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1.
Int J Environ Res Public Health ; 18(10)2021 05 18.
Article in English | MEDLINE | ID: covidwho-1234733

ABSTRACT

During the coronavirus disease 2019 (COVID-19) pandemic, scientific authorities strongly suggested the use of face masks (FMs). FM materials (FMMs) have to satisfy the medical device biocompatibility requirements as indicated in the technical standard EN ISO 10993-1:2018. The biologic evaluation must be confirmed by in vivo tests to verify cytotoxicity, sensitisation, and skin irritation. Some of these tests require an extensive period of time for their execution, which is incompatible with an emergency situation. In this study, we propose to verify the safety of FMMs combining the assessment of 3-[4,5-dimethylthiazolyl-2]-2,5-diphenyltetrazolium bromide (MTT) with quantification of nitric oxide (NO) and interleukin-6 (IL-6), as predictive markers of skin sensitisation or irritation based on human primary fibroblasts. Two hundred and forty-two FMMs were collected and classified according to spectrometer IR in polypropylene, paper, cotton, polyester, polyethylene terephthalate, 3-dimensional printing, and viscose. Of all FMMs tested, 50.8% passed all the assays, 48% failed at least one, and only 1.2% failed all. By a low cost, rapid and highly sensitive multi assays strategy tested on human skin fibroblasts against a large variety of FMMs, we propose a strategy to promptly evaluate biocompatibility in wearable materials.


Subject(s)
COVID-19 , Pandemics , Humans , Masks , SARS-CoV-2 , Textiles
2.
Biophysics (Oxf) ; 66(1): 155-163, 2021.
Article in English | MEDLINE | ID: covidwho-1206008

ABSTRACT

It is shown that the inhalation of gaseous nitric oxide (gNO) or sprayed aqueous solutions of binuclear dinitrosyl iron complexes with glutathione or N-acetyl-L-cysteine by animals or humans provokes no perceptible hypotensive effects. Potentially, these procedures may be useful in COVID-19 treatment. The NO level in complexes with hemoglobin in blood decreases as the gNO concentration in the gas flow produced by the Plazon system increases from 100 to 2100 ppm, so that at 2000 ppm more than one-half of the gas can be incorporated into dinitrosyl complexes formed in tissues of the lungs and respiratory tract. Thus, the effect of gNO inhalation may be similar to that observed after administration of solutions of dinitrosyl iron complexes, namely, to the presence of dinitrosyl iron complexes with thiol-containing ligands in lung and airway tissues. With regard to the hypothesis posited earlier that these complexes can suppress coronavirus replication as donors of nitrosonium cations (Biophysics 65, 818, 2020), it is not inconceivable that administration of gNO or chemically synthesized dinitrosyl iron complexes with thiol-containing ligands may help treat COVID-19. In tests on the authors of this paper as volunteers, the tolerance concentration of gNO inhaled within 15 min was approximately 2000 ppm. In tests on rats that inhaled sprayed aqueous solutions of dinitrosyl iron complexes, their tolerance dose was approximately 0.4 mmol/kg body weight.

3.
Brain Behav Immun Health ; 14: 100255, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1163390

ABSTRACT

Nitric oxide (NO) is a ubiquitous signaling molecule that is critical for supporting a plethora of processes in biological organisms. Among these, its role in the innate immune system as a first line of defense against pathogens has received less attention. In asthma, levels of exhaled NO have been utilized as a window into airway inflammation caused by allergic processes. However, respiratory infections count among the most important triggers of disease exacerbations. Among the multitude of factors that affect NO levels are psychological processes. In particular, longer lasting states of psychological stress and depression have been shown to attenuate NO production. The novel SARS-CoV-2 virus, which has caused a pandemic, and with that, sustained levels of psychological stress globally, also adversely affects NO signaling. We review evidence on the role of NO in respiratory infection, including COVID-19, and stress, and argue that boosting NO bioavailability may be beneficial in protection from infections, thus benefitting individuals who suffer from stress in asthma or SARS-CoV-2 infection.

4.
Multidiscip Respir Med ; 15(1): 664, 2020 Jan 28.
Article in English | MEDLINE | ID: covidwho-1088995

ABSTRACT

BACKGROUND: Medical face masks are integral personal protective equipment against infectious airborne disease and become scarce during epidemic outbreaks such as COVID-19. A novel, sustainably manufactured face mask with antimicrobial and anti-inflammatory properties from oil of Folium Plectranthii amboinicii can be an effective alternative to internationally sold masks. METHODS: This prospective, randomized study assigned subjects (n=67) to either conventional surgical face mask or Lamdong Medical College (LMC) face mask for three hours. Fractional concentration of nitric oxide in exhaled breath (FENO) and peak expiratory flow (PEF) was measured before and after mask use. Subjective reporting on respiratory symptoms was also analyzed. Masks were then incubated and analyzed for microorganism growth. RESULTS: Subjects assigned the LMC mask had a lowered FENO (p<0.05) compared to conventional face masks after mask wearing. Subjects with LMC mask use reported higher comfortability (p<0.05), breathability (p<0.05), and lower allergy symptoms (p<0.05). The LMC mask has visually less microorganism growth in the cultured medium, measured by sterile ring radius. CONCLUSIONS: The LMC face mask is a renewably manufactured personal protective tool with antibacterial capacity that can serve as an effective alternative to internationally sold surgical face mask during shortage of mask due to COVID-19.

5.
Clin Sci (Lond) ; 135(2): 387-407, 2021 01 29.
Article in English | MEDLINE | ID: covidwho-1054073

ABSTRACT

The two axes of the renin-angiotensin system include the classical ACE/Ang II/AT1 axis and the counter-regulatory ACE2/Ang-(1-7)/Mas1 axis. ACE2 is a multifunctional monocarboxypeptidase responsible for generating Ang-(1-7) from Ang II. ACE2 is important in the vascular system where it is found in arterial and venous endothelial cells and arterial smooth muscle cells in many vascular beds. Among the best characterized functions of ACE2 is its role in regulating vascular tone. ACE2 through its effector peptide Ang-(1-7) and receptor Mas1 induces vasodilation and attenuates Ang II-induced vasoconstriction. In endothelial cells activation of the ACE2/Ang-(1-7)/Mas1 axis increases production of the vasodilator's nitric oxide and prostacyclin's and in vascular smooth muscle cells it inhibits pro-contractile and pro-inflammatory signaling. Endothelial ACE2 is cleaved by proteases, shed into the circulation and measured as soluble ACE2. Plasma ACE2 activity is increased in cardiovascular disease and may have prognostic significance in disease severity. In addition to its enzymatic function, ACE2 is the receptor for severe acute respiratory syndrome (SARS)-coronavirus (CoV) and SARS-Cov-2, which cause SARS and coronavirus disease-19 (COVID-19) respectively. ACE-2 is thus a double-edged sword: it promotes cardiovascular health while also facilitating the devastations caused by coronaviruses. COVID-19 is associated with cardiovascular disease as a risk factor and as a complication. Mechanisms linking COVID-19 and cardiovascular disease are unclear, but vascular ACE2 may be important. This review focuses on the vascular biology and (patho)physiology of ACE2 in cardiovascular health and disease and briefly discusses the role of vascular ACE2 as a potential mediator of vascular injury in COVID-19.


Subject(s)
Angiotensin I/metabolism , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/metabolism , Peptide Fragments/metabolism , Proto-Oncogene Proteins/metabolism , Receptors, G-Protein-Coupled/metabolism , Vascular Diseases/virology , Animals , Blood Vessels/enzymology , Humans , Proto-Oncogene Mas , Receptor, Angiotensin, Type 2/metabolism , Renin-Angiotensin System , SARS-CoV-2/metabolism , Vascular Diseases/metabolism
6.
J Antibiot (Tokyo) ; 74(4): 260-265, 2021 04.
Article in English | MEDLINE | ID: covidwho-997818

ABSTRACT

The emergence of SARS-CoV-2, the causative agent of COVID-19, highlights the increasing need for new and effective antiviral and antimicrobial agents. The FDA has recently banned several active ingredients used in hand sanitizers, including triclosan and benzethonium chloride. Nitric oxide (NO) is involved in the innate immune response and is a major component of macrophage-mediated attack on foreign viruses and bacteria. The specific aim of this study was to assess the antibacterial effects of 2-(N,N-diethylamino)-diazenolate-2-oxide (DEA-NONOate) against Escherichia coli (E. coli). A bacterial growth assay was compared to an adenosine triphosphate (ATP) activity assay at various time points to assess effects of DEA-NONOate on E. coli growth. A UV/Vis spectrophotometer was used to determine concentration of E. coli by measuring optical density (OD) at 630 nm. A luminescent assay was used to measure ATP activity correlating to viable cells. DEA-NONOate at a concentration of 65 mM was able to inhibit the growth of E. coli with the same efficacy as 1 µg ml-1 concentration of ciprofloxacin. Both the OD and ATP assays demonstrated a 99.9% reduction in E. coli. Both a 1 µg ml-1 concentration of ciprofloxacin and a 65 mM concentration of DEA-NONOate achieved 99.9% inhibition of E. coli, verified using both optical density measurement of bacterial cultures in 96 well plates and a luminescent ATP activity assay. The bactericidal effects of DEA-NONOate against E. coli is proof-of-concept to pursue evaluation of nitric oxide-based formulations as antimicrobial and antiviral agents as hand sanitizers.


Subject(s)
Escherichia coli/drug effects , Hydrazines/pharmacology , Adenosine Triphosphate/metabolism , Anti-Bacterial Agents/pharmacology , Ciprofloxacin/pharmacology , Hand Sanitizers/chemistry , Humans , Luminescent Measurements , Pilot Projects , Spectrophotometry, Ultraviolet
7.
Crit Care Explor ; 2(11): e0277, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-939581

ABSTRACT

Treatment options are limited for patients with respiratory failure due to coronavirus disease 2019. Conventional oxygen therapy and awake proning are options, but the use of high-flow nasal cannula and continuous positive airway pressure are controversial. There is an urgent need for effective rescue therapies. Our aim is to evaluate the role of inhaled nitric oxide 160 ppm as a possible rescue therapy in nonintubated coronavirus disease 2019 patients. DESIGN: Retrospective evaluation of coronavirus disease 2019 patients in respiratory distress receiving nitric oxide gas as rescue therapy. SETTING: Massachusetts General Hospital, between March 18, 2020, and May 20, 2020, during the local coronavirus disease 2019 surge. PATIENTS: Coronavirus disease 2019 patients at high risk for acute hypoxemic respiratory failure with worsening symptoms despite use of supplemental oxygen and/or awake proning. INTERVENTIONS: Patients received nitric oxide at concentrations of 160 ppm for 30 minutes twice per day via a face mask until resolution of symptoms, discharge, intubation, or the transition to comfort measures only. MEASUREMENTS AND MAIN RESULTS: Between March 18, 2020, and May 20, 2020, five patients received nitric oxide inhalation as a rescue therapy for coronavirus disease 2019 at Massachusetts General Hospital. All received at least one dosage. The three patients that received multiple treatments (ranging from five to nine) survived and were discharged home. Maximum methemoglobin concentration after 30 minutes of breathing nitric oxide was 2.0% (1.7-2.3%). Nitrogen dioxide was below 2 ppm. No changes in mean arterial pressure or heart rate were observed during or after nitric oxide treatment. Oxygenation and the respiratory rate remained stable during and after nitric oxide treatments. For two patients, inflammatory marker data were available and demonstrate a reduction or a cessation of escalation after nitric oxide treatment. CONCLUSIONS: Nitric oxide at 160 ppm may be an effective adjuvant rescue therapy for patients with coronavirus disease 2019.

8.
Med Hypotheses ; 146: 110378, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-912500

ABSTRACT

In December 2019, in China, a disease derived from a new beta coronavirus (SARS-CoV-2) was reported, which was termed coronavirus disease 2019 (COVID-19). Currently, it is known that endothelial cell dysfunction is a critical event in the infection by this virus. However, in a representative percentage of patients with COVID-19, neither cardiovascular disease nor diabetes mellitus, which could be linked with endothelial dysfunction, has been reported. Previous evidence has shown the presence of early endothelial dysfunction in healthy subjects but with a family history of type 2 diabetes (FH-DM2), where glucose metabolism, the synthesis of nitric oxide (NO), reactive oxygen species (ROS), as well as expression of genes involved with their synthesis are impaired. Besides, in subjects with an FH-DM2, the presence of hyperinsulinemia and high glucose levels are common events that could favor the infection of endothelial cells by the coronavirus. Interestingly, both events have been reported in patients with COVID-19, in whom hyperinsulinemia increases the surface expression of ACE2 through a diminution of ADAMTS17 activity; whereas hyperglycemia induces higher expression of ACE2 in different tissues, including microvascular endothelial cells from the pancreatic islets, favoring chronic hyperglycemia and affecting the release of insulin. Therefore, we hypothesized that an FH-DM2 should be considered an important risk factor, since the individuals with this background develop an early endothelial dysfunction, which would increase the susceptibility and severity of infection and damage to the endothelium, in the patient infected with the SARS-CoV-2.


Subject(s)
COVID-19/etiology , COVID-19/pathology , Diabetes Mellitus, Type 2/complications , Endothelium, Vascular/pathology , Angiotensin-Converting Enzyme 2/physiology , COVID-19/physiopathology , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/physiopathology , Disease Susceptibility , Endothelium, Vascular/physiopathology , Host Microbial Interactions/physiology , Humans , Models, Biological , Pandemics , Receptors, Virus/physiology , Risk Factors , SARS-CoV-2/pathogenicity
9.
BMC Pulm Med ; 20(1): 269, 2020 Oct 16.
Article in English | MEDLINE | ID: covidwho-873971

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has spread to almost 100 countries, infected over 31 M patients and resulted in 961 K deaths worldwide as of 21st September 2020. The major clinical feature of severe COVID-19 requiring ventilation is acute respiratory distress syndrome (ARDS) with multi-functional failure as a result of a cytokine storm with increased serum levels of cytokines. The pathogenesis of the respiratory failure in COVID-19 is yet unknown, but diffuse alveolar damage with interstitial thickening leading to compromised gas exchange is a plausible mechanism. Hypoxia is seen in the COVID-19 patients, however, patients present with a distinct phenotype. Intracellular levels of nitric oxide (NO) play an important role in the vasodilation of small vessels. To elucidate the intracellular levels of NO inside of RBCs in COVID-19 patients compared with that of healthy control subjects. METHODS: We recruited 14 COVID-19 infected cases who had pulmonary involvement of their disease, 4 non-COVID-19 healthy controls (without pulmonary involvement and were not hypoxic) and 2 hypoxic non-COVID-19 patients subjects who presented at the Masih Daneshvari Hospital of Tehran, Iran between March-May 2020. Whole blood samples were harvested from patients and intracellular NO levels in 1 × 106 red blood cells (RBC) was measured by DAF staining using flow cytometry (FACS Calibour, BD, CA, USA). RESULTS: The Mean florescent of intensity for NO was significantly enhanced in COVID-19 patients compared with healthy control subjects (P ≤ 0.05). As a further control for whether hypoxia induced this higher intracellular NO, we evaluated the levels of NO inside RBC of hypoxic patients. No significant differences in NO levels were seen between the hypoxic and non-hypoxic control group. CONCLUSIONS: This pilot study demonstrates increased levels of intracellular NO in RBCs from COVID-19 patients. Future multi-centre studies should examine whether this is seen in a larger number of COVID-19 patients and whether NO therapy may be of use in these severe COVID-19 patients.


Subject(s)
Carbon Dioxide/metabolism , Coronavirus Infections/metabolism , Erythrocytes/metabolism , Hypoxia/metabolism , Nitric Oxide/metabolism , Oxygen/metabolism , Pneumonia, Viral/metabolism , Adult , Aged , Aged, 80 and over , Asymptomatic Diseases , Betacoronavirus , Blood Gas Analysis , COVID-19 , Case-Control Studies , Coronavirus Infections/blood , Coronavirus Infections/complications , Female , Flow Cytometry , Humans , Hypoxia/blood , Hypoxia/etiology , Male , Middle Aged , Pandemics , Partial Pressure , Pilot Projects , Pneumonia, Viral/blood , Pneumonia, Viral/complications , Pulmonary Disease, Chronic Obstructive/blood , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/metabolism , SARS-CoV-2 , Vasodilation , Young Adult
10.
Virus Res ; 291: 198202, 2021 01 02.
Article in English | MEDLINE | ID: covidwho-867170

ABSTRACT

The endogenous free radical nitric oxide (NO) plays a pivotal role in the immunological system. NO has already been reported as a potential candidate for use in the treatment of human coronavirus infections, including COVID-19. In fact, inhaled NO has been used in clinical settings for its antiviral respiratory action, and in the regulation of blood pressure to avoid clot formation. In this mini-review, we discuss recent progress concerning the antivirus activity of NO in clinical, pre-clinical and research settings, and its beneficial effects in the treatment of clinical complications in patients infected with coronaviruses and other respiratory viral diseases, including COVID-19. We also highlight promising therapeutic effects of NO donors allied to nanomaterials to combat COVID-19 and other human coronavirus infections. Nanomaterials can be designed to deliver sustained, localized NO release directly at the desired application site, enhancing the beneficial effects of NO and minimizing the side effects. Challenges and perspectives are presented to open new fields of research.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Nanoparticles/therapeutic use , Nitric Oxide/therapeutic use , Administration, Inhalation , Antiviral Agents/administration & dosage , Coronavirus Infections/drug therapy , Drug Delivery Systems , Humans , Nanoparticles/administration & dosage , Nitric Oxide/administration & dosage
11.
J Biol Regul Homeost Agents ; 34(6): 1971-1975, 2020.
Article in English | MEDLINE | ID: covidwho-814874

ABSTRACT

SARS-Cov-2 infection causes local and systemic inflammation mediated by pro-inflammatory cytokines and COX-2 eicosanoid products with metabolic dysfunction and tissue damage that can lead to patient death. These effects are primarily induced by IL-1 cytokines, which are involved in the elevation of hepatic acute phase proteins and fever. IL-1 has a broad spectrum of biological activities and participates in both innate and acquired immunity. In infections, IL-1 induces gene expression and synthesis of several cytokines/chemokines in both macrophages and mast cells (MCs). The activation of MCs triggers the secretion of mediators stored in the granules, and the de novo synthesis of pro-inflammatory cytokines. In microorganism infections, the release of IL-1 macrophage acts on adhesion molecules and endothelial cells leading to hypotension and septic shock syndrome. IL-1 activated by SARS-CoV-2 stimulates the secretion of TNF, IL-6 and other cytokines, a pro-inflammatory complex that can lead to cytokine storm and be deleterious in both lung and systemically. In SARS-CoV-2 septic shock, severe metabolic cellular abnormalities occur which can lead to death. Here, we report that SARS-CoV-2 induces IL-1 in macrophages and MCs causing the induction of gene expression and activation of other pro-inflammatory cytokines. Since IL-1 is toxic, its production from ubiquitous MCs and macrophages activated by SARS-CoV-2 can also provokes both gastrointestinal and brain disorders. Furthermore, in these immune cells, IL-1 also elevates nitric oxide, and the release of inflammatory arachidonic acid products such as prostaglndins and thromboxane A2. All together these effects can generate cytokine storm and be the primary cause of severe inflammation with respiratory distress and death. Although, IL-1 administered in low doses may be protective; when it is produced in high doses in infectious diseases can be detrimental, therefore, IL-1 blockade has been studied in many human diseases including sepsis, resulting that blocking it is absolutely necessary. This definitely nurtures hope for a new effective therapeutic treatment. Recently, two interesting anti-IL-1 cytokines have been widely described: IL-37 and IL-1Ra. IL-37, by blocking IL-1, has been observed to have anti-inflammatory action in rodents in vivo and in transfected cells. It has been reported that IL-37 is a very powerful protein which inhibits inflammation and its inhibition can be a valid therapeutic strategy. IL-37 is a natural suppressor of inflammation that is generated through a caspase-1 that cleaves pro-IL-37 into mature IL-37 which translocates to the nucleus and inhibits the transcription of pro-inflammatory genes; while IL-1Ra inhibits inflammation by binding IL-1 to its IL-1R (receptor). We firmly believe that blocking IL-1 with an anti-inflammatory cytokine such as IL-37 and/or IL-1Ra is an effective valid therapy in a wide spectrum of inflammatory disorders including SARS-CoV-2-induced COVID-19. Here, we propose for the first time that IL-37, by blocking IL-1, may have an important role in the therapy of COVID-19.


Subject(s)
COVID-19/immunology , Cytokine Release Syndrome/virology , Interleukin-1/immunology , Cytokines/immunology , Humans , Macrophages/virology , Mast Cells/virology
12.
Med Hypotheses ; 143: 110142, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-671909

ABSTRACT

BACKGROUND: Pulmonary hypertension is a significant complication for some patients with COVID-19 pneumonia, especially those requiring intensive care. Tachyphylaxis to the current therapy, inhaled nitric oxide (iNO), is also common. In vitro, folic acid directly increases nitric oxide (NO) production and extends its duration of action; effects which could be of benefit in reversing pulmonary hypertension and severe hypoxaemia. Our work has shown that, in the systemic circulation, folic acid in high dose rapidly improves nitric oxide mediated vasodilation, by activating endothelial nitric oxide synthase (eNOS). HYPOTHESIS: A similar effect of high dose folic acid on pulmonary endothelial function would be expected from the same mechanism and would lead to improvement in pulmonary perfusion. We therefore hypothesise that folic acid, 5 mg or greater, is a useful therapeutic option for pulmonary hypertension and/or refractory severe hypoxaemia, in patients with severe COVID-19 associated pneumonia in whom NO therapy is considered, with a very low risk of adverse effects.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Folic Acid/therapeutic use , Hypertension, Pulmonary/drug therapy , Nitric Oxide/metabolism , Pandemics , Pneumonia, Viral/complications , Administration, Inhalation , Animals , COVID-19 , Endothelium, Vascular/drug effects , Endothelium, Vascular/physiology , Enzyme Activation/drug effects , Folic Acid/administration & dosage , Folic Acid/pharmacology , Humans , Hypertension, Pulmonary/complications , Hypoxia/drug therapy , Hypoxia/etiology , Mice , Nitric Oxide/administration & dosage , Nitric Oxide/therapeutic use , Nitric Oxide Synthase Type III/drug effects , SARS-CoV-2 , Tachyphylaxis
13.
Nitric Oxide ; 103: 29-30, 2020 10 01.
Article in English | MEDLINE | ID: covidwho-666023

ABSTRACT

Most outcomes of COVID-19 are associated with dysfunction of the vascular system, particularly in the lung. Inhalation of nitric oxide (NO) gas is currently being investigated as a treatment for patients with moderate to severe COVID-19. In addition to the expected vasodilation effect, it has been also suggested that NO potentially prevents infection by SARS-CoV-2. Since NO is an unstable radical molecule that is easily oxidized by multiple mechanisms in the human body, it is practically difficult to control its concentration at lesions that need NO. Inorganic nitrate and/or nitrite are known as precursors of NO that can be produced through chemical as well enzymatic reduction. It appears that this NO synthase (NOS)-independent mechanism has been overlooked in the current developing of clinical treatments. Here, I suggest the missing link between nitrate and COVID-19 in terms of hypoxic NO generation.


Subject(s)
Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Nitrates/metabolism , Nitric Oxide/metabolism , Nitrites/metabolism , Pneumonia, Viral/drug therapy , Antiviral Agents/metabolism , Ascorbic Acid/chemistry , Ascorbic Acid/therapeutic use , COVID-19 , Coronavirus Infections/metabolism , Coronavirus Infections/prevention & control , Endothelium-Dependent Relaxing Factors/metabolism , Humans , Nitrates/blood , Nitrites/blood , Nitrites/chemistry , Pandemics/prevention & control , Pneumonia, Viral/metabolism , Pneumonia, Viral/prevention & control , SARS-CoV-2 , Vasodilation/drug effects
15.
Acta Paediatr ; 109(8): 1539-1544, 2020 08.
Article in English | MEDLINE | ID: covidwho-458994

ABSTRACT

The world is facing an explosive COVID-19 pandemic. Some cases rapidly develop deteriorating lung function, which causes deep hypoxaemia and requires urgent treatment. Many centres have started treating patients in the prone position, and oxygenation has improved considerably in some cases. Questions have been raised regarding the mechanisms behind this. The mini review provides some insights into the role of supine and prone body positions and summarises the latest understanding of the responsible mechanisms. The scope for discussion is outside the neonatal period and entirely based on experimental and clinical experiences related to adults. The human respiratory system is a complex interplay of many different variables. Therefore, this mini review has prioritised previous and ongoing research to find explanations based on three scientific areas: gravity, lung structure and fractal geometry and vascular regulation. It concludes that gravity is one of the variables responsible for ventilation/perfusion matching but in concert with lung structure and fractal geometry, ventilation and regulation of lung vascular tone. Since ventilation distribution does not change between supine and prone positions, the higher expression of nitric oxide in dorsal lung vessels than in ventral vessels is likely to be the most important mechanism behind enhanced oxygenation in the prone position.


Subject(s)
Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Hypoxia/prevention & control , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , COVID-19 , Humans , Pandemics , Prone Position/physiology
16.
Microbes Infect ; 22(4-5): 168-171, 2020.
Article in English | MEDLINE | ID: covidwho-275089

ABSTRACT

The nasal cavity and turbinates play important physiological functions by filtering, warming and humidifying inhaled air. Paranasal sinuses continually produce nitric oxide (NO), a reactive oxygen species that diffuses to the bronchi and lungs to produce bronchodilatory and vasodilatory effects. Studies indicate that NO may also help to reduce respiratory tract infection by inactivating viruses and inhibiting their replication in epithelial cells. In view of the pandemic caused by the novel coronavirus (SARS-CoV-2), clinical trials have been designed to examine the effects of inhaled nitric oxide in COVID-19 subjects. We discuss here additional lifestyle factors such as mouth breathing which may affect the antiviral response against SARS-CoV-2 by bypassing the filtering effect of the nose and by decreasing NO levels in the airways. Simple devices that promote nasal breathing during sleep may help prevent the common cold, suggesting potential benefits against coronavirus infection. In the absence of effective treatments against COVID-19, the alternative strategies proposed here should be considered and studied in more detail.


Subject(s)
Betacoronavirus , Coronavirus Infections/drug therapy , Nitric Oxide/administration & dosage , Nitric Oxide/therapeutic use , Pneumonia, Viral/drug therapy , Administration, Intranasal , Betacoronavirus/drug effects , COVID-19 , Coronavirus Infections/prevention & control , Humans , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , SARS-CoV-2 , Viral Load/drug effects
17.
Int Immunopharmacol ; 84: 106528, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-72527

ABSTRACT

Isodeoxyelephantopin (IDET) has been identified as an anti-tumor natural constituent whose anti-tumor activity and mechanism have been widely investigated. Since the occurrence and development of cancer usually accompany with inflammation, and tumor signaling shares many components with inflammation signaling, the agents with anti-tumor activity are likely to possess anti-inflammation potential. Thus, the current study aims to demonstrate the anti-inflammatory activity along with the underlying mechanism of IDET in lipopolysaccharide (LPS)-primed macrophages. By using Griess method and ELISA, we found that in both bone marrow derived macrophages and alveolar macrophage cell line, IDET, at relatively low concentrations (0.75, 1.5 and 3 µM), could inhibit LPS-induced expression of various pro-inflammatory mediators including nitric oxide (NO) generated by inducible nitric oxide synthase (iNOS), interleukin (IL)-6, monocyte chemotactic protein-1 (MCP-1) and IL-1ß. Meanwhile, in activated MH-S cells, the inhibitory action of IDET on mRNA expression levels of these cytokines was also detected using qPCR. Mechanistically, the effects of IDET on two key inflammatory signalings, nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) pathways, were determined in LPS-activated MH-S cells by reporter gene along with western blot assays. On the one hand, IDET suppressed NF-κB signaling via down-regulating phosphorylation and degradation of inhibitor of NF-κB (IκB)-α and the subsequent p65 translocation. On the other hand, IDET dampened AP-1 signaling through attenuating phosphorylation of both c-jun N-terminal kinase 1/2 (JNK1/2) and extracellular signal regulated kinase 1/2 (ERK1/2). Our study indicates that IDET might be a promising constituent from the anti-inflammatory herb Elephantopus scaber Linn. in mitigating inflammatory conditions, especially respiratory inflammation.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Lactones/pharmacology , Macrophages/drug effects , Sesquiterpenes/pharmacology , Animals , Asteraceae , Cells, Cultured , Cytokines/genetics , Cytokines/immunology , Lipopolysaccharides/pharmacology , Macrophages/immunology , Male , Mice , Mice, Inbred BALB C , NF-kappa B/immunology , Nitric Oxide/immunology , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/immunology , Transcription Factor AP-1/immunology
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