Tadalafil for the treatment of benign prostatic hyperplasia

Introduction: In men, lower urinary tract symptoms (LUTS) are primarily attributed to benign prostatic hyperplasia (BPH). Therapeutic options are targeted to relax prostate smooth muscle and/or reduce prostate enlargement.

Areas covered: This article reviews the major preclinical and clinical data on PDE5 inhibitors with a specific focus on tadalafil. It includes details of the role of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) – PDE5 pathway in the LUT organs (bladder and prostate) in addition to the available data on tadalafil in patients with LUTS secondary to BPH with or without erectile dysfunction (ED).

Expert opinion: Preclinical and clinical data have clearly demonstrated that PDE5 inhibitors induce bladder and prostate relaxation, which contributes to the improvement seen in storage symptoms in both animal models of bladder and prostate hypercontractility. Tadalafil is effective both as a monotherapy and add-on therapy in patients with LUTS secondary to BPH. Furthermore, as LUTS-BPH and ED are urological disorders that commonly coexist in aging men, tadalafil is more advantageous than α1-adrenoceptors and should be used as the first option. Tadalafil is a safe and tolerable therapy and unlike α1- adrenoceptors and 5-alpha reductase inhibitors, which can cause sexual dysfunctions, tadalafil improves sexual function.     

Direct Observation of a Cyclic Vinyl Polymer Prepared by Anionic Polymerization using N‐Heterocyclic Carbene and Subsequent Ring‐Closure without Highly Diluted Conditions

A 1:1 adduct of methyl sorbate (MS) and 1,3‐di‐tert‐butylimidazol‐2‐ylidene (NHCtBu) initiates anionic polymerization of a nonconjugated polar alkene, allyl methacrylate (AMA) in toluene at ?20 °C. After the monomer is consumed quantitatively using a bulky aluminum Lewis acid, methylaluminum bis(2,6‐di‐tert‐butyl‐4‐methylphenoxide) (MAD), as an additive, successive ring‐closure occurs without highly dilute conditions to give a cyclic poly(AMA) containing α‐terminal MS unit, and an M_n of 8.8 × 10³?58.5 × 10³ with a narrow molecular dispersity index (M_w/M_n = 1.1₄–1.3₇). The lack of a need for dilution is due to the fact that an α‐terminal NHCtBu group is acting as the counter cation for the propagating center in the polymerization. From ¹H NMR and matrix assisted laser desorption/ionization (MALDI‐TOF) mass spectra, combined with transmittance electron microscope (TEM) observation of a synthesized poly(AMA) with longer alkyl side chains prepared via a thiol‐ene click reaction, it is concluded that once the monomer is consumed, nucleophilic attack at the neighboring methine of the α‐terminal NHCtBu residue by the propagating anionic center causes ring‐closing to cyclic poly(AMA).     

Classification and cyclic fatigue evaluation of new kinematics for endodontic instruments

This study evaluated the effect of new motions of the motor TriAuto ZX2 on the cyclic fatigue of endodontic instruments. Vortex Blue 35.06 instruments were divided into four groups (n = 10) and tested for fatigue in a curved artificial canal (90° and 2 mm radius) using the following motions: continuous rotation (CR), Optimum Torque Reverse (OTR) set at 180° and the Optimum Glide Path (OGP), which was tested at 90° and 240°. The time to fracture (TTF) and the lengths of the fractured fragments were recorded. The mean TTF was significantly different among the groups (anova , P < 0.05): OGP 90° (213.39 ± 27.45), OTR 180° (121.24 ± 17.03), OGP 240° (45.24 ± 5.61) and CR (8.43 ± 1.27). Weibull analysis confirmed the shortest life expectancy for CR and the longest survival for OGP at 90°. The resistance to fatigue was affected by motions and pre‐set angles. The proprietary movements that are currently available for endodontic instruments were classified according to their kinematics.     

Heterodetic bicyclic decapeptide cyclo (Glu1 -Leu2 -Pro3-Gly4-Ser5-Ile6-Pro7-Ala8) cyclo-(1γ-5β) Phe9-Gly10

Bycyclic peptides are useful model molecules that can mimic the constrained local folding of a great number of natural peptides and proteins, such as ionophoric peptides, enzyme active site, and ligand-receptor active site. The synthesis of the bicyclic title compound with the liquid phase method is described with experimental details. Of particular interest is the heterodetic closure of the second ring. The peptide showed a complexing activity with metal cations like Ba²⁺, Ca²⁺, and Mg²⁺ . The free bicyclic peptide conformation in solution has been studied by means of NMR spectroscopy and a plausible structure model worked out with model building on NMR constraints is proposed.     

心先安佐治小儿病毒性心肌炎临床疗效分析

目的:分析心先安佐治小儿病毒性心肌炎的临床疗效。方法:136例病毒性心肌炎患儿随机分为治疗组及对照组,在相同的 基础治疗条件下,治疗组应用心先安2～5mg kg,加液静滴,每天2次。结果:心先安组;痊愈51例(75%),好转12例(17.65%),无效5例(7. 35%),总有效92.65%。对照组痊愈41例(60.29%),好转14例(20.59%),无效13例(19.12%),总有效80.88%。两组相比、差异有显著性 (x2=4.09,P<0.005)。结论:心先安治疗小儿病毒性心肌炎疗效确切,且安全、可靠。     

The participation of adenosine receptors in the adenosine 5''-triphosphate-induced relaxation in the isolated rabbit corpus cavernosum penis

AIM: To investigate the participation of adenosine receptors in the adenosine 5'-triphosphate (ATP)-induced relaxation in the corpus cavernosum penis (CCP) of rabbits. METHODS: The ATP-induced relaxation was assessed on the noradrenaline precontracted CCP of rabbits in the presence and absence of 8-(3-chlorostyryl)caffeine (CSC); an adenosine A(2A) receptor antagonist; alloxazine and MRS1754; adenosine A(2B) receptor antagonists; and ARL67156, an inhibitor of ecto-nucleoside triphosphate diphosphohydrolases. RESULTS: Adenosine and ATP relaxed the noradrenaline precontracted CCP of rabbits in a concentration-dependent manner. The adenosine- and ATP-induced relaxations were suppressed by alloxazine and MRS1754, but not by 8-(3-chlorostyryl)caffeine. ARL67156 potentiated the ATP-induced relaxation but not the adenosine-induced one. MRS1754 suppressed the ATP-induced relaxation potentiated by ARL67156. CONCLUSIONS: The above results suggest that, in the CCP of rabbits, the adenosine receptor mediating adenosine-induced relaxation is of the A(2B) receptor and the ATP directly causes relaxation through the A(2B) receptor on the CCP.     

Alteration of Human Placental Vascular Tone by Antiarrhythmic Medications In Vitro

Antiarrhythmic and Placental Vessels. Introduction : Antiarrhythmic medications are commonly used during pregnancy for treatment of maternal or fetal arrhythmias, but little is known about their effect on human placental vascular tone and, consequently, placental blood flow. The objective of this study was to evaluate the tone responses caused by antiarrhythmic medications in human placental vessels from normal term pregnancies in vitro.
Methods and Results : Isolated human placental arteries and veins from uncomplicated term pregnancies incubated in Krebs'-bicarbonate under 5% oxygen/5% carbon dioxide/balance nitrogen (PO₂ 35 to 38 torr) were exposed to cumulative doses of quinidine, procainamide, lidocaine, flecainide, propranolol, amiodarone, verapamil, digoxin, and adenosine after submaximal contraction with 5-hydroxytryptamine. The study was conducted both in the presence and absence of endothelium. The addition of the tested medications caused a significant, dose-dependent relaxation of human placental arteries and veins except for adenosine, which induced a sustained, dose-dependent contraction of human placental vessels regardless of the presence or absence of tone. Removal of the endothelium did not alter these responses.
Conclusions : Based on these results, the medications tested should have no decremental effect on placental blood flow, with the possible exception of adenosine, which causes significant. dosedependent contraction of human placental vessels in vitro. Should similar contraction be present in vivo, it may have an adverse effect on the fetus when administering adenosine to pregnant women at term or during labor.     

Chronic opioid treatment of neuroblastoma X dorsal root ganglion neuron hybrid F11 cells results in elevated GM1 ganglioside and cyclic adenosine monophosphate levels and onset of naloxone-evoked decreases in membrane K+ currents

Prolongation of the action potential duration of dorsal root ganglion (DRG) neurons by low (nM) concentrations of opioids occurs through activation of excitatory opioid receptors that are positively coupled via G_s regulatory protein to adenylate cyclase. Previous results suggested GM1 ganglioside to have an essential role in regulating this excitatory response, but not the inhibitory (APD-shortening) response to higher (μM) opioid concentrations. Furthermore, it was proposed that synthesis of GM1 is upregulated by prolonged activation of excitatory opioid receptor functions. To explore this possibility we have utilized cultures of hybrid F11 cells to carry out closely correlated electrophysiological and biochemical analyses of the effects of chronic opioid treatment on a homogeneous population of clonal cells which express many functions characteristic of DRG neurons. We show that chronic opioid exposure of F11 cells does, in fact, result in elevated levels of GM1 as well as cyclic adenosine monophosphate (AMP), concomitant with the onset of opioid excitatory supersensitivity as manifested by naloxone-evoked decreases in voltage-dependent membrane K⁺ currents. Such elevation of GM1 would be expected to enhance the efficacy of excitatory opioid receptor activation of the G_s/adenylate cyclase/cyclic AMP system, thereby providing a positive feedback mechanism that may account for the remarkable supersensitivity of chronic opioid-treated neurons to the excitatory effects of opioid agonists as well as antagonists. These in vitro findings may provide novel insights into the mechanisms underlying naloxone-precipitated withdrawal syndromes and opioid-induced hyperalgesia after chronic opiatf addiction in vivo. © 1995 Wiley-Liss, Inc.     

三磷酸腺苷-氯化镁冷稀释血停搏液的实验研究及临床应用

用液体闪烁计数法测定离体再灌注兔心肌线粒体内４５Ｃａ２＋的放射性强度．观察三磷酸腺苷－氯化镁冷稀释血停搏液和冷稀释血停搏液对缺血再灌注兔心肌线粒体内４５Ｃａ２＋的影响．结果表明，在３０ｍｉｎ以内使用冷稀释血停搏液组兔心肌线粒体内４５Ｃａ２＋放射性强度高于三磷酸腺苷－氯化镁冷稀释血停搏液组（Ｐ＜０．０５），而６０ｍｉｎ时冷稀释血停搏液组的放射性强度稍高或接近于三磷酸腺苷－氯化镁冷稀释血停搏液组，差异无显著性（Ｐ＞０．０５）．在２７例心内直视手术中使用三磷酸腺苷－氯化镁冷稀释血停搏液均获良好效果．