- Email: [email protected]
Relation of Body Mass Index (BMI) with the risk of developing BPH
230
229 EFFECT OF DOXAZOSIN ON ISCHEMIA-INDUCED CONTRACTILITY OF THE RABBIT PROSTATE Azadzoi
INCREASED
Kazem, Siroky Mike, Babayan Richard
Urology Research, States of America
Boston
INTRODUCTION
University;
Boston
& OBJECTIVES:
IDENTIFICATION OF A NOVEL PROSTATIC PROTEIN THAT IS RECOGNISED BY SERUM ANTIBODIES OF PATIENTS WITH BENIGN PROSTATIC HYPERPLASIA AND NOT BY ANTIBODIES OF HEALTHY
VA Medical
Centers,
Boston,
INDIVIDUALS
United
The mechanism
of bladder outlet obstruction that specific pathophysiologic changes within the prostatic gland, independent of prostate volume, may be responsible for ureteral obstruction. Our studies with the rabbit model showed that chronic ischemia causes a significant increase in the contractile reactivity of prostatic tissue. Our aim was to examine the effect of doxazosin, an alpha-l adrenergic antagonist, on ischemia-induced overcontractility of the rabbit prostate.
in benign prostatic hyperplasia (BPH) is unclear. Recent studies have suggested
MATERIAL & METHODS: Male New Zealand
white rabbits (3.5-4 kg) were divided into 2 groups: chronic prostatic ischemia (CPI, n=IO) and age-matched control (CON, n=6). The CPI group underwent balloon endothelial injury of the iliac arteries and received a 0.5% cholesterol diet; the CON group received a regular diet. After 10 weeks, iliac arterial and prostatic blood flows were measured by ultrasonic and laser Doppler flowmeters. Prostatic strips were processed for isometric tension
measurement in the organ bath. RESULTS: Mean iliac artery and prostatic blood flow were significantly in the CPI group compared with the CON group (PfO.05). Histology
decreased confirmed diffuse atherosclerotic occlusive disease in the right and left iliac arteries in the CPI group. Chronic ischemia significantly increased electrical field stimulation (EFS)-
induced neurogenic contraction of prostatic strips and caused marked supersensitivity to noreoineohrine (Pf0.05). Tissue treatment with doxazosin caused a significant decreask in rontractions to kFS in the CPI and CON groups (PEO.05). After tieatment with doxazosin, contraction to EFS of ischemic prostatic tissue was similar to doxazosin contraction of prostatic tissue from the CON group. Furthermore, significantly decreased contraction of prostatic tissue in response to norepinephrine in the CPI and CON groups (Pf0.05). After treatment with doxazosin, contraction of ischemic prostatic tissue in response to norepinephrine was comparable to contraction of prostatic tissue from the CON group. CONCLUSIONS: CPI caused a significant increase in the contractile reactivity of Doxazosin effectively rabbit prostatic smooth muscle to EFS and norepinephrine. normalised ischemia-induced increased contractions of the rabbit prostatic tissue. After treatment with doxazosin, contractility of the ischemic prostatic tissue was similar to contractility of tissue from the healthy animals. Ischemia-induced increased contractility of the prostate appears to involve functional changes in the adrenergic pathway.
Steiner Georg’,Memaran-Dadgar Posch Martin2
Nima’ , Reithmayr
Franz’, Langer Dina’.
‘Urology, University of Vienna, Vienna, Austria, ?Medical Statistics, University of Vienna, Vienna. Austria INTRODUCTION & OBJECTIVES: To investigate whether the development of benign prostatic hyperplasia (BPH) is associated with expression of new or overexpression of existing antigens which are not tolerated by the immune system BPH patient’s sera were screened for autoreactivity. MATERIAL & METHODS: Sera of 65 patients with BPH entered this study. As control, sera of 20 healthy men between 20 and 30 years of age were used. Reactivity of normal and BPH-patients’ sera was analysed by Western blotting using 7 different BPH tissue and ceil extracts and anti-human IgG and IgA. Control experiments were performed on extracts derived from kidney, foreskin, keratinocytes, and LNCaP cells. A total of 38.000 reactive protein bands were identified and analysed for their molecular weight. Search for prostatic proteins that reacted significantly more frequently with BPH patients’sera when compared to control sera revealed 8 protein bands (p-values:
RESULTS:
CONCLUSIONS: Our data suggest that BPH pathogenesis influences the humoral immune response. Further characterisation of these BPH-sera reactive proteins might help to establish a serum-based assay for defining BPH. Source of funding: Research grant by Merck. Sharp & Dohme and Departmental.
231 RELATION
OF BODY
DEVELOPING Hollieer
MASS
INDEX
(BMI) WITH
THE
RISK
OF
BPH
Steohan,
Schneider
Eric, Madersbacher
Stephan,
Thalmann
232 ASSOCIATION OF POLYMORPHISMS WITHIN ANDROGEN RECEPTOR-5aIfa-REDUCTASEAND PSA-GENES WITH PROSTATE VOLUME, CLINICAL PARAMETERS AND ENDOCRINE STATUS IN ELDERLY MEN
George,
Studer Urs
Madersbacher Stephan’, Schatzl Geo$, Gsur Andrea2, Haidinger Gerald’, Haitel Andrea’, Vutuc Christian*, Micksche Michael*, Marberger Michael’
Urology, Inselspital Bern, Beme Switzerland
‘University Austria
INTRODUCTION
& OBJECTIVES:
In obese
patients
the estrogen:
androgen ratio is increased. Serum estrogen levels also increase in men with age, absolutely
or relative
mammalian
to testosterone
levels.
species that develops BPH, estrogens
In the dog,
the only
induce experimentally
other BPH.
The goal of this study is to determine whether patients with a high BMI (kgm’) present a higher risk for developing MATERIAL
& METHODS:
survey for Switzerland
BPH independently
1992/93),
including
health
7930 men were used.
Means and percentiles of body weight, body height and BMI were calculated men of different (25.00-29.99).
Overweight
grade II ([email protected]),
were compared RESULTS:
age groups.
was defined as a BMI>25
and grade III (BMI=40.00)].
for
[grade I
These data
to 150 patients treated for BPH.
In all three age groups (group I: 45-54 years, group II: 55-64 years,
group III: 65+) BMI in patients treated for BPH is higher than in the general male population
Berne,
Switzerland,
*University
of Vienna,
Vienna,
INTRODUCTION & OBJECTIVES: Identification of genetic markers for the development of BPH would be a major step toward a comprehensive understanding of this diseases and for the design of clinical trials and chemopreventive stategies. The aim of this study was to assess the impact of polymorphisms of three important genes within the androgen pathway on prostate volume, clinical parameters and endocrine status in men.
of age.
Data from the first national representative
(conducted
of Berne,
(group I: p=O.179, group II: p=O.o08 and group III: p=O.O03;
MATERIAL & METHODS: Elderly men with lower urinary tract symptoms underwent clinical and endocrine workup. In parallel, polymorphisms within the Sa-reductase gene (SRD5A2 V89L and A49T), the androgen receptor gene (AR: number of CAG-repeats), and the PSA gene (A-G substitution at position 158) were determined by polymerase chain reaction and restriction-length polymorphism analysis using DNA from peripheral blood. RESULTS: 190 men (66.5+9.2 years of age) were analysed. The number of CAG-repeats within the AR and the PSA polymorphism revealed no relevant associations to clinical and endocrine parameters. Individuals carrying the mutated SRD5A2 A49T allele (5.3% of the total population) had significantly larger prostates (54+28: vs. 39+16), higher PSA levels (12.2 versus 4.3 ngiml) and a 35% reduction in prostatic stroma/epithelial cell ratio than those with the wild type genotype. Men with the mutated SRD5A2 V89L had lower testosterone serum levels.
overall p=O.OOl). CONCLUSIONS:
In our data, men treated for BPH have a significantly
BMI than the general consequence European
population
of the higher estrogen Urology
Supplements
in Switzerland.
Whether
higher
this is only a
: androgen ratio remains to be determined. 1 (2002) No. 1, pp. 60
CONCLUSIONS: In contrast to prostate cancer, polymorphisms within AR and PSA genes do not seem to be of relevance for benign prostatic hyperplasia. Polymorphisms within the Sa-reductase gene are interesting biomarkers in that individuals carrying the mutated A49T allele had larger prostates, higher PSA levels and lower S/E-cell ratios suggesting an increased 5a-reductase activity.
229 EFFECT OF DOXAZOSIN ON ISCHEMIA-INDUCED CONTRACTILITY OF THE RABBIT PROSTATE Azadzoi
INCREASED
Kazem, Siroky Mike, Babayan Richard
Urology Research, States of America
Boston
INTRODUCTION
University;
Boston
& OBJECTIVES:
IDENTIFICATION OF A NOVEL PROSTATIC PROTEIN THAT IS RECOGNISED BY SERUM ANTIBODIES OF PATIENTS WITH BENIGN PROSTATIC HYPERPLASIA AND NOT BY ANTIBODIES OF HEALTHY
VA Medical
Centers,
Boston,
INDIVIDUALS
United
The mechanism
of bladder outlet obstruction that specific pathophysiologic changes within the prostatic gland, independent of prostate volume, may be responsible for ureteral obstruction. Our studies with the rabbit model showed that chronic ischemia causes a significant increase in the contractile reactivity of prostatic tissue. Our aim was to examine the effect of doxazosin, an alpha-l adrenergic antagonist, on ischemia-induced overcontractility of the rabbit prostate.
in benign prostatic hyperplasia (BPH) is unclear. Recent studies have suggested
MATERIAL & METHODS: Male New Zealand
white rabbits (3.5-4 kg) were divided into 2 groups: chronic prostatic ischemia (CPI, n=IO) and age-matched control (CON, n=6). The CPI group underwent balloon endothelial injury of the iliac arteries and received a 0.5% cholesterol diet; the CON group received a regular diet. After 10 weeks, iliac arterial and prostatic blood flows were measured by ultrasonic and laser Doppler flowmeters. Prostatic strips were processed for isometric tension
measurement in the organ bath. RESULTS: Mean iliac artery and prostatic blood flow were significantly in the CPI group compared with the CON group (PfO.05). Histology
decreased confirmed diffuse atherosclerotic occlusive disease in the right and left iliac arteries in the CPI group. Chronic ischemia significantly increased electrical field stimulation (EFS)-
induced neurogenic contraction of prostatic strips and caused marked supersensitivity to noreoineohrine (Pf0.05). Tissue treatment with doxazosin caused a significant decreask in rontractions to kFS in the CPI and CON groups (PEO.05). After tieatment with doxazosin, contraction to EFS of ischemic prostatic tissue was similar to doxazosin contraction of prostatic tissue from the CON group. Furthermore, significantly decreased contraction of prostatic tissue in response to norepinephrine in the CPI and CON groups (Pf0.05). After treatment with doxazosin, contraction of ischemic prostatic tissue in response to norepinephrine was comparable to contraction of prostatic tissue from the CON group. CONCLUSIONS: CPI caused a significant increase in the contractile reactivity of Doxazosin effectively rabbit prostatic smooth muscle to EFS and norepinephrine. normalised ischemia-induced increased contractions of the rabbit prostatic tissue. After treatment with doxazosin, contractility of the ischemic prostatic tissue was similar to contractility of tissue from the healthy animals. Ischemia-induced increased contractility of the prostate appears to involve functional changes in the adrenergic pathway.
Steiner Georg’,Memaran-Dadgar Posch Martin2
Nima’ , Reithmayr
Franz’, Langer Dina’.
‘Urology, University of Vienna, Vienna, Austria, ?Medical Statistics, University of Vienna, Vienna. Austria INTRODUCTION & OBJECTIVES: To investigate whether the development of benign prostatic hyperplasia (BPH) is associated with expression of new or overexpression of existing antigens which are not tolerated by the immune system BPH patient’s sera were screened for autoreactivity. MATERIAL & METHODS: Sera of 65 patients with BPH entered this study. As control, sera of 20 healthy men between 20 and 30 years of age were used. Reactivity of normal and BPH-patients’ sera was analysed by Western blotting using 7 different BPH tissue and ceil extracts and anti-human IgG and IgA. Control experiments were performed on extracts derived from kidney, foreskin, keratinocytes, and LNCaP cells. A total of 38.000 reactive protein bands were identified and analysed for their molecular weight. Search for prostatic proteins that reacted significantly more frequently with BPH patients’sera when compared to control sera revealed 8 protein bands (p-values:
RESULTS:
CONCLUSIONS: Our data suggest that BPH pathogenesis influences the humoral immune response. Further characterisation of these BPH-sera reactive proteins might help to establish a serum-based assay for defining BPH. Source of funding: Research grant by Merck. Sharp & Dohme and Departmental.
231 RELATION
OF BODY
DEVELOPING Hollieer
MASS
INDEX
(BMI) WITH
THE
RISK
OF
BPH
Steohan,
Schneider
Eric, Madersbacher
Stephan,
Thalmann
232 ASSOCIATION OF POLYMORPHISMS WITHIN ANDROGEN RECEPTOR-5aIfa-REDUCTASEAND PSA-GENES WITH PROSTATE VOLUME, CLINICAL PARAMETERS AND ENDOCRINE STATUS IN ELDERLY MEN
George,
Studer Urs
Madersbacher Stephan’, Schatzl Geo$, Gsur Andrea2, Haidinger Gerald’, Haitel Andrea’, Vutuc Christian*, Micksche Michael*, Marberger Michael’
Urology, Inselspital Bern, Beme Switzerland
‘University Austria
INTRODUCTION
& OBJECTIVES:
In obese
patients
the estrogen:
androgen ratio is increased. Serum estrogen levels also increase in men with age, absolutely
or relative
mammalian
to testosterone
levels.
species that develops BPH, estrogens
In the dog,
the only
induce experimentally
other BPH.
The goal of this study is to determine whether patients with a high BMI (kgm’) present a higher risk for developing MATERIAL
& METHODS:
survey for Switzerland
BPH independently
1992/93),
including
health
7930 men were used.
Means and percentiles of body weight, body height and BMI were calculated men of different (25.00-29.99).
Overweight
grade II ([email protected]),
were compared RESULTS:
age groups.
was defined as a BMI>25
and grade III (BMI=40.00)].
for
[grade I
These data
to 150 patients treated for BPH.
In all three age groups (group I: 45-54 years, group II: 55-64 years,
group III: 65+) BMI in patients treated for BPH is higher than in the general male population
Berne,
Switzerland,
*University
of Vienna,
Vienna,
INTRODUCTION & OBJECTIVES: Identification of genetic markers for the development of BPH would be a major step toward a comprehensive understanding of this diseases and for the design of clinical trials and chemopreventive stategies. The aim of this study was to assess the impact of polymorphisms of three important genes within the androgen pathway on prostate volume, clinical parameters and endocrine status in men.
of age.
Data from the first national representative
(conducted
of Berne,
(group I: p=O.179, group II: p=O.o08 and group III: p=O.O03;
MATERIAL & METHODS: Elderly men with lower urinary tract symptoms underwent clinical and endocrine workup. In parallel, polymorphisms within the Sa-reductase gene (SRD5A2 V89L and A49T), the androgen receptor gene (AR: number of CAG-repeats), and the PSA gene (A-G substitution at position 158) were determined by polymerase chain reaction and restriction-length polymorphism analysis using DNA from peripheral blood. RESULTS: 190 men (66.5+9.2 years of age) were analysed. The number of CAG-repeats within the AR and the PSA polymorphism revealed no relevant associations to clinical and endocrine parameters. Individuals carrying the mutated SRD5A2 A49T allele (5.3% of the total population) had significantly larger prostates (54+28: vs. 39+16), higher PSA levels (12.2 versus 4.3 ngiml) and a 35% reduction in prostatic stroma/epithelial cell ratio than those with the wild type genotype. Men with the mutated SRD5A2 V89L had lower testosterone serum levels.
overall p=O.OOl). CONCLUSIONS:
In our data, men treated for BPH have a significantly
BMI than the general consequence European
population
of the higher estrogen Urology
Supplements
in Switzerland.
Whether
higher
this is only a
: androgen ratio remains to be determined. 1 (2002) No. 1, pp. 60
CONCLUSIONS: In contrast to prostate cancer, polymorphisms within AR and PSA genes do not seem to be of relevance for benign prostatic hyperplasia. Polymorphisms within the Sa-reductase gene are interesting biomarkers in that individuals carrying the mutated A49T allele had larger prostates, higher PSA levels and lower S/E-cell ratios suggesting an increased 5a-reductase activity.