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Pathophysiology diabetic injury

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https://www.readbyqxmd.com/read/28526762/exacerbation-of-thromboinflammation-by-hyperglycemia-precipitates-cerebral-infarct-growth-and-hemorrhagic-transformation
#1
Jean-Philippe Desilles, Varouna Syvannarath, Véronique Ollivier, Clément Journé, Sandrine Delbosc, Célina Ducroux, William Boisseau, Liliane Louedec, Lucas Di Meglio, Stéphane Loyau, Martine Jandrot-Perrus, Louis Potier, Jean-Baptiste Michel, Mikael Mazighi, Benoit Ho-Tin-Noé
BACKGROUND AND PURPOSE: Admission hyperglycemia is associated with a poor outcome in acute ischemic stroke. How hyperglycemia impacts the pathophysiology of acute ischemic stroke remains largely unknown. We investigated how preexisting hyperglycemia increases ischemia/reperfusion cerebral injury. METHODS: Normoglycemic and streptozotocin-treated hyperglycemic rats were subjected to transient middle cerebral artery occlusion. Infarct growth and brain perfusion were assessed by magnetic resonance imaging...
May 19, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28520942/emerging-roles-for-micrornas-in-diabetic-microvascular-disease-novel-targets-for-therapy
#2
Yu Zhang, Xinghui Sun, Basak Icli, Mark W Feinberg
Chronic, low-grade systemic inflammation and impaired microvascular function are critical hallmarks in the development of insulin resistance. Accordingly, insulin resistance is a major risk factor for type 2 diabetes and cardiovascular disease. Accumulating studies demonstrate that restoration of impaired function of the diabetic macro- and microvasculature may ameliorate a range of cardiovascular disease states and diabetes-associated complications. In this review, we focus on the emerging role of microRNAs (miRNAs), noncoding RNAs that fine-tune target gene expression and signaling pathways, in insulin-responsive tissues and cell types important for maintaining optimal vascular homeostasis and preventing the sequelae of diabetes-induced end organ injury...
April 1, 2017: Endocrine Reviews
https://www.readbyqxmd.com/read/28495930/adamts13-retards-progression-of-diabetic-nephropathy-by-inhibiting-intrarenal-thrombosis-in-mice
#3
Nirav Dhanesha, Prakash Doddapattar, Mehul R Chorawala, Manasa K Nayak, Koichi Kokame, Janice M Staber, Steven R Lentz, Anil K Chauhan
OBJECTIVE: ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type I repeats-13) prevents microvascular thrombosis by cleaving prothrombogenic ultralarge von Willebrand factor (VWF) multimers. Clinical studies have found association between reduced ADAMTS13-specific activity, ultralarge VWF multimers, and thrombotic angiopathy in patients with diabetic nephropathy. It remains unknown, however, whether ADAMTS13 deficiency or ultralarge VWF multimers have a causative effect in diabetic nephropathy...
May 11, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28476763/plasma-biomarkers-and-kidney-function-decline-in-early-and-established-diabetic-kidney-disease
#4
Steven G Coca, Girish N Nadkarni, Yuan Huang, Dennis G Moledina, Veena Rao, Jane Zhang, Bart Ferket, Susan T Crowley, Linda F Fried, Chirag R Parikh
Biomarkers of diverse pathophysiologic mechanisms may improve risk stratification for incident or progressive diabetic kidney disease (DKD) in persons with type 2 diabetes. To evaluate such biomarkers, we performed a nested case-control study (n=190 cases of incident DKD and 190 matched controls) and a prospective cohort study (n=1156) using banked baseline plasma samples from participants of randomized, controlled trials of early (ACCORD) and advanced (VA NEPHRON-D) DKD. We assessed the association and discrimination obtained with baseline levels of plasma TNF receptor-1 (TNFR-1), TNFR-2, and kidney injury molecule-1 (KIM-1) for the outcomes of incident DKD (ACCORD) and progressive DKD (VA-NEPHRON-D)...
May 5, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28476630/membrane-lipid-therapy-a-historical-perspective-of-membrane-targeted-therapies-from-lipid-bilayer-structure-to-the-pathophysiological-regulation-of-cells
#5
REVIEW
Pablo V Escribá
Our current understanding of membrane lipid composition, structure and functions has led to the investigation of their role in cell signaling, both in healthy and pathological cells. As a consequence, therapies based on the regulation of membrane lipid composition and structure have been recently developed. This novel field, known as Membrane Lipid Therapy, is growing and evolving rapidly, providing treatments that are now in use or that are being studied for their application to oncological disorders, Alzheimer's disease, spinal cord injury, stroke, diabetes, obesity, and neuropathic pain...
May 2, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28473473/the-emerging-role-of-nadph-oxidase-nox5%C3%A2-in-vascular-disease
#6
EDITORIAL
Jay C Jha, Anna M D Watson, Geetha Mathew, Lisanne C de Vos, Karin Jandeleit-Dahm
Oxidative stress is a consequence of up-regulation of pro-oxidant enzyme-induced reactive oxygen species (ROS) production and concomitant depletion of antioxidants. Elevated levels of ROS act as an intermediate and are the common denominator for various diseases including diabetes-associated macro-/micro-vascular complications and hypertension. A range of enzymes are capable of generating ROS, but the pro-oxidant enzyme family, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs), are the only enzymes known to be solely dedicated to ROS generation in the vascular tissues, kidney, aortas and eyes...
May 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28431381/zeaxanthin-ameliorates-high-glucose-induced-mesangial-cell-apoptosis-through-inhibiting-oxidative-stress-via-activating-akt-signalling-pathway
#7
Changjiang Ying, Lei Chen, Shanshan Wang, Yizhen Mao, Hongwei Ling, Wei Li, Xiaoyan Zhou
Oxidative stress is a critical factor in the pathophysiology of diabetic kidney disease. Previous study shows that hyperglycaemia aggravates renal injury through oxidative stress in diabetic model, and antioxidants have beneficial effect on diabetic kidney disease. However, the role of antioxidants in the progression of diabetic kidney disease is poorly understood. The aim of this study was to clarify whether zeaxanthin, an antioxidant, could ameliorate mesangial cell injury and if so, identify the related mechanism underlying this protective effect...
June 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28426518/pathophysiologic-insight-into-mesoamerican-nephropathy
#8
Magdalena Madero, Fernando E García-Arroyo, Laura-Gabriela Sánchez-Lozada
PURPOSE OF REVIEW: Mesoamerican nephropathy (MeN) is an emerging pathophysiological entity of Chronic kidney desease (CKD) not related to traditional risk factors (diabetes and hypertension) that have caused thousands of deaths in Central America, mainly in sugarcane workers. The focus of this review is to discuss the risk factors and probable mechanisms involved in the initiation and progression of this devastating disease. RECENT FINDINGS: Frequent episodes of subclinical Acute kidney injury caused by repetitive heat stress, dehydration, and strenuous work have been regarded as the main risk factors for MeN...
April 19, 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28409327/heat-shock-proteins-and-kidney-disease-perspectives-of-hsp-therapy
#9
REVIEW
Natalia Chebotareva, Irina Bobkova, Evgeniy Shilov
Heat shock proteins (HSPs) mediate a diverse range of cellular functions, prominently including folding and regulatory processes of cellular repair. A major property of these remarkable proteins, dependent on intracellular or extracellular location, is their capacity for immunoregulation that optimizes immune activity while avoiding hyperactivated inflammation. In this review, recent investigations are described, which examine roles of HSPs in protection of kidney tissue from various traumatic influences and demonstrate their potential for clinical management of nephritic disease...
May 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28408494/o-glcnacylation-and-cardiovascular-disease
#10
REVIEW
JaLessa N Wright, Helen E Collins, Adam R Wende, John C Chatham
The post-translational modification of serine and threonine residues of proteins found in numerous subcellular locations by O-linked N-acetylglucosamine (O-GlcNAc) is emerging as a key mediator of many cardiovascular pathophysiological processes. Early studies implicated increased protein O-GlcNAcylation as contributing to the cardiovascular complications associated with diabetes, whereas subsequent studies demonstrated that acute increases in O-GlcNAc levels were protective against ischemia/reperfusion injury...
April 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28379021/-type-2-diabetes-mellitus-and-chronic-kidney-disease
#11
Peter Ponťuch
The number of type 2 diabetic patients is increasing world-wide and a prediction of prevalence of chronic kidney disease up to 2025 in European diabetic population is alarming. Albuminuria and estimated glomerular filtration rate are cardinal biochemical parameters in diagnostics of diabetic nephropathy. Following diagnostic methods are also used: renal ultrasonography, ophthalmoscopy and in not clarified cases renal biopsy. Long-term optimal glycemic control, efficient antihypertensive treatment by angiotensin converting enzyme inhibitor, or angiotensin receptor blocker and recommended protein intake is a cornerstone of therapy...
2017: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/28323921/emerging-roles-for-micrornas-in-diabetic-microvascular-disease-novel-targets-for-therapy
#12
Yu Zhang, Xinghui Sun, Basak Icli, Mark W Feinberg
Chronic, low-grade systemic inflammation and impaired microvascular function are critical hallmarks in the development of insulin resistance. Accordingly, insulin resistance is a major risk factor for type 2 diabetes and cardiovascular disease. Accumulating studies demonstrate that restoration of impaired function of the diabetic macro- and microvasculature may ameliorate a range of cardiovascular disease states and diabetes-associated complications. In this review, we focus on the emerging role of microRNAs (miRNAs), noncoding RNAs that fine-tune target gene expression and signaling pathways, in insulin-responsive tissues and cell types important for maintaining optimal vascular homeostasis and preventing the sequelae of diabetes-induced end organ injury...
April 1, 2017: Endocrine Reviews
https://www.readbyqxmd.com/read/28298952/insights-for-oxidative-stress-and-mtor-signaling-in-myocardial-ischemia-reperfusion-injury-under-diabetes
#13
REVIEW
Dajun Zhao, Jian Yang, Lifang Yang
Diabetes mellitus (DM) displays a high morbidity. The diabetic heart is susceptible to myocardial ischemia/reperfusion (MI/R) injury. Impaired activation of prosurvival pathways, endoplasmic reticulum (ER) stress, increased basal oxidative state, and decreased antioxidant defense and autophagy may render diabetic hearts more vulnerable to MI/R injury. Oxidative stress and mTOR signaling crucially regulate cardiometabolism, affecting MI/R injury under diabetes. Producing reactive oxygen species (ROS) and reactive nitrogen species (RNS), uncoupling nitric oxide synthase (NOS), and disturbing the mitochondrial quality control may be three major mechanisms of oxidative stress...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28295872/cellular-crosstalk-inflammatory-signals-and-enhanced-microvascular-permeability
#14
Jerome W Breslin
Microvascular leakage remains a significant clinical problem for which there is no specific therapeutic available. This Special Topics issue of the journal Microcirculation features reviews pertaining to the cellular and molecular mechanisms that control the integrity of the microvascular barrier. Meegan et al [1] summarize recent research findings about how neutrophil extracellular traps and how these can cause injury to the microvascular barrier. Zhang et al [2] highlight the microvascular response to advanced glycation end products that are formed as part of the pathophysiology of diabetes mellitus...
March 14, 2017: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/28267434/dietary-phytochemicals-in-the-protection-against-oxysterol-induced-damage
#15
REVIEW
Antonio Cilla, Amparo Alegría, Alessandro Attanzio, Guadalupe Garcia-Llatas, Luisa Tesoriere, Maria A Livrea
The intake of fruits and vegetables is associated with reduced incidence of many chronic diseases. These foods contain phytochemicals that often possess antioxidant and free radical scavenging capacity and show anti-inflammatory action, which are also the basis of other bioactivities and health benefits, such as anticancer, anti-aging, and protective action for cardiovascular diseases, diabetes mellitus, obesity and neurodegenerative disorders. Many factors can be included in the etiopathogenesis of all of these multifactorial diseases that involve oxidative stress, inflammation and/or cell death processes, oxysterols, i...
March 3, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28259681/stem-cell-laden-hyaluronic-acid-based-spongy-like-hydrogels-for-an-integrated-healing-of-diabetic-wounds-pathophysiologies
#16
Lucília Pereira da Silva, Tírcia Carlos Santos, Daniel Barreira Rodrigues, Rogério Pedro Pirraco, Mariana Teixeira Cerqueira, Rui Luís Reis, Vitor Manuel Correlo, Alexandra Pinto Marques
The correlation between the pathophysiologies of diabetic foot ulcerations is yet to be established and improved treatments are still required. We propose a strategy that directs inflammation, neo-vascularization and neo-innervation of diabetic wounds. Aiming to potentiate a relevant secretome for nerve regeneration, stem cells were pre-cultured in hyaluronic acid-based spongy-like hydrogels under neurogenic/standard media prior transplantation into diabetic mice full-thickness wounds. Acellular spongy-like hydrogels and empty wounds were used as controls...
March 1, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28241825/non-alcoholic-fatty-liver-disease
#17
REVIEW
Brent A Neuschwander-Tetri
Non-alcoholic fatty liver disease has emerged a major challenge because of it prevalence, difficulties in diagnosis, complex pathogenesis, and lack of approved therapies. As the burden of hepatitis C abates over the next decade, non-alcoholic fatty liver disease will become the major form of chronic liver disease in adults and children and could become the leading indication for liver transplantation. This overview briefly summarizes the most recent data on the pathophysiology, diagnosis, and treatment of non-alcoholic fatty liver disease...
February 28, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28230738/clinical-implications-of-20-hydroxyeicosatetraenoic-acid-in-the-kidney-liver-lung-and-brain-an-emerging-therapeutic-target
#18
REVIEW
Osama H Elshenawy, Sherif M Shoieb, Anwar Mohamed, Ayman O S El-Kadi
Cytochrome P450-mediated metabolism of arachidonic acid (AA) is an important pathway for the formation of eicosanoids. The ω-hydroxylation of AA generates significant levels of 20-hydroxyeicosatetraenoic acid (20-HETE) in various tissues. In the current review, we discussed the role of 20-HETE in the kidney, liver, lung, and brain during physiological and pathophysiological states. Moreover, we discussed the role of 20-HETE in tumor formation, metabolic syndrome and diabetes. In the kidney, 20-HETE is involved in modulation of preglomerular vascular tone and tubular ion transport...
February 20, 2017: Pharmaceutics
https://www.readbyqxmd.com/read/28223003/treatment-of-metformin-intoxication-complicated-by-lactic-acidosis-and-acute-kidney-injury-the-role-of-prolonged-intermittent-hemodialysis
#19
Giuseppe Regolisti, Riccardo Antoniotti, Filippo Fani, Paolo Greco, Enrico Fiaccadori
Metformin intoxication with lactic acidosis, a potentially lethal condition, may develop in diabetic patients when the drug dose is inappropriate and/or its clearance is reduced. Diagnosis and therapy may be delayed due to nonspecific symptoms at presentation, with severe anion gap metabolic acidosis and elevated serum creatinine values being the most prominent laboratory findings. Confirmation requires measurement of serum metformin by high-performance liquid chromatography-tandem mass spectrometry, but this technique is available only at specialized institutions and cannot be relied on as a guide to immediate treatment...
February 17, 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28215037/the-italian-dystonia-registry-rationale-design-and-preliminary-findings
#20
Giovanni Defazio, M Esposito, G Abbruzzese, C L Scaglione, G Fabbrini, G Ferrazzano, S Peluso, R Pellicciari, A F Gigante, G Cossu, R Arca, L Avanzino, F Bono, M R Mazza, L Bertolasi, R Bacchin, R Eleopra, C Lettieri, F Morgante, M C Altavista, L Polidori, R Liguori, S Misceo, G Squintani, M Tinazzi, R Ceravolo, E Unti, L Magistrelli, M Coletti Moja, N Modugno, M Petracca, N Tambasco, M S Cotelli, M Aguggia, A Pisani, M Romano, M Zibetti, A R Bentivoglio, A Albanese, P Girlanda, A Berardelli
The Italian Dystonia Registry is a multicenter data collection system that will prospectively assess the phenomenology and natural history of adult-onset dystonia and will serve as a basis for future etiological, pathophysiological and therapeutic studies. In the first 6 months of activity, 20 movement disorders Italian centres have adhered to the registry and 664 patients have been recruited. Baseline historical information from this cohort provides the first general overview of adult-onset dystonia in Italy...
February 18, 2017: Neurological Sciences
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