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Robert M. Levin - One of the best experts on this subject based on the ideXlab platform.

  • Bladder outlet obstruction accelerates Bladder carcinogenesis
    BJUI, 2008
    Co-Authors: Seiji Matsumoto, Nobutaka Shimizu, Tadashi Hanai, Hirotsugu Uemura, Robert M. Levin
    Abstract:

    OBJECTIVE To examine the correlation between partial Bladder outlet obstruction (PBOO) and Bladder carcinogenesis. MATERIALS AND METHODS Female Wistar rats (6 weeks old) were divided into three groups of 10 each: group 1 was exposed to n-butyl-n-butanol nitrosamine (BBN, a carcinogen) in drinking water for 8 weeks; group 2 had PBOO induced surgically after exposure to BBN for 8 weeks; group 3 had a sham operation and the rats drank normal water (control group). After 20 weeks, all of the rats were killed humanely and their Bladders analysed. RESULTS There were no significant differences in body weight among the groups. The Bladder weight of group 2 was significantly greater than either group 1 or group 3. Histopathologically, Bladder smooth muscle hypertrophy was the major cause of the increased Bladder weight for group 2. In group 2 there were increases in Bladder wall thickness and many nipple-shaped urothelial tumours. Basic fibroblast growth factor and hypoxia-inducible factor-1α expression were significantly greater in group 2 than in groups 1 and 3. CONCLUSIONS Exposure of the Bladder to carcinogens during Bladder hyperplasia and hypertrophy induced by PBOO results in a greater incidence of superficial Bladder carcinoma.

  • Metabolic basis for contractile dysfunction following chronic partial Bladder outlet obstruction in rabbits
    Molecular and Cellular Biochemistry, 1999
    Co-Authors: Denise A. Nigro, Alan J. Wein, Niels Haugaard, Robert M. Levin
    Abstract:

    Prior studies have shown that partial outlet obstruction of the rabbit Bladder causes a progressive increase in Bladder mass, a progressive decrease in the contractile response to different forms of stimulation, and a selective decrease in the activity of mitochondrial enzymes. In this investigation the contractile responses to field stimulation and bethanechol were directly correlated with the activity of citrate synthase as a function of both the duration of obstruction and the Bladder mass. Partial Bladder outlet obstruction was surgically induced in twenty New Zealand White rabbits. The Bladders were then rapidly excised at 30, 40, 90, 105 or 150 days post obstruction. The contractile responses to field stimulation (32 Hz) and bethanechol (250 μM) were determined. The remainder of the Bladders were frozen and used for citrate synthase activity determinations. The data were grouped for analysis both by the duration of obstruction and by the Bladder mass. Chronic partial outlet obstruction caused a parallel decline in the activity of citrate synthase and in the response of the obstructed tissue to stimulation.

  • mitochondrial and mitochondia related nuclear genetic function in rabbit urinary Bladder following reversal of outlet obstruction
    Molecular and Cellular Biochemistry, 1999
    Co-Authors: Christina A Nevelmcgarvey, Robert M. Levin, Dorothea Rohrmann, Alan P Hudson
    Abstract:

    Partial outlet obstruction of the rabbit urinary Bladder causes increased tissue hypertrophy and decreased contractility of that organ; we showed that, in an experimental rabbit model, both correlate closely with alterations in the status and expression of mitochondrial (mt), and mt-related nuclear, genetic parameters in Bladder smooth muscle. Here we investigate the rate and overall level of recovery of mt and nuclear genetic function following reversal of outlet obstruction in the same animal model. Release from outlet obstruction at 28 days resulted in improvement in both level of hypertrophy and contractile function in all Bladders studied. However, Bladders fell into two groups based on whether relative copy mt genome number per cell was above or below that of unobstructed controls. Bladders with high mt DNA content adjusted organellar genome copy number toward normal post-reversal but did not properly adjust mt transcript levels; mt-related nuclear transcripts in these samples showed recovery. Bladders with low mt DNA content showed no adjustment of those levels toward normal post-reversal but did show some adjustment in other mt and nuclear genetic parameters. Thus, a limiting factor for return of normal Bladder function following reversal of outlet obstruction may be recovery of normal mt genetic performance.

  • Modulation of Urinary Bladder Function by Sex Hormones in Streptozotocin-Diabetic Rats
    The Journal of Urology, 1994
    Co-Authors: Berit Eika, Robert M. Levin, Penelope A. Longhurst
    Abstract:

    AbstractThe modulation of urinary Bladder function by sex hormones was examined in castrated and sham-operated male and female streptozotocin-diabetic rats. Male and female diabetic rats weighed less than age-matched controls and had significantly greater serum glucose levels and Bladder weights. Castration had no effect on Bladder mass and did not alter the diabetes-induced changes in rat or Bladder mass. Protein concentrations were significantly increased and collagen concentrations were significantly decreased in Bladders from diabetic rats compared with nondiabetics. Sex or castration had no effects on protein or collagen concentration of Bladders from nondiabetic and diabetic rats. There were no differences in water consumption and urine excretion between male and female nondiabetic rats, and no effects of castration were observed on micturition in nondiabetic rats. Ovariectomy followed by diabetes caused a significant increase in urine excretion compared with diabetes alone. Ovariectomized diabetic ...

  • Modulation of urinary Bladder function by sex hormones in streptozotocin-diabetic rats.
    The Journal of urology, 1994
    Co-Authors: Berit Eika, Robert M. Levin, Penelope A. Longhurst
    Abstract:

    The modulation of urinary Bladder function by sex hormones was examined in castrated and sham-operated male and female streptozotocin-diabetic rats. Male and female diabetic rats weighed less than age-matched controls and had significantly greater serum glucose levels and Bladder weights. Castration had no effect on Bladder mass and did not alter the diabetes-induced changes in rat or Bladder mass. Protein concentrations were significantly increased and collagen concentrations were significantly decreased in Bladders from diabetic rats compared with non-diabetics. Sex or castration had no effects on protein or collagen concentration of Bladders from nondiabetic and diabetic rats. There were no differences in water consumption and urine excretion between male and female nondiabetic rats, and no effects of castration were observed on micturition in nondiabetic rats. Ovariectomy followed by diabetes caused a significant increase in urine excretion compared with diabetes alone. Ovariectomized diabetic rats had increased mean and maximal micturition volumes when compared with other female rats. Orchiectomy had no effects on the expected increases in micturition associated with diabetes. Diabetes in male rats caused significant increases in contractile responses of Bladder strips to field stimulation, carbachol, KCl and high concentrations of ATP. In both nondiabetic and diabetic groups, orchiectomy had no effects on the contractile responses compared with sham operation. Similarly, in Bladder strips from diabetic females, contractile responses to carbachol, KCl and high concentrations of ATP were significantly increased compared with those of nondiabetics, and were unchanged by ovariectomy. However, ovariectomy in nondiabetic rats caused significant decreases in contractile responsiveness to nerve stimulation, effects which were only partially prevented by diabetes. The data suggest that there are few differences between male and female rats in their sensitivity to streptozotocin and the effects of diabetes on micturition, Bladder collagen and protein concentration, and the responsiveness of Bladder strips to contractile agents. The changes in Bladder function observed after induction of diabetes do not appear to be related to changes in sex hormone levels. The major differences noted between males and females were the decreased responsiveness of Bladders from nondiabetic ovariectomized female rats to field stimulation. In conjunction with previous data obtained in this laboratory, the study suggests that the responses to field stimulation are more sensitive to the effects of ovariectomy than are the responses to contractile agonists.

Penelope A. Longhurst - One of the best experts on this subject based on the ideXlab platform.

  • Modulation of Urinary Bladder Function by Sex Hormones in Streptozotocin-Diabetic Rats
    The Journal of Urology, 1994
    Co-Authors: Berit Eika, Robert M. Levin, Penelope A. Longhurst
    Abstract:

    AbstractThe modulation of urinary Bladder function by sex hormones was examined in castrated and sham-operated male and female streptozotocin-diabetic rats. Male and female diabetic rats weighed less than age-matched controls and had significantly greater serum glucose levels and Bladder weights. Castration had no effect on Bladder mass and did not alter the diabetes-induced changes in rat or Bladder mass. Protein concentrations were significantly increased and collagen concentrations were significantly decreased in Bladders from diabetic rats compared with nondiabetics. Sex or castration had no effects on protein or collagen concentration of Bladders from nondiabetic and diabetic rats. There were no differences in water consumption and urine excretion between male and female nondiabetic rats, and no effects of castration were observed on micturition in nondiabetic rats. Ovariectomy followed by diabetes caused a significant increase in urine excretion compared with diabetes alone. Ovariectomized diabetic ...

  • Modulation of urinary Bladder function by sex hormones in streptozotocin-diabetic rats.
    The Journal of urology, 1994
    Co-Authors: Berit Eika, Robert M. Levin, Penelope A. Longhurst
    Abstract:

    The modulation of urinary Bladder function by sex hormones was examined in castrated and sham-operated male and female streptozotocin-diabetic rats. Male and female diabetic rats weighed less than age-matched controls and had significantly greater serum glucose levels and Bladder weights. Castration had no effect on Bladder mass and did not alter the diabetes-induced changes in rat or Bladder mass. Protein concentrations were significantly increased and collagen concentrations were significantly decreased in Bladders from diabetic rats compared with non-diabetics. Sex or castration had no effects on protein or collagen concentration of Bladders from nondiabetic and diabetic rats. There were no differences in water consumption and urine excretion between male and female nondiabetic rats, and no effects of castration were observed on micturition in nondiabetic rats. Ovariectomy followed by diabetes caused a significant increase in urine excretion compared with diabetes alone. Ovariectomized diabetic rats had increased mean and maximal micturition volumes when compared with other female rats. Orchiectomy had no effects on the expected increases in micturition associated with diabetes. Diabetes in male rats caused significant increases in contractile responses of Bladder strips to field stimulation, carbachol, KCl and high concentrations of ATP. In both nondiabetic and diabetic groups, orchiectomy had no effects on the contractile responses compared with sham operation. Similarly, in Bladder strips from diabetic females, contractile responses to carbachol, KCl and high concentrations of ATP were significantly increased compared with those of nondiabetics, and were unchanged by ovariectomy. However, ovariectomy in nondiabetic rats caused significant decreases in contractile responsiveness to nerve stimulation, effects which were only partially prevented by diabetes. The data suggest that there are few differences between male and female rats in their sensitivity to streptozotocin and the effects of diabetes on micturition, Bladder collagen and protein concentration, and the responsiveness of Bladder strips to contractile agents. The changes in Bladder function observed after induction of diabetes do not appear to be related to changes in sex hormone levels. The major differences noted between males and females were the decreased responsiveness of Bladders from nondiabetic ovariectomized female rats to field stimulation. In conjunction with previous data obtained in this laboratory, the study suggests that the responses to field stimulation are more sensitive to the effects of ovariectomy than are the responses to contractile agonists.

  • comparison of urinary Bladder function in rats with hereditary diabetes insipidus streptozotocin induced diabetes mellitus and nondiabetic osmotic diuresis
    The Journal of Urology, 1994
    Co-Authors: Penelope A. Longhurst, Berit Eika, Robert M. Levin
    Abstract:

    Abstract In vivo and in vitro Bladder function were studied in three different models of increased diuresis: 1) Brattleboro rats with hereditary diabetes insipidus (di/di), 2) Sprague-Dawley rats with streptozotocin-induced diabetes mellitus (STZ), and 3) Sprague-Dawley rats with increased diuresis due to 5% sucrose added to the drinking water. When compared with controls, all three models showed Bladder mass, increased water consumption and urine output, higher mean and maximal increased micturition volumes, and greater Bladder capacity and compliance by in vitro cystometry. The changes were more extensive in di/di rats than in STZ and sucrose-drinking rats. The concentration of Bladder collagen decreased in all three rat models when compared with controls. However, the collagen concentration of STZ Bladders was significantly lower than the collagen concentration of di/di and sucrose Bladders, suggesting that the decrease in Bladder collagen concentration associated with experimental diabetes mellitus is only partly related to the increased diuresis. Contractile function was studied using a whole Bladder model. Responses of whole Bladders from control and diabetic rats to electrical field stimulation, carbachol and KCl were identical. Volume-pressure relations of the isolated whole Bladder showed that the magnitude of the contractile response to KCl is constant at intravesical volumes ranging from about 10 to 95% of cystometrical Bladder capacity. Bladders from Brattleboro di/di rats and STZ rats showed a rightward shift of volume-passive pressure curves when compared with appropriate controls. Bladders from sucrose-drinking rats had volume-passive pressure curves similar to the Bladders from controls. This study suggests that while contractile function remains intact with increased diuresis, the passive function changes, with the Bladder becoming more distensible.

  • comparison of urinary Bladder function in 6 and 24 month male and female rats
    The Journal of Urology, 1992
    Co-Authors: Penelope A. Longhurst, Berit Eika, Robert E. Leggett, Robert M. Levin
    Abstract:

    Abstract Micturition characteristics, collagen composition, and in vitro urinary Bladder strip contractility were examined in young adult (six month) and old (24 month) male and female Fischer 344 rats. Although young female rats consumed significantly less water than young males, there were no differences in volumes of urine excreted. Old females excreted significantly more urine than old males, but there were no differences in volumes of water consumed. Old male rats had similar micturition frequencies during the light and dark cycles, in contrast to females and young males, where the number of micturitions during the dark cycle was significantly greater than those during the light cycle. The mean and maximal micturition volumes were significantly greater in old males compared to young males and old females during both the light and dark cycles. Bladders from female rats weighed significantly less than Bladders from males of the same age, and the Bladders from young rats weighed less than those of old rats. The protein and collagen concentrations were significantly less in Bladder bodies from young females than old females. The amount of collagen resistant to digestion by Pronase, and thus thought to be cross-linked, was significantly greater in Bladders from old rats compared to young. No differences between groups were found in the contractile responses of Bladder base strips. There were trends for the absolute contractile responses of Bladder body strips from old males to field stimulation, carbachol, ATP, and KCl to be larger than the other groups, and for strips from the young females to be smaller. The responses of strips from young females to field stimulation and KCl were significantly less than those of young males or old females, and responses to 10~3 M ATP were less than those of old females. Responses of strips from old males to 60 mM KC1 were significantly greater than those of young males. The differences in contractility could be attributed to the differences in strip mass. It appears, therefore, that urinary Bladder function in male and female rats is unaffected by increasing age between 6 and 24 months.

  • Urinary Bladder function in the tight-skin mouse.
    The Journal of Urology, 1992
    Co-Authors: Penelope A. Longhurst, Berit Eika, Robert E. Leggett, Robert M. Levin
    Abstract:

    Abstract Tight-skin mice develop hypertrophy of connective tissue and tendons, associated with increases in collagen concentration in skin, heart, lungs, and tail. The Bladders from these mice have not previously been examined. Because of the purported importance of collagen in Bladder wall structure and compliance, we examined collagen content, micturition characteristics, and length-tension relationships in Bladders from tight-skin mice. Bladder collagen content and concentration were approximately 70% greater in 5-6 month tight-skin mice than age-matched controls, but Bladder mass, protein content, and protein concentration were similar. Tight-skin mice urinated larger volumes more frequently during the light cycle, and the functional Bladder capacity appeared to be greater than that of controls. There was a small shift to the right of the passive length-tension curves of Bladder strips from tight-skin mice, but the shift was not statistically significant. The magnitude of active tension development was the same. The data suggest that Bladder collagen concentration does not necessarily determine Bladder capacity or compliance. It is suggested that other factors, such as the ratio of collagen subtypes or the collagemelastin ratio may have more importance for the maintenance of Bladder distension.

Berit Eika - One of the best experts on this subject based on the ideXlab platform.

  • Modulation of Urinary Bladder Function by Sex Hormones in Streptozotocin-Diabetic Rats
    The Journal of Urology, 1994
    Co-Authors: Berit Eika, Robert M. Levin, Penelope A. Longhurst
    Abstract:

    AbstractThe modulation of urinary Bladder function by sex hormones was examined in castrated and sham-operated male and female streptozotocin-diabetic rats. Male and female diabetic rats weighed less than age-matched controls and had significantly greater serum glucose levels and Bladder weights. Castration had no effect on Bladder mass and did not alter the diabetes-induced changes in rat or Bladder mass. Protein concentrations were significantly increased and collagen concentrations were significantly decreased in Bladders from diabetic rats compared with nondiabetics. Sex or castration had no effects on protein or collagen concentration of Bladders from nondiabetic and diabetic rats. There were no differences in water consumption and urine excretion between male and female nondiabetic rats, and no effects of castration were observed on micturition in nondiabetic rats. Ovariectomy followed by diabetes caused a significant increase in urine excretion compared with diabetes alone. Ovariectomized diabetic ...

  • Modulation of urinary Bladder function by sex hormones in streptozotocin-diabetic rats.
    The Journal of urology, 1994
    Co-Authors: Berit Eika, Robert M. Levin, Penelope A. Longhurst
    Abstract:

    The modulation of urinary Bladder function by sex hormones was examined in castrated and sham-operated male and female streptozotocin-diabetic rats. Male and female diabetic rats weighed less than age-matched controls and had significantly greater serum glucose levels and Bladder weights. Castration had no effect on Bladder mass and did not alter the diabetes-induced changes in rat or Bladder mass. Protein concentrations were significantly increased and collagen concentrations were significantly decreased in Bladders from diabetic rats compared with non-diabetics. Sex or castration had no effects on protein or collagen concentration of Bladders from nondiabetic and diabetic rats. There were no differences in water consumption and urine excretion between male and female nondiabetic rats, and no effects of castration were observed on micturition in nondiabetic rats. Ovariectomy followed by diabetes caused a significant increase in urine excretion compared with diabetes alone. Ovariectomized diabetic rats had increased mean and maximal micturition volumes when compared with other female rats. Orchiectomy had no effects on the expected increases in micturition associated with diabetes. Diabetes in male rats caused significant increases in contractile responses of Bladder strips to field stimulation, carbachol, KCl and high concentrations of ATP. In both nondiabetic and diabetic groups, orchiectomy had no effects on the contractile responses compared with sham operation. Similarly, in Bladder strips from diabetic females, contractile responses to carbachol, KCl and high concentrations of ATP were significantly increased compared with those of nondiabetics, and were unchanged by ovariectomy. However, ovariectomy in nondiabetic rats caused significant decreases in contractile responsiveness to nerve stimulation, effects which were only partially prevented by diabetes. The data suggest that there are few differences between male and female rats in their sensitivity to streptozotocin and the effects of diabetes on micturition, Bladder collagen and protein concentration, and the responsiveness of Bladder strips to contractile agents. The changes in Bladder function observed after induction of diabetes do not appear to be related to changes in sex hormone levels. The major differences noted between males and females were the decreased responsiveness of Bladders from nondiabetic ovariectomized female rats to field stimulation. In conjunction with previous data obtained in this laboratory, the study suggests that the responses to field stimulation are more sensitive to the effects of ovariectomy than are the responses to contractile agonists.

  • comparison of urinary Bladder function in rats with hereditary diabetes insipidus streptozotocin induced diabetes mellitus and nondiabetic osmotic diuresis
    The Journal of Urology, 1994
    Co-Authors: Penelope A. Longhurst, Berit Eika, Robert M. Levin
    Abstract:

    Abstract In vivo and in vitro Bladder function were studied in three different models of increased diuresis: 1) Brattleboro rats with hereditary diabetes insipidus (di/di), 2) Sprague-Dawley rats with streptozotocin-induced diabetes mellitus (STZ), and 3) Sprague-Dawley rats with increased diuresis due to 5% sucrose added to the drinking water. When compared with controls, all three models showed Bladder mass, increased water consumption and urine output, higher mean and maximal increased micturition volumes, and greater Bladder capacity and compliance by in vitro cystometry. The changes were more extensive in di/di rats than in STZ and sucrose-drinking rats. The concentration of Bladder collagen decreased in all three rat models when compared with controls. However, the collagen concentration of STZ Bladders was significantly lower than the collagen concentration of di/di and sucrose Bladders, suggesting that the decrease in Bladder collagen concentration associated with experimental diabetes mellitus is only partly related to the increased diuresis. Contractile function was studied using a whole Bladder model. Responses of whole Bladders from control and diabetic rats to electrical field stimulation, carbachol and KCl were identical. Volume-pressure relations of the isolated whole Bladder showed that the magnitude of the contractile response to KCl is constant at intravesical volumes ranging from about 10 to 95% of cystometrical Bladder capacity. Bladders from Brattleboro di/di rats and STZ rats showed a rightward shift of volume-passive pressure curves when compared with appropriate controls. Bladders from sucrose-drinking rats had volume-passive pressure curves similar to the Bladders from controls. This study suggests that while contractile function remains intact with increased diuresis, the passive function changes, with the Bladder becoming more distensible.

  • comparison of urinary Bladder function in 6 and 24 month male and female rats
    The Journal of Urology, 1992
    Co-Authors: Penelope A. Longhurst, Berit Eika, Robert E. Leggett, Robert M. Levin
    Abstract:

    Abstract Micturition characteristics, collagen composition, and in vitro urinary Bladder strip contractility were examined in young adult (six month) and old (24 month) male and female Fischer 344 rats. Although young female rats consumed significantly less water than young males, there were no differences in volumes of urine excreted. Old females excreted significantly more urine than old males, but there were no differences in volumes of water consumed. Old male rats had similar micturition frequencies during the light and dark cycles, in contrast to females and young males, where the number of micturitions during the dark cycle was significantly greater than those during the light cycle. The mean and maximal micturition volumes were significantly greater in old males compared to young males and old females during both the light and dark cycles. Bladders from female rats weighed significantly less than Bladders from males of the same age, and the Bladders from young rats weighed less than those of old rats. The protein and collagen concentrations were significantly less in Bladder bodies from young females than old females. The amount of collagen resistant to digestion by Pronase, and thus thought to be cross-linked, was significantly greater in Bladders from old rats compared to young. No differences between groups were found in the contractile responses of Bladder base strips. There were trends for the absolute contractile responses of Bladder body strips from old males to field stimulation, carbachol, ATP, and KCl to be larger than the other groups, and for strips from the young females to be smaller. The responses of strips from young females to field stimulation and KCl were significantly less than those of young males or old females, and responses to 10~3 M ATP were less than those of old females. Responses of strips from old males to 60 mM KC1 were significantly greater than those of young males. The differences in contractility could be attributed to the differences in strip mass. It appears, therefore, that urinary Bladder function in male and female rats is unaffected by increasing age between 6 and 24 months.

  • Urinary Bladder function in the tight-skin mouse.
    The Journal of Urology, 1992
    Co-Authors: Penelope A. Longhurst, Berit Eika, Robert E. Leggett, Robert M. Levin
    Abstract:

    Abstract Tight-skin mice develop hypertrophy of connective tissue and tendons, associated with increases in collagen concentration in skin, heart, lungs, and tail. The Bladders from these mice have not previously been examined. Because of the purported importance of collagen in Bladder wall structure and compliance, we examined collagen content, micturition characteristics, and length-tension relationships in Bladders from tight-skin mice. Bladder collagen content and concentration were approximately 70% greater in 5-6 month tight-skin mice than age-matched controls, but Bladder mass, protein content, and protein concentration were similar. Tight-skin mice urinated larger volumes more frequently during the light cycle, and the functional Bladder capacity appeared to be greater than that of controls. There was a small shift to the right of the passive length-tension curves of Bladder strips from tight-skin mice, but the shift was not statistically significant. The magnitude of active tension development was the same. The data suggest that Bladder collagen concentration does not necessarily determine Bladder capacity or compliance. It is suggested that other factors, such as the ratio of collagen subtypes or the collagemelastin ratio may have more importance for the maintenance of Bladder distension.

Antoine E Khoury - One of the best experts on this subject based on the ideXlab platform.

  • acellular Bladder matrix allografts in the regeneration of functional Bladders evaluation of large segment 24 cm2 substitution in a porcine model
    BJUI, 2000
    Co-Authors: Paul A Merguerian, Gordon A Mclorie, Pramod P Reddy, D J Barrieras, Gregory J Wilson, K Woodhouse, Darius J Bagli, Antoine E Khoury
    Abstract:

    Objectives To evaluate the use of a large-segment (> 24 cm2) Bladder substitution with porcine Bladder acellular matrix allograft (BAMA) in a large animal model. Materials and methods Bladders were harvested from pigs at the time of necropsy and subjected to detergent and enzymatic extractions to render them acellular. The BAMA produced had the surgical handling and suture-retaining properties of normal Bladder tissue. Six pigs had BAMA segments implanted under general anaesthesia, through a low midline abdominal incision and after partial cystectomy. The defect was repaired with a BAMA patch (mean size 43.88 cm2, range 12–72), with no urinary diversion. Two animals each were then killed at 9, 16 and 30 days and the Bladders explanted. The native Bladder and BAMA patch were analysed morphometrically to evaluate cellular re-population and matrix re-organization. Results All animals survived surgery; there were no urinary leaks and no stones detected in any of the Bladders. At 9 days there was a diffuse infiltration with acute inflammatory cells, but no areas of necrosis. There were isolated areas of smooth muscle cell (SMC) infiltration of the BAMA. At 16 days the luminal surface was lined with a single layer of urothelium, there was stromal infiltration with disorganized SMC and angiogenesis, with mature vessels in the BAMA patch. At 30 days the urothelium was multilayered with organizing groups of SMCs and angiogenesis. The highest cell density was at the periphery of the repopulated BAMA patch, decreasing towards the centre. Conclusions The implantation of large patches of BAMA is technically feasible and may prove to be a viable surgical alternative to Bladder augmentation with intestinal segments. The advantages of BAMA include the potential for complete and functional regeneration of a Bladder substitute. This model provides a tool with which to obtain a better understanding of the cellular and molecular aspects of matrix re-population.

  • the sensitivity of pressure specific Bladder volume versus total Bladder capacity as a measure of Bladder storage dysfunction
    The Journal of Urology, 1994
    Co-Authors: Ezekiel H Landau, Bernard M Churchill, Venkata R Jayanthi, Robert F Gilmour, Robert E Steckler, Gordon A Mclorie, Antoine E Khoury
    Abstract:

    Abstract Assessment of Bladder storage function requires an accurate measure of Bladder capacity and pressure. Pressure specific Bladder volume is the volume that a Bladder can accommodate at a specified pressure. A total of 21 consecutive children with neurogenic Bladders who were candidates for Bladder augmentation based on standard clinical criteria (upper urinary tract deterioration, incontinence and infection) was studied to determine the efficacy of pressure specific Bladder volume as a measure of Bladder dysfunction. Urodynamic indexes were compared to previously established nomograms. All 21 patients had Bladder volumes at pressures of 30 cm. water or less, which decreased below the 5th percentile as determined by the nomogram. In 7 patients (33%) normal total Bladder capacity was achieved at the expense of elevated storage pressures. Pressure specific Bladder volume provides a better measure of Bladder storage function than total Bladder capacity because it relates volume to intravesical pressure, does not rely on a subjective end point to Bladder filling, and is objective and reproducible.

  • The sensitivity of pressure specific Bladder volume versus total Bladder capacity as a measure of Bladder storage dysfunction.
    The Journal of urology, 1994
    Co-Authors: Ezekiel H Landau, Bernard M Churchill, Venkata R Jayanthi, Robert F Gilmour, Robert E Steckler, Gordon A Mclorie, Antoine E Khoury
    Abstract:

    Assessment of Bladder storage function requires an accurate measure of Bladder capacity and pressure. Pressure specific Bladder volume is the volume that a Bladder can accommodate at a specific pressure. A total of 21 consecutive children with neurogenic Bladders who were candidates for Bladder augmentation based on standard clinical criteria (upper urinary tract deterioration, incontinence and infection) was studied to determine the efficacy of pressure specific Bladder volume as a measure of Bladder dysfunction. Urodynamic indexes were compared to previously established nomograms. All 21 patients had Bladder volumes at pressures of 30 cm. water or less, which decreased below the 5th percentile as determined by the nomogram. In 7 patients (33%) normal total Bladder capacity was achieved at the expense of elevated storage pressures. Pressure specific Bladder volume provides a better measure of Bladder storage function than total Bladder capacity because it relates volume to intravesical pressure, does not rely on a subjective end point to Bladder filling, and is objective and reproducible.

Alan J. Wein - One of the best experts on this subject based on the ideXlab platform.

  • smooth muscle hypertrophy following partial Bladder outlet obstruction is associated with overexpression of non muscle caldesmon
    American Journal of Pathology, 2004
    Co-Authors: Erik Zhang, Alan J. Wein, Raimund Stein, Shaohua Chang, Yongmu Zheng, Stephen A Zderic, Samuel Chacko
    Abstract:

    Partial Bladder outlet obstruction (PBOO) induces remodeling of urinary Bladder smooth muscle (detrusor). We demonstrate an increase in Bladder wall mass, muscle bundle size, and a threefold increase in the cross-sectional area of detrusor myocytes following PBOO in male New Zealand White rabbits compared to that of controls. Some Bladders with detrusor hypertrophy function close to normal (compensated), whereas others were dysfunctional (decompensated), showing high intravesical pressure, large residual urine volume, and voiding difficulty. We analyzed the expression of smooth muscle-specific caldesmon (h-CaD) and non-muscle (l-CaD) by Western blotting, RT-PCR, and real-time PCR. The expression of l-CaD is increased significantly at the mRNA and protein levels in the decompensated Bladders compared to that of normal and compensated Bladders. The CaD was also co-localized with myosin containing cytoplasmic fibrils in cells dissociated from obstructed Bladders and cultured overnight. Our data show that the inability of decompensated Bladders to empty, despite detrusor hypertrophy, is associated with an overexpression of l-CaD. The level of l-CaD overexpression might be a useful marker to estimate the degree of detrusor remodeling and contractile dysfunction in PBOO.

  • Metabolic basis for contractile dysfunction following chronic partial Bladder outlet obstruction in rabbits
    Molecular and Cellular Biochemistry, 1999
    Co-Authors: Denise A. Nigro, Alan J. Wein, Niels Haugaard, Robert M. Levin
    Abstract:

    Prior studies have shown that partial outlet obstruction of the rabbit Bladder causes a progressive increase in Bladder mass, a progressive decrease in the contractile response to different forms of stimulation, and a selective decrease in the activity of mitochondrial enzymes. In this investigation the contractile responses to field stimulation and bethanechol were directly correlated with the activity of citrate synthase as a function of both the duration of obstruction and the Bladder mass. Partial Bladder outlet obstruction was surgically induced in twenty New Zealand White rabbits. The Bladders were then rapidly excised at 30, 40, 90, 105 or 150 days post obstruction. The contractile responses to field stimulation (32 Hz) and bethanechol (250 μM) were determined. The remainder of the Bladders were frozen and used for citrate synthase activity determinations. The data were grouped for analysis both by the duration of obstruction and by the Bladder mass. Chronic partial outlet obstruction caused a parallel decline in the activity of citrate synthase and in the response of the obstructed tissue to stimulation.

  • effects of pregnancy on adrenergic function in the rabbit urinary Bladder
    Neurourology and Urodynamics, 1992
    Co-Authors: Yatching Tong, Alan J. Wein, Robert M. Levin
    Abstract:

    Pregnancy induces morphological as well as functional changes in the urinary tract. Urinary frequency, incontinence, and an increase in residual urine are common clinical findings during gestation. Previous studies from this laboratory have shown a decreased cholinergic response and cholinergic receptor density in the urinary Bladders of pregnant rabbits. In the present study, the adrenergic functions of the Bladders of pregnant and virgin New Zealand White rabbits were compared using isolated muscle strips. Dose-response curves showed that the contractile responses to epinephrine (alpha and beta agonist) and methoxamine (alpha agonist) were significantly reduced in tissues from the base and the mid-segment, but not the body of the pregnant rabbit Bladders. No significant difference was observed in the degree of isoproterenol (beta agonist) induced relaxations between the two groups. Thus, the results demonstrated a decreased alpha responsiveness in the midsegment and base of the pregnant Bladders. Physiologically, a decrease in alpha tone at the Bladder base would be advantageous for Bladder emptying as the resultant relaxation at the Bladder outlet theoretically would alleviate the effect of decreased Bladder body contractility as well as any mechanical stress imposed on the urethra by the enlarging uterus.

  • effects of sensitization on female guinea pig urinary Bladder function in vivo and in vitro studies
    The Journal of Urology, 1991
    Co-Authors: Penelope A. Longhurst, Robert M. Levin, Alan J. Wein
    Abstract:

    Abstract Although Bladder inflammation is known clinically to produce a variety of symptoms including urgency, frequency, and pain, there are only a few experimental studies that directly relate Bladder inflammation with urodynamic and functional alterations. We have used the sensitized guinea pig model to study the effects of inflammation on micturition parameters, cystometry, and in vitro Bladder contractility. This model depends on the allergic response of the Bladder mucosa to ovalbumin, an otherwise non-irritative agent, as an antigen. In vivo exposure of the Bladder to ovalbumin via urethral catheterization induced a prompt and marked increase in the number of micturitions in antigen-sensitized guinea pigs. Ovalbumin had no effects on the micturition parameters in the control group. Using in vivo cystometry, intravesical exposure to ovalbumin induced a significant decrease in both the pressure at which micturition was induced, and the volume at which micturition was induced. Ovalbumin had no effect on cystometric parameters of the control animals. In vitro exposure of whole-Bladder preparations to ovalbumin induced a significant contractile response only in the Bladders isolated from the sensitized guinea pigs. The responses of the isolated Bladders to field stimulation and bethanechol were identical for Bladders from both sensitized and control animals. In conclusion, exposure of the Bladder to ovalbumin in the sensitized animal induced an increase in the frequency of micturitions and a decrease in the pressure and volume at which micturition was induced. Thus, intravesical exposure of the Bladder mucosa to a substance that the Bladder has been sensitized to can induce alterations in micturition that are consistent with the clinical symptoms of “urgency and frequency”.

  • comparison of urinary Bladder function in sexually mature and immature male and female rats
    The Journal of Urology, 1990
    Co-Authors: Alexa L. Chun, Richard C Harkaway, Alan J. Wein, Robert M. Levin
    Abstract:

    Abstract Although studies exist using both male and female rats, there are virtually no studies that compare male and female Bladder function. In this initial study, in-vivo and in-vitro urinary Bladder function was investigated in two age groups of male and female rats (sexually immature and sexually mature). These studies compare in-vivo micturition behavior (water intake, urine output, frequency and volume per micturition); and in-vitro whole Bladder function (Bladder volume/pressure relationships, the ability of the in-vitro Bladders to generate pressure and empty in response to bethanechol and field stimulation). The results can be summarized as follows: 1) The 24 hour water intake, urine output, and volume per micturition for the mature male rats was significantly greater than that of the mature females with no significant differences among the immature females, mature females, or immature males. 2) There were no significant differences in the frequency of micturition between the 4 groups. 3) Although the average plateau pressures (cystometrograms) of the immature and mature female Bladders were greater than that of the immature and mature male Bladders, the compliance was similar for all groups. 4) The maximum pressure response of the mature female Bladder was significantly greater than pressures generated by Bladders in the other three groups; there were no age or sex related differences in the bethanechol log ED50 values. 5) There were no age or sex-related differences in the bethanechol log ED50 values or maximal expulsion responses. 6) Field stimulated Bladders from mature animals generated significantly greater intravesical pressures than Bladders from immature animals, but, there were no significant differences in maximal pressures attained between mature male and female Bladders nor between immature male and female Bladders. In conclusion, micturition behavior, and the maximal pressure response to bethanechol changed dramatically with sexual maturity. These results are consistent with the idea that estrogen and other hormones may have a marked influence on Bladder function and micturition behavior. (J. Urol, 143: 1267–1271, 1990)