 weeks. The supersensitivity did not increase further by combining urinary diversion with section of the preganglionic bladder nerves (decentralization). From the present results it may be concluded that in decentralized and hypertrophied bladders not only hypertrophy per se, previously studied (Ekström et al. 1985), but also loss of nerve impulse traffic (cf. urinary diversion) contribute to the development of supersensitivity.     

Responses of the denervated rat urinary bladder to alfa adrenoceptor stimulation.

The contractile responses of the rat detrusor muscle to noradrenaline were increased 2-3 weeks after partial denervation but had returned to control values 6-9 weeks after the denervation, probably because of reinnervation of denervated muscle cells. 6-9 weeks after partial denervation the excitatory alpha-adrenoceptor mediated response to stimulation of the remaining intact nerves was predominant, masking the subsequent inhibitory beta-receptor response, which at this time was seen only after alpha-receptor blockade. The possibility of an outgrowth of adrenergic fibres activating alpha-receptors in muscle cells normally not innervated by adrenergic nerves is discussed.     

Spinal opioid receptors and inhibition of urinary bladder motility in vivo

The effects of intrathecal injections of morphine and other opioid receptor selective drugs were tested on urinary bladder contractions in the anesthetized rat. Morphine produced dose-related inhibition of bladder motility which was abolished by naloxone. This action was also observed with mu- and delta-opioid receptor agonists but not with a kappa-opioid receptor agonist. These observations appear related to the urinary retention seen clinically with epidural administrations of morphine and support the hypothesis that urinary bladder activity is influenced by spinal opioid mechanisms involving mu- and delta-opioid receptors.     

In vivo motor effects of loperamide on the rat urinary bladder

Bladder motility recordings were performed in anaesthetized rats and the effect of the peripherally active opiate agonist loperamide on urinary bladder function was studied. Regional intra-arterial administration of loperamide (0.01–2 mg kg^-1) induced weak bladder contraction per se. Loperamide caused an effective dose-dependent inhibition of bladder motility induced by regional injection of the receptor agonists acetylcholine (ACh) and substance P (SP), as well as by peripheral motor nerve stimulation (PNS). Pretreatment with naloxone (0.5 mg kg^-1) partially antagonized the inhibitory action of loperamide on the nerve-mediated detrusor contraction. However, the depression of the motor responses induced by the receptor agonists ACh and SP was not influenced. It is suggested that the demonstrated inhibitory effect of loperamide on bladder motility is partially mediated by peripheral opioid receptors. The main non-opioid part of the inhibition might be a direct smooth muscle action.     

Inflammatory pseudotumour of the urinary bladder

An inflammatory pseudotumour that arose in the urinary bladder of a 33-year-old woman is reported. This is the twelfth reported example of this unusual non-neoplastic lesion that may be mistaken for a sarcoma. The lesion was composed predominantly of spindle cells that by routine light microscopical, ultrastructural and immunohistochemical examination had features consistent with myofibroblasts. Awareness of this unusual lesion is important to prevent its misinterpretation.     

Pseudosarcomatous lesions of the urinary bladder

The clinical, microscopical, immunocytochemical and ultrastructural features of five cases of benign mesenchymal proliferative lesions of the urinary bladder, mimicking sarcoma, are presented. Four of the five patients are alive and disease-free following diagnosis, an interval ranging from 9 months to 9 years, mean 4 years. A fifth patient, who had a pseudosarcomatous stromal response adjacent to a urinary transitional cell carcinoma, now has invasive transitional cell carcinoma. The lesions revealed a striking microscopical, immunocytochemical and ultrastructural similarity to nodular fasciitis, suggesting the lesions represented a bizarre mesenchymal proliferative response to inflammation.     

Composite paraganglioma-ganglioneuroma of the urinary bladder

Presented herein is the case of a 73-year-old man, complaining of dysuria, who had a composite paraganglioma-ganglioneuroma of the urinary bladder (CPGUB). At cystoscopy a submucosal tumor was found in the urinary bladder and resected after transurethral biopsy. The levels of serum catecholamine and 24 h urinary excretion of catecholamine and vanillylmandelic acid were elevated. Grossly, the resected tumor, measuring 4 x 3 x 2.5 cm, had a brownish cut surface with no necrosis and hemorrhage. Histologically, the tumor had alternating cellular and fibrous areas. The cellular areas consisted of polygonal cells, arranged in well-defined nests (Zellballen) and positive for Grimelius staining, with abundant amphophilic to acidophilic cytoplasm, occasionally containing eosinophilic hyaline globules and brown pigments. Although the nuclei of several polygonal cells were bizarre, mitoses and vascular invasion were not found. Fibrous areas consisted of spindle cells, resembling Schwann cell, admixed with ganglionic cells. To the authors' knowledge, only four cases of CPGUB have been reported in the English-language literature. Detailed reported cases and the present case showed no malignant features, such as extra-bladder infiltration and metastasis, and no recurrence in the short length of follow up. Accumulation of long-term follow-up cases may provide valuable prognostic information on this composite tumor.     

Leiomyosarcoma of the urinary bladder: a diagnostic challenge in urine cytology

Most of the available data in the literature describe the cytomorphological features of exfoliated malignant epithelial cells in urine. There are no established diagnostic features that characterize the morphology of exfoliated malignant mesenchymal tumor in urine. Here we highlight the problems in the diagnosis of these groups of tumors. The presence of discohesive atypical cells which lack features of an epithelial nature should make one suspicious of this group of tumors.     

Primary signet-ring cell carcinoma of the urinary bladder

Signet-ring cell carcinoma of the urinary bladder is a rare tumour, accounting for approximately 0.24% of all bladder malignancies. In this study, the clinicopathological findings in 13 cases are described. This malignancy is far more common in men than in women (ratio 11:2). The distribution by age and clinical symptoms can not distinguish it from transitional cell carcinoma. The tumour behaves like other high grade malignancies, presenting frequently at an advanced stage, and having an unfavourable clinical outcome. No special therapy seems superior to another.     

The prevalence and character of the muscularis mucosae of the human urinary bladder

We report the results of a histological evaluation of 335 consecutive autopsy specimens of apparently normal urinary bladder for the presence of a complete, partial or minimal muscularis mucosae. There were 164 females (49%) and 171 males (51%), ranging in age from 20 weeks of gestation to 102 years. A muscularis mucosae was present in 117 bladders (35%). The female to male ratio was 2:1, with 45% of female and 25% of male bladders containing a muscularis mucosae. The muscularis mucosae was complete in one case (1%), partial in 23 cases (6%) and minimal in 93 cases (28%). The occurrence of a partial or complete muscularis mucosae was ten times more likely in women than men. The presence of a muscularis mucosae in both women and men was not associated with any known disease process, nor was it related to patient age.     

Inflammatory pseudotumor of the urinary bladder with an aberrant expression of cytokeratin

A case of inflammatory pseudotumor of the urinary bladder in a 47 year old Japanese male patient is presented. Inflammatory pseudotumor of the urinary bladder is a benign but rare proliferative lesion of the submucosal stroma, easily mistaken for a malignant neoplasm. Based on the clinical diagnosis of bladder cancer by cystoscopy and magnetic resonance imaging (MRI), urologists started chemotherapy before results of the histological report were available which described inflammatory pseudotumor on the biopsy. Biopsied materials showed marked proliferation of irregularly bundled spindle ceils, varied in size and shape and separated in severe loose myxoid stroma with moderate infiltration of the inflammatory cells and capillary proliferations. At a glance, these findings resemble the sarcomatous pattern. However neither severe nuclear atypism nor atypical mitoses were present. Immunohistochemically, these spindle cells, which were positive for vimentin and α-smooth muscle actin, showed a diffuse aberrant expression of cytokeratin. Some of them were positive for phosphotungstic acid hematoxylin. Electron microscopy revealed only the fibroblasts. No recurrence has been observed for 10 months. These findings indicate that inflammatory pseudotumor is a benign mesenchymal lesion that must be discriminated from true sarcoma to avoid subjecting the patient to unnecessary therapy. Only careful histological examination can enable a successful diagnosis.     

Cutaneous nerve regeneration in the rat: reinnervation of the denervated skin by regenerative but not by collateral sprouting

The functional regeneration of cutaneous chemosensitive nerves responsible for the initiation of the neurogenic inflammatory response has been studied in rat hind paw skin. The qualitative and quantitative estimation of plasma extravasation induced by mustard oil, a skin irritant which induces an inflammatory response by the neurogenic route, proved to be a reliable and objective method for studying the regeneration of these cutaneous nerves. The results indicate a complete functional reinnervation by chemosensitive sensory nerves of the skin area previously denervated by crushing the corresponding peripheral nerve. It is concluded that these particular unmyelinated sensory nerves regenerate by means of regenerative sprouting but apparently lack the ability for collateral sprouting. The significance of the present findings in relation to the mechanisms of cutaneous nerve regeneration is discussed.     

Carcinoma of the urinary bladder with a lymphomatous appearance

We present the first report of bladder carcinoma that demonstrates a mixture of two distinct histological patterns resembling malignant lymphoma. The patient was a 79-year-old man. One of the histological patterns was a diffuse growth of monomorphic carcinoma cells, and the other was a dense lymphoplasmacytic infiltrate, obscuring the carcinoma. The tumor cells showing both patterns expressed cytokeratin and epithelial membrane antigen, but not lymphoid markers. Careful immunohistochemical evaluation should be done when diagnosing urinary bladder carcinomas resembling lymphomas (other than primary lymphomas).     

Shortening induced deactivation in the guinea-pig urinary bladder

Shortening induced deactivation, the depressant effect of active muscle shortening on the subsequently measured isometric force, has been shown in smooth muscle strips and rings. The guinea-pig bladder permits the investigation of this phenomenon in a whole organ preparation. Previous work in our laboratory showed that shortening of the in vitro guinea-pig detrusor muscle had a depressant effect on the isovolumetric pressure that could be generated immediately afterwards. To test the hypothesis that this was caused by deactivation, the effects of active and passive detrusor shortening on the subsequently measured isovolumetric pressure were compared. The isovolumetric pressures measured after 5 min periods of recovery were taken as control values. It was found that the isovolumetric pressure after passive shortening was 7% smaller than the isovolumetric pressure without preceding shortening. This difference was ascribed to viscoelastic relaxation during shortening. Active shortening had an additional 8% depressant effect on isovolumetric pressure compared with passive shortening. The effects of active and passive shortening differed significantly. It was concluded that shortening induced deactivation in the guinea-pig urinary bladder smooth muscle in toto can be considered proven. The fact that deactivation is shown both by striated and smooth muscle preparations is in line with the assumption that it is caused by reduced actin-myosin interaction. The hypothesis that (in striated muscle) the latter is effected by a decrease in troponin–calcium binding, however, needs reconsideration.     

Nitric oxide inhibits arginine-vasotocin-induced increase of water osmotic permeability in frog urinary bladder

The present study addressed the question of whether nitric oxide (NO) participates in regulation of osmotic water permeability in the urinary bladder of the frog Rana temporaria L. Experiments were carried out on isolated, paired hemi-bladders filled with amphibian Ringer solution diluted 1:10 with distilled water. Sodium nitroprusside (SNP, 125–250 µM), an NO donor, markedly attenuated the increase of osmotic water flow elicited by arginine-vasotocin (AVT) (AVT 10^–10 M: 2.20±0.26; AVT plus 200 µM SNP: 1.21±0.15 µl/min cm², n=20, P<0.001). This effect of SNP was apparent only in the presence of 50 µM zaprinast, an inhibitor of the cGMP-specific phosphodiesterase-5 (PDE5). In the presence of zaprinast, SNP elevated cGMP production significantly both in control and AVT-stimulated urinary bladders, but had no effect on the level of cAMP (AVT 5×10^–10 M: 7.6±0.6; AVT plus SNP 200 µM: 7.5±0.4 pmol/mg protein, n=8, N.S.). 1H-[1,2,4]-oxadiazole-[4,3-a]-quinoxalin-1-one (ODQ, 25–100 µM), an inhibitor of soluble guanylate cyclase, enhanced the AVT-induced water flow, decreased the SNP-stimulated increase of cGMP in the bladder tissue and almost abolished the inhibitory effect of SNP on the AVT-induced hydroosmotic response. 8-(p-Chlorophenylthio)-cGMP (8-pCPT-cGMP, 25 or 50 µM), a membrane-permeable cGMP analogue specific for cGMP-dependent protein kinase (PKG), inhibited, whereas 2 µM KT-5823, an inhibitor of PKG, significantly stimulated the increase of water flow induced by AVT. The inhibitory effect of SNP on AVT-induced water flow was almost completely reversed by KT-5823, but not by 50–100 µM erythro-9-[2-hydroxy-3-nonyl]adenine (EHNA), an inhibitor of cGMP-activated PDE2. Immunohistochemistry of urinary bladder slices with antibodies against different types of NO synthase (NOS) revealed a positive immunostaining for neuronal NOS (nNOS) in the mucosal epithelium. These results suggest that in the frog urinary bladder endogenous NO is involved in regulation of water osmotic permeability. NO inhibits the AVT-induced increase of water flow at least partly by activation of PKG, which interferes with the hydroosmotic effect of AVT probably at (a) post-cAMP step(s).     

Lymphomas of mucosa-associated lymphoid tissue arising in the urinary bladder

The clinical, histological and immunohistochemical findings in five primary lymphomas of the urinary bladder are reported. One patient had both lymphoma and transitional cell carcinoma of the bladder. All of the lymphomas showed histological features of mucosa-associated lymphoid tissue (MALT) lymphomas with centrocyte-like cells in all cases. One patient with pre-existing cystitis glandularis showed lymphoepithelial lesions. Biopsies from four patients contained reactive germinal centres and, in two of these, there was follicular colonization by tumour cells. In three patients, repeat biopsies, over several years, showing the changes of MALT lymphoma, were diagnosed as cystitis. We suggest that a large proportion of primary lymphomas of the bladder are lymphomas of MALT and that the characteristic morphological and immunohistochemical features of these tumours should be sought in biopsies containing large numbers of lymphoid cells.