The Experts below are selected from a list of 35685 Experts worldwide ranked by ideXlab platform
Ingrid Sjogren - One of the best experts on this subject based on the ideXlab platform.
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the effect of diet induced obesity on toxicological parameters in the polygenic Sprague Dawley Rat model
Toxicologic Pathology, 2018Co-Authors: Jennifer M Rojas, Florian Bolze, Inger Thorup, Jette Nowak, Charlotte M Dalsgaard, Mikala Skydsgaard, Line Olrik Berthelsen, Kevin Keane, Henrik Soeborg, Ingrid SjogrenAbstract:The obese rodent serves as an indispensable tool for proof-of-concept efficacy and mode-of-action pharmacology studies. Yet the utility of this disease model as an adjunct to the conventional healthy animal in the nonclinical safety evaluation of anti-obesity pharmacotherapies has not been elucidated. Regulatory authorities have recommended employing disease models in toxicology studies when necessary. Our study investigated standard and exploRatory toxicology parameters in the high-fat diet (HFD)-induced obese, polygenic Sprague-Dawley Rat model in comparison to chow diet (CD)-fed controls. We sought to establish feasibility of the model for safety testing and relevance to human obesity pathophysiology. We report that both sexes fed a 45% kcal HFD for 29 weeks developed obesity and metabolic derangements that mimics to a certain extent, common human obesity. Minor clinical pathologies were observed in both sexes and considered related to CD versus HFD differences. Histopathologically, both sexes exhibited mild obesity-associated findings in brown and subcutaneous white fat, bone, kidneys, liver, lung, pancreas, salivary parotid glands, and skeletal muscle. We conclude that chronic HFD feeding in both sexes led to the development of an obese but otherwise healthy Rat. Therefore, the diet-induced obese Sprague-Dawley Rat may serve as a suitable model for evaluating toxicity findings encountered with anti-obesity compounds.
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Supplemental Material, DS7_TPX_10.1177_0192623318803557 - The Effect of Diet-induced Obesity on Toxicological Parameters in the Polygenic Sprague-Dawley Rat Model
2018Co-Authors: Jennifer M Rojas, Florian Bolze, Inger Thorup, Jette Nowak, Charlotte M Dalsgaard, Mikala Skydsgaard, Line Olrik Berthelsen, Henrik Soeborg, Kevin A. Keane, Ingrid SjogrenAbstract:Supplemental Material, DS7_TPX_10.1177_0192623318803557 for The Effect of Diet-induced Obesity on Toxicological Parameters in the Polygenic Sprague-Dawley Rat Model by Jennifer M. Rojas, Florian Bolze, Inger Thorup, Jette Nowak, Charlotte M. Dalsgaard, Mikala Skydsgaard, Line O. Berthelsen, Kevin A. Keane, Henrik Søeborg, Ingrid Sjögren, Jes T. Jensen, Johannes J. Fels, Hanne K. Offenberg, Lærke W. Andersen, and Majken Dalgaard in Toxicologic Pathology
Ralph J. Jensen - One of the best experts on this subject based on the ideXlab platform.
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Effects of Dopamine D2-Like Receptor Antagonists on Light Responses of Ganglion Cells in Wild-Type and P23H Rat Retinas.
PLOS ONE, 2015Co-Authors: Ralph J. JensenAbstract:In animal models of retinitis pigmentosa the dopaminergic system in the retina appears to be dysfunctional, which may contribute to the debilitated sight experienced by retinitis pigmentosa patients. Since dopamine D2-like receptors are known to modulate the activity of dopaminergic neurons, I examined the effects of dopamine D2-like receptor antagonists on the light responses of retinal ganglion cells (RGCs) in the P23H Rat model of retinitis pigmentosa. Extracellular electrical recordings were made from RGCs in isolated transgenic P23H Rat retinas and wild-type Sprague-Dawley Rat retinas. Intensity-response curves to flashes of light were evaluated prior to and during bath application of a dopamine D2-like receptor antagonist. The dopamine D2/D3 receptor antagonists sulpiride and eticlopride and the D4 receptor antagonist L-745,870 increased light sensitivity of P23H Rat RGCs but decreased light sensitivity in Sprague-Dawley Rat RGCs. In addition, L-745,870, but not sulpiride or eticlopride, reduced the maximum peak responses of Sprague-Dawley Rat RGCs. I describe for the first time ON-center RGCs in P23H Rats that exhibit an abnormally long-latency (>200 ms) response to the onset of a small spot of light. Both sulpiride and eticlopride, but not L-745,870, reduced this ON response and brought out a short-latency OFF response, suggesting that these cells are in actuality OFF-center cells. Overall, the results show that the altered dopaminergic system in degeneRate retinas contributes to the deterioRated light responses of RGCs.
Nurul Cholifah Lutfiana - One of the best experts on this subject based on the ideXlab platform.
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darapladib inhibits atherosclerosis development in type 2 diabetes mellitus Sprague Dawley Rat model
Endocrine Regulations, 2018Co-Authors: Titin Andri Wihastuti, Sri Andarini, Teuku Heriansyah, Yuni Hendrati Sulfia, Zuhrotus Sholichah, Hanifa Hanifa, Aditya Angela Adam, Jeki Refialdinata, Nurul Cholifah LutfianaAbstract:OBJECTIVE Increase in the low-density lipoprotein (LDL) level in diabetes mellitus and atherosclerosis is related to lipoprotein associated phospholipase A2 (Lp-PLA2). Lp-PLA2 is an enzyme that produces lysophosphatidylcholine (LysoPC) and oxidized nonesterified fatty acids (oxNEFA). LysoPC regulates inflammation mediators, including intra-cellular adhesion molecule-1 (ICAM-1). Darapladib is known as a Lp-PLA2 specific inhibitor. The aim of this study was to reveal the effect of darapladib on the foam cell number, inducible nitric oxide synthase (iNOS), and ICAM-1 expression in aorta at early stages of the atherosclerosis in type 2 diabetes mellitus Sprague-Dawley Rat model. METHODS Thirty Sprague-Dawley male Rats were divided into 3 main groups: control, Rats with type 2 diabetes mellitus (T2DM), and T2DM Rats treated with darapladib (T2DM-DP). Each group was divided into 2 subgroups according the time of treatment: 8-week and 16-week treatment group. Fasting blood glucose, insulin resistance, and lipid profile were measured and analyzed to ensure T2DM model. The foam cells number were detected using hematoxylin-eosin (HE) staining and the expression of iNOS and ICAM-1 was analyzed using double immunofluorescence staining. RESULTS Induction of T2DM in male Sprague-Dawley Rats after high fat diet and streptozotocin injection was confirmed by elevated levels of total cholesterol and LDL and increased fasting glucose and insulin levels compared to controls after both times of treatment. Moreover, T2DM in Rats induced a significant increase (p<0.05) in the foam cells number and iNOS and ICAM-1 expression in aorta compared to controls after both treatment times. Darapladib treatment significantly reduced (p<0.05) foam cells number as well as iNOS expression in aorta in Rats with T2DM after both treatment times. A significant decrease (p<0.05) in ICAM-1 expression in aorta was observed after darapladib treatment in Rats with T2DM only after 8 weeks of treatment. CONCLUSION Our data indicate that darapladib can decrease the foam cells number, iNOS, and ICAM-1 expression in aorta at the early stages of atherosclerosis in T2DM Rat model.
Jennifer M Rojas - One of the best experts on this subject based on the ideXlab platform.
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the effect of diet induced obesity on toxicological parameters in the polygenic Sprague Dawley Rat model
Toxicologic Pathology, 2018Co-Authors: Jennifer M Rojas, Florian Bolze, Inger Thorup, Jette Nowak, Charlotte M Dalsgaard, Mikala Skydsgaard, Line Olrik Berthelsen, Kevin Keane, Henrik Soeborg, Ingrid SjogrenAbstract:The obese rodent serves as an indispensable tool for proof-of-concept efficacy and mode-of-action pharmacology studies. Yet the utility of this disease model as an adjunct to the conventional healthy animal in the nonclinical safety evaluation of anti-obesity pharmacotherapies has not been elucidated. Regulatory authorities have recommended employing disease models in toxicology studies when necessary. Our study investigated standard and exploRatory toxicology parameters in the high-fat diet (HFD)-induced obese, polygenic Sprague-Dawley Rat model in comparison to chow diet (CD)-fed controls. We sought to establish feasibility of the model for safety testing and relevance to human obesity pathophysiology. We report that both sexes fed a 45% kcal HFD for 29 weeks developed obesity and metabolic derangements that mimics to a certain extent, common human obesity. Minor clinical pathologies were observed in both sexes and considered related to CD versus HFD differences. Histopathologically, both sexes exhibited mild obesity-associated findings in brown and subcutaneous white fat, bone, kidneys, liver, lung, pancreas, salivary parotid glands, and skeletal muscle. We conclude that chronic HFD feeding in both sexes led to the development of an obese but otherwise healthy Rat. Therefore, the diet-induced obese Sprague-Dawley Rat may serve as a suitable model for evaluating toxicity findings encountered with anti-obesity compounds.
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Supplemental Material, DS7_TPX_10.1177_0192623318803557 - The Effect of Diet-induced Obesity on Toxicological Parameters in the Polygenic Sprague-Dawley Rat Model
2018Co-Authors: Jennifer M Rojas, Florian Bolze, Inger Thorup, Jette Nowak, Charlotte M Dalsgaard, Mikala Skydsgaard, Line Olrik Berthelsen, Henrik Soeborg, Kevin A. Keane, Ingrid SjogrenAbstract:Supplemental Material, DS7_TPX_10.1177_0192623318803557 for The Effect of Diet-induced Obesity on Toxicological Parameters in the Polygenic Sprague-Dawley Rat Model by Jennifer M. Rojas, Florian Bolze, Inger Thorup, Jette Nowak, Charlotte M. Dalsgaard, Mikala Skydsgaard, Line O. Berthelsen, Kevin A. Keane, Henrik Søeborg, Ingrid Sjögren, Jes T. Jensen, Johannes J. Fels, Hanne K. Offenberg, Lærke W. Andersen, and Majken Dalgaard in Toxicologic Pathology
Trygve B Leergaard - One of the best experts on this subject based on the ideXlab platform.
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waxholm space atlas of the Rat brain hippocampal region three dimensional delineations based on magnetic resonance and diffusion tensor imaging
NeuroImage, 2015Co-Authors: Lisa Jannicke Kjonigsen, Jan G Bjaalie, Sveinung Lillehaug, Trygve B LeergaardAbstract:Abstract Atlases of the Rat brain are widely used as reference for orientation, planning of experiments, and as tools for assigning location to experimental data. Improved quality and use of magnetic resonance imaging (MRI) and other tomographical imaging techniques in Rats have allowed the development of new three-dimensional (3-D) volumetric brain atlas templates. The Rat hippocampal region is a commonly used model for basic research on memory and learning, and for preclinical investigations of brain disease. The region features a complex anatomical organization with multiple subdivisions that can be identified on the basis of specific cytoarchitectonic or chemoarchitectonic criteria. We here investigate the extent to which it is possible to identify boundaries of divisions of the hippocampal region on the basis of high-resolution MRI contrast. We present the boundaries of 13 divisions, identified and delineated based on multiple types of image contrast observed in the recently published Waxholm Space MRI/DTI template for the Sprague Dawley Rat brain (Papp et al., Neuroimage 97:374–386, 2014). The new detailed delineations of the hippocampal formation and parahippocampal region (Waxholm Space atlas of the Sprague Dawley Rat brain, v2.0) are shared via the INCF Software Center ( http://software.incf.org/ ), where also the MRI/DTI reference template is available. The present update of the Waxholm Space atlas of the Rat brain is intended to facilitate interpretation, analysis, and integRation of experimental data from this anatomically complex region.
