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https://www.readbyqxmd.com/read/28212619/brain-and-liver-pathology-amyloid-deposition-and-interferon-responses-among-older-hiv-positive-patients-in-the-late-haart-era
#1
Isaac H Solomon, Umberto De Girolami, Sukrutha Chettimada, Vikas Misra, Elyse J Singer, Dana Gabuzda
BACKGROUND: HIV+ patients on highly active antiretroviral therapy (HAART) with suppressed viral loads have a low incidence of HIV-associated dementia, but increased prevalence of milder forms of HIV-associated neurocognitive disorders (HAND). These milder forms of HAND are often associated with minimal histological abnormalities, and their pathophysiology is unclear. Comorbidities, altered amyloid metabolism, accelerated brain aging, and activated interferon responses are suspected to play a role in HAND pathogenesis in HAART-treated persons...
February 17, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28211040/anti-cd3-treatment-upregulates-pd-1-expression-on-activated-effector-t-cells-and-severely-impairs-their-inflammatory-capacity
#2
Maja Wallberg, Asha Recino, Jenny Phillips, Duncan Howie, Margaux Vienne, Christopher Paluch, Miyuki Azuma, F Susan Wong, Herman Waldmann, Anne Cooke
T cells play a key role in the pathogenesis of type 1 diabetes, and targeting the CD3 component of the TCR complex provides one therapeutic approach. Anti-CD3 treatment can reverse overt disease in spontaneously diabetic non-obese diabetic mice, an effect proposed to, at least in part, be caused by a selective depletion of pathogenic cells. We have used a transfer model to further investigate the effects of anti-CD3 treatment on green fluorescent protein (GFP)(+) islet-specific effector T cells in vivo. The GFP expression allowed us to isolate the known effectors at different time points during treatment to assess cell presence in various organs as well as gene expression and cytokine production...
February 17, 2017: Immunology
https://www.readbyqxmd.com/read/28208043/the-australasian-diabetes-data-network-first-national-audit-of-children-and-adolescents-with-type-1-diabetes
#3
Helen Phelan, Helen Clapin, Loren Bruns, Fergus J Cameron, Andrew M Cotterill, Jennifer J Couper, Elizabeth A Davis, Kim C Donaghue, Craig A Jefferies, Bruce R King, Richard O Sinnott, Elaine B Tham, Jerry K Wales, Timothy W Jones, Maria E Craig
OBJECTIVES: To assess glycaemic control, anthropometry and insulin regimens in a national sample of Australian children and adolescents with type 1 diabetes. DESIGN: Cross-sectional analysis of de-identified, prospectively collected data from the Australasian Diabetes Data Network (ADDN) registry. SETTING: Five paediatric diabetes centres in New South Wales, Queensland, South Australia, Victoria and Western Australia. PARTICIPANTS: Children and adolescents (aged 18 years or under) with type 1 diabetes of at least 12 months' duration for whom data were added to the ADDN registry during 2015...
February 20, 2017: Medical Journal of Australia
https://www.readbyqxmd.com/read/28199363/infrapopliteal-angioplasty-using-a-combined-angiosomal-reperfusion-strategy
#4
G K Ambler, A L Stimpson, B G Wardle, D C Bosanquet, U K Hanif, S Germain, C Chick, N Goyal, C P Twine
INTRODUCTION: Infra-popliteal angioplasty continues to be widely performed with minimal evidence to guide practice. Endovascular device selection is contentious and there is even uncertainty over which artery to treat for optimum reperfusion. Direct reperfusion (DR) targets the artery supplying the ischaemic tissue. Indirect reperfusion (IR) targets an artery supplying collaterals to the ischaemic area. Our unit practice for the last eight years has been to attempt to open all tibial arteries at the time of angioplasty...
2017: PloS One
https://www.readbyqxmd.com/read/28196832/gpr55-a-new-promising-target-for-metabolism
#5
Eva Tuduri, Monica Imbernon, Rene Bautista, Marta Tojo, Johan Fernø, Carlos Diéguez, Rubén Nogueiras
GPR55 is a G-protein coupled receptor (GPCR) that has been identified as a new cannabinoid receptor. Given the wide localization of GPR55 in brain and peripheral tissues, this receptor has emerged as a regulator of multiple biological actions. Lysophosphatidylinositol (LPI) is generally accepted as the endogenous ligand of GPR55. In this review, we will focus on the role of GPR55 in energy balance and glucose metabolism. We will summarize its actions on feeding, nutrient partitioning, gastrointestinal motility and insulin secretion in preclinical models and the scarce data available in humans...
February 14, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28194400/eating-the-dead-to-keep-atherosclerosis-at-bay
#6
REVIEW
Megan L Brophy, Yunzhou Dong, Hao Wu, H N Ashiqur Rahman, Kai Song, Hong Chen
Atherosclerosis is the primary cause of coronary heart disease (CHD), ischemic stroke, and peripheral arterial disease. Despite effective lipid-lowering therapies and prevention programs, atherosclerosis is still the leading cause of mortality in the United States. Moreover, the prevalence of CHD in developing countries worldwide is rapidly increasing at a rate expected to overtake those of cancer and diabetes. Prominent risk factors include the hardening of arteries and high levels of cholesterol, which lead to the initiation and progression of atherosclerosis...
2017: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28194256/retinal-diseases-associated-with-oxidative-stress-and-the-effects-of-a-free-radical-scavenger-edaravone
#7
REVIEW
Tomomi Masuda, Masamitsu Shimazawa, Hideaki Hara
Oxidative stress plays a pivotal role in developing and accelerating retinal diseases including age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), and retinal vein occlusion (RVO). An excess amount of reactive oxygen species (ROS) can lead to functional and morphological impairments in retinal pigment epithelium (RPE), endothelial cells, and retinal ganglion cells (RGCs). Here we demonstrate that edaravone, a free radical scavenger, decreased apoptotic cell death, oxidative damage to DNA and lipids, and angiogenesis through inhibiting JNK and p38 MAPK pathways in AMD, glaucoma, DR, and RVO animal models...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28190920/acute-alloxan-renal-toxicity-in-the-rat-initially-causes-degeneration-of-thick-ascending-limbs-of-henle
#8
Yui Terayama, Yasushi Kodama, Tetsuro Matsuura, Kiyokazu Ozaki
Alloxan (AL) is a material well-known to induce diabetes. Prior to inducing a prolonged diabetic state, AL causes acute tubulointerstitial nephritis. However, the precise primary target site and mechanism of its nephrotoxicity remain unclear. The objective of this study was to evaluate the morphological characteristics relevant to acute renal toxicity following AL administration. Rats were intravenously treated with AL. Eight hours after AL treatment, aquaporin 1-negative and Na/K pump-positive thick ascending limbs of Henle (TAL) were degenerated in the outer medulla...
January 2017: Journal of Toxicologic Pathology
https://www.readbyqxmd.com/read/28188251/population-impact-efficiency-of-benefit-targeted-versus-risk-targeted-statin-prescribing-for-primary-prevention-of-cardiovascular-disease
#9
Mark J Pletcher, Michael Pignone, Jamie A Jarmul, Andrew E Moran, Eric Vittinghoff, Thomas Newman
BACKGROUND: Benefit-targeted statin prescribing may be superior to risk-targeted statin prescribing (the current standard), but the impact and efficiency of this approach are unclear. METHODS AND RESULTS: We analyzed the National Health and Nutrition Examination Survey (NHANES) using an open-source model (the Prevention Impact and Efficiency Model) to compare targeting of statin therapy according to expected benefit (benefit-targeted) versus baseline risk (risk-targeted) in terms of projected population-level impact and efficiency...
February 10, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28183563/effect-of-basal-insulin-dosage-on-blood-glucose-concentration-in-ambulatory-surgery-patients-with-type-2-diabetes
#10
Linda J Demma, Karen T Carlson, Elizabeth W Duggan, John Gordon Morrow, Guillermo Umpierrez
STUDY OBJECTIVE: Among patients with type 2 diabetes treated with insulin, perioperative hyperglycemia and hypoglycemia may cause undesirable symptoms, surgery delay or cancellation, or unexpected hospitalization. Our objective was to compare preoperative glargine dosing regimens on perioperative glycemic control in patients undergoing ambulatory surgery. DESIGN: Observational study. SETTING: Pre- and postoperative holding areas. PATIENTS: One hundred fifty patients with type 2 diabetes using a once daily, evening insulin glargine regimen undergoing ambulatory surgery were included...
February 2017: Journal of Clinical Anesthesia
https://www.readbyqxmd.com/read/28182694/insulin-treatment-prevents-wounding-associated-changes-in-tissue-and-circulating-neutrophil-mmp-9-and-ngal-in-diabetic-rats
#11
Maryam Abdollahi, Taria Shin Yi Ng, Alireza Rezaeizadeh, Sarah Aamidor, Stephen M Twigg, Danqing Min, Susan V McLennan
Neutrophils are important for wound repair, but their persistence can impair the healing process. Neutrophils express matrix metalloproteinases including MMP-9 and its regulator neutrophil gelatinase associated lipocalin (NGAL). Whether wounding affects neutrophil MMP-9 and NGAL in diabetic animals is not known. Skin wound tissue MMP-9 and NGAL was examined by qRT-PCR and immunohistochemistry in control, diabetic and insulin treated diabetic rats. The temporal expression of MMP-9 and NGAL mRNA, MMP-9 activity and the NGAL/MMP-9 complex was also investigated in an implant model and their circulating neutrophils...
2017: PloS One
https://www.readbyqxmd.com/read/28176508/a-structured-therapeutic-education-program-for-children-and-adolescents-with-type-1-diabetes-an-analysis-of-the-efficacy-of-the-pediatric-education-for-diabetes-project
#12
Alessandra Mauri, Susanna Schmidt, Valentina Sosero, Maria Sambataro, Laura Nollino, Francesco Fabris, Anna Corò, Antonella Scantamburlo, Michela Cazziola-Merlotto, Tania Ciani, Michele Tessarin, Agostino Paccagnella
BACKGROUND: Therapeutic education for Type 1 Diabetes involves the process of transmitting knowledge and developing the skills and behavior required to treat the disease. guidelines agree on stressing the importance of therapeutic educational intervention in teaching self-management skills to children and adolescents with Type 1 Diabetes (T1D). This study presents the results of the "Pediatric Education for Type 1 Diabetes (T1D)" (PED) project, specifically designed for children and adolescents aged 6 to 16, and structured on guidelines indications, as part of a broader clinical-educational intervention for Type 1 diabetes...
February 7, 2017: Minerva Pediatrica
https://www.readbyqxmd.com/read/28176326/identification-of-novel-inhibitors-of-the-amino-acid-transporter-b-0-at1-slc6a19-a-potential-target-to-induce-protein-restriction-and-to-treat-type-2-diabetes
#13
Qi Cheng, Nishank Shah, Angelika Bröer, Stephen Fairweather, Yang Jiang, Dieter Schmoll, Ben Corry, Stefan Bröer
BACKGROUND AND PURPOSE: The neutral amino acid transporter B(0) AT1 (SLC6A19) has recently been identified as a possible target to treat type 2 diabetes and related disorders. B(0) AT1 mediates the Na(+) -dependent uptake of all neutral amino acids. For surface expression and catalytic activity, B(0) AT1 requires coexpression of collectrin (TMEM27). In this study, we established tools to identify and evaluate novel inhibitors of B(0) AT1. EXPERIMENTAL APPROACH: A CHO-based cell line was generated, stably expressing collectrin and B(0) AT1...
February 8, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28174167/serum-n1-methylnicotinamide-is-associated-with-coronary-artery-disease-in-chinese-patients
#14
Ming Liu, Jihong Chu, Yang Gu, Haibo Shi, Rusheng Zhang, Lingzhun Wang, Jiandong Chen, Le Shen, Peng Yu, Xiaohu Chen, Wenzheng Ju, Zhenxing Wang
BACKGROUND: We previously reported that serum N(1)-methylnicotinamide (me-Nam), an indicator of nicotinamide N-methyltransferase activity, is associated with obesity and diabetes mellitus in Chinese patients. However, whether nicotinamide N-methyltransferase plays a role in human coronary artery disease (CAD) remains to be elucidated. We aim to investigate the associations of serum me-Nam with CAD in Chinese patients. METHODS AND RESULTS: Serum me-NAM was measured by liquid chromatography-mass spectrometry in patients with (n=230) or without (n=103) CAD as defined by coronary angiography...
February 7, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28170413/baseline-assessment-of-who-s-target-for-both-availability-and-affordability-of-essential-medicines-to-treat-non-communicable-diseases
#15
Margaret Ewen, Marjolein Zweekhorst, Barbara Regeer, Richard Laing
BACKGROUND: WHO has set a voluntary target of 80% availability of affordable essential medicines, including generics, to treat major non-communicable diseases (NCDs), in the public and private sectors of countries by 2025. We undertook a secondary analysis of data from 30 surveys in low- and middle-income countries, conducted from 2008-2015 using the World Health Organization (WHO)/Health Action International (HAI) medicine availability and price survey methodology, to establish a baseline for this target...
2017: PloS One
https://www.readbyqxmd.com/read/28167322/-nlrp3-inflammasome-blockade-reduces-liver-inflammation-and-fibrosis-in-experimental-nash-in-mice
#16
Auvro R Mridha, Alexander Wree, Avril A B Robertson, Matthew M Yeh, Casey D Johnson, Derrick M Van Rooyen, Fahrettin Haczeyni, Narci C-H Teoh, Christopher Savard, George N Ioannou, Seth L Masters, Kate Schroder, Matthew A Cooper, Ariel E Feldstein, Geoffrey C Farrell
BACKGROUND AND AIMS: NOD-like receptor protein 3 (NLRP3) inflammasome activation occurs in NAFLD. We used the first small molecule NLRP3 inhibitor, MCC950, to test whether inflammasome blockade alters inflammatory recruitment and liver fibrosis in two murine models of steatohepatitis. METHODS: We fed foz/foz and wildtype (Wt) mice atherogenic diet 16 weeks, gavaged MCC950 or vehicle until 24 weeks, then determining NAFLD phenotype. In mice fed methionine/choline deficient (MCD) diet, we gavaged MCC950 or vehicle 6 weeks and determined effects on liver fibrosis...
February 3, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28166324/effect-of-intensive-blood-pressure-control-on-gait-speed-and-mobility-limitation-in-adults-75-years-or-older-a-randomized-clinical-trial
#17
Michelle C Odden, Carmen A Peralta, Dan R Berlowitz, Karen C Johnson, Jeffrey Whittle, Dalane W Kitzman, Srinivasan Beddhu, John W Nord, Vasilios Papademetriou, Jeff D Williamson, Nicholas M Pajewski
Importance: Intensive blood pressure (BP) control confers a benefit on cardiovascular morbidity and mortality; whether it affects physical function outcomes is unknown. Objective: To examine the effect of intensive BP control on changes in gait speed and mobility status. Design, Setting, and Participants: This randomized, clinical trial included 2636 individuals 75 years or older with hypertension and no history of type 2 diabetes or stroke who participated in the Systolic Blood Pressure Intervention Trial (SPRINT)...
February 6, 2017: JAMA Internal Medicine
https://www.readbyqxmd.com/read/28164132/nlrp3-inflammasome-expression-and-signaling-in-human-diabetic-wounds-and-in-high-glucose-induced-macrophages
#18
Xiaotian Zhang, Jiezhi Dai, Li Li, Hua Chen, Yimin Chai
Introduction. To investigate the contribution and mechanism of NLRP3 inflammasome expression in human wounds in diabetes mellitus and in high glucose induced macrophages. Methods. In the present study, we compared the expression of NLRP3 inflammasome in debridement wound tissue from diabetic and nondiabetic patients. We also examined whether high glucose induces NLRP3 inflammasome expression in cultures THP-1-derived macrophages and the influence on IL-1β expression. Results. The expressions of NLRP3, caspase1, and IL-1β, at both the mRNA and protein level, were significantly higher in wounds of diabetic patients compared with nondiabetic wounds (P < 0...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28162804/impairment-of-endoplasmic-reticulum-is-involved-in-%C3%AE-cell-dysfunction-induced-by-microcystin-lr
#19
Yanyan Zhao, Qing Cao, Yaojia He, Qingju Xue, Liqiang Xie, Yunjun Yan
Microcystins (MCs) widely distributed in freshwaters have posed a significant risk to human health. Previous studies have demonstrated that exposure to MC-LR impairs pancreatic islet function, however, the underlying mechanisms still remain unclear. In the present study, we explored the role of endoplasmic reticulum (ER) impairment in β-cell dysfunction caused by MC-LR. The result showed that MC-LR modified ER morphology evidenced by increased ER amount and size at low doses (15, 30 or 60 μM) and vacuolar and dilated ER ultrastructure at high doses (100 or 200 μM)...
February 2, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28161619/combination-of-metformin-with-chemotherapeutic-drugs-via-different-molecular-mechanisms
#20
REVIEW
Mei Peng, Kwame Oteng Darko, Ting Tao, Yanjun Huang, Qiongli Su, Caimei He, Tao Yin, Zhaoqian Liu, Xiaoping Yang
Metformin, a widely prescribed drug for treating type II diabetes, is one of the most extensively recognized metabolic modulators which has shown an important anti-cancer property. However, fairly amount of clinical trials on its single administration have not demonstrated a convincing efficiency yet. Thus, recent studies tend to combine metformin with clinical commonly used chemotherapeutic drugs to decrease their toxicity and attenuate their tumor resistance. These strategies have displayed promising clinical benefits...
January 23, 2017: Cancer Treatment Reviews
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