المؤلفون: Eva Mühle, Bernd Epe, Sabine Guth, Jan G. Hengstler, Gerhard Eisenbrand, Richard H. Stadler, Angelika Roth, Hans-Ulrich Humpf, Patrick Diel, Christoph van Thriel, Karolina Edlund, Carsten Watzl, Sabine E. Kulling, Angela Mally, Stephanie Hüser, Elke Röhrdanz, Henry Jäger, Tilman Grune, Michael A. Nitsche, Edmund Wascher, Rosemarie Marchan, Hans-Georg Joost, Volker Heinz, Ute Nöthlings, Alfonso Lampen, Doris Marko, Karl-Heinz Engel, Rudi F. Vogel, Thomas Henle, Gisela H. Degen, Stefan Vieths

المصدر: Archives of Toxicology
Archives of toxicology, 95(7):2571-2587

مصطلحات موضوعية: Risk analysis, Reply, medicine.medical_specialty, Health, Toxicology and Mutagenesis, Pharmacology toxicology, MEDLINE, Pharmacology/Toxicology, Occupational Medicine/Industrial Medicine, Environmental Health, Biomedicine, general, 010501 environmental sciences, Toxicology, 01 natural sciences, 03 medical and health sciences, Human health, chemistry.chemical_compound, Fluorides, Fluoride toxicity, Environmental health, Epidemiology, Medicine, Animals, Longitudinal Studies, 0105 earth and related environmental sciences, 030505 public health, business.industry, Drinking Water, Confounding, General Medicine, ddc, Europe, Epidemiologic Studies, Lebensmitteltoxikologie, chemistry, Homogeneous, 0305 other medical science, business

الوصف: Since the addition of fluoride to drinking water in the 1940s, there have been frequent and sometimes heated discussions regarding its benefits and risks. In a recently published review, we addressed the question if current exposure levels in Europe represent a risk to human health. This review was discussed in an editorial asking why we did not calculate benchmark doses (BMD) of fluoride neurotoxicity for humans. Here, we address the question, why it is problematic to calculate BMDs based on the currently available data. Briefly, the conclusions of the available studies are not homogeneous, reporting negative as well as positive results; moreover, the positive studies lack control of confounding factors such as the influence of well-known neurotoxicants. We also discuss the limitations of several further epidemiological studies that did not meet the inclusion criteria of our review. Finally, it is important to not only focus on epidemiological studies. Rather, risk analysis should consider all available data, including epidemiological, animal, as well as in vitro studies. Despite remaining uncertainties, the totality of evidence does not support the notion that fluoride should be considered a human developmental neurotoxicant at current exposure levels in European countries.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::21196e4ee2367d87fce96c6cc4c40e6dTest
http://europepmc.org/articles/PMC8241794Test

المؤلفون: Marianne Hege, Anna Janina Engstler, Annika Höhn, Richard Kehm, Cheng Jun Jin, Otto W. Witte, Annette Brandt, Anika Nier, Christian Schmeer, Anja Baumann, Ina Bergheim, Tilman Grune

المصدر: American Journal of Physiology-Gastrointestinal and Liver Physiology. 318:G736-G747

مصطلحات موضوعية: Liver Cirrhosis, Male, Senescence, Aging, medicine.medical_specialty, Physiology, Apoptosis, Inflammation, Mice, Insulin resistance, Malate Dehydrogenase, Fibrosis, Physiology (medical), Internal medicine, Animals, Medicine, RNA, Messenger, Risk factor, Receptor, Mice, Knockout, Membrane Glycoproteins, Hepatology, biology, business.industry, Gastroenterology, medicine.disease, Receptor, Insulin, Endotoxins, Mice, Inbred C57BL, Toll-Like Receptor 4, Glucose, Endocrinology, Gene Expression Regulation, Liver, Insulin Receptor Substrate Proteins, biology.protein, Female, medicine.symptom, Carrier Proteins, business, Lipopolysaccharide binding protein, Biomarkers, Acute-Phase Proteins

الوصف: Aging is a risk factor in the development of many diseases, including liver-related diseases. The two aims of the present study were 1) to determine how aging affects liver health in mice in the absence of any interventions and 2) if degenerations observed in relation to blood endotoxin levels are critical in aging-associated liver degeneration. Endotoxin levels and markers of liver damage, mitochondrial dysfunction, insulin resistance, and apoptosis as well as the Toll-like receptor 4 (Tlr-4) signaling cascade were studied in liver tissue and blood, respectively, of 3- and 24-mo-old male C57BL/6J mice. In a second set of experiments, 3- to 4-mo-old and 14-mo-old female lipopolysaccharide-binding protein (LBP)−/− mice and littermates fed standard chow, markers of liver damage, insulin resistance, and mitochondrial dysfunction were assessed. Plasma activity of aspartate aminotransferase and histological signs of hepatic inflammation and fibrosis were significantly higher in old C57BL/6J mice than in young animals. The number of neutrophils, CD8α-positive cells, and mRNA expression of markers of apoptosis were also significantly higher in livers of old C57BL/6J mice compared with young animals, being also associated with a significant induction of hepatic Tlr-4 and LBP expression as well as higher endotoxin levels in peripheral blood. Compared with age-matched littermates, LBP−/− mice display less signs of senescence in liver. Taken together, our data suggest that, despite being fed standard chow, old mice developed liver inflammation and beginning fibrosis and that bacterial endotoxin may play a critical role herein. NEW & NOTEWORTHY Old age in mice is associated with marked signs of liver degeneration, hepatic inflammation, and fibrosis. Aging-associated liver degeneration is associated with elevated bacterial endotoxin levels and an induction of lipopolysaccharide-binding protein (LBP) and Toll-like receptor 4-dependent signaling cascades in liver tissue. Furthermore, in old aged LBP−/− mice, markers of senescence seem to be lessened, supporting the hypothesis that bacterial endotoxin levels might be critical in aging-associated decline of liver.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::43e62c968c1bcd4e8f3dad45d8f458acTest
https://doi.org/10.1152/ajpgi.00345.2018Test

المؤلفون: Jana Raupbach, C. Herpich, Tilman Grune, Kristina Norman, Christiane Ott, Bastian Kochlik, Daniela Weber

المصدر: The journals of gerontology, 77(5):934-940

مصطلحات موضوعية: Male, Aging, medicine.medical_specialty, medicine.medical_treatment, Insulins, Deoxyglucose, medicine.disease_cause, chemistry.chemical_compound, Mice, Postprandial, Fasting, Glyoxal, 3-Deoxyglucosone, Methylglyoxal, Internal medicine, Medicine, Animals, Humans, Aged, Age differences, business.industry, Insulin, Pyruvaldehyde, Mice, Inbred C57BL, Endocrinology, Glucose, chemistry, Cohort, Female, Geriatrics and Gerontology, business, Magnesium Oxide, Oxidative stress

الوصف: Dicarbonyl stress describes the increased formation of 1,2-dicarbonyl compounds and is associated with age-related pathologies. The role of dicarbonyl stress in healthy aging is poorly understood. In a preliminary study, we analyzed 1,2-dicarbonyl compounds, namely 3-deoxyglucosone (3-DG), glyoxal (GO), and methylglyoxal (MGO) in plasma of older (25 months, n = 11) and younger (5 months, n = 14) male C57BL/6J (B6) mice via ultra performance liquid chromatography tandem mass spectrometry. Postprandial 3-DG was higher in younger compared to older mice, whereas no differences were found for GO and MGO. Subsequently, in the main study, we analyzed fasting serum of older women (OW, 72.4 ± 6.14 years, n = 19) and younger women (YW, 27.0 ± 4.42 years, n = 19) as well as older men (OM, 74.3 ± 5.20 years, n = 15) and younger men (YM, 27.0 ± 3.34, n = 15). Serum glucose, insulin, 1,2-dicarbonyl concentrations, and markers of oxidative stress were quantified. In a subgroup of this cohort, an oral dextrose challenge was performed, and postprandial response of 1,2-dicarbonyl compounds, glucose, and insulin were measured. In women, there were no age differences regarding fasting 1,2-dicarbonyl concentrations nor the response after the oral dextrose challenge. In men, fasting MGO was significantly higher in OM compared to YM (median: 231 vs 158 nM, p = .006), whereas no age differences in fasting 3-DG and GO concentrations were found. Glucose (310 ± 71.8 vs 70.8 ± 11.9 min·mmol/L) and insulin (7 149 ± 1 249 vs 2 827 ± 493 min·µIU/mL) response were higher in OM compared to YM, which did not translate into a higher 1,2-dicarbonyl response in older individuals. Overall, aging does not necessarily result in dicarbonyl stress, indicating that strategies to cope with 1,2-dicarbonyl formation can remain intact.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::638819470c018f249a6dccf7e9c84a3fTest
https://pubmed.ncbi.nlm.nih.gov/34726231Test

المؤلفون: Ralf Dechend, Wolfgang M. Kuebler, Sophie Van Linthout, Kathleen Pappritz, Kristin Kräker, Cathleen John, Tilman Grune, Ulrich Kintscher, Till Schütte, Carsten Tschöpe, Daniel Ritter, Dominik N. Müller, Jana Grune, Niklas Beyhoff, Nadine Haase, Christiane Ott

المصدر: Cardiovascular Ultrasound, Vol 17, Iss 1, Pp 1-14 (2019)
Cardiovascular Ultrasound

مصطلحات موضوعية: Male, Cardiac function curve, medicine.medical_specialty, lcsh:Diseases of the circulatory (Cardiovascular) system, Image quality, Heart Ventricles, Robust statistics, 030204 cardiovascular system & hematology, Tracing, Ventricular Function, Left, 030218 nuclear medicine & medical imaging, Mice, Ventricular Dysfunction, Left, 03 medical and health sciences, 0302 clinical medicine, Data acquisition, Lv dysfunction, medicine, Animals, Radiology, Nuclear Medicine and imaging, Angiology, Lv function, business.industry, Small animals, Reproducibility of Results, LV systolic function, General Medicine, Rats, 3. Good health, Disease Models, Animal, How I do it article, Cardiovascular and Metabolic Diseases, Echocardiography, lcsh:RC666-701, Female, Rats, Transgenic, Cardiology and Cardiovascular Medicine, business, Algorithm, Algorithms, Automated border detection

الوصف: Echocardiography is the most commonly applied technique for non-invasive assessment of cardiac function in small animals. Manual tracing of endocardial borders is time consuming and varies with operator experience. Therefore, we aimed to evaluate a novel automated two-dimensional software algorithm (Auto2DE) for small animals and compare it to the standard use of manual 2D-echocardiographic assessment (2DE). We hypothesized that novel Auto2DE will provide rapid and robust data sets, which are in agreement with manually assessed data of animals. 2DE and Auto2DE were carried out using a high-resolution imaging-system for small animals. First, validation cohorts of mouse and rat cine loops were used to compare Auto2DE against 2DE. These data were stratified for image quality by a blinded expert in small animal imaging. Second, we evaluated 2DE and Auto2DE in four mouse models and four rat models with different cardiac pathologies. Automated assessment of LV function by 2DE was faster than conventional 2DE analysis and independent of operator experience levels. The accuracy of Auto2DE-assessed data in healthy mice was dependent on cine loop quality, with excellent agreement between Auto2DE and 2DE in cine loops with adequate quality. Auto2DE allowed for valid detection of impaired cardiac function in animal models with pronounced cardiac phenotypes, but yielded poor performance in diabetic animal models independent of image quality. Auto2DE represents a novel automated analysis tool for rapid assessment of LV function, which is suitable for data acquisition in studies with good and very good echocardiographic image quality, but presents systematic problems in specific pathologies. Electronic supplementary material The online version of this article (10.1186/s12947-019-0156-0) contains supplementary material, which is available to authorized users.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dc3ee2bc3f544a721d8801322798ef08Test
http://link.springer.com/article/10.1186/s12947-019-0156-0Test

المؤلفون: Annika Höhn, Tilman Grune, Richard Kehm, Stefanie Deubel, Jana Rückriemen, Daniela Weber

المصدر: Nutrition & Diabetes, Vol 9, Iss 1, Pp 1-5 (2019)
Nutrition & Diabetes

مصطلحات موضوعية: Blood Glucose, Glycation End Products, Advanced, 0301 basic medicine, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Nitric Oxide Synthase Type II, 030209 endocrinology & metabolism, Type 2 diabetes, Carbohydrate metabolism, Diet, High-Fat, Brief Communication, Diet, Carbohydrate-Restricted, Islets of Langerhans, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Glycation, Insulin-Secreting Cells, Internal medicine, Diabetes mellitus, Dietary Carbohydrates, Internal Medicine, medicine, Hyperinsulinemia, Animals, Insulin, Obesity, ddc:610, Pentosidine, lcsh:RC620-627, 030109 nutrition & dietetics, business.industry, Pancreatic islets, medicine.disease, lcsh:Nutritional diseases. Deficiency diseases, Endocrinology, Postprandial, medicine.anatomical_structure, Diabetes Mellitus, Type 2, chemistry, Hyperglycemia, Tyrosine, Institut für Ernährungswissenschaft, business

الوصف: Diet-induced hyperglycemia is described as one major contributor to the formation of advanced glycation end products (AGEs) under inflammatory conditions, crucial in type 2 diabetes progression. Previous studies have indicated high postprandial plasma AGE-levels in diabetic patients and after long-term carbohydrate feeding in animal models. Pancreatic islets play a key role in glucose metabolism; thus, their susceptibility to glycation reactions due to high amounts of dietary carbohydrates is of special interest. Therefore, diabetes-prone New Zealand Obese (NZO) mice received either a carbohydrate-free, high-fat diet (CFD) for 11 weeks or were additionally fed with a carbohydrate-rich diet (CRD) for 7 days. In the CRD group, hyperglycemia and hyperinsulinemia were induced accompanied by increasing plasma 3-nitrotyrosine (3-NT) levels, higher amounts of 3-NT and inducible nitric oxide synthase (iNOS) within pancreatic islets. Furthermore, N-ε-carboxymethyllysine (CML) was increased in the plasma of CRD-fed NZO mice and substantially higher amounts of arg-pyrimidine, pentosidine and the receptor for advanced glycation end products (RAGE) were observed in pancreatic islets. These findings indicate that a short-term intervention with carbohydrates is sufficient to form endogenous AGEs in plasma and pancreatic islets of NZO mice under hyperglycemic and inflammatory conditions.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6f1a6a2cfd17e49bcc7fc3df8a7cbc46Test
http://link.springer.com/article/10.1038/s41387-019-0077-xTest

المؤلفون: Andreas Pfeiffer, Sascha Rohn, Stephanie Sucher, Natalia Rudovich, Daniele Yumi Sunaga-Franze, Silke Hornemann, Mariya Markova, Daniela Weber, Olga Pivovarova-Ramich, Jens Raila, Tilman Grune, Sascha Sauer

المصدر: Redox Biology
Redox Biology, Vol 29, Iss, Pp-(2020)

مصطلحات موضوعية: 0301 basic medicine, medicine.medical_specialty, Antioxidant, medicine.medical_treatment, Clinical Biochemistry, Type 2 diabetes, medicine.disease_cause, Biochemistry, Antioxidants, Nitric oxide, Plant protein, 03 medical and health sciences, chemistry.chemical_compound, Animal protein, 0302 clinical medicine, Internal medicine, medicine, Animals, lcsh:QH301-705.5, Aged, Plant Proteins, Antioxidant status, lcsh:R5-920, business.industry, Nitrotyrosine, Organic Chemistry, Retinol, Middle Aged, Malondialdehyde, medicine.disease, Diet, 030104 developmental biology, Endocrinology, chemistry, Diabetes Mellitus, Type 2, lcsh:Biology (General), Oxidative stress, Technology Platforms, business, lcsh:Medicine (General), 030217 neurology & neurosurgery, Research Paper

الوصف: High-protein diet is a promising strategy for diabetes treatment supporting body weight control, improving glycaemic status, cardiovascular risk factors and reducing liver fat. Here, we investigated effects of diets high in animal (AP) or plant (PP) protein on oxidative stress and antioxidant status in individuals with type 2 diabetes (T2DM). 37 obese individuals (age 64.3 ± 1.0 years) with T2DM were randomized to an isocaloric diet (30 energy(E)% protein, 30 E% fat and 40 E% carbohydrates) rich in AP or PP for 6 weeks. Markers of oxidative and nitrosative stress and antioxidant status in plasma and nitrate/nitrite levels in urine were assessed. Gene expression in subcutaneous adipose tissue (SAT) was analysed by RNA-Seq and real-time PCR. Both AP and PP diets similarly reduced plasma levels of malondialdehyde (PAP = 0.003, PPP = 1.6 × 10−4) and protein carbonyls (PAP = 1.2 × 10−4, PPP = 3.0 × 10−5) over 6 weeks. Nitrotyrosine (NT) increased upon both AP and PP diets (PAP = 0.005, PPP = 0.004). SAT expression of genes involved in nitric oxide (NO) and oxidative stress metabolism and urine NO metabolite (nitrate/nitrite) levels were not changed upon both diets. Plasma levels of carotenoids increased upon PP diet, whereas retinol, alpha- and gamma-tocopherol slightly decreased upon both diets. AP and PP diets similarly improve oxidative stress but increase nitrosative stress markers in individuals with T2DM. Mechanisms of the NT regulation upon high-protein diets need further investigation.
Graphical abstract Image 1
Highlights • Effects of 6-week isocaloric diets high in animal (AP) or plant (PP) protein in subjects with type 2 diabetes were studied. • AP and PP diets reduced plasma levels of malondialdehyde and protein carbonyls and increased nitrotyrosine. • Expression of genes of nitric oxide (NO) and oxidative stress metabolism and urine NO metabolite levels were not changed. • Plasma retinol and tocopherol decreased upon both diets, and carotenoids increased upon PP diet.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2ba583d0ec382e9e7292d576378f436bTest
http://europepmc.org/articles/PMC6909130Test

المؤلفون: Bastian Kochlik, Daniela Weber, Tilman Grune

المصدر: Current Opinion in Clinical Nutrition & Metabolic Care. 20:349-359

مصطلحات موضوعية: 0301 basic medicine, medicine.medical_specialty, Biomedical Research, Psychological intervention, Medicine (miscellaneous), 030209 endocrinology & metabolism, medicine.disease_cause, Antioxidants, Healthy Aging, 03 medical and health sciences, 0302 clinical medicine, Functional Food, Intervention (counseling), Internal medicine, Animals, Humans, Medicine, Healthy aging, Beneficial effects, 030109 nutrition & dietetics, Nutrition and Dietetics, business.industry, Healthy subjects, Reproducibility of Results, Intervention studies, Oxidative Stress, Chronic Disease, Dietary Supplements, Patient Compliance, Observational study, Diet, Healthy, business, Biomarkers, Oxidative stress

الوصف: Purpose of review The aim of this article is to present a brief overview of recently published articles assessing oxidative stress markers in nutritional studies. Recent findings Intervention and observational studies were carried out in both, healthy subjects and patients and describe the association of foodstuffs as well as isolated nutrients with biomarkers of oxidative stress. The results from human intervention studies on healthy participants and patients are controversial. Long-term interventions (>8 weeks) seem to be more effective than short-term or single-dose interventions. Results are difficult to compare because not only the methods used, also the assessed biomarkers and outcomes were very diverse. In addition, studies vary in the compounds and doses used, duration, participants and so on. Different biomarkers (damaged molecules together with antioxidants from different compartments) should be assessed to evaluate the true 'redox-status' of an individual and the impact of a nutritional intervention. Summary Both observational and interventional studies performed in healthy participants and patients show possible beneficial effects of nutrients and foodstuffs by improving oxidative stress markers and antioxidant enzyme activities. Biomarkers should be standardized to allow better comparison of results of antioxidant intervention studies.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6e9feaa6e37ec175e109c815a2ff2945Test
https://doi.org/10.1097/mco.0000000000000388Test

المؤلفون: Cornelia Weikert, Fabian Schumacher, Adrian McCann, Thomas Laeger, Klaus Abraham, Annette Schürmann, Silke Schumacher, Tilman Grune, Daniela Weber, Bastian Kochlik, Teresa Castaño-Martinez, Ronald Biemann, Burkhard Kleuser

المصدر: The FASEB Journal

مصطلحات موضوعية: Blood Glucose, Leptin, Male, vegan, 0301 basic medicine, obesity, Medizin, Mice, Obese, Type 2 diabetes, Weight Gain, Biochemistry, Mice, chemistry.chemical_compound, Methionine, 0302 clinical medicine, energy expenditure, Insulin, vegetarian, medicine.anatomical_structure, Adipose Tissue, Liver, Energy expenditure, Adiponectin, Biotechnology, medicine.medical_specialty, Body weight, 03 medical and health sciences, Internal medicine, Genetics, medicine, Animals, Humans, ddc:610, Fibroblast, Molecular Biology, Institut für Biochemie und Biologie, Vegans, business.industry, Research, Insulin sensitivity, medicine.disease, Animal Feed, Obesity, Diet, Fibroblast Growth Factors, 030104 developmental biology, Endocrinology, Diabetes Mellitus, Type 2, chemistry, Hyperglycemia, business, Biomarkers, 030217 neurology & neurosurgery

الوصف: Dietary methionine restriction (MR) is well known to reduce body weight by increasing energy expenditure (EE) and insulin sensitivity. An elevated concentration of circulating fibroblast growth factor 21 (FGF21) has been implicated as a potential underlying mechanism. The aims of our study were to test whether dietary MR in the context of a high-fat regimen protects against type 2 diabetes in mice and to investigate whether vegan and vegetarian diets, which have naturally low methionine levels, modulate circulating FGF21 in humans. New Zealand obese (NZO) mice, a model for polygenic obesity and type 2 diabetes, were placed on isocaloric high-fat diets (protein, 16 kcal%; carbohydrate, 52 kcal%; fat, 32 kcal%) that provided methionine at control (Con; 0.86% methionine) or low levels (0.17%) for 9 wk. Markers of glucose homeostasis and insulin sensitivity were analyzed. Among humans, low methionine intake and circulating FGF21 levels were investigated by comparing a vegan and a vegetarian diet to an omnivore diet and evaluating the effect of a short-term vegetarian diet on FGF21 induction. In comparison with the Con group, MR led to elevated plasma FGF21 levels and prevented the onset of hyperglycemia in NZO mice. MR-fed mice exhibited increased insulin sensitivity, higher plasma adiponectin levels, increased EE, and up-regulated expression of thermogenic genes in subcutaneous white adipose tissue. Food intake and fat mass did not change. Plasma FGF21 levels were markedly higher in vegan humans compared with omnivores, and circulating FGF21 levels increased significantly in omnivores after 4 d on a vegetarian diet. These data suggest that MR induces FGF21 and protects NZO mice from high-fat diet–induced glucose intolerance and type 2 diabetes. The normoglycemic phenotype in vegans and vegetarians may be caused by induced FGF21. MR akin to vegan and vegetarian diets in humans may offer metabolic benefits via increased circulating levels of FGF21 and merits further investigation.—Castaño-Martinez, T., Schumacher, F., Schumacher, S., Kochlik, B., Weber, D., Grune, T., Biemann, R., McCann, A., Abraham, K., Weikert, C., Kleuser, B., Schürmann, A., Laeger, T. Methionine restriction prevents onset of type 2 diabetes in NZO mice.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::32fce7dae86e47640c8d52c56ebce8c5Test
https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&origin=inward&scp=85067269530Test

المؤلفون: Anna Foryst-Ludwig, Annelie Blumrich, Tilman Grune, Daniel Messroghli, Sarah Jeuthe, Christiane Ott, Cathleen Drescher, Sarah Brix, Jana Grune, Wolfgang M. Kuebler, Ulrich Kintscher

المصدر: Cardiovascular Ultrasound
Cardiovascular Ultrasound, Vol 16, Iss 1, Pp 1-13 (2018)

مصطلحات موضوعية: 0301 basic medicine, medicine.medical_specialty, lcsh:Diseases of the circulatory (Cardiovascular) system, Cardiac Volume, Echocardiography, Three-Dimensional, Mice, Obese, 030204 cardiovascular system & hematology, Imaging phantom, 03 medical and health sciences, Mice, 0302 clinical medicine, Volumetry, Internal medicine, Image Interpretation, Computer-Assisted, Preclinical imaging, medicine, Image Processing, Computer-Assisted, Animals, Radiology, Nuclear Medicine and imaging, Heart Failure, Observer Variation, Reproducibility, Ejection fraction, 3D echocardiography, medicine.diagnostic_test, business.industry, Small animals, Ultrasound, Reproducibility of Results, Magnetic resonance imaging, Stroke Volume, General Medicine, Stroke volume, medicine.disease, Magnetic Resonance Imaging, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, lcsh:RC666-701, Echocardiography, Heart failure, Technical Notes, Cardiology and Cardiovascular Medicine, business, Biomedical engineering

الوصف: Background The assessment of ventricular volumes using conventional echocardiography methods is limited with regards to the need of geometrical assumptions. In the present study, we aimed to evaluate a novel commercial system for three-dimensional echocardiography (3DE) in preclinical models by direct comparison with conventional 1D- and 2D-echocardiography (1DE; 2DE) and the gold-standard technique magnetic resonance imaging (MRI). Further, we provide a standard operating protocol for image acquisition and analysis with 3DE. Methods 3DE was carried out using a 30 MHz center frequency transducer coupled to a Vevo®3100 Imaging System. We evaluated under different experimental conditions: 1) in vitro phantom measurements served as controlled setting in which boundaries were clearly delineated; 2) a validation cohort composed of healthy C57BL/6 J mice and New Zealand Obese (NZO) mice was used in order to validate 3DE against cardiac MRI; 3) a standard mouse model of pressure overload induced-heart failure was investigated to estimate the value of 3DE. Results First, in vitro volumetry revealed good agreement between 3DE assessed volumes and the MRI-assessed volumes. Second, cardiac volume determination with 3DE showed smaller mean differences compared to cardiac MRI than conventional 1DE and 2DE. Third, 3DE was suitable to detect reduced ejection fractions in heart failure mice. Fourth, inter- and intra-observer variability of 3DE showed good to excellent agreement regarding absolute volumes in healthy mice, whereas agreement rates for the relative metrics ejection fraction and stroke volume demonstrated good to moderate observer variabilities. Conclusions 3DE provides a novel method for accurate volumetry in small animals without the need for spatial assumptions, demonstrating a technique for an improved analysis of ventricular function. Further validation work and highly standardized image analyses are required to increase reproducibility of this approach. Electronic supplementary material The online version of this article (10.1186/s12947-018-0128-9) contains supplementary material, which is available to authorized users.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a5c02296da43f2d2df3a9e32b31501f7Test
https://pubmed.ncbi.nlm.nih.gov/29966517Test

المؤلفون: Tobias Jung, Kerstin Nowotny, Annika Höhn, Tilman Grune, Daniela Weber

المصدر: Biomolecules, 5(1): 194-222
Biomolecules, Vol 5, Iss 1, Pp 194-222 (2015)
Biomolecules

مصطلحات موضوعية: Glycation End Products, Advanced, medicine.medical_specialty, endocrine system diseases, type 2 diabetes mellitus, lcsh:QR1-502, Oxidative phosphorylation, Review, Bioinformatics, medicine.disease_cause, Biochemistry, lcsh:Microbiology, Pathogenesis, Insulin resistance, Glycation, Internal medicine, Diabetes mellitus, Insulin-Secreting Cells, insulin resistance, medicine, diabetic complications, Animals, Humans, oxidative stress, Chronic stress, Molecular Biology, Cell Death, business.industry, β cell dysfunction, advanced glycation end products, Type 2 Diabetes Mellitus, medicine.disease, Endocrinology, Diabetes Mellitus, Type 2, business, Oxidative stress

الوصف: Type 2 diabetes mellitus (T2DM) is a very complex and multifactorial metabolic disease characterized by insulin resistance and β cell failure leading to elevated blood glucose levels. Hyperglycemia is suggested to be the main cause of diabetic complications, which not only decrease life quality and expectancy, but are also becoming a problem regarding the financial burden for health care systems. Therefore, and to counteract the continually increasing prevalence of diabetes, understanding the pathogenesis, the main risk factors, and the underlying molecular mechanisms may establish a basis for prevention and therapy. In this regard, research was performed revealing further evidence that oxidative stress has an important role in hyperglycemia-induced tissue injury as well as in early events relevant for the development of T2DM. The formation of advanced glycation end products (AGEs), a group of modified proteins and/or lipids with damaging potential, is one contributing factor. On the one hand it has been reported that AGEs increase reactive oxygen species formation and impair antioxidant systems, on the other hand the formation of some AGEs is induced per se under oxidative conditions. Thus, AGEs contribute at least partly to chronic stress conditions in diabetes. As AGEs are not only formed endogenously, but also derive from exogenous sources, i.e., food, they have been assumed as risk factors for T2DM. However, the role of AGEs in the pathogenesis of T2DM and diabetic complications—if they are causal or simply an effect—is only partly understood. This review will highlight the involvement of AGEs in the development and progression of T2DM and their role in diabetic complications.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::61023e9eb885cffcfb4a0f34549fa973Test
https://repository.publisso.de/resource/frl:6406002Test