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C1-2 dysfunction

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https://www.readbyqxmd.com/read/28621447/metformin-prevents-vascular-prostanoid-release-alterations-induced-by-a-high-fat-diet-in-rats
#1
H J Lee, S M Cantú, A S Donoso, M R Choi, H A Peredo, A M Puyó
Perivascular adipose tissue dysfunction induced by high-fat feeding leads to alterations in the modulation of inflammation, contractile activity of the vascular smooth muscle and endothelial function, all risk factors in the development of hypertension. Metformin, an activator of AMP-activated protein kinase (AMPK), is currently the first-line drug treatment for type 2 diabetes (T2DM) and metabolic syndrome. Besides its glucose-lowering effect, there is an interest in actions of this drug with potential relevance in cardiovascular diseases...
June 16, 2017: Autonomic & Autacoid Pharmacology
https://www.readbyqxmd.com/read/28415010/structure-and-biological-properties-of-mixed-ligand-cu-ii-schiff-base-complexes-as-potential-anticancer-agents
#2
Yi Gou, Jinlong Li, Boyi Fan, Bohui Xu, Min Zhou, Feng Yang
We synthesized two mixed-ligand Cu(II) complexes containing different aroylhydrazone ligands and a pyridine co-ligand, namely, [Cu(L1)(Py)] (C1) and [Cu(L2)(Py)(Br)] (C2) (L1 = (E)-2-hydroxy-N'-((2-hydroxynaphthalen-1-yl)methylene)benzohydrazide, Py = pyridine, L2 = (E)-2-hydroxy-N'-(phenyl(pyridin-2-yl)methylene)benzohydrazide), and assessed their chemical and biological properties to understand their marked activity. C2 showed better anticancer activity than C1 in various human cancer cell lines, including the cisplatin-resistant lung cancer cell line A549cisR...
April 12, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28328347/prevention-of-hereditary-angioedema-attacks-with-a-subcutaneous-c1-inhibitor
#3
RANDOMIZED CONTROLLED TRIAL
Hilary Longhurst, Marco Cicardi, Timothy Craig, Konrad Bork, Clive Grattan, James Baker, Huamin H Li, Avner Reshef, James Bonner, Jonathan A Bernstein, John Anderson, William R Lumry, Henriette Farkas, Constance H Katelaris, Gordon L Sussman, Joshua Jacobs, Marc Riedl, Michael E Manning, Jacques Hebert, Paul K Keith, Shmuel Kivity, Sergio Neri, Donald S Levy, Maria L Baeza, Robert Nathan, Lawrence B Schwartz, Teresa Caballero, William Yang, Ioana Crisan, María D Hernandez, Iftikhar Hussain, Michael Tarzi, Bruce Ritchie, Pavlina Králíčková, Mar Guilarte, Syed M Rehman, Aleena Banerji, Richard G Gower, Debra Bensen-Kennedy, Jonathan Edelman, Henrike Feuersenger, John-Philip Lawo, Thomas Machnig, Dipti Pawaskar, Ingo Pragst, Bruce L Zuraw
BACKGROUND: Hereditary angioedema is a disabling, potentially fatal condition caused by deficiency (type I) or dysfunction (type II) of the C1 inhibitor protein. In a phase 2 trial, the use of CSL830, a nanofiltered C1 inhibitor preparation that is suitable for subcutaneous injection, resulted in functional levels of C1 inhibitor activity that would be expected to provide effective prophylaxis of attacks. METHODS: We conducted an international, prospective, multicenter, randomized, double-blind, placebo-controlled, dose-ranging, phase 3 trial to evaluate the efficacy and safety of self-administered subcutaneous CSL830 in patients with type I or type II hereditary angioedema who had had four or more attacks in a consecutive 2-month period within 3 months before screening...
March 23, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28260735/mechanisms-of-left-ventricular-dysfunction-assessed-by-layer-specific-strain-analysis-in-patients-with-repaired-tetralogy-of-fallot
#4
Mariko Yamada, Ken Takahashi, Maki Kobayashi, Kana Yazaki, Hirobumi Takayasu, Katsumi Akimoto, Masahiko Kishiro, Akio Inage, Tadahiro Yoshikawa, In-Sam Park, Keisuke Nakanishi, Shiori Kawasaki, Toshiaki Shimizu
BACKGROUND: Left ventricular (LV) dysfunction in patients with repaired tetralogy of Fallot (rTOF) is an important risk factor for adverse outcomes. The aim of this study was to assess the details and time course of such LV dysfunction using layer-specific strain analysis by echocardiography.Methods and Results:The 66 patients with rTOF (mean age, 16.3±9.3 years) were divided into 3 groups (T1: 4-10 years, T2: 11-20 years, T3: 21-43 years), and 113 controls of similar age (mean age, 17...
March 3, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/27923782/comparing-arterial-function-parameters-for-the-prediction-of-coronary-heart-disease-events-the-multi-ethnic-study-of-atherosclerosis-mesa
#5
Elizabeth K Hom, Daniel A Duprez, David R Jacobs, David A Bluemke, Lyndia C Brumback, Joseph F Polak, Carmen A Peralta, Philip Greenland, Sheryl L Magzamen, João A C Lima, Alban Redheuil, David M Herrington, James H Stein, Dhananjay Vaidya, Pamela Ouyang, Joel D Kaufman
Arterial dysfunction has been linked to decline in cardiac function and increased risk of cardiovascular disease events. We calculated the value of arterial function, measured at baseline (2000-2002), in predicting time to first coronary heart disease (CHD) event (median follow-up, 10.2 years) among participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Measures included the following: C1 and C2, derived from diastolic pulse contour analysis from the radial artery blood pressure waveform obtained by tonometry (n = 6,336); carotid distensibility and Young's elastic modulus at the carotid artery, derived from carotid artery ultrasonography (n = 6,531 and 6,528); and aortic distensibility, measured using cardiac magnetic resonance imaging (n = 3,677)...
December 15, 2016: American Journal of Epidemiology
https://www.readbyqxmd.com/read/27769893/phenylethanolamine-n-methyltransferase-gene-expression-in-adrenergic-neurons-of-spontaneously-hypertensive-rats
#6
Julie Grandbois, Sandhya Khurana, Kelly Graff, Phong Nguyen, Leah Meltz, T C Tai
Epinephrine is synthesised by the catecholamine biosynthetic enzyme, phenylethanolamine N-methyltransferase (PNMT), primarily in chromaffin cells of the adrenal medulla and secondarily in brainstem adrenergic neurons of the medulla oblongata. Epinephrine is an important neurotransmitter/neurohormone involved in cardiovascular regulation; however, overproduction is detrimental with negative outcomes such as cellular damage, cardiovascular dysfunction, and hypertension. Genetic mapping studies have linked elevated expression of PNMT to hypertension...
December 2, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27586038/developmental-delay-in-motor-skill-acquisition-in-niemann-pick-c1-mice-reveals-abnormal-cerebellar-morphogenesis
#7
Paola Caporali, Francesco Bruno, Giampiero Palladino, Jessica Dragotto, Laura Petrosini, Franco Mangia, Robert P Erickson, Sonia Canterini, Maria Teresa Fiorenza
Niemann-Pick type C1 (NPC1) disease is a lysosomal storage disorder caused by defective intracellular trafficking of exogenous cholesterol. Purkinje cell (PC) degeneration is the main sign of cerebellar dysfunction in both NPC1 patients and animal models. It has been recently shown that a significant decrease in Sonic hedgehog (Shh) expression reduces the proliferative potential of granule neuron precursors in the developing cerebellum of Npc1 (-/-) mice. Pursuing the hypothesis that this developmental defect translates into functional impairments, we have assayed Npc1-deficient pups belonging to the milder mutant mouse strain Npc1 (nmf164) for sensorimotor development from postnatal day (PN) 3 to PN21...
2016: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/27559458/clinical-presentation-of-cervical-myelopathy-at-c1-2-level
#8
Yasutaka Murahashi, Tsuneo Takebayashi, Yoshinori Terashima, Hajime Tsuda, Mitsunori Yoshimoto, Toshihiko Yamashita
STUDY DESIGN: Single-center retrospective study. PURPOSE: To clarify the clinical features of cervical myelopathy at the C1-2 level. OVERVIEW OF LITERATURE: Methods for distinguishing the affected level based on myelomere symptoms or dysfunction of the conducting pathway were established. However, no symptoms have been identified as being specific to the C1-2 level segment. METHODS: We evaluated 24 patients with cervical myelopathy due to spinal cord compression at the C1-2 level...
August 2016: Asian Spine Journal
https://www.readbyqxmd.com/read/27554845/a-novel-role-for-small-molecule-glycomimetics-in-the-protection-against-lipid-induced-endothelial-dysfunction-involvement-of-akt-enos-and-nrf2-are-signaling
#9
Ayman M Mahmoud, Fiona L Wilkinson, Alan M Jones, James A Wilkinson, Miguel Romero, Juan Duarte, M Yvonne Alexander
BACKGROUND: Glycomimetics are a diverse array of saccharide-inspired compounds, designed to mimic the bioactive functions of glycosaminoglycans. Therefore, glycomimetics represent a unique source of novel therapies to target aberrant signaling and protein interactions in a wide range of diseases. We investigated the protective effects of four newly synthesized small molecule glycomimetics against lipid-induced endothelial dysfunction, with an emphasis on nitric oxide (NO) and oxidative stress...
January 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27499185/serological-evidence-of-infection-with-rodent-borne-hepatitis-e-virus-hev-c1-or-antigenically-related-virus-in-humans
#10
Kenta Shimizu, Sugihiro Hamaguchi, Cuong Chi Ngo, Tian-Cheng Li, Shuji Ando, Kumiko Yoshimatsu, Shumpei P Yasuda, Takaaki Koma, Rie Isozumi, Yoshimi Tsuda, Hiromi Fujita, Thuy Thanh Pham, Mai Quynh LE, Anh Duc Dang, Tuan Quang Nguyen, Lay-Myint Yoshida, Koya Ariyoshi, Jiro Arikawa
Zoonotic potential of a rat-derived hepatitis E virus (HEV), designated as HEV-C1, remains unknown. To evaluate the risk for HEV-C1 infection in humans, paired sera of 208 hospitalized febrile patients collected from 2001 to 2003 in Hanoi, Vietnam, were examined for IgG antibodies to HEV-C1 and genotype 1 HEV (HEV-1), which is common in humans. IgG antibodies to virus-like particles (VLPs) of HEV-C1 and/or HEV-1 were detected from 99 of the 208 convalescent sera in enzyme-linked immunosorbent assay (ELISA)...
December 1, 2016: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/27307499/cerebrospinal-fluid-calbindin-d-concentration-as-a-biomarker-of-cerebellar-disease-progression-in-niemann-pick-type-c1-disease
#11
Allison Bradbury, Jessica Bagel, Maureen Sampson, Nicole Farhat, Wenge Ding, Gary Swain, Maria Prociuk, Patricia O'Donnell, Kenneth Drobatz, Brittney Gurda, Christopher Wassif, Alan Remaley, Forbes Porter, Charles Vite
Niemann-Pick type C (NPC) 1 disease is a rare, inherited, neurodegenerative disease. Clear evidence of the therapeutic efficacy of 2-hydroxypropyl-β-cyclodextrin (HPβCD) in animal models resulted in the initiation of a phase I/IIa clinical trial in 2013 and a phase IIb/III trial in 2015. With clinical trials ongoing, validation of a biomarker to track disease progression and serve as a supporting outcome measure of therapeutic efficacy has become compulsory. In this study, we evaluated calcium-binding protein calbindin D-28K (calbindin) concentrations in the cerebrospinal fluid (CSF) as a biomarker of NPC1 disease...
August 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27230912/intradural-synovial-cyst-of-the-atlantoaxial-joint-a-case-report
#12
Sebastian Hartmann, Anja Tschugg, Pujan Kavakebi, Claudius Thomé
BACKGROUND: Intradural synovial cysts of the cervical spine represent a rare disease entity, causing stenosis of the spinal canal and thereby leading to progressive myelopathy. In particular, at the cranio-cervical junction early intervention is necessary to prevent permanent neurological dysfunction. We present the case of a 74-year-old man who presented with moderate cervicogenic headache, gait disturbance and progressive left-sided weakness. Magnetic resonance imaging (MRI) of the cervical spine confirmed a left-sided cystic mass located anteriorly at the craniovertebral junction compressing the surrounding structures...
August 2016: Acta Neurochirurgica
https://www.readbyqxmd.com/read/27138869/type-2-diabetic-patients-with-diabetic-retinopathy-and-concomitant-microalbuminuria-showed-typical-diabetic-glomerulosclerosis-and-progressive-renal-dysfunction
#13
Tatsumi Moriya, Madoka Matsubara, Eriko Kishihara, Yuki Yoshida, Motoshi Ouchi
AIMS: To determine whether or not diabetic retinopathy (DR) in type 2 diabetic patients can predict the renal functional decline. METHODS: We examined 32 normo-microalbuminuric type 2 diabetic patients by renal biopsy (23 men, age 49±10yrs) divided into two groups according to the presence (n=19) or absence (n=13) of DR. Electron microscopic morphometry including mesangial fractional volume [Vv(Mes/glom)] were performed and light microscopic tissues were categorized as: C1, normal/near normal renal structure; C2, typical diabetic glomerulopathy; C3, atypical injury patterns...
August 2016: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/26868691/contributions-of-nondiastolic-factors-to%C3%A2-exercise-intolerance-in-heart-failure-with-preserved-ejection-fraction
#14
Wojciech Kosmala, Aleksandra Rojek, Monika Przewlocka-Kosmala, Andrzej Mysiak, Bozena Karolko, Thomas H Marwick
BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) has a complex etiology. Factors responsible for development of impaired exercise tolerance and disease progression are incompletely defined. OBJECTIVES: The authors sought to define the contributions of contractile reserve, ventriculo-arterial coupling (VAC) reserve, and chronotropic response to the progression of HFpEF. METHODS: We performed echocardiography at rest and immediately post-cardiopulmonary exercise test in 207 patients (63 ± 8 years of age) with stage C heart failure (HF) (exertional dyspnea, New York Heart Association functional class II to III, exercise capacity <80% of normal, left ventricular ejection fraction >50%, and diastolic dysfunction) and 60 patients with stage B HF (normal exercise tolerance with left ventricular hypertrophy, and/or reduced global longitudinal strain, with diastolic dysfunction)...
February 16, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/26839380/s-glutathiolation-impairs-phosphoregulation-and-function-of-cardiac-myosin-binding-protein-c-in-human-heart-failure
#15
Konstantina Stathopoulou, Ilka Wittig, Juliana Heidler, Angelika Piasecki, Florian Richter, Simon Diering, Jolanda van der Velden, Friedrich Buck, Sonia Donzelli, Ewald Schröder, Paul J M Wijnker, Niels Voigt, Dobromir Dobrev, Sakthivel Sadayappan, Thomas Eschenhagen, Lucie Carrier, Philip Eaton, Friederike Cuello
Cardiac myosin-binding protein C (cMyBP-C) regulates actin-myosin interaction and thereby cardiac myocyte contraction and relaxation. This physiologic function is regulated by cMyBP-C phosphorylation. In our study, reduced site-specific cMyBP-C phosphorylation coincided with increased S-glutathiolation in ventricular tissue from patients with dilated or ischemic cardiomyopathy compared to nonfailing donors. We used redox proteomics, to identify constitutive and disease-specific S-glutathiolation sites in cMyBP-C in donor and patient samples, respectively...
May 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/26377703/presumptive-acute-non-compressive-nucleus-pulposus-extrusion-in-11-cats-clinical-features-diagnostic-imaging-findings-treatment-and-outcome
#16
Frances E Taylor-Brown, Steven De Decker
Objectives The aim of the study was to describe the clinical features, diagnostic imaging findings, treatment and outcome in cats diagnosed with presumptive acute non-compressive nucleus pulposus extrusion. Methods Medical records and imaging studies of cats diagnosed with presumptive acute non-compressive nucleus pulposus extrusion were retrospectively reviewed. Information on long-term outcome was acquired from patient records and from either owners or referring veterinary surgeons via a telephone questionnaire...
January 2017: Journal of Feline Medicine and Surgery
https://www.readbyqxmd.com/read/26280899/complement-modulation-of-anti-aging-factor-klotho-in-ischemia-reperfusion-injury-and-delayed-graft-function
#17
RANDOMIZED CONTROLLED TRIAL
G Castellano, A Intini, A Stasi, C Divella, M Gigante, P Pontrelli, R Franzin, M Accetturo, A Zito, M Fiorentino, V Montinaro, G Lucarelli, P Ditonno, M Battaglia, A Crovace, F Staffieri, B Oortwijn, E van Amersfoort, G Pertosa, G Grandaliano, L Gesualdo
Klotho is an anti-aging factor mainly produced by renal tubular epithelial cells (TEC) with pleiotropic functions. Klotho is down-regulated in acute kidney injury in native kidney; however, the modulation of Klotho in kidney transplantation has not been investigated. In a swine model of ischemia/reperfusion injury (IRI), we observed a remarkable reduction of renal Klotho by 24 h from IRI. Complement inhibition by C1-inhibitor preserved Klotho expression in vivo by abrogating nuclear factor kappa B (NF-kB) signaling...
January 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/26111105/plasma-derived-c1-inh-for-managing-hereditary-angioedema-in-pediatric-patients-a-systematic-review
#18
REVIEW
Timothy J Craig, Lynda C Schneider, Andrew J MacGinnitie
Presently, medications approved for children with Hereditary Angioedema (HAE) are extremely limited. This is especially the case for children under 12 years of age. For this reason we reviewed and summarized the data on treatment of children with HAE. Available data indicate that plasma derived C1-inhibitor is a safe, effective treatment option for HAE in pediatric patients, including those below 12 years of age. Other therapies are also appear safe for the under 12 year of age, but less data are available...
September 2015: Pediatric Allergy and Immunology
https://www.readbyqxmd.com/read/26037664/fusing-functional-mri-and-diffusion-tensor-imaging-measures-of-brain-function-and-structure-to-predict-working-memory-and-processing-speed-performance-among-inter-episode-bipolar-patients
#19
Benjamin S McKenna, Rebecca J Theilmann, Ashley N Sutherland, Lisa T Eyler
Evidence for abnormal brain function as measured with diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) and cognitive dysfunction have been observed in inter-episode bipolar disorder (BD) patients. We aimed to create a joint statistical model of white matter integrity and functional response measures in explaining differences in working memory and processing speed among BD patients. Medicated inter-episode BD (n=26; age=45.2±10.1 years) and healthy comparison (HC; n=36; age=46...
May 2015: Journal of the International Neuropsychological Society: JINS
https://www.readbyqxmd.com/read/25963506/changes-in-anatomical-and-functional-connectivity-of-parkinson-s-disease-patients-according-to-cognitive-status
#20
Boyu Chen, Guo Guang Fan, Hu Liu, Shanshan Wang
PURPOSE: This study assesses the patterns of structural and functional connectivity damage in patients with Parkinson's disease dementia (PDD) compared with cognitively unimpaired Parkinson's disease patients (PD-Cu) and healthy controls (HC). MATERIALS AND METHODS: Resting state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor magnetic resonance imaging (DTI) scans were obtained from 30 PD and 21 sex- and age-matched HC. The between-group difference in posterior cingulate (PCC) functional connectivity (FC) was performed to assess FC dysfunction...
July 2015: European Journal of Radiology
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