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. 相似文献
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 Mn of 8.8 × 103?58.5 × 103 with a narrow molecular dispersity index (Mw/Mn = 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). 相似文献
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. 相似文献
To understand in situ behavior of osteocytes, we characterized a model of osteocytes in their native bone matrix and demonstrated real-time biologic activity of osteocytes while bending the bone matrix. Using 43 male Sprague-Dawley rats, dumbbell-shaped explants were harvested from stainless steel femoral implants after 6-12 weeks and incubated in culture medium or fixed. Sixteen specimens were used to determine bone volume density (BV/TV), volumetric bone mineral density (BMD) and histology for different implantation periods. Osteocyte viability was evaluated by L-lactate dehydrogenase (LDH) activity in 12 cultured explants. Confocal microscopy was used to assess tracer diffusion in three explants and changes in osteocyte pH of a mechanically loaded explant. From 6 to 12 weeks, explant BV/TV and volumetric BMD trended up 92.5% and 101%, respectively. They were significantly and highly correlated. Tissues were uniformly intramembranous and all bone cell types were present. Explants maintained LDH activity through culture day 8. Diffusion at 200 microM was limited to 1,209 Da. Explants appeared capable of reproducing complex bone biology. This model may be useful in understanding osteocyte mechanotransduction in the context of a physiologically relevant bone matrix. 相似文献
Summary Previous studies of Alcian blue-induced birefringence in adult avian cortical bone showed that a short period of intermittent
loading rapidly produces an increased level of orientation of proteoglycans within the bone tissue. In the absence of further
loading, this persists for over 24 hours. We have proposed that this phenomenon could provide a means for “capturing” the
effects of transient strains, and so provide a persistent, constantly updated strain-related influence on osteocyte populations
related to the bones' averaged recent strain history, in effect, a “strain memory” in bone tissue. In our present study, we
use the Alcian blue-induced birefringence technique to demonstrate that proteoglycan orientation also occurs after intermittent
loading of both cortical and cancellous mammalian bonein vivo andin vitro. We also show that the change in birefringence is proportional to the magnitude of the applied strain, and that the reorientation
occurs rapidly, reaching a maximal value after only 50 loading cycles. Examination of electron micrographs of bone tissue
after staining with cupromeronic blue allows direct visualization and quantification of the change in proteoglycan orientation
produced by loading. This shows that intermittent loading is associated with a realignment of the proteoglycan protein cores,
bringing them some 5 degrees closer to the direction of collagen fibrils in the bone matrix. 相似文献
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. 相似文献
Athletes participating in unilateral dominant sports are useful models for investigating skeletal responses to mechanical loading as they provide controlled evidence in the absence of completing a randomized controlled trial. Throwing athletes may be an additional model for this purpose as they overload their dominant upper extremity enabling the contralateral side to act as an internal control and load the bones of the upper extremity purely via the generation of internal (i.e. muscular) forces without superposition of externally applied loads (i.e. impact with an external object). The aim of this study was to investigate upper extremity bone adaptation in throwing athletes and explore factors that predict this adaptation. Two cohorts were recruited—male baseball players (throwers; n = 15) and matched controls (controls; n = 15). Each subject was assessed for shoulder range and strength, and upper extremity bone mass, structure and estimated strength. Throwers had substantially greater skeletal differences between their dominant and nondominant upper extremities than controls, indicating that throwing induces greater adaptation than induced by habitual loading of the dominant upper extremity. Bone adaptation in throwers was localized to the humerus, with the midshaft humerus in the dominant upper extremity of throwers having enhanced bone mass, structure and estimated strength. The largest effect was for estimated strength of the midshaft humerus which had 30% greater polar moment of inertia (IP) in throwers and suggests adaptation to resist torsional loads. The skeletal effect of throwing at the midshaft humerus was influenced by playing position with pitchers and catchers displaying greater dominant-to-nondominant differences than fielders, and was predicted by years throwing and dominant-to-nondominant difference in upper arm lean cross-sectional area. The latter two variables explained 67% of the variance in dominant-to-nondominant differences in IP. Collectively, these data indicate that throwing induces substantial adaptation within the midshaft humerus. Adaptation was primarily in the direction of torsion which is consistent with biomechanical and injury data suggesting throwing introduces high magnitude torsional forces. As the magnitude of adaptation in throwers was equivalent to that observed in athletes participating in other unilateral dominant sports, throwers represent an alternative model for investigating the skeletal effects of mechanical loading. 相似文献