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[The role of pharmacological preconditioning in renal ischemic and reperfusion injury].
Kostina, DA, Pokrovskaya, TG, Olefir, YV, Yavorskii, AN, Elagin, VV
Urologiia (Moscow, Russia : 1999). 2017;(5):139-144
Abstract
Renal ischemic and reperfusion injury resulting in acute renal failure is a multidisciplinary problem at the junction of pathophysiology, transplantology, urology, nephrology, cardiac surgery and pharmacology. One of renal protection strategies is using the phenomenon of preconditioning. Preconditioning is one of the ways to adopt a tissue to repeated short-term effects of damaging factors to induce an enhanced tolerance to the long period of hypoxia and/or ischemia. There are multiple cellular and molecular mechanisms of the renal protective effects of preconditioning stimuli, but the key effectors and signaling molecules are ATP-dependent potassium channels, nitric oxide synthase, nitric oxide, and mitochondrial pore. Contradictory data on the protective effect of ischemic preconditioning allow searching for approaches to pharmacological correction of ischemic and reperfusion injuries. The article provides data on possible ways of using erythropoietin, darbepoetin and phosphodiesterase 5 inhibitors.
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Evaluation and Management of Erectile Dysfunction in the Hypertensive Patient.
Patel, JP, Lee, EH, Mena-Hurtado, CI, Walker, CN
Current cardiology reports. 2017;(9):89
Abstract
PURPOSE OF REVIEW The prevalence of hypertension and erectile dysfunction has steadily increased, and greater than 40% of men with erectile dysfunction concurrently share a diagnosis of hypertension. The treatment of the patient with both diseases poses a clinical challenge as both are closely correlated and share multiple overlapping risk factors.To address the recognized knowledge gap among clinicians who care for these patients, we will review the current literature on the diagnosis and treatment of erectile dysfunction in the hypertensive patient and will provide recommendations for the management of this challenging patient population. RECENT FINDINGS The pharmacological treatment of hypertension may adversely affect sexual function, and certain treatments for erectile dysfunction are contraindicated or cautioned against with certain antihypertensive agents. In review of the literature, we find that the clinician should opt to use an angiotensin-receptor blocker followed by an angiotensin-converting enzyme inhibitor or calcium channel blocker for the treatment of hypertension in patients with erectile dysfunction. Other agents require careful consideration for adverse effects on sexual function. Men with erectile dysfunction should be assessed for cardiovascular fitness for sexual activity, and PDE-5 inhibitors remain the first-line treatment for erectile dysfunction.
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A Perspective on Middle-Aged and Older Men With Functional Hypogonadism: Focus on Holistic Management.
Grossmann, M, Matsumoto, AM
The Journal of clinical endocrinology and metabolism. 2017;(3):1067-1075
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Abstract
CONTEXT Middle-aged and older men (≥50 years), especially those who are obese and suffer from comorbidities, not uncommonly present with clinical features consistent with androgen deficiency and modestly reduced testosterone levels. Commonly, such men do not demonstrate anatomical hypothalamic-pituitary-testicular axis pathology but have functional hypogonadism that is potentially reversible. EVIDENCE ACQUISITION Literature review from 1970 to October 2016. EVIDENCE SYNTHESIS Although definitive randomized controlled trials are lacking, evidence suggests that in such men, lifestyle measures to achieve weight loss and optimization of comorbidities, including discontinuation of offending medications, lead to clinical improvement and a modest increase in testosterone. Also, androgen deficiency-like symptoms and end-organ deficits respond to targeted treatments (such as phosphodiesterase-5 inhibitors for erectile dysfunction) without evidence that hypogonadal men are refractory. Unfortunately, lifestyle interventions remain difficult and may be insufficient even if successful. Testosterone therapy should be considered primarily for men who have significant clinical features of androgen deficiency and unequivocally low testosterone levels. Testosterone should be initiated either concomitantly with a trial of lifestyle measures, or after such a trial fails, after a tailored diagnostic work-up, exclusion of contraindications, and appropriate counseling. CONCLUSIONS There is modest evidence that functional hypogonadism responds to lifestyle measures and optimization of comorbidities. If achievable, these interventions may have demonstrable health benefits beyond the potential for increasing testosterone levels. Therefore, treatment of underlying causes of functional hypogonadism and of symptoms should be used either as an initial or adjunctive approach to testosterone therapy.
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Recognizing and treating Raynaud phenomenon.
Thoelen, K, Maiers, K, Bondi, KA, Covino, J
JAAPA : official journal of the American Academy of Physician Assistants. 2015;(11):40-4
Abstract
Raynaud phenomenon is an episodic ischemia caused by cold, emotional stimuli, or rheumatologic disorders, and is more common in women than men. This article describes the clinical presentation of Raynaud phenomenon and how to diagnose and appropriately treat patients and prevent complications. Research on the use of different pharmacologic interventions for Raynaud phenomenon is ongoing and treatment options are expanding.
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Phosphodiesterase type 5 inhibitors and kidney disease.
Afsar, B, Ortiz, A, Covic, A, Gaipov, A, Esen, T, Goldsmith, D, Kanbay, M
International urology and nephrology. 2015;(9):1521-8
Abstract
Chronic kidney disease (CKD) represents a worldwide health problem. Traditionally, the nephroprotective treatment for CKD aims to slow progression to end-stage renal disease and includes dietary protein restriction, correction of metabolic acidosis, and renin-angiotensin system blockers. However, current standard therapeutic options may not be enough for preventing CKD progression in a subset of patients making necessary to develop novel therapeutic options to further slow renal function loss. Phosphodiesterase type 5 (PDE5) inhibitors represent a class of drugs traditionally used to treat erectile dysfunction and pulmonary hypertension. However, recent evidence suggests that PDE5 inhibitors may have additional therapeutic effects, such as cardioprotection and cerebrovascular protection. In the current review, we summarize PDE5 inhibitors' utility in disease states and clinical conditions related to kidney disease such as systemic hypertension and acute and chronic kidney injury and discuss the mechanisms explaining possible kidney protective roles of PDE5 inhibitors. A recently completed phase 2 trials demonstrated that the long-acting PDE5 inhibitor PF-00489791 decreased albuminuria in patients with overt diabetic nephropathy when added on top of renin-angiotensin system blockade.
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Advances in the pathophysiology and treatment of heart failure with preserved ejection fraction.
Tannenbaum, S, Sayer, GT
Current opinion in cardiology. 2015;(3):250-8
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PURPOSE OF REVIEW With the failure of multiple trials to identify a successful therapy for heart failure with preserved ejection fraction (HFpEF), attention has shifted to defining specific phenotypes within the HFpEF spectrum in an effort to develop a targeted approach to treatment. Here we summarize the most recent studies investigating the pathophysiology and clinical features of HFpEF, and discuss recent clinical trials in the context of developing treatments that look toward the underlying cause of this disorder. RECENT FINDINGS Advances in basic science and clinical research have further characterized HFpEF, identifying multiple pathophysiological mechanisms that ultimately lead to exercise intolerance and volume overload. The success of small studies focused on specific subsets of the HFpEF population has promoted the concept that there may not be one treatment strategy that can universally be applied to HFpEF. SUMMARY HFpEF is associated with significant morbidity and mortality and accounts for approximately half of patients with chronic heart failure. HFpEF is a complex disease, encompassing a diverse cohort of patients and marked by the presence of multiple etiological mechanisms. The failure to develop successful therapies for the management of HFpEF may be because of inadequate standardization of the HFpEF diagnosis, overly broad inclusion criteria and inadequate differentiation of disease subtypes. Given the heterogeneity among patients with HFpEF, much of the current research is focused on understanding of pathophysiology and identifying disease phenotypes that may respond to a targeted treatment approach. Several newer approaches, including neprilysin inhibition and device therapy, offer promise for a new era of HFpEF treatment.
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Pulmonary hypertension and pregnancy: an overview.
Gei, A, Montúfar-Rueda, C
Clinical obstetrics and gynecology. 2014;(4):806-26
Abstract
Pulmonary hypertension is a syndrome infrequently associated with pregnancy. Despite advancements in therapy during the past 25 years and encouraging reports of improved outcomes, pulmonary arterial hypertension remains a devastating disease with a significantly reduced lifespan. This disorder should still be considered a contraindication to pregnancy. The decision of a patient to continue the pregnancy should be supported by an empathetic group of health care professionals who would optimize their treatment and hopefully their pregnancy outcomes and survival after delivery. We overview here different aspects of the diagnosis, evaluation, management, and counseling of patients suffering from pulmonary hypertension during pregnancy.
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Testosterone supplementation and sexual function: a meta-analysis study.
Corona, G, Isidori, AM, Buvat, J, Aversa, A, Rastrelli, G, Hackett, G, Rochira, V, Sforza, A, Lenzi, A, Mannucci, E, et al
The journal of sexual medicine. 2014;(6):1577-92
Abstract
INTRODUCTION The role of testosterone supplementation (TS) as a treatment for male sexual dysfunction remains questionable. AIM: The aim of this study was to attempt a meta-analysis on the effect of TS on male sexual function and its synergism with the use of phosphodiesterase type 5 inhibitor (PDE5i). METHODS An extensive Medline, Embase, and Cochrane search was performed. MAIN OUTCOME MEASURES All randomized controlled trials (RCTs) comparing the effect of TS vs. placebo or the effect of TS as add on to PDE5is on sexual function were included. Data extraction was performed independently by two of the authors (A. M. Isidori and G. Corona), and conflicts resolved by the third investigator (M. Maggi). RESULTS Out of 1,702 retrieved articles, 41 were included in the study. In particular, 29 compared TS vs. placebo, whereas 12 trials evaluated the effect of TS as add on to PDE5is. TS is able to significantly ameliorate erectile function and to improve other aspects of male sexual response in hypogonadal patients. However, the presence of possible publication bias was detected. After applying "trim and fill" method, the positive effect of TS on erectile function and libido components retained significance only in RCTs partially or completely supported by pharmaceutical companies (confidence interval [0.04-0.53] and [0.12; 0.52], respectively). In addition, we also report that TS could be associated with an improvement in PDE5i outcome. These results were not confirmed in placebo-controlled studies. The majority of studies, however, included mixed eugonadal/hypogonadal subjects, thus imparting uncertainty to the statistical analyses. CONCLUSIONS TS plays positive effects on male sexual function in hypogonadal subjects. The role of TS is uncertain in men who are not clearly hypogonadal. The apparent difference between industry-supported and independent studies could depend on trial design more than on publication bias. New RCTs exploring the effect of TS in selected cases of PDE5i failure that persistently retain low testosterone levels are advisable.
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[Diastolic heart failure].
Wachter, R
Der Internist. 2014;(6):663-8
Abstract
BACKGROUND Heart failure with preserved ejection fraction (i.e. diastolic heart failure) accounts for about half of heart failure cases. The aim of this review is to reflect current knowledge regarding the epidemiology, pathophysiology and treatment. RESULTS Diastolic heart failure patients are principally elderly and predominantly female. Numerous pathophysiological alterations in this disease have been shown and recent therapeutic recommendations include control of cardiovascular risk factors and symptoms. New therapeutic options, such as inhibition of late sodium current, aldosterone receptor blockade, combined inhibition of AT1 receptor and the enzyme neprilysin, and phosphodiesterase 5 inhibition are discussed in this review and ongoing clinical trials are also briefly presented. CONCLUSION Diastolic heart failure remains a cardiac disease which is difficult to treat; however, new study results allow a better definition of a population of patients who could benefit from specific therapies.
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Current and advancing treatments for pulmonary arterial hypertension in childhood.
Zijlstra, WM, Ploegstra, MJ, Berger, RM
Expert review of respiratory medicine. 2014;(5):615-28
Abstract
Pulmonary arterial hypertension (PAH) is a severe and progressive intrinsic disease of the precapillary lung vasculature. Since the introduction of PAH-targeted drugs, survival of PAH patients seems to have improved. Randomized controlled trials have led to evidence-based guidelines to direct treatment in adults. However, since disease characteristics differ between adults and children, it is hazardous to simply extrapolate these guidelines to children. Moreover, pediatric data on treatment strategies and how to assess treatment response remain virtually absent. Optimal treatment strategies are highly needed to guide therapy and improve survival in children with PAH. This review provides an overview of currently available treatments for PAH and the limited efficacy and safety data in children (with the exclusion of perinatal pulmonary vascular diseases, as persistent pulmonary hypertension of the newborn). We also discuss potential treatment goals and how the available data can be translated into treatment strategies in pediatric PAH.