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https://www.readbyqxmd.com/read/28092472/using-biomarkers-to-predict-and-to-prevent-cardiotoxicity-of-cancer-therapy
#1
Daniela Cardinale, Gina Biasillo, Michela Salvatici, Maria Teresa Sandri, Carlo Maria Cipolla
Cardiotoxicity is a common complication that may compromise the clinical effectiveness of anticancer therapy. The current standard for monitoring cardiac function detects cardiotoxicity only when a functional impairment has already occurred, not allowing for any early preventive strategy. Areas covered: A novel approach, based on the use of biomarkers has recently emerged, resulting in a very effective tool for early, real-time identification, and monitoring of cardiotoxicity. In particular, cardiac troponin elevation during chemotherapy allows to identify patients more prone to develop myocardial dysfunction and cardiac events...
January 16, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28068517/rapid-analysis-of-drug-dissolution-by-paper-spray-ionization-mass-spectrometry
#2
Yang Liu, Ning Liu, Ya-Nan Zhou, Lan Lin, Lan He
With a great quantity of solid dosage tested by dissolution technology, developing a rapid and sensitive method to access the content of drug within dissolution media is highly desired by analysts and scientists. Traditionally, dissolution media is not compatible with mass spectrometry since the inorganic salts in the media might damage the mass spectrometer. Here, paper spray ionization mass spectrometry (PSI-MS), one of the ambient mass spectrometry technologies, is developed to characterize the content of drugs in dissolution media...
December 23, 2016: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28060547/the-safety-of-sacubitril-valsartan-for-the-treatment-of-chronic-heart-failure
#3
Jeffrey M Tyler, John R Teerlink
Sacubitril-valsartan is a combination drug that contains the neprilysin inhibitor sacubitril and angiotensin II receptor blocker valsartan. In 2015, the US Food and Drug Administration approved sacubitril-valsartan for treatment of heart failure patients with reduced ejection fraction and New York Heart Association class II-IV symptoms following a large, Phase III clinical trial (PARADIGM-HF) that demonstrated a 20% reduction in the combined primary end-point of death from cardiovascular cause or hospitalization for heart failure compared to enalapril...
January 6, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28044466/brief-communication-plasma-lipid-oxidation-predicts-atherosclerotic-status-better-than-cholesterol-in-diabetic-apolipoprotein-e-deficient-mice
#4
Karen Ekkelund Petersen, Jens Lykkesfeldt, Kirsten Raun, Günaj Rakipovski
Increased levels of oxidative stress have been suggested to play a detrimental role in the development of diabetes-related vascular complications. Here, we investigated whether the concentration of malondialdehyde, a marker of lipid oxidation correlated to the degree of aortic plaque lesions in a proatherogenic diabetic mouse model. Three groups of apolipoprotein E knockout mice were studied for 20 weeks, a control, a streptozotocin-induced diabetic, and a diabetic enalapril-treated group. Enalapril was hypothesized to lower oxidative stress level and thus the plaque burden...
January 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28043809/physical-training-associated-with-enalapril-but-not-to-losartan-results-in-better-cardiovascular-autonomic-effects
#5
Karina Delgado Maida, Ada Clarice Gastaldi, Tabata de Paula Facioli, João Eduardo de Araújo, Hugo Celso Dutra de Souza
BACKGROUND: We investigated the cardiovascular autonomic effects of physical training associated with Enalapril or Losartan pharmacological treatments in spontaneously hypertensive rats (SHR). METHODS: SHRs, 18weeks of age (N=48) was assigned to either sedentary (N=24) and trained (N=24; aerobic training by swimming for 10wk). Each group was subdivided in 3 subgroups (N=8) vehicle (control); Enalapril (10mg·kg(-1)·d(-1)); and Losartan (5mg·kg(-1)·d(-1)). All animals received a 10-week treatment in drinking water...
December 24, 2016: Autonomic Neuroscience: Basic & Clinical
https://www.readbyqxmd.com/read/28041700/a-comparison-study-of-the-echocardiographic-changes-in-hypertensive-patients-treated-with-telmisartan-vs-enalapril
#6
Najah R Hadi, Mohammad S Abdulzahra, Laith M Al-Huseini, Hayder A Al-Aubaidy
BACKGROUND: Hypertension-induced cardiac dysfunction is variable among different anti-hypertensive medications. This study compares the effects of telmisartan and enalapril on echocardiographic parameters in hypertensive patients. MATERIALS AND METHODS: This was a randomised single blinded study. Eighty hypertensive patients were included in this study and they were randomly allocated into two study groups: Group 1 included 40 patients who took telmisartan 80mg once daily for six months...
December 22, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/28040266/angiotensin-ii-at1-receptor-signaling-is-necessary-for-cyclooxygenase-2-dependent-postnatal-nephron-generation
#7
Stefanie Frölich, Patrick Slattery, Dominique Thomas, Itamar Goren, Nerea Ferreiros, Boye L Jensen, Rolf M Nüsing
Deletion of cyclooxygenase-2 (COX-2) causes impairment of postnatal kidney development. Here we tested whether the renin angiotensin system contributes to COX-2-dependent nephrogenesis in mice after birth and whether a rescue of impaired renal development and function in COX-2(-/-) mice was achievable. Plasma renin concentration in mouse pups showed a birth peak and a second peak around day P8 during the first 10 days post birth. Administration of the angiotensin II receptor AT1 antagonist telmisartan from day P1 to P3 did not result in cortical damage...
December 28, 2016: Kidney International
https://www.readbyqxmd.com/read/28025096/early-vs-late-intervention-of-high-fat-low-dose-streptozotocin-treated-c57bl-6j-mice-with-enalapril-%C3%AE-lipoic-acid-menhaden-oil-or-their-combination-effect-on-diabetic-neuropathy-related-endpoints
#8
Matthew S Yorek, Alexander Obrosov, Hanna Shevalye, Lawrence J Coppey, Randy H Kardon, Mark A Yorek
We have previously demonstrated that enalapril, α-lipoic acid and menhaden (fish) oil has potential as a treatment for diabetic peripheral neuropathy. In this study we sought to determine the efficacy of these treatments individually or in combination on multiple neuropathic endpoints in a high fat fed low dose streptozotocin treated mouse, a model of type 2 diabetes, following early or late intervention. Four or twelve weeks after the onset of hyperglycemia, diabetic mice were treated with enalapril, α-lipoic acid, menhaden oil or their combination for 12 weeks...
December 23, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/28024961/efficacy-and-safety-of-sacubitril-valsartan-lcz696-in-japanese-patients-with-chronic-heart-failure-and-reduced-ejection-fraction-rationale-for-and-design-of-the-randomized-double-blind-parallel-hf-study
#9
Hiroyuki Tsutsui, Shinichi Momomura, Yoshihiko Saito, Hiroshi Ito, Kazuhiro Yamamoto, Tomomi Ohishi, Naoko Okino, Weinong Guo
BACKGROUND: The prognosis of heart failure patients with reduced ejection fraction (HFrEF) in Japan remains poor, although there is growing evidence for increasing use of evidence-based pharmacotherapies in Japanese real-world HF registries. Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor shown to reduce mortality and morbidity in the recently completed largest outcome trial in patients with HFrEF (PARADIGM-HF trial). The prospectively designed phase III PARALLEL-HF (Prospective comparison of ARNI with ACE inhibitor to determine the noveL beneficiaL trEatment vaLue in Japanese Heart Failure patients) study aims to assess the clinical efficacy and safety of LCZ696 in Japanese HFrEF patients, and show similar improvements in clinical outcomes as the PARADIGM-HF study enabling the registration of LCZ696 in Japan...
December 23, 2016: Journal of Cardiology
https://www.readbyqxmd.com/read/28004291/sacubitril-valsartan-lcz696-in-heart-failure
#10
Yasser Khder, Victor Shi, John J V McMurray, Martin P Lefkowitz
It has been known since the 1990s that long-term morbidity and mortality is improved in patients with heart failure with reduced ejection fraction (HFrEF) by treatments that target the renin-angiotensin-aldosterone system (RAAS). It has also long been thought that enhancement of the activity of natriuretic peptides (NPs) could potentially benefit patients with HFrEF, but multiple attempts to realize this benefit had failed over the years - until 2014, when a large, phase III, randomized, controlled clinical trial (PARADIGM-HF) was completed comparing sacubitril/valsartan with enalapril, a well-established treatment for HFrEF...
December 22, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28002889/variability-in-response-to-albuminuria-lowering-drugs-true-or-random
#11
S I Petrykiv, D de Zeeuw, F Persson, P Rossing, R T Gansevoort, G D Laverman, H J L Heerspink
AIMS: Albuminuria lowering drugs have shown different effect size in different individuals. Since urine albumin levels are known to vary considerably from day-to-day, we questioned whether the between-individual variability in albuminuria response after therapy initiation reflects a random variability or a true response variation to treatment. In addition, we questioned whether the response variability is drug dependent. METHODS: To determine whether the response to treatment is random or a true drug response, we correlated in six clinical trials the change in albuminuria during placebo or active treatment (on-treatment) with the change in albuminuria during wash-out (off-treatment)...
December 21, 2016: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27982380/access-to-and-use-of-high-blood-pressure-medications-in-brazil
#12
Sotero Serrate Mengue, Andréa Dâmaso Bertoldi, Luiz Roberto Ramos, Mareni Rocha Farias, Maria Auxiliadora Oliveira, Noemia Urruth Leão Tavares, Paulo Sergio Dourado Arrais, Vera Lucia Luiza, Tatiane da Silva Dal Pizzol
OBJECTIVE: To analyze the access to and use of medicines for high blood pressure among the Brazilian population according to social and demographic conditions. METHODS: Analysis of data from Pesquisa Nacional Sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos (PNAUM - National Survey on Access, Use and Promotion of Rational Use of Medicines), a nationwide cross-sectional, population-based study, with probability sampling, carried out between September 2013 and February 2014 in urban households in the five Brazilian regions...
December 2016: Revista de Saúde Pública
https://www.readbyqxmd.com/read/27977852/unequivocal-evidence-supporting-the-segregated-flow-intestinal-model-that-discriminates-intestine-versus-liver-first-pass-removal-in-pbpk-modeling
#13
K Sandy Pang, Qi Joy Yang, Keumhan Noh
Merits of the segregated flow model (SFM), highlighting the intestine as an inert serosa and active enterocyte c regions, with a smaller fractional (fQ  < 0.3) intestinal flow (QI ) perfusing the enterocyte region, were described. Less drug in the circulation reaches the enterocytes due to the lower flow (fQ QI ) in comparison to drug absorbed from the gut lumen, fostering the idea of route-dependent intestinal removal. The SFM was superior over the traditional model (TM), which views the serosa and enterocytes as a well-mixed tissue perfused by 100% QI ...
December 15, 2016: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/27974807/long-term-neprilysin-inhibition-implications-for-arnis
#14
REVIEW
Duncan J Campbell
Neprilysin has a major role in both the generation and degradation of bioactive peptides. LCZ696 (valsartan/sacubitril, Entresto), the first of the new ARNI (dual-acting angiotensin-receptor-neprilysin inhibitor) drug class, contains equimolar amounts of valsartan, an angiotensin-receptor blocker, and sacubitril, a prodrug for the neprilysin inhibitor LBQ657. LCZ696 reduced blood pressure more than valsartan alone in patients with hypertension. In the PARADIGM-HF study, LCZ696 was superior to the angiotensin-converting enzyme inhibitor enalapril for the treatment of heart failure with reduced ejection fraction, and LCZ696 was approved by the FDA for this purpose in 2015...
December 15, 2016: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/27920083/nocturnal-antihypertensive-treatment-in-patients-with-type-1-diabetes-with-autonomic-neuropathy-and-non-dipping-a-randomised-placebo-controlled-double-blind-cross-over-trial
#15
Henrik Øder Hjortkjær, Tonny Jensen, Klaus F Kofoed, Ulrik M Mogensen, Per Ejlstrup Sigvardsen, Lars Køber, Karen Lisa Hilsted, Helle Corinth, Simone Theilade, Jannik Hilsted
OBJECTIVES: Cardiovascular autonomic neuropathy (CAN) and abnormal circadian blood pressure (BP) rhythm are independent cardiovascular risk factors in patients with diabetes and associations between CAN, non-dipping of nocturnal BP and coronary artery disease have been demonstrated. We aimed to test if bedtime dosing (BD) versus morning dosing (MD) of the ACE inhibitor enalapril would affect the 24-hour BP profile in patients with type 1 diabetes (T1D), CAN and non-dipping. SETTING: Secondary healthcare unit in Copenhagen, Denmark...
December 5, 2016: BMJ Open
https://www.readbyqxmd.com/read/27915452/chronic-enalapril-treatment-increases-transient-outward-potassium-current-in-cardiomyocytes-isolated-from-right-ventricle-of-spontaneously-hypertensive-rats
#16
Luiz Fernando Rodrigues Junior, Ana Carolina de Azevedo Carvalho, Enildo Broetto Pimentel, José Geraldo Mill, José Hamilton Matheus Nascimento
It has been well established that chronic pressure overload resulting from hypertension leads to ventricular hypertrophy and electrophysiological remodeling. The transient outward potassium current (I to) reduction described in hypertensive animals delays ventricular repolarization, leading to complex ventricular arrhythmias and sudden death. Antihypertensive drugs, as angiotensin-converting enzyme inhibitors (ACEi), can restore I to and reduce the incidence of arrhythmic events. The purpose of this study was to evaluate the differential effects of long-term treatment with ACEi or direct-acting smooth muscle relaxant on the I to of left and right ventricle myocytes of spontaneously hypertensive rats (SHR)...
December 3, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/27908347/prognostic-implications-of-changes-in-n-terminal-pro-b-type-natriuretic-peptide-in-patients-with-heart-failure
#17
Michael R Zile, Brian L Claggett, Margaret F Prescott, John J V McMurray, Milton Packer, Jean L Rouleau, Karl Swedberg, Akshay S Desai, Jianjian Gong, Victor C Shi, Scott D Solomon
BACKGROUND: Natriuretic peptides (NP) have prognostic value in heart failure (HF), although the clinical importance of changes in NP from baseline is unclear. OBJECTIVES: The authors assessed whether a reduction in N-terminal pro-B-type NP (NT-proBNP) was associated with a decrease in HF hospitalization and cardiovascular mortality (primary endpoint) in patients with HF and reduced ejection fraction, whether treatment with sacubitril/valsartan reduced NT-proBNP below specific partition values more than enalapril, and whether the relationship between changes in NT-proBNP and changes in the primary endpoint were dependent on assigned treatment...
December 6, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27905115/treatment-for-hereditary-angioedema-with-normal-c1-inh-and-specific-mutations-in-the-f12-gene-hae-fxii
#18
K Bork, K Wulff, G Witzke, J Hardt
Hereditary angioedema with normal C1 esterase inhibitor and mutations in the F12 gene (HAE-FXII) is associated with skin swellings, abdominal pain attacks, and the risk of asphyxiation due to upper airway obstruction. It occurs nearly exclusively in women. We report our experience treating HAE-FXII with discontinuation of potential trigger factors and drug therapies. The study included 72 patients with HAE-FXII. Potential triggers included estrogen-containing oral contraceptives (eOC), hormonal replacement therapy, or angiotensin-converting enzyme inhibitors...
November 6, 2016: Allergy
https://www.readbyqxmd.com/read/27903643/effects-of-antihypertensive-agents-on-intestinal-contractility-in-the-spontaneously-hypertensive-rat-angiotensin-receptor-system-downregulation-by-losartan
#19
Glen Stephen Patten, Mahinda Yapa Abeywardena
Hypertension is an inflammatory condition controlled by the renin angiotensin system and is linked to kidney disease, diabetes mellitus, and recently to dysfunction of the gut. The aim of this study was to determine what effect antihypertensive drug treatments may have on intestinal function of the spontaneously hypertensive rat (SHR). In the first experiment, SHRs were treated with enalapril, hydralazine, or with no treatment as a control. In the second experiment, SHRs were treated with losartan or with no treatment as a control...
February 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27895519/portal-hypertension-an-uncommon-clinical-manifestation-of-takayasu-arteritis-in-a-9-year-old-child
#20
Cristina N Herrera, Javier E Tomala-Haz
Takayasu arteritis (TA) is the third most common childhood vasculitis and its clinical manifestations depend on the arteries involved. We report a case of a 9-year-old boy with multiple aneurysms in carotid and iliac arteries, subclavian and coronary arteries, and abdominal aorta. At the age of 7 years, he presented with recurrent fever and hepatosplenomegaly. An angio-computed tomography scan showed aneurysms in the left subclavian artery, abdominal aorta, and both proximal iliac arteries. He was diagnosed with TA and was treated with corticosteroids, aspirin, and enalapril...
2016: Open Access Rheumatology: Research and Reviews
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