Effect of a Novel Molybdenum Ascorbate Complex on Ex Vivo Myocardial Performance in Chemical??Diabetes Mellitus

Drugs in R&D ◽  
2006 ◽  
Vol 7 (2) ◽  
pp. 119-125 ◽  
Author(s):  
Tom L Broderick ◽  
John Bailey ◽  
Karen J Gagnon ◽  
Sarah J Lord ◽  
Christopher M Vogels ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Ex Vivo ◽  
Myocardial Performance ◽  
Chemical Diabetes

scholarly journals Melatonin-Pretreated Mesenchymal Stem Cells Improved Cognition in a Diabetic Murine Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Shaimaa Nasr Amin ◽  
Nivin Sharawy ◽  
Nashwa El Tablawy ◽  
Dalia Azmy Elberry ◽  
Mira Farouk Youssef ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Stem Cells ◽  
Animal Model ◽  
Mesenchymal Stem Cells ◽  
Synaptic Plasticity ◽  
Object Recognition ◽  
Ex Vivo ◽  
Type I ◽  
Positive Effects ◽  
Tnf Α

Diabetes mellitus (DM) is a multisystem endocrine disorder affecting the brain. Mesenchymal stem cells (MSCs) pretreated with Melatonin have been shown to increase the potency of MSCs. This work aimed to compare Melatonin, stem cells, and stem cells pretreated with Melatonin on the cognitive functions and markers of synaptic plasticity in an animal model of type I diabetes mellitus (TIDM). Thirty-six rats represented the animal model; six rats for isolation of MSCs and 30 rats were divided into five groups: control, TIDM, TIDM + Melatonin, TIDM + Stem cells, and TIDM + Stem ex vivo Melatonin. Functional assessment was performed with Y-maze, forced swimming test and novel object recognition. Histological and biochemical evaluation of hippocampal Neuroligin 1, Sortilin, Brain-Derived Neurotrophic Factor (BDNF), inducible nitric oxide synthase (iNOS), toll-like receptor 2 (TLR2), Tumor necrosis factor-alpha (TNF-α), and Growth Associated Protein 43 (GAP43). The TIDM group showed a significant decrease of hippocampal Neuroligin, Sortilin, and BDNF and a significant increase in iNOS, TNF-α, TLR2, and GAP43. Melatonin or stem cells groups showed improvement compared to the diabetic group but not compared to the control group. TIDM + Stem ex vivo Melatonin group showed a significant improvement, and some values were restored to normal. Ex vivo melatonin-treated stem cells had improved spatial working and object recognition memory and depression, with positive effects on glucose homeostasis, inflammatory markers levels and synaptic plasticity markers expression.

Abstract 616: MicroRNA miR-29b is a Mediator of Aortic Stiffness and Hypertension in a Murine Model of Type 2 Diabetes Mellitus

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Uwe Raaz ◽  
Isabel N Schellinger ◽  
Lars Maegdefessel ◽  
Joshua M Spin ◽  
Gerd Hasenfuss ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Pulse Pressure ◽  
Aortic Stiffness ◽  
Target Genes ◽  
Ex Vivo ◽  
Matrix Remodeling ◽  
Collagen Deposition ◽  
Arterial Stiffening ◽  
Vascular Stiffening ◽  
Aortic Stiffening

Background: Accelerated arterial stiffening is a complication of diabetes mellitus and associated with the development of hypertension. Arterial stiffening results from extensive extracellular matrix remodeling (elastin breakdown, collagen accumulation). MicroRNA miR-29b directly regulates the expression of genes governing fibrosis (such as COL1A1, COL3A1) and elastin breakdown ( MMP2, MMP9 ). However, its impact on aortic stiffness is unclear. Objective: This study was designed to investigate the role of miR-29b as potential mediator of diabetic aortic stiffening. Methods and Results: Serial ex vivo mechanical testing of the thoracic aorta and volume-pressure recording (VPR) based tail-cuff blood pressure measurements revealed that aortic stiffening precedes blood (pulse) pressure elevations in diabetic db/db mice. Vascular stiffening was accompanied by increased elastin fragmentation and collagen deposition (EvG and Picrosirius Red staining). qRT-PCR, in-situ hybridization and immunohistochemistry revealed decreased expression of miR-29b and de-repression of target genes ( Col1A1, COL3A1, MMP2, MMP9 ) in db/db mice compared to controls. Investigating the mechanistic significance of miR-29b for arterial stiffening, forced downregulation of miR-29b (via systemic LNA-miR-29b inhibitor application) results in enhanced elastin fragmentation, increased medial collagen deposition, aortic stiffness and augmented pulse pressure. Conclusions: In conclusion this study identifies miR-29b as a regulator and potential therapeutic target of diabetic aortic stiffening.

Assessment of donor heart viability during ex vivo heart perfusion

2015 ◽  
Vol 93 (10) ◽  
pp. 893-901 ◽  
Author(s):  
Christopher W. White ◽  
Emma Ambrose ◽  
Alison Müller ◽  
Yun Li ◽  
Hoa Le ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Vascular Resistance ◽  
Ex Vivo ◽  
Lactate Concentration ◽  
Left Ventricular ◽  
Coronary Vascular Resistance ◽  
Myocardial Performance ◽  
Donor Heart ◽  
Functional Parameters ◽  
Heart Perfusion

Ex vivo heart perfusion (EVHP) may facilitate resuscitation of discarded donor hearts and expand the donor pool; however, a reliable means of demonstrating organ viability prior to transplantation is required. Therefore, we sought to identify metabolic and functional parameters that predict myocardial performance during EVHP. To evaluate the parameters over a broad spectrum of organ function, we obtained hearts from 9 normal pigs and 37 donation after circulatory death pigs and perfused them ex vivo. Functional parameters obtained from a left ventricular conductance catheter, oxygen consumption, coronary vascular resistance, and lactate concentration were measured, and linear regression analyses were performed to identify which parameters best correlated with myocardial performance (cardiac index: mL·min–1·g–1). Functional parameters exhibited excellent correlation with myocardial performance and demonstrated high sensitivity and specificity for identifying hearts at risk of poor post-transplant function (ejection fraction: R2 = 0.80, sensitivity = 1.00, specificity = 0.85; stroke work: R2 = 0.76, sensitivity = 1.00, specificity = 0.77; minimum dP/dt: R2 = 0.74, sensitivity = 1.00, specificity = 0.54; tau: R2 = 0.51, sensitivity = 1.00, specificity = 0.92), whereas metabolic parameters were limited in their ability to predict myocardial performance (oxygen consumption: R2 = 0.28; coronary vascular resistance: R2 = 0.20; lactate concentration: R2 = 0.02). We concluded that evaluation of functional parameters provides the best assessment of myocardial performance during EVHP, which highlights the need for an EVHP device capable of assessing the donor heart in a physiologic working mode.

scholarly journals In vivo and ex vivo effects of propofol on myocardial performance in rats with obstructive jaundice

2011 ◽  
Vol 11 (1) ◽  
Author(s):  
Hong-Mei Ren ◽  
Li-Qun Yang ◽  
Zhi-Qiang Liu ◽  
Cai-Yang Chen ◽  
Chi-Wai Cheung ◽  
...  
Keyword(s):  
Obstructive Jaundice ◽  
Ex Vivo ◽  
Myocardial Performance

Loss of TM-Dependent PC-Activation Predisposes to Diabetic Nephropathy: Potential Role of Endothelial Apoptosis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1029-1029
Author(s):  
Berend Isermann ◽  
Madhusudhan Thati ◽  
Ilya Vinnikov ◽  
Stefanie Herzog ◽  
Sina Huntscha ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Caspase 3 ◽  
Ex Vivo ◽  
Vascular Complications ◽  
Diabetic Control ◽  
Endothelial Damage ◽  
Current Data ◽  
Diabetic Patients ◽  
Glomerular Damage

Abstract Increased levels of soluble thrombomodulin (TM) in patients with diabetes mellitus are considered a marker of endothelial damage. It is unknown whether the loss of endothelial TM-function contributes to the progression of vascular complications in diabetes mellitus. To address whether the loss of TM-dependent protein C (PC) activation contributes to diabetic complications such as diabetic nephropathy two animal models were employed: (1) TMPro mice, which have been previously described and carry a point mutation in the TM-gene (E404P), resulting in a loss of TM-dependent PC-activation, and (2) hPC mice, which carry a transgene resulting in the expression of a mutant “hyperactivatable” PC, which can be activated by thrombin in the absence of TM. The mutant PC could be captured from plasma samples of hPC mice and activated ex vivo by thrombin in the absence of TM. hPC mice had a prolonged bleeding time. Following induction of diabetes by streptozotocin TAT levels were increased in diabetic control (wild type) mice and to a larger extent in TMPro mice, but not in diabetic hPC mice. In comparison to diabetic control mice the kidney weight was increased in diabetic TMPro mice, but not in diabetic hPC mice. Albuminuria was increased in diabetic TMPro mice and reduced in diabetic hPC mice in comparison to diabetic control mice, indicating increased glomerular damage in TMPro mice and partial protection from glomerular damage in hPC mice. Consistently, using a histological score glomerular damage was more severe in diabetic TMPro mice in comparison to diabetic control mice, while diabetic hPC mice were protected. Preliminary data suggest that the observed changes are associated with increased apoptosis in glomeruli of diabetic TMPro mice. Using HUVECs we were able to establish that high glucose concentrations (30 mM) reduce TM-dependent PC activation. The reduced TM-dependent PC activation is associated with increased apoptosis. Glucose induced apoptosis in HUVECs is associated with an increased Bax/Bcl-2 ratio, increased translocation of Bax into mitochondria, and increased caspase-3 activation. Activated PC normalizes the Bax/Bcl-2 ratio, prevents translocation of Bax, and reduces caspase-3 activity. Further studies using TRAPs and inhibitory antibodies established that the antiapoptotic effect of aPC in glucose stressed endothelial cells is mediated through a Par-1 and EPCR-dependent mechanism. The current data strongly suggest that the loss of the endothelial TM-PC system is not just a marker of endothelial damage in diabetic patients, but rather contributes to the progression of diabetic vascular complications.

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