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Pathophysiology diabetic injury

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https://www.readbyqxmd.com/read/28992340/gremlin-and-renal-diseases-ready-to-jump-the-fence-to-clinical-utility
#1
Sergio Mezzano, Alejandra Droguett, Carolina Lavoz, Paola Krall, Jesús Egido, Marta Ruiz-Ortega
The current therapeutic strategy for the treatment of chronic kidney diseases only ameliorates disease progression. During renal injury, developmental genes are re-expressed and could be potential therapeutic targets. Among those genes reactivated in the adult damaged kidney, Gremlin is of particular relevance since recent data suggest that it could be a mediator of diabetic nephropathy and other progressive renal diseases. Earlier studies have shown that Gremlin is upregulated in trans-differentiated renal proximal tubular cells and in several chronic kidney diseases associated with fibrosis...
July 8, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28992221/the-diabetes-pandemic-suggests-unmet-needs-for-ckd-with-diabetes-in-addition-to-diabetic-nephropathy-implications-for-pre-clinical-research-and-drug-testing
#2
Lidia Anguiano Gómez, Yutian Lei, Satish Kumar Devarapu, Hans-Joachim Anders
Curing 'diabetic nephropathy' is considered an unmet medical need of high priority. We propose to question the concept of 'diabetic nephropathy' that implies diabetes as the predominant cause of kidney disease, which may not apply to the majority of type 2 diabetics approaching end-stage kidney disease. With the onset of diabetes, hyperglycaemia/sodium-glucose co-transporter-2-driven glomerular hyperfiltration promotes nephron hypertrophy, which, however, on its own, causes proteinuria not before a decade later, probably because podocyte hypertrophy can usually accommodate an increase in the filtration surface...
July 31, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28974008/higher-mortality-in-trauma-patients-is-associated-with-stress-induced-hyperglycemia-but-not-diabetic-hyperglycemia-a-cross-sectional-analysis-based-on-a-propensity-score-matching-approach
#3
Cheng-Shyuan Rau, Shao-Chun Wu, Yi-Chun Chen, Peng-Chen Chien, Hsiao-Yun Hsieh, Pao-Jen Kuo, Ching-Hua Hsieh
Background: Stress-induced hyperglycemia (SIH) is a form of hyperglycemia secondary to stress and commonly occurs in patients with trauma. Trauma patients with SIH have been reported to have an increased risk of mortality. However, information regarding whether these trauma patients with SIH represent a distinct group with differential outcomes when compared to those with diabetic hyperglycemia (DH) remains limited. Methods: Diabetes mellitus (DM) was determined by patient history and/or admission glycated hemoglobin (HbA1c) ≥6...
September 30, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28962149/dl-3-n-butylphthalide-protects-endothelial-cells-against-advanced-glycation-end-product-induced-injury-by-attenuating-oxidative-stress-and-inflammation-responses
#4
Chang-Yun Liu, Zhen-Hua Zhao, Zhi-Ting Chen, Chun-Hui Che, Zhang-Yu Zou, Xiao-Min Wu, Sheng-Gen Chen, Yuan-Xiao Li, Han-Bin Lin, Xiao-Fan Wei, Jie You, Hua-Pin Huang
Endothelial dysfunction, regarded as a key step in the pathophysiological course of diabetic vascular complications, is initiated and deteriorated by advanced glycation end products (AGEs). DL-3-n-butylphthalide (DL-NBP) has been proven to have protective effects on neurons and vascular endothelial cells against ischemic and anoxic damage. The aim of the present study was to investigate whether NBP is able to attenuate AGE-induced endothelial dysfunction in vitro, and also elucidate the possible underlying mechanism...
September 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28933311/mg17-a-novel-triazole-derivative-abrogated-neuroinflammation-and-related-neurodegenerative-symptoms-in-rodents
#5
Gangadhar Matharasala, Ganesh Samala, Yogeeswari Perumal
The objective of present study is to explore multiple effects of the compound MG17 and relate them to achieve better therapeutic potential against neuroinflammation related disorders. We examined whether our compound is acting through regulating neuroinflammatory mediators. We have done some preliminary behavioral studies to shortlist the derivatives using rodent models of peripheral nerve injury in our earlier publication and now we extended our screening studies to explore the test compounds efficacy on other related peripheral neurological disorders such as Streptozotocin-induced diabetic peripheral neuropathy (DPN) and methyl mercury (MeHg) induced neurodegeneration in rats...
September 19, 2017: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/28926566/guidelines-for-the-management-of-a-brain-death-donor-in-the-rhesus-macaque-a-translational-transplant-model
#6
Tiffany J Zens, Juan S Danobeitia, Peter J Chlebeck, Laura J Zitur, Scott Odorico, Kevin Brunner, Jennifer Coonen, Saverio Capuano, Anthony M D'Alessandro, Kristina Matkowskyj, Weixiong Zhong, Jose Torrealba, Luis Fernandez
INTRODUCTION: The development of a translatable brain death animal model has significant potential to advance not only transplant research, but also the understanding of the pathophysiologic changes that occur in brain death and severe traumatic brain injury. The aim of this paper is to describe a rhesus macaque model of brain death designed to simulate the average time and medical management described in the human literature. METHODS: Following approval by the Institutional Animal Care and Use Committee, a brain death model was developed...
2017: PloS One
https://www.readbyqxmd.com/read/28919014/regulation-and-function-of-endothelial-glycocalyx-layer-in-vascular-diseases
#7
REVIEW
Irina Sieve, Anja K Münster-Kühnel, Denise Hilfiker-Kleiner
In the vascular system, the endothelial surface layer (ESL) as the inner surface of blood vessels affects mechanotransduction, vascular permeability, rheology, thrombogenesis, and leukocyte adhesion. It creates barriers between endothelial cells and blood and neighbouring cells. The glycocalyx, composed of glycoconjugates and proteoglycans, is an integral component of the ESL and a key element in inter- and intracellular communication and tissue homeostasis. In pathophysiological conditions (atherosclerosis, infection, ischemia/reperfusion injury, diabetes, trauma and acute lung injury) glycocalyx-degrading factors, i...
September 12, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/28915969/hyperglycemia-in-acute-ischemic-stroke-is-it-time-to-re-evaluate-our-understanding
#8
Rwoof Reshi, Chris Streib, Mustapha Ezzeddine, Michelle Biros, Benjamin Miller, Kamakshi Lakshminarayan, David Anderson, Agnieszka Ardelt
Among 700,000 new and recurrent ischemic stroke patients per year, forty percent are hyperglycemic on admission. In-vitro, hyperglycemia is toxic to neurons. Acute ischemic stroke patients who are hyperglycemic on admission experience higher morbidity and mortality. Results of multiple trials have provided no evidence supporting benefit in achieving normoglycemia. On the contrary, there is some evidence that tight glycemic control in acute brain injury is associated with poor outcome. Current consensus derived guidelines from the American Heart Association/American Stroke Association recommend an upper limit of blood glucose of 140-180mg/dl, as there is no evidence to support strict control...
September 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28915329/mitophagy-as-a-protective-mechanism-against-myocardial-stress
#9
Jihoon Nah, Shigeki Miyamoto, Junichi Sadoshima
Mitochondria are dynamic organelles that can undergo fusion, fission, biogenesis, and autophagic elimination to maintain mitochondrial quality control. Since the heart is in constant need of high amounts of energy, mitochondria, as a central energy supply source, play a crucial role in maintaining optimal cardiac performance. Therefore, it is reasonable to assume that mitochondrial dysfunction is associated with the pathophysiology of heart diseases. In non-dividing, post-mitotic cells such as cardiomyocytes, elimination of dysfunctional organelles is essential to maintaining cellular function because non-dividing cells cannot dilute dysfunctional organelles through cell division...
September 12, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28904427/micrornas-involvement-in-renal-pathophysiology-a-bird-s-eye-view
#10
REVIEW
P Jaswani, S Prakash, A Dhar, R K Sharma, N Prasad, S Agrawal
MicroRNAs (miRNAs) are known to suppress gene expression by binding to messenger RNAs and in turn regulate different pathophysiological processes. Transforming growth factor-β, mitogen-activated protein kinase signaling, and Wnt signaling-like major pathways associated with miRNAs are involved with kidney diseases. The discovery of miRNAs has provided new insights into kidney pathologies and may provide effective therapeutic strategies. Research has demonstrated the role of miRNAs in a variety of kidney diseases including diabetic nephropathy, lupus nephritis, hypertension, nephritic syndrome, acute kidney injury, renal cell carcinoma, and renal fibrosis...
September 2017: Indian Journal of Nephrology
https://www.readbyqxmd.com/read/28900398/role-of-hydrogen-sulfide-in-retinal-diseases
#11
REVIEW
Jiantong Du, Hongfang Jin, Liu Yang
As the third gasotransmitter, hydrogen sulfide (H2S) plays a crucial role in the physiology and pathophysiology of many systems in the body, such as the nervous, cardiovascular, respiratory, and gastrointestinal systems. The mechanisms for its effects, including inhibiting ischemic injury, reducing oxidative stress damage, regulating apoptosis, and reducing the inflammation reaction in different systems, have not been fully understood. Recently, H2S and its endogenous synthesis pathway were found in the mammalian retina...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28880010/chronic-pancreatitis
#12
REVIEW
Jorg Kleeff, David C Whitcomb, Tooru Shimosegawa, Irene Esposito, Markus M Lerch, Thomas Gress, Julia Mayerle, Asbjørn Mohr Drewes, Vinciane Rebours, Fatih Akisik, J Enrique Domínguez Muñoz, John P Neoptolemos
Chronic pancreatitis is defined as a pathological fibro-inflammatory syndrome of the pancreas in individuals with genetic, environmental and/or other risk factors who develop persistent pathological responses to parenchymal injury or stress. Potential causes can include toxic factors (such as alcohol or smoking), metabolic abnormalities, idiopathic mechanisms, genetics, autoimmune responses and obstructive mechanisms. The pathophysiology of chronic pancreatitis is fairly complex and includes acinar cell injury, acinar stress responses, duct dysfunction, persistent or altered inflammation, and/or neuro-immune crosstalk, but these mechanisms are not completely understood...
September 7, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28843828/vinpocetine-mitigates-proteinuria-and-podocytes-injury-in-a-rat-model-of-diabetic-nephropathy
#13
Walaa Wadie, Dalia M El-Tanbouly
Podocyte injury and glomerular basement membrane thickening have been considered as essential pathophysiological events in diabetic nephropathy. The aim of this study was to investigate the possible beneficial effects of vinpocetine on diabetes-associated renal damage. Male Wistar rats were made diabetic by injection of streptozotocin (STZ). Diabetic rats were treated with vinpocetine in a dose of 20mg/kg/day for 6 weeks. Treatment with vinpocetine resulted in a marked decrease in the levels of blood glucose, glycosylated haemoglobin, creatinine, blood urea nitrogen, urinary albumin and albumin/creatinine ratio along with an elevation in creatinine clearance rate...
November 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28822390/physiologic-features-of-brain-death
#14
Eno-Obong Essien, Kristina Fioretti, Thomas M Scalea, Deborah M Stein
Brain death is known to be associated with physiologic derangements but their incidence is poorly described. Knowledge of the changes that occur during brain death is important for management of the potential organ donor. Thus, we sought to characterize the pathophysiology that occurs during brain death in patients with traumatic injuries. All brain-dead patients over a 10-year period were identified from the trauma registry at a level 1 urban trauma center. Patient demographics, injury characteristics, and clinical data for defining organ dysfunction were reviewed for the 24 hours surrounding brain-death declaration...
August 1, 2017: American Surgeon
https://www.readbyqxmd.com/read/28780716/epigenetics-a-potential-key-mechanism-involved-in-the-pathogenesis-of-cardiorenal-syndromes
#15
REVIEW
Grazia Maria Virzì, Anna Clementi, Alessandra Brocca, Massimo de Cal, Claudio Ronco
Epigenetics is defined as the heritable changes in gene expression patterns which are not directly encoded by modifications in the nucleotide DNA sequence of the genome, including higher order chromatin organization, DNA methylation, cytosine modifications, covalent histone tail modifications, and short non-coding RNA molecules. Recently, much attention has been paid to the role and the function of epigenetics and epimutations in the cellular and subcellular pathways and in the regulation of genes in the setting of both kidney and cardiovascular disease...
August 5, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28768320/effects-of-sodium-glucose-cotransporter-2-inhibitors-for-the-treatment-of-patients-with-heart-failure-proposal-of-a-novel-mechanism-of-action
#16
Milton Packer, Stefan D Anker, Javed Butler, Gerasimos Filippatos, Faiez Zannad
Importance: Only 1 class of glucose-lowering agents-sodium-glucose cotransporter 2 (SGLT2) inhibitors-has been reported to decrease the risk of cardiovascular events primarily by reducing the risk of the development or progression of heart failure. In a landmark trial called Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes [EMPA-REG Outcomes], long-term treatment with empagliflozin prevented fatal and nonfatal heart failure events but did not reduce the risk of myocardial infarction or stroke in diabetic patients...
September 1, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/28748185/novel-actions-of-growth-hormone-in-podocytes-implications-for-diabetic-nephropathy
#17
REVIEW
Dhanunjay Mukhi, Rajkishor Nishad, Ram K Menon, Anil Kumar Pasupulati
The kidney regulates water, electrolyte, and acid-base balance and thus maintains body homeostasis. The kidney's potential to ensure ultrafiltered and almost protein-free urine is compromised in various metabolic and hormonal disorders such as diabetes mellitus (DM). Diabetic nephropathy (DN) accounts for ~20-40% of mortality in DM. Proteinuria, a hallmark of renal glomerular diseases, indicates injury to the glomerular filtration barrier (GFB). The GFB is composed of glomerular endothelium, basement membrane, and podocytes...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28736244/the-use-of-stable-isotopes-in-the-study-of-human-pathophysiology
#18
Evelina Charidemou, Tom Ashmore, Julian L Griffin
The growing prevalence of metabolic diseases including fatty liver disease and Type 2 diabetes has increased the emphasis on understanding metabolism at the mechanistic level and how it is perturbed in disease. Metabolomics is a continually expanding field that seeks to measure metabolites in biological systems during a physiological stimulus or a genetic alteration. Typically, metabolomics studies provide total pool sizes of metabolites rather than dynamic flux measurements. More recently there has been a resurgence in approaches that use stable isotopes (e...
July 20, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28713160/pathogenic-roles-of-microvesicles-in-diabetic-retinopathy
#19
REVIEW
Wei Zhang, Song Chen, Ming-Lin Liu
Diabetic retinopathy (DR) is a common complication of diabetes and has been recognized as the leading cause of blindness in adults. Several interrelated molecular pathways are involved in the development of DR. Microvesicles (MVs) are cell membrane vesicles, which carry many biologic molecules, such as mRNAs, microRNAs, transcription factors, membrane lipids, membrane receptors, and other proteins. They may be involved in intercellular communication that can promote inflammation, angiogenesis, and coagulation...
July 17, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28691103/role-of-nonalcoholic-fatty-liver-disease-as-risk-factor-for-drug-induced-hepatotoxicity
#20
Julie Massart, Karima Begriche, Caroline Moreau, Bernard Fromenty
BACKGROUND: Obesity is often associated with nonalcoholic fatty liver disease (NAFLD), which refers to a large spectrum of hepatic lesions including fatty liver, nonalcoholic steatohepatitis (NASH) and cirrhosis. Different investigations showed or suggested that obesity and NAFLD are able to increase the risk of hepatotoxicity of different drugs. Some of these drugs could induce more frequently an acute hepatitis in obese individuals whereas others could worsen pre-existing NAFLD. AIM: The main objective of the present review was to collect the available information regarding the role of NAFLD as risk factor for drug-induced hepatotoxicity...
February 2017: Journal of Clinical and Translational Research
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