Efficacy and Side Effects of Drugs Commonly Used for the Treatment of Lower Urinary Tract Symptoms Associated With Benign Prostatic Hyperplasia.

Benign prostatic hyperplasia (BPH) is the most common benign disease of the prostate gland and is caused by benign hyperplasia of the smooth muscle cells and stromal cells in this important gland. BPH is also the most common disease underlying lower urinary tract symptoms (LUTS). The incidence of BPH increases with age and affects more than half of all men 50 years or older. BPH mainly exerts effects on urinary function and can seriously reduce a patient's quality of life. At present, treatment for BPH aims primarily to improve the quality of life and reduce the risk of BPH-related complications. Pharmacological therapy is recommended for moderate-to-severe cases of LUTS that are suggestive of BPH. A range of drugs is currently available to treat this condition, including α1-adrenoceptor antagonists, 5α-reductase inhibitors (5-ARIs), phosphodiesterase type 5 inhibitors (PDE5Is), muscarinic receptor antagonists (MRAs), ß3-adrenoceptor agonists, and plant extracts. Of these, the most commonly used drugs in the clinic are α1-adrenoceptor antagonists, 5-ARIs, and combination therapy. However, these drugs exert their effects via various mechanisms and are associated with adverse reactions. The purpose of this review is to provide current comprehensive perspectives on the mechanisms of action, efficacy, and adverse reactions associated with the drugs most commonly used for the treatment of BPH.

[Expression and Clinical Significance of Late Endosomal/Lysosomal Adaptor,Mitogen-activated Protein Kinase and Mammalian Target of Rapamycin Activator 3 in Bladder Carcinoma].

Objective To investigate the expression and clinical significance of late endosomal/lysosomal adaptor,mitogen-activated protein kinase and mammalian target of rapamycin activator 3(LAMTOR3)in bladder carcinoma.Methods Oncomine and Expression Atlas were used to extract the useful mining gene chip database for analyzing the expression of LAMTOR3 in bladder carcinoma tissues and cell lines,and the correlation of LAMTOR3 with the clinicopathological features were analyzed.RT-PCR,Western blot,and immunohistochemistry were performed to detect the expression of LAMTOR3 in bladder carcinoma cell lines,specimens,and adjacent normal tissues for verifying the results exploited from the above databases.Results The Expression Atlas showed that LAMTOR3 had high expressions in Hs172.T,HT-1376,RT4,JMSU-1,and T24 cell lines among 20 bladder carcinoma cell lines,among which the LAMTOR3 expression was different.Oncomine reported that LAMTOR3 expression in bladder carcinoma,including invasive(t=2.857,P=0.005)and non-invasive carcinoma(t=3.105,P=0.003),was significantly higher than that in adjacent normal tissues.The expression of LAMTOR3 was positively correlated with pathological grade(P<0.05).The expressions of LAMTOR3 mRNA in bladder carcinoma cell lines,including UMUC3(t=10.84,P=0.0084),J82(t=21.75,P=0.0021),5637(t=45.88,P=0.0005),and T24(t=87.58,P=0.0001)were significantly higher than that in normal bladder cell line SV-HUC-1,while its expression in bladder carcinoma tissues was significantly higher than that in adjacent normal tissues(P<0.05),so was its protein level in tissues(P<0.05).Immunohistochemistry showed that LAMTOR3 protein was over-expressed in bladder carcinoma tissues;its level in invasive carcinoma tissues was higher than that in no-invasive carcinoma tissues and was related closely with the clinical stages(χ 2=9.189,P=0.002),pathological grades(χ 2=4.746,P=0.029),and lymphatic metastasis(χ 2=6.210,P=0.013)but had no significant correlation to sex(χ 2=0.965,P=0.326),age(χ 2=2.126,P=0.145),and distant metastasis(χ 2=1.261,P=0.261).Conclusion LAMTOR3 is highly expressed in bladder carcinoma cell lines and tissues and plays a key role in the development and progression of bladder carcinoma.

beta1-Adrenergic receptor polymorphisms influence the response to metoprolol monotherapy in patients with essential hypertension.

OBJECTIVES: The human beta(1)-adrenergic receptor, an important therapeutic target in cardiovascular diseases, has 2 common functional polymorphisms (Ser49Gly and Gly389Arg). Our study aimed to confirm that beta(1)-adrenergic receptor polymorphisms affect the blood pressure response to metoprolol monotherapy in the Chinese population with hypertension. METHODS: beta(1)-Adrenergic receptor genotype was determined by polymerase chain reaction-restriction fragment length polymorphism assay for 223 patients with essential hypertension. Sixty-one patients with certain beta(1)-adrenergic receptor diplotypes, 18 for 49Ser389Arg/49Ser389Arg, 15 for 49Ser389Arg/49Gly389Arg, 19 for 49Ser389Gly/49Gly389Arg, and 9 for 49Ser389Gly/49Ser389Gly, were selected from those 61 for measurement of the antihypertensive effect of metoprolol. Patients were given 25 mg metoprolol every 12 hours for 4 weeks. Heart rate and blood pressure were measured weekly for the duration of metoprolol therapy. RESULTS: The descent of systolic blood pressure after metoprolol administration was significantly different among genotype groups (10.4% +/- 4.0%, 2.8% +/- 4.7%, and 1.1% +/- 1.5% for Arg389Arg, Gly389Arg, and Gly389Gly patients, respectively; P < .001). We also found a similar difference in changes of diastolic blood pressure (6.1% +/- 4.3%, 2.2% +/- 4.2%, and 0.9% +/- 4.0%, respectively; P < .001) and mean arterial pressure (8.1% +/- 3.5%, 2.5% +/- 3.0%, and 1.0% +/- 2.5%, respectively; P > .001) for Arg389Arg, Gly389Arg, and Gly389Gly patients. Ser49Gly variance exhibited a smaller contribution to the antihypertensive effect of metoprolol. Systolic blood pressure decreased significantly in Ser49 homozygous patients compared with Ser49Gly patients (8.4% +/- 3.2% versus 5.3% +/- 5.2%, P = .047). There was a highly significant relationship between diplotype and blood pressure during treatment. Systolic blood pressure significantly decreased in 49Ser389Arg/49Ser389Arg (12.0% +/- 3.8%, P < .001) and 49Ser389Arg/49Gly389Arg (8.4% +/- 5.5%, P < .001) patients, with the decrease in the former being more pronounced (P = .023). We also found a significant decrease in diastolic blood pressure (6.5% +/- 4.7% versus 5.7% +/- 3.2%, respectively; both P < .001) and mean arterial pressure (8.8% +/- 3.2% versus 6.9% +/- 3.7%, respectively; both P < .001) in 49Ser389Arg/49Ser389Arg and 49Ser389Arg/49Gly389Arg patients. However, blood pressure did not change significantly in 49Ser389Gly/49Gly389Arg and 49Ser389Gly/49Ser389Gly patients (all P > .05). CONCLUSIONS: beta(1)-Adrenergic receptor polymorphism was associated with different blood pressure responses to metoprolol therapy in patients with essential hypertension. 49Ser389Arg/49Ser389Arg and 49Ser389Arg/49Gly389Arg patients were good responders to metoprolol therapy; 49Ser389Arg/49Ser389Arg patients had a larger systolic blood pressure reduction than 49Ser389Arg/49Gly389Arg patients did. 49Ser389Gly/49Gly389Arg and 49Ser389Gly/49Ser389Gly patients were nonresponders to metoprolol antihypertensive therapy.