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Test drugs were evaluated for their ability to alter the convulsant activity of pentylenetetrazol (PTZ) in young adult female rats, in pseudopregnant rats with prolonged exposure to high levels of progesterone (and its neurosteroid metabolites), and in pseudopregnant rats 24 h after acute withdrawal of neurosteroids by treatment with the 5alpha-reductase inhibitor finasteride. Test drugs were administered at doses equivalent to twice their ED50 values for protection against PTZ-induced clonic seizures in naive young adult female rats.
Tricyclic antidepressants and selective serotonin reuptake inhibitors are considered in theory to induce the outflow of neurotransmitters, norepinephrine, and serotonin from the synapses as a consequence of inhibiting their reuptake into the nerve terminals, resulting in the stimulation of glial cells surrounding the synapses in the brain. Then, we have investigated the direct actions of neurotransmitters on glial cell metabolism and function using rat C6 glioma cells as an in vitro model system and suggested that these neurotransmitters induce their differentiation probably through the production of 5alpha-reduced neurosteroids. On the other hand, the stimulation of the glioma cells with serotonin has been reported to enhance brain-derived neurotrophic factor (BDNF) gene expression, which may be closely related to the beneficial effects of antidepressant drugs. In the present study, to evaluate BDNF expression in differentiated glial cells, the glioma cells were pretreated with progesterone, and the effect of serotonin on BDNF messenger RNA levels in these cells was examined. Progesterone pretreatment enhanced the stimulatory action of serotonin on BDNF gene expression, and the enhancement of serotonin action observed in the cells pretreated with progesterone was almost completely abolished by finasteride, an inhibitor of the enzyme involved in the production of 5alpha-reduced neurosteroids. These findings propose the possibility that neurosteroid-mediated glial cell differentiation may result in the enhancement of serotonin-stimulated BDNF gene expression, which is considered to contribute to the survival, regeneration, and plasticity of neuronal cells in the brain, and hence, leading to the improvement of mood disorders and other symptoms in depressive patients.
1593 patients with prostate surgery (APS and RTU-P) during 6 years (1996-2001) were revised. APS 35%, RTU-P 65%. Revision of all pathological anatomy of surgical specimens and the evolutions of the patients with CPI.
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We describe 5 men with urinary retention and indwelling urethral catheters who were treated with repetitive prostatic massage, antimicrobials, alpha blockers, and--in 2 cases--finasteride. We retrospectively reviewed the charts of all patients presenting to the genitourinary clinic with indwelling urinary catheters during a 1-year period. Five men (mean age, 70 years; range, 64-76; SD 4.47) presented to the Manila Genitourinary Clinic (Cebu Branch), Cebu, Philippines, wearing indwelling urinary catheters placed for acute urinary retention. Urologists had told all 5 men that they needed to undergo transurethral resection of the prostate (TURP). The Cebu genitourinary physician removed the catheters, instituted repetitive prostatic massage, and diagnosed all 5 patients with prostatitis. All 5 patients received repetitive prostatic massage, alpha-blocker medication, and antibiotic therapy, whereas finasteride was given to 2 patients. During treatment, statistically significant improvements occurred in global symptom severity scores, urethral white blood cell (WBC) counts, WBC counts of the expressed prostatic secretions (EPS), EPS red blood cell (RBC) counts, urinary WBC counts, and urinary RBC counts. Fluorescing Chlamydia elementary bodies disappeared in 3 of the 4 positive patients by the end of treatment. (One patient was not available for retesting.) Repetitive prostatic massage, antimicrobial therapy, alpha-blocker therapy, and--in 2 cases--finasteride enabled catheter removal in all 5 men (100%) as well as successful urination in all 5 men (100%). TURP has been prevented for a mean of 2.53 years (range, 16-38 months).
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At 1 year after treatment, the prostate volume was reduced by 24.5% +/- 10.01% (P < .001) in group 1 and by 26.1% +/- 5.06% (P < .001) in group 2. One year after withdrawal of the 5ARIs, the prostate volume had increased by 20.7% +/- 14.1% (P < .001) and 18.6% +/- 7.4% (P < .001) in groups 1 and 2, respectively, compared with at the end of 1 year of treatment. Furthermore, the International Prostate Symptom Score had significantly deteriorated at 1 year after cessation of the 5ARIs in both groups compared with the values at the end of 1 year of combination therapy.
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Information was obtained from published scientific articles, IMS market analysis data and surveys among primary care practitioners and urologists.
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In phase 1 at 1 year prostate specific antigen had decreased by 2.4 ng/ml (-46.7%), and prostate volume had decreased 7.1 ml (-17.9%). Prostate cancer was detected in 27 of 97 (27.8%) patients and the mean minimum prostate specific antigen velocity from a nadir of 0.4 ng/ml was 0.6 ng/ml. In phase 2, 48 of 179 (26.8%) men underwent repeat biopsy at a mean of 14.6 months. Of these 48 men 26 (54.1%) were found to have prostate cancer. Of the 26 men in whom prostate cancer was detected 20 (76.9%) were found to have Gleason score 7 or greater disease.
Telomere-specific fluorescence in situ hybridization (FISH) analysis was performed in normal-appearing stromal, basal epithelial, and luminal epithelial cells in biopsies from men randomized to the placebo arm of the Prostate Cancer Prevention Trial. Prostate cancer cases (N = 32) were either detected on a biopsy performed for cause or at the end of the study per trial protocol, and controls (N = 50), defined as negative for cancer on an end-of-study biopsy performed per trial protocol (e.g., irrespective of indication), were sampled. Logistic regression was used to estimate the association between mean telomere length of the particular cell populations, cell-to-cell telomere length variability, and risk of prostate cancer.
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In our institution, surgery for BPH decreased by 17.6% in the decade, with patients having surgery when older, at a mean (sd) of 69.1 (8.57) vs 72.3 (7.59) years, i.e. 3.1 years older (P = 0.028), but with similar comorbidities. Reasons for surgery in 1992/2002, respectively, were AUR in 41/37%, and symptoms worsening in 48/51%. The few cases of haematuria and bladder stone were similarly distributed in both groups. Pharmacology for BPH was prescribed in 46% of patients in 1992, phytotherapy being the most common (89%), whereas in 2002, 82% (P < 0.01) were treated, most of them with alpha-adrenergic antagonists (79%). Open surgery was indicated in 18.8% of patients in 1992 (mean adenoma weight 73.8 g, sd 37.12) and in 28.6% in 2002 (79.8 g, sd 35.41; P = 0.625). The mean (sd) hospital stay was 8.9 (4.06) vs 5.0 (1.22) days in 1992 and 2002, respectively (P < 0.01) for transurethral resection, and 14.1 (5.74) vs 8.7 (4.83) for open adenectomy (P = 0.013). The complication rate was similar for both groups.
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A few women have asked me whether finasteride, taken by their partners for male pattern baldness, will affect their pregnancies. The product monograph is very alarming: it sounds as if even handling the medication could cause harm, especially to a male fetus. Should a man stop taking finasteride if his partner is planning pregnancy or is pregnant? What is the risk to the fetus if its mother accidentally handles crushed or broken tablets?
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Before using risk calculators users must consider the properties of the underlying populations and what are the included or unavailable risk factors, and compare these to the patient. When these prerequisites are disregarded, dissimilarities will result in grossly inaccurate predictions for individual patients.
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Secretions of chloride (Cl(-))- and bicarbonate (HCO3(-))-rich fluid by the seminal vesicles could involve cystic fibrosis transmembrane regulator (CFTR), which activity can be stimulated by cAMP generated from the reaction involving adenylate cyclase (AC). In this study, we investigated levels of CFTR, AC, and cAMP in the seminal vesicles under testosterone influence. Orchidectomized adult male rats received 7-day treatment with 125 or 250 μg/kg/day of testosterone with or without flutamide or finasteride. At the end of the treatment, animals were sacrificed and seminal vesicles were harvested for analyses of CFTR and AC protein expression level by Western blotting. Distribution of CFTR and AC in seminal vesicles was observed by immunohistochemistry. Levels of cAMP and dihydrotestosterone in seminal vesicle homogenates were measured by ELISA. Cystic fibrosis transmembrane regulator, AC, and cAMP levels increased with increasing doses of testosterone (P < 0.05 compared to nontreated orchidectomized rats). Cystic fibrosis transmembrane regulator and AC were expressed at the apical membrane of the epithelium lining the seminal vesicle lumen with higher expression levels observed in testosterone-treated rats than in non-treated orchidectomized rats (P < 0.05). The inhibitory effects of flutamide or finasteride on these parameters were greater in 250 μg/kg/day testosterone-treated rats than their effects in 125 μg/kg/day testosterone-treated rats. Higher dihydrotestosterone levels were observed in seminal vesicle homogenates after treatment with 250 μg/kg/day than with 125 μg/kg/day of testosterone (P < 0.05). Increased levels of CFTR, AC, and cAMP in seminal vesicles might contribute toward an increase in Cl(-) and HCO3(-) concentrations in the seminal fluid as reported under testosterone influence.
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The Proscar Long-term Efficacy and Safety Study (PLESS) was a 4-year study designed to evaluate the effects of finasteride versus placebo in men with lower urinary tract symptoms (LUTS), clinical evidence of BPH, and no evidence of prostate cancer. A self-administered questionnaire was employed to quantify LUTS at baseline. Receiver operating characteristics (ROC) curves were used to assess baseline characteristics from patients treated with placebo as predictors of outcomes. The characteristics assessed included the overall symptom score (Quasi-AUA SI), separate voiding and filling subscores, prostate volume (PV) and serum prostate-specific antigen (PSA) levels.
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Finasteride acts by blocking the conversion of testosterone to 5a-dihydrotestosterone, the active androgen metabolite in the human prostate. In large, double-blind, placebo-controlled phase III-studies recruiting over 1,600 patients, it was shown that the administration of Finasteride, either 5 or 1 mg a day, reduced the size of the prostate by a mean of 22%, following 6 months of therapy. Despite this reduction in prostate size, urinary flow rate only improved by a mean of 1.7 ml per second, and symptom score improved only marginally, but statistically significantly different from placebo. The future role for Finasteride therapy is emerging but it appears as if patients with mild to moderate symptoms would be a group who could benefit the most. Whether or not Finasteride can stop the long-term natural course of benign prostatic hyperplasia has still to be demonstrated.
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Previous studies have shown that male BRCA mutation carriers stand at increased risk of developing prostate cancer and have concerns about developing cancer. Genetic counseling practitioners often discuss strategies for reducing the risk of cancer for patients at high risk due to their genetic background. Addressing modifiable health habits is one such strategy. Unfortunately, modifiable risk factors for prostate cancer have only been documented in the general population and have not yet been studied in the BRCA carrier subpopulation. Therefore, this study aimed to identify modifiable risk factors for prostate cancer in BRCA carriers. We examined prostate cancer risk factors in 74 men who were part of families with a BRCA mutation. This study examined nine dichotomous variables including: exercise, history of vasectomy, smoking history, alcohol use, finasteride use, statin use, aspirin use, coffee use, and vitamin use. The survey was sent to all cases of prostate cancer in the Hereditary Cancer Center Database at Creighton University with a known BRCA status. This study confirmed the protective benefits of daily aspirin use, which have been observed in previous studies of the general population, and suggests its benefit in BRCA carriers. Protective benefits from regular vigorous exercise and daily coffee use trended towards significance, but neither factor withstood the Bonferroni Correction for multiple comparisons.
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This study assessed the preferences of urologists in the diagnosis and treatment of BPH, which will serve as an important reference for updating and improving China's current BPH clinical practice guideline.
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Levodopa (L-DOPA), the gold standard treatment for Parkinson's disease (PD), eventually causes L-DOPA-induced dyskinesia (LID) in up to 80% of patients. In the 6-hydroxydopamine (6-OHDA) rat model of PD, L-DOPA induces a similar phenomenon, which has been termed abnormal involuntary movement (AIM). We previously demonstrated that BMY-14802 suppresses AIM expression in this model.
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Long-term finasteride treatment (24 to 30 months) results in a marked involution of the prostate epithelium, which continues to progress for many months after clinical effects stabilize. The effect on the epithelium is similar in the peripheral and transition zones for both morphometric and volumetric changes. Progressive contraction of the prostate epithelium appears to constitute the underlying mechanism for sustained action of finasteride.
Serenoa repens extract is a popular phytotherapeutic agent in men with lower urinary tract symptoms. Although the exact mechanism of action is unknown, the agent is generally well accepted for its easy availability and good tolerability. This paper reviews the evidence of its efficacy in comparison with placebo, 5-alpha reductase inhibitor and alpha-1 adrenoreceptor antagonist.
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Finasteride, a 5alpha-reductase blocker, was administered for 3 days to female wild-type or delta knockout mice. Then, animals were tested in the elevated plus maze, following acute administration of THP, lorazepam, flumazenil, or 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), and results compared to vehicle-injected controls. CA1 hippocampal GABAR alpha4 subunit levels were assessed by Western blot.
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Our data demonstrate that the discontinuation of 5ARIs during combination therapy induces prostate regrowth, as well as aggravation of symptoms in men with BPH. This result, therefore, suggests that the life-long use of 5ARIs should be considered for the prevention of BPH progression.
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The Prostate Cancer Prevention Trial demonstrated that finasteride could reduce the incidence of prostate cancer by 25%. However, its use was also associated with an increased risk of high grade cancer resulting in uncertainty surrounding the net benefits of therapy.
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In this study, optimized freeze-dried finasteride nanoparticles (NPs) were prepared from drug nanosuspension formulation that was developed using the bottom-up technique. The effects of four formulation and processing variables that affect the particle size and solubility enhancement of the NPs were explored using the response surface optimization design. The optimized formulation was morphologically characterized using transmission electron microscopy (TEM). Physicochemical interaction among the studied components was investigated. Crystalline change was investigated using X-ray powder diffraction (XRPD). Crystal growth of the freeze-dried NPs was compared to the corresponding aqueous drug nanosuspension. Freeze-dried NPs formulation was subsequently loaded into hard gelatin capsules that were examined for in vitro dissolution and pharmacokinetic behavior. Results revealed that in most of the studied variables, some of the quadratic and interaction effects had a significant effect on the studied responses. TEM image illustrated homogeneity and shape of the prepared NPs. No interaction among components was noticed. XRPD confirmed crystalline state change in the optimized NPs. An enhancement in the dissolution rate of more than 2.5 times from capsules filled with optimum drug NPs, when compared to capsules filled with pure drug, was obtained. Crystal growth, due to Ostwald ripening phenomenon and positive Gibbs free energy, was reduced following lyophilization of the nanosuspension formulation. Pharmacokinetic parameters from drug NPs were superior to that of pure drug and drug microparticles. In conclusion, freeze-dried NPs based on drug nanosuspension formulation is a successful technique in enhancing stability, solubility, and in vitro dissolution of poorly water-soluble drugs with possible impact on the drug bioavailability.
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To evaluate patients willingness to share the costs of 2 medications (often described as "lifestyle medications"): sildenafil for erectile dysfunction and finasteride for hair loss, which are not routinely covered by the Department of Veterans Affairs (VA) healthcare system.
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We searched the literature for recently published articles discussing new treatment options as well as mechanisms involved in alopecia. We discuss the use of stem cells, growth factors, cellular pathways and robotic hair transplant, among other emerging therapies used for alopecia.
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These questions were investigated in a case-control study nested within the prostate cancer prevention trial (PCPT) with 1,798 biopsy-proven prostate cancer cases and 1,798 matched controls.
The relative risk (RR) of a crushing error occurring in the postintervention period compared to the preintervention period. A crushing error was defined as the crushing of a medication considered unsuitable to be crushed based on standard reference sources. Data were collected using direct (disguised) observation of nurses during drug administration.