勃起功能障碍与血管内皮功能关系的研究进展

血管内皮功能在阴茎勃起过程中扮演了十分重要的角色,血管内皮功能障碍是ED的病理基础之一。测量肱动脉血流介导的血管扩张功能是目前血管内皮功能主要的评估方法。改善血管内皮功能的治疗能改善阴茎勃起功能。ED是心血管疾病的先兆,及早发现ED并给予适当治疗,在改善生活质量的同时有助于降低未来心血管疾病的风险。     

Endothelial Dysfunction and Atherosclerosis

There is increasing evidence that the vascular endothelium is an important functional component of the blood vessel wall, actively participating in normal vascular physiology as well as the pathogenesis of vascular diseases such as atherosclerosis. The localized modulation of vascular endothelium to a nonadaptive functional state can be termed endothelial dysfunction. This article provides a brief overview of the multiple vital functions of endothelium, and a working concept of endothelial dysfunction especially as it relates to atherosclerosis and its thrombotic complications.     

神经营养因子与糖尿病性勃起功能障碍

目前研究表明,神经营养因子在各类神经的发育、分化和再生过程中发挥了重要作用。局部神经营养因子的异常变化是糖尿病性周围神经病变的发病机制之一。糖尿病性勃起功能障碍发病原因众多,而其中重要的一点就是勃起神经的损伤。神经营养因子对于勃起神经损伤导致的勃起功能障碍有明确的治疗作用,最近发现其对糖尿病性勃起功能障碍实验动物也有类似效果。神经营养因子对治疗糖尿病性勃起功能障碍开辟了一条新的思路。     

Endocrine Crosstalk Between Muscle and Bone

The musculoskeletal system is a complex organ comprised of the skeletal bones, skeletal muscles, tendons, ligaments, cartilage, joints, and other connective tissue that physically and mechanically interact to provide animals and humans with the essential ability of locomotion. This mechanical interaction is undoubtedly essential for much of the diverse shape and forms observed in vertebrates and even in invertebrates with rudimentary musculoskeletal systems such as fish. It makes sense from a historical point of view that the mechanical theories of musculoskeletal development have had tremendous influence of our understanding of biology, because these relationships are clear and palpable. Less visible to the naked eye or even to the microscope is the biochemical interaction among the individual players of the musculoskeletal system. It was only in recent years that we have begun to appreciate that beyond this mechanical coupling of muscle and bones, these 2 tissues function at a higher level through crosstalk signaling mechanisms that are important for the function of the concomitant tissue. Our brief review attempts to present some of the key concepts of these new concepts and is outline to present muscles and bones as secretory/endocrine organs, the evidence for mutual genetic and tissue interactions, pathophysiological examples of crosstalk, and the exciting new directions for this promising field of research aimed at understanding the biochemical/molecular coupling of these 2 intimately associated tissues.     

Environmental Exposures—The Missing Link in Immune Responses After Transplantation

In transplantation, immunosuppression has been directed at controlling acute responses, but treatment of chronic rejection has been ineffective. It is possible that factors that have previously been unaccounted for, such as exposure to inhaled pollution, ultraviolet light, or loss of the normal equilibrium between the gut immune system and the outside environment may be responsible for shifting immune responses to an effector/inflammatory phenotype, which leads to loss of self‐tolerance and graft acceptance, and a shift towards autoimmunity and chronic rejection. Cells of the immune system are in a constant balance of effector response, regulation, and quiescence. Endogenous and exogenous signals can shift this balance through the aryl hydrocarbon receptor, which serves as a thermostat to modulate the response one way or the other, both at mucosal surfaces of interface organs to the outside environment, and in the internal milieu. Better understanding of this balance will identify a target for maintenance of self‐tolerance and continued graft acceptance in patients who have achieved a “steady state” after transplantation.     

Crosstalk Between Sensory Nerves and Cancer in Bone

Purpose of Review

Sensory nerves (SNs) richly innervate bone and are a component of bone microenvironment. Cancer metastasis in bone, which is under the control of the crosstalk with bone microenvironment, induces bone pain via excitation of SNs innervating bone. However, little is known whether excited SNs in turn affect bone metastasis.

Recent Findings

Cancer cells colonizing bone promote neo-neurogenesis of SNs and excite SNs via activation of the acid-sensing nociceptors by creating pathological acidosis in bone, evoking bone pain. Denervation of SNs or inhibition of SN excitation decreases bone pain and cancer progression and increases survival in preclinical models. Importantly, patients with cancers with increased SN innervation complain of cancer pain and show poor outcome.

Summary

SNs establish the crosstalk with cancer cells to contribute to bone pain and cancer progression in bone. Blockade of SN excitation may have not only analgesic effects on bone pain but also anti-cancer actions on bone metastases.

     

Albuminuria and Kidney Function Independently Predict Cardiovascular and Renal Outcomes in Diabetes

There are limited data regarding whether albuminuria and reduced estimated GFR (eGFR) are separate and independent risk factors for cardiovascular and renal events among individuals with type 2 diabetes. The Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) study examined the effects of routine BP lowering on adverse outcomes in type 2 diabetes. We investigated the effects of urinary albumin-to-creatinine ratio (UACR) and eGFR on the risk for cardiovascular and renal events in 10,640 patients with available data. During an average 4.3-yr follow-up, 938 (8.8%) patients experienced a cardiovascular event and 107 (1.0%) experienced a renal event. The multivariable-adjusted hazard ratio for cardiovascular events was 2.48 (95% confidence interval 1.74 to 3.52) for every 10-fold increase in baseline UACR and 2.20 (95% confidence interval 1.09 to 4.43) for every halving of baseline eGFR, after adjustment for regression dilution. There was no evidence of interaction between the effects of higher UACR and lower eGFR. Patients with both UACR >300 mg/g and eGFR <60 ml/min per 1.73 m² at baseline had a 3.2-fold higher risk for cardiovascular events and a 22.2-fold higher risk for renal events, compared with patients with neither of these risk factors. In conclusion, high albuminuria and low eGFR are independent risk factors for cardiovascular and renal events among patients with type 2 diabetes.Diabetes is a major global health problem, currently affecting an estimated 246 million people worldwide, with a doubling of this prevalence expected in the next 30 yr.¹ Compared with people without diabetes, affected individuals are at increased risk for both cardiovascular events and kidney disease.^2,3 Increased urinary albumin excretion (albuminuria) and reduced GFR both have been demonstrated to be risk factors for progressive kidney failure and cardiovascular disease.^4–9Guidelines therefore recommend the annual assessment of albuminuria and GFR, and this has become accepted as common practice.^10–13 Although both renal functional parameters are believed to be risk factors for cardiovascular events,^4–9 there are limited data as to whether these two factors are associated with adverse outcomes independent not only of other known cardiovascular risk factors but also of each other in people with type 2 diabetes.^14–19The BP-lowering arm of the Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) study recently reported that the routine administration of a fixed combination of the angiotensin-converting enzyme inhibitor perindopril and the diuretic indapamide to a broad cross-section of patients with type 2 diabetes reduced the risk for cardiovascular and kidney outcomes, regardless of initial BP level.²⁰ More recently, the glucose-lowering arm of ADVANCE reported that intensive glucose lowering based on gliclazide (modified release) reduced the risk for new or worsening nephropathy.²¹ Herein, we present the findings of observational analyses examining the association between albuminuria and GFR at baseline or during follow-up and the risk for cardiovascular events and renal events in type 2 diabetes.     

Cost-Effectiveness of Aliskiren in Type 2 Diabetes,Hypertension, and Albuminuria

The Aliskiren in the Evaluation of Proteinuria in Diabetes (AVOID) trial demonstrated that adding aliskiren, an oral direct renin inhibitor, at a dosage of 300 mg/d to the highest approved dosage of losartan and optimal antihypertensive therapy reduces albuminuria over 6 mo among patients with type 2 diabetes, hypertension, and albuminuria. The cost-effectiveness of this therapy, however, is unknown. Here, we used a Markov model to project progression to ESRD, life years, quality-adjusted life years, and lifetime costs for aliskiren plus losartan versus losartan. We used data from the AVOID study and the Irbesartan in Diabetic Nephropathy Trial (IDNT) to estimate probabilities of progression of renal disease. We estimated probabilities of mortality for ESRD and other comorbidities using data from the US Renal Data System, US Vital Statistics, and published studies. We based pharmacy costs on wholesale acquisition costs and based costs of ESRD and transplantation on data from the US Renal Data System. We found that adding aliskiren to losartan increased time free of ESRD, life expectancy, and quality-adjusted life expectancy by 0.1772, 0.1021, and 0.0967 yr, respectively. Total expected lifetime health care costs increased by $2952, reflecting the higher pharmacy costs of aliskiren and losartan ($7769), which were partially offset by savings in costs of ESRD ($4860). We estimated the cost-effectiveness of aliskiren to be $30,500 per quality-adjusted life year gained. In conclusion, adding aliskiren to losartan and optimal therapy in patients with type 2 diabetes, hypertension, and albuminuria may be cost-effective from a US health care system perspective.Recent clinical trials have shown that reductions in albuminuria with agents that inhibit the renin-angiotensin-aldosterone system (RAAS; e.g., angiotensin-converting enzyme inhibitors or angiotensin receptor blockers), as defined by a urinary albumin-creatinine ratio (UACR) or urinary albumin excretion rate (UAER), can delay progression of renal disease in patients with hypertension and type 2 diabetes.^1–5 Albuminuria is associated with fatal and nonfatal cardiovascular events and progression toward ESRD,^1,2,6 and reductions in albuminuria have been widely used as surrogate markers of renoprotection.^7,8The Aliskiren in the Evaluation of Proteinuria in Diabetes (AVOID) trial was a multicenter, randomized, double-blind study to assess the efficacy and safety of adding aliskiren, an oral direct renin inhibitor, at a dosage of 300 mg/d to the highest approved dosage of losartan (100 mg/d) and optimal antihypertensive therapy in patients with type 2 diabetes, hypertension, and albuminuria.⁹ At the end of 6 mo of follow-up, aliskiren 300 mg/d significantly reduced mean UACR by 20% (P = 0.0009) and overnight UAER by 18% versus placebo (P = 0.009). Although the AVOID trial demonstrated that adjunctive treatment with aliskiren 300 mg/d reduces albuminuria during 6 mo in these patients, it did not examine the potential long-term clinical and economic consequences of such treatment.The objective of this study was to evaluate, from the US health care system perspective, the potential cost-effectiveness of lifetime treatment with aliskiren 300 mg/d plus losartan 100 mg/d and optimal antihypertensive therapy (aliskiren plus losartan) versus lifetime treatment with losartan 100 mg/d and optimal antihypertensive therapy alone (losartan only) in patients with type 2 diabetes, hypertension, and albuminuria. We evaluated cost-effectiveness using a Markov model (Figure 1).¹⁰ The initial distribution of the population across disease states and probabilities of progression from microalbuminuria (MA) and early overt nephropathy (EON) to advanced overt nephropathy (AON) were from the AVOID trial (11Open in a separate windowFigure 1.Markov state transition model. Ovals represent health states. Patients are assumed to transition among states every 6 mo on the basis of transition probabilities in

The Link Between Benign Prostatic Hyperplasia and Inflammation

ContextBenign prostatic hyperplasia (BPH) is one of the most common diseases associated with the aging process in men, particularly men aged >50 yr, yet only a few predictive factors have been identified. In recent years, attention has focused on the role of prostatic inflammation in the pathogenesis and progression of BPH.ObjectiveThis article reviews recent findings related to the potential link between local and systemic inflammation and BPH.Evidence acquisitionIn March 2013, at the annual meeting of the European Association of Urology in Milan, Italy, a satellite symposium entitled “Benign Prostatic Hypertrophy (BPH) and Inflammation, from Lab to Clinic,” was held with the goal of reviewing the latest data relating to the link between inflammation and BPH. This paper is based on one of the presentations at this symposium. A structured PubMed literature search was performed, and emphasis was placed on results from the past 10 yr.Evidence synthesisBPH is characterized by progressive hyperplasia of stromal and glandular cells, and clinically it is defined by lower urinary tract symptoms. In recent years, there has been accumulating evidence linking prostatic inflammation with BPH. The inflammatory infiltrates observed in patients with BPH are composed primarily of chronically activated T-lymphocytes. Cytokines and growth factors released from inflammatory cells create a proinflammatory environment that may support the fibromuscular growth seen in BPH and may also be responsible for inducing a state of relative hypoxia as a result of the increased oxygen demand of the proliferating cells. A number of clinical studies have confirmed the presence of inflammatory infiltrate in men with BPH, and this infiltrate has been shown to be involved in the pathogenesis, clinical appearance, and progression of this disorder. There is evidence emerging that systemic inflammation may also play a role in BPH, since in men with metabolic syndrome there was a significant correlation between prostate diameter/volume and the number of metabolic syndrome components.ConclusionsIt is clear that a number of different mechanisms are involved in the development and progression of BPH. Prostatic inflammation is an important feature, since it appears to be involved in the pathogenesis, symptomatology, and progression of the disease.