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Miguel Fontecha-Barriuso, Diego Martin-Sanchez, Olga Ruiz-Andres, Jonay Poveda, Maria Dolores Sanchez-Niño, Lara Valiño-Rivas, Marta Ruiz-Ortega, Alberto Ortiz, Ana Belén Sanz
Epigenetics refers to heritable changes in gene expression patterns not caused by an altered nucleotide sequence, and includes non-coding RNAs and covalent modifications of DNA and histones. This review focuses on functional evidence for the involvement of DNA and histone epigenetic modifications in the pathogenesis of kidney disease and the potential therapeutic implications. There is evidence of activation of epigenetic regulatory mechanisms in acute kidney injury (AKI), chronic kidney disease (CKD) and the AKI-to-CKD transition of diverse aetiologies, including ischaemia-reperfusion injury, nephrotoxicity, ureteral obstruction, diabetes, glomerulonephritis and polycystic kidney disease...
March 9, 2018: Nephrology, Dialysis, Transplantation
Paras Ali, Sofia Butt, Nazli Hossain
OBJECTIVE: To evaluate the practice of Eclampsia management at a tertiary care public sector hospital. PATIENTS & METHODS: We conducted criteria based audit of 93 Eclampsia patients admitted in Gynae unit III, Civil hospital and Dow University of Health Sciences Karachi, between 1st January 2016 and 31st December 2016. Management practices were assessed using evidence-based criteria for care. A clinical criteria for standards of care were developed from Royal College of Obstetrician & Gynecologist (RCOG/NICE) guidelines, World Health Organization (WHO) manual, twelve criteria were identified for the audit purpose...
January 2018: Pregnancy Hypertension
Bharat Kumar, Jennifer Strouse, Melissa Swee, Petar Lenert, Manish Suneja
INTRODUCTION: Hydralazine is an antihypertensive medication that has been associated with drug-induced lupus erythematosus (DIL) as well as ANCA-associated vasculitis (AAV). Although rare, early diagnosis is critical since drug cessation is the mainstay of therapy. This retrospective study aims to characterize the clinical, laboratory, and histopathologic features of this disease. METHODS: Once approval was obtained from the Institutional Review Board at the University of Iowa, all patients carrying a diagnosis of vasculitis (ICD9 code: 447...
January 12, 2018: Seminars in Arthritis and Rheumatism
Ezinne Ozurumba, Omana Mathew, Katsuri Ranganna, Myung Choi, Adebayo Oyekan
BACKGROUND: Hypoxia inducible factor (HIF)/prolyl hydroxylase domain (PHD)-containing proteins are involved in renal adaptive response to high salt (HS). Peroxisome proliferator activated receptor alpha (PPARα), a transcription factor involved in fatty acid oxidation is implicated in the regulation of renal function. As both HIF-1α/PHD and PPARα contribute to the adaptive changes to altered oxygen tension, this study tested the hypothesis that PHD-induced renal adaptive response to HS is PPARα-dependent...
March 28, 2018: Journal of Basic and Clinical Physiology and Pharmacology
M Florencia Iulita, Diane Vallerand, Mélissa Beauvillier, Nathalie Haupert, Corinne A Ulysse, Audrey Gagné, Nathalie Vernoux, Sonia Duchemin, Michaël Boily, Marie-Ève Tremblay, Hélène Girouard
BACKGROUND: Angiotensin II (Ang II), a peptide hormone involved in the development of hypertension, causes systemic and cerebral inflammation, affecting brain regions important for blood pressure control. The cause-and-effect relationship between hypertension and inflammation is two-way, but the role of blood pressure in the induction of cerebral inflammation is less clear. The vulnerability of specific brain regions, particularly those important for memory, is also of interest. METHODS: We used molecular biology approaches, immunohistochemistry, and electron microscopy to examine the interdependence between the hypertensive and pro-inflammatory effects of Ang II...
February 28, 2018: Journal of Neuroinflammation
John N Cranmer, Julia Dettinger, Kimberly Calkins, Minnie Kibore, Onesmus Gachuno, Dilys Walker
BACKGROUND: Globally, the rate of reduction in delivery-associated maternal and perinatal mortality has been slow compared to improvements in post-delivery mortality in children under five. Improving clinical readiness for basic obstetric emergencies is crucial for reducing facility-based maternal deaths. Emergency readiness is commonly assessed using tracers derived from the maternal signal functions model. OBJECTIVE-METHOD: We compare emergency readiness using the signal functions model and a novel clinical cascade...
2018: PloS One
Therese Woodring, Ronnie Abraham, Stephanie Frisch
Cutaneous leukocytoclastic vasculitis (LCV) can occur as skin-limited disease or as part a systemic vasculitis. Appropriate workup includes the evaluation of antineutrophil cytoplasmic antibodies (ANCAs), with a positive titer raising concern for the associated primary vasculitides including microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), or eosinophilic granulomatosis with polyangiitis (EGPA). In the absence of systemic findings, however, a drug etiology must also be considered. Tumor necrosis factor (TNF) inhibitors, propylthiouracil, levamisole-adulterated cocaine, hydralazine, and minocycline have been previously documented to induce ANCA-positive vasculitis (APV), which may present with conspicuously high ANCA titers...
August 15, 2017: Dermatology Online Journal
Richard H Tran, Ahmed Aldemerdash, Patricia Chang, Carla A Sueta, Brystana Kaufman, Josephine Asafu-Adjei, Orly Vardeny, Eliza Daubert, Khalid A Alburikan, Anna M Kucharska-Newton, Sally C Stearns, Jo E Rodgers
BACKGROUND: Modification of guideline-directed medical therapy (GDMT) in hospitalized patients with heart failure (HF) has not been extensively evaluated. METHODS: The community surveillance arm of the Atherosclerosis Risk in Communities Study identified 6959 HF hospitalizations from 2005 to 2011. Predictors of GDMT modification and survival were assessed using multivariable logistic regression and Cox proportional hazards models. RESULTS: For 5091 hospitalizations, patient mean age was 75 years old, 53% were female, 69% were Caucasian, and 81% had acute decompensated HF (ADHF)...
February 9, 2018: Pharmacotherapy
Kirsten L Cleary, Zainab Siddiq, Cande V Ananth, Jason D Wright, Gloria Too, Mary E DʼAlton, Alexander M Friedman
OBJECTIVE: To evaluate temporal trends in use of antihypertensive medications during delivery hospitalizations complicated by preeclampsia and risk of maternal stroke over the same time period. METHODS: The Perspective database was used to perform a retrospective cohort study evaluating antihypertensive drugs dispensed during delivery hospitalizations complicated by preeclampsia from 2006 to the first quarter of 2015. Medications evaluated included nifedipine, hydralazine, and oral and intravenous labetalol...
March 2018: Obstetrics and Gynecology
Abeje Ambaw, Lingxing Zheng, Mitali A Tambe, Katherine E Strathearn, Glen Acosta, Scott A Hubers, Fang Liu, Seth A Herr, Jonathan Tang, Alan Truong, Elwood Walls, Amber Pond, Jean-Christophe Rochet, Riyi Shi
Growing evidence suggests that oxidative stress plays a critical role in neuronal destruction characteristic of Parkinson's disease (PD). However, the molecular mechanisms of oxidative stress-mediated dopaminergic cell death are far from clear. In the current investigation, we tested the hypothesis that acrolein, an oxidative stress and lipid peroxidation (LPO) product, is a key factor in the pathogenesis of PD. Using a combination of in vitro, in vivo, and cell free models, coupled with anatomical, functional, and behavioral examination, we found that acrolein was elevated in 6-OHDA-injected rats, and behavioral deficits associated with 6-OHDA could be mitigated by the application of the acrolein scavenger hydralazine, and mimicked by injection of acrolein in healthy rats...
January 29, 2018: Molecular and Cellular Neurosciences
Nancy Apenova, Hui Peng, Markus Hecker, Markus Brinkmann
Previous research has characterized the important role of aldehyde oxidases (AOX) in biotransformation of N-heterocyclic therapeutic drugs and environmental contaminants in mammals. Research pertaining to AOX activity in non-mammalian vertebrates, however, is scarce, despite its biological role as a potentially important metabolic pathway for xenobiotics. One of the limiting factors of research on AOX is that available photometric methods are relatively insensitive, limited in throughput, and prone to cross-reactivity from other enzymes...
January 9, 2018: Toxicology and Applied Pharmacology
Yongji Yan, Chao Wang, Yiqin Lu, Huijie Gong, Zhun Wu, Xin Ma, Hongzhao Li, Baojun Wang, Xu Zhang
The number of patients with adrenal aldosterone-producing adenomas (APAs) has gradually increased. However, even after adenoma resection, some patients still suffer from high systolic blood pressure (SBP), which is possibly due to great arterial remodeling. Moreover, mineralocorticoid receptors (MRs) were found to be expressed in vascular smooth muscle cells (VSMCs). This study aims to determine whether MR antagonism protects the aorta from aldosterone-induced aortic remolding. Male rats were subcutaneously implanted with an osmotic minipumps and randomly divided into four groups: control; aldosterone (1 μg/h); aldosterone plus a specific MR antagonist, eplerenone (100 mg/kg/day); and aldosterone plus a vasodilator, hydralazine (25 mg/kg/day)...
November 21, 2017: Journal of Physiology and Biochemistry
Michael Stowasser, Ashraf Ahmed, Zeng Guo, Martin Wolley, Jacobus Ungerer, Brett McWhinney, Marko Poglitsch, Richard Gordon
Widespread application of the plasma aldosterone/renin ratio (ARR) as a screening test has led to the recognition that primary aldosteronism (PA) is the most common specifically treatable and potentially curable form of hypertension, accounting for 5-10% of patients. Maximal detection requires accurate diagnostic approaches and awareness and control of factors that confound results, including most antihypertensives, posture, time of day, dietary salt, and plasma potassium. Recent studies have revealed potential for false positives in patients on beta-adrenoceptor blockers, and, when direct renin concentration (but not plasma renin activity) is used to measure renin, in women during the luteal phase of the menstrual cycle or receiving estrogen-containing contraceptives or hormonal replacement therapy...
December 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
Jorge A Irizarry-Caro, Carmelo Carmona-Rivera, Daniella M Schwartz, Sami S Khaznadar, Mariana J Kaplan, Peter C Grayson
OBJECTIVE: Aberrant neutrophil extracellular trap (NET) formation has been implicated as a mechanism to induce autoreactivity in individuals at risk of autoimmune diseases. The objective of this study was to assess whether medications implicated in cases of drug-induced autoimmunity (hydralazine and procainamide) and medications less commonly associated with drug-induced autoimmunity (minocycline and clozapine) induce NET formation and/or prevent NET degradation. METHODS: Human neutrophils were incubated with the drugs of interest and resultant NET formation was quantified by fluorescent microscopy...
November 9, 2017: Arthritis & Rheumatology
Amr H Sawalha
No abstract text is available yet for this article.
November 9, 2017: Arthritis & Rheumatology
J F Kayibanda, C Girouard, J-P Grégoire, E Demers, J Moisan
BACKGROUND: The evidence-based heart failure (HF) drug treatment is made of a β-blocker and an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker, or hydralazine + isosorbide dinitrate. Little is known about sex-based difference in adherence to the evidence-based HF drug treatment. OBJECTIVES: To assess among new users of the evidence-based HF drug treatment, the association between sex and 1) persistence with the treatment 1 year after its initiation, 2) implementation of the treatment among those who persisted, and 3) overall adherence to treatment in the year following its initiation...
October 28, 2017: Research in Social & Administrative Pharmacy: RSAP
Waseem Amjad, Geevarghese John, Sharifova Gulru
No abstract text is available yet for this article.
October 16, 2017: American Journal of Therapeutics
Nancy M Albert, Dana A Drzayich Antol, Richard W DeClue, Adrianne Waldman Casebeer, Yong Li, Stephen Stemkowski, Chun-Lan Chang
INTRODUCTION: Factors associated with mortality for patients with heart failure and reduced ejection fraction (HFrEF) are known; however, the association between initial pharmacotherapy (IPT) and mortality is unclear in real-world settings. METHODS: Using a retrospective design and claims database, 14,359 Medicare patients with HFrEF from August 2010 to July 2015 were identified. Index date was first HF claim. IPT was mono- or combo-angiotensin-converting enzyme inhibitor (ACEI), angiotensin II receptor blocker (ARB), beta-blocker (BB), hydralazine-nitrate (HN), and aldosterone antagonist (AA) within 1 year post-index...
October 2017: Advances in Therapy
Cecily E Allen, Mark A Doll, David W Hein
Hydralazine is used in the treatment of essential hypertension and is under investigation for epigenetic therapy in the treatment of neoplastic and renal diseases. N -acetyltransferase (NAT) 2 exhibits a common genetic polymorphism in human populations. After recombinant expression in yeast, human NAT2 exhibited an apparent Lineweaver-Burk constant ( K- m ) value (20.1 ± 8.8 μ M) for hydralazine over 20-fold lower than the apparent K- m value (456 ± 57 μ M) for recombinant human NAT1 ( P = 0.0016). The apparent V max value for recombinant human NAT1 (72...
December 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Rachel D Crouch, Anna L Blobaum, Andrew S Felts, P Jeffrey Conn, Craig W Lindsley
Aldehyde oxidase (AO) and xanthine oxidase (XO) are molybdo-flavoenzymes that catalyze oxidation of aromatic azaheterocycles. Differences in AO activity have been reported among various species including rat, human, and monkey. Herein we report a species difference in the enzymes responsible for metabolism of mGlu5 NAM VU0424238 (VU238, auglurant). Hepatic S9 incubations with AO and XO specific inhibitors hydralazine and allopurinol indicated that rat and cynomolgus monkey both oxidized VU238 to the 6-oxopyrimidine metabolite M1 via an AO-mediated pathway, whereas secondary oxidation to the 2,6-dioxopyrimidine metabolite M2 was mediated predominantly by AO in monkey and XO in rat...
September 22, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
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