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Vascular pharmacology

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https://www.readbyqxmd.com/read/28435296/spotlight-on-bevacizumab-and-its-potential-in-the-treatment-of-malignant-pleural-mesothelioma-the-evidence-to-date
#1
REVIEW
Pavel A Levin, Jonathan E Dowell
Malignant pleural mesothelioma (MPM) is a rare, but aggressive cancer. Surgery and radiation offer limited benefit, and systemic chemotherapy remains the primary treatment modality for the majority of patients. Vascular endothelial growth factor (VEGF) and its receptor have been recognized as important players in the biology of this disease. Bevacizumab is a monoclonal antibody that binds VEGF and blocks its interaction with the VEGF receptor. Recent studies have shown benefit with the addition of bevacizumab to the combination of cisplatin and pemetrexed in MPM...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28432604/phosphate-imbalance-in-patients-with-heart-failure
#2
REVIEW
E C Christopoulou, T D Filippatos, E Megapanou, M S Elisaf, G Liamis
Patients with heart failure often exhibit electrolyte abnormalities, such as hyponatremia or hypokalemia/hyperkalemia. Although not as common as the other electrolyte disturbances observed in patients with heart failure, phosphate imbalance is also of high importance in this population. The aim of this review is to present the mechanisms of low or high phosphate serum levels in patients with heart failure and its role in the pathogenesis and progression of heart dysfunction. Hypophosphatemia in patients with heart failure may be the result of co-existing electrolyte and acid-base abnormalities, pharmacological treatments, decreased intestinal absorption or secondary to sympathetic nervous system activation and co-morbidities, such as diabetes mellitus or heavy alcohol consumption...
April 22, 2017: Heart Failure Reviews
https://www.readbyqxmd.com/read/28430357/reactive-oxygen-species-key-regulators-in-vascular-health-and-diseases
#3
REVIEW
Qishan Chen, Qiwen Wang, Jianhua Zhu, Qingzhong Xiao, Li Zhang
Reactive oxygen species (ROS) are a group of small reactive molecules that play critical roles in the regulation of various cell functions and biological processes. In the vascular system, physiological levels of ROS are essential for normal vascular functions including endothelial homeostasis and smooth muscle cell contraction. In contrast, uncontrolled overproduction of ROS resulted from imbalance of ROS generation and elimination, leads to the development of vascular diseases. Excessive ROS cause vascular cell damages, recruitment of inflammatory cells, lipid peroxidation, activation of metalloproteinases, and deposition of extracellular matrix, collectively leading to vascular remodeling...
April 21, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28428256/regulation-of-lung-endothelial-permeability-and-inflammatory-responses-by-prostaglandin-a2-role-of-ep4-receptor
#4
Tomomi Ohmura, Yufeng Tian, Nicolene Sarich, Yunbo Ke, Angelo Meliton, Alok S Shah, Katrin Andreasson, Konstantin G Birukov, Anna A Birukova
A role of prostaglandin A2 (PGA2) in modulation of vascular endothelial function remains unknown. We investigated effects of PGA2 on pulmonary endothelial cell (EC) permeability and inflammatory activation and identified a receptor mediating these effects. PGA2 enhanced the EC barrier and protected against barrier dysfunction caused by vasoactive peptide thrombin and proinflammatory bacterial wall lipopolysacharide (LPS). Receptor screening using pharmacologic and molecular inhibitory approaches identified EP4 as a novel PGA2 receptor...
April 20, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28428070/no-production-and-potassium-channels-activation-induced-by-crotalus-durissus-cascavella-underlie-mesenteric-artery-relaxation
#5
S S Santos, R L C Jesus, L O Simões, W P Vasconcelos, I A Medeiros, R C Veras, L L Casais-E-Silva, D F Silva
Animal toxins are natural resources for pharmacological studies. The venom of Crotalus durissus cascavella (C.d. cascavella) may be a source in the bio-prospecting of new anti-hypertensive agents. The aim of this study was to investigate vascular effects of the venom of C.d. cascavella in normotensive rats. Studies were performed using isolated mesenteric artery segments and aortic endothelial cells. The cumulative administration of the venom of C.d. cascavella (0.001-30 μg/mL) on phenylephrine (Phe; 10 μM) pre-contracted rings induced a concentration-dependent vasorelaxation in the presence of vascular endothelium (Emax = 47...
April 18, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28423385/guidelines-for-the-management-of-diabetic-macular-edema-by-the-european-society-of-retina-specialists-euretina
#6
Ursula Schmidt-Erfurth, Jose Garcia-Arumi, Francesco Bandello, Karina Berg, Usha Chakravarthy, Bianca S Gerendas, Jost Jonas, Michael Larsen, Ramin Tadayoni, Anat Loewenstein
Diabetic retinal disease is envisioned to become the plague of the coming decades with a steep increase of worldwide diabetes incidence followed by a substantial rise in retinal disease. Improvements in diagnostic and therapeutic care have to cope with this dilemma in a clinically and socioeconomically efficient manner. Laser treatment has found a less destructive competitor in pharmacological treatments. As a consequence of recent rigorous clinical trials, laser photocoagulation is no longer recommended for the treatment of diabetic macular edema (DME), and anti-vascular endothelial growth factor therapy has emerged as first-line therapy...
April 20, 2017: Ophthalmologica. Journal International D'ophtalmologie
https://www.readbyqxmd.com/read/28419216/lav-bpifb4-isoform-modulates-enos-signaling-through-ca2-pkc-alpha-dependent-mechanism
#7
Chiara Carmela Spinelli, Albino Carrizzo, Anna Ferrario, Francesco Villa, Antonio Damato, Mariateresa Ambrosio, Michele Madonna, Giacomo Frati, Sergio Fucile, Miriam Sciaccalunga, Mario Capunzo, Gaetano Calì, Luciano Milanesi, Anna Maciag, Annibale Alessandro Puca, Carmine Vecchione
Aims: Aging is associated with impairment of endothelial nitric oxide synthase (eNOS) and progressive reduction in endothelial function. A genetic study on long-living individuals - who are characterized by delays in aging and in the onset of cardiovascular disease - previously revealed I229V ( rs2070325 ) in BPIFB4 as a longevity-associated variant (LAV); the LAV protein enhanced endothelial NO production and vasorelaxation through a PERK/14-3-3/HSP90 signal. Here, we further characterize the molecular mechanisms underlying LAV-BPIFB4-dependent enhancement of vascular function...
April 13, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28415790/hyperglycemia-via-activation-of-thromboxane-a2-receptor-impairs-the-integrity-and-function-of-blood-brain-barrier-in-microvascular-endothelial-cells
#8
Zhihong Zhao, Jue Hu, Xiaoping Gao, Hui Liang, Haiya Yu, Suosi Liu, Zhan Liu
Diabetes is one of high risk factors for cardio- and cerebra-vascular diseases, including stroke, atherosclerosis and hypertension. This study was conducted to elucidate whether and how thromboxane receptor (TPr) activation contributes to blood-brain barrier (BBB) dysfunction in diabetes. Human brain microvascular endothelial cells (HBMECs) were cultured. The levels of phosphorylated endothelial nitric oxide synthase (eNOS) at Ser1177 (p-eNOS) and Akt at Ser473 (p-Akt) were assayed by western blot. Exposure of HBMECs to either high glucose (HG) or thromboxane A2 (TxA2) mimetic U46619, significantly reduced p-eNOS and p-Akt...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413972/xanthine-oxidase-and-its-role-as-target-in-cardiovascular-disease-cardiovascular-protection-by-enzyme-inhibition
#9
Mirjam Schuchardt, Jaqueline Herrmann, Markus Tölle, Markus van der Giet
BACKGROUND: Formerly, hyperuricemia was mainly restricted to the rich population, but now-a-days it is a condition affecting wide parts of western civilization. Although only a minority of our population develops clinically relevant symptomatic hyperuricemia, there is growing evidence that elevated serum uric acid levels might be associated with elevated cardiovascular risk and cardiovascular disease progression. But it is not clear whether uric acid is just a biomarker or exerts detrimental effects itself...
April 17, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28412915/early-functional-and-structural-microvascular-changes-in-hypertension-related-to-aging
#10
Roger de Moraes, Eduardo Tibirica
It is becoming increasingly clear that both microvascular network alterations and subsequent tissue perfusion defects may precede and predict the development of arterial hypertension and other cardiovascular and metabolic diseases, including diabetes and metabolic syndrome. Moreover, the subsequent functional and structural alterations in microvascular reactivity and density, as well as alterations in the macrocirculation characteristic of physiologic vascular aging, contribute to the development of target organ damage...
April 12, 2017: Current Hypertension Reviews
https://www.readbyqxmd.com/read/28407743/new-drugs-new-toxicities-severe-side-effects-of-modern-targeted-and-immunotherapy-of-cancer-and-their-management
#11
REVIEW
Frank Kroschinsky, Friedrich Stölzel, Simone von Bonin, Gernot Beutel, Matthias Kochanek, Michael Kiehl, Peter Schellongowski
Pharmacological and cellular treatment of cancer is changing dramatically with benefits for patient outcome and comfort, but also with new toxicity profiles. The majority of adverse events can be classified as mild or moderate, but severe and life-threatening complications requiring ICU admission also occur. This review will focus on pathophysiology, symptoms, and management of these events based on the available literature.While standard antineoplastic therapy is associated with immunosuppression and infections, some of the recent approaches induce overwhelming inflammation and autoimmunity...
April 14, 2017: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/28406703/chronic-administration-of-quercetin-induces-biomechanical-and-pharmacological-remodeling-in-the-rat-coronary-arteries
#12
A Monori-Kiss, F Kiss, J M Restifo, E Monos, G L Nadasy
Acute dilation brought about by the dietary flavonoid quercetin in coronary arterioles has been described earlier, but no information is available on its chronic effects. Male Wistar rats (body weight about 190 g) were divided to two groups: the quercetin-treated group (n=22) had quercetin supplementation of approximately 30 mg/kg/day, whereas the control group (n=20) had none. After eight weeks of treatment, intramural coronary arterioles with identical passive diameters (178+/-14 and 171+/-9 microm) were prepared and their biomechanics and pharmacological reactivities were tested using pressure arteriography ex vivo...
April 12, 2017: Physiological Research
https://www.readbyqxmd.com/read/28399106/-current-approaches-to-management-of-patients-with-mild-cognitive-impairment
#13
V V Zakharov, D O Gromova
Mild cognitive impairment (MCI) is an intermediate stage between normal aging and dementia. The prevalence of MCI among elderly people is 12-17% but the risk of progression of cognitive impairment and development of dementia during 5 years is up to 70%. Cerebral vascular diseases and initial stages of neurodegenerative processes are the cause of MCI. Clinical characteristics of MCI depend on the main etiological factor. To decrease the severity of symptoms and prevent the progression of cognitive impairment in MCI patients, pharmacotherapy and non-medication methods, including diet optimization, stimulation of mental and physical activity, are used...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/28393188/a-heptameric-peptide-purified-from-spirulina%C3%A2-sp-gastrointestinal-hydrolysate-inhibits-angiotensin-i-converting-enzyme-and-angiotensin%C3%A2-ii-induced-vascular-dysfunction-in-human-endothelial-cells
#14
Seong-Yeong Heo, Seok-Chun Ko, Chang Su Kim, Gun-Woo Oh, Bomi Ryu, Zhong-Ji Qian, Geunhyung Kim, Won Sun Park, Il-Whan Choi, Thi Tuong Vy Phan, Soo-Jin Heo, Do-Hyung Kang, Myunggi Yi, Won-Kyo Jung
In this study, a marine microalga Spirulina sp.-derived protein was hydrolyzed using gastrointestinal enzymes to produce an angiotensin I (Ang I)-converting enzyme (ACE) inhibitory peptide. Following consecutive purification, the potent ACE inhibitory peptide was composed of 7 amino acids, Thr-Met‑Glu‑Pro‑Gly‑Lys-Pro (molecular weight, 759 Da). Analysis using the Lineweaver-Burk plot and molecular modeling suggested that the purified peptide acted as a mixed non-competitive inhibitor of ACE...
April 4, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28392425/t-cadherin-promotes-autophagy-and-survival-in-vascular-smooth-muscle-cells-through-mek1-2-erk1-2-axis-activation
#15
Emmanouil Kyriakakis, Agne Frismantiene, Boris Dasen, Dennis Pfaff, Olga Rivero, Klaus-Peter Lesch, Paul Erne, Therese J Resink, Maria Philippova
Autophagy is an evolutionary conserved intracellular catabolic process of vital importance to cell and tissue homeostasis. Autophagy is implicated in the pathogenesis of atherosclerosis but participating cells, molecular mechanisms and functional outcomes have not been fully elucidated. T-cadherin, an atypical glycosylphosphatidylinositol-anchored member of the cadherin superfamily of adhesion molecules, is upregulated on smooth muscle cells (SMCs)(1) in atherosclerotic lesions. Here, using rat and murine aortic SMCs as experimental models, we surveyed the ability of T-cadherin to regulate autophagy in SMCs during serum-starvation stress...
April 6, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28389228/brachyury-drives-formation-of-a-distinct-vascular-branchpoint-critical-for-fetal-placental-arterial-union-in-the-mouse-gastrula
#16
Adriana M Rodriguez, Dexter X Jin, Adam D Wolfe, Maria M Mikedis, Lauren Wierenga, Maleka P Hashmi, Christoph Viebahn, Karen M Downs
How the fetal-placental arterial connection is made and positioned relative to the embryonic body axis, thereby ensuring efficient and directed blood flow to and from the mother during gestation, is not known. Here we use a combination of genetics, timed pharmacological inhibition in living mouse embryos, and three-dimensional modeling to link two novel architectural features that, at present, have no status in embryological atlases. The allantoic core domain (ACD) is the extraembryonic extension of the primitive streak into the allantois, or pre-umbilical tissue; the vessel of confluence (VOC), situated adjacent to the ACD, is an extraembryonic vessel that marks the site of fetal-placental arterial union...
April 4, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28376818/smokers-making-a-quit-attempt-using-e-cigarettes-with-or-without-nicotine-or-prescription-nicotine-replacement-therapy-impact-on-cardiovascular-function-isme-nrt-a-study-protocol
#17
Markos Klonizakis, Helen Crank, Anil Gumber, Leonie S Brose
BACKGROUND: The estimated number of cigarette smokers in the world is 1.3 billion, expected to rise to 1.7 billion by 2025, with 10 million smokers living in the U.K. Smoking is the leading, preventable death-cause worldwide, being responsible for almost 650,000 deaths in the E.U. annually. A combination of pharmacological interventions, including nicotine replacement therapy, bupropion and varenicline, and behavioural support is the most effective approach to smoking cessation. However, even the best methods have high relapse rates of approximately 75% within 6 months...
April 4, 2017: BMC Public Health
https://www.readbyqxmd.com/read/28376510/impact-of-intravitreal-pharmacotherapies-including-antivascular-endothelial-growth-factor-and-corticosteroid-agents-on-diabetic-retinopathy
#18
REVIEW
Charles C Wykoff
PURPOSE OF REVIEW: Diabetic retinopathy is common and increasing in prevalence. Pharmacologic management of diabetic macular edema (DME) has improved tremendously over the last decade with the use of two families of intravitreally administered medications: antivascular endothelial growth factor-specific agents and corticosteroids. Clinical evaluation of these pharmaceuticals has demonstrated that they can have a substantial impact on diabetic retinopathy severity levels and the underlying retinal vasculature itself...
May 2017: Current Opinion in Ophthalmology
https://www.readbyqxmd.com/read/28373630/a-novel-lipoprotein-a-lowering-drug-d-47-decreases-neointima-thickening-after-vascular-injury
#19
Yutaka Nakaya, Daiju Fukuda, Takashi Oyamada, Kazuo Ogawa, Nagakatsu Harada, Hironori Nakagami, Ryuichi Morishita, Masataka Sata, Hiroshi Sakaue
Although Lp(a) have been thought to be a cardiovascular risk factor, it is unclear whether lowering Lp(a) levels reduces the risk of cardiovascular diseases. No pharmacological agents which selectively reduce serum Lp(a) levels, and Lp(a) is present in primate but absent in common laboratory animals such as mice and pigs. In the present study we used transgenic mice of human Lp(a) and tested effect a novel Lp(a) lowering drug D-47 on neointima formation after vascular injury. D-47 successfully decreased plasma levels of Lp(a) and possibly inhibited neointima formation in Lp(a) transgenic mice...
2017: Journal of Medical Investigation: JMI
https://www.readbyqxmd.com/read/28372535/klf11-is-an-epigenetic-mediator-of-drd2-dopaminergic-signaling-in-endometriosis
#20
Elliott G Richards, Ye Zheng, Chandra C Shenoy, Alessandra J Ainsworth, Abigail A Delaney, Tiffanny L Jones, Zaraq Khan, Gaurang S Daftary
Endometriosis is a heterogeneous, recalcitrant disease that affects 10% of reproductive-age women. Resistance to conventional therapy critically raises the need for novel treatment options that target specific, dysregulated underlying molecular mechanisms. Dopamine receptor 2 (DRD2) has been shown to be associated with vascularity and fibrosis in endometriosis. Transcription factor KLF11 has been implicated in the pathogenesis of several human endocrine and reproductive tract diseases including endometriosis...
January 1, 2017: Reproductive Sciences
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