Suramin protects from cisplatin-induced acute kidney injury.

Cisplatin, a commonly used cancer chemotherapeutic, has a dose-limiting side effect of nephrotoxicity. Approximately 30% of patients administered cisplatin suffer from kidney injury, and there are limited treatment options for the treatment of cisplatin-induced kidney injury. Suramin, which is Federal Drug Administration-approved for the treatment of trypanosomiasis, improves kidney function after various forms of kidney injury in rodent models.

Mitochondrial Biogenesis as a Pharmacological Target: A New Approach to Acute and Chronic Diseases.

Mitochondrial dysfunction is a key pathophysiological component of many acute and chronic diseases. Maintenance of mitochondrial homeostasis through the balance of mitochondrial turnover, fission and fusion, and generation of new mitochondria via mitochondrial biogenesis is critical for tissue health. Pharmacological activation of mitochondrial biogenesis can enhance oxidative metabolism and tissue bioenergetics, and improve organ function in conditions characterized by mitochondrial dysfunction.

Comparing LCZ696 with enalapril according to baseline risk using the MAGGIC and EMPHASIS-HF risk scores: an analysis of mortality and morbidity in PARADIGM-HF.

Background: Although most patients in the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial had mild symptoms, there is a poor correlation between reported functional limitation and prognosis in heart failure.

Objectives: The aim of this study was to examine the spectrum of risk in PARADIGM-HF and the effect of LCZ696 across that spectrum.

Methods: This study analyzed rates of the primary composite outcome of cardiovascular death or heart failure hospitalization, its components, and all-cause mortality using the MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure) and EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) risk scores to categorize patients.

Interrelation Between Oxidative Stress and Complement Activation in Models of Age-Related Macular Degeneration.

Millions of individuals older than 50-years suffer from age-related macular degeneration (AMD). Associated with this multifactorial disease are polymorphisms of complement factor genes and a main environmental risk factor-oxidative stress. Until now the linkage between these risk factors for AMD has not been fully understood.

Characterization of subgroups of heart failure patients with preserved ejection fraction with possible implications for prognosis and treatment response.

Background: Patients with heart failure and preserved ejection fraction (HFpEF) have a poor prognosis, and no therapies have been proven to improve outcomes. It has been proposed that heart failure, including HFpEF, represents overlapping syndromes that may have different prognoses. We present an exploratory study of patients enrolled in the Irbesartan in Heart Failure with Preserved Ejection Fraction Study (I-PRESERVE) using latent class analysis (LCA) with validation using the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM)-Preserved study to identify HFpEF subgroups.

Efficacy and safety of LCZ696 (sacubitril-valsartan) according to age: insights from PARADIGM-HF.

Background: The age at which heart failure develops varies widely between countries and drug tolerance and outcomes also vary by age. We have examined the efficacy and safety of LCZ696 according to age in the Prospective comparison of angiotensin receptor neprilysin inhibitor with angiotensin converting enzyme inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure trial (PARADIGM-HF).

Methods: In PARADIGM-HF, 8399 patients aged 18-96 years and in New York Heart Association functional class II-IV with an LVEF ≤40% were randomized to either enalapril or LCZ696.

The cpk model of recessive PKD shows glutamine dependence associated with the production of the oncometabolite 2-hydroxyglutarate.

Since polycystic kidney disease (PKD) was first noted over 30 years ago to have neoplastic parallels, there has been a resurgent interest in elucidating neoplasia-relevant pathways in PKD. Taking a nontargeted metabolomics approach in the B6(Cg)-Cys1(cpk/)J (cpk) mouse model of recessive PKD, we have now characterized metabolic reprogramming in these tissues, leading to a glutamine-dependent TCA cycle shunt toward total 2-hydroxyglutarate (2-HG) production in cpk compared with B6 wild-type kidney tissue. After confirmation of increased 2-HG expression in immortalized collecting duct cpk cells as well as in human autosomal recessive PKD tissue using targeted analysis, we show that the increase in 2-HG is likely due to glutamine-sourced α-ketoglutarate.

Effect of the angiotensin-receptor-neprilysin inhibitor LCZ696 compared with enalapril on mode of death in heart failure patients.

Aims: The angiotensin-receptor-neprilysin inhibitor (ARNI) LCZ696 reduced cardiovascular deaths and all-cause mortality compared with enalapril in patients with chronic heart failure in the prospective comparison of ARNI with an Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial. To more completely understand the components of this mortality benefit, we examined the effect of LCZ696 on mode of death.

Methods And Results: PARADIGM-HF was a prospective, double-blind, randomized trial in 8399 patients with chronic heart failure, New York Heart Association Class II-IV symptoms, and left ventricular ejection fraction ≤40% receiving guideline-recommended medical therapy and followed for a median of 27 months.

Identification and Characterization of the Androgen Receptor From the American Alligator, Alligator mississippiensis.

Androgens are essential for the development, reproduction, and health throughout the life span of vertebrates, particularly during the initiation and maintenance of male sexual characteristics. Androgen signaling is mediated by the androgen receptor (AR), a member of the steroid nuclear receptor superfamily. Mounting evidence suggests that environmental factors, such as exogenous hormones or contaminants that mimic hormones, can disrupt endocrine signaling and function.

Assessment of appropriate antibiotic prescribing for urinary tract infections in an internal medicine clinic.

Objectives: Urinary tract infections (UTIs) are one of the most common infections encountered in ambulatory care and inpatient settings. Although these infections are common, not all patients are prescribed an appropriate antibiotic or duration of therapy. The primary objective of this analysis was to evaluate the appropriateness of antibiotic selection and duration of therapy for patients in an adult internal medicine clinic diagnosed as having a UTI.

Induction of hyaluronan production by oncogenic KSHV and the contribution to viral pathogenesis in AIDS patients.

Kaposi sarcoma-associated herpesvirus (KSHV) is the etiologic agent for Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL), malignancies arising primarily in immunocompromised patients particularly AIDS-patients, which still lack effective therapy. Hyaluronan (HA) is a large glucuronic acid and has been found closely related to multiple functions in cancer cells, although its role in viral oncogenesis remains largely unknown. Here we provide first evidence that KSHV de novo infection induces HA production from primary endothelial cells through upregulation of HA synthase gene 1 (Has1) and a multifunctional glycoprotein, CD147.

Left ventricular layer function in hypertension assessed by myocardial strain rate using novel one-beat real-time three-dimensional speckle tracking echocardiography with high volume rates.

We recently developed novel software to measure phasic strain rate (SR) using automated one-beat real-time three-dimensional speckle tracking echocardiography (3D-STE) with high volume rates. We tested the hypothesis that left ventricular (LV) systolic function and relaxation analyzed by SR with the novel 3D-STE in hypertension (HTN) with hypertrophy may be impaired in the endocardium before there is LV systolic dysfunction. We measured LV longitudinal, radial and circumferential SR in patients with HTN (n=80, 69±7 years) and age-matched normotensive controls (n= 60, 69±10 years) using 3D-STE.

A novel ultrasound predictor of pulmonary capillary wedge pressure assessed by the combination of left atrial volume and function: A speckle tracking echocardiography study.

Background: We hypothesized that a development of a novel index based on the combination of left atrial volume (LAV) and left atrial (LA) function evaluated by the time-LA volume curve using speckle tracking echocardiography (STE) would be accurate and useful to estimate pulmonary capillary wedge pressure (PCWP). Our goal was to develop a novel index of PCWP based on a combination of LAV and LA function using STE.

Methods: A cross-validation study was performed with the patients divided into a training study to define the novel index (n=50) and a testing study to validate the index (n=196).

One-year results of simultaneous laser in situ keratomileusis and small-aperture corneal inlay implantation for hyperopic presbyopia: comparison by age.

Purpose: To compare by age the safety, efficacy, and patient satisfaction after simultaneous laser in situ keratomileusis (LASIK) and small-aperture corneal inlay implantation (Kamra) for hyperopic presbyopia.

Setting: Shinagawa LASIK Center, Tokyo, Japan.

Design: Retrospective comparative cohort study.

Angiotensin receptor neprilysin inhibition compared with enalapril on the risk of clinical progression in surviving patients with heart failure.

Background: Clinical trials in heart failure have focused on the improvement in symptoms or decreases in the risk of death and other cardiovascular events. Little is known about the effect of drugs on the risk of clinical deterioration in surviving patients.

Methods And Results: We compared the angiotensin-neprilysin inhibitor LCZ696 (400 mg daily) with the angiotensin-converting enzyme inhibitor enalapril (20 mg daily) in 8399 patients with heart failure and reduced ejection fraction in a double-blind trial.

Evidence for a time-dependent association between FOLR1 expression and survival from ovarian carcinoma: implications for clinical testing. An Ovarian Tumour Tissue Analysis consortium study.

Background: Folate receptor 1 (FOLR1) is expressed in the majority of ovarian carcinomas (OvCa), making it an attractive target for therapy. However, clinical trials testing anti-FOLR1 therapies in OvCa show mixed results and require better understanding of the prognostic relevance of FOLR1 expression. We conducted a large study evaluating FOLR1 expression with survival in different histological types of OvCa.

Hypertension in the United States, 1999 to 2012: progress toward Healthy People 2020 goals.

Background: To reduce the cardiovascular disease burden, Healthy People 2020 established US hypertension goals for adults to (1) decrease the prevalence to 26.9% and (2) raise treatment to 69.5% and control to 61.

Angiotensin-neprilysin inhibition versus enalapril in heart failure.

Background: We compared the angiotensin receptor-neprilysin inhibitor LCZ696 with enalapril in patients who had heart failure with a reduced ejection fraction. In previous studies, enalapril improved survival in such patients.

Methods: In this double-blind trial, we randomly assigned 8442 patients with class II, III, or IV heart failure and an ejection fraction of 40% or less to receive either LCZ696 (at a dose of 200 mg twice daily) or enalapril (at a dose of 10 mg twice daily), in addition to recommended therapy.

The natural history of left ventricular geometry in the community: clinical correlates and prognostic significance of change in LV geometric pattern.

Objectives: This study sought to evaluate pattern and clinical correlates of change in left ventricular (LV) geometry over a 4-year period in the community; it also assessed whether the pattern of change in LV geometry over 4 years predicts incident cardiovascular disease (CVD), including myocardial infarction, heart failure, and cardiovascular death, during an additional subsequent follow-up period.

Background: It is unclear how LV geometric patterns change over time and whether changes in LV geometry have prognostic significance.

Methods: This study evaluated 4,492 observations (2,604 unique Framingham Heart Study participants attending consecutive examinations) to categorize LV geometry at baseline and after 4 years.

The role of PTSD in adjudicating violent crimes.

PTSD was formalized as a diagnosis by the American Psychiatric Association in 1980 with the publication of the Diagnostic and Statistical Manual of Mental Disorders (DSM), 3rd edition. Since that time, the diagnosis has been widely utilized in the courts including the use in criminal proceedings. PTSD may play a role in the assessment of violent crimes both as a possible contributing factor in the perpetrators as well as a consequence in the victims.

Evidence for pericyte origin of TSC-associated renal angiomyolipomas and implications for angiotensin receptor inhibition therapy.

Nearly all patients with tuberous sclerosis complex (TSC) develop renal angiomyolipomas, although the tumor cell of origin is unknown. We observed decreased renal angiomyolipoma development in patients with TSC2- polycystic kidney disease 1 deletion syndrome and hypertension that were treated from an early age with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers compared with patients who did not receive this therapy. TSC-associated renal angiomyolipomas expressed ANG II type 1 receptors, platelet-derived growth factor receptor-β, desmin, α-smooth muscle actin, and VEGF receptor 2 but did not express the adipocyte marker S100 or the endothelial marker CD31.

Randomized, double-blind, placebo-controlled study of sitaxsentan to improve impaired exercise tolerance in patients with heart failure and a preserved ejection fraction.

Objectives: The purpose of this study was to evaluate the efficacy and safety of the selective endothelin type A (ETA) receptor antagonist sitaxsentan in patients who have heart failure with preserved ejection fraction (HFpEF).

Background: Fifty percent of heart failure (HF) patients have a preserved ejection fraction. No treatment has been shown to improve their clinical outcomes.