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    Effect of age on rabbit bladder function and structure following partial outlet obstruction
    (Lippincott Williams & Wilkins, 2005) Ağartan, Canan Aldırmaz; Whitbeck, Catherine; Chichester, Paul; Kogan, Barry A.; Levin, Robert M.
    Purpose: We determined whether young and old rabbits respond differently to partial bladder outlet obstruction. Materials and Methods: A total of 16 male New Zealand White rabbits were separated into 2 groups of 8 each. Group 1 consisted of young rabbits (age 7 weeks) and group 2 consisted of old rabbits (age 2 years). Four rabbits per group underwent partial outlet obstructions and 4 underwent sham operation. Four weeks following surgery individual bladder strips were used for contractile studies and the remaining tissue was examined histologically. Results: Contractile responses to all forms of stimulation between the young and old sham operated groups were similar. Contractile responses to all forms of stimulation were significantly decreased to the same degree in the 2 obstructed groups. However, the rate of tension generation to field stimulation was decreased to a significantly greater degree in young vs old bladders. Although young and old bladders showed smooth muscle hypertrophy, older rabbits showed significantly greater thickening of the serosa than young rabbits. Young rabbits showed significant inflammation, hemorrhage and expansion of the lamina propria, whereas old rabbits showed none of these characteristics. Conclusions: Although there were only minor differences in the physiological response of young and old bladders to obstruction, young rabbits showed a significantly greater degree of histological damage. This may have been due to the thinner wall and greater sensitivity to distention.
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    Effect of age on the response to in vitro ischemia and reperfusion of the rabbit bladder
    (Karger, 2007) Ağartan, Canan Aldırmaz; Leggett, Robert E.; Kogan, Barry A.; Levin, Robert M.
    Background/ Aims: Urinary bladder dysfunction secondary to outlet obstruction is a common condition, seen in both children and adults. Using in vitro models of ischemia/ reperfusion ( I/ R), we compared the contractile and biochemical responses of bladders isolated from young and old rabbits. Materials and Methods: Fourteen male New Zealand White rabbits were separated into two groups of 7. Group 1 ( young) included rabbits 6 - 7 weeks old and group 2 ( old) consisted of rabbits 2 years old. Isolated bladder body strips were subjected to in vitro I/R, and the effects on contractility were determined. The strips were then frozen and stored for quantitative malondialdehyde ( MDA) analysis. Results: Contractile responses of young and old rabbit bladders to all forms of stimulation - field stimulation ( FS), carbachol and potassium chloride ( KCl) - were equal. The rate of tension to 32 Hz FS was significantly higher for group 1 in comparison with group 2. The old and young rabbits were equally sensitive to I/R in regard to FS, but the old rabbits were more sensitive to I/R in regard to carbachol and KCl stimulation. Basal MDA concentration of both young and aged bladder strips were similar. Ischemia mediated a significant increase in MDA in bladder strips from both young and old rabbits, but the MDA level was significantly greater for the young than for the old. Conclusion: Although the level of oxidative damage was greater in the young rabbit bladders, functionally, the old rabbit bladders were more sensitive to I/ R damage. Copyright (c) 2007 S. Karger AG, Basel.
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    Effect of ethanol on protection of urinary bladder function by grape suspensions
    (Elsevier Science Inc, 2005) Ağartan, Canan Aldırmaz; Whitbeck, Catherine; Chichester, Paul; Levin, Robert M.
    Objectives. To compare the protective effects of grape suspensions prepared in an aqueous vehicle with grape suspensions prepared in an 8% ethanol vehicle in rabbits subjected to partial outlet obstruction. The hypothesis was that the presence of ethanol would increase the absorption of the beneficial components of the grape suspensions and thus increase their protective ability. The use of ethanol in these studies was not to simulate wine. Methods. A total of 48 New Zealand white rabbits were separated into eight groups of 6 rabbits each. Groups 1 and 3 were pretreated by oral gavage for 3 weeks with grape suspensions in water; groups 2 and 4 were treated with vehicle. Groups 5 and 7 were treated with the grape suspensions in 8% ethanol, and groups 6 and 8 were treated with ethanol vehicle. Groups 1, 2, 5, and 6 underwent sham operations, and groups 3, 4, 7, and 8 underwent partial outlet obstruction. Three weeks after surgery, the rabbits were evaluated. Results. The bladder weight had significantly increased in all obstructed groups. The contractile responses to field stimulation and carbachol were reduced in all obstructed groups, although the responses in both grape-treated groups were greater than both vehicle-treated groups. The contractile responses to potassium chloride were significantly reduced by partial outlet obstruction in both obstructed groups similarly. Conclusions. Both grape suspensions provided protection against obstructive-induced bladder dysfunction. The ethanol preparation of the grape suspension was not better than the aqueous preparation.
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    Effect of partial outlet obstruction on nitrotyrosine content and distribution within the rabbit bladder
    (Springer, 2005) Levin, Robert M.; Ağartan, Canan Aldırmaz; Leggett, Robert E.; Whitbeck, Catherine; Chichester, Paul; Neuman, Paul; Johnson, Arnold
    Purpose: Evidence indicates that free radicals are etiological factors in obstructive bladder disease. However, it is not clear which species of reactive oxygen or nitrogen species mediate the damage. The current studies were designed to determine if partial outlet obstruction in rabbits results in the generation of nitrotyrosine (NT). Materials and methods: Sixteen rabbits were separated into four groups of four. The rabbits in groups 1 and 2 underwent sham operation while rabbits in groups 3 and 4 underwent partial outlet obstruction. The rabbits in groups 1 and 3 were evaluated after 1 week of obstruction and the rabbits in groups 2 and 4 were evaluated after 2 weeks of obstruction. A separate group of four controls were evaluated simultaneously with the sham and obstructed rabbits. Four rabbits from each group were evaluated after 1 and 2 weeks of obstruction. Four control rabbits were also evaluated. Isolated strips were evaluated for contractile responses and NT content of the mucosa and muscle were quantitated by Western blot analysis. Results: (1) The mucosa contains both 42 and 62 kD proteins exhibiting a strong nitrotyrosine signal; the muscle presents a signal only at 62 kD. (2) The sham operations had no effect on nitrotyrosine distribution or content. (3) The nitrotyrosine of both mucosal proteins and the muscle protein are increased in the 1 week obstructed bladder; whereas, only the 62 kD signal is increased in the two week obstructed bladder mucosa. (4) The contractile response to FS are reduced to a significantly greater degree than the responses to carbachol, KCl, or ATP. Conclusions: These studies clearly demonstrated that partial outlet obstruction in rabbits results in significant increases in nitrotyrosine within the bladder and may contribute to the contractile dysfunctions mediated by partial outlet obstruction.
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    Protection of urinary bladder function by grape suspension
    (Wiley, 2004) Ağartan, Canan Aldırmaz; Whitbeck, Catherine; Sokol, Rebekah; Chichester, Paul; Levin, Robert M.
    Urinary bladder dysfunction secondary to BPH is a major affliction of aging men. A rabbit model of partial outlet obstruction was used to evaluate the ability of a standardized grape suspension to protect the bladder against obstructive bladder dysfunction. Twenty-four New Zealand White rabbits were separated into four groups of six rabbits each. Groups 1 and 3 were pretreated by oral gavage for 3 weeks with a standardized grape suspension suspended in water; groups 2 and 4 were treated with vehicle. Groups 1 and 3 received sham operations after 3 weeks of treatment; groups 2 and 4 received partial outlet obstruction by surgically placing a silk ligature loosely around the urethra. At 3 weeks following surgery, in vivo and in vitro bladder functions were evaluated. Based on both in vivo and in vitro studies, the grape suspension significantly reduced the severity of obstructed bladder dysfunction. This is consistent with the hypothesis that ischemia is a major etiological factor in obstructive dysfunction, and treatment with antioxidants and membrane stabilization compounds such as those in the grape suspension can be effective in the treatment of obstructive bladder pathology.

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