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Pathophysiology diabetic injury

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https://www.readbyqxmd.com/read/28060743/2017-update-on-the-relationship-between-diabetes-and-colorectal-cancer-epidemiology-potential-molecular-mechanisms-and-therapeutic-implications
#1
REVIEW
Nieves González, Isabel Prieto, Laura Del Puerto-Nevado, Sergio Portal-Nuñez, Juan Antonio Ardura, Marta Corton, Beatriz Fernández-Fernández, Oscar Aguilera, Carmen Gomez-Guerrero, Sebastián Mas, Juan Antonio Moreno, Marta Ruiz-Ortega, Ana Belen Sanz, Maria Dolores Sanchez-Niño, Federico Rojo, Fernando Vivanco, Pedro Esbrit, Carmen Ayuso, Gloria Alvarez-Llamas, Jesús Egido, Jesús García-Foncillas, Alberto Ortiz, Diabetes Cancer Connect Consortium
Worldwide deaths from diabetes mellitus (DM) and colorectal cancer increased by 90% and 57%, respectively, over the past 20 years. The risk of colorectal cancer was estimated to be 27% higher in patients with type 2 DM than in non-diabetic controls. However, there are potential confounders, information from lower income countries is scarce, across the globe there is no correlation between DM prevalence and colorectal cancer incidence and the association has evolved over time, suggesting the impact of additional environmental factors...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28027072/spectrum-of-drug-induced-chronic-diarrhea
#2
Nissy A Philip, Nazir Ahmed, Capecomorin S Pitchumoni
The evaluation of a patient with chronic diarrhea can be quite frustrating, as it is expensive and involves multiple diagnostic studies. Moreover, identification of a drug as a cause of chronic diarrhea is a challenge in patients taking multiple medications. The disease may either be associated with intestinal mucosal changes, mimicking diseases such as celiac disease, or purely functional, with no histopathologic change. Drug-induced diarrhea may or may not be associated with malabsorption of nutrients, and a clinical improvement may occur within days of discontinuation of the drug, or may take longer when associated with mucosal injury...
February 2017: Journal of Clinical Gastroenterology
https://www.readbyqxmd.com/read/28003360/downregulation-of-insulin-receptor-substrate-1-during-hyperglycemia-induces-vascular-smooth-muscle-cell-dedifferentiation
#3
Gang Xi, Christine Wai, Morris F White, David R Clemmons
Diabetes is a major risk factor for the development of atherosclerosis but the mechanism by which hyperglycemia accelerates lesion development is not well defined. Insulin and insulin like growth factor-I (IGF-I)1 signal through the scaffold protein insulin receptor substrate-1(IRS-1). In diabetes IRS-1 is down regulated and cells become resistant to insulin. Under these conditions the IGF-I receptor signals through an alternate scaffold protein, SHPS-1, resulting in pathophysiologic stimulation of vascular smooth muscle cell (VSMC) migration and proliferation...
December 21, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27976413/medicinal-chemistry-pharmacology-and-clinical-implications-of-trpv1-receptor-antagonists
#4
REVIEW
Mojgan Aghazadeh Tabrizi, Pier Giovanni Baraldi, Stefania Baraldi, Stefania Gessi, Stefania Merighi, Pier Andrea Borea
Transient receptor potential vanilloid 1 (TRPV1) is an ion channel expressed on sensory neurons triggering an influx of cations. TRPV1 receptors function as homotetramers responsive to heat, proinflammatory substances, lipoxygenase products, resiniferatoxin, endocannabinoids, protons, and peptide toxins. Its phosphorylation increases sensitivity to both chemical and thermal stimuli, while desensitization involves a calcium-dependent mechanism resulting in receptor dephosphorylation. TRPV1 functions as a sensor of noxious stimuli and may represent a target to avoid pain and injury...
December 15, 2016: Medicinal Research Reviews
https://www.readbyqxmd.com/read/27974711/skin-wound-healing-an-update-on-the-current-knowledge-and-concepts
#5
Heiko Sorg, Daniel J Tilkorn, Stephan Hager, Jörg Hauser, Ursula Mirastschijski
BACKGROUND: The integrity of healthy skin plays a crucial role in maintaining physiological homeostasis of the human body. The skin is the largest organ system of the body. As such, it plays pivotal roles in the protection against mechanical forces and infections, fluid imbalance, and thermal dysregulation. At the same time, it allows for flexibility to enable joint function in some areas of the body and more rigid fixation to hinder shifting of the palm or foot sole. Many instances lead to inadequate wound healing which necessitates medical intervention...
December 15, 2016: European Surgical Research. Europäische Chirurgische Forschung. Recherches Chirurgicales Européennes
https://www.readbyqxmd.com/read/27941788/small-molecule-inhibition-of-stoml3-oligomerization-reverses-pathological-mechanical-hypersensitivity
#6
Christiane Wetzel, Simone Pifferi, Cristina Picci, Caglar Gök, Diana Hoffmann, Kiran K Bali, André Lampe, Liudmila Lapatsina, Raluca Fleischer, Ewan St John Smith, Valérie Bégay, Mirko Moroni, Luc Estebanez, Johannes Kühnemund, Jan Walcher, Edgar Specker, Martin Neuenschwander, Jens Peter von Kries, Volker Haucke, Rohini Kuner, James F A Poulet, Jan Schmoranzer, Kate Poole, Gary R Lewin
The skin is equipped with specialized mechanoreceptors that allow the perception of the slightest brush. Indeed, some mechanoreceptors can detect even nanometer-scale movements. Movement is transformed into electrical signals via the gating of mechanically activated ion channels at sensory endings in the skin. The sensitivity of Piezo mechanically gated ion channels is controlled by stomatin-like protein-3 (STOML3), which is required for normal mechanoreceptor function. Here we identify small-molecule inhibitors of STOML3 oligomerization that reversibly reduce the sensitivity of mechanically gated currents in sensory neurons and silence mechanoreceptors in vivo...
December 12, 2016: Nature Neuroscience
https://www.readbyqxmd.com/read/27941647/the-role-of-erk1-2-in-the-development-of-diabetic-cardiomyopathy
#7
REVIEW
Zheng Xu, Jian Sun, Qian Tong, Qian Lin, Lingbo Qian, Yongsoo Park, Yang Zheng
Diabetes mellitus is a chronic metabolic condition that affects carbohydrate, lipid and protein metabolism and may impair numerous organs and functions of the organism. Cardiac dysfunction afflicts many patients who experience the oxidative stress of the heart. Diabetic cardiomyopathy (DCM) is one of the major complications that accounts for more than half of diabetes-related morbidity and mortality cases. Chronic hyperglycemia and hyperlipidemia from diabetes mellitus cause cardiac oxidative stress, endothelial dysfunction, impaired cellular calcium handling, mitochondrial dysfunction, metabolic disturbances, and remodeling of the extracellular matrix, which ultimately lead to DCM...
December 8, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27914709/podocyte-specific-chemokine-c-c-motif-receptor-2%C3%A2-overexpression-mediates-diabetic-renal-injury-in%C3%A2-mice
#8
Hanning You, Ting Gao, Wesley M Raup-Konsavage, Timothy K Cooper, Sarah K Bronson, W Brian Reeves, Alaa S Awad
Inflammation is a central pathophysiologic mechanism that contributes to diabetes mellitus and diabetic nephropathy. Recently, we showed that macrophages directly contribute to diabetic renal injury and that pharmacological blockade or genetic deficiency of chemokine (C-C motif) receptor 2 (CCR2) confers kidney protection in diabetic nephropathy. However, the direct role of CCR2 in kidney-derived cells such as podocytes in diabetic nephropathy remains unclear. To study this, we developed a transgenic mouse model expressing CCR2 specifically in podocytes (Tg[NPHS2-Ccr2]) on a nephropathy-prone (DBA/2J) and CCR2-deficient (Ccr2(-/-)) background with heterozygous Ccr2(+/-) littermate controls...
November 30, 2016: Kidney International
https://www.readbyqxmd.com/read/27896904/contrast-induced-encephalopathy-following-cardiac-catheterization
#9
Roberto Spina, Neil Simon, Romesh Markus, David Wm Muller, Krishna Kathir
OBJECTIVES: To describe the epidemiology, pathophysiology, clinical presentation, and management of contrast-induced encephalopathy (CIE) following cardiac catheterization. BACKGROUND: CIE is an acute, reversible neurological disturbance directly attributable to the intra-arterial administration of iodinated contrast medium. METHODS: The PubMed database was searched and all cases in the literature were retrieved and reviewed. RESULTS: 52 reports of CIE following cardiac catheterization were found...
November 29, 2016: Catheterization and Cardiovascular Interventions
https://www.readbyqxmd.com/read/27889567/prognostic-value-of-plasma-apelin-concentrations-at-admission-in-patients-with-st-segment-elevation-acute-myocardial-infarction
#10
Jordi Sans-Roselló, Gregori Casals, Xavier Rossello, Bernardino González de la Presa, Montserrat Vila, Albert Duran-Cambra, Manuel Morales-Ruiz, Andreu Ferrero-Gregori, Wladimiro Jiménez, Alessandro Sionis
BACKGROUND: The use of plasma biomarkers is relevant for the prognosis of ST-segment elevation myocardial infarction (STEMI) patients. Apelin, an adipocytokine, plays a pivotal role in the pathophysiology of both ischemia/reperfusion injury and its potential subsequent heart failure. We evaluated apelin concentrations at admission as a biomarker to assess risk of 6-month mortality. METHODS: Consecutive patients with STEMI were recruited from January 2012 to January 2013 (n=250)...
November 24, 2016: Clinical Biochemistry
https://www.readbyqxmd.com/read/27883184/epigenetics-in-reactive-and-reparative-cardiac-fibrogenesis-the-promise-of-epigenetic-therapy
#11
REVIEW
Asish K Ghosh, Rahul Rai, Panagiotis Flevaris, Douglas E Vaughan
Epigenetic changes play a pivotal role in the development of a wide spectrum of human diseases including cardiovascular diseases, cancer, diabetes, and intellectual disabilities. Cardiac fibrogenesis is a common pathophysiological process seen during chronic and stress-induced accelerated cardiac aging. While adequate production of extracellular matrix (ECM) proteins is necessary for post-injury wound healing, excessive synthesis and accumulation of extracellular matrix protein in the stressed or injured hearts causes decreased or loss of lusitropy that leads to cardiac failure...
November 24, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27872031/penile-prosthesis-infections-a-review-of-risk-factors-prevention-and%C3%A2-treatment
#12
REVIEW
Miguel Pineda, Arthur L Burnett
INTRODUCTION: Inflatable penile prosthesis (IPP) surgery has been performed for more than 40 years. IPP infection rates have decreased owing to advances in manufacturing and surgical technique but have remained a devastating complication. AIMS: To describe the pathophysiology of infections, examine evidence associating clinical risk factors with IPP infection, assess the benefit of techniques aimed at preventing and managing infection, and discuss future directions...
October 2016: Sexual Medicine Reviews
https://www.readbyqxmd.com/read/27798458/the-angiotensin-type-2-receptor-and-the-kidney
#13
Antonio A B Peluso, Robson A S Santos, Thomas Unger, U Muscha Steckelings
PURPOSE OF REVIEW: Angiotensin II is a main regulator of kidney function. Renal actions mediated by the angiotensin AT1 receptor have been well known for many years. In contrast, several details of angiotensin AT2 receptor actions in kidney physiology and pathophysiology were only described very recently. These findings are reviewed in this article. RECENT FINDINGS: Regarding the role of the angiotensin AT2 receptor in kidney physiology, a major recent finding was that the AT2 receptor-mediated inhibition of Na-H exchanger-3 and Na/K-ATPase in the renal proximal tubules is caused by internalisation of these transporters, thus reducing reabsorption and increasing natriuresis/diuresis...
January 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/27784010/clinical-application-of-biomarkers-in-heart-failure-with-a-preserved-ejection-fraction-a-review
#14
Aakash Garg, Deepti Virmani, Sahil Agrawal, Chirag Agarwal, Abhishek Sharma, Giulio Stefanini, John B Kostis
Heart failure with a preserved ejection fraction (HFpEF) is increasingly prevalent and a leading cause of morbidity and mortality worldwide. HFpEF has a complex pathophysiology, with recent evidence suggesting that an interaction of cardiovascular and noncardiovascular comorbidities (e.g. obesity, hypertension, diabetes, coronary artery disease, and chronic kidney disease) induces an inflammatory state that eventually leads to myocardial structural and functional alterations. Current ACCF/AHA guidelines suggest incorporation of biomarkers along with clinical and imaging tools to establish the diagnosis and disease severity in heart failure (HF)...
October 27, 2016: Cardiology
https://www.readbyqxmd.com/read/27783269/anion-channels-of-mitochondria
#15
Devasena Ponnalagu, Harpreet Singh
Mitochondria are the "power house" of a cell continuously generating ATP to ensure its proper functioning. The constant production of ATP via oxidative phosphorylation demands a large electrochemical force that drives protons across the highly selective and low-permeable mitochondrial inner membrane. Besides the conventional role of generating ATP, mitochondria also play an active role in calcium signaling, generation of reactive oxygen species (ROS), stress responses, and regulation of cell-death pathways...
October 26, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27768755/in-vivo-evaluation-of-the-visual-pathway-in-streptozotocin-induced-diabetes-by-diffusion-tensor-mri-and-contrast-enhanced-mri
#16
Swarupa Kancherla, William J Kohler, Yolandi van der Merwe, Kevin C Chan
Visual function has been shown to deteriorate prior to the onset of retinopathy in some diabetic patients and experimental animal models. This suggests the involvement of the brain's visual system in the early stages of diabetes. In this study, we tested this hypothesis by examining the integrity of the visual pathway in a diabetic rat model using in vivo multi-modal magnetic resonance imaging (MRI). Ten-week-old Sprague-Dawley rats were divided into an experimental diabetic group by intraperitoneal injection of 65 mg/kg streptozotocin in 0...
2016: PloS One
https://www.readbyqxmd.com/read/27754096/os-21-01-nox1-or-nox4-deletion-prevents-type-1-diabetes-induced-endothelial-dysfunction
#17
Pierre Paradis, Sofiane Ouerd, Noureddine Idris-Khodja, Michelle Trindade, Suellen C Coelho, Karin A Jandeleit-Dahm, Ernesto L Schiffrin
OBJECTIVE: The prognosis of type-1 diabetes remains poor and is primarily related to the increased risk of vascular complications. Overproduction of reactive oxygen species by NADPH oxidase (NOX) is believed to play an important role in diabetes-related vascular injury. NOX1 may play a role in the macrovascular disease, whereas NOX4 may have protective actions. Nevertheless, their role in diabetic microangiopathy is less well understood. We hypothesized that deletion of Nox1 would prevent diabetes-induced endothelial dysfunction and vascular remodeling of small arteries whereas Nox4 would exaggerate vascular injury...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27753836/sy-05-2-progression-of-hypertensive-heart-disease-new-therapeutic-approach
#18
Masatsugu Horiuchi
Hypertensive patients have greater chances of such cardiovascular events as stroke, coronary heart disease, heart or renal failure, peripheral artery disease, and dementia. It is also well recognized that diabetes increases the cardiovascular risks in concert with hypertension. Therefore, main goals for an innovation of anti-hypertensive therapy would be to achieve further risk reduction by targeting the functional, metabolic, and structural alterations associated with hypertension. Professors Dzau and Braunwald et al proposed the concept of "the cardiovascular disease continuum" in 1991, and that hypertension may trigger the chain of events, leading to end-stage heart disease; however, this concept was quite new at that time, and there was some discussion whether "the cardiovascular disease continuum" is true or not...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27736813/longitudinal-changes-in-measured-glomerular-filtration-rate-renal-fibrosis-and-biomarkers-in-a-rat-model-of-type-2-diabetic-nephropathy
#19
Zhi Su, Deborah Widomski, Ji Ma, Marian Namovic, Arthur Nikkel, Laura Leys, Lauren Olson, Katherine Salte, Diana Donnelly-Roberts, Timothy Esbenshade, Steve McGaraughty
BACKGROUND: Obese ZSF-1 rats display many features of human type II diabetes including nephropathy (DN). The study aimed to further understand the relevance of this model to DN, for which glomerular filtration rate (GFR), renal fibrosis and several urinary/tissue biomarkers was followed over 24 weeks in ZSF-1 rats. METHODS: Intact/sham or uninephrectomized male and female ZSF-1 rats were studied. GFR was measured by transdermal clearance of fluorescein isothiocyanate-sinistrin...
October 14, 2016: American Journal of Nephrology
https://www.readbyqxmd.com/read/27707498/the-metabolic-stress-response-to-burn-trauma-current-understanding-and-therapies
#20
REVIEW
Craig Porter, Ronald G Tompkins, Celeste C Finnerty, Labros S Sidossis, Oscar E Suman, David N Herndon
Major burns provoke a profound stress response, which is unrivalled in terms of its magnitude and duration. Evidence suggests that the pathophysiological stress response to severe burn trauma persists for several years after injury. Thus, there is a pressing need for novel strategies that mitigate this response and restore normal metabolic function in patients with burns. This is the first in a Series of three papers about the care of people with burns. In this paper, we review the current knowledge of the stress response to burn trauma, with a focus on hypermetabolism, muscle wasting, and stress-induced diabetes...
October 1, 2016: Lancet
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