["Why visit a medical congress?" : Knowledge transfer between Germany and Sweden using the example of the 1929 DGU meeting in Munich]. / "Warum besucht man Kongresse?" : Deutsch-schwedischer Wissenstransfer am Beispiel des DGU-Kongresses in München 1929.

Drawing on contemporary publications in German and Swedish/Scandinavian journals and biographies as well as conference proceedings of the German Society of Urology (DGU), this paper examines the Swedish impressions of the 1929 DGU meeting in Munich. It focusses on why the Swedish delegates visited the congress and how they evaluated their congress experiences for their Scandinavian peers. Finally, the article shows to what extent a knowledge transfer from the DGU Congress to Sweden took place.

Autonomic nervous control of the urinary bladder.

The autonomic nervous system plays an important role in the regulation of the urinary bladder function. Under physiological circumstances, noradrenaline, acting mainly on ß(3) -adrenoceptors in the detrusor and on α(1) (A) -adrenoceptors in the bladder outflow tract, promotes urine storage, whereas neuronally released acetylcholine acting mainly on M(3) receptors promotes bladder emptying. Under pathophysiological conditions, however, this system may change in several ways. Firstly, there may be plasticity at the levels of innervation and receptor expression and function. Secondly, non-neuronal acetylcholine synthesis and release from the urothelium may occur during the storage phase, leading to a concomitant exposure of detrusor smooth muscle, urothelium and afferent nerves to acetylcholine and noradrenaline. This can cause interactions between the adrenergic and cholinergic system, which have been studied mostly at the post-junctional smooth muscle level until now. The implications of such plasticity are being discussed.

Role of desmin in active force transmission and maintenance of structure during growth of urinary bladder.

Role of the intermediate filament protein desmin in hypertrophy of smooth muscle was examined in desmin-deficient mice (Des(-/-)). A partial obstruction of the urethra was created, and after 9-19 days bladder weight increased approximately threefold in both Des(-/-) and wild type (Des(+/+)) animals. Bladder growth was associated with the synthesis of actin and myosin. In the hypertrophic Des(+/+) bladder, the relative content of desmin increased. In Des(-/-)mice, desmin was absent. No alterations in the amount of vimentin were observed. Although Des(-/-) obstructed bladders were capable of growth, they had structural changes with a partial disruption of the wall. Des(-/-)bladders had slightly lower passive stress and significantly lower active stress compared with Des(+/+). Des(-/-)preparations had lower shortening velocity. During hypertrophy, these structural and mechanical alterations in the Des(-/-)urinary bladder became more pronounced. In conclusion, desmin in the bladder smooth muscle is not needed for growth but has a role in active force transmission and maintenance of wall structure.

Changes in intracellular calcium concentration and P2X1 receptor expression in hypertrophic rat urinary bladder smooth muscle.

AIMS: Contractile responses to purinergic activation in the urinary bladder are altered in outflow obstruction (O). We determined if the lowered contractile response to adenosine triphosphate (ATP) in obstructed rat urinary bladder was due to changes in calcium handling or in P2X1 purinoceptor density. MATERIALS AND METHODS: O was created in rat by partial ligature of the urethra, with non-obstructed rats as controls (C). Force and intracellular calcium were measured in bladder strips activated with ATP. Tissue was sectioned for light and electron microscopy and analyzed with Western blot using a P2X1 antibody. RESULTS: Bladder weight increased from 66 +/- 3 (C) to 206 +/- 17 mg (O) (n = 6). ATP gave a transient contractile response which was decreased in the obstructed strips (C: 161 +/- 20; O: 63 +/- 16% of high-K+ force). Intracellular calcium concentration after ATP activation in the obstructed bladder muscle was about 50% of that in the control preparations (C: 669 +/- 110; O: 335 +/- 59 nM). Half-time for calcium influx was increased in the O group. P2X1 immunoreactivity per unit bladder weight was similar in the two groups. Cell membrane area per unit wet weight was decreased in the O group. CONCLUSIONS: Attenuated contractile responses to ATP in obstructed rat urinary bladder are due to a lowered rate of calcium influx and maximal peak calcium concentration. This change in Ca2+transients is not due to a decrease in P2X1 receptor density in the smooth muscle cell membranes. Possibly, the increase in cell volume buffers the rapid and transient influx of Ca2+ following purinoceptor activation in the obstructed bladder.

Regeneration of detrusor muscle after subtotal cystectomy in the rat: effects on contractile proteins and bladder mechanics.

The aim of the present study was to determine to what extent adult rats can produce new contracting bladder muscle and to see if such newly formed bladder tissue possesses characteristic mechanical properties or whether the ability to recover mechanically is so pronounced that the prehistory of the bladder is unimportant. Subtotal cystectomy was performed in adult female rats, leading to a pronounced decrease in total bladder weight. At 10 weeks, bladder weight had normalized. The histological appearance of such bladders was similar to that of the controls. Active and passive length-tension relations for the detrusor muscle were determined in controls and up to 10 weeks after surgery. Immediately after surgery active and passive forces showed a leftward shift and maximum active force decreased markedly. With time the length-tension curves shifted back to normal, but a decreased active force still remained at 10 weeks. Detrusor actin concentration and detrusor myosin/actin ratio were unaffected by the subtotal cystectomy. Intermediate filament protein/actin ratio showed a significant but transitory increase. We conclude that there is a remarkable recovery of detrusor muscle function after subtotal cystectomy, leading to a normalization of optimum length for active force and a net synthesis of contractile and cytoskeletal proteins. The ability to produce active force does, however, not fully recover.

Up-regulation of bradykinin response in rat and human bladder smooth muscle.

PURPOSE: Responses to bradykinin were investigated in vitro in isolated control and hypertrophic smooth muscle strips from rat bladder. MATERIALS AND METHODS: Bladder hypertrophy was induced by a 10-day period of partial urinary outflow obstruction. In addition, human bladder strips were also investigated. RESULTS: Bradykinin (1 nM. to 1 microM.) caused contractions in all tissues studied. In the freshly isolated rat bladder preparations bradykinin induced contractions were similar and of small amplitude in control and hypertrophic tissues. After a 4-hour equilibratory period contractile responses to bradykinin and the B1 specific bradykinin receptor agonist desArg9 bradykinin were slightly increased in the controls but there was approximately a 6-fold increase in the hypertrophic muscle strips. After 4 hours of equilibration the human bladder strips showed a smaller but still significant increase in contractile response to bradykinin. Indomethacin, a cyclooxygenase inhibitor, almost abolished the increased response, which suggests that prostanoids are involved in the up-regulated response. The protein synthesis inhibitor cycloheximide inhibited up-regulation by approximately 50% in hypertrophic and control muscle strips from rat bladder and normal muscle from human bladder. CONCLUSIONS: These results demonstrate that bradykinin receptor responses are present in rat and human detrusor muscle and they can be up-regulated in vitro. Experiments on hypertrophic rat bladder revealed that this process is enhanced in hypertrophy.

Structural changes in the rat bladder after acute outlet obstruction.

The urinary bladder of adult female rats was subjected to complete outlet obstruction for periods of up to 24 h. Within 2 h the obstruction led to a rise in intravesical pressure to about 80 mmH2O. Subsequently, the pressure remained high but declined slightly. After 24 h of complete obstruction the bladder was maximally distended, but its volume was similar to that of a control bladder fully distended, indicating that overstretch (or overdistension) occurs only to a very limited degree. After 6 h of obstruction there was congestion of all the intramural blood vessels and extravasation of red blood cells from some vessels of the mucosa. At 12 h and 24 h the extravasation was very substantial and there was also infiltration of erythrocytes in the muscle layer. Ultrastructurally, there were several damaged nerve endings (but no changes in the nerve trunks) and, occasionally, damaged muscle cells. Removal of the obstruction after 24 h was followed by resorption of the extravasate, partly by phagocytosis by muscle cells, a process which lasted 4-6 days, and by 7 days damaged varicosities and muscle cells became uncommon. We conclude that the changes observed in the bladder wall following complete obstruction are caused more by haemorrhage and ischaemia than by overstretch and that the changes are reversed when outlet conditions are normalized.

Sprouting of bladder nerves into cystoplastic cecal segment in the rat.

Incorporation of bowel into the bladder (enterocystoplasty) has been widely used to increase bladder capacity. It has been reported by others that the response of smooth muscle from the cystoplastic segment of the intestine shifts from that of the intestine (relaxation to alpha-agonists and ATP) to that of the bladder (contraction to alpha-agonists and ATP). This suggests a functional integration of the intestinal muscle into the bladder; the mechanisms are unknown. The aims of the present study were (1) to elucidate if there are signs of bladder nerves sprouting across the anastomosis into the intestinal segment, and (2) to study what happens with the intrinsic innervation of the intestinal segment. As a model, we used cecocystoplasty in rats. The bladder was opened and a patch of cecum with intact vascular supply was anastomosed to the bladder. After two to 11 months the rats were sacrificed and the bladders mounted as wholemounts and stained for acetylcholinesterase-containing nerves, or embedded in paraffin for histology. A pronounced degeneration of the myenteric plexus was found in the cecal segments. In some areas, this had proceeded to the extent that the ganglia were isolated ovoid lumps of cells with no apparent connection to other ganglia. Areas lacking ganglia and nerve trunks but still with muscle could be found in all specimens. Abundant axon bundles were demonstrated sprouting from the cut bladder nerves close to the anastomosis. The bundles spread out in a fan-like pattern or were organized as fewer thicker nerves. There were many nerve bundles entering the cecal segment where they branched and the diameter decreased till they no longer became visible. Some nerves reached surviving lumps of myenteric ganglion cells. The results show that the bladder nerves sprout into the anastomosed cecal segment. It is reasonable to assume that these nerves are responsible for the changes in receptor pharmacological properties of the cecal smooth muscle towards that of bladder muscle.

The distribution of intramural nerves in urinary bladder after partial denervation in the female rat.

We evaluated the degree of neuronal plasticity following a partial denervation of the rat urinary bladder. Using acetylcholinesterase staining we found that the postganglionic nerves from the pelvic ganglion reach the intact bladder as 1-4 nerve trunks on each side, slightly ventral and caudal to the ureteral orifices. Normally a few thinner nerves also reach the bladder posterolateral to the ureterovesical junction. The nerves ventral to the ureters run in the ventral longitudinal muscle layer as well-defined trunks with a pattern that does not differ much from one animal to another. The nerves reaching the bladder dorsolaterally innervate the dorsolateral aspects in a more irregular fashion. Some anastomoses are found across the midline between nerves from either side. This nerve pattern is already in place in newborn rats. After removal of the pelvic ganglion on one side in the adult rat the ipsilateral ventral nerves rapidly degenerate, whereas some dorsolateral nerves usually survive. Axons from the intact ventral nerves can be seen crossing over to the denervated side in the anastomoses. After 13 weeks the surviving ventral nerves, which normally run at some distance from the ventral midline, now run in the midline with equal amounts of ventral longitudinal muscle on either side, and with their branches evenly distributed to both sides. The same pattern is seen after 27 weeks. Unilateral ganglionectomy in 3-week-old rats leads to the same changes in nerve distribution as in the adult rat. We conclude that there is a high degree of plasticity in the bladder innervation following a partial denervation, and that this plasticity includes the distribution of its main intramural nerve trunks.

Cystometrical evaluation of acute and chronic overdistension in the rat urinary bladder.

The urodynamic effects of an experimental, partial infravesical outlet obstruction in rats were studied and compared with the effects in sham-operated controls, and in animals that had undergone 24 h of total outlet obstruction. The animals were studied up to 42 days after surgery. Bladder weight increased with time in the partially obstructed group to reach a final value of 6 times that of the control. In water loading experiments micturition volume was unaffected by sham operation. In the partially obstructed bladders it decreased initially but normalized with time. In the group that had undergone 24 h of total obstruction micturition volume also decreased initially but then became significantly higher than in the controls. In cystometry experiments the partially obstructed bladders developed a considerable residual urine and increased threshold and micturition pressures. Detrusor instability was present already after 10 days. Also in the cystometry experiments the bladders that had been totally obstructed for 24 h had increased micturition volumes. Residual volume was only slightly affected by atropine in the control and partially obstructed bladders but increased 7-fold in rats in which the bladder had been totally obstructed for 24 h 42 days previously. We conclude that there is a close relationship between bladder weight, residual volume and micturition pressure in the partially obstructed bladder, and that 24 h of total obstruction results in disturbances of bladder function that might be related to denervation phenomena previously reported by others.

Contractile properties of ureters from rats with infravesical urinary outlet obstruction.

Mechanical properties of ureters from rats with infravesical urinary outflow obstruction were studied in vitro. Urinary outflow obstruction was created by partial ligation of the urethra in female rats. After 10 days a marked hypertrophy of the urinary bladder and a dilatation of the ureters were observed. Proximal and distal segments of the ureters from these animals were isolated and mounted in a wire myograph for force registration. Comparisons were made with ureters from control rats. The ureters from the rats with urinary outflow obstruction exhibited a large increase in lumen diameter and an unchanged thickness of the muscle layer. These data suggest that the dilatation of the ureters is associated with growth of the smooth muscle in the wall. All ureter preparations were relaxed in normal physiological salt solution. When the extracellular K+ concentration was increased to 20 mM the dilated ureters became spontaneously active. At [K+] in the range 20-40 mM in the presence of noradrenaline (10(-5) M) all ureters exhibited high-frequency spontaneous contractions. The dilated ureters had a lower frequency of spontaneous contractions and a higher force. The results show a pronounced remodelling of the ureter wall following infravesical outlet obstruction. The structural changes were associated with alterations in the contraction pattern of the preparations, most probably reflecting changes in the excitation-contraction coupling of the growing cells.

Nitrergic and cholinergic innervation of the rat lower urinary tract after pelvic ganglionectomy.

The possible coexistence of nitric oxide (NO) and acetylcholine in the rat major pelvic ganglion (MPG) was examined by double immunohistochemistry using antisera raised against NO synthase (NOS) and choline acetyltransferase (ChAT). The smooth muscle responses of the isolated bladder and urethra were recorded after bilateral cryoganglionectomy of the MPG, focusing on the possible development of denervation supersensitivity. In the MPG, NOS immunoreactivity (ir) was seen in a large number of cell bodies, but it was not as abundant as ChAT-ir cell bodies. Double immunolabeling showed that all NOS-ir cell bodies also displayed ChAT-ir. In ganglionectomized bladders, the electrical field stimulation (EFS)-evoked contractile response was markedly reduced. When compared with control bladders, detrusor strips from ganglionectomized rats were more sensitive to carbachol as revealed by a lower negative logarithm of the drug concentration eliciting 50% relaxation (6.5 +/- 0.04 vs. 5.9 +/- 0.07). In the urethra, the NO-mediated relaxant response to EFS was practically abolished by ganglionectomy, whereas no difference was found in sensitivity to 3-morpholinosydnonimine hydrochloride (SIN-1). SIN-1 produced an equal increase in tissue levels of guanosine 3',5'-cyclic monophosphate in urethral preparations from control and ganglionectomized rats. The results suggest that the NOS-ir nerves that mediate inhibition of rat urethral smooth muscle tone originate from the MPG and contain ChAT. No denervation supersensitivity to nitrergic stimulation was observed in the urethra after ganglionectomy.

Homotransplant of pelvic ganglion into bladder wall in adult rats.

In these experiments a large portion of the pelvic ganglion of adult female rats was transplanted into the wall of the urinary bladder of the same animals. The morphology and fine structure of the transplants were studied in whole-mounts and in sections for light and electron microscopy, from two days up to four months after operation. The general architecture of the ganglion was preserved in all the transplants. The vascularization was re-established. Nerves grew out of the transplant and connections with the original intramural nerves of the bladder wall were established. All the synapses degenerated at the time of transplantation; new synapses began to reappear on the ganglion neurons in the oldest transplants. Although some neurons in the transplant degenerated during the first few days, the majority of neurons survived for the full length of the experiments (four months). Satellite glial cells and small intensely fluorescent cells had a similar structure and distribution as in control ganglia. The results show that the homotransplant of pelvic neurons into the bladder has a high rate of success, in terms of survival, maintenance of fine structure, growth and re-connections; these neurons of adult organisms display plastic and regenerative abilities.

Shortening velocity is different in longitudinal and circular muscle layers of the rabbit urethra.

The aim of the study was to investigate whether the functional difference between circular and longitudinal muscles in the female rabbit urethra is reflected in their shortening properties and lactate dehydrogenase (LDH) activity. For mechanical experiments the preparations were chemically skinned to avoid influence of membrane-related mechanisms and to enable maximal activation. Force velocity relations and the maximal shortening velocity (v(max)) were determined using the isotonic quick-release method. The v(max) was three times higher in longitudinal muscle. LDH isoform pattern was determined on agarose gels. The M-subunit, favourable for lactate formation, constituted 70% of the total in both types of muscle. There was no difference in the LDH isoform pattern despite the marked difference in v(max). We conclude that the difference in v(max) reflects differences in the contractile machinery itself. These mechanical characteristics are advantageous for the role of the circular as a tonic muscle contracting during bladder filling, and the longitudinal as a phasic muscle active in opening up the urethra during micturition.

Acute contractile effects of epidermal growth factor on bladder smooth muscles. An in vivo and in vitro study in rats.

Chronic treatment with epidermal growth factor (EGF) stimulates growth of all wall layers of the urinary tract in pigs and rats. Herein, we investigated the acute effects of EGF on detrusor smooth muscle activity. For in vivo examination, awake rats received EGF (75 micrograms/kg) intravenously and detrusor smooth muscle activity was monitored cystometrically. The EGF bolus caused no alteration in diuresis but a doubling of the micturition frequency, a 25% increase in micturition pressures, and increased irregular baseline contractile activity. For in vitro examination detrusor smooth muscle strips were exposed to EGF (1 microgram/ml). EGF caused contraction and increase in the spontaneous activity. In conclusion, EGF increases rat detrusor smooth muscle contractile activity in vivo and in vitro. The finding suggests that a direct effect of EGF on bladder smooth muscles is part of the genesis to the growth of the detrusor smooth muscle observed after chronic EGF treatment.

Partial obstruction of the rat urinary bladder: effects on mitochondria and mitochondrial glucose metabolism in detrusor smooth muscle cells.

The aim of the present study was to measure mitochondrial function in the obstructed rat bladder, which does not seem to have impaired contractility in vivo. The animals were unoperated control rats and rats with a 12-day partial urinary outlet obstruction. The obstruction increased bladder weight 3-fold. The relative volume (3.5%) in the detrusor smooth muscle cells composed of mitochondria was unaffected by obstruction. Obstruction did not affect malate dehydrogenase and citrate synthase activity when expressed relative to unit bladder weight. There was, however, a significant decrease in enzyme activity when expressed relative to protein content. This was due to an increased relative protein content in the obstructed bladders. Total enzyme activities per bladder were increased. Oxygen consumption rates in maximally activated intact control and obstructed preparations in other studies corresponded to a citrate synthase (rate-limiting enzyme) activity only 10% of the maximal enzyme activity found in the present study. We conclude that there is a considerable safety margin in mitochondrial function in intact rat detrusor muscle cells, and that detrusor smooth muscle cells can hypertrophy without any impaired mitochondrial function.

Old age does not affect shortening velocity or content of contractile and cytoskeletal proteins in the rat detrusor smooth muscle.

The influence of old age on mechanical properties of the urinary bladder was investigated using smooth muscle strips from urinary bladders of control (14-16 weeks) and old-age (104 weeks) female Sprague-Dawley rats. Bladder weight of the aged rats had increased by about 30%. The maximal shortening velocity and stiffness in skinned activated urinary bladder fibers from old animals were unchanged compared to controls. The relative content of intermediate filament proteins to actin and the relative content of myosin to actin was unchanged. The concentration of myosin was unchanged (about 6.5 microg/mg wet weight). The results suggest that old age is not associated with pronounced changes in the cellular contractile and cytoskeletal proteins or in the mechanical properties of the contractile machinery. The age-related changes in mechanical properties previously reported for intact smooth muscle from urinary bladder are most likely due to alterations in the activation systems.