Statin, testosterone and phosphodiesterase 5-inhibitor treatments and age related mortality in diabetes

AIM To determine how statins, testosterone(T) replacement therapy(TRT) and phosphodiesterase 5-inhibitors(PDE5I) influence age related mortality in diabetic men.METHODS We studied 857 diabetic men screened for the BLAST study, stratifying them(mean follow-up = 3.8 years) into:(1) Normal T levels/untreated(total T > 12 nmol/L and free T > 0.25 nmol/L), Low T/untreated and Low T/treated;(2) PDE5I/untreated and PDE5I/treated; and(3) statin/untreated and statin/treated groups. The relationship between age and mortality, alone and with T/TRT, statin and PDE5 I treatment was studied using logistic regression. Mortality probability and 95%CI were calculated from the above models for each individual. RESULTS Age was associated with mortality(logistic regression, OR = 1.10, 95%CI: 1.08-1.13, P < 0.001). With all factors included, age(OR = 1.08, 95%CI: 1.06-1.11, P < 0.001), Low T/treated(OR = 0.38, 95%CI: 0.15-0.92, P = 0.033), PDE5I/treated(OR = 0.17, 95%CI: 0.053-0.56, P = 0.004) and statin/treated(OR = 0.59, 95%CI: 0.36-0.97, P = 0.038) were associated with lower mortality. Age related mortality was as described by Gompertz, r2 = 0.881 when Ln(mortality) was plotted against age. The probability of mortality and 95%CI(from logistic regression) of individuals, treated/untreated with the drugs, alone and in combination was plotted against age. Overlap of 95%CI lines was evident with statins and TRT. No overlap was evident with PDE5 I alone and with statins and TRT, this suggesting a change in the relationship between age and mortality. CONCLUSION We show that statins, PDE5 I and TRT reduce mortality in diabetes. PDE5 I, alone and with the other treatments significantly alter age related mortality in diabetic men.

The use of antimuscarinics,phosphodiesterase type Ⅴ inhibitors and phytotherapy for lower urinary tract symptoms in men

Besides the mainstay of α-blockers and 5α-reductase inhibitors,other forms of medical therapy complete the armamentarium in the treatment of lower urinary tract symptoms(LUTS)in men.These treatments can target specific symptoms as well as associated symptoms that would affect the quality of life of the patients.Many patients are bothered by storage symptoms,more so than the voiding symptoms.Antimuscarinics are efficacious and safe,provided the patients do not have high post void residual urine.Many patients with LUTS also have erectile dysfunction,and phosphodiesterase type Ⅴ inhibitors are effective in relieving both LUTS as well as erectile dysfunction for such patients.Phytotherapy provides a popular and safe treatment for LUTS,however,the efficacy of the treatment has not been proven in well conducted prospective randomized controlled studies.

Effect of phosphodiesterase inhibitors in the bladder

Many aging men will experience lower urinary tract symptoms(LUTS).Phosphodiesterase type 5(PDE5)inhibitors have shown promise in treating LUTS in these patients.PDE5 inhibitors mediate their effects through several pathways including cAMP,NO/cGMP,Kchannel modulated pathways,and the L-cysteine/H2S pathway.PDE5 inhibitors exert their effect in muscle cells,nerve fibers,and interstitial cells(ICs).The use of PDE5 inhibitors led to improvement in LUTS.This included urodynamic parameters.PDE5 inhibitors may play a significant role in LUTS due to their effect on the bladder rather than the prostate.

Isolation and identification of an isomeric sildenafil analogue as an adulterant in an instant coffee premix

The proliferation of adulterated health foods and beverages in the market demands a comprehensive analytical strategy to identify the adulterants,particularly those of isomeric phosphodiesterase 5(PDE5)inhibitors.An instant coffee premix(ICP)purchased from an online retailer was flagged for suspected adulteration through PDE5 inhibition assay.The ICP was then analysed using suspected-target and non-targeted screenings of a liquid chromatography-quadrupole time-of-flight mass spectrometry.Based on these findings,a PDE5 inhibitor initially assigned as compound X was isolated from the ICP by employing a liquid chromatography-diode array detection before its structural elucidation with liquid chromatography-ultraviolet(LC-UV)spectroscopy and nuclear magnetic resonance(NMR)spectroscopy.The suspected-target screening matched the protonated molecule([MþH]þ)precursor ion of compound X at m/z 499.2310 with two suspected analytes that are structural isomers of one another.The fragmentation patterns of compound X were comparable to those analogues in the dithiocarbodenafil group through the non-targeted screening.These findings,complemented by the LC-UV and NMR spectroscopy data,together with the chromatographic separation of related structural isomers,conclude the identity of compound X.To our best knowledge,this is the first study to report the presence of 3,5-dimethylpiperazinyl-dithiodesmethylcarbodenafil in an ICP sample.

Activation of the cGMP/protein kinase G system in breast cancer by the dopamine receptor-1

Despite recent advances in the detection and treatment of breast cancer,many shortcomings remain,providing incentives to search for new therapeutic targets.This review provides information on the expression and actions of dopamine receptor-1(D1R)in breast cancer.D1R is overexpressed in a significant number of primary breast tumors,characterized by having an aggressive phenotype and predicting a shorter survival time for patients.Activation of D1R in breast cancer cells by selective agonists caused suppression of cell viability,stimulation of apoptosis,inhibition of cell invasion,and an increase in chemosensitivity.Instead of being linked to the cAMP/PKA system as expected,D1R in breast cancer is linked to the activation of the cGMP/protein kinase G(PKG)pathway.Fenoldopam,a peripheral D1R agonist that does not penetrate the brain,dramatically suppressed the growth of breast cancer xenografts in immune-deficient mice.A new imaging system for detecting D1R-expressing tumors and metastases was also developed.The review offers a novel concept that D1R can serve as a biomarker for prognosis in advanced breast cancer and its agonists can be used as effective and personalized therapeutics in a subpopulation of patients with D1R-expressing breast tumors.Several drugs,some of which are FDA-approved,that bypass the D1R and directly activate the cGMP/PKG apoptotic system,are also identified.

Effects of obstructive sleep apnea and its treatment over the erectile function： a systematic review

可勃起的机能障碍(编辑) 与大量病原学被认为一个条件。妨碍的睡觉呼吸暂停(OSA ) 症候群是为我们打算在在 OSA 和性缺陷之间的关系上总结当前的证据的编辑的更小的学习风险因素之一，集中于以提供给 OSA 病人的不同治疗的可勃起的功能的结果。系统的评论被进行，选择与 OSA 和编辑的生理学有关的文章，并且到在可勃起、性的功能的 OSA 症候群和他们的报导结果的治疗。在 OSA 组的编辑的更高的流行被出版了。然而，可勃起的功能上的这效果是否发生在 OSA 严厉的全部范围，仍然保持不清楚。几个假设被建议解释这个协会的生理学。为有编辑的 OSA 病人的治疗在大多数研究在性参数完成了有意义的改进的连续积极航线压力。需求上的 Phosphodiesterase 类型 5 禁止者(iPDE5 ) 作为为在病人的这亚群的编辑的治疗有用，与高满足率。为证实的 OSA 的外科的治疗用 mandible 的前进设备在治疗的性满足上在可勃起的功能，和效果上受益仍然是未定义的。