Central nervous control of micturition and urine storage.

The micturition reflex is one of the autonomic reflexes, but the release of urine is regulated by voluntary neural mechanisms that involve centers in the brain and spinal cord. The micturition reflex is a bladder-to-bladder contraction reflex for which the reflex center is located in the rostral pontine tegmentum (pontine micturition center: PMC). There are two afferent pathways from the bladder to the brain. One is the dorsal system and the other is the spinothalamic tract. Afferents to the PMC ascend in the spinotegmental tract, which run through the lateral funiculus of the spinal cord. The efferent pathway from the PMC also runs through the lateral funiculus of the spinal cord to inhibit the thoracolumbar sympathetic nucleus and the sacral pudendal nerve nucleus, while promoting the activity of the sacral parasymapathetic nucleus. Inhibition of the sympathetic nucleus and pudendal nerve nucleus induces relaxation of the bladder neck and the external urethral sphincter, respectively. There are two centers that inhibit micturition in the pons, which are the pontine urine storage center and the rostral pontine reticular formation. In the lumbosacral cord, excitatory glutamatergic and inhibitory glycinergic/GABAergic neurons influence both the afferent and efferent limbs of the micturition reflex. The activity of these neurons is affected by the pontine activity. There are various excitatory and inhibitory areas co-existing in the brain, but the brain has an overall inhibitory effect on micturition, and thus maintains continence. For micturition to occur, the cerebrum must abate its inhibitory influence on the PMC.     

A case of metachronous adenocarcinoma of the urinary bladder and the right upper urinary tract

Bilateral hydronephrosis identified by a local physician brought a 65-year-old man to our hospital. Emergency percutaneous nephrostomy was bilaterally established for obstructive renal failure. After recovering renal function, the patient underwent radical cystectomy under the diagnosis of invasive bladder cancer and the construction of an ileal conduit. The pathology reported well differentiated adenocarcinoma (pT2, pL1, pV1). Five years after the surgery, gross hematuria developed. A computed tomographic scan revealed right hydronephrosis with a solid mass in the upper calyx. The urinary cytology was negative. The patient underwent right nephrectomy in May, 1999. The pathology then revealed well differentiated adenocarcinoma in the renal pelvis and ureter (pT3, pL0, pV0 and pT1, pL0, pV0, respectively). He is alive with mild chronic renal insufficiency with evidence of tumor at ten months after surgery. To our knowledge, this is the first case of metachronous adenocarcinoma of the urinary bladder and the upper urinary tract reported in the Japanese literature.     

Compensatory renal hypertrophy and changes of renal function following nephrectomy

We studied the changes in the serum creatinine level and the volume of the remaining kidney following nephrectomy using contrast-enhanced compounded tomogram (CT) scans. Twenty-five patients undergoing nephrectomy for renal cell carcinoma without obvious disease in the remaining kidney were carefully followed for a period of at least two years at our hospital. Twelve patients received follow-up CT scans each year after nephrectomy. The ellipsoid volume of the kidney was calculated by measuring the 3-dimensional size on CT scans. The mean relative volume (%) of the remaining kidney increased up to year 3 postoperatively, and the final mean relative volume at varying periods from years 2 to 7 was 120%. Kidneys that were smaller prior to nephrectomy showed a tendency to have a larger final relative volume after nephrectomy, although there was no significant correlation between the kidney volume prior to nephrectomy and at final measurement. The mean serum creatinine level was significantly increased at one year after nephrectomy, but it decreased significantly over time. Therefore, both compensatory renal hypertrophy and improved renal function seemed to be established within several years after nephrectomy. However, the improvement of serum creatinine was delayed compared with the increase of kidney volume. That is, renal plasma flow might be increased early by compensatory renal hypertrophy, followed within a few years by an increase in glomerular filtration and a decrease of serum creatinine.     

Neuromedin s is a novel anorexigenic hormone

A novel 36-amino acid neuropeptide, neuromedin S (NMS), has recently been identified in rat brain and has been shown to be an endogenous ligand for two orphan G protein-coupled receptors, FM-3/GPR66 and FM-4/TGR-1. These receptors have been identified as neuromedin U (NMU) receptor type 1 and type 2, respectively. In this study, the physiological role of the novel peptide, NMS, on feeding regulation was investigated. Intracerebroventricular (icv) injection of NMS decreased 12-h food intake during the dark period in rats. This anorexigenic effect was more potent and persistent than that observed with the same dose of NMU. Neuropeptide Y, ghrelin, and agouti-related protein-induced food intake was counteracted by coadministration of NMS. Icv administration of NMS increased proopiomelanocortin mRNA expression in the arcuate nucleus (Arc) and CRH mRNA in the paraventricular nucleus (PVN). Pretreatment with SHU9119 (antagonist for alpha-MSH) and alpha-helical corticotropin-releasing factor-(9-41) (antagonist for CRH) attenuated NMS-induced suppression of 24-h food intake. After icv injection of NMS, Fos-immunoreactive cells were detected in both the PVN and Arc. When neuronal multiple unit activity was recorded in the PVN before and after icv injection of NMS, a significant increase in firing rate was observed 5 min after administration, and this increase continued for 100 min. These results suggest that the novel peptide, NMS, may be a potent anorexigenic hormone in the hypothalamus, and that expression of proopiomelanocortin mRNA in the Arc and CRH mRNA in the PVN may be involved in NMS action on feeding.     

The fifth neurohypophysial hormone receptor is structurally related to the V2-type receptor but functionally similar to V1-type receptors

The neurohypophysial peptides of the vasopressin (VP) and oxytocin (OT) families regulate salt and water homeostasis and reproduction through distinct G protein-coupled receptors. The current thinking is that there are four neurohypophysial hormone receptors (V1aR, V1bR, V2R, and OTR) in vertebrates, and their evolutionary history is still debated. We report the identification of a fifth neurohypophysial hormone receptor (V2bR) from the holocephalan elephant fish. This receptor is similar to conventional V2R (V2aR) in sequence, but induced Ca(2+) signaling in response to vasotocin (VT), the non-mammalian VP ortholog; such signaling is typical of V1-type receptors. In addition, V1aR, V1bR and OTR were also isolated from the elephant fish. Further screening revealed that orthologous V2bRs are widely distributed throughout the jawed vertebrates, and that the V2bR family is subdivided into two subfamilies: the fish specific type-1, and a type-2 that is characteristically found in tetrapods. Analysis suggested that the mammalian V2bR may have lost its function. Based on molecular phylogenetic, synteny and functional analyses, we propose a new evolutionary history for the neurohypophysial hormone receptors in vertebrates as follows: the first duplication generated V1aR/V1bR/OTR and V2aR/V2bR lineages; after divergence from the V2bR lineage, the V2aRs evolved to use cAMP as a second messenger, while the V2bRs retained the original Ca(2+) signaling system. Future studies on the role of V2bR in the brain, heart, kidney and reproductive organs, in which it is highly expressed, will open a new research field in VP/VT physiology and evolution.     

Effects of phosphodiesterase type 5 inhibitor,tadalafil, on continence reflex in rats

Introduction and hypothesis

Effects of tadalafil, a phosphodiesterase type 5 inhibitor, on the urethral continence reflex induced by sneezing were investigated.

Methods

The amplitude of urethral pressure responses during sneezing (A-URS) and urethral baseline pressure (UBP) were measured in female rats using a microtransducer-tipped catheter. Sneeze leak-point pressure (S-LPP), defined as the lowest amount of pressure required to induce fluid leakage from the urethral orifice during sneezing, was measured in rats with stress urinary incontinence (SUI) induced by vaginal distension. Values were determined before and after tadalafil administration.

Results

Tadalafil dose dependently and significantly decreased A-URS and S-LPP. At the highest dose tested (6.0 mg/kg), A-URS and S-LPP decreased from 49.7 to 32.3 and from 63.9 to 44.2 cmH₂O, respectively, whereas UBP did not significantly change.

Conclusions

Tadalafil attenuated the sneeze-induced urethral continence reflex by relaxing the striated muscles of the external urethral sphincter.     

An alternative procedure for the creation of an ileal conduit in patients undergoing pelvic exenteration: dextrotransmesenteric location

Ileal conduits have long been accepted as a standard method for urinary diversion, but conventional ileal conduits are not always suitable for patients whose ureters are for the greater part compromised by neoplasm or preoperative irradiation, resulting in a shortening of the ureters. Bowel migration into the large cavity, which develops after pelvic organ removal, appears to cause tension on the ureteroileal anastomotic site. Dextrotransmesenteric placement of an ileal conduit may provide easy access to the shortened ureters without exerting pressure on the anastomosis. We employed this procedure in seven patients undergoing pelvic exenteration with relatively minimal morbidity.