benzofurans and Prostatic-Hyperplasia

We investigated the benefits of the BK. Castration was performed by bilateral orchiectomy under ketamine anesthesia. A rat model of BPH was established by daily intramuscular administration of testosterone propionate plus 17β-estradiol for 8 weeks. Model rats were administered combinations of 20 mg/kg LDD175, 0.01 mg/kg tamsulosin and 1 mg/kg finasteride once daily by oral gavage for 4 weeks from week 6 to 9 post-surgery. Intraurethral pressure induced by electrostimulation of the hypogastric nerve was measured at the end of administration. Body and genitourinary organ weights were recorded, serums were assayed for hormone concentrations, and tissues were subjected to histopathology, and analyses of α1-adrenoceptor mRNA and protein expression levels after treatment.. Combined LDD175, tamsulosin, and finasteride significantly decreased prostatic index, serum hormone levels, epithelial thickness, and prostate expression of α1-adrenoceptors in BPH model rats. The 3-drug combination was more effective than any other combination or LDD175 alone.. These results suggest that LDD175 addition to tamsulosin and finasteride may be beneficial for the treatment of BPH patients who do not respond to tamsulosin plus finasteride.

Topics: Administration, Oral; Animals; Benzofurans; Disease Models, Animal; Drug Therapy, Combination; Finasteride; Indoles; Male; Prostatic Hyperplasia; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, alpha-1; Sulfonamides; Tamsulosin; Testosterone

To investigate the effect of 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid, a new benzofuroindole derivative, on the intraurethral pressure in a rat model of benign prostatic hyperplasia.. Benign prostatic hyperplasia was induced by testosterone and 17β-estradiol, which were administered intramuscularly once a day for 12 weeks. The effects of 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid and tamsulosin on the intraurethral pressure induced by the electrostimulation of hypogastric nerves after a single intravenous injection of 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid (10 mg/kg) or tamsulosin (10 μg/kg) were evaluated in a benign prostatic hyperplasia model. The electrostimulation-induced intraurethral pressure was measured just before and after the injection of 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid. Bodyweight and genitourinary organ weights were recorded, and serums and tissues were subjected to hormone assays and histopathology. In addition, the expression of α1-adrenoceptors in the prostate was measured by western blotting.. The benign prostatic hyperplasia groups showed increased prostatic index, increased concentrations of testosterone, free testosterone and estradiol in serum, and increased epithelial thickness of the prostate. An injection of 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid or tamsulosin significantly inhibited the elevation of electrostimulation-induced intraurethral pressure. In addition, 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid did not cause a significant change in the blood pressure compared with tamsulosin. While the benign prostatic hyperplasia group showed increased the expression of α1-adrenoceptors, the 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid or tamsulosin injection into a rat model of benign prostatic hyperplasia decreased the expression of α1-adrenoceptors.. These findings show that 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid might be beneficial for lowering the intraurethral pressure associated with benign prostatic hyperplasia, and it could represent a therapeutic option for benign prostatic hyperplasia patients.

Topics: Animals; Benzofurans; Disease Models, Animal; Electric Stimulation; Estradiol; Humans; Indoles; Male; Pressure; Prostatic Hyperplasia; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, alpha-1; Sulfonamides; Tamsulosin; Urethra

Patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) often present with voiding and storage symptoms, which may require combination therapy with an alpha blocker and an antimuscarinic (AM). This study compared treatment persistence in LUTS/BPH patients on alpha blocker monotherapy with those using combination alpha blocker and AM therapy (AB/AM).. Retrospective analysis of anonymized patient longitudinal prescription reimbursement claims data. All patients who had claims for any of four alpha blocker medications and six AM agents during an index period from April 1, 2011 to March 31, 2012 were included. For the combination therapy group, the effect of adherence with the AM medication on persistence to the alpha blocker was examined.. Patients on AB/AM combination therapy remained on alpha blockers for longer than those on alpha blocker monotherapy (p = 0.04); 92.4% were persistent at 3 months versus 89.0%, and at 1 year 50.8% were persistent versus 49.6%, respectively. The highest number of days on therapy was reported for tamsulosin plus solifenacin. As confirmed by multivariate analysis, patients with the highest adherence to AM medication (= 80%) persisted on alpha blockers for longer than those with the lowest (< 50%) adherence (p < 0.05).. Patients taking an AM in combination with an alpha blocker showed greater persistence with alpha blocker treatment over a 1 year period. When an AM is combined with an alpha blocker in patients with LUTS/BPH, the additional medication burden does not have a negative impact on persistence and may even improve it.

Topics: Administrative Claims, Healthcare; Adrenergic alpha-Antagonists; Aged; Benzofurans; Doxazosin; Drug Therapy, Combination; Humans; Longitudinal Studies; Male; Mandelic Acids; Medication Adherence; Middle Aged; Muscarinic Antagonists; Ontario; Prazosin; Prostatic Hyperplasia; Prostatism; Pyrrolidines; Quinazolines; Retrospective Studies; Solifenacin Succinate; Sulfonamides; Tamsulosin; Tolterodine Tartrate

A nation-wide questionnaire survey on the past history of diseases and symptoms was conducted in 2005. The questionnaire was administered by mail to the 1258 registered Yusho patients, inguiring about the past incidence of 15 regions of malignant neoplasm, 42 diseases, and 5 symptoms. Out of the 717 patients responded to the questionnaire, 34 patients born after the Yusho outbreak were excluded, leaving 683 patients as the study subjects. Their mean age (SD) was 62.7 (14.0) years, ranging from 39 to 97 years old. Seven percent of the patients acknowledged the past history of malignant neoplasm in one or more regions. More than 40% admitted the past history of dental diseases, pain of joints, numbness of limbs, fatigue, headache, cough and sputum. Osteoporosis and myoma of the uterus, respectively, were reported by 22.8% and 15.6% of women. 14.2% of men reported prostatic hypertrophy. Logistic regression analysis was performed to estimate the association of the past history of diseases with the blood lipid level of 2,3,4,7,8-pentachlorodibenzofuran adjusting for sex and age. In the whole study subjects, 306 patients were measured the PeCDF level once or more in the years from 2001 to 2005. We found statistically significant elevation of the proportion of the patients with the past history of prostatic hypertrophy with increasing blood lipid level of 2,3,4,7,8-PeCDF (P = 0.03). The marginally significant positive association between the proportion of the patients with the past history of hypertension and 2,3,4,7,8-PeCDF was observed (P = 0.06).

Topics: Adult; Aged; Aged, 80 and over; Benzofurans; Biomarkers; Comorbidity; Female; Food Contamination; Humans; Incidence; Japan; Lipids; Logistic Models; Male; Medical History Taking; Middle Aged; Neoplasms; Oryza; Plant Oils; Polychlorinated Biphenyls; Prostatic Hyperplasia; Stomatognathic Diseases; Surveys and Questionnaires