LUTS: Lower Urinary Tract Symptoms最新文献

Objectives: We investigated the efficacy of dutasteride add-on therapy to α-1 adrenoceptor antagonists in patients with benign prostate hyperplasia (BPH) in relation to the transitional zone index (TZI) and evaluated the cutoff value of TZI that predicted improvements of subjective symptoms at 6 months.

Methods: Male BPH patients with prostate volume (PV) ≥ 30 mL receiving dutasteride 0.5 mg/d for 6 months as add-on therapy along with α-1 adrenoceptor antagonists were enrolled. PV, transitional zone volume (TZV), TZI, International Prostate Symptom Score (IPSS), and uroflowmetry parameters before and at 6 months with dutasteride add-on treatment were evaluated.

Results: Eighty-three patients were included. The changes of total IPSS, IPSS voiding subscore, IPSS quality of life score, and voided volume were significantly correlated with TZI. Among baseline parameters, TZV and TZI were significantly associated with the changes of total IPSS in univariate analysis, and only TZI remained as an independent predictive factor for improving total IPSS in multivariate analysis (odds ratio -8.3, P = .048). The cutoff point of TZI for predicting an improvement of the total IPSS by 6 points or more was 0.67 (area under the curve 0.71, sensitivity 0.62, specificity 0.79).

Conclusions: A higher TZI was significantly associated with improvement of subjective symptoms but not uroflowmetric findings for BPH patients with 6 months of dutasteride add-on therapy along with α-1 adrenoceptor antagonists, and the predictive value of TZI for effective dutasteride add-on therapy was higher than 0.67. BPH patients using α-1 adrenoceptor antagonists with a TZI higher than 0.67 can be good candidates for add-on dutasteride therapy.

Objectives: Muscarinic M₃ (M₃ ) receptors mediate cholinergic smooth muscle contraction of the bladder. Current drugs targeting bladder M₃ receptors for micturition disorders have a risk of cholinergic side effects due to excessive receptor activation and insufficient selectivity. We investigated the effect of ASP8302, a novel positive allosteric modulator (PAM) of M₃ receptors, on bladder function in rats.

Methods: Modulation of carbachol-induced increases in intracellular Ca²⁺ was assessed in cells expressing rat muscarinic receptors. Potentiation of bladder contractions was evaluated using isolated rat bladder strips and by measuring intravesical pressure in anesthetized rats. Conscious cystometry was performed to investigate the effects on residual urine volume and voiding efficiency in rat voiding dysfunction models induced by the α₁ -adrenoceptor agonist midodrine and muscarinic receptor antagonist atropine, and bladder outlet obstruction. To assess potential side effects, the number of stools and tracheal insufflation pressure were measured in conscious and anesthetized rats, respectively.

Results: ASP8302 demonstrated PAM effects on the rat M₃ receptor in cell assays, and augmented cholinergic bladder contractions both in vivo and in vitro. ASP8302 improved voiding efficiency and reduced residual urine volume in two voiding dysfunction models as effectively as distigmine bromide, but unlike distigmine bromide did not affect the number of stools or tracheal insufflation pressure.

Conclusions: Our results in rats indicate that ASP8302 improves voiding dysfunction by potentiating bladder contraction with fewer effects on cholinergic responses in other organs, and suggest a potential advantage over current cholinomimetic drugs for treating micturition disorders caused by insufficient bladder contraction.

Objectives: The current study is designed to evaluate and compare the histological changes in the surgical samples of prostate taken from patients undergoing transurethral resection of prostate (TURP) for benign prostate hyperplasia (BPH) with different sizes.

Methods: Prostate surgical tissue samples were obtained from BPH patients undergoing TURP after taking informed consent. Ultrasound measure of prostatic weight and prostate-specific antigen (PSA) levels were obtained from the patients along with other clinical and demographic details. Tissue samples were fixed, processed, sectioned and stained with hematoxylin and eosin and Masson's trichrome to look for histological features, specifically smooth muscle proliferation. Immunohistochemical expression of bone morphogenetic protein (BMP)-2 was recorded to assess the calcification potential.

Results: Fifty-nine surgical samples were obtained from the patients of age range 50-90 years and body mass index (BMI) 15.6-33.3 kg/m² . The range of ultrasound measures of prostate weight was 20-137 g with PSA ranged 1.03-93.3 ng/mL. Patients with small-sized prostate had significant severe smooth muscle proliferation (P < .001). Prostate size/weight had significant positive association with BMI (P < 0.001, r = 0.543) and negative association with BMP-2 (P < 0.001, r = -0.654). Samples with severe smooth muscle proliferation were with increased BMP-2 expression (P < .001) and higher levels of PSA levels (P = 0.004). BMP-2 expression revealed positive significant association with PSA (P < .001, r = 0.432).

Conclusion: From this study we conclude that BPH patients with small-sized glands and high PSA levels have increased smooth muscle proliferation and calcification potential causing the symptoms of lower urinary tract symptoms in these patients.