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https://www.readbyqxmd.com/read/28742189/novel-endogenous-negative-modulators-of-platelet-function-as-potential-anti-thrombotic-targets
#1
Y-J Li, H-X Zhu, D Zhang, H-C Li, P Ma, L-Y Huang
Platelets are megakaryocyte-derived nuclear-free fragments that participate in cardiovascular diseases including acute myocardial infarction, ischemic stroke, hypertension, and atherosclerosis. At the endothelium damage site, platelets interact with sub-endothelial matrix proteins such as glycoprotein VI/Fc receptor γ-chain (GPVI/FcRγ), G protein-coupled receptor/phospholipase Cγ(β) (GPCR/PLCγ(β)), Rho/RhoK and integrin. The activation of these signaling pathways triggers intracellular calcium increase and causes platelet adhesion, aggregation, granule release and finally thrombus formation...
July 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28742187/pulmonell-hypertension-vanligt-vid-kronisk-lungsjukdom-europeiska-riktlinjer-kring-utredning-och-behandling
#2
David Kylhammar, Göran Rådegran
Pulmonary hypertension due to lung diseases In 2015 the European Society of Cardiology and European Respiratory Society published new guidelines on the diagnosis and treatment of pulmonary hypertension (PH). PH due to lung diseases and/or hypoxia was classified as a separate entity. PH is common in lung diseases, but seldom severe. Nevertheless, the presence of PH in a patient with lung disease is associated with worse outcome. If there is clinical suspicion of PH in a patient with lung disease, echocardiography is recommended, and if there are signs of severe PH and/or severe right ventricular dysfunction the patient should be referred to a PH expert centre...
July 21, 2017: Läkartidningen
https://www.readbyqxmd.com/read/28741243/the-pharmacogenomic-and-metabolomic-predictors-of-ace-inhibitor-and-angiotensin-ii-receptor-blocker-effectiveness-and-safety
#3
Hania K Flaten, Andrew A Monte
Hypertension (HTN) is the most common chronic disease in the USA. Hypertensive patients frequently require repeat primary care visits to find an effective drug or drug combination to control their disease. Currently, patients are prescribed drugs for HTN based on race, age, and comorbidities and although the current guidelines are reasonable starting points for prescribing, 50% of hypertensive patients still fail to achieve target blood pressures. Despite numerous strategies to improve compliance, drug effectiveness, and optimization of initial drug choice, effectiveness has remained largely unchanged over the past two decades...
July 24, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28740412/prevalence-of-diabetes-and-obesity-in-association-with-prematurity-and-growth-restriction
#4
REVIEW
Gretchen Kopec, Prem S Shekhawat, Maroun J Mhanna
Intrauterine growth restriction (IUGR) is when fetuses and newborn infants have not reached their true growth potential as genetically defined. Fetuses with IUGR develop in a less than ideal environment that leads to epigenetic changes and marks infants' metabolism for the rest of their lives. Epigenetic changes affect insulin-like growth factor-1 (IGF-1) levels and lead to insulin resistance and ultimately to a metabolic syndrome. The metabolic syndrome is a constellation of illnesses that raise one's risk for type 2 diabetes mellitus, coronary artery disease, and ischemic heart disease, including hypertension, dyslipidemia, central obesity, insulin resistance, and inflammation...
2017: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/28739840/mitochondrial-sirtuins-in-cardiometabolic-diseases
#5
REVIEW
Xiaoqiang Tang, Xiao-Feng Chen, Hou-Zao Chen, De-Pei Liu
Mitochondria are heterogeneous and essentially contribute to cellular functions and tissue homeostasis. Mitochondrial dysfunction compromises overall cell functioning, tissue damage, and diseases. The advances in mitochondrion biology increase our understanding of mitochondrial dynamics, bioenergetics, and redox homeostasis, and subsequently, their functions in tissue homeostasis and diseases, including cardiometabolic diseases (CMDs). The functions of mitochondria mainly rely on the enzymes in their matrix...
August 15, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28738750/pregnancy-outcome-in-patients-with-takayasu-s-arteritis-cohort-study-and-review-of-the-literature
#6
Michal Kirshenbaum, Michal J Simchen, Ramat Gan
OBJECTIVE: To investigate the clinical features of pregnancy in women with Takayasu's arteritis managed in a tertiary medical center and review the literature in order to establish the course and recommended follow up and treatment for these pregnancies. MATERIALS AND METHODS: Retrospective analysis of 20 pregnancies in 6 women with Takayasu's arteritis. Patients were recruited from the high risk pregnancy clinics at Sheba Medical Center, where follow up included strict control of blood pressure and treatment of obstetric and disease related complications...
July 24, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28737258/preclinical-alterations-in-myocardial-microstructure-in-people-with-metabolic-syndrome
#7
Jennifer E Ho, Youssef Rahban, Harpaul Sandhu, Pranoti G Hiremath, Nir Ayalon, Fuzhong Qin, Alejandro J Perez, Jill Downing, Deepa M Gopal, Susan Cheng, Wilson S Colucci
OBJECTIVE: Metabolic syndrome (MetS) can lead to myocardial fibrosis, diastolic dysfunction, and eventual heart failure. This study evaluated alterations in myocardial microstructure in people with MetS by using a novel algorithm to characterize ultrasonic signal intensity variation. METHODS: Among 254 participants without existing cardiovascular disease (mean age 42 ± 11 years, 75% women), there were 162 with MetS, 47 with obesity without MetS, and 45 nonobese controls...
July 24, 2017: Obesity
https://www.readbyqxmd.com/read/28736636/biological-agents-in-gastrointestinal-cancers-adverse-effects-and-their-management
#8
REVIEW
Nivedita Arora, Arjun Gupta, Preet Paul Singh
Biological therapy comprises agents that by virtue of their unique mechanisms of action, are able to specifically incite a response against or target malignant cells. They differ from conventional chemotherapy with regard to mechanisms of action, indications and side effect profile. Biologic agents have revolutionized therapy for a number of malignancies. In the setting of gastrointestinal (GI) malignancies, agents targeting vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (Her2/Neu) and epidermal growth factor receptor (EGFR) have proven to be invaluable additions to chemotherapy...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28736316/early-actions-of-anti-vascular-endothelial-growth-factor-vascular-endothelial-growth-factor-receptor-drugs-on-angiogenic-blood-vessels
#9
Basel Sitohy, Sunghee Chang, Tracey E Sciuto, Elizabeth Masse, Mei Shen, Peter M Kang, Shou-Ching Jaminet, Laura E Benjamin, Rupal S Bhatt, Ann M Dvorak, Janice A Nagy, Harold F Dvorak
Tumors induce their heterogeneous vasculature by secreting vascular endothelial growth factor (VEGF)-A. Anti-VEGF/VEGF receptor (VEGFR) drugs may treat cancer but the underlying mechanisms remain unclear. An adenovirus expressing VEGF-A (Ad-VEGF-A(164)) replicates the tumor vasculature in mice without tumor cells. Mother vessels (MV) are the first angiogenic vessel type to form in tumors and following Ad-VEGF-A(164). Multiday treatments with a VEGF trap reverted MV back to normal microvessels. We now show that, within hours, a single dose of several anti-VEGF drugs collapsed MV to form glomeruloid microvascular proliferations (GMP), accompanied by only modest endothelial cell death...
July 20, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28735903/genetics-of-non-syndromic-childhood-obesity-and-the-use-of-high-throughput-dna-sequencing-technologies
#10
REVIEW
Ana Carolina Proença da Fonseca, Claudio Mastronardi, Angad Johar, Mauricio Arcos-Burgos, Gilberto Paz-Filho
BACKGROUND: Childhood obesity is a serious public health problem associated with the development of several chronic diseases, such as type 2 diabetes mellitus, dyslipidemia, and hypertension. The elevated prevalence of obesity is mostly due to inadequate diet and lifestyle, but it is also influenced by genetic factors. OBJECTIVES: To review recent advances in the field of the genetics of obesity. We summarize the list of genes associated with the rare non-syndromic forms of obesity, and explain their function...
June 16, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28735660/case-detection-and-diagnosis-of-primary-aldosteronism-the-consensus-of-taiwan-society-of-aldosteronism
#11
Vin-Cent Wu, Ya-Hui Hu, Leay Kiaw Er, Ruoh-Fang Yen, Chia-Hui Chang, Ya-Li Chang, Ching-Chu Lu, Chin-Chen Chang, Jui-Hsiang Lin, Yen-Hung Lin, Tzung-Dau Wang, Chih-Yuan Wang, Shih Te Tu, Shih-Chieh Jeff Chueh, Ching-Chung Chang, Fen-Yu Tseng, Kwan-Dun Wu
BACKGROUND/PURPOSE: Even though the increasing clinical recognition of primary aldosteronism (PA) as a public health issue, its heightened risk profiles and the availability of targeted surgical/medical treatment being more understood, consensus in its diagnosis and management based on medical evidence, while recognizing the constraints of our real-world clinical practice in Taiwan, has not been reached. METHODS: The Taiwan Society of Aldosteronism (TSA) Task Force acknowledges the above-mentioned issues and reached this Taiwan PA consensus at its inaugural meeting, in order to provide updated information of internationally acceptable standards, and also to incorporate our local disease characteristics into the management of PA...
July 20, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/28735097/protecting-the-heart-through-mk2-modulation-toward-a-role-in-diabetic-cardiomyopathy-and-lipid-metabolism
#12
REVIEW
Matthieu Ruiz, Lise Coderre, Bruce Gordon Allen, Christine Des Rosiers
Various signaling pathways have been identified in the heart as important players during development, physiological adaptation or pathological processes. This includes the MAPK families, particularly p38MAPK, which is involved in several key cellular processes, including differentiation, proliferation, apoptosis, inflammation, metabolism and survival. Disrupted p38MAPK signaling has been associated with several diseases, including cardiovascular diseases (CVD) as well as diabetes and its related complications...
July 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28734660/efficacy-and-tolerability-of-combination-therapy-versus-monotherapy-with-candesartan-and-or-amlodipine-for-dose-finding-in-essential-hypertension-a-phase-ii-multicenter-randomized-double-blind-clinical-trial
#13
Il Suk Sohn, Chong-Jin Kim, Taehoon Ahn, Ho-Joong Youn, Hui-Kyung Jeon, Sang Hyun Ihm, Eun Joo Cho, Woo-Baek Chung, Shung Chull Chae, Woo-Shik Kim, Chang-Wook Nam, Seong-Mi Park, Ji-Yong Choi, Young-Kwon Kim, Taek-Jong Hong, Hae-Young Lee, Jang-Hyun Cho, Eun-Seok Shin, Jung-Han Yoon, Tae-Hyun Yang, Myung-Ho Jeong, Jun-Hee Lee, Joong-Il Park
PURPOSE: Intensive blood pressure (BP) lowering is important for the treatment of hypertension; however, it has been a challenge to achieve target BP in many patients. The purpose of this study was to explore the optimal dosage of a fixed-dose combination of candesartan cilexetil (CAN) and amlodipine besylate (AML), by examining the tolerability and efficacy of CAN/AML combination therapy compared with those of monotherapy with either drug in patients with essential hypertension. METHODS: This Phase II multicenter, randomized, double-blind clinical trial enrolled patients aged 19 years or older with essential hypertension, defined as a mean sitting diastolic BP (msDBP) between 95 and 115 mm Hg, and a mean sitting systolic BP (msSBP) of <200 mm Hg after a 2-week placebo run-in period...
July 19, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28733751/evaluation-of-the-safety-and-efficacy-of-metoprolol-infusion-for-children-and-adolescents-with-hypertensive-crises-a-retrospective-case-series
#14
Rola Saqan, Hanan Thiabat
BACKGROUND: Acute severe hypertension occurs infrequently in pediatric patients and, consequently, data on the efficacy and safety of most antihypertensive agents, as well as the adverse events associated with these agents, are very limited in this population. In this case series, we evaluated the use of metoprolol infusion in children with hypertensive emergencies. METHODS: The study population comprised children younger than 18 years who had been admitted to the pediatric intensive care unit at King Abdullah University Hospital with blood pressure above the 99th percentile for age, height, and sex and who were symptomatic at the time of presentation...
July 21, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28732007/a-data-driven-modeling-approach-to-identify-disease-specific-multi-organ-networks-driving-physiological-dysregulation
#15
Warren D Anderson, Danielle DeCicco, James S Schwaber, Rajanikanth Vadigepalli
Multiple physiological systems interact throughout the development of a complex disease. Knowledge of the dynamics and connectivity of interactions across physiological systems could facilitate the prevention or mitigation of organ damage underlying complex diseases, many of which are currently refractory to available therapeutics (e.g., hypertension). We studied the regulatory interactions operating within and across organs throughout disease development by integrating in vivo analysis of gene expression dynamics with a reverse engineering approach to infer data-driven dynamic network models of multi-organ gene regulatory influences...
July 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28731929/impact-of-aortic-rather-than-brachial-pulsatile-haemodynamics-on-variations-in-end-organ-measures-across-the-full-adult-blood-pressure-range
#16
Bryan Hodson, Gavin R Norton, Imraan Ballim, Carlos D Libhaber, Pinhas Sareli, Angela J Woodiwiss
AIMS: To determine the extent to which the adverse effects of blood pressure (BP) are mediated by pulsatile haemodynamic changes across the normotensive as compared with the hypertensive adult brachial BP range, and whether aortic rather than brachial pulsatile changes best index these effects. METHODS: In 1307 community participants, the contribution of pulsatile haemodynamics (applanation tonometry and SphygmoCor software) to variations in left ventricular mass index (LVMI) (echocardiography) (n = 920), carotid intima-media thickness (IMT) (n = 712) and estimated glomerular filtration rate (eGFR) (n = 1164) were assessed...
July 20, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28731289/current-status-of-achieving-blood-pressure-target-and-its-clinical-correlates-in-japanese-type-2-diabetes
#17
Hiroki Yokoyama, Shin-Ichi Araki, Koichi Kawai, Koichi Hirao, Yoshio Kurihara, Hiroaki Seino, Hiroshi Takamura, Hidekatsu Sugimoto, Akira Okada, Hiroshi Maegawa
AIMS/INTRODUCTION: To investigate the current status of achieved blood pressure levels in association with the number of antihypertensive drug classes as of 2013, and to explore the clinical correlates with achievement of target blood pressure in a large-scale cohort of Japanese subjects with type 2 diabetes. MATERIALS AND METHODS: A nationwide survey was conducted including 12,811 subjects with type 2 diabetes. Subjects were divided by achieved blood pressure, <130/80 or 140/90 mmHg, and the number of drug classes taken...
July 21, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28730936/an-industry-update-what-is-the-latest-news-in-therapeutic-delivery
#18
Iain Simpson
This Industry Update covers the period from 1 through 30 April 2017, and is based on information sourced from company press releases, scientific literature, patents and various news websites. Biogen expanded its portfolio of developmental drugs targeting neurological diseases by licensing a drug from Bristol-Myers Squibb which is currently under investigation for the treatment of progressive supranuclear palsy. Takeda announced a deal with NuBiyota focused on developing treatments for gastrointestinal disorders, based on the manipulation of microbes living in the gut...
July 2017: Therapeutic Delivery
https://www.readbyqxmd.com/read/28730648/calcineurin-inhibitor-withdrawal-or-tapering-for-kidney-transplant-recipients
#19
REVIEW
Krishna M Karpe, Girish S Talaulikar, Giles D Walters
BACKGROUND: Calcineurin inhibitors (CNI) can reduce acute transplant rejection and immediate graft loss but are associated with significant adverse effects such as hypertension and nephrotoxicity which may contribute to chronic rejection. CNI toxicity has led to numerous studies investigating CNI withdrawal and tapering strategies. Despite this, uncertainty remains about minimisation or withdrawal of CNI. OBJECTIVES: This review aimed to look at the benefits and harms of CNI tapering or withdrawal in terms of graft function and loss, incidence of acute rejection episodes, treatment-related side effects (hypertension, hyperlipidaemia) and death...
July 21, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28728897/1-3-oxazole-based-selective-picomolar-inhibitors-of-cytosolic-human-carbonic-anhydrase-ii-alleviate-ocular-hypertension-in-rabbits-potency-is-supported-by-x-ray-crystallography-of-two-leads
#20
Marta Ferraroni, Laura Luccarini, Emanuela Masini, Mikhail Korsakov, Andrea Scozzafava, Claudiu T Supuran, Mikhail Krasavin
Two lead 1,3-oxazole-based carbonic anhydrase inhibitors (CAIs) earlier identified as selective, picomolar inhibitors of hCA II (a cytosolic target for treatment of glaucoma) have been investigated further. Firstly, they were found to be conveniently synthesized on multigram scale, which enables further development. These compounds were found to be comparable in efficacy to dorzolamide eye drops when applied in the eye drop form as well. Finally, the reasons for unusually high potency of these compounds became understood from their high-resolution X-ray crystallography structures...
July 11, 2017: Bioorganic & Medicinal Chemistry
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