Development of a Novel Translational Model of Vibration Injury to the Spine to Study Acute Injury in Vivo

2012 ◽  
Author(s):  
Beth A. Winkelstein
Keyword(s):  
Acute Injury ◽  
Translational Model

scholarly journals In Vivo Histopathologic Comparison of the Acute Injury Following Treatment With Five Fractional Ablative Laser Devices

2010 ◽  
Vol 30 (3) ◽  
pp. 457-464 ◽  
Author(s):  
J. P. Farkas ◽  
J. A. Richardson ◽  
C. F. Burrus ◽  
J. E. Hoopman ◽  
S. A. Brown ◽  
...  
Keyword(s):  
Acute Injury ◽  
Laser Devices ◽  
Ablative Laser ◽  
Fractional Ablative Laser

Pifithrin-α, an inhibitor of p53 transactivation, alters the inflammatory process and delays tendon healing following acute injury

2007 ◽  
Vol 292 (1) ◽  
pp. R321-R327 ◽  
Author(s):  
David Marsolais ◽  
Claude H. Côté ◽  
Jérôme Frenette
Keyword(s):  
Extracellular Matrix ◽  
Inflammatory Process ◽  
Tendon Repair ◽  
Tendon Healing ◽  
Tendon Injury ◽  
Acute Injury ◽  
Inflammatory Phase ◽  
Load To Failure ◽  
Transcription Factor P53

Transcription factor p53, which was initially associated with cancer, has now emerged as an important regulator of inflammation and extracellular matrix homeostasis, two processes highly relevant to tendon repair. The goal of this study was to evaluate the effect of a p53 transactivation inhibitor, namely, pifithrin-α, on the pathophysiological sequence following collagenase-induced tendon injury. Administration of pifithrin-α during the inflammatory phase reduced the accumulation of neutrophils and macrophages by 30 and 40%, respectively, on day 3 postinjury. Pifithrin-α failed to reduce the percentage of apoptotic cells following collagenase injection but delayed functional recovery. In uninjured Achilles tendons, pifithrin-α increased metalloprotease activity 2.4-fold. Accordingly, pifithrin-α reduced the collagen content in intact tendons as well as in injured tendons 7 days posttrauma compared with placebo. The effect of pifithrin-α on load to failure and stiffness was also evaluated. The administration of pifithrin-α during the inflammatory phase did not significantly decrease the functional deficit 3 days posttrauma. More importantly, load to failure and stiffness were significantly decreased in the pifithrin-α group from day 7 to day 28 compared with placebo. Overall, our results suggest that administration of pifithrin-α alters the inflammatory process and delays tendon healing. The present findings also support the concept that p53 can regulate extracellular matrix homeostasis in vivo.

scholarly journals Ventilator-induced lung-injury in mouse models: Is there a trap?

2021 ◽  
Vol 37 (1) ◽  
Author(s):  
Jon Petur Joelsson ◽  
Saevar Ingthorsson ◽  
Jennifer Kricker ◽  
Thorarinn Gudjonsson ◽  
Sigurbergur Karason
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Mouse Models ◽  
Mechanical Strain ◽  
Acute Injury ◽  
In Vivo Studies ◽  
Cellular Interactions ◽  
Ventilator Induced Lung Injury

AbstractVentilator-induced lung injury (VILI) is a serious acute injury to the lung tissue that can develop during mechanical ventilation of patients. Due to the mechanical strain of ventilation, damage can occur in the bronchiolar and alveolar epithelium resulting in a cascade of events that may be fatal to the patients. Patients requiring mechanical ventilation are often critically ill, which limits the possibility of obtaining patient samples, making VILI research challenging. In vitro models are very important for VILI research, but the complexity of the cellular interactions in multi-organ animals, necessitates in vivo studies where the mouse model is a common choice. However, the settings and duration of ventilation used to create VILI in mice vary greatly, causing uncertainty in interpretation and comparison of results. This review examines approaches to induce VILI in mouse models for the last 10 years, to our best knowledge, summarizing methods and key parameters presented across the studies. The results imply that a more standardized approach is warranted.

scholarly journals PL - 033 A translational model of muscle protein synthetic bioactivity in vitro, ex vivo and in vivo

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Brian Carson ◽  
Robert Davies ◽  
Joseph Bass ◽  
Catherine Norton ◽  
Bijal Patel ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stable Isotope ◽  
Resistance Exercise ◽  
Ex Vivo ◽  
Muscle Protein ◽  
Muscle Growth ◽  
Translational Model ◽  
Nutrient Feeding

Objective The aim of this research was the development and validation of a translational model for the evaluation of exercise and nutrient stimulated muscle protein synthesis (MPS). To achieve this overall aim, three primary objectives had to be realised: (i) Development of an in vitro skeletal muscle cell bioassay to measure muscle growth and MPS; (ii) Development of an ex vivo model to evaluate the humoral effect on MPS in response to nutrient feeding and exercise; (iii) Use of a stable isotope technique to evaluate MPS in response to nutrient feeding and exercise in vivo. Methods To develop a novel in vitro skeletal muscle cell bioassay to measure muscle growth and MPS, C2C12 myoblasts were proliferated and subsequently differentiated to myotubes over 8 days in DMEM (2% HS). Changes in cell behavior and adhesion properties were monitored by measuring impedance via interdigitated microelectrodes using the xCELLigence system. MPS was measured by puromycin incorporation using the SUnSET technique, intracellular signalling measured by western blot, and myotube thickness by microscopy. To demonstrate the capability to monitor nutrient regulation of muscle growth, media was conditioned with a known potent regulator of MPS (leucine) in a dose response experiment (0.20 - 2.0 mM). To establish the ability of the bioassay to measure the humoral effect of MPS in response to feeding and exercise, media was conditioned by ex vivo human serum from fasted, rested, fed (protein and isonitrogenous non-essential amino acid (NEAA) control)  and post-exercise conditions. To evaluate MPS in response to nutrient feeding and exercise in vivo, acute MPS (5 h) was assessed by measuring stable isotope deuterium oxide (D2O) incorporation into m. vastus lateralis skeletal muscle following consumption of either a Whey Protein (WP) or an isonitrogenous NEAA control combined with resistance exercise in resistance trained males. Results In vitro experiments observed a dose-response effect with a 32 % increase in cell index and a 27 % increase in cell thickness after 2 h in the presence of 2.0 mM leucine when compared with control myotubes. Ex vivo serum following ingestion of NEAA had no effect on protein signalling or MPS whereas WP fed serum significantly increased mTOR, P70S6K and 4E-BP1 phosphorylation (p<0.01, p<0.05) compared to fasted serum. Furthermore, the effect of WP fed serum on protein signalling and MPS was significantly increased (p<0.01, p<0.05) compared to NEAA fed serum.  Ex vivo human serum following resistance exercise was also increased MPS (29 %) and phosphorylation of mTOR (6 %), p70S6K (12 %) and 4EBP1 (7 %), compared with resting serum. These ex vivo/in vitro findings translated to the in vivo model as myofibrillar fractional synthetic rates (myoFSR) (Basal 0.068±0.002%h-1 vs. WP 0.084±0.006 %h-1, p=0.033) and absolute synthetic rates (ASR) (Basal 10.34±1.01 vs. WP 13.18±0.71 g.day-1, p=0.026) were increased from basal levels only when resistance exercise was combined with WP ingestion and not the NEAA control (NEAA MPS 0.072±0.004%h-1, NEAA ASR 10.23±0.80 g.day-1).  Thus, ingestion of WP in combination with resistance training augments acute MPS responses in resistance trained young men. Conclusions We have developed a translational model of muscle protein synthetic bioactivity using in vitro, ex vivo and in vivo methodologies. We have shown that we can impact MPS in vitro using ex vivo human serum to condition media, that MPS in vitro is differentially regulated by ex vivo serum containing bioactive WP compared to a non-bioactive NEAA control, and that this tranlates for resistance exercise combined with WP in humans when MyoFSR is measured using stable isotope technology.  These experiments demonstrate that ex vivo/in vitro experiments translate to the in vivo model and these methods can be used to inform both exercise and nutrient human interventions. 

Restitution of barrier and transport function of porcine colon after acute mucosal injury

1988 ◽  
Vol 255 (1) ◽  
pp. G62-G71 ◽  
Author(s):  
R. A. Argenzio ◽  
C. K. Henrikson ◽  
J. A. Liacos
Keyword(s):  
Short Circuit ◽  
Short Circuit Current ◽  
Mucosal Injury ◽  
Acute Injury ◽  
Surface Epithelium ◽  
Mucosal Permeability ◽  
Nacl Transport ◽  
Crypt Epithelium

Acute injury of the porcine colonic epithelium was induced in vivo with the bile salt, deoxycholate. A concentration of 15 mM for 30 min completely destroyed the surface epithelium and induced a marked increase in mucosal permeability to mannitol. The crypt epithelium however was not significantly affected. Within 8 min of recovery, the colonic surface was reepithelialized with flattened, migrating cells, and within 40 min, mucosal permeability to mannitol was normalized. In vitro studies showed that in these early stages of recovery, NaCl transport, short-circuit current, and resistance were markedly impaired, whereas the theophylline-induced secretory response remained intact. Recovery of absorptive function paralleled the transition from flattened to columnar surface epithelium and was complete within 2 h. Results suggest that 1) active migratory events play an important role in rapid restitution of an epithelial barrier, 2) active absorption of ions is much slower to recover, and 3) active secretory events are intact and probably originate in the crypt epithelium.

Abstract P280: Deletion of Cardiac Ankyrin Repeat Kinase Reduces Ischemia/Reperfusion Injury in the Heart in Vivo

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Ronald J Vagnozzi ◽  
Gregory Gatto ◽  
Lara Kallander ◽  
Victoria Ballard ◽  
Brian Lawhorn ◽  
...  
Keyword(s):  
Infarct Size ◽  
Troponin I ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Serum Levels ◽  
Ankyrin Repeat ◽  
Ischemic Heart ◽  
Acute Injury ◽  
Wild Type

Ischemic heart disease impacts millions of Americans and can progress to heart failure. Current therapies do not address this progression and new therapeutic targets are needed. One novel potential target is cardiac ankyrin repeat kinase (CARK, also troponin I interacting kinase; TNNI3K). CARK is expressed only in the heart and is significantly up-regulated in failing human hearts. Beyond this, little is known about CARK’s biological roles. To determine CARK’s function in the injured heart we subjected transgenic (Tg) mice expressing wild-type or kinase-inactive (KI) CARK to 30 minutes of LV ischemia followed by 24 hours of reperfusion (I/R). CARK-Tg mice had significantly larger infarcts (32.2% AAR vs 16.1% in WT littermates, p<0.05) following I/R. Cardiac troponin I (cTnI) serum levels were also significantly elevated in CARK-Tg mice after 24h, consistent with increased injury. Conversely, infarct size was decreased in mice expressing KI CARK and levels of cTnI were reduced, suggesting that blocking CARK activity may protect against acute injury. To test this, we employed an inducible, cardiac-specific knockout mouse (CARK-KO). CARK-KO mice showed a significant reduction in infarct size (20.52% vs 32.9%, p=0.01) as well as cTnI levels post-I/R. To confirm these findings, wild-type mice were treated with a small molecule CARK inhibitor and then were subjected to I/R. CARK inhibition significantly reduced infarct size (10.92% vs 21.74% p<0.01) as well as serum levels of cTnI. These data indicate that loss of CARK reduces myocyte injury and death after I/R. To examine the mechanism of this effect, primary NRVM were either transduced with a CARK adenovirus or treated with one of two selective CARK inhibitors, and then subjected to oxidative stress using H2O2. CARK over-expression worsened, while CARK inhibition significantly blunted H2O2 - induced apoptosis. Taken together, these data suggest that CARK plays an adverse role in the heart’s response to ischemia, in part by increasing apoptosis. Furthermore, inhibition of CARK may protect the ischemic heart by limiting initial cell loss and thus reducing infarct size. These findings enhance understanding of CARK’s role in the heart and provide evidence for CARK as a novel therapeutic target for ischemic injury.

Functional alterations of alveolar macrophages subjected to smoke exposure and antioxidant lazaroids

1999 ◽  
Vol 15 (5) ◽  
pp. 464-469 ◽  
Author(s):  
Shengjun Wang ◽  
R. Clark Lantz ◽  
Mary W. Vermeulen ◽  
Guan Jie Chen ◽  
Veronica Breceda ◽  
...  
Keyword(s):  
Lung Injury ◽  
Alveolar Macrophages ◽  
Cell Injury ◽  
Mrna Level ◽  
Smoke Exposure ◽  
Acute Injury ◽  
Smoke Control ◽  
Protein Levels ◽  
Tnf Α

Acute inhalation of diesel fuel-polycarbonate plastic (DFPP) smoke causes severe lung injury, leading to acute respiratory distress syndrome (ARDS) and death. It has been reported that the initiation of acute lung injury is associated with the activation of pulmonary alveolar macrophages (PAM). To further explore the pathogenesis, alveolar macrophages (AM) of New Zealand rabbits ventilated and exposed to a 60 tidal volume of DFPP smoke in vivo were recovered at 1 h post-smoke. Smoke exposure induced significant increases in both mRNA and protein levels for PAM tumor necrosis factor-α (TNF-α), when compared to smoke control. Smoke also induced a biphasic response (inhibited at 2 h, enhanced at 24 h after cell isolation) in the production of superoxide (O2−) by PAM. However, aerosolized lazaroid, U75412E (1.6 mg/kg body weight), significantly attenuated smoke-induced expression in AM TNF-α at the protein level but not at the mRNA level, and smoke-induced changes in AM production of O2−. This study suggests that highly expressing AM TNF-α following smoke may be a key contributor to the cascade that establishes an acute injury process and exacerbates oxidant-derived cell injury. Whereas, the lazaroid may ameliorate smoke-induced lung injury by attenuating AM TNF-α release, in addition to its primary antioxidative mechanism.

scholarly journals In Vivo Interstitial Migration of Primitive Macrophages Mediated by JNK-Matrix Metalloproteinase 13 Signaling in Response to Acute Injury

2008 ◽  
Vol 181 (3) ◽  
pp. 2155-2164 ◽  
Author(s):  
Yong Zhang ◽  
Xue-Tao Bai ◽  
Kang-Yong Zhu ◽  
Yi Jin ◽  
Min Deng ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Acute Injury ◽  
Matrix Metalloproteinase 13
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