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Biomedical subjects

B Uvelius

Publications and source records attributed to B Uvelius.

At least 37 records · Page 2Linked to original sources
PubMed1996

Denervation and outlet obstruction induce a net synthesis of contractile and cytoskeletal proteins in the urinary bladder of the male rat.

The concentrations of the contractile proteins actin and myosin and the cytoskeletal protein desmin were determined in urinary bladders from normal rats, and from rats with bladder outlet obstruction or denervation. Ten days of obstruction or total denervation by bilateral removal of the pelvic ganglia resulted in an almost fourfold increase in bladder weight. Actin and myosin concentrations did not change significantly. The total amount of actin was 1624 +/- 235 micrograms in the control bladder. In the obstructed and denervated bladders it increased significantly to 6277 +/-648 micrograms and 7671 +/- 835 micrograms, respectively. The desmin/actin ratio was 0.237 +/- 0.012 in the control bladders, and increased significantly to 0.369 +/- 0.015 in the obstructed and 0.343 +/- 0.022 in the denervated bladders. Partial denervation by removal of the pelvic ganglion on one side only increased bladder weight by 52%, but did not increase the desmin/actin ratio. The content of actin in such bladders increased by 82%. Both obstruction (which increases the functional load of the detrusor muscle cells) and denervation (which produces bladder paralysis) are known to induce hypertrophy of the detrusor smooth muscle cells. The study shows that the desmin/actin ratio and the total amount of contractile proteins increase in response to the hypertrophy as such, and not to the work performed by the smooth muscle cells, and that the nerves have no trophic influence on the growth response. Also, even a limited lesion of the bladder innervation is associated with growth and a net increase in the amount of contractile proteins.

Actins↗
PubMed1996

Growth resistance-sized arteries in response to bladder hypertrophy in the rat: time-course, DNA-synthesis and LDH-isoform pattern.

Bladder growth was induced by partial urethral obstruction. Bladder hypertrophy was evident at 53 h after obstruction and continued over a 6 weeks period. Small bladder arteries were taken from fixed anatomical locations of the bladder circulation, mounted in a small vessel myograph and the optimal diameter for maximal isometric force development was determined (Lmax K+ = 125 mM stimulation). Bladder hypertrophy was associated with an enlarged Lmax from 53h onward (compared with sham-operated controls) and Lmax continued to increase until 10 days after urethral obstruction. Between 10 days and 6 weeks no further increase of the diameter was observed. Increased diameters in vitro were accompanied by a transiently increased [3H] Thymidine uptake in the small arteries which peaked at 53 h after obstruction but was still above background at 10 days. At this time point, small arterial growth was associated with a significant relative increase in the M isoform of LDH as determined with agarose electrophoresis on tissue homogenates. Thus organ growth induced small vessel growth in the rat is characterized by a rapid onset, increased but transient DNA-turnover and LDH-isoform changes. The latter mimic changes seen in other types of smooth muscle growth.

Animals↗
PubMed1996

Acute effects of unilateral pelvic ganglionectomy on urinary bladder function in vivo in the male rat.

Mean and maximal micturition volumes following a standardized water intake were determined before and up to three days after unilateral pelvic ganglionectomy or sham operation in adult male rats. Sham operation did not change the volumes. Unilateral ganglionectomy on the other hand decreased significantly both mean and maximal micturition volumes (and thus increased micturition frequency). The effect was most pronounced 1 day after ganglionectomy, but was still significant after 3 days. Cystometrograms were recorded without and with atropine (1 mg/kg) before operation and 1, 2 or 3 days after sham-operation or ganglionectomy. Micturition pressure decreased to about 50% 1 day after ganglionectomy and remained at this level. Atropine decreased micturition pressure in the controls to about 55% of the initial. The atropine resistant pressure response in the ganglionectomized rats amounted to 90% after 1 day, and was still above 70% after 3 days. The sham-operated controls had no residual urine without or with atropine. The unilaterally ganglionectomized animals had no residual urine in the absence of atropine, but after administration of the drug the animals rapidly developed a significant residual urine.

Animals↗
PubMed1996

Effects of ovariectomy on mechanical properties and collagen content in rabbit lower urinary tract smooth muscle.

Fourteen female rabbits underwent ovariectomy or were sham-operated six weeks before investigation. Detrusor and urethral strips (longitudinal and circular urethral muscle fibers were studied separately) were prepared and length-tension relations studied in organ baths experiments. In addition, the specimens were examined for collagen content. Maximal active tension in the detrusor, longitudinal and circular urethral preparations, determined as the response to K+ (124mM), was reached when the length of the strips was 178 +/- 8% (n = 7), 153 +/- 9% (n = 5), and 127 +/- 5% (n = 7) of the resting length, respectively. Ovariectomy did not alter the length for development of maximal active tension. In detrusor strips, ovariectomy caused a significant increase in maximal active tension from 39 +/- 7 mN (sham-operated rabbits) to 79 +/- 11 mN (p < 0.01), despite an unchanged relative amount of smooth muscle. The maximal active tension produced in the urethra was lower (15-25 mN) than in the detrusor, and not significantly affected by ovariectomy. Approximately 40% of the dry defatted tissue weight of the detrusor consisted of collagen, whereas corresponding value in the urethra was 50-60%. Ovariectomy had no effect on tissue collagen concentrations. In conclusion, ovariectomy for six weeks did not affect the passive mechanical properties or the collagen concentration in rabbit lower urinary tract smooth muscle, but increased the responsiveness of the detrusor muscle to K+ (124 mM).

Animals↗
PubMed1995

Nitric oxide synthase-immunoreactive, adrenergic, cholinergic, and peptidergic nerves of the female rat urinary tract: a comparative study.

The distribution and frequency of NO synthase (NOS)-immunoreactive (IR) nerves in relation to the general autonomic innervation, adrenergic, cholinergic and some peptidergic nerves, were investigated in the female rat urinary tract. NOS nerves were very frequent in the smooth musculature of the urethra together with cholinergic, adrenergic and neuropeptide Y (NPY)-IR nerves, whereas vasoactive intestinal peptide (VIP)-IR and calcitonin-gene-related peptide (CGRP)-IR nerves were much less abundant. NOS-IR, CGRP-IR and cholinergic nerves were also frequent in the longitudinal smooth musculature of the distal ureters and the ureteral orifices into the bladder, where no adrenergic, NPY-IR and VIP-IR nerves were found. In contrast, in the detrusor NOS-IR nerves were scarce. Bilateral pelvic ganglionectomy very pronouncedly decreased the number of any of the populations of nerves studied, whereas bilateral pelvic decentralization selectively reduced the number of CGRP-IR nerves in all structures and locations. Outflow obstruction very overtly reduced the number of NOS-IR nerves in parallel with the general autonomic innervation. Thus, in the rat female urinary tract, NOS-containing nerves particularly occur in regions with sphincteric functions such as urethra and ureteric orifices. In these regions NO may exert a transmitter role, both directly or by interaction with other transmitters/modulators.

Adrenergic Fibers↗
PubMed1995

Intramural neurones appear in the urinary bladder wall following excision of the pelvic ganglion in the rat.

The entire bladder of female rats was stained for acetylcholinesterase activity, in order to make visible all the intramural nerves. Ganglion neurones were never observed within the bladder wall of adult controls. In contrast, 2, 13 or 27 weeks after unilateral pelvic ganglion destruction a few intramural neurones were consistently observed along the remnants of nerves in the originally denervated half of the bladder. These neurones were often gathered into clusters of 5-15, inside a nerve or closely connected to it, with a faintly stained nerve leading to them and a more heavily stained nerve leading from them. The origin of the new intramural ganglion neurones is unknown, but they probably migrate after ganglionectomy, possibly from some accessory ganglion close to the bladder.

Acetylcholinesterase↗
PubMed1995

Effects of purinoceptor agonists on smooth muscle from hypertrophied rat urinary bladder.

Tension responses induced by the purinoceptor agonists ATP and the stable ATP analogue alpha, beta-methylene ATP were investigated in isolated muscle strips from normal and hypertrophic urinary bladders from the rat. Hypertrophy was induced by a partial ligation of the urethra giving an increase in mean bladder weight from 65 mg to 300 mg. Activation with ATP and alpha, beta-methylene ATP caused phasic, concentration-dependent, contractions. The sensitivity to ATP was about 100-fold lower than that for alpha, beta-methylene ATP. The force of the contractions induced by the purinoceptor agonists was significantly lower in the hypertrophied bladder compared to the controls. The kinetics of the ATP-induced responses was studied by photolytic release of ATP from caged-ATP in intact fibre bundles. The rate of contraction following photolytic release of ATP was slower, and the force amplitude lower, in the hypertrophic preparations compared to the controls. The results suggest changes in the purinoceptor function or in the responses of the contractile system to transient increases in intracellular Ca2+ in the hypertrophic bladder.

Adenosine Triphosphate↗
PubMed1995

Lactate dehydrogenase activity and isoform distribution in the rat pelvic ganglion: effects of diabetes and bladder outlet obstruction.

We have previously shown that the intramural motor nerves in the rat bladder can function in anoxic conditions. The present study aims to explore the distribution and activity of lactate dehydrogenase (LDH), the key enzyme for ATP generation in anoxia. The activity and isoform distribution pattern of LDH was studied in pelvic ganglia from male and female rats. A histochemical investigation showed that the LDH activity was intense in the ganglion cells, and weak in the other tissue components (nerve bundles, connective tissue). The male pelvic ganglion weighted 55% more than the female pelvic ganglion, the enzyme activity per unit ganglion weight was 60% higher and the total LDH activity was 155% higher. The isoform distribution was similar, with M4 being dominant isoform, followed by M3H. Infravesical outlet obstruction in the female rat induced a threefold increase in ganglion weight, and the total LDH activity increased twofold. In this hypertrophic female ganglion a decreased relative amount of M4, and an increased amount of MH3, was found. Diabetes in the male rat had no effect on ganglion weight or its contents and isoform distribution of LDH.

Animals↗
PubMed1995

Development of smooth muscle hypertrophy is closely associated with increased gene expression of insulin-like growth factor binding protein-2 and -4.

The aim of the present investigation was to study the role of the IGF system in the development of smooth muscle hypertrophy. Hypertrophy was initiated by partial ligation of the urethra in female Sprague-Dawley rats. The solution hybridization assay was used to analyse the mRNA levels. Ligation of the urethra induced a sustained increase in bladder wet weight during the following 6-week period studied. IGF-I mRNA increased from 1 to 3 amol/micrograms DNA 1-day after ligation, peaked at 3-days (4-fold), and normalized 6-weeks after ligation. In hypertrophying bladder, IGFBP-2 and -4 mRNA increased sharply during the first 10 days (5-fold) and remained elevated during the 6-week period. The IGF-I receptor mRNA did not change significantly. Removal of the obstruction 10 days after ligation caused a regression of bladder wet weight, and resulted in normalization of IGF-I, IGFBP-2 and -4 mRNA. The results show a close correlation between progression or regression of smooth muscle hypertrophy and differential regulation of IGF-I, IGFBP-2 and -4 mRNA, indicating that the IGF system may play a role in smooth muscle hypertrophy.

Animals↗
PubMed1995

Nitric oxide synthase-containing neurons in rat parasympathetic, sympathetic and sensory ganglia: a comparative study.

In rats, the distribution of nerve structures staining for NADPH-diaphorase, and showing immunoreactivities for nitric oxide synthase (NOS), tyrosine hydroxylase and various neuropeptides was studied in sensory ganglia (dorsal root, nodose and trigeminal ganglia), in sympathetic ganglia (superior cervical, stellate, coeliac-superior and inferior mesenteric ganglia), parasympathetic ganglia (sphenopalatine, submandibular, sublingual and otic ganglia), and in the mixed parasympathetic/sympathetic ganglia (major pelvic ganglia). The coincidence of neuronal cell bodies with strong NOS-immunoreactivity and strong NADPH diaphorase reactivity was almost total. The relative proportions of NOS-immunoreactive nerve cell bodies were largest in parasympathetic ganglia and major pelvic ganglia followed by sensory ganglia. In sympathetic ganglia no NOS-immunoreactive neuronal cell bodies could be detected. In parasympathetic and major pelvic ganglia, there was a very significant neuronal co-localization of immunoreactivities for NOS and vasoactive intestinal polypeptide (VIP). This was almost total in major pelvic ganglia, in which NOS-/VIP-immunoreactive nerve cell bodies were separate from sympathetic (tyrosine hydroxylase-/neuropeptide Y-immunoreactive), suggesting that NOS-/VIP-immuno-reactive neurons might also be parasympathetic.

Animals↗
PubMed1995

Ureteric growth in a Goettingen minipig induced by epidermal growth factor. A case report.

We have recently discovered that prolonged systemic administration of epidermal growth factor (EGF) induces a remarkable growth of all wall layers of the urinary tract in minipigs. In the present paper, we report the most pronounced changes induced by 4 weeks of systemic EGF challenge in two pigs treated for four weeks with either solvent or EGF (30 micrograms/kg/day), respectively. The EGF treated ureter was longer and thicker with an approximately four fold increase in diameter. All wall layers were enlarged. The urothelium was increased from 5 to 10 cellular rows with basal hyperplasia and an increased number of goblet cells and cells with intracytoplasmic lumina in the luminal half. In the muscular coat, the bundles of hypertrophied cells and intervening connective tissue were enlarged. The present paper suggests a possible in vivo approach to increase the amount of tissue needed in reconstructive surgery of the urinary tract.

Animals↗
PubMed1994

Reversal of muscle hypertrophy in the rat urinary bladder after removal of urethral obstruction.

We studied the ultrastructure of the bladder musculature after first inducing hypertrophy by means of urethral obstruction and subsequently removing the obstruction. With hypertrophy the bladder musculature increases ten-fold or more in volume; after de-obstruction approximately 4/5 of the hypertrophic muscle weight and volume is lost within six weeks. In spite of this very large decrease in muscle mass there is no degeneration of muscle cells or nerve endings or of other cell types in the de-obstructed bladder either at 5 days or at 6 weeks. The individual muscle cells are smaller in size than in the hypertrophic bladder but still larger than control muscle cells. The decrease in muscle cell size is more substantial than the decrease in muscle cell surface. There are no lysosomes or other signs of intracellular degradation in any cells of the muscle layer. The musculature contains a very large amount of intercellular material, mainly collagen. This study documents the great plasticity of the musculature in the reduction of muscle mass after de-obstruction. However, some of the fine structural features are almost as different from the controls as in the hypertrophic muscle.

Animals↗
PubMed1994

Structure and mechanics of growing arterial microvessels from hypertrophied urinary bladder in the rat.

Rat bladder hypertrophy, induced by a partial ligation of the urethra, was used to study the accompanying changes of microvascular smooth muscle mechanics, pharmacology and morphology. A segment of a microarterial vessel to the bladder was taken from a defined anatomical location and studied in a wire myograph in vitro at the length for maximal isometric force development (Lmax). After 10 days of ligation, bladder hypertrophy resulted in a microvascular growth response compared to non-operated controls which was characterized by (i) an increase of the calculated diameter at Lmax from 134 +/- 5 microns to 222 +/- 19 microns; (ii) an increase of the media thickness from 22.4 +/- 1.9 microns to 32.2 +2- 3.0 microns; (iii) an increase of the active tension from 1.42 +/- 0.28 mN/mm to 3.06 +/- 0.33 mN/mm; (iv) no change of the wall/lumen ratio (from 0.83 +/- 0.10 to 0.79 +/- 0.15). Normalized length/force relations (active, passive and total) did not differ significantly between microarteries from control and hypertrophic bladders. Microvascular smooth muscle growth was also associated with a decreased sensitivity to K(+)-induced depolarization and an increased sensitivity to alpha 1-adrenergic stimulation. No differences were noted regarding the Ca2+ sensitivity of force during K(+)-induced depolarization. The results suggest that microvascular growth (1) is immediately and positively influenced by the organ growth; (2) results in a functional resetting of the microvascular segments towards larger diameters without gross morphological or mechanical alterations; and (3) is accompanied by pharmacological alterations of the smooth muscle reactivity.

Animals↗
PubMed1994

Increase in insulin-like growth factor I in hypertrophying smooth muscle.

The present study focuses on the role of the insulin-like growth factor (IGF) system in the development of smooth muscle hypertrophy. Hypertrophy was initiated by partial ligation of portal vein or urethra in female Sprague-Dawley rats weighing approximately 220 g. Levels of mRNA were analyzed by solution hybridization. Seven days after ligation, the wet weight of the portal vein was increased about threefold and the concentration of IGF-I mRNA was increased fourfold. The bladder wet weight was increased twofold 3 days after ligation and fourfold 10 days after ligation. IGF-I mRNA in the bladder was elevated 3-fold after 3 days and 2.5-fold after 10 days, whereas IGF binding protein 2 mRNA was increased approximately 2-fold after 3 days and 5-fold after 10 days. IGF-I receptor mRNA in the hypertrophying bladder remained unchanged. Increased levels of IGF-I were demonstrated with immunohistochemistry in both hypertrophying portal vein and urinary bladder. The results show a specific increase in IGF-I mRNA as well as an increased IGF-I immunoreactivity during hypertrophy of smooth muscle, which suggests that the local IGF-system may play a role in smooth muscle hypertrophy.

Animals↗
PubMed1993

A rat model for investigation of spinal mechanisms in detrusor instability associated with infravesical outflow obstruction.

A rat model of infravesical outflow obstruction was modified to allow cystometric investigation in conscious, free-moving animals after intrathecal drug administration. The catheter position and extent of drug distribution were controlled by injection of dye and dissection of the spinal canal. Continuous cystometries were performed in awake normal rats as well as rats with bladder hypertrophy and hyperactivity following infravesical outflow obstruction. In some animals of each group, cystometry was performed with simultaneous recording of intra-abdominal pressure. The possible effects of the presence of the intrathecal catheter were studied, as well as the effects of saline, local anesthetics, morphine and naloxone administered through the catheter. Neither the presence of the intrathecal catheter nor injection of saline affected the cystometric pattern. Bupivacaine (50 micrograms) produced paralysis of both lower extremities and a complete, though reversible, suppression of micturition in normal rats. In rats with hypertrophy, intrathecal bupivacaine in doses of 50 micrograms and 100 micrograms produced decreases in micturition pressure, increases in bladder capacity and dribbling incontinence. However, the amplitude of spontaneous contractile activity increased after the administration. The inhibitory effects of morphine (0.5-10 micrograms) on micturition in normal rats, which were rapidly reversed by naloxone, were in accordance with results obtained in previous studies in anesthetized animals. Rats with bladder hypertrophy showed a similar response to morphine and naloxone. However, the bladder hyperactivity was not inhibited by morphine. We conclude that the present model seems reliable for the study of spinal mechanisms in the development of detrusor instability associated with infravesical outflow obstruction.

Animals↗
PubMed1993

Effect of decentralization or contralateral ganglionectomy on obstruction-induced hypertrophy of rat urinary bladder muscle and pelvic ganglion.

After urethral obstruction the musculature of the rat urinary bladder undergoes extensive hypertrophy, irrespective of whether its innervation is intact or whether one of the two pelvic ganglia has been decentralized or excised. Even the excision of both ganglia does not inhibit muscle hypertrophy. The presence of nerves is not a prerequisite for the muscle growth to occur. The stimulus for growth resides in the bladder itself, and the present and previous observations are in agreement with the notion that the distension of the muscle is a primary stimulus for muscle growth. With bladder hypertrophy, the pelvic ganglion neurons undergo hypertrophy, even when they are devoid of their preganglionic input. Synaptic connection with the preganglionic fibres and stimuli from the spinal cord are not prerequisites for neuronal hypertrophy. However, the hypertrophy is less marked in the decentralized ganglion neurons than in the neurons of the contralateral intact ganglion. With bladder hypertrophy and contralateral ganglionectomy, the neuronal hypertrophy is greater than with either procedure alone, suggesting that the two forms of neuronal growth stimulation can be added to each other.

Animals↗
PubMed1993

Lactate dehydrogenase activity and isoform distribution in the rat urinary bladder: effects of outlet obstruction and its removal.

The rat urinary bladder responded to infravesical obstruction by an increased weight. The weight began to increase after 3 days of obstruction. After 10 days the weight gain had become significant, but increased further with time. At 90 days the bladders weighed 12 times the initial weight. Lactate dehydrogenase (LDH) activity per unit bladder weight increased with the duration of the obstruction. The increase was significant in the 90 day group. The isoform pattern of LDH was determined. For the control group the M3H form was dominant, with M4 second; M4 became the dominant isoform after 3 days of obstruction. The relative amount of M4 had increased by 80% after 90 days. In one group, which was first obstructed for 10 days and then had the obstruction removed for 4 weeks, bladder weight and LDH isoform pattern were normal. We suggest that the changes in isoform pattern in the obstructed bladder reflect a metabolic adaptation to the prolonged voiding time and the increased detrusor pressure, with a consequently compromised oxygen supply, and that the changes are reversible if the outlet conditions are normalized.

Animals↗