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Urinary glycosaminoglycans excretion and the effect of dimethyl sulfoxide in an experimental model of non-bacterial cystitis

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Urinary Glycosaminoglycans Excretion and the Effect of Dimethyl

Sulfoxide in an Experimental Model of Non-Bacterial Cystitis

Roberto Soler, Homero Bruschini, Jose C. Truzzi, Joao R. Martins, Niels O. Camara, Maria T. Alves, Katia R. Leite, Helena B. Nader, Miguel Srougi, Valdemar Ortiz

Division of Urology (RS, JCT, VO), Division of Molecular Biology (JRM, HBN), Division of Nephrology (NOC) and Division of Pathology (MTA), Federal University of Sao Paulo, UNIFESP, and Division of Urology (HB, KRL, MS), University of Sao Paulo, USP, Sao Paulo, SP, Brazil

ABSTRACT

Purpose: :HUHSURGXFHGDQRQEDFWHULDOH[SHULPHQWDOPRGHOWRDVVHVVEODGGHULQÀDPPDWLRQDQGXULQDU\JO\FRVDPLQRJO\-FDQV*$*H[FUHWLRQDQGH[DPLQHGWKHHIIHFWRIGLPHWK\OVXOIR[LGH'062

Materials and Methods:)HPDOHUDWVZHUHLQVWLOOHGZLWKHLWKHUSURWDPLQHVXOIDWH36JURXSVRUVWHULOHVDOLQHFRQWURO JURXSV$WGLIIHUHQWGD\VDIWHUWKHSURFHGXUHKXULQHDQGEODGGHUVDPSOHVZHUHREWDLQHG8ULQDU\OHYHOVRIK\DOXURQLF DFLG+$DQGVXOIDWHGJO\FRVDPLQRJO\FDQV6*$*ZHUHGHWHUPLQHG$OVRWRHYDOXDWHWKHHIIHFWRI'062DQLPDOV ZHUHLQVWLOOHGZLWKHLWKHU'062RUVDOLQHKRXUVDIWHU36LQVWLOODWLRQ7RHYDOXDWHWKHHIIHFWRI'062LQKHDOWK\ EODGGHUVUDWVZHUHLQVWLOOHGZLWK'062DQGFRQWUROVZLWKVDOLQH

Results: ,QWKH36JURXSVEODGGHULQÀDPPDWLRQZDVREVHUYHGZLWKSRO\PRUSKRQXFOHDUFHOOVGXULQJWKH¿UVWGD\VDQGO\P-SKRPRQRQXFOHDULQWKHODVWGD\V+$DQG6*$*KDGSHDNVRIXULQDU\H[FUHWLRQDWWKHst and 7thGD\DIWHU36LQMHFWLRQ

'062VLJQL¿FDQWO\UHGXFHGEODGGHULQÀDPPDWLRQ,QFRQWUDVWLQKHDOWK\EODGGHUV'062SURGXFHGPLOGLQÀDPPDWLRQ DQGDQLQFUHDVHLQXULQDU\+$OHYHOVDIWHUDQGGD\VDQGDQLQFUHDVHRI6*$*OHYHOLQGD\V$QLPDOVLQVWLOOHGZLWK 36DQGWUHDWHGZLWK'062KDGVLJQL¿FDQWO\UHGXFHGOHYHOVRIXULQDU\+$RQO\DWWKHstGD\8ULQDU\6*$*&UOHYHOV

ZHUHVLPLODULQDOOJURXSV

Conclusions:,QFUHDVHGXULQDU\OHYHOVRI*$*ZHUHDVVRFLDWHGZLWKEODGGHULQÀDPPDWLRQLQD36LQGXFHGF\VWLWLVPRGHO '062VLJQL¿FDQWO\UHGXFHGWKHLQÀDPPDWRU\SURFHVVDIWHUXURWKHOLDOLQMXU\&RQYHUVHO\WKLVGUXJSURYRNHGPLOGLQÀDP -PDWLRQLQQRUPDOPXFRVD'062WUHDWPHQWZDVVKRZQWRLQÀXHQFHXULQDU\+$H[FUHWLRQ

Key words: cystitis; dimethyl sulfoxide; glycosaminoglycans; rats; protamines

Int Braz J Urol. 2008; 34: 503-11

INTRODUCTION

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Impaired barrier function of bladder

(2)

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MATERIALS AND METHODS

Animals and Induction of Bladder

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catheter was inserted into the bladder and the urine

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Experimental Groups

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Histopathology

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Measurement of Urinary Hyaluronic Acid

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Measurement of Urinary Sulfated GAG

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Statistical Analysis

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RESULTS

Histopathology

PS and Control Groups

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DMSO Groups

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GAG Measurement

PS and Control Groups

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(4)

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DMSO Groups

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COMMENTS

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(5)

Table 1 – Pathological features in DMSO groups.

Group EdemaJUDGH Vascular Congestion

JUDGH PMN Count (median)

Mast Cell Count(median)

LMN Count

(median)

1 day

Q 7 daysQ Q 1 day 7 daysQ Q 1 day 7 daysQ Q 1 day 7 daysQ Q 1 day 7 daysQ

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also described in biopsies and cell culture obtained

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of action and effects on bladder tissue function are

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support the initial complaint from some patients of

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-ÀDPPDWLRQRUDIWHULQMXU\+$PD\HLWKHUEHGHJUDGHG Figure 3 – Urinary GAG measurement. Time course of effects of intravesical PS or saline instillation on urinary HA (A) and urinary 6*$*%7KHFRQFHQWUDWLRQVZHUHQRUPDOL]HGE\XULQDU\FUHDWLQLQH9DOXHVDUHPHDQV“6'3SRLQWVRQWKH36WLPHFRXUVH YVWKRVHRQWKHFRQWUROWLPHFRXUVH†3FRPSDULVRQEHWZHHQ36JURXSV+$GD\YVGD\GD\YVGD\6*$*GD\ YVGD\VDQG

Table 2 – Urinary GAG levels in DMSO groups.

Group HA/Cr QJPJ S-GAG—JPJ

1 day

Q 7 daysQ Q 1 day 7 daysQ

6DOLQH “ “ “ “

'062 “ “ “ “

366DOLQH “‡ “ “ “

36'062 “ “ “ “

(8)

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CONFLICT OF INTEREST

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(9)

EDITORIAL COMMENT

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Dr. Robert E. Hurst

Oklahoma University Cancer Institute and Oklahoma University Health Sciences Center Oklahoma City, Oklahoma, USA

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Accepted after revision:

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Correspondence address:

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Referências

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