scholarly journals Viral Respiratory Pathogens and Lung Injury

2021 ◽  
Vol 34 (3) ◽  
Author(s):  
Nicola Clementi ◽  
Sreya Ghosh ◽  
Maria De Santis ◽  
Matteo Castelli ◽  
Elena Criscuolo ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Cell Damage ◽  
Clinical Manifestations ◽  
Upper Airway ◽  
Patient Specific ◽  
Respiratory Pathogens ◽  
Human Respiratory Tract ◽  
Immune Mediated ◽  
Life Threatening ◽  
Viral Respiratory

SUMMARY Several viruses target the human respiratory tract, causing different clinical manifestations spanning from mild upper airway involvement to life-threatening acute respiratory distress syndrome (ARDS). As dramatically evident in the ongoing SARS-CoV-2 pandemic, the clinical picture is not always easily predictable due to the combined effect of direct viral and indirect patient-specific immune-mediated damage. In this review, we discuss the main RNA (orthomyxoviruses, paramyxoviruses, and coronaviruses) and DNA (adenoviruses, herpesviruses, and bocaviruses) viruses with respiratory tropism and their mechanisms of direct and indirect cell damage. We analyze the thin line existing between a protective immune response, capable of limiting viral replication, and an unbalanced, dysregulated immune activation often leading to the most severe complication. Our comprehension of the molecular mechanisms involved is increasing and this should pave the way for the development and clinical use of new tailored immune-based antiviral strategies.

scholarly journals Could metabolomics drive the fate of COVID-19 pandemic? A narrative review on lights and shadows

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Michele Mussap ◽  
Vassilios Fanos
Keyword(s):  
Molecular Mechanisms ◽  
Vascular Dysfunction ◽  
Asymptomatic Infection ◽  
Multiple Organ ◽  
Therapeutic Interventions ◽  
Patient Specific ◽  
Wide Range ◽  
Life Threatening ◽  
The Individual ◽  
Host Metabolism

Abstract Human Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection activates a complex interaction host/virus, leading to the reprogramming of the host metabolism aimed at the energy supply for viral replication. Alterations of the host metabolic homeostasis strongly influence the immune response to SARS-CoV-2, forming the basis of a wide range of outcomes, from the asymptomatic infection to the onset of COVID-19 and up to life-threatening acute respiratory distress syndrome, vascular dysfunction, multiple organ failure, and death. Deciphering the molecular mechanisms associated with the individual susceptibility to SARS-CoV-2 infection calls for a system biology approach; this strategy can address multiple goals, including which patients will respond effectively to the therapeutic treatment. The power of metabolomics lies in the ability to recognize endogenous and exogenous metabolites within a biological sample, measuring their concentration, and identifying perturbations of biochemical pathways associated with qualitative and quantitative metabolic changes. Over the last year, a limited number of metabolomics- and lipidomics-based clinical studies in COVID-19 patients have been published and are discussed in this review. Remarkable alterations in the lipid and amino acid metabolism depict the molecular phenotype of subjects infected by SARS-CoV-2; notably, structural and functional data on the lipids-virus interaction may open new perspectives on targeted therapeutic interventions. Several limitations affect most metabolomics-based studies, slowing the routine application of metabolomics. However, moving metabolomics from bench to bedside cannot imply the mere determination of a given metabolite panel; rather, slotting metabolomics into clinical practice requires the conversion of metabolic patient-specific data into actionable clinical applications.

scholarly journals Intracranial Haemorrhage as a Fatal Complication of Evans Syndrome: A Case Report

2019 ◽  
Vol 2 (2) ◽  
pp. 66-69
Author(s):  
Olita Shilpakar ◽  
Bibek Rajbhandari ◽  
Bipin Karki ◽  
Umesh Bogati
Keyword(s):  
Intracranial Haemorrhage ◽  
Early Recognition ◽  
Clinical Manifestations ◽  
Health Care Facilities ◽  
Evans Syndrome ◽  
Fatal Complication ◽  
Hematologic Disorder ◽  
Immune Mediated ◽  
Life Threatening ◽  
Immune Neutropenia

Evans syndrome is a rare hematologic disorder characterized by the presence of simultaneous or sequential direct Coombs-positive autoimmune hemolytic anemia (AIHA), immune-mediated thrombocytopenia and/or immune neutropenia without any known underlying etiology. Spontaneous intracranial hemorrhage is a rare and life-threatening complication in patients with Evans syndrome and very few cases have been reported to date. We report a case of a thirty-two- year-old female with intracranial haemorrhage with underlying Evans syndrome who presented with the clinical manifestations of headache, vomiting and altered sensorium and succumbed to the fatal complication despite resuscitative measures. This also emphasizes the importance of early recognition of symptoms and immediate presentation to health care facilities for aggressive management of the patient.

scholarly journals Viral Infections of the Upper Airway in the Setting of COVID-19: A Primer for Rhinologists

2020 ◽  
Vol 35 (1) ◽  
pp. 122-131
Author(s):  
Erick Yuen ◽  
David A. Gudis ◽  
Nicholas R. Rowan ◽  
Shaun A. Nguyen ◽  
Rodney J. Schlosser
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Viral Infections ◽  
Current Knowledge ◽  
Middle Eastern ◽  
Upper Airway ◽  
Respiratory Viruses ◽  
Respiratory Pathogens ◽  
Infectious Agents ◽  
Tract Infections ◽  
Viral Respiratory

Background Viral respiratory tract infections are associated with a significant burden of disease and represent one of the leading causes of mortality worldwide. The current Coronavirus Disease 2019 (COVID-19) pandemic highlights the devastating toll that respiratory viruses have on humanity and the desperate need to understand the biological characteristics that define them in order to develop efficacious treatments and vaccines. To date, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has infected nearly 600 times more people and resulted in 200 times more deaths relative to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV) combined. Objective Through this review, we aim to summarize the key characteristics of respiratory viruses that hold global significance, with a focus on SARS-CoV-2. Our goal is to disseminate our current knowledge of these infectious agents to otolaryngologists, in particular rhinologists, practicing in the COVID-19 era. Methods The general and clinical characteristics of selected respiratory viruses along with available viral treatments and vaccines are reviewed. Results There has been significant progress in our understanding of the epidemiology and pathogenesis of various respiratory viruses. However, despite the advancement in knowledge, efficacious vaccines and antiviral treatments remain elusive for most respiratory viruses. The dire need for these scientific discoveries is highlighted by the recent COVID-19 pandemic, which has prompted investigators worldwide to conduct clinical trials at an accelerated timeline in an effort to reduce the morbidity and mortality associated with SARS-CoV-2 infection. Rhinologists will continue to remain on the front-lines of pandemics associated with respiratory viruses. Conclusion In light of these unprecedented times, the need to understand the nuances of these viral respiratory pathogens, especially SARS-CoV-2, cannot be overemphasized. This knowledge base is of particular importance to otolaryngologists, whose expertise in the upper airway coincides with the anatomic tropism of these infectious agents.

scholarly journals Is Tolerance Broken in Autoimmunity?

2017 ◽  
Vol 10 ◽  
pp. 117955571771271
Author(s):  
Dama Laxminarayana
Keyword(s):  
Autoimmune Diseases ◽  
Molecular Mechanisms ◽  
Clinical Manifestations ◽  
Symptomatic Treatment ◽  
Cellular Events ◽  
Life Threatening ◽  
Benign Disorders ◽  
Autoimmune Pathogenesis ◽  
System Organ

Autoimmune diseases are classified into about 80 different types based on their specificity related to system, organ and/or tissue. About 5% of the western population is affected by this anomaly, but its worldwide incidence is unknown. Autoimmune diseases are heterogeneous in nature and clinical manifestations range from benign disorders to life-threatening conditions. Autoimmunity strikes at any stage of life, but age and/or gender also play role in onset of some of these anomalies. The autoimmune pathogenesis is initiated by the origination of autoantigens, which leads to the development of autoantibodies followed by auto-immunogenicity and the ultimate onset of autoimmunity. There is a lack of suitable therapies to treat autoimmune diseases, because mechanisms involved in the onset of these anomalies were poorly understood. Present therapies are limited to symptomatic treatment and come with severe side effects. Here, I described the molecular mechanisms and cellular events involved in the initiation of autoimmunity and proposed better strategies to modulate such molecular and cellular anomalies, which will help in preventing and/or controlling autoimmune pathogenesis and ultimately aid in enhancing the quality of life.

scholarly journals Transfusion-Related Acute Lung Injured (TRALI): Current Concepts

2015 ◽  
Vol 9 (1) ◽  
pp. 92-96 ◽  
Author(s):  
P Álvarez ◽  
R Carrasco ◽  
C Romero-Dapueto ◽  
R.L Castillo
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Molecular Mechanisms ◽  
Clinical Symptoms ◽  
Clinical Problem ◽  
Clinical Findings ◽  
Cellular Targets ◽  
Immune Mediated ◽  
Life Threatening

Transfusion-related acute lung injury (TRALI) is a life-threatening intervention that develops within 6 hours of transfusion of one or more units of blood, and is an important cause of morbidity and mortality resulting from transfusion. It is necessary to dismiss other causes of acute lung injury (ALI), like sepsis, acute cardiogenic edema, acute respiratory distress syndrome (ARDS) or bacterial infection. There are two mechanisms that lead to the development of this syndrome: immune-mediated and no immune- mediated TRALI. A common theme among the experimental TRALI models is the central importance of neutrophils in mediating the early immune response, and lung vascular injury. Central clinical symptoms are dyspnea, tachypnea, tachycardia, cyanosis and pulmonary secretions, altogether with other hemodynamic alterations, such as hypotension and fever. Complementary to these clinical findings, long-term validated animal models for TRALI should allow the determination of the cellular targets for TRALI-inducing alloantibodies as well as delineation of the underlying pathogenic molecular mechanisms, and key molecular mediators of the pathology. Diagnostic criteria have been established and preventive measures have been implemented. These actions have contributed to the reduction in the overallnumber of fatalities. However, TRALI still remains a clinical problem. Any complication suspected of TRALI should immediately be reported.

scholarly journals Animal Model of Severe Fever With Thrombocytopenia Syndrome Virus Infection

2022 ◽  
Vol 12 ◽  
Author(s):  
Jiawen Sun ◽  
Yuan-Qin Min ◽  
Yunjie Li ◽  
Xiulian Sun ◽  
Fei Deng ◽  
...  
Keyword(s):  
Animal Models ◽  
Molecular Mechanisms ◽  
Clinical Manifestations ◽  
Medical Problem ◽  
Future Research ◽  
Antiviral Therapies ◽  
Treatment And Prevention ◽  
Animal Infection ◽  
Life Threatening ◽  
Severe Fever

Severe fever with thrombocytopenia syndrome (SFTS), an emerging life-threatening infectious disease caused by SFTS bunyavirus (SFTSV; genus Bandavirus, family Phenuiviridae, order Bunyavirales), has been a significant medical problem. Currently, there are no licensed vaccines or specific therapeutic agents available and the viral pathogenesis remains largely unclear. Developing appropriate animal models capable of recapitulating SFTSV infection in humans is crucial for both the study of the viral pathogenic processes and the development of treatment and prevention strategies. Here, we review the current progress in animal models for SFTSV infection by summarizing susceptibility of various potential animal models to SFTSV challenge and the clinical manifestations and histopathological changes in these models. Together with exemplification of studies on SFTSV molecular mechanisms, vaccine candidates, and antiviral drugs, in which animal infection models are utilized, the strengths and limitations of the existing SFTSV animal models and some important directions for future research are also discussed. Further exploration and optimization of SFTSV animal models and the corresponding experimental methods will be undoubtedly valuable for elucidating the viral infection and pathogenesis and evaluating vaccines and antiviral therapies.

scholarly journals Genetic Variants in the FGB and FGG Genes Mapping in the Beta and Gamma Nodules of the Fibrinogen Molecule in Congenital Quantitative Fibrinogen Disorders Associated with a Thrombotic Phenotype

2020 ◽  
Vol 21 (13) ◽  
pp. 4616
Author(s):  
Tomas Simurda ◽  
Monika Brunclikova ◽  
Rosanna Asselta ◽  
Sonia Caccia ◽  
Jana Zolkova ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Clinical Manifestations ◽  
Cell Interaction ◽  
Fibrin Clot ◽  
Congenital Defects ◽  
Blood Clots ◽  
Life Threatening ◽  
Congenital Afibrinogenemia ◽  
Insoluble Polymer ◽  
Fibrinogen Molecule

Fibrinogen is a hexameric plasmatic glycoprotein composed of pairs of three chains (Aα, Bβ, and γ), which play an essential role in hemostasis. Conversion of fibrinogen to insoluble polymer fibrin gives structural stability, strength, and adhesive surfaces for growing blood clots. Equally important, the exposure of its non-substrate thrombin-binding sites after fibrin clot formation promotes antithrombotic properties. Fibrinogen and fibrin have a major role in multiple biological processes in addition to hemostasis and thrombosis, i.e., fibrinolysis (during which the fibrin clot is broken down), matrix physiology (by interacting with factor XIII, plasminogen, vitronectin, and fibronectin), wound healing, inflammation, infection, cell interaction, angiogenesis, tumour growth, and metastasis. Congenital fibrinogen deficiencies are rare bleeding disorders, characterized by extensive genetic heterogeneity in all the three genes: FGA, FGB, and FGG (enconding the Aα, Bβ, and γ chain, respectively). Depending on the type and site of mutations, congenital defects of fibrinogen can result in variable clinical manifestations, which range from asymptomatic conditions to the life-threatening bleeds or even thromboembolic events. In this manuscript, we will briefly review the main pathogenic mechanisms and risk factors leading to thrombosis, and we will specifically focus on molecular mechanisms associated with mutations in the C-terminal end of the beta and gamma chains, which are often responsible for cases of congenital afibrinogenemia and hypofibrinogenemia associated with thrombotic manifestations.

A dangerous cause of airway obstruction: deep neck infection

2020 ◽  
Keyword(s):  
Airway Obstruction ◽  
Upper Airway ◽  
Deep Neck Infection ◽  
Jugular Vein Thrombosis ◽  
Neck Infection ◽  
Vein Thrombosis ◽  
Lethal Complications ◽  
Life Threatening ◽  
Fascial Spaces ◽  
Emergency Doctors

Deep neck infection (DNI) is an infection in the fascial spaces of the neck. Complications of DNI, including mediastinitis, internal jugular vein thrombosis, and upper airway obstruction, are severe and potentially life threatening. Therefore, early identification and accurate management of DNI are essential. We review the anatomy of the deep spaces of the neck to determine the route of DNI spread so that emergency doctors, physicians, and otorhinolaryngologists can quickly recognize the development of lethal complications of DNI, such as asphyxia from airway obstruction.

scholarly journals Dual threat of comorbidity of celiac disease and systemic lupus erythematosus

2021 ◽  
Vol 49 (5) ◽  
pp. 030006052110122
Author(s):  
Yimin Ma ◽  
Duanming Zhuang ◽  
Zhenguo Qiao
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Celiac Disease ◽  
Lupus Erythematosus ◽  
Clinical Manifestations ◽  
Failure To Thrive ◽  
Severe Malnutrition ◽  
Systemic Lupus ◽  
Electrolyte Disorders ◽  
Diagnostic Challenge ◽  
Immune Mediated

Celiac disease (CD) is a chronic immune-mediated intestinal disease that is characterized by production of autoantibodies directed against the small intestine. The main clinical manifestations of CD are typically defined as those related to indigestion and malabsorption. These manifestations include unexplained diarrhea or constipation, abdominal pain, bloating, weight loss, anemia, failure-to-thrive in children, and decreased bone density. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by heterogeneous clinical manifestations, which may also involve the gastrointestinal tract. Comorbidity of CD and SLE is rare, and the overlapping symptoms and nonspecific clinical presentation may pose a diagnostic challenge to clinicians. We report here a case of SLE with CD, which mainly manifested as recurrent diarrhea, uncorrectable electrolyte disorders, and severe malnutrition. Through review, we hope to further improve our understanding and diagnostic level of this combination of diseases.

scholarly journals Impairing flow-mediated endothelial remodeling reduces extravasation of tumor cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gautier Follain ◽  
Naël Osmani ◽  
Valentin Gensbittel ◽  
Nandini Asokan ◽  
Annabel Larnicol ◽  
...  
Keyword(s):  
Blood Flow ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
Metastatic Progression ◽  
Metastatic Dissemination ◽  
Secondary Tumors ◽  
Flow Profiles ◽  
Endothelial Response ◽  
Life Threatening

AbstractTumor progression and metastatic dissemination are driven by cell-intrinsic and biomechanical cues that favor the growth of life-threatening secondary tumors. We recently identified pro-metastatic vascular regions with blood flow profiles that are permissive for the arrest of circulating tumor cells. We have further established that such flow profiles also control endothelial remodeling, which favors extravasation of arrested CTCs. Yet, how shear forces control endothelial remodeling is unknown. In the present work, we aimed at dissecting the cellular and molecular mechanisms driving blood flow-dependent endothelial remodeling. Transcriptomic analysis of endothelial cells revealed that blood flow enhanced VEGFR signaling, among others. Using a combination of in vitro microfluidics and intravital imaging in zebrafish embryos, we now demonstrate that the early flow-driven endothelial response can be prevented upon specific inhibition of VEGFR tyrosine kinase and subsequent signaling. Inhibitory targeting of VEGFRs reduced endothelial remodeling and subsequent metastatic extravasation. These results confirm the importance of VEGFR-dependent endothelial remodeling as a driving force of CTC extravasation and metastatic dissemination. Furthermore, the present work suggests that therapies targeting endothelial remodeling might be a relevant clinical strategy in order to impede metastatic progression.

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