Biomedical subjects

O R Hayek

Publications and source records attributed to O R Hayek.

8 recordsLinked to original sources

PubMed2000

Vascular endothelial growth factor-A expression in the rat ventral prostate gland and the early effects of castration.

BACKGROUND: Blood flow to the rat ventral prostate gland is drastically reduced during the very early period after castration, and this reduction coincides with the appearance of striking degenerative changes within the prostatic vascular system. These early effects on the prostate vascular system are likely to be important for the subsequent regression of the ventral prostate that occurs in response to castration. Since the endothelial cells of the ventral prostate do not express androgen receptor protein (AR), we proposed that these early effects might be indirectly mediated by changes in the local expression of vascular regulatory factors. In order to evaluate whether vascular endothelial growth factor-A (VEGF-A) might be among the primary mediators of these effects, we measured expression of VEGF-A mRNA and protein in the rat ventral prostate gland prior to and within the first 3 days after castration. METHODS: Ventral prostate tissues were obtained from control (unoperated) rats, sham-operated rats, or rats at sequential daily intervals (1-3 days) after castration. A quantitative RNase protection assay and a comparative RT-PCR assay were used to evaluate the extent to which the expression of VEGF-A mRNA in the ventral prostate was affected by castration. In situ immunohistochemistry, using an anti-VEGF-A antibody, was performed to localize VEGF-A protein in the various cells of the tissue. Western blot analysis and a quantitative ELISA assay using anti-VEGF-A antibodies were performed to determine how VEGF-A protein expression in the rat ventral prostate was affected by castration. RESULTS: Results of VEGF-A mRNA analysis in the rat ventral prostate gland during the first 3 days after castration showed a biphasic change characterized by a transient reduction of VEGF-A mRNA expression (by approximately 50%) on the second day after castration that was restored to higher than control levels by the third day after castration. Immunohistochemical analysis for VEGF-A in control and castrated ventral prostates showed that the prostatic epithelial and smooth muscle cells were the major source of VEGF-A expression in this tissue. Quantitative analysis of VEGF-A protein expression by Western blot and ELISA methods confirmed a biphasic change in the expression of the polypeptide that correlated well with the results of the mRNA analyses. CONCLUSIONS: VEGF-A expression in the ventral prostate gland of the Sprague-Dawley rat is downregulated on the second day after castration but returns to control levels by the third day after castration. Since critical changes in the ventral prostate vascular system are already evident by 1 day after castration, we believe that these findings indicate that VEGF-A is not likely to be the critical or sole mediator of the early effects of castration on the vascular system of the rat ventral prostate gland.

Androgens↗

PubMed2000

Acute increase in blood flow to the rat bladder subsequent to partial bladder outlet obstruction.

Partial obstruction of the rat bladder outlet initiates a multi-step process during which the bladder progressively loses its functional ability. The first step in this progression is bladder hypertrophy; the organ dramatically increases in size and weight to compensate for the effects of obstruction. Unoperated female rats, age-matched, sham-obstructed rats, and rats that received a partial bladder outlet obstruction were studied. During the first 24 hours after partial bladder outlet obstruction, relative bladder blood flow was measured using a fluorescent microsphere infusion technique and laser Doppler imaging. Nitric oxide synthase (NOS) activities of control and obstructed rat bladder tissues were determined using an enzymatic assay that measures the conversion of (3)H-L-arginine to (3)H-L-citrulline. Using the microsphere infusion technique, a significant increase in blood flow to the obstructed rat bladder was observed during the first 24 hours after partial bladder outlet obstruction. Relative bladder blood flow increased approximately sixfold at 4 and 6 hours post-obstruction and remained elevated through 24 hours of obstruction. Sham operations (evaluated after 6 hours after surgery) resulted in a minor increase in blood flow that did not reach statistical significance. Relative blood flow to the spleen, measured in the same rats, was not significantly changed. Laser Doppler measurements also identified a significant increase in rat bladder blood flow after outlet obstruction and showed that increased blood flow could be detected as early as 1 hour post-obstruction. Interestingly, despite the significant differences in bladder blood flow between control and early post-obstructed rat bladders, NOS activities of control and obstructed rat bladders were comparable. The increase in bladder blood flow precedes the urothelial, fibroblast and smooth muscle cell hyperplasia, and the smooth muscle hypertrophy that occurs after obstruction. We propose that, in response to surgical induction of partial outlet obstruction, acute up-regulation of bladder blood flow may be an initiating factor for subsequent bladder cell proliferation and smooth muscle hypertrophy. Neurourol. Urodynam. 19:195-208, 2000.

Animals↗

PubMed2000

Role of herbal compounds (PC-SPES) in hormone-refractory prostate cancer: two case reports.

PURPOSE: Herbal therapies are unconventional treatments that have been used for several different diseases. PC-SPES is an herbal mixture, composed of eight different herbs (chrysanthemum, isatis, licorice, Ganoderma lucidum, Panax pseudo-ginseng, Rabdosia rubescens, saw palmetto, and scutellaria), which has been used as an alternative in the treatment of prostate cancer. We report two cases of hormone-refractory prostate cancer patients, who showed a favorable response to therapy with this herbal combination, controlling the progression of the disease. METHODS: We report two cases of biopsy proven prostate cancer patients with metastatic disease, treated with total androgen blockade, progressing to an androgen-independent status. These patients were offered traditional therapies for hormone-resistant prostate cancer, and they chose to take PC-SPES. The follow-up as well as their evolution are described. RESULTS: PC-SPES extract decreased the prostate-specific antigen (PSA) value for both patients from an initial value of 100 and 386 ng/mL to 24 and 114 ng/mL after 1 year and 4 months, respectively, remaining stable until now. No gynecomastia or hot flashes were observed in these patients and the treatment was well tolerated. CONCLUSION: PC-SPES has shown a strong estrogenic in vitro and in vivo activity as an alternative tool in the management of prostate cancer patients. These cases suggest that PC-SPES might have some potential activity against hormone-independent prostate cancers.

Aged↗

PubMed2000

Hypertension is associated with severe erectile dysfunction.

PURPOSE: The prevalence and severity of erectile dysfunction in patients with hypertension need to be further evaluated. We evaluate medical and hypertension status, and erectile function in patients with hypertension. MATERIALS AND METHODS: The International Index of Erectile Function, which is a detailed questionnaire, including well established components to evaluate patient medical history, hypertension status and erectile dysfunction, was mailed to 476 male patients of the outpatient Hypertension Center of Columbia Presbyterian Medical Center. RESULTS: The questionnaire was completed by 104 (22.3%) patients, and mean age was 62.2 years (range 34 to 75). Of the patients 84.8% were sexually active and 68. 3% had various degrees of erectile dysfunction, which was mild in 7. 7%, moderate in 15.4% and severe in 45.2%. Compared to the general population of erectile dysfunction cases in the literature our study population with hypertension had a higher incidence of severe erectile dysfunction. Although correlations of antihypertensive medications with incidence of erectile dysfunction did not reach statistical significance, there was a clear trend with patients treated with diuretics and beta-blockers having the highest incidence and those treated with alpha-blockers having the lowest incidence of erectile dysfunction. CONCLUSIONS: In addition to the observation that erectile dysfunction is more prevalent in patients with hypertension than in an age matched general population, our study shows that it is more severe in those with hypertension than in the general population.

Adolescent↗

PubMed1999

The microvascular architecture of the rat vagina revealed by image analysis of vascular corrosion casts.

BACKGROUND: Female sexual dysfunction is a common but poorly understood human condition. One of the aspects hindering progress in this area is the lack of appropriate animal models that can be used to study the complex factors involved in this sexual health problem. Recently, attention has focused on the probable role of vascular dynamics of the genital organs and their potential for impact on female sexuality. The objective of this study was to provide a better description of the vascular anatomy of the female rat vagina and external genital organs in an attempt to better develop this as an animal model to study female sexual dysfunction. METHODS: Young female (nonestrous) virgin rats were anesthetized, the abdominal aorta was cannulated, and the distal vasculature was flushed and fixed in vivo for histological studies or for subsequent infusion with Mercox resin for vascular corrosion casting. Vascular corrosion casts of the external genitalia (vagina and vulva) were studied using a scanning electron microscope (SEM). Fixed tissue specimens were also embedded and sectioned for histochemical and immunohistochemical analysis. RESULTS: Scanning electron microscopy imaging allowed a description of the vascular and microvascular system of the nonestrous female rat genitalia. Major feeding vessels were located laterally in the muscular and serosal layers of the vagina with a complex system of interanastomosing collaterals between these large lateral trunks. The sub-epithelial region of the vaginal wall contains a dense and rich network of capillaries that perfuse the epithelium. These data were corroborated by two- dimensional histochemistry and immunostaining for endothelial and smooth muscle cells on paraffin-embedded thin sections of the female vagina and vulva. CONCLUSION: This study provides the first detailed three-dimensional en bloc view of the macro- and microvascular anatomy of the female rat vagina and vulva. The findings suggest an active interaction between the microvasculature and the epithelial cells of the vaginal wall. This study will provide the basic anatomic groundwork for future experiments on perturbations of the vascular system of the rat female genitalia in response to hormonal stimuli and various disease states.

Animals↗

PubMed1999

Effects of a phytotherapeutic agent, PC-SPES, on prostate cancer: a preliminary investigation on human cell lines and patients.

OBJECTIVES: To evaluate the in vitro activity of PC-SPES, a complex phytotherapeutic agent, against prostate cancer cell lines, and to assess its activity in suppressing serum prostate specific antigen (PSA) level in patients with prostate cancer. PATIENTS AND METHODS: Four variant prostate cancer cell lines (LNCaP and an apoptosis-resistant derivative, LNCaP-bcl-2, PC3 and DU145) were exposed to three different concentrations of PC-SPES extract. Cell viability was measured at 3, 4 and 5 days of exposure using a colorimetric assay and was compared with control cultures receiving aliquots of the ethanolic extraction medium alone. Clinically, a prospective study was initiated in patients with prostate cancer who refused conventional therapy or who had failed previous cryosurgery, radiation therapy and/or hormonal therapy. The patients were treated with PC-SPES (three capsules of 320 mg/day). The serum PSA responses and side-effects were evaluated. RESULTS: All cultured prostate cancer cell lines showed a significant dose-dependent reduction in cellular viability (compared with control cultures) by exposure to 4 and 6 microL of PC-SPES extract/mL of culture medium (P<0.001). In contrast to the hormone-insensitive cell lines tested (LNCaP-bcl-2, PC-3 and DU-145), only the hormone-sensitive cell line LNCaP was affected by the lowest dose of PC-SPES extract tested (2 microL/mL medium). In the prospective clinical trial of 33 patients, with a mean (range) follow-up of 6.8 (2-24) months after initiating PC-SPES therapy, serum PSA levels were lower in 87% at 2 months and in 78% at 6 months (n=18, P=0.026). The side-effects in these patients were nipple tenderness in two (6%) and leg clots requiring heparinization in two (6%). No gynaecomastia or hot flashes were observed in this group and the treatment was well tolerated. CONCLUSIONS: In this preliminary study, an extract of the phytotherapeutic agent PC-SPES was active in suppressing the growth of cultured hormone-sensitive and -insensitive prostate cancer cell lines. In the small clinical study, PC-SPES therapy decreased serum PSA levels in most patients. However, a longer follow-up and more patients will be required to evaluate the long-term efficacy of this new phytotherapy.

Aged↗

PubMed1999

The necessity of a second prostate biopsy cannot be predicted by PSA or PSA derivatives (density or free:total ratio) in men with prior negative prostatic biopsies.

Serum prostate specific antigen, prostate specific antigen density and free:total prostate specific antigen are known to be useful for determining the risk of prostate cancer in patients undergoing prostate cancer screening. The patient with a positive biopsy presents no future prostate specific antigen dilemma. Those with negative biopsies often go on to numerous repeat biopsies. Our goal was to establish criteria that could be used to identify patients who will require repeat prostate biopsies (possibly false negative initial biopsy), while not exposing the low risk population (probable true negative initial biopsy) to additional invasive procedures. Between March 1991 and March 1998, 148 patients who had a biopsy for an elevated prostate specific antigen value (4.1-10.0) or an altered digital rectal examination, had no cancer found in the specimen. From these, 51 (34.4%) had repeated biopsies, while the others persisted on close follow-up. We examined their serum prostate specific antigen, prostate specific antigen density and free:total prostate specific antigen value, as well as their age and histology results of the initial and repeat biopsy, to determine if any predictor of the need for a repeat biopsy could be identified. Eight (15.7%) from 51 men who had repeat biopsy had prostate cancer detected. Forty three (84.3%) patients persisted with a negative biopsy, despite filling the criteria for re-biopsy. Multivariate analysis failed to identify any significant predictors of prostate cancer in the repeat biopsy group. Despite initial success, the prostate specific antigen derivatives and free:total prostate specific antigen have not safely limited the number of biopsies performed for an abnormal prostate specific antigen (4.1-10.0). Neither prostate specific antigen density nor free:total prostate specific antigen predicted the need for repeat biopsy in this specific group. The results of this ongoing study demonstrate that to date, prostate specific antigen and prostate specific antigen derivatives can not be utilized to determine which patients will be at high risk for requiring repeat prostate biopsy. All patients must be closely monitored for evidence of a change in status from benign to malignant disease, and new markers for this purpose are urgently needed.

Aged↗

PubMed1999

Castration induces acute vasoconstriction of blood vessels in the rat prostate concomitant with a reduction of prostatic nitric oxide synthase activity.

PURPOSE: Previous studies demonstrating a rapid and drastic reduction of blood flow to the rat prostate gland resulting from castration caused us to consider the influence of castration on the state of vascular constriction and on the activity of the vascular tone-regulating factors (nitric oxide synthase and cyclic GMP) in the rat prostate. MATERIALS AND METHODS: Sections of ventral prostate glands obtained from intact and castrated rats were analyzed for the mean areas within smooth muscle-coated blood vessels using a computerized microscopic image analysis system. Nitric oxide synthase (NOS) levels were measured in prostatic extracts from unoperated or castrated rats using an enzyme assay system that measures conversion of 3H-L-arginine to citruline. Cyclic GMP levels were measured in prostatic extracts from unoperated or castrated rats using a competitive radioimmunoassay system. RESULTS: The mean area within ventral prostate smooth muscle-coated blood vessels was reduced 39% at 24 hours after castration (p = 0.039) and 47.7% at 48 hours after castration (p = 0.039). NOS activity measured in prostatic extracts was reduced 38% at 24 hours (p = 0.0012) and 51.6% at 36 hours after castration (p = 0.0001) compared with the control group of noncastrated rats. Finally, prostatic cGMP levels were reduced 55.8% (p = 0.0018) at 36 hours after castration when compared with controls rats. CONCLUSION: Within 24 hours after castration, the lumenal areas of smooth muscle-coated blood vessels in the rat prostate gland were found to be significantly reduced. This vasoconstriction was associated with a significant reduction of prostatic NOS activity as well as a reduction in the prostatic levels of the NOS co-factor, cGMP. Thus, acute vasoconstriction is a prominent early event associated with rat prostate regression in response to castration and likely contributes to the regression of the tissue.

Animals↗