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https://www.readbyqxmd.com/read/28790111/amiloride-an-old-diuretic-drug-is-a-potential-therapeutic-agent-for-multiple-myeloma
#1
Elizabeta Rojas, Luis Corchete, Laura San Segundo, Juan F Martínez-Blanch, Francisco M Codoñer, Teresa Paíno, Noemi Puig, Ramón García-Sanz, Maria Victoria Mateos, Enrique M Ocio, Irena Misiewicz-Krzeminska, Norma C Gutiérrez
<br />The search for new drugs that control the continuous relapses of multiple myeloma is still required. Here, we report for the first time the potent anti-myeloma activity of amiloride, an old potassium-sparing diuretic approved for the treatment of hypertension and edema due to heart failure.<br /><br />Experimental Design:  <p>Myeloma cell lines and primary samples were used to evaluate cytotoxicity of amiloride. In vivo studies were carried out in a xenograft mouse model. The mechanisms of action were investigated using RNA-Seq, qRT-PCR, immunoblotting and immunofluorescence assays...
August 8, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28768320/effects-of-sodium-glucose-cotransporter-2-inhibitors-for-the-treatment-of-patients-with-heart-failure-proposal-of-a-novel-mechanism-of-action
#2
Milton Packer, Stefan D Anker, Javed Butler, Gerasimos Filippatos, Faiez Zannad
Importance: Only 1 class of glucose-lowering agents-sodium-glucose cotransporter 2 (SGLT2) inhibitors-has been reported to decrease the risk of cardiovascular events primarily by reducing the risk of the development or progression of heart failure. In a landmark trial called Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes [EMPA-REG Outcomes], long-term treatment with empagliflozin prevented fatal and nonfatal heart failure events but did not reduce the risk of myocardial infarction or stroke in diabetic patients...
August 2, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/28763342/apparent-resistant-hypertension-and-the-risk-of-vascular-events-and-mortality-in-patients-with-manifest-vascular-disease
#3
Nicolette G C van der Sande, Esther de Beus, Michiel L Bots, Michiel Voskuil, Peter J Blankestijn, Frank Visseren, Wilko Spiering
OBJECTIVE: Patients with apparent resistant hypertension (aRH) are at increased risk for developing cardiovascular disease. It is unknown if this condition is related to increased cardiovascular risk in patients with clinically manifest vascular disease. METHODS: In 6191 hypertensive patients with clinically manifest vascular disease, we evaluated the risk of subsequent vascular events and mortality between patients with controlled hypertension, uncontrolled hypertension, controlled aRH, and uncontrolled aRH...
July 29, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28748888/childhood-idiopathic-steroid-resistant-nephrotic-syndrome-at-a-single-center-in-khartoum
#4
El-Tigani M A Ali, Hanna F K Makki, Mohamed B Abdelraheem, Salwa O Makke, Rashid A Allidir
Prevalence, clinicopathological features, and outcome of childhood idiopathic steroid-resistant nephrotic syndrome (ISRNS) vary in different countries. We report on these parameters in a single center in Khartoum. We retrospectively reviewed all the records of children with idiopathic nephrotic syndrome (INS) followed up in the pediatric renal unit, Soba Hospital, Khartoum between 2001 and 2012. ISRNS was defined as no remission within four weeks of daily prednisolone at a dose of 60 mg/m2. In 430 children with INS 130 (28%) had SRNS with a mean age of 7...
July 2017: Saudi Journal of Kidney Diseases and Transplantation
https://www.readbyqxmd.com/read/28739647/compensatory-distal-reabsorption-drives-diuretic-resistance-in-human-heart-failure
#5
Veena S Rao, Noah Planavsky, Jennifer S Hanberg, Tariq Ahmad, Meredith A Brisco-Bacik, Francis P Wilson, Daniel Jacoby, Michael Chen, W H Wilson Tang, David Z I Cherney, David H Ellison, Jeffrey M Testani
Understanding the tubular location of diuretic resistance (DR) in heart failure (HF) is critical to developing targeted treatment strategies. Rodents chronically administered loop diuretics develop DR due to compensatory distal tubular sodium reabsorption, but whether this translates to human DR is unknown. We studied consecutive patients with HF (n=128) receiving treatment with loop diuretics at the Yale Transitional Care Center. We measured the fractional excretion of lithium (FELi), the gold standard for in vivo assessment of proximal tubular and loop of Henle sodium handling, to assess sodium exit after loop diuretic administration and FENa to assess the net sodium excreted into the urine...
July 24, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28733448/pathophysiology-of-cardiorenal-syndrome-in-patients-with-heart-failure-potential-therapeutic-targets
#6
Hiroyuki Takahama, Masafumi Kitakaze
Despite the development of pharmacological inventions and new non-pharamacological techniques to prevent and treat HF, the mortality rate in patients with symptomatic HF remains high. To conquer these difficulties, the pathophysiology of HF should be considered within a wide range of views. Given the diverse mechanisms of HF pathophysiology, renal and cardiac functions have close and complementary interconnections. Recent studies suggest that communication between kidney and heart through bidirectional pathways causes significant pathological changes...
July 21, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28728476/a-perspective-on-diuretic-resistance-in-chronic-congestive-heart-failure
#7
Niel Shah, Raef Madanieh, Mehmet Al Kan, Muhammad U Dogar, Constantine E Kosmas, Timothy J Vittorio
Chronic congestive heart failure (CHF) is a complex disorder characterized by inability of the heart to keep up the demands on it, followed by the progressive pump failure and fluid accumulation. Although the loop diuretics are widely used in heart failure (HF) patients, both pharmacodynamic and pharmacokinetic alterations are thought to be responsible for diuretic resistance in these patients. Strategies to overcome diuretic resistance include sodium intake restriction, changes in diuretic dose and route of administration and sequential nephron diuretic therapy...
July 1, 2017: Therapeutic Advances in Cardiovascular Disease
https://www.readbyqxmd.com/read/28711449/intrarenal-flow-alterations-during-transition-from-euvolemia-to-intravascular-volume-expansion-in-heart-failure-patients
#8
Petra Nijst, Pieter Martens, Matthias Dupont, W H Wilson Tang, Wilfried Mullens
OBJECTIVES: The goal of this study was to assess: 1) the intrarenal flow in heart failure (HF) patients during the transition from euvolemia to intravascular volume overload; and 2) the relationship between intrarenal flow and diuretic efficiency. BACKGROUND: Intrarenal blood flow alterations may help to better understand impaired volume handling in HF. METHODS: Resistance index (RI) and venous impedance index (VII) were assessed in 6 healthy subjects, 40 euvolemic HF patients with reduced ejection fraction (HFrEF) and 10 HF patients with preserved ejection fraction (HFpEF)...
July 6, 2017: JACC. Heart Failure
https://www.readbyqxmd.com/read/28706401/influence-of-west-african-ethnicity-and-gender-on-beta-cell-function-and-insulin-sensitivity-in-essential-hypertensives-treated-with-hydrochlorothiazide-and-hydrochlorothiazide-lisinopril-combination
#9
Micheal Olamoyegun, Babatope Kolawole, Adesuyi A L Ajayi
OBJECTIVE: To assess the effects of hydrochlorothiazide (HCT) given alone and in combination with an angiotensin-converting enzyme inhibitor (ACEI) on beta-cell function in a negroid population to further explore possible ethnic differences in the effect of antihypertensive drugs on homeostasis model assessment - insulin resistance (HOMA-IR). MATERIALS AND METHODS: A total of 80 newly diagnosed Nigerian essential hypertensive patients were assigned to receive either HCT 25 mg daily or both HCT and lisinopril (Lis; 25/10 mg daily) in an open-label study for 12 weeks...
April 2017: Journal of Pharmacology & Pharmacotherapeutics
https://www.readbyqxmd.com/read/28700781/efficacy-and-safety-of-spironolactone-in-acute-heart-failure-the-athena-hf-randomized-clinical-trial
#10
Javed Butler, Kevin J Anstrom, G Michael Felker, Michael M Givertz, Andreas P Kalogeropoulos, Marvin A Konstam, Douglas L Mann, Kenneth B Margulies, Steven E McNulty, Robert J Mentz, Margaret M Redfield, W H Wilson Tang, David J Whellan, Monica Shah, Patrice Desvigne-Nickens, Adrian F Hernandez, Eugene Braunwald
Importance: Persistent congestion is associated with worse outcomes in acute heart failure (AHF). Mineralocorticoid receptor antagonists administered at high doses may relieve congestion, overcome diuretic resistance, and mitigate the effects of adverse neurohormonal activation in AHF. Objective: To assess the effect of high-dose spironolactone and usual care on N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels compared with usual care alone. Design, Setting, and Participants: This double-blind and placebo (or low-dose)-controlled randomized clinical trial was conducted in 22 US acute care hospitals among patients with AHF who were previously receiving no or low-dose (12...
July 12, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/28699016/position-related-renal-perfusion-disturbances-as-a-possible-underestimated-mechanism-in-patients-with-resistant-hypertension-a-case-vignette
#11
Jan Schiefer, Holger Amthauer, Philipp Genseke, Peter R Mertens, Christos Chatzikyrkou
PURPOSE: In patients with resistant hypertension and large blood pressure fluctuations, the role of orthostatic hypertension, associated with position-dependent renal perfusion disturbances, has not been investigated in detail yet. METHODS: In this regard, four patients from our outpatient clinic were investigated by the use of 24-h ambulatory blood pressure monitoring (ABPM), active standing test, renal duplex sonography and Tc99m-mercaptoacetyltriglycine [MAG3] renal scintigraphy in supine and upright position...
July 11, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28695313/elderly-patients-with-chronic-kidney-disease-have-higher-risk-of-hyperparathyroidism
#12
Rosilene M Elias, Rosa M A Moysés
PURPOSE: As the world's population ages, the incidence of chronic kidney disease (CKD) is growing. There is ongoing debate regarding whether high levels of parathyroid hormone (PTH) would be more common in elderly than young patients, and which factors are driven the risk of secondary hyperparathyroidism (SHPT), independent of renal function. METHODS: Elderly patients (age ≥ 65 years, N = 518) were compared to a 1:1 sex- and estimated glomerular filtration rate (eGFR)-matched sample of young patients (age < 65 years), in a cross-sectional analysis...
July 10, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28682031/-the-peritoneal-ultrafiltration-in-patients-with-cardio-renal-disease
#13
Roberto Corciulo, Simone Corciulo
In Italy, the congestive heart failure is the leading cause of hospitalization and despite advances in therapy, the long-term prognosis is poor. Congestive heart failure is associated with advanced varying degrees of chronic renal disease that identify the cardio-renal syndrome type 2. High-dose diuretic therapy often fail to solve the water overload that is frequently the cause of death. The resistance to diuretics aggravates the state of the patient's edema and consequently morbidity and mortality. In the acute stage, the extracorporeal ultrafiltration unable to repair over hydration but needs frequent access weekly or midweek at the dialysis center...
March 2017: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/28674911/the-basic-metabolic-profile-in-heart-failure-marker-and-modifier
#14
REVIEW
Ahmed Elfar, Kamalanathan K Sambandam
PURPOSE OF REVIEW: The physiologic determinants of each of the components of the basic metabolic profile in patients with heart failure will be explored. Additionally, the review will discuss the prognostic value of alterations in the basic metabolic profile as well as their effects on management. RECENT FINDINGS: Abnormalities in the basic metabolic profile have significant correlation with clinical outcomes and can modify treatment in heart failure. Hypochloremia has recently received increased attention for these reasons...
August 2017: Current Heart Failure Reports
https://www.readbyqxmd.com/read/28666228/high-throughput-quantification-of-8-antihypertensive-drugs-and-active-metabolites-in-human-plasma-using-uplc-ms-ms
#15
Bart C H van der Nagel, Jorie Versmissen, Soma Bahmany, Teun van Gelder, Birgit C P Koch
BACKGROUND: To assess drug adherence of patients with hypertension, an analytical method was developed and validated using ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The method includes eight frequently prescribed antihypertensive drugs from four classes and their active metabolites: angiotensin converting enzyme inhibitors enalapril and perindopril (active metabolites respectively enalaprilate and perindoprilate), angiotensin II receptor blockers losartan (with the active metabolite losartan carboxylic acid) and valsartan, calcium channel blockers amlodipine and nifedipine and diuretics hydrochlorothiazide and spironolactone (with the active metabolite canrenone)...
June 19, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28613081/maintenance-of-negative-fluid-balance-can-improve-endothelial-and-cardiac-functions-in-primary-hypertensive-patients
#16
Ali Yeşiltepe, Oguzhan Sıtkı Dizdar, Hasan Gorkem, Engin Dondurmacı, Eyup Ozkan, Ali Koç, Ahmet Oguz Baktır, Ali Ihsan Gunal
PURPOSE: The issue of unidentified volume expansion is well recognized as a cause for resistance to antihypertensive therapy. The aim of study is to identify contribution of negative fluid balance to hypertension control and impact on endothelial and cardiac functions among primary hypertensive patients who do not have kidney failure. MATERIALS AND METHODS: This is a prospective interventional study with one-year follow-up. Preceded by volume status measurements were performed by a body composition monitor (BCM), the patients were put on ambulatory blood pressure monitoring for 24 hours...
June 14, 2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/28612323/risk-assessment-and-outcomes-of-vasoplegia-after-cardiac-surgery
#17
Athanasios Tsiouris, Lynn Wilson, Ala S Haddadin, James J Yun, Abeel A Mangi
OBJECTIVE: The aim of this study was to analyze risk factors and outcomes of vasoplegia after cardiac surgery based on our experience with almost 2000 cardiac operations performed at our institution. METHODS: We retrospectively analyzed patients who underwent cardiac surgery with cardiopulmonary bypass (CPB) between 2011 and 2013. Data were available for a total of 1992 patients. We defined vasoplegia as hypotension with persistently low systemic vascular resistance (<800 dyn/s/cm) and preserved Cardiac Index (>2...
June 13, 2017: General Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28597403/resistant-hypertension-mechanisms-and-treatment
#18
REVIEW
Andrew Y Hwang, Eric Dietrich, Carl J Pepine, Steven M Smith
PURPOSE OF REVIEW: Emerging evidence suggests that multiple mechanisms may be responsible for the development of treatment-resistant hypertension (TRH). This review aims to summarize recent data on potential mechanisms of resistance and discuss current pharmacotherapeutic options available in the management of TRH. RECENT FINDINGS: Excess sodium and fluid retention, increased activation of the renin-angiotensin-aldosterone system, and heightened activity of the sympathetic nervous system appear to play an important role in development of TRH...
July 2017: Current Hypertension Reports
https://www.readbyqxmd.com/read/28595464/the-effects-of-baroreflex-activation-therapy-on-blood-pressure-and-sympathetic-function-in-patients-with-refractory-hypertension-the-rationale-and-design-of-the-nordic-bat-study
#19
Daniel Gordin, Fadl Elmula M Fadl Elmula, Bert Andersson, Anders Gottsäter, Johan Elf, Thomas Kahan, Kent Lodberg Christensen, Pirkka Vikatmaa, Leena Vikatmaa, Thomas Bastholm Olesen, Per-Henrik Groop, Michael Hecht Olsen, Ilkka Tikkanen
OBJECTIVE: To explore the effects of baroreflex activation therapy (BAT) on hypertension in patients with treatment resistant or refractory hypertension. METHODS: This investigator-initiated randomized, double-blind, 1:1 parallel-design clinical trial will include 100 patients with refractory hypertension from 6 tertiary referral hypertension centers in the Nordic countries. A Barostim Neo System will be implanted and after 1 month patients will be randomized to either BAT for 16 months or continuous pharmacotherapy (BAT off) for 8 months followed by BAT for 8 months...
June 8, 2017: Blood Pressure
https://www.readbyqxmd.com/read/28588673/modulatory-effects-of-hydrochlorothiazide-and-triamterene-on-resistant-hypertension-patients
#20
Haibin Gong, Yun Li, Cheng Zheng, Tian-Tian Du, Bing-Quan Luo, Min Pang
The present study explored the modulatory potential of hydrochlorothiazide and triamterene on resistant hypertension patients. The mechanistic information for resistant hypertension was explored by studying the pressure-natriuresis curves between the salt sensitive population and non-salt sensitive population. A cohort of 23 patients with non-hypertension (NH) (13 males and 10 females; aged from 23 to 62 years), 26 patients with controlled hypertension (CH) (14 males and 12 females; aged from 19 to 72 years) and 23 patients with resistant hypertension (RH) (13 males and 10 females; aged from 19 to 76 years) were selected...
June 2017: Experimental and Therapeutic Medicine
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