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Biomedical subjects

R M Levin

Publications and source records attributed to R M Levin.

At least 19 recordsLinked to original sources
PubMed1999

Effect of diltiazem and pinacidil on the response of the rabbit urinary bladder to repetitive stimulation and in vitro ischemia.

The effect of repetitive stimulation, in the presence and absence of diltiazem or pinacidil, on the contractile responses of isolated strips of rabbit bladder detrusor to field stimulation and carbachol, after 2 hr of incubation in a medium that serves as an in vitro model of ischemia (oxygen and substrate depleted Tyrode's solution), was determined. Our results are summarized as follows: a) The magnitude of the contractile dysfunctions after in vitro ischemia was enhanced by repetitive stimulation. b) Pre-incubation of isolated strips of detrusor with diltiazem (50 microM) inhibited the contractile responses to field stimulation (FS) and carbachol by 43 and 50%, respectively. Pinacidil (100 microM) inhibited the contractile responses to FS and carbachol by 37 and 32%, respectively. c) Neither diltiazem nor pinacidil protected the bladder strips against the effects of 2 hr of incubation in in vitro ischemia medium. However, d) both pinacidil and diltiazem reduced the level of contractile dysfunctions induced by repetitive stimulation. In conclusion, the contractile response to FS was significantly more sensitive to in vitro ischemia and repetitive stimulation than was the contractile response to carbachol. Both diltiazem and pinacidil protected the contractile responses to FS and carbachol from the degenerative effects of repetitive stimulation, but not from the effects of in vitro ischemia.

Animals↗
PubMed1999

Fatty acid profiles in normal and obstructed rabbit bladder smooth muscle and mucosa.

Partial bladder outlet obstruction results in progressive loss in contractile and specific cellular and subcellular membrane functions. There is evidence that ischemic activation of proteolytic and lipolytic enzymes play a major role in the etiology of bladder dysfunction secondary to partial outlet obstruction. The specific aims of the current study were to determine the fatty acid profiles in normal rabbit bladder smooth muscle and mucosa and to determine the effect of partial outlet obstruction on the distribution and content of free and total fatty acids. Fatty acids were isolated by extraction from obstructed and normal bladder smooth muscle and mucosal homogenates, and samples were analyzed by gas chromatography. All samples contained palmitic, stearic, oleic, linoleic, and arachidonic acids. A 100% increase in total fatty acid concentration was observed in the obstructed bladder muscle tissue relative to normal bladders, although the concentration of total arachidonic acid remained constant in the two groups. Significantly higher levels of free arachidonic acid were observed in the obstructed bladder muscle group compared to the normal group. No changes were observed in fatty acid concentrations or distributions in bladder mucosa. These data show that fatty acid composition is altered as a result of bladder obstruction and support the idea that obstruction increases the activity of lipase activity and/or decreases acyl transferase activity. Neurourol. Urodynam. 18:697-711, 1999.

Animals↗
PubMed1999

Effect of partial outflow obstruction on the distribution of free fatty acids and phospholipids in the rabbit bladder.

The urinary bladder is separated into two distinct components, the mucosal epithelium (urothelium) and the underlying detrusor smooth muscle. Specific bladder dysfunctions such as partial outlet obstruction may contribute to the breakdown and damage of cell membranes. The major component of cell membranes is phospholipids, and the release of free fatty acids (FFA) from membrane phospholipids is suggestive of degradative lipase activity. The current investigation is concerned with the effect of partial outlet obstruction on the subcellular distribution of free fatty acids and phospholipids (PL) in rabbit bladder muscle and mucosa. Partial outlet obstructions were surgically created in mature male New Zealand White rabbits by standard methodology. At 2 weeks following surgery, rabbits were euthanized and the bladders, removed and separated into smooth muscle and mucosa. Muscle and mucosa were homogenized and separated by differential centrifugation to obtain separate subcellular fractions including plasma membranes, mitochondria, microsomes, and cytosol. The homogenate and supernatant fraction, free of membranes, were also saved. The free-fatty-acid (FFA) and choline-containing phospholipid (PL) content and the rate of generation of FFA were quantitated using in vitro enzymatic colorimetric methods. Relative to controls there was a significant increase in the FFA content of the obstructed smooth muscle and an increase in the PL content of the obstructed mucosa. There was an increase in FFA content in the mitochondrial fraction and a decrease in the supernatant of the obstructed smooth muscle. The PL content was reduced in the obstructed smooth muscle microsomal and supernatant fractions and was increased in the supernatant fraction of the mucosa. Endogenous lipase activity among control bladders was more than 10-fold greater in mucosa than in muscle. The FFA generation of the smooth muscle was significantly reduced by partial outlet obstruction. In conclusion, partial outlet obstruction causes bladder dysfunction due to activation of enzymes that hydrolyze cellular and subcellular membranes. The increase in endogenous lipase activity and generation of FFA among obstructed bladders indicates that the pathological state affects the membrane structure needed for normal bladder function.

Animals↗
PubMed1999

Biochemical evaluation of obstructive bladder dysfunction in men secondary to BPH: a preliminary report.

OBJECTIVES: In the rabbit, two of the major cellular alterations that mediate bladder dysfunction secondary to partial outlet obstruction are a decreased ability of the sarcoplasmic reticulum (SR) to store and release Ca2+, and mitochondrial dysfunction. The objective of the current study was to determine whether SR and mitochondrial dysfunctions are associated with symptomatic benign prostatic hyperplasia (BPH) in men. METHODS: Bladder biopsies were obtained from men with symptomatic BPH and from age-matched men with no urologic dysfunction. Each biopsy was analyzed for the following enzyme activities: malate dehydrogenase and citrate synthase (mitochondrial markers) and the sarcoplasmic reticular enzyme Ca2+ -dependent adenosine triphosphatase (ATPase). These values were compared with the enzyme activities of control rabbit bladder smooth muscle and bladder smooth muscle obtained from rabbits subjected to 2 weeks of partial outlet obstruction. RESULTS: The enzymatic activities of all three enzymes are significantly lower in human bladder smooth muscle than in rabbit bladder smooth muscle. The maximal activities of all three enzymes are significantly lower in human bladder samples obtained from men with diagnosed obstructive uropathy than in men of equal age with no urologic dysfunction. CONCLUSIONS: These studies demonstrate that similar to the response of the rabbit to partial outlet obstruction, obstructive dysfunction secondary to BPH is characterized by mitochondrial and SR dysfunction.

Animals↗
PubMed1999

Sucrose diuresis protects rat bladder from outlet partial obstruction-induced contractile dysfunction.

OBJECTIVES: Evidence is accumulating that bladder dysfunction caused by experimental partial obstruction of the bladder outlet can be reduced or reversed by treatment that results in upregulation of bladder function, even in the presence of obstruction. Inducing diuresis in rats or rabbits results in a significant increase in bladder mass and increased contractility in response to stimulation. The objective of the present study was to determine whether diuresis-induced amplification of bladder function in the rat could protect the bladder from contractile dysfunctions caused by partial outlet obstruction. METHODS: Thirty-two rats were separated into four groups of 8 rats each. Groups 2 and 4 were fed 5% sucrose instead of water; groups 1 and 3 were fed only water. Three weeks later, partial outlet obstructions were created in groups 3 and 4. After 4 weeks of obstruction, all bladders were rapidly excised and cut into longitudinal strips; each strip was mounted in an isolated muscle bath for contractile studies. RESULTS: Sucrose-induced diuresis caused a moderate but significant increase in bladder mass. Partial outlet obstruction stimulated significant increases in bladder mass in both water-drinking and sucrose-drinking groups; the bladder mass of sucrose-drinking rats, however, increased less than that of water-drinking rats. In water-drinking rats, partial outlet obstruction resulted in significantly decreased bladder strip contractility in vitro in response to field stimulation (1 to 32 Hz), carbachol (0.1 to 22 microM), and KCl (120 mM). After 3 weeks of sucrose-induced diuresis, partial obstruction of the rat bladder outlet did not result in decreased in vitro contractile responses to any form of stimulation applied. CONCLUSIONS: Sucrose-induced diuresis caused an increase in bladder mass and an increase in contractile strength, consequently protecting the rat bladder from the contractile dysfunctions that usually follow partial outlet obstruction.

Animals↗
PubMed1999

Correlation of calcium-activated ATPase activity, lipid peroxidation, and the contractile response of rabbit corporal smooth muscle treated with in vitro ischemia.

Oxygen and glucose are critical to support the survival and integrity of all smooth muscles. Hypoxia alone has been demonstrated to suppress the contractile response of corporal smooth muscle, and one might expect simultaneous deprivation of oxygen and glucose (in vitro model of ischemia) to exert more serious damage to corporal smooth muscle contraction. The effect of in vitro ischemia on the pharmacological responses of isolated rabbit corporal smooth muscle was correlated with the level of tissue lipid peroxidation. The effects of in vitro ischemia were as follows: (1) In vitro ischemia resulted in an 85% reduction in the contractile response to phenylephrine; (2) more than a 50% reduction in the activity of thapsigargin-sensitive calcium-activated ATPase activity of the microsomes (sarcoplasmic reticulum [SR]); (3) more than a fourfold increase in the tissue concentration of thiobarbituric acid reactive substances (TBARS) (level of lipid peroxidation). In conclusion, stimulation of lipid peroxidation in part may be responsible for the decrease in thapsigargin-sensitive calcium-activated ATPase activity of the SR (SERCA), and the correlated decrease in the contractile response to phenylephrine in response to ischemia.

Adenosine Triphosphatases↗
PubMed1999

Mitochondrial and mitochondrial-related nuclear genetic function in rabbit urinary bladder following reversal of outlet obstruction.

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.

Animals↗
PubMed1999

Metabolic basis for contractile dysfunction following chronic partial bladder outlet obstruction in rabbits.

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 microM) 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.

Animals↗
PubMed1999

Mitochondrial involvement in bladder function and dysfunction.

Benign bladder pathology resulting from prostatic hypertrophy or other causes is a significant problem associated with ageing in humans. This condition is characterized by increased bladder mass, decreased urinary flow rate, decreased compliance, and these and other changes in bladder function often subject patients to increased risk of urinary tract infection. While the physiologic attributes of benign bladder pathology have been extensively described in humans and in various animal model systems, the biochemical and molecular genetic bases for that pathology have only recently been investigated in detail. Studies demonstrate that mitochondrial energy production and utilization are severely impaired in bladder smooth muscle during benign bladder disease, and to a large extent this realization has provided a rational basis for understanding the characteristic alterations in urinary flow and compliance in bladder tissue. Recent investigations targeting the detailed molecular basis for impaired mitochondrial function in the disease have shown that performance of the organellar genetic system, and to a large extent that of relevant portions of the nuclear genetic system as well, is severely aberrant in bladder tissue. In this article, we discuss the physiologic aspects of benign bladder disease, summarize biochemical evidence for the altered mitochondrial energy metabolism that appears to underlie bladder pathology, review the structure and function of the mitochondrial genetic system, and discuss molecular genetic studies of that system which have begun to provide a mechanistic explanation for the biochemical and physiological abnormalities that characterize the disease. We also discuss areas for further research which will be critically important in increasing our understanding of the detailed causes of benign bladder pathology.

Aging↗
PubMed1999

Metabolic aspects of urinary bladder filling.

Urinary bladder compliance allows the bladder to fill to near capacity without a large increase in intravesical pressure. Bladder compliance is composed of two interrelated factors: passive characteristics of the connective tissue elements of the bladder, and active properties of the smooth muscle elements. The tension generated by the smooth muscle elements can significantly affect bladder compliance. This study utilized an in-vitro whole-bladder model in rabbits to determine the effects of hypoxia, alterations in calcium concentrations, and muscarinic agonists and antagonists on bladder capacity and compliance. The urinary bladder was excised together with a short segment of proximal urethra. A catheter was inserted into the bladder via the dome and the urethra was canulated with a saline-filled tube. The bladder was mounted in an isolated bath containing Tyrode's buffer. The catheter was connected to a pressure transducer to monitor the intravesical pressure and connected to a saline-filled i.v. bag. The weight of the saline bag was continually monitored. The height of the saline bag was set to 80 mmH2O above the baseline intravesical pressure. Bladder filling was started by opening the bladder to the saline reservoir. Intravesical pressure, rate of pressure increase, rate of volume increase, and maximal volume were digitally recorded. The bladder filling was repeated while the whole bladder was subjected to hypoxia, high calcium concentration, the presence of EGTA, carbachol, atropine and tetrodotoxin, respectively. Results are summarized as follows: (a) control bladder filling was biphasic, there was an initial rapid rise in intravesical pressure followed by a slower linear rise to the pre-set pressure; (b) hypoxia significantly decreased the initial rate of the rise in intravesical pressure, increased the rate of bladder filling, and significantly increased final bladder volume; (c) incubation of the bladder in the presence of EGTA also significantly decreased the initial rate of intravesical pressure rise, increased the rate of filling and also significantly increased the final bladder volume; (d) high concentrations of calcium increased the initial rate of rise in intravesical pressure; (e) carbachol significantly increased the rate of intravesical pressure rise, decreased the rate of bladder filling, and significantly decreased final bladder volume; (f) atropine and tetrodotoxin (TTX) had no effects on bladder filling. In summary, alterations in muscle tone had significant effects on bladder capacity and compliance.

Animals↗
PubMed1999

Struma ovarii and hyperthyroidism.

Struma ovarii is a teratoma of the ovaries that contains a large amount of thyroid tissue. Like the cervical thyroid gland, this ectopic thyroid tissue can become autonomous. We present a case of hyperthyroidism caused by thyroid tissue in a large ovarian cystic teratoma and provide detailed endocrinological, radiological, and pathological preoperative and postoperative data. This is also the first documented case of struma ovarii in association with a secreting pituitary tumor. In addition, we provide a retrospective pathological analysis of 1390 surgically removed ovarian tumors at 2 major academic centers.

Adult↗
PubMed1999

Correlation of EGTA and calcium-blocking agents on the response of the bladder to in vitro ischemia.

The effects of repetitive field stimulation (model of hyperrelexia) on the responses of isolated strips of rabbit urinary bladder to FS and carbachol were evaluated under a variety of incubation conditions. Compared to control conditions, 2 h of repetitive FS in normal, oxygenated Tyrode's solution followed by incubation for 1 h with no stimulation resulted in a 50% decrease in contractile response to FS and a 30% decrease in the response to carbachol. Incubation in the absence of O2 and glucose was used as an in vitro model for ischemia. Repetitive stimulation during in vitro ischemia resulted in a significantly greater decrease in the contractile responses to FS and carbachol than did in vitro ischemia without repetitive stimulation. The magnitude of contractile dysfunctions in response to both stimuli were significantly reduced in the presence of EGTA (calcium chelator), diltiazem (calcium channel blocker) or pincidil (potassium channel opener). Incubation with thapsigargin (SR calcium uptake inhibitor) + ryanodine (SR calcium storage inhibitor) had no effect. The results of these studies indicate that inhibition of Ca2+ entry reduces the contractile dysfunctions induced by repetitive stimulation in the presence of in vitro ischemia. Inhibition of Ca2+i storage and release had no significant effect on the magnitude of contractile dysfunctions induced by repetitive stimulation an in vitro ischemia.

Animals↗
PubMed1999

Rabbit versus rat urinary bladder: effects of in vitro hypoxia.

PURPOSE: Studies indicate that bladder hypoxia may be an etiological factor for lower urinary tract dysfunction. Rat and rabbit are two species of experimental animals used frequently to study lower urinary tract function and dysfunction. The objective of this study was to compare directly effects of in vitro hypoxia on contractile responses of rat and rabbit urinary bladder to different forms of stimulation. METHODS: Sexually mature male New Zealand White rabbits and Sprague-Dawley rats were compared. Each bladder was excised while the animal was anesthetized, and longitudinal bladder strips were cut, then mounted in organ baths. A tension of 2 g was placed on all strips. Effects of 1, 2, 3 and 4 h hypoxia followed by 1 h of reoxygenation on contractile responses of bladder strips to field stimulation (FS), carbachol (100 micromol/l), ATP (1 mmol/l) and KCl (120 mmol/l) were determined. RESULTS: Contractility, per unit tissue mass, of rat bladder strips was significantly greater than that of rabbit bladder strips in response to FS (all frequencies), carbachol, KCl and ATP. Hypoxia (followed by reoxygenation) resulted in time-dependent progressive reduction in contractile responses of bladder strips to all stimuli. Rat bladder was significantly more sensitive to hypoxia than rabbit bladder in response to FS and carbachol. Hypoxia induced similar effects on rat and rabbit bladder responses to ATP and KCl. CONCLUSION: Rat bladder neurogenic and cholinergic responses are significantly more sensitive to hypoxia than are those of rabbit bladder, which may be due to the rat bladder's greater contractile force generation and previously reported higher Ca2+-ATPase activity.

Animals↗
PubMed1999

Effects of in vivo ischemia on contractile responses of rabbit bladder to field stimulation, carbachol, ATP and KCl.

Rabbits were subjected to bilateral ischemia for 3, 6, or 18 h then euthanized and their bladders excised. Isolated strips of rabbit bladder detrusor were incubated in normal Tyrode's solution and contractile responses to FS, carbachol, ATP, and KCl measured. Maximal contraction, maximal rate of tension generation, and length of time to maximal contraction were determined. These studies revealed that contractile responses to FS (neurogenic stimulation) were most affected by ischemia. Contractile responses to carbachol, ATP and KCl were all similarly sensitive to ischemia.

Adenosine Triphosphate↗
PubMed1998

Use of abdominal fascia to create partial outlet obstruction in rabbits.

Partial outlet obstruction has been used for a considerable period of time as an animal model for the urodynamic changes that occur with the progressive obstruction of benign prostatic hyperplasia (BPH). Although there are many models of partial outlet obstruction, one common feature is that the degree of obstruction produced is inconsistent. The current study evaluates the responses of the bladder to a partial outlet obstruction created using an autologous fascial collar from harvested rectus fascia. The results demonstrate that although there was a moderate and variable increase in bladder mass, the alterations in the contractile responses to field stimulation (FS), carbamyl choline (carbachol), KCl, and adenosine 5'-triphosphate (ATP) were less severe than other models of partial outlet obstruction. Specifically, there was an approximate 40% decrease in the magnitude of the contractile response to FS but no significant changes in the magnitude of the contractile responses to carbachol, KCl, or ATP. Further analysis of the contractile responses demonstrated that there was a greater decrease in the rate of tension generation than in the magnitude of response for FS, and a significant increase in the time to maximal tension. Although there were no decreases in the magnitude of the responses to carbachol, KCl, or ATP, there were significant reductions in the rate of tension generation for carbachol and KCl and significant increases in the time to maximal tension for carbachol and ATP. Applying less tension over a wider area, the fascial collar provided a consistent and reproducible mild partial outlet obstruction.

Adenosine Triphosphate↗
PubMed1998

Effects of hypoxia, calcium, carbachol, atropine and tetrodotoxin on the filling of the in-vitro rabbit whole bladder.

PURPOSE: The urinary bladder stores urine at low intravesical pressure and empties the urine efficiently and completely. Bladder compliance is the property that allows the bladder to fill to near capacity without a large increase in intravesical pressure. The current study utilized an in vitro whole bladder model to determine the effects of hypoxia, alterations in extracellular calcium concentration, carbachol and atropine on bladder capacity and compliance. METHODS: Mature male New Zealand White rabbits were used in this study. The urinary bladder was excised from the rabbit together with a short segment of proximal urethra and mounted in a 400 ml. isolated bath containing Tyrode's buffer. Bladder filling was started by opening the bladder to a saline reservoir placed 80 cm. above the bladder. Intravesical pressure, rate of pressure increase, rate of volume increase, and maximal volume were digitally recorded. The bladder filling was repeated while the whole bladder was subjected to hypoxia, high calcium concentration, the presence of EGTA, carbachol, atropine and tetrodotoxin respectively. RESULTS: Results are summarized as follows: 1) Bladder filling was biphasic. There was an initial rapid rise in intravesical pressure followed by a slower rise. The final bladder volume averaged 46 ml. 2) Hypoxia significantly decreased the initial rate of the rise in intravesical pressure, increased the rate of bladder filling, and increased bladder volume by 43%. 3) Incubation of the bladder in the presence of EGTA also significantly decreased the initial rate of intravesical pressure rise, increased the rate of filling and increased bladder volume by 39%. 4) High concentrations of calcium increased the initial rate of rise in intravesical pressure. 5) Carbachol significantly increased the rate of intravesical pressure rise, decreased the rate of bladder filling, and decreased bladder volume. 6) Atropine and tetrodotoxin (TTX) had no effects on bladder filling. CONCLUSION: In summary, alterations in muscle tone had significant effects on bladder capacity and compliance.

Animals↗