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Gignac, Marc-Antoine. "Anne Lagerwall, Le principe ex injuria jus non oritur en droit international, Bruxelles, Bruylant, 2016." Revue québécoise de droit international 30, no. 2 (2017): 261. http://dx.doi.org/10.7202/1064688ar.
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Shany, Yuval. "Legal Entitlements, Changing Circumstances and Intertemporality: A Comment on the Creation of Israel and the Status of Palestine." Israel Law Review 49, no. 3 (October 21, 2016): 391–408. http://dx.doi.org/10.1017/s0021223716000224.
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The events surrounding the establishment of the State of Israel in 1948 and the ensuing Palestinian naqba (disaster) have generated an abundance of legal literature. It is beyond the ambitions of this article to revisit all or most of the existing literature, or to strive and comprehensively discuss the various legal propositions they consider. Instead, it offers a critical assessment of some of the legal conclusions offered by one of the most influential experts in the field – Professor James Crawford – who, in the second edition of his seminal treatise The Creation of States in International Law, discusses at some length the events surrounding the creation of Israel and the status of Palestine. Section 2 of the article offers some general observations on the continued relevance of the events surrounding the creation of Israel. In particular, it raises the question of the relationship between the principles of ex injuria non oritur jus and ex factis oritur jus in the Israeli–Palestinian context. Section 3 examines the legal significance of the 1922 League of Nations Mandate and Crawford's position concerning its validity. Sections 4 and 5 adopt a similar examination with regard to two other historic events of potential legal significance, namely the 1947 UN General Assembly Resolution 181 (the Partition Resolution) and Israel's 1948 Declaration of Independence. Section 5 also briefly examines Crawford's conclusions relating to the status of Palestine, and Section 6 concludes.
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Janev, Igor. "Uncertain Future and Prospects of the Prespa Agreement between Macedonia and Greece." Advances in Politics and Economics 3, no. 2 (March 31, 2020): p1. http://dx.doi.org/10.22158/ape.v3n2p1.
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In the present article we discuss the future and prospects of the Prespa Agreement, concluded on June 17, 2018, between Macedonia and Greece aiming at resolving their “difference” over the name of Macedonia. The analysis is carried out by examining the legal aspects of United Nations Security Council Resolution 817 (1993) recommending the admission of Macedonia to UN membership but imposing on the applicant a provisional name (pending the settlement of difference over the applicant’s name), in particular its legal consistence with the provisions of Vienna Convention on the Law of Treaties (1969) and with the general jus cogens norms of International Law enshrined in the UN Charter. It is concluded that the UN SC Res.817 (1993) is by itself an ultra vires act and cannot serve as a legal basis for the Prespa Agreement (ex injuria jus not oritur), that the Prespa Agreement violates the provisions of the Vienna Convention on the Law of Treaties and the peremptory norms of International Law, particularly the principle of self-determination and enters into legal matters that belong stricto sensu to the domain of domestic jurisdiction of Macedonia. For these reasons the Prespa Agreement cannot be considered a legally valid treaty and, consequently, and Agreement can be subject of unilateral termination under provisions of Vienna Convention on the Law of Treaties (1969).
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Orrego G., Jaime, Juan Camilo Mosquera-Hernández, Santiago Ardila-Giraldo, Laura Torres-Canchala, Edgar Alzate, and Juan Pablo Benavidez. "Técnica EXIT como manejo de la vía aérea en masas gigantes congénitas de cuello." Revista Chilena de Pediatría 91, no. 3 (June 19, 2020): 398. http://dx.doi.org/10.32641/rchped.v91i3.1385.
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Las masas congénitas de cabeza y cuello se asocian a asfixia perinatal e injuria cerebral con elevada mortalidad. La técnica EXIT (Ex Útero Intrapartum Treatment) consiste en asegurar la vía aérea del neonato, sin interrumpir la oxigenación y perfusión materno-fetal a través del soporte placentario. Esta técnica no ha sido estandarizada en países de medianos ingresos.Objetivo: Describir el caso clínico de 2 neonatos manejados mediante la técnica EXIT.Caso Clínico: Se reportan dos casos, uno con malformación linfática diagnosticada a la semana 20 gestación y el segundo con tiromegalia y polihidramnios diagnosticados a la semana 35 de gestación. En ambos casos, durante la cesárea se realizó la técnica EXIT con un equipo conformado por neonatólogo, ginecólogo, anestesiólogo, cirujano pediatra, otorrinolaringólogo, enfermero y terapeuta respiratorio. En los dos pacientes se logró asegurar la vía aérea mediante intubación orotraqueal al primer intento. En el caso 1 se confirmó la malformación linfática y recibió escleroterapia, y en el caso 2 se diagnosticó hipotiroidismo congénito asociado a bocio, que fue manejado con levotiroxina. Los pacientes se mantuvieron 7 y 9 días con ventilación mecánica invasiva respectivamente y egresaron sin complicaciones respiratorias.Conclusiones: La técnica EXIT en estos casos fue un procedimiento seguro, llevado a cabo sin inconvenientes. Se necesita un equipo multidisciplinario y la disponibilidad de una unidad de cuidados intensivos neonatales, con el objetivo de reducir potenciales complicaciones y garantizar el manejo postnatal. Para lograr su ejecución, es indispensable el diagnóstico prenatal oportuno.
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Hou, Bingbing, Mingquan Wang, Ziyan Song, Qiushi He, and Zongyao Hao. "Renal puncture access using a blunt needle: proposal of the blunt puncture concept." World Journal of Urology 40, no. 4 (January 14, 2022): 1035–41. http://dx.doi.org/10.1007/s00345-021-03927-8.
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Abstract Purpose Severe haemorrhage in percutaneous nephrolithotomy (PCNL) is an alarming event, and preventing injury to renal major vessels is a challenge. We evaluated the efficiency of a blunt needle in renal puncture procedures. Methods We first retrospectively reviewed the embolization images of post-PCNL patients to analyse the types of arteries injured, which were considered target arteries. Then, either a blunt needle or a conventional needle was used to directly puncture target arteries in ex vivo porcine kidneys and to establish renal access ex vivo and in vivo. The primary outcome was the incidence of target artery injuries, which were observed by digital subtraction angiography, nephroscopy and 3-dimensional endocasts. The secondary outcome was the rate of excreted fluid per access. Results The segmental and interlobar arteries were the most common types of injured arteries that needed to be embolized after PCNL. When these arteries were punctured directly, blunt needles reduced injury (1/20 vs. 16/20; OR 4.750; 95% CI 1.966–11.478; P < .001) by 76% compared to injuries induced by conventional needles. Moreover, the blunt needle group also had a significantly lower incidence of these arteries’ injuries ex vivo due to renal puncture and yielded a lower rate of excreted fluid in ex vivo and in vivo renal puncture procedures. Conclusion A blunt needle for renal puncture can be effective in reducing injury to renal major arteries and the accompanying haemorrhage. We propose the concept of blunt puncture, which may be a promising method for achieving safe renal access in PCNL.
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Campbell, Kristin, Karen Foster-Schubert, Liren Xiao, Catherine Alfano, Lisa Cadmus Bertram, Catherine Duggan, Melinda Irwin, and Anne McTiernan. "Injuries in Sedentary Individuals Enrolled in a 12-Month, Randomized, Controlled, Exercise Trial." Journal of Physical Activity and Health 9, no. 2 (February 2012): 198–207. http://dx.doi.org/10.1123/jpah.9.2.198.
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Background:The risk of musculoskeletal injury with the introduction of moderate-to-vigorous exercise in sedentary adults is not well established. The purpose of this report is to examine the effect of a 12-month exercise intervention on musculoskeletal injury and bodily pain in predominately overweight, sedentary men (n = 102) and women (n = 100), ages 40 to 75 years.Methods:Participants were randomized to a moderate-to-vigorous aerobic exercise intervention (EX) (6 d/wk, 60 min/d, 60% to 85% max. heart rate) or usual lifestyle control (CON). Participants completed a self-report of musculoskeletal injury and body pain at baseline and 12-months.Results:The number of individuals reporting an injury (CON; 28% vs. EX; 28%, P = .95) did not differ by group. The most commonly injured site was lower leg/ankle/foot. The most common causes of injury were sports/physical activity, home maintenance, or “other.” In the control group, bodily pain increased over the 12 months compared with the exercise group (CON −7.9, EX −1.4, P = .05). Baseline demographics and volume of exercise were not associated with injury risk.Conclusions:Previously sedentary men and women randomized to a 12-month aerobic exercise intervention with a goal of 360 min/wk reported the same number of injuries as those in the control group and less bodily pain.
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Davis, Ryan S., Sharon Hood, and Barbara J. Bentz. "Fire-injured ponderosa pine provide a pulsed resource for bark beetles." Canadian Journal of Forest Research 42, no. 12 (December 2012): 2022–36. http://dx.doi.org/10.1139/x2012-147.
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Bark beetles can cause substantial mortality of trees that would otherwise survive fire injuries. Resin response of fire-injured northern Rocky Mountain ponderosa pine ( Pinus ponderosa Douglas ex P. Lawson & C. Lawson) and specific injuries that contribute to increased bark beetle attack susceptibility and brood production are unknown. We monitored ponderosa pine mortality and resin flow and bark beetle colonization and reproduction following a prescribed fire in Idaho and a wildfire in Montana. The level of fire-caused tree injury differed between the two sites, and the level of tree injury most susceptible to bark beetle attack and colonization also differed. Strip-attacked trees alive 3 years post-fire had lower levels of bole and crown injury than trees mass attacked and killed by bark beetles, suggesting that fire-injured trees were less well defended. Brood production of western pine beetle ( Dendroctonus brevicomis LeConte) did not differ between fire-injured and uninjured trees, although mountain pine beetle ( Dendroctonus ponderosae Hopkins) brood production was low in both tree types, potentially due to competition with faster developing bark beetle species that also colonized trees. Despite a large number of live trees remaining at both sites, bark beetle response to fire-injured trees pulsed and receded within 2 years post-fire, potentially due to a limited number of trees that could be easily colonized.
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Boyer, Richard B., Nathaniel D. Kelm, D. Colton Riley, Kevin W. Sexton, Alonda C. Pollins, R. Bruce Shack, Richard D. Dortch, Lillian B. Nanney, Mark D. Does, and Wesley P. Thayer. "4.7-T diffusion tensor imaging of acute traumatic peripheral nerve injury." Neurosurgical Focus 39, no. 3 (September 2015): E9. http://dx.doi.org/10.3171/2015.6.focus1590.
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Diagnosis and management of peripheral nerve injury is complicated by the inability to assess microstructural features of injured nerve fibers via clinical examination and electrophysiology. Diffusion tensor imaging (DTI) has been shown to accurately detect nerve injury and regeneration in crush models of peripheral nerve injury, but no prior studies have been conducted on nerve transection, a surgical emergency that can lead to permanent weakness or paralysis. Acute sciatic nerve injuries were performed microsurgically to produce multiple grades of nerve transection in rats that were harvested 1 hour after surgery. High-resolution diffusion tensor images from ex vivo sciatic nerves were obtained using diffusion-weighted spin-echo acquisitions at 4.7 T. Fractional anisotropy was significantly reduced at the injury sites of transected rats compared with sham rats. Additionally, minor eigenvalues and radial diffusivity were profoundly elevated at all injury sites and were negatively correlated to the degree of injury. Diffusion tensor tractography showed discontinuities at all injury sites and significantly reduced continuous tract counts. These findings demonstrate that high-resolution DTI is a promising tool for acute diagnosis and grading of traumatic peripheral nerve injuries.
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Seo, Tae-Beom, Yeong-Hyun Cho, Hyuk Sakong, and Young-Pyo Kim. "Effect of treadmill exercise and bone marrow stromal cell engraftment on activation of BDNF-ERK-CREB signaling pathway in the crushed sciatic nerve." Journal of Exercise Rehabilitation 17, no. 6 (December 27, 2021): 403–9. http://dx.doi.org/10.12965/jer.2142626.313.
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The effect of combined approach of exercise training and bone marrow stromal cell (BMSC) engraftment on activation of brain-derived neurotrophic factor (BDNF)-extracellular signal-regulated kinase 1 and 2 (ERK1/2)-cyclic adenosine monophosphate response element-binding protein (CREB) signaling pathway after sciatic nerve injury (SNI) was investigated. Sixty male Sprague-Dawley rats divided into the normal control, nonexercise (NEX), exercise training (EX), BMSC transplantation (TP), and exercise training+BMSC transplantation (EX+TP) groups 4 weeks after SCI. Exercise training was carried out on the treadmill device at 5–10 m/min for 20 min for 4 weeks. Single dose of 5× 106 harvested BMSC was injected into the injury area of the injured sciatic nerve. In order to evaluate induction levels of BDNF-ERK1/2-CREB signaling molecules in the whole cell and nuclear cell lysates of the injured sciatic nerve, we applied Western blot analysis. BDNF was significantly increased only in EX+TP compared to NEX, EX, and TP groups. Phosphoinositide-dependent kinase-1 was more increased in EX, TP, and EX+TP groups than NEX group, but EX+TP group showed the most upregulation of phosphorylated protein kinase B compared to other groups. In addition, in the whole cell lysate, phosphorylated ERK1/2, but not activating transcription factor-3 (ATF-3) and phosphorylated CREB, was significantly increased in TP and EX+TP groups. In the nuclear cell lysate, ATF-3 and phosphorylated CREB were strongly activated in EX+TP group compared to EX group. Regular exercise training combined with BMSC engraftment would seem to be more effective in controlling activation of regeneration-related signaling pathway after SNI.
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Bosque, Marc, Ramon Margalef, Oscar Carvajal, David Álvarez, and Manel M. Santafe. "Dry Needling Produces Mild Injuries Irrespective to Muscle Stiffness and Tension in Ex Vivo Mice Muscles." Pain Research and Management 2022 (July 5, 2022): 1–10. http://dx.doi.org/10.1155/2022/8920252.
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Numerous studies have suggested that the myofascial trigger points are responsible for most of the myofascial pain syndrome, so it seems reasonable that its destruction is a good therapeutic solution. The effectiveness of dry needling (DN) has been confirmed in muscles with myofascial trigger points, hypertonicity, and spasticity. The objective of this study is to analyze the need of repetitive punctures on muscles in different situations. The levator auris longus (LAL) muscle and gastrocnemius muscle from adult male Swiss mice were dissected and maintained alive, while being submerged in an oxygenated Ringer’s solution. DN was evaluated under four animal models, mimicking the human condition: normal healthy muscles, muscle fibers with contraction knots, muscles submerged in a depolarizing Ringer solution (KCl-CaCl2), and muscles submerged in Ringer solution with formalin. Thereafter, samples were evaluated with optical microscopy (LAL) and scanning electron microscopy (gastrocnemius). Healthy muscles allowed the penetration of needles between fibers with minimal injuries. In muscles with contraction knots, the needle separated many muscle fibers, and several others were injured, while blood vessels and intramuscular nerves were mostly not injured. Muscles submerged in a depolarizing solution inducing sustained contraction showed more injured muscular fibers and several muscle fibers separated by the needle. Finally, the muscles submerged in Ringer solution with formalin showed a few number of injured muscular fibers and abundant muscle fibers separated by the needle. Scanning electron microscopy images confirm the optical analyses. In summary, dry needling is a technique that causes mild injury irrespective of the muscle tone.
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Aertker, Benjamin M., Akshita Kumar, Fanni Cardenas, Franciska Gudenkauf, David Sequeira, Alan R. Prossin, Amit K. Srivastava, Charles S. Cox, and Supinder S. Bedi. "PET Imaging of Peripheral Benzodiazepine Receptor Standard Uptake Value Increases After Controlled Cortical Impact, a Rodent Model of Traumatic Brain Injury." ASN Neuro 13 (January 2021): 175909142110141. http://dx.doi.org/10.1177/17590914211014135.
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Traumatic brain injury (TBI) is a chronic, life threatening injury for which few effective interventions are available. Evidence in animal models suggests un-checked immune activation may contribute to the pathophysiology. Changes in regional density of active brain microglia can be quantified in vivo with positron emission topography (PET) with the relatively selective radiotracer, peripheral benzodiazepine receptor 28 (11 C-PBR28). Phenotypic assessment (activated vs resting) can subsequently be assessed (ex vivo) using morphological techniques. To elucidate the mechanistic contribution of immune cells in due to TBI, we employed a hybrid approach involving both in vivo (11 C-PBR28 PET) and ex vivo (morphology) to elucidate the role of immune cells in a controlled cortical impact (CCI), a rodent model for TBI. Density of activated brain microglia/macrophages was quantified 120 hours after injury using the standardized uptake value (SUV) approach. Ex vivo morphological analysis from specific brain regions using IBA-1 antibodies differentiated ramified (resting) from amoeboid (activated) immune cells. Additional immunostaining of PBRs facilitated co-localization of PBRs with IBA-1 staining to further validate PET data. Injured animals displayed greater PBR28suv when compared to sham animals. Immunohistochemistry demonstrated elevated density of amoeboid microglia/macrophages in the ipsilateral dentate gyrus, corpus callosum, thalami and injury penumbra of injured animals compared to sham animals. PBR co-stained with amoeboid microglia/macrophages in the injury penumbra and not with astrocytes. These data suggest the technologies evaluated may serve as bio-signatures of neuroinflammation following severe brain injury in small animals, potentially enabling in vivo tracking of neuroinflammation following TBI and cellular-based therapies.
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Khairunnisa, Astry, and Pipit Pitriani. "Sepaktakraw Players Injuries Event." JUARA : Jurnal Olahraga 5, no. 1 (September 26, 2019): 1–7. http://dx.doi.org/10.33222/juara.v5i1.624.
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Sepaktakraw basically requires acrobatic skills (ex: backflip, sunback spike, split, etc) that has high difficulty in playing it. The aim of this study was to look the incident of injuries (injury body parts, type of injury, and mechanism of injury). This study used descriptive research methods. 40 male and female athletes participated in the pre-season for Indonesian national competition (PON) 2020. The instruments used were questionnaires and interviews regarding the injury body parts, types of injuries and mechanisms injury. The results showed that the most damage experienced by sepaktakraw players occurred at the ankle (27%) with the type of sprained injury (47.5%) and was most widely known by server-positioned players and killer/spiker compilation when they did serve movements (27%) and spike (30%).
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Chang, Chu-Yuan, Min-Zong Liang, Ching-Chih Wu, Pei-Yuan Huang, Hong-I. Chen, Shaw-Fang Yet, Jin-Wu Tsai, Cheng-Fu Kao, and Linyi Chen. "WNT3A Promotes Neuronal Regeneration upon Traumatic Brain Injury." International Journal of Molecular Sciences 21, no. 4 (February 21, 2020): 1463. http://dx.doi.org/10.3390/ijms21041463.
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The treatment of traumatic brain injury (TBI) remains a challenge due to limited knowledge about the mechanisms underlying neuronal regeneration. This current study compared the expression of WNT genes during regeneration of injured cortical neurons. Recombinant WNT3A showed positive effect in promoting neuronal regeneration via in vitro, ex vivo, and in vivo TBI models. Intranasal administration of WNT3A protein to TBI mice increased the number of NeuN+ neurons without affecting GFAP+ glial cells, compared to control mice, as well as retained motor function based on functional behavior analysis. Our findings demonstrated that WNT3A, 8A, 9B, and 10A promote regeneration of injured cortical neurons. Among these WNTs, WNT3A showed the most promising regenerative potential in vivo, ex vivo, and in vitro.
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Blits, Bas, Paul A. Dijkhuizen, Wim T. J. M. C. Hermens, Lisette K. E. Van Esseveldt, Gerard J. Boer, and Joost Verhaagen. "The Use of Adenoviral Vectors and Ex Vivo Transduced Neurotransplants: Towards Promotion of Neuroregeneration." Cell Transplantation 9, no. 2 (March 2000): 169–78. http://dx.doi.org/10.1177/096368970000900204.
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Regeneration of injured axons following injury depends on a delicate balance between growth-promoting and growth-inhibiting factors. Overexpression of neurotrophin genes seems a promising strategy to promote regeneration. Trophic genes can be overexpressed at the site of injury at the axonal stumps, or at the perikaryal level of the injured neuron. Transduction of the neural cells can be achieved by applying adenoviral vectors, either directly in vivo or—in the case of neurotransplantation—as an ex vivo approach. In both cases it would create a more permissive environment for axonal growth and therefore in functional regeneration. In this article, the feasibility of the use of adenoviral vectors in several neuroregeneration models–-in particularly in spinal cord lesion models and the biological clock transplantation model–-is illustrated. The results show that the adenoviral vectors can be a powerful tool to study the effects of overexpression of genes in an in vivo paradigm of nerve regeneration or nerve outgrowth. The potential use of adenoviral vectors and ex vivo transduced neurotransplants is discussed.
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Nguyen, Thuy-Tien N., David R. Sory, Harsh D. Amin, Sara M. Rankin, and William G. Proud. "Platform development for primary blast injury studies." Trauma 21, no. 2 (May 15, 2018): 141–46. http://dx.doi.org/10.1177/1460408618776035.
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Explosion-related injuries are currently the most commonly occurring wounds in modern conflicts. They are observed in both military and civilian theatres, with complex injury pathophysiologies. Primary blast injuries are the most frequently encountered critical injuries experienced by victims close to the explosion. They are caused by large and rapid pressure changes of the blast waves which produce a wide range of loading patterns resulting in varied injuries. Well-characterised experimental loading devices which can reproduce the real mechanical characteristics of blast loadings on biological specimens in in vivo, ex vivo, and in vitro models are essential in determining the injury mechanisms. This paper discusses the performance and application of platforms, including shock tubes, mechanical testing machines, drop-weight rigs, and split-Hopkinson pressure bar, with regards to the replication of primary blast.
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MacRae, Priscilla Gilliam, Michael E. Feltner, and Sibylle Reinsch. "A 1-Year Exercise Program for Older Women: Effects on Falls, Injuries, and Physical Performance." Journal of Aging and Physical Activity 2, no. 2 (April 1994): 127–42. http://dx.doi.org/10.1123/japa.2.2.127.
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This study examined the effects of a 1-year low intensity exercise program in community dwelling older women on falls, injuries, and risk factors for falls such as poor balance, muscular weakness, and gait abnormalities. Eighty older women were assigned to an exercise (Ex,n= 42) or attention control (Co,n= 38) group. During the 1-year study, 36% of the Ex group experienced a fall compared to 45% of the Co group (χ2= 0.22,p≥ 0.05). None of the 10 fallers in the Ex group suffered an injury that required medical attention, compared with 3 of the 14 fallers (21%) in the Co group. Further analyses indicated that the Co group declined significantly in isometric strength of the knee extensors and ankle dorsiflexors while the Ex group did not change significantly across the 1-year study. On measures of hip abductor strength, balance, and gait, the groups were not significantly different from each other pre- to post intervention.
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Ohtsubo, Shin, Masakazu Ishikawa, Naosuke Kamei, Yasumu Kijima, Osami Suzuki, Toru Sunagawa, Yukihito Higashi, Haruchika Masuda, Takayuki Asahara, and Mitsuo Ochi. "The therapeutic potential of ex vivo expanded CD133+ cells derived from human peripheral blood for peripheral nerve injuries." Journal of Neurosurgery 117, no. 4 (October 2012): 787–94. http://dx.doi.org/10.3171/2012.7.jns111503.
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Object CD133+ cells have the potential to enhance histological and functional recovery from peripheral nerve injury. However, the number of CD133+ cells safely obtained from human peripheral blood is extremely limited. To address this issue, the authors expanded CD133+ cells derived from human peripheral blood using the serum-free expansion culture method and transplanted these ex vivo expanded cells into a model of sciatic nerve defect in rats. The purpose of this study was to determine the potential of ex vivo expanded CD133+ cells to induce or enhance the repair of injured peripheral nerves. Methods Phosphate-buffered saline (PBS group [Group 1]), 105 fresh CD133+ cells (fresh group [Group 2]), 105 ex vivo expanded CD133+ cells (expansion group [Group 3]), or 104 fresh CD133+ cells (low-dose group [Group 4]) embedded in atelocollagen gel were transplanted into a silicone tube that was then used to bridge a 15-mm defect in the sciatic nerve of athymic rats (10 animals per group). At 8 weeks postsurgery, histological and functional evaluations of the regenerated tissues were performed. Results After 1 week of expansion culture, the number of cells increased 9.6 ± 3.3–fold. Based on the fluorescence-activated cell sorting analysis, it was demonstrated that the initial freshly isolated CD133+ cell population contained 93.22% ± 0.30% CD133+ cells and further confirmed that the expanded cells had a purity of 59.02% ± 1.58% CD133+ cells. However, the histologically and functionally regenerated nerves bridging the defects were recognized in all rats in Groups 2 and 3 and in 6 of 10 rats in Group 4. The nerves did not regenerate to bridge the defect in any of the rats in Group 1. Conclusions The authors' results show that ex vivo expanded CD133+ cells derived from human peripheral blood have a therapeutic potential similar to fresh CD133+ cells for peripheral nerve injuries. The ex vivo procedure that can be used to expand CD133+ cells without reducing their function represents a novel method for developing cell therapy for nerve defects in a clinical setting.
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Lee, Chang Woo, Kazumasa Fukushima, Arvydas Usas, Lin Xin, Dalip Pelinkovic, Vladimir Martinek, George Somogyi, Paul D. Robbins, Freddie H. Fu, and Johnny Huard. "BIOLOGICAL INTERVENTION BASED ON CELL AND GENE THERAPY TO IMPROVE MUSCLE HEALING AFTER LACERATION." Journal of Musculoskeletal Research 04, no. 04 (December 2000): 265–77. http://dx.doi.org/10.1142/s0218957700000264.
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Muscle laceration is a challenging problem in traumatology and is common in sports injuries, with functional recovery remaining slow and incomplete. Even though muscles retain their ability to regenerate after injury, muscles' healing process after such injuries has been found to be very slow and often leads to incomplete muscle recovery. Growth factors may have a role in enhancing recovery. Our previous study showed that IGF-1, β-FGF and NGF can improve myoblast proliferation and differentiation in vitro. We then investigated whether the delivery of IGF-1 would improve muscle healing after injuries. We observed that muscle regeneration was enhanced in lacerated muscles treated with IGF-1 protein, which consequently led to an improvement in muscle healing. However, the rapid clearance and short biological half-lives of these proteins may have limited the success of this approach. We then investigated the efficiency of gene therapy based on adenovirus to deliver a stable expression of the growth factor IGF-1. Although a slight improvement in the healing process occurred in the muscle injected with adenovirus (AIGF), the combination of myoblast transplantation and gene therapy with the ex vivo approach further improved the healing process. The injection of normal myoblasts into the injured muscle led to the best improvement of muscle healing at two weeks post-injection. Implantation of normal minced muscle into mdx mice was also capable of improving muscle healing at 2–4 weeks post-implantation. These studies will further our understanding of muscle healing post-injury and help in the development of strategies to promote efficient muscle healing and complete functional recovery after common muscle injuries.
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Jiang, Wenqian, Youwen Tan, Mengjie Cai, Ting Zhao, Fei Mao, Xu Zhang, Wenrong Xu, Zhixin Yan, Hui Qian, and Yongmin Yan. "Human Umbilical Cord MSC-Derived Exosomes Suppress the Development of CCl4-Induced Liver Injury through Antioxidant Effect." Stem Cells International 2018 (2018): 1–11. http://dx.doi.org/10.1155/2018/6079642.
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Mesenchymal stem cells (MSCs) have been increasingly applied into clinical therapy. Exosomes are small (30–100 nm in diameter) membrane vesicles released by different cell types and possess the similar functions with their derived cells. Human umbilical cord MSC-derived exosomes (hucMSC-Ex) play important roles in liver repair. However, the effects and mechanisms of hucMSC-Ex on liver injury development remain elusive. Mouse models of acute and chronic liver injury and liver tumor were induced by carbon tetrachloride (CCl4) injection, followed by administration of hucMSC-Ex via the tail vein. Alleviation of liver injury by hucMSC-Ex was determined. We further explored the production of oxidative stress and apoptosis in the development of liver injury and compared the antioxidant effects of hucMSC-Ex with frequently used hepatic protectant, bifendate (DDB) in liver injury. hucMSC-Ex alleviated CCl4-induced acute liver injury and liver fibrosis and restrained the growth of liver tumors. Decreased oxidative stress and apoptosis were found in hucMSC-Ex-treated mouse models and liver cells. Compared to bifendate (DDB) treatment, hucMSC-Ex presented more distinct antioxidant and hepatoprotective effects. hucMSC-Ex may suppress CCl4-induced liver injury development via antioxidant potentials and could be a more effective antioxidant than DDB in CCl4-induced liver tumor development.
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Bridges, Janis, Andrew Worth, and Kevin Frame. "Effect of a calcaneo-tibial screw on medial and lateral stability of the canine tarsocrural joint ex vivo." Veterinary and Comparative Orthopaedics and Traumatology 30, no. 05 (2017): 331–38. http://dx.doi.org/10.3415/vcot-16-12-0160.
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SummaryObjective: To evaluate the use of a temporary calcaneo-tibial screw for stabilization of the tarsocrural joint in dogs with surgically treated collateral ligament injury.Methods: The degree of varus and valgus laxity of the tarsocrural joint in various states of injury and stabilization was measured in paired cadaveric limbs of Greyhound dogs. The angle of varus or valgus laxity was calculated following simulated collateral ligament injury (long collateral ligament only, long and short collateral ligaments, and bilateral long and short collateral ligaments) and stabilization with a calcaneo-tibial screw.Results: The joint was significantly more stable after placement of a calcaneo-tibial screw compared to limbs with any combination of injured collateral ligaments. There was not a significant difference between stability of the intact limb compared to the injured limb with calcaneo-tibial screw fixation.Clinical significance: Calcaneo-tibial screw fixation appears to be an adequate method of stabilizing the tarsocrural joint following collateral ligament injury, and warrants clinical evaluation as a less expensive alternative to external skeletal fixation application. It is likely that this method would need to be supplemented with a cranial half cast to prevent screw failure during weight bearing.
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Butler, Benjamin, Thuy-Tien Nguyen, Alun Williams, Andrew Tucker, William G. Proud, and Katherine A. Brown. "Use of a Shock Tube Platform in the Replication of Blast Lung Injury." EPJ Web of Conferences 250 (2021): 01024. http://dx.doi.org/10.1051/epjconf/202125001024.
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War and asymmetrical conflicts are becoming increasingly prevalent in the modern world. Due to improvements in conflict medicine, survivable injuries are now more severe than they once were. Therefore, it is now more important than ever that there exist scientific and engineering methods for replicating wartime injuries in the context of the laboratory. We have developed one such method: a shock tube platform for testing ex vivo samples of the porcine respiratory system. Using this platform, we can, to some extent, simulate the pathophysiological consequences of blast lung. This is a condition commonly present in victims of explosive blasts, both those due to typical armaments and Improvised Explosive Devices (IEDs). Presented here are the results of experiments conducted using porcine bronchiole tissue as ex vivo organ cultures. Data presented show epithelial damage, consistent with known trauma-induced cell injury that can lead to acute respiratory distress syndrome (ARDS).
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Scafidi, Susanna, Jennifer Jernberg, Gary Fiskum, and Mary C. McKenna. "Metabolism of Exogenous [2,4-13C]β-Hydroxybutyrate Following Traumatic Brain Injury in 21-22-Day-Old Rats: An Ex Vivo NMR Study." Metabolites 12, no. 8 (July 29, 2022): 710. http://dx.doi.org/10.3390/metabo12080710.
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Traumatic brain injury (TBI) is the leading cause of morbidity in young children. Acute dysregulation of oxidative glucose metabolism within the first hours after injury is a hallmark of TBI. The developing brain relies on ketones as well as glucose for energy. Thus, the aim of this study was to determine the metabolism of ketones early after TBI injury in the developing brain. Following the controlled cortical impact injury model of TBI, 21–22-day-old rats were infused with [2,4-13C]β-hydroxybutyrate during the acute (4 h) period after injury. Using ex vivo 13C-NMR spectroscopy, we determined that 13C-β-hydroxybutyrate (13C-BHB) metabolism was increased in both the ipsilateral and contralateral sides of the brain after TBI. Incorporation of the label was significantly higher in glutamate than glutamine, indicating that 13C-BHB metabolism was higher in neurons than astrocytes in both sham and injured brains. Our results show that (i) ketone metabolism was significantly higher in both the ipsilateral and contralateral sides of the injured brain after TBI; (ii) ketones were extensively metabolized by both astrocytes and neurons, albeit higher in neurons; (iii) the pyruvate recycling pathway determined by incorporation of the label from the metabolism of 13C-BHB into lactate was upregulated in the immature brain after TBI.
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Wittmann, Andreas, Nenad Kralj, Jan Köver, Klaus Gasthaus, and Friedrich Hofmann. "Study of Blood Contact in Simulated Surgical Needlestick Injuries With Single or Double Latex Gloving." Infection Control & Hospital Epidemiology 30, no. 1 (January 2009): 53–56. http://dx.doi.org/10.1086/593124.
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Objective.Needlestick injuries are the most common injuries that occur among operation room personnel in the health care service. The risk of infection after a needlestick injury during surgery greatly depends on the quantity of pathogenic germs transferred at the point of injury. The aim of this study was to measure the quantity of blood transferred at the point of a percutaneous injury by using radioactively labeled blood.Design.This study was conducted to evaluate the risk of infection through blood contact by simulating surgical needlestick injuries ex vivo. The tests were conducted by puncturing single and double latex gloves with diverse sharp devices and objects that were contaminated with Technetium solution–labeled blood.Results.A mean volume of 0.064 μL of blood was transferred in punctures with the an automatic lancet at a depth of 2.4 mm through 1 layer of latex. When the double-gloving indicator technique was used, a mean volume of only 0.011 μL of blood was transferred (median, 0.007 μL); thus, by wearing 2 pairs of gloves, the transferred volume of blood was reduced by a factor of 5.8.Conclusions.The results revealed that double gloving leads to a significant reduction in the quantity of blood transferred during needlestick injury.
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Zeng, Lingyu, Wenyi Lu, Lan Ding, Wen Ju, Jianlin Qiao, and Kailin Xu. "PEDF Can Rescue the Inhibition of Injured Endothelial Cells on Hematopoietic Stem Cell Expansion Ex Vivo." Blood 134, Supplement_1 (November 13, 2019): 5008. http://dx.doi.org/10.1182/blood-2019-127978.
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Introduction: Endothelial cells (ECs) provide a fertile niche for hematopoietic stem cell (HSC) maintenance, differentiation, and migration.Several studies have indicated that bone marrow (BM) vascular niche was impaired after HSC transplantation and severely inhibited hematopoietic reconstruction. Pigment epithelium-derived factor (PEDF) is an important potential cytoprotection and therapeutic agent for injured cells. The direct role of the injured endothelial cells on hematopoietic stem cells and whether PEDF has protective effect in this system remain unknown. This study aims to observe the influence of enjured ECs on HSCs and to explore the role of PEDF in endothelial-HSC coculture system. Methods: Injury of Endothelial cells by two important preparative regimenconditioning radiation and Busulfan respectively was evaluated with CCK8 assay. The expression of endothelial tight junctions(TJs),adherent junctions related molecules and endothelial to Mesenchymal Transition molecules such as ZO-1, Occludin,VE-cadherin, ICAM, α-SMA, CD31 and VCAM were detected by RT-qPCR, flow cytometry, immunofluorescence and western blot. The effects of injured endothelial cells on HSC self-renewal, differentiation, cell cycle and apoptosis were evaluated by flow cytometry, photography, viable cell count and clone formation assay. Hematopoiesis regulation factors SCF, IL-6, TGF-β and TNF-α were detected by ELISA. The protective effect of PEDF was also explored. Results: Both radiation and Busulfan could decrease cell viability of endothelial cells. The expression level of ZO-1, Occludin, VE-cadherin, ICAM, CD31 and VCAM were decreased and α-SMA was increased when EC exposed to radiation or Busulfan suggesting endothelial activation, impaired EC permeability and endothelial to Mesenchymal Transition after EC injured. Compared with normal endothelial cells and hematopoietic stem cell co-culture group, the HSC% of injured endothelial cells and hematopoietic stem cells co-cultured group were significantly decreased, the cell colony formation ability was decreased, the proportion of mature cells increased, and the damage of endothelial cells could not maintain the characteristics of HSC, weakened the self-renewal and multidirectional differentiation potential of HSC and promoted the maturation of HSC. After the administration of PEDF, endothelial to Mesenchymal Transition of EC was suppressed and the EC permeability was improved. Most importantly, the proportion of HSC was significantly increased, and the proportion of mature cells decreased in the coculture system. Conclusion: Injured endothelial cells can inhibit proliferation of hematopoietic stem cells, self-renewal and promote HSC differentiation. PEDF could ameliorate endothelial injury and promote HSC expansion by suppressing endothelial-mesenchymal transition and protecting TJs and AJs. Disclosures No relevant conflicts of interest to declare.
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Patar, Azim, Peter Dockery, Siobhan McMahon, and Linda Howard. "Ex Vivo Rat Transected Spinal Cord Slices as a Model to Assess Lentiviral Vector Delivery of Neurotrophin-3 and Short Hairpin RNA against NG2." Biology 9, no. 3 (March 15, 2020): 54. http://dx.doi.org/10.3390/biology9030054.
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The failure of the spinal cord to regenerate can be attributed both to a lack of trophic support for regenerating axons and to upregulation of inhibitory factors such as chondroitin sulphate proteoglycans including NG2 following injury. Lentiviral vector-mediated gene therapy is a possible strategy for treating spinal cord injury (SCI). This study investigated the effect of lentiviral vectors expressing Neurotrophin-3 (NT-3) and short-hairpin RNA against NG2 (NG2 sh) to enhance neurite outgrowth in in vitro and ex vivo transection injury models. Conditioned medium from cells transduced with NT-3 or shNG2 lentiviruses caused a significant increase in neurite length of primary dorsal root ganglia neurons compared to the control group in vitro. In an ex vivo organotypic slice culture (OSC) transduction with Lenti-NT-3 promoted axonal growth. Transducing OSCs with a combination of Lenti-NT-3/NG2 sh lead to a further increase in axonal growth but only in injured slices and only within the region adjacent to the site of injury. These findings suggest that the combination of lentiviral NT-3 and NG2 sh reduced NG2 levels and provided a more favourable microenvironment for neuronal regeneration after SCI. This study also shows that OSCs may be a useful platform for studying glial scarring and potential SCI treatments.
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Prudhomme, Thomas, Delphine Kervella, Stéphanie Le Bas-Bernardet, Diego Cantarovich, Georges Karam, Gilles Blancho, and Julien Branchereau. "Ex situ Perfusion of Pancreas for Whole-Organ Transplantation: Is it Safe and Feasible? A Systematic Review." Journal of Diabetes Science and Technology 14, no. 1 (August 13, 2019): 120–34. http://dx.doi.org/10.1177/1932296819869312.
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Introduction: Pancreas transplantation is currently one of the best treatments proposed in highly selected patients with unstable and brittle type 1 diabetes. The objective of pancreas transplantation is to restore normoglycemia and avoid the occurrence of complications associated with diabetes. Graft pancreatitis and thrombosis, arising from ischemia reperfusion injuries, are major causes of graft loss in the postoperative period. Ex situ perfusion, in hypothermic or normothermic settings, allowed to improve ischemic reperfusion injury in other organ transplantations (kidney, liver, or lung). The development of pancreatic graft perfusion techniques would limit these ischemic reperfusion injuries. Objective: Evaluation of the safety and feasibility of ex situ perfusion of pancreas for whole-organ transplantation. Methods: English literature about pancreas perfusion was analyzed using electronic database Medline via PubMed (1950-2018). Exclusion criteria were studies that did not specify the technical aspects of machine perfusion and studies focused only on pancreas perfusion for islet isolation. Results: Hypothermic machine perfusion for pancreas preservation has been evaluated in nine studies and normothermic machine perfusion in ten studies. We evaluated machine perfusion model, types of experimental model, anatomy, perfusion parameters, flushing and perfusion solution, length of perfusion, and comparison between static cold storage and perfusion. Conclusions: This review compared ex vivo machine perfusion of experimental pancreas for whole-organ transplantation. Pancreas perfusion is feasible and could be a helpful tool to evaluate pancreas prior to transplantation. Pancreas perfusion (in hypothermic or normothermic settings) could reduce ischemic reperfusion injuries, and maybe could avoid pancreas thrombosis and reduce morbidity of pancreas transplantation.
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Giesen, Peter, Billie Fyfe, John Fallon, Merce Roque, Milton Mendlowitz, Maria Rossikhina, Arabinda Guha, Juan Badimon, Yale Nemerson, and Mark Taubman. "Intimal Tissue Factor Activity Is Released from the Arterial Wall after Injury." Thrombosis and Haemostasis 83, no. 04 (2000): 622–28. http://dx.doi.org/10.1055/s-0037-1613874.
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SummaryTissue factor (TF), the initiator of coagulation, has been implicated as a critical mediator of arterial thrombosis. Previous studies have demonstrated that TF is rapidly induced in the normal rodent arterial wall by balloon injury, but is not associated with fibrin deposition. A second injury, however, performed 10–14 days after the first, is followed by small platelet-fibrin microthrombi. This study was undertaken to better localize active TF in balloon-injured rat arteries and to explore possible mechanisms underlying the apparent discrepancy between injury-induced TF expression and the lack of large platelet-fibrin thrombi. By immunohistochemistry, TF antigen was first detected in the media 24 h after injury to rat aortas, and subsequently accumulated in the neointima. Using an ex vivo flow chamber, no TF activity (Factor Xa generation) was found on the luminal surface of normal or injured aortas. Wiping the luminal surface with a cotton swab exposed TF activity in all vessels; levels were increased ≈3-fold in arteries containing a neointima. The exposed TF activity was rapidly washed into the perfusate, rendering the luminal surface inactive. The loss of luminal TF into the circulation may attenuate thrombosis at sites of arterial injury.
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De Blasio, Daiana, Stefano Fumagalli, Luca Longhi, Franca Orsini, Alessandro Palmioli, Matteo Stravalaci, Gloria Vegliante, et al. "Pharmacological inhibition of mannose-binding lectin ameliorates neurobehavioral dysfunction following experimental traumatic brain injury." Journal of Cerebral Blood Flow & Metabolism 37, no. 3 (July 20, 2016): 938–50. http://dx.doi.org/10.1177/0271678x16647397.
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Mannose-binding lectin is present in the contusion area of traumatic brain-injured patients and in that of traumatic brain-injured mice, where mannose-binding lectin-C exceeds mannose-binding lectin-A. The reduced susceptibility to traumatic brain injury of mannose-binding lectin double knock-out mice (mannose-binding lectin−/−) when compared to wild type mice suggests that mannose-binding lectin may be a therapeutic target following traumatic brain injury. Here, we evaluated the effects of a multivalent glycomimetic mannose-binding lectin ligand, Polyman9, following traumatic brain injury in mice. In vitro surface plasmon resonance assay indicated that Polyman9 dose-dependently inhibits the binding to immobilized mannose residues of plasma mannose-binding lectin-C selectively over that of mannose-binding lectin-A. Male C57Bl/6 mice underwent sham/controlled cortical impact traumatic brain injury and intravenous treatment with Polyman9/saline. Ex-vivo surface plasmon resonance studies confirmed that Polyman9 effectively reduces the binding of plasma mannose-binding lectin-C to immobilized mannose residues. In vivo studies up to four weeks post injury, showed that Polyman9 induces significant improvement in sensorimotor deficits (by neuroscore and beam walk), promotes neurogenesis (73% increase in doublecortin immunoreactivity), and astrogliosis (28% increase in glial fibrillary acid protein). Polyman9 administration in brain-injured mannose-binding lectin−/− mice had no effect on post-traumatic brain-injured functional deficits, suggestive of the specificity of its neuroprotective effects. The neurobehavioral efficacy of Polyman9 implicates mannose-binding lectin-C as a novel therapeutic target for traumatic brain injury.
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Dilley, Katelyn K., Pamela A. Borden, Yueqiao Qu, Andrew E. Heidari, Karthik R. Prasad, Yan Li, Chung Ho Sun, et al. "Potential-Driven Electrochemical Clearing of Ex Vivo Alkaline Corneal Injuries." Translational Vision Science & Technology 11, no. 1 (January 21, 2022): 32. http://dx.doi.org/10.1167/tvst.11.1.32.
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Konrad, Ildiko, Andrea Hauser, Suzanne Sauer, Zhongyan Li, Hans-Jürgen Wester, Frank Bengel, Markus Schwaiger, et al. "Non-invasive imaging of glycoprotein VI binding to injured arterial lesions." Thrombosis and Haemostasis 93, no. 05 (2005): 910–13. http://dx.doi.org/10.1160/th04-10-0660.
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SummaryGlycoprotein VI (GPVI) is the major platelet collagen receptor and plays a critical role in the process of thrombosis at sites of atherosclerotic lesions. This study evaluates the feasibility of radiolabeled soluble GPVI to identify injured arterial lesions. Radiolabeling was carried out using the iodogen method and resulted in the radioiodinated GPVI in radiochemical yields between 97–100%. The biodistribution of [125I]GPVI was determined in normal mice and demonstrated a blood clearance halftime of approximately 5.5 hours. Vascular lesions were induced in the carotid artery in wild type and ApoE -/- mice. Immediately after injury radioiodinated GPVI was injected intravenously. Binding of [123I]GPVI to carotid lesions was assessed by szinti-graphic in vivo imaging. Carotid arteries were explanted for ex vivo autoradiography and histological characterization of the lesion. In vivo and ex vivo imaging revealed substantial accumulation of radioiodinated GPVI in the injured artery wall, with a ratio of lesion to control vessel of 3:1 and 7:1, respectively. Because GPVI is the critical collagen receptor that mediates platelet adhesion to vascular lesions, soluble radiolabeled GPVI may be an agent for non-invasive imaging of thrombogenic thus, vulnerable atherosclerotic plaques.
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Shuvarin, Aleksey, and Vadim Kharin. "Life after sports: legal aspects of social guarantees of ex-athletes." Current Issues of the State and Law, no. 14 (2020): 187–96. http://dx.doi.org/10.20310/2587-9340-2020-4-14-187-196.
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Sport is a very important component of our life. Many people play sports as a hobby, on an amateur level. However, for some people, sport is a part of their life, and they are engaged in sports activities at a professional level. The work shows the positive and negative sides of sports as a profession. In particular, after leaving the “high-performance sport”, outstanding and famous athletes become coaches, businessmen, political, public figures, etc. However, a completely different plot of life awaits people who receive injuries that are incompatible with further engaging in professional sports at the height of their career. If they do not achieve permanent excellent results, and do not reach the “Olympus of glory”, they become useless to anyone. To alleviate these consequences of athletes who are forced to end their professional careers due to injury, European countries have certain social support programs that help athletes cope with crises. At the same time, evaluating our legislation, we can note that at the moment in the Russian Federation there is no well-established system of social support programs for professional athletes who are forced to leave the “high-performance sport”.
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Irpachi, Kalpana, and Poonam Malhotra Kapoor. "Understanding Heart Transplantation—Gift of Life." Journal of Cardiac Critical Care TSS 01, no. 02 (December 2017): 72–81. http://dx.doi.org/10.1055/s-0038-1626675.
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AbstractHeart transplantation (HTx) provides a longer and better quality of life to patients with end-stage heart failure when all other options of treatment have been exhausted. There are nearly 500 heart donors yearly in India. Approximately 60 cases of HTx are performed every year; 70% survival rate is for nearly 1 year whereas 30% survival rate is for 10 years. Scarcity of donors is further complicated by the use of single organ, heart injury with common brain-death injuries, difficulty with ex vivo preservation, heart disease among donors, and complexity of the operation.
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Huang, Jing, Rui Tian, Yongqiang Yang, Rong Jiang, Jie Dai, Li Tang, and Li Zhang. "The SIRT1 inhibitor EX-527 suppresses mTOR activation and alleviates acute lung injury in mice with endotoxiemia." Innate Immunity 23, no. 8 (September 27, 2017): 678–86. http://dx.doi.org/10.1177/1753425917733531.
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It is generally regarded that Sirtuin 1 (SIRT1), a longevity factor in mammals, acts as a negative regulator of inflammation. However, recent studies also found that SIRT1 might be a detrimental factor under certain inflammatory circumstance. In this study, the potential pathophysiological roles and the underlying mechanisms of SIRT1 in a mouse model with endotoxemia-associated acute lung injury were investigated. The results indicated that treatment with the selective SIRT1 inhibitor EX-527 suppressed LPS-induced elevation of TNF-α and IL-6 in plasma. Treatment with EX-527 attenuated LPS-induced histological abnormalities in lung tissue, which was accompanied with decreased myeloperoxidase level and suppressed induction of tissue factor and plasminogen activator inhibitor-1. Treatment with EX-527 also suppressed LPS-induced phosphorylation of eukaryotic translation initiation factor-binding protein 1 (4E-BP1). Co-administration of a mammalian target of rapamycin (mTOR) activator 3-benzyl-5-[(2-nitrophenoxy) methyl]-dihydrofuran-2 (3H)-one (3BDO) abolished the inhibitory effects of EX-527 on 4E-BP1 phosphorylation. Meanwhile, the inhibitory effects of EX-527 on IL-6 induction and the beneficial effects of EX-527 on lung injury were partially reversed by 3BDO. This study suggests that selective inhibition of SIRT1 by EX-527 might alleviate endotoxemia-associated acute lung injury partially via suppression of mTOR, which implies that SIRT1 selective inhibitors might have potential value for the pharmacological intervention of inflammatory lung injury.
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Krüger, Leandi, Tiffany A. Pridgen, Ellie R. Taylor, Katherine S. Garman, and Anthony T. Blikslager. "Lubiprostone protects esophageal mucosa from acid injury in porcine esophagus." American Journal of Physiology-Gastrointestinal and Liver Physiology 318, no. 4 (April 1, 2020): G613—G623. http://dx.doi.org/10.1152/ajpgi.00086.2019.
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Esophageal injury from acid exposure related to gastroesophageal reflux disease is a common problem and a risk factor for development of Barrett’s esophagus and esophageal adenocarcinoma. Our previous work highlights the benefits of using porcine esophagus to study human esophageal disease because of the similarities between porcine and human esophagus. In particular, esophageal submucosal glands (ESMGs) are present in human esophagus and proximal porcine esophagus but not in rodent esophagus. Although CFTR is expressed in the ducts of ESMGs, very little is known about CFTR and alternate anion channels, including ClC-2, in the setting of acid-related esophageal injury. After finding evidence of CFTR and ClC-2 in the basal layers of the squamous epithelium, and in the ducts of the ESMGs, we developed an ex vivo porcine model of esophageal acid injury. In this model, esophageal tissue was placed in Ussing chambers to determine the effect of pretreatment with the ClC-2 agonist lubiprostone on tissue damage related to acid exposure. Pretreatment with lubiprostone significantly reduced the level of acid injury and significantly augmented the recovery of the injured tissue ( P < 0.05). Evaluation of the interepithelial tight junctions showed well-defined membrane localization of occludin in lubiprostone-treated injured tissues. Pretreatment of tissues with the Na+-K+-2Cl− cotransporter inhibitor bumetanide blocked lubiprostone-induced increases in short-circuit current and inhibited the reparative effect of lubiprostone. Furthermore, inhibition of ClC-2 with ZnCl2 blocked the effects of lubiprostone. We conclude that ClC-2 contributes to esophageal protection from acid exposure, potentially offering a new therapeutic target. NEW & NOTEWORTHY This research is the first to describe the presence of anion channels ClC-2 and CFTR localized to the basal epithelia of porcine esophageal mucosa and the esophageal submucosal glands. In the setting of ex vivo acid exposure, the ClC-2 agonist lubiprostone reduced acid-related injury and enhanced recovery of the epithelial barrier. This work may ultimately provide an alternate mechanism for treating gastroesophageal reflux disease.
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Giraud, Sébastien, Clara Steichen, Pierre Couturier, Solenne Tillet, Vanessa Mallet, Rémi Coudroy, Jean-Michel Goujon, Patrick Hannaert, and Thierry Hauet. "Influence of Hypoxic Preservation Temperature on Endothelial Cells and Kidney Integrity." BioMed Research International 2019 (June 4, 2019): 1–15. http://dx.doi.org/10.1155/2019/8572138.
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Ischemia-reperfusion (IR) injury is unavoidable during organ transplantation and impacts graft quality. New paradigms are emerging including preservation at higher temperature than “hypothermia” or “cold”: although 4°C remains largely used for kidney preservation, recent studies challenged this choice. We and others hypothesized that a higher preservation temperature, closer to physiological regimen, could improve organ quality. For this purpose, we used an in vitro model of endothelial cells exposed to hypoxia-reoxygenation sequence (mimicking IR) and an ex vivo ischemic pig kidneys static storage model. In vitro, 19°C, 27°C, and 32°C provided protection against injuries versus 4°C, by reducing cell death, mitochondrial dysfunction, leukocyte adhesion, and inflammation. However, ex vivo, the benefits of 19°C or 32°C were limited, showing similar levels of tissue preservation damage. Ex vivo 4°C-preserved kidneys displayed a trend towards reduced damage, including apoptosis. Macrophage infiltration, tubulitis, and necrosis were increased in the 19°C and 32°C versus 4°C preserved kidneys. Thus, despite a trend for an advantage of subnormothermia as preservation temperature, our in vitro and ex vivo models bring different insights in terms of preservation temperature effect. This study suggests that temperature optimization for kidney preservation will require thorough investigation, combining the use of complementary relevant models and the design of elaborated preservation solution and new technologies.
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Jiang, Hailun, Jianguo Xing, Jiansong Fang, Linlin Wang, Yu Wang, Li Zeng, Zhuorong Li, and Rui Liu. "Tilianin Protects against Ischemia/Reperfusion-Induced Myocardial Injury through the Inhibition of the Ca2+/Calmodulin-Dependent Protein Kinase II-Dependent Apoptotic and Inflammatory Signaling Pathways." BioMed Research International 2020 (October 9, 2020): 1–18. http://dx.doi.org/10.1155/2020/5939715.
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Tilianin is a naturally occurring phenolic compound with a cardioprotective effect against myocardial ischemia/reperfusion injury (MIRI). The aim of our study was to determine the potential targets and mechanism of action of tilianin against cardiac injury induced by MIRI. An in silico docking model was used in this study for binding mode analysis between tilianin and Ca2+/calmodulin-dependent protein kinase II (CaMKII). Oxygen-glucose deprivation/reperfusion- (OGD/R-) injured H9c2 cardiomyocytes and ischemia/reperfusion- (I/R-) injured isolated rat hearts were developed as in vitro and ex vivo models, respectively, which were both treated with tilianin in the absence or presence of a specific CaMKII inhibitor KN93 for target verification and mechanistic exploration. Results demonstrated the ability of tilianin to facilitater the recovery of OGD/R-induced cardiomyocyte injury and the maintenance of cardiac function in I/R-injured hearts. Tilianin interacted with CaMKIIδ with an efficient binding performance, a favorable binding score, and restraining p-CaMKII and ox-CaMKII expression in cardiomyocytes injured by MIRI. Importantly, inhibition of CaMKII abolished tilianin-mediated recovery of OGD/R-induced cardiomyocyte injury and maintenance of cardiac function in I/R-injured hearts, accompanied by the disability to protect mitochondrial function. Furthermore, the protective effects of tilianin towards mitochondrion-associated proapoptotic and antiapoptotic protein counterbalance and c-Jun N-terminal kinase (JNK)/nuclear factor- (NF-) κB-related inflammation suppression were both abolished after pharmacological inhibition of CaMKII. Our investigation indicated that the inhibition of CaMKII-mediated mitochondrial apoptosis and JNK/NF-κB inflammation might be considered as a pivotal mechanism used by tilianin to exert its protective effects on MIRI cardiac damage.
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R., Margalef, Bosque M., and Santafé MM. "Dry needling in situations with varying degrees of muscle tone: an ex vivo study." Revista Fisioterapia Invasiva / Journal of Invasive Techniques in Physical Therapy 02, no. 02 (December 2019): 113. http://dx.doi.org/10.1055/s-0039-3401884.
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Abstract Introduction Numerous studies support the fact that myofascial trigger points are responsible for the clinical findings in myofascial pain syndrome, therefore it is reasonable to believe that the destruction of the same via dry needling may be an optimal solution. However, this technique has not been assessed in relation to muscle tone. Methods The experiments were performed with the levator auris longus (LAL) muscle of Swiss adult mice. The muscles, once extracted from the animal, were maintained ex vivo using normal oxygenated Ringer solution. Once these were extracted, they were extended upon a Sylgard® surface, maintained in vivo at all times. In these conditions, 15 insertions were performed with dry needling needles (0.25 mm X 25mm; AguPunt) in the attempt to avoid repeating needling on the same site. Different degrees of muscle tone were obtained as follows (from lesser to greater tone): healthy animals; animal model of myofascial trigger points (PGM); muscles which, once extracted were treated with ClK 30 mM and ClCa2 5mM; formaldehyde. Immediately after treatment, the muscles were dyed with methylene blue. Results The muscle fibers of healthy muscles are mostly pushed aside by the needle, practically without injury. Muscles with MTrPs are more injured than healthy muscles because of the use of dry needling, albeit only partially. The tone acquired with ClK and ClCa2 is more powerful and generalized, therefore, dry needling creates a greater injury. Lastly, formaldehyde provokes a powerful increase of muscle tension, however the injury produced by dry needling is not so noteworthy, due to the fact that the muscle fibers fixed with formaldehyde are extremely resistant. Conclusions Dry needling is a technique which, overall, provokes limited lesions, independent of the muscle tone.
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Borges, EL, MB Pinheiro, A. Eleto-Silva, MV Caliari, and MG Rodrigues-Machado. "Glycogen content is affected differently in acute pulmonary and extra-pulmonary lung injury." Human & Experimental Toxicology 28, no. 9 (September 2009): 583–90. http://dx.doi.org/10.1177/0960327109106998.
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Acute respiratory distress syndrome (ARDS) is the most severe form of acute lung injury (ALI). The aim of the present study was to investigate whether paraquat-induced acute pulmonary and extra-pulmonary lung injury (ALI-P and ALI-EX, respectively), in rats, affects glycogen content in different tissues. This measurement could indicate performance limitations of tissues, a new biochemical aspect of ARDS. ALI-P and ALI-EX were induced by injection into the trachea (0.5 mg/kg) and intraperitoneally (20 mg/kg) 24 hours prior to tissue collection. The control groups (CTRL) received the same volume of saline. Glycogen content (mg/g tissue) from different tissues was measured using the anthrone reagent. Glycogen content in the heart and kidney was higher in the ALI-EX group than the CTRL-EX group. Glycogen content in the gastrocnemius muscle was lower in the ALI-EX group than the CTRL-EX group. However, there were no significant differences in glycogen content in the diaphragm in the ALI-EX and ALI-P groups or in the gastrocnemius, heart and kidney in the ALI-P group when compared to the respective controls. ALI-EX caused a greater thickening of the alveolar walls, more areas of atelectasis and a greater abundance of inflammatory cells in comparison to ALI-P. These results demonstrate that glycogen content in ALI, induced by an herbicide that is highly toxic to humans and animals, is altered in different tissues depending on the location of the injury.
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Inci, Ilhan, Luca Ampollini, Stephan Arni, Wolfgang Jungraithmayr, Demet Inci, Sven Hillinger, Boris Leskosek, Peter Vogt, and Walter Weder. "Ex Vivo Reconditioning of Marginal Donor Lungs Injured by Acid Aspiration." Journal of Heart and Lung Transplantation 27, no. 11 (November 2008): 1229–36. http://dx.doi.org/10.1016/j.healun.2008.07.027.
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M G, Raj Kumar, and Srinivasa Reddy P. "Diagnosing injuries caused by Indian wild boar: A case report." JOURNAL OF CLINICAL AND BIOMEDICAL SCIENCES 10, no. 2 (June 15, 2020): 66–68. http://dx.doi.org/10.58739/jcbs/v10i2.1.
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Wild boars are medium sized mammals commonly seen in Europe, Asia, North Africa and Greater Sun-da Island and India. Sus scrofa cristatus species is commonly seen in India. They are primarily nocturnal animal and are generally shy in nature, so incidences of attack by wild boar are rare. They are dangerous due to their razor sharp tusks, which can cause serious injuries. Wild boar attacks are under reported in the medical litera-ture. Attacks on humans by wild animals causing fatal injuries are not uncommon in rural and forest areas of India. This is the case of a 55-year-old male farmer who was assaulted from by an adult wild boar. Autopsy ex-amination revealed multiple penetrating injuries, bilateral rib fractures and an anorectal injury. Unlike the inju-ries inflicted by wild cats, canines and bulls, the hallmark of boar attack is the infliction of multiple penetrating injuries to the lower part of the body. As the victims of wild boar attack are usually recovered from rural forest areas, the investigating officers could be misled as to the nature of infliction of these multiple, fatal penetrating injuries to a possible homicide. This case is reported for its rarity, for the awareness of the possible injuries in such unnatural deaths, and for the factors predisposing to a boar attack. It is concluded that fatal penetrating injuries caused by this type of attack can be associated with extensive soft-tissue damage despite externally appearing to be simple puncture wounds. Keywords: Wild boar, penetrating injuries, anorectal injury
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Kural, Mehmet H., Guohao Dai, Laura E. Niklason, and Liqiong Gui. "An Ex Vivo Vessel Injury Model to Study Remodeling." Cell Transplantation 27, no. 9 (August 10, 2018): 1375–89. http://dx.doi.org/10.1177/0963689718792201.
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Objective: Invasive coronary interventions can fail due to intimal hyperplasia and restenosis. Endothelial cell (EC) seeding to the vessel lumen, accelerating re-endothelialization, or local release of mTOR pathway inhibitors have helped reduce intimal hyperplasia after vessel injury. While animal models are powerful tools, they are complex and expensive, and not always reflective of human physiology. Therefore, we developed an in vitro 3D vascular model validating previous in vivo animal models and utilizing isolated human arteries to study vascular remodeling after injury. Approach: We utilized a bioreactor that enables the control of intramural pressure and shear stress in vessel conduits to investigate the vascular response in both rat and human arteries to intraluminal injury. Results: Culturing rat aorta segments in vitro, we show that vigorous removal of luminal ECs results in vessel injury, causing medial proliferation by Day-4 and neointima formation, with the observation of SCA1+ cells (stem cell antigen-1) in the intima by Day-7, in the absence of flow. Conversely, when endothelial-denuded rat aortae and human umbilical arteries were subjected to arterial shear stress, pre-seeding with human umbilical ECs decreased the number and proliferation of smooth muscle cell (SMC) significantly in the media of both rat and human vessels. Conclusion: Our bioreactor system provides a novel platform for correlating ex vivo findings with vascular outcomes in vivo. The present in vitro human arterial injury model can be helpful in the study of EC-SMC interactions and vascular remodeling, by allowing for the separation of mechanical, cellular, and soluble factors.
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Askenase, Michael H., Brittany A. Goods, Hannah E. Beatty, Arthur F. Steinschneider, Sofia E. Velazquez, Artem Osherov, Margaret J. Landreneau, et al. "Longitudinal transcriptomics define the stages of myeloid activation in the living human brain after intracerebral hemorrhage." Science Immunology 6, no. 56 (February 19, 2021): eabd6279. http://dx.doi.org/10.1126/sciimmunol.abd6279.
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Opportunities to interrogate the immune responses in the injured tissue of living patients suffering from acute sterile injuries such as stroke and heart attack are limited. We leveraged a clinical trial of minimally invasive neurosurgery for patients with intracerebral hemorrhage (ICH), a severely disabling subtype of stroke, to investigate the dynamics of inflammation at the site of brain injury over time. Longitudinal transcriptional profiling of CD14+ monocytes/macrophages and neutrophils from hematomas of patients with ICH revealed that the myeloid response to ICH within the hematoma is distinct from that in the blood and occurs in stages conserved across the patient cohort. Initially, hematoma myeloid cells expressed a robust anabolic proinflammatory profile characterized by activation of hypoxia-inducible factors (HIFs) and expression of genes encoding immune factors and glycolysis. Subsequently, inflammatory gene expression decreased over time, whereas anti-inflammatory circuits were maintained and phagocytic and antioxidative pathways up-regulated. During this transition to immune resolution, glycolysis gene expression and levels of the potent proresolution lipid mediator prostaglandin E2 remained elevated in the hematoma, and unexpectedly, these elevations correlated with positive patient outcomes. Ex vivo activation of human macrophages by ICH-associated stimuli highlighted an important role for HIFs in production of both inflammatory and anti-inflammatory factors, including PGE2, which, in turn, augmented VEGF production. Our findings define the time course of myeloid activation in the human brain after ICH, revealing a conserved progression of immune responses from proinflammatory to proresolution states in humans after brain injury and identifying transcriptional programs associated with neurological recovery.
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Shmueli, Benjamin, and Yuval Sinai. "Victim Pays Damages to Tortfeasor: The When and Wherefore." McGill Law Journal 61, no. 2 (August 10, 2016): 275–331. http://dx.doi.org/10.7202/1037249ar.
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Is there a reality in which the victim pays damages to the tortfeasor? This article analyzes Calabresi and Melamed’s liability rule for the damaging party (Rule 4), where the damaged party has the right to prevent pollution if the polluter is compensated first. Under the conventional application of this rule, the victim first collects the money and compensates the injurer, and only then is the injurer required to eliminate the nuisance (ex ante). There is no reference to a possibility of the injurer first eliminating the nuisance and only then receiving compensation (ex post). We argue that the timing of the payment should be changed when the activity causing the nuisance has social and economic value. Each version of the rule advances the aggregate welfare in some sense, but also harms it in another. The primary aim of the present article is to introduce a new model for Rule 4 that would guide legislators, regulators, and judges in deciding when to order compensation as a condition for eliminating the nuisance and when to order the injurer to remove the nuisance first and only then collect the funds. This article also introduces a comparative perspective that reveals the potential use of the ex post version of Rule 4, as manifest in sources of the Jewish legal tradition. This comparison further bolsters our proposal in favour of a division between ex ante and ex post versions of the rule. Ultimately, offering two versions for the implementation of Rule 4 would better enable the adaptation of a suitable solution according to the circumstances and thus would widen the possibilities for the rule’s use.
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Karnicki, Krzysztof, Robert Leadley, Sangita Baxi, Thomas Peterson, Waldemar Wysokinski, and Robert McBane. "Comparison of PD0348292, a selective factor Xa inhibitor, to antiplatelet agents for the inhibition of arterial thrombosis." Thrombosis and Haemostasis 99, no. 04 (2008): 759–66. http://dx.doi.org/10.1160/th07-09-0576.
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SummaryThe objective of this study was to determine if orally-administered PD0348292, a direct specific factor Xa inhibitor, inhibits thrombosis following porcine carotid arterial injury comparably to aspirin or clopidogrel alone or in combination. We further sought to determine whether the antithrombotic efficacy in vivo could be predicted using an ex-vivo perfusion chamber. Oral treatments included: PD0348292 (0.4, 0.9, or 4.3 mg/kg); PD0348292 (0.4 mg/kg) plus aspirin (325 mg); aspirin; clopidogrel (75 mg); aspirin plus clopidogrel; or vehicle (n=6–10/group). Aspirin and clopidogrel were administered 27 and four hours pre-injury and PD0348292 or vehicle was administered four hours pre-injury. Both carotid arteries were crush-injured, and thrombus was measured by detection of 111In-platelets over 30 minutes. Prior to injury, the antithrombotic efficacy was assessed by ex-vivo perfusion chamber platelet deposition. PD0348292 produced dose-dependent prothrombin time (0.9- to 2.9-fold) and aPTT (1.4- to 2.5-fold) prolongations. Bleeding times were significantly prolonged in each active drug group compared to vehicle, but were not significantly different between drug groups. PD0348292 significantly inhibited arterial platelet deposition (x106/cm2) at 4.3(549 ± 1,066), 0.9 (399 ± 162) and 0.4 mg/kg (531 ± 470) compared to vehicle (2,242 ± 1,443). Aspirin (992 ± 973), clopidogrel (537 ± 483), clopidogrel plus aspirin (228 ± 66) or PD0348292 plus aspirin (558 ± 317) also significantly inhibited platelet deposition, although these values were not significantly different than with any dose of PD348292. Perfusion chamber platelet deposition correlated significantly with in-vivo anti-thrombotic response. In conclusion, PD0348292 inhibited arterial thrombosis comparable to aspirin plus clopidogrel. Perfusion chamber methodology may be useful in predicting in-vivo antithrombotic efficacy.
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Chaiyasan, Wanachat, Sangly P. Srinivas, Pattravee Niamprem, and Waree Tiyaboonchai. "PENETRATION OF HYDROPHILIC SULFORHODAMINE B ACROSS THE PORCINE CORNEA EX-VIVO." International Journal of Applied Pharmaceutics 10, no. 6 (November 22, 2018): 94. http://dx.doi.org/10.22159/ijap.2018v10i6.28505.
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Objective: Sulforhodamine B (SRB) is a hydrophilic tracer whose fluorescence is unaffected by pH unlike that of carboxyfluorescein. Therefore, SRB may serve as a better tracer when there are significant changes in pH. Thus, in this study, the suitability of SRB to assess the barrier properties of the cellular layers of the cornea was examined using a custom-built confocal scanning micro-fluorometer (CSMF). Methods: The dye solution (0.1% SRB) was prepared in PBS-Ca2+and three experiments were performed ex vivo using freshly isolated porcine eyes. First, we investigated the penetration of SRB across the endothelium by injection of the dye into the anterior chamber. Next, we measured the penetration of SRB across the epithelium after exposing the ocular surface to the dye. Finally, we examined the penetration after exposure to the dye with detergent (Tween 20) and exposure to the dye concomitant with microneedle injuries. The dye concentration profiles across the cornea were measured using CSMF.Results: SRB penetrated the corneal endothelium readily into the stroma following injection into the anterior chamber in a time-dependent manner. Despite accumulation in the stroma, SRB did not partition into the epithelium. In agreement with these findings, the dye did not cross the epithelium after topical administration. Co-administration with Tween 20 and injury to the epithelium with microneedles, however, led to penetration of the dye into the stroma.Conclusions: SRB is a hydrophilic dye that can be used as an alternative fluorescent tracer to assess the barrier function of the cellular layers of the cornea.
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Maclean, Glenn, Stephanie Brister, and Michael Buchanan. "Selective and Sustained Inhibition of Surface-bound Thrombin Activity by Intimatan/Heparin Cofactor II and Its Relevance to Assessing Systemic Anticoagulation In Vivo, Ex Vivo and In Vitro." Thrombosis and Haemostasis 86, no. 09 (2001): 909–13. http://dx.doi.org/10.1055/s-0037-1616149.
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SummaryWe compare the relative activities of surface-bound and fluid-phase thrombin and their inhibition by heparin and Intimatan, a novel heparin cofactor II (HCII) agonist. In vitro, we compared the observed amidolytic activities of fluid-phase and surface-bound thrombin with the expected activities based upon 125I-specific activity. In vivo, we compared the inhibitory effects of heparin and Intimatan on thrombin activity bound to injured vessel walls. In vitro, the correlations between observed and expected activities of fluid-phase and surface-bound thrombin, were: r = 0.9974, p < 0.001; and r = 0.9678, p < 0.001; respectively. In vivo, injured vessel wall surface-bound thrombin activity persisted for > 24 h. This activity was not inhibited by heparin, but was inhibited by Intimatan, p < 0.001.We conclude that surface-bound thrombin is as active as fluid-phase thrombin and remains protected from inhibition by heparin, thereby contributing to vessel wall thrombogenicity following injury. In contrast, surface-bound thrombin is inhibited by Intimatan, thereby effectively decreasing vessel wall thrombogenicity following injury in vivo.
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Hlawaty, Hanna, Aurélie San Juan, Marie-Paule Jacob, Roger Vranckx, Didier Letourneur, and Laurent J. Feldman. "Inhibition of MMP-2 gene expression with small interfering RNA in rabbit vascular smooth muscle cells." American Journal of Physiology-Heart and Circulatory Physiology 293, no. 6 (December 2007): H3593—H3601. http://dx.doi.org/10.1152/ajpheart.00517.2007.
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Matrix metalloproteinase-2 (MMP-2) is constitutively expressed in vascular smooth muscle cells (VSMCs). Using small interfering RNA (siRNA), we evaluated the effect of MMP-2 inhibition in VSMCs in vitro and ex vivo. Rabbit VSMCs were transfected in vitro with 50 nmol/l MMP-2 siRNA or scramble siRNA. Flow cytometry and confocal microscopy showed cellular uptake of siRNA in ∼80% of VSMCs. MMP-2 mRNA levels evaluated by real-time RT-PCR, pro-MMP-2 activity from conditioned culture media evaluated by gelatin zymography, and VSMC migration were reduced by 44 ± 19%, 43 ± 14%, and 36 ± 14%, respectively, in MMP-2 siRNA-transfected compared with scramble siRNA-transfected VSMCs ( P < 0.005 for all). Ex vivo MMP-2 siRNA transfection was performed 2 wk after balloon injury of hypercholesterolemic rabbit carotid arteries. Fluorescence microscopy showed circumferential siRNA uptake in neointimal cells. Gelatin zymography of carotid artery culture medium demonstrated a significant decrease of pro-MMP-2 activity in MMP-2 siRNA-transfected compared with scramble siRNA-transfected arteries ( P < 0.01). Overall, our results demonstrate that in vitro MMP-2 siRNA transfection in VSMCs markedly inhibits MMP-2 gene expression and VSMC migration and that ex vivo delivery of MMP-2 siRNA in balloon-injured arteries reduces pro-MMP-2 activity in neointimal cells, suggesting that siRNA could be used to modify arterial biology in vivo.
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Philips, Matthew F., Gustav Mattiasson, Tadeusz Wieloch, Anders Björklund, Barbro B. Johansson, Gregor Tomasevic, Alberto Martínez-Serrano, et al. "Neuroprotective and behavioral efficacy of nerve growth factor—transfected hippocampal progenitor cell transplants after experimental traumatic brain injury." Journal of Neurosurgery 94, no. 5 (May 2001): 765–74. http://dx.doi.org/10.3171/jns.2001.94.5.0765.
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Object. Immortalized neural progenitor cells derived from embryonic rat hippocampus (HiB5), were transduced ex vivo with the gene for mouse nerve growth factor (NGF) to secrete NGF (NGF-HiB5) at 2 ng/hr/105 cells in culture. Methods. Fifty-nine male Wistar rats weighing 300 to 370 g each were anesthetized with 60 mg/kg sodium pentobarbital and subjected to lateral fluid-percussion brain injury of moderate severity (2.3–2.4 atm, 34 rats) or sham injury (25 rats). At 24 hours postinjury, 2 µl (150,000 cells/µl) of [3H]thymidine-labeled NGF-HiB5 cells were transplanted stereotactically into three individual sites in the cerebral cortex adjacent to the injury site (14 rats). Separate groups of brain-injured rats received nontransfected (naive [n])-HiB5 cells (12 animals) or cell suspension vehicle (eight animals). One week postinjury, animals underwent neurological evaluation for motor function and cognition (Morris water maze) and were killed for histological, autoradiographic, and immunocytochemical analysis. Viable HiB5 cell grafts were identified in all animals, together with reactive microglia and macrophages located throughout the periinjured parenchyma and grafts (OX-42 immunohistochemistry). Brain-injured animals transplanted with either NGF-HiB5 or n-HiB5 cells displayed significantly improved neuromotor function (p < 0.05) and spatial learning behavior (p < 0.005) compared with brain-injured animals receiving microinjections of vehicle alone. A significant reduction in hippocampal CA3 cell death was observed in brain-injured animals receiving transplants of NGF-HiB5 cells compared with those receiving n-HiB5 cells or vehicle (p < 0.025). Conclusions. This study demonstrates that immortalized neural stem cells that have been retrovirally transduced to produce NGF can markedly improve cognitive and neuromotor function and rescue hippocampal CA3 neurons when transplanted into the injured brain during the acute posttraumatic period.
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Blits, Bas, Gerard J. Boer, and Joost Verhaagen. "Pharmacological, Cell, and Gene Therapy Strategies to Promote Spinal Cord Regeneration." Cell Transplantation 11, no. 6 (September 2002): 593–613. http://dx.doi.org/10.3727/000000002783985521.
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In this review, recent studies using pharmacological treatment, cell transplantation, and gene therapy to promote regeneration of the injured spinal cord in animal models will be summarized. Pharmacological and cell transplantation treatments generally revealed some degree of effect on the regeneration of the injured ascending and descending tracts, but further improvements to achieve a more significant functional recovery are necessary. The use of gene therapy to promote repair of the injured nervous system is a relatively new concept. It is based on the development of methods for delivering therapeutic genes to neurons, glia cells, or nonneural cells. Direct in vivo gene transfer or gene transfer in combination with (neuro)transplantation (ex vivo gene transfer) appeared powerful strategies to promote neuronal survival and axonal regrowth following traumatic injury to the central nervous system. Recent advances in understanding the cellular and molecular mechanisms that govern neuronal survival and neurite outgrowth have enabled the design of experiments aimed at viral vector-mediated transfer of genes encoding neurotrophic factors, growth-associated proteins, cell adhesion molecules, and antiapoptotic genes. Central to the success of these approaches was the development of efficient, nontoxic vectors for gene delivery and the acquirement of the appropriate (genetically modified) cells for neurotransplantation. Direct gene transfer in the nervous system was first achieved with herpes viral and E1-deleted adenoviral vectors. Both vector systems are problematic in that these vectors elicit immunogenic and cytotoxic responses. Adeno-associated viral vectors and lentiviral vectors constitute improved gene delivery systems and are beginning to be applied in neuroregeneration research of the spinal cord. Ex vivo approaches were initially based on the implantation of genetically modified fibroblasts. More recently, transduced Schwann cells, genetically modified pieces of peripheral nerve, and olfactory ensheathing glia have been used as implants into the injured spinal cord.
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Meers, Caroline M., Walter De Wever, Eric Verbeken, Shana Wauters, Robin Vos, Bart M. Vanaudenaerde, Stéphanie I. De Vleeschauwer, Geert M. Verleden, Toni E. Lerut, and Dirk Van Raemdonck. "A Porcine Model to Study Ex Vivo Reconditioning of Injured Donor Lungs." Journal of Surgical Research 166, no. 2 (April 2011): e175-e185. http://dx.doi.org/10.1016/j.jss.2009.09.028.
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