scholarly journals Coronavirus disease 2019 may be driven by an overactivation of the renin-angiotensin-aldosterone system 

2020 ◽  
Author(s):  
Susanne Rysz ◽  
Jonathan Al-Saadi ◽  
Maria Farm ◽  
Francesca Campoccia Jalde ◽  
Margareta Klein ◽  
...  
Keyword(s):  
Distress Syndrome ◽  
Clinical Laboratory ◽  
Laboratory Data ◽  
Large Animal Model ◽  
Large Animal ◽  
Rt Pcr ◽  
Subsequent Increase ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
New Treatments

Abstract SARS-CoV-2 enters the cell through the ACE2 receptor, which is considered one of the main inhibitors in the Renin-Angiotensin-Aldosterone System (RAAS).1​ ,2 The virus has been shown to downregulate the ACE2 receptor, leading to a subsequent increase in the vasopressoragentangiotensinII.3​ Evidently,criticalcoronavirusdisease2019(COVID-19)is thought to be due to a dysregulated immune response, causing a cytokine-release syndrome eventually leading to acute respiratory distress syndrome (ARDS).4​ ,5 ​However, several reports on clinical laboratory features and case-descriptions of critically ill patients with COVID-19 show discrepancies compared to typical ARDS. Here, we show that infusing swines with angiotensin II induces a pathophysiological syndrome closely resembling that of patients with RT-PCR-positive COVID-19. By using multimodal clinical imaging of patients, comparing laboratory data and translational histological features, we show that it is highly likely that an increase in RAAS is one, if not the main, pathogenic feature in critical COVID-19. Furthermore, it is plausible that this large animal model can be used to screen for potential new treatments for patients with severe COVID-19 and that MRI lung perfusion can be used to evaluate the outcome of potential treatments targeting the pathophysiological syndrome.

scholarly journals Coronavirus disease 2019 may be driven by an overactivation of the renin-angiotensin-aldosterone system 

2020 ◽  
Author(s):  
Susanne Rysz ◽  
Jonathan Al-Saadi ◽  
Maria Farm ◽  
Francesca Campoccia Jalde ◽  
Margareta Klein ◽  
...  
Keyword(s):  
Distress Syndrome ◽  
Clinical Laboratory ◽  
Laboratory Data ◽  
Large Animal Model ◽  
Large Animal ◽  
Rt Pcr ◽  
Subsequent Increase ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
New Treatments

Abstract SARS-CoV-2 enters the cell through the ACE2 receptor, which is considered one of the main inhibitors in the Renin-Angiotensin-Aldosterone System (RAAS).1​ ,2 The virus has been shown to downregulate the ACE2 receptor, leading to a subsequent increase in the vasopressoragentangiotensinII.3​ Evidently,criticalcoronavirusdisease2019(COVID-19)is thought to be due to a dysregulated immune response, causing a cytokine-release syndrome eventually leading to acute respiratory distress syndrome (ARDS).4​ ,5 ​However, several reports on clinical laboratory features and case-descriptions of critically ill patients with COVID-19 show discrepancies compared to typical ARDS. Here, we show that infusing swines with angiotensin II induces a pathophysiological syndrome closely resembling that of patients with RT-PCR-positive COVID-19. By using multimodal clinical imaging of patients, comparing laboratory data and translational histological features, we show that it is highly likely that an increase in RAAS is one, if not the main, pathogenic feature in critical COVID-19. Furthermore, it is plausible that this large animal model can be used to screen for potential new treatments for patients with severe COVID-19 and that MRI lung perfusion can be used to evaluate the outcome of potential treatments targeting the pathophysiological syndrome.

scholarly journals A novel large animal model of smoke inhalation-induced acute respiratory distress syndrome

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Premila D. Leiphrakpam ◽  
Hannah R. Weber ◽  
Andrea McCain ◽  
Roser Romaguera Matas ◽  
Ernesto Martinez Duarte ◽  
...  
Keyword(s):  
Animal Model ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Distress Syndrome ◽  
Inhalation Injury ◽  
Smoke Inhalation ◽  
Large Animal Model ◽  
Large Animal ◽  
X Ray ◽  
Chest X Ray

Abstract Background Acute respiratory distress syndrome (ARDS) is multifactorial and can result from sepsis, trauma, or pneumonia, amongst other primary pathologies. It is one of the major causes of death in critically ill patients with a reported mortality rate up to 45%. The present study focuses on the development of a large animal model of smoke inhalation-induced ARDS in an effort to provide the scientific community with a reliable, reproducible large animal model of isolated toxic inhalation injury-induced ARDS. Methods Animals (n = 21) were exposed to smoke under general anesthesia for 1 to 2 h (median smoke exposure = 0.5 to 1 L of oak wood smoke) after the ultrasound-guided placement of carotid, pulmonary, and femoral artery catheters. Peripheral oxygen saturation (SpO2), vital signs, and ventilator parameters were monitored throughout the procedure. Chest x-ray, carotid, femoral and pulmonary artery blood samples were collected before, during, and after smoke exposure. Animals were euthanized and lung tissue collected for analysis 48 h after smoke inhalation. Results Animals developed ARDS 48 h after smoke inhalation as reflected by a decrease in SpO2 by approximately 31%, PaO2/FiO2 ratio by approximately 208 (50%), and development of bilateral, diffuse infiltrates on chest x-ray. Study animals also demonstrated a significant increase in IL-6 level, lung tissue injury score and wet/dry ratio, as well as changes in other arterial blood gas (ABG) parameters. Conclusions This study reports, for the first time, a novel large animal model of isolated smoke inhalation-induced ARDS without confounding variables such as cutaneous burn injury. Use of this unique model may be of benefit in studying the pathophysiology of inhalation injury or for development of novel therapeutics.

scholarly journals Diagnosis Challenges, Management, and Outcome of Infants Born to Mothers With COVID 19

2020 ◽  
Author(s):  
Gabriela Zaharie ◽  
Monica Hasmasanu ◽  
Daniel Muresan ◽  
Tunde Kovacs ◽  
Melinda Matyas
Keyword(s):  
Hospital Stay ◽  
Pregnant Women ◽  
Distress Syndrome ◽  
Laboratory Data ◽  
Perinatal Transmission ◽  
Risk Category ◽  
Rt Pcr ◽  
Medical Assistance ◽  
High Risk Category ◽  
Pcr Test

Abstract Background: Severe acute respiratory distress syndrome with Coronavirus 2 (SARS-CoV-2) infection affected the pregnant women during the pandemics. Immunological particularity of this population and the increased need for medical assistance put this population in a high-risk category for SARS-Cov-2 infection.Because of high contamination risk and limited studies about vertical transmission, the labor and delivery of positive women require special conditions. Cesarean section is probably the best option for delivery of infants to reduce the risk of infection during birth.Aim: Our study aims to present the management and outcome of infants born to mothers confirmed with coronavirus disease 2019 (COVID19) before delivery.Material and methods: This is longitudinal, retrospective study, analyzing demographics, laboratory data and management of neonates born of mothers with diagnosis of SARS-Cov -2 infection.Results: 5 neonates were born of SARS-Cov-2 positive mothers , all by C- section and had negative real time –PCR ( RT-PCR) test. None of them was breastfed during hospital stay. The negative RT-PCR test allowed us to reduce the hospital stay of infants and care them in non –isolated area.Conclusion: In our study, vertical or perinatal transmission of the infection was not present. The testing of the pregnant women, their isolation and delivery in safe conditions for the medical staff were possible, using adequate protection equipment to limit their infection and the risk for the newborns.

scholarly journals Collagenase-Induced Patellar Tendinopathy with Neovascularization: First Results towards a Piglet Model of Musculoskeletal Embolization

Biomedicines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 2
Author(s):  
Julien Ghelfi ◽  
Marylène Bacle ◽  
Olivier Stephanov ◽  
Hélène de Forges ◽  
Ian Soulairol ◽  
...  
Keyword(s):  
Animal Model ◽  
Histological Analysis ◽  
Patellar Tendinopathy ◽  
Large Animal Model ◽  
Large Animal ◽  
Test Results ◽  
Collagenase Injection ◽  
First Results ◽  
Endovascular Approach ◽  
New Treatments

Background: Therapeutic strategies targeting neovessels responsible for musculoskeletal chronic pain have emerged, including neovessels embolization. Our study aimed to develop a large animal model of patellar tendinopathy with neovascularization. Methods: Nine 3-month-old male piglets (18 patellar tendons) received percutaneous injections of increasing doses of collagenase (0 to 50 mg) at day 0 (D0). Tendinopathy was evaluated by ultrasound (D7 and D14). Neovascularization was evaluated visually and on angiographies. Bonar score was used for histological analysis (D14). Correlations were evaluated using Spearman’s rank (Rs) test. Results: Research protocol was well tolerated. All tendons were enlarged with a median increase of 31.58% [25–40.28] at D7 (p = 0.244) at D7 and 57.52% [48.41–91.45] at D14 (p = 0.065). Tendons with collagenase injection had more hypoechoic changes, with one tendon rupture (p = 0.012). Neovascularization was reported above 5 mg collagenase (p < 0.01) at D7 and D14 with dose-related neovessels induction (Rs = 0.8, p < 0.001). The Bonar score increased above 5 mg collagenase, correlated with the dose (Rs = 0.666, p = 0.003). Conclusions: The study shows the feasibility, safety and reproducibility of this new large animal model of patellar tendinopathy with neovascularization after collagenase injection. It will allow studying new treatments on direct embolization of neovessels by endovascular approach.

Method used to establish a large animal model of drug-induced acute kidney injury

2021 ◽  
pp. 153537022098175
Author(s):  
Si-Yang Wang ◽  
Chao-Yang Zhang ◽  
Guang-Yan Cai ◽  
Xiang-Mei Chen
Keyword(s):  
Acute Kidney Injury ◽  
Animal Model ◽  
Health Hazard ◽  
Kidney Injury ◽  
Basic Research ◽  
Large Animal Model ◽  
Large Animal ◽  
Drug Induced ◽  
Large Animal Models ◽  
New Treatments

Acute kidney injury is a serious health hazard disease due to its complex etiology and lack of effective treatments, resulting in high medical costs and high mortality. At present, a large number of basic research studies on acute kidney injury have been carried out. However, acute kidney injury models established in rodents sometimes do not simulate the course of human disease well. Research in large animal models of acute kidney injury is relatively rare, and methods to build a mature model of acute kidney injury have failed. Because its kidney anatomy and morphology are very similar to those in humans, the mini pig is an ideal animal in which to model kidney disease. Nephrotoxic drug-induced acute kidney injury has a high incidence. In this study, we established models of acute kidney injury induced by two drugs (gentamicin and cisplatin). Finally, the model of cisplatin-induced acute kidney injury was developed successfully, but we found the model of gentamycin-induced acute kidney injury was not reproducible. Compared to other models, these models better represent acute kidney injury caused by antibiotics and chemotherapeutic drugs and provide a basis for the study of new treatments for acute kidney injury in a large animal model.

scholarly journals A Novel Large Animal Model of Smoke Inhalation-Induced Acute Respiratory Distress Syndrome

2021 ◽  
Author(s):  
Premila Leiphrakpam ◽  
Hannah Weber ◽  
Andrea McCain ◽  
Roser Romaguera Matas ◽  
Ernesto Martinez Duarte ◽  
...  
Keyword(s):  
Animal Model ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Distress Syndrome ◽  
Inhalation Injury ◽  
Smoke Inhalation ◽  
Large Animal Model ◽  
Large Animal ◽  
X Ray ◽  
Chest X Ray

Abstract Background Acute respiratory distress syndrome (ARDS) is multifactorial and can result from sepsis, trauma, or pneumonia, amongst other primary pathologies. It is one of the major causes of death in critically ill patients with a reported mortality rate up to 45%. The present study focuses on the development of a large animal model of smoke inhalation-induced ARDS in an effort to provide the scientific community with a reliable, reproducible large animal model of isolated toxic inhalation injury-induced ARDS. Methods Animals (n = 21) were exposed to smoke under general anesthesia for 1 to 2 hours (median smoke exposure = 0.5 to 1 liter of oak wood smoke) after the ultrasound-guided placement of carotid, pulmonary, and femoral artery catheters. Peripheral oxygen saturation (SpO2), vital signs, and ventilator parameters were monitored throughout the procedure. Chest x-ray, carotid, femoral and pulmonary artery blood samples were collected before, during, and after smoke exposure. Animals were euthanized and lung tissue collected for analysis 48 hours after smoke inhalation. Results Animals developed ARDS 48 hours after smoke inhalation as reflected by a decrease in SpO2 by approximately 31%, PaO2/FiO2 ratio by approximately 208, and development of bilateral, diffuse infiltrates on chest x-ray. Study animals also demonstrated a significant increase in IL-6 level, lung tissue injury score and wet/dry ratio, as well as changes in other arterial blood gas (ABG) parameters. Conclusions This study reports, for the first time, a novel large animal model of isolated smoke inhalation-induced ARDS without confounding variables such as cutaneous burn injury. Use of this unique model may be of benefit in studying the pathophysiology of inhalation injury or for development of novel therapeutics.

scholarly journals Cell therapy for ARDS: efficacy of endobronchial versus intravenous administration and biodistribution of MAPCs in a large animal model

2019 ◽  
Vol 6 (1) ◽  
pp. e000308 ◽  
Author(s):  
Nayra Cardenes ◽  
Paola Aranda-Valderrama ◽  
Jonathan P Carney ◽  
Jacobo Sellares Torres ◽  
Diana Alvarez ◽  
...  
Keyword(s):  
Stem Cells ◽  
Distress Syndrome ◽  
Large Animal Model ◽  
Intravenous Route ◽  
Large Animal ◽  
Sheep Model ◽  
Mechanically Ventilated ◽  
Multipotent Adult Progenitor Cells ◽  
Routes Of Administration ◽  
Pet Ct

IntroductionBone marrow-derived multipotent adult progenitor cells (MAPCs) are adult allogeneic adherent stem cells currently investigated clinically for use in acute respiratory distress syndrome (ARDS). To date, there is no agreement on which is the best method for stem cells delivery in ARDS. Here, we compared the efficacy of two different methods of administration and biodistribution of MAPC for the treatment of ARDS in a sheep model.MethodsMAPC were labelled with [18F] fluoro-29-deoxy-D-glucose and delivered by endobronchial (EB) or intravenous route 1 hour after lipopolysaccharide infusion in sheep mechanically ventilated. PET/CT images were acquired to determine the biodistribution and retention of the cells at 1 and 5 hours of administration.ResultsThe distribution and retention of the MAPC was dependent on the method of cell administration. By EB route, PET images showed that MAPC remained at the site of administration and no changes were observed after 5 hours, whereas with intravenous route, the cells had broad biodistribution to different organs, being the lung the main organ of retention at 1 and 5 hours. MAPC demonstrated an equal effect on arterial oxygenation recovery by either route of administration.ConclusionThe EB or intravenous routes of administration of MAPC are both effective for the treatment of ARDS in an acute sheep model, and the effect of MAPC therapy is not dependent of parenchymal integration or systemic biodistribution.

scholarly journals Characteristics and neural-like differentiation of mesenchymal stem cells derived from foetal porcine bone marrow

2013 ◽  
Vol 33 (2) ◽  
Author(s):  
Ying Liu ◽  
Limei Liu ◽  
Xin Ma ◽  
Yupeng Yin ◽  
Bo Tang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Large Animal Model ◽  
Large Animal ◽  
Mrna Levels ◽  
Rt Pcr ◽  
Reverse Transcription Pcr ◽  
Stem Cell Source ◽  
Transcription Factor 4

MSCs (mesenchymal stem cells) are a stem cell source that can be easily obtained from bone marrow. Despite the increasing importance of the pig as a large animal model, little is known about foetal pMSCs (porcine MSCs). In this study, we observed the gene expression of pluripotent markers in foetal pMSCs and the capacity of pMSCs to differentiate into adipocytes, osteocytes and neural-like cells using quantitative RT–PCR (reverse transcription–PCR), normal histological staining and immunohistochemistry. Foetal pMSCs have either a spindle or a flattened shape, and flow cytometry revealed the expression of the MSC-related proteins CD44 and CD105 (endoglin) but not CD34 and CD45. pMSCs express pluripotent markers such as Oct4 (octamer-binding transcription factor 4) and Nanog at the protein and mRNA levels. qRT-PCR (quantitative real-time PCR) analyses revealed that pMSCs expressed nestin [for NSCs (neural stem cells)]. Immunocytochemical and RT–PCR data showed that 29% and 23% of pMSCs expressed MAP2 (microtubule-associated protein 2) for neurons and β-tubulin III (Tuj1) for immature neurons, respectively, after induction of neural differentiation. These findings demonstrate the plasticity of pMSCs and their potential for use in cellular replacement therapy for neural diseases.

scholarly journals Isolation and Characterization of Multipotent Canine Urine-Derived Stem Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Yan Xu ◽  
Tao Zhang ◽  
Yang Chen ◽  
Qiang Shi ◽  
Muzhi Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Canine Model ◽  
Large Animal Model ◽  
Large Animal ◽  
Isolated Cells ◽  
Musculoskeletal Tissue ◽  
Isolation And Characterization ◽  
Successful Isolation ◽  
New Treatments

Current cell-based therapies on musculoskeletal tissue regeneration were mostly determined in rodent models. However, a direct translation of those promising cell-based therapies to humans exists a significant hurdle. For solving this problem, canine has been developed as a new large animal model to bridge the gap from rodents to humans. In this study, we reported the isolation and characterization of urine-derived stem cells (USCs) from mature healthy beagle dogs. The isolated cells showed fibroblast-like morphology and had good clonogenicity and proliferation. Meanwhile, these cells positively expressed multiple markers of MSCs (CD29, CD44, CD90, and CD73), but negatively expressed for hematopoietic antigens (CD11b, CD34, and CD45). Additionally, after induction culturing, the isolated cells can be differentiated into osteogenic, adipogenic, chondrogenic, and tenogenic lineages. The successful isolation and verification of USCs from canine were useful for studying cell-based therapies and developing new treatments for musculoskeletal injuries using the preclinical canine model.

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