Luni Chen - Academia.edu (original) (raw)

Papers by Luni Chen

Research paper thumbnail of in vitroでの一酸化窒素によるSARS-CoV-2の複製の緩和【JST・京大機械翻訳】

Research paper thumbnail of Effects of inhaled carbon monoxide and glucocorticoids in porcine endotoxin sepsis

International Journal of Clinical and Experimental Medicine, Feb 6, 2011

Recent animal studies have demonstrated that pre-treatment with inhaled carbon monoxide (iCO) exe... more Recent animal studies have demonstrated that pre-treatment with inhaled carbon monoxide (iCO) exert anti-inflammatory effects in various septic models. In all these models, there is no information whether iCO might act therapeutically after the onset of septic damage. The objective of this study was to investigate the potential anti-inflammatory effects of iCO to treat established injury in a model of porcine endotoxin sepsis. Five groups of pigs (n=6 in each group), were studied under anesthesia and mechanical ventilation: healthy control group (HC); lipopolysaccharide (LPS) groups, animals received continuous IV infusion of LPS for 6 hours; 2.5 hours after of LPS infusion treated groups received either: 250 ppm of iCO for 3.5 h, (LPS+CO group); 3 mg/Kg hydrocorti-sone bolus [Steroid (ST)], (LPS+ST group); or both steroid and iCO, (LPS+CO+ST group). Measurements of haemodynamics, blood gases, respiratory mechanics and biochemistry of organ function, were made. At the end of the exp...

Research paper thumbnail of and Göran Hedenstierna. Cyclooxygenase inhibitor blocks

rebound response after NO inhalation in an endotoxin model.

Research paper thumbnail of Inhaled nitric oxide

Use of nitric acid (NO) inhalable oxide in the form of gaseous nitric oxide or a nitric oxide don... more Use of nitric acid (NO) inhalable oxide in the form of gaseous nitric oxide or a nitric oxide donor, in combination with a cyclooxygenase inhibitor for the manufacture of a medicament for treating pulmonary vasoconstriction or constriction of the airways in a mammal, especially man, in order to counteract a hypo- or non-response to treatment with gaseous nitric oxide or a provider of nitric only oxide, and / or to counteract a rebound response in the case of withdrawal of treatment with nitric oxide gas or a donor of nitric oxide only.

Research paper thumbnail of Enhanced anti-inflammatory effects by steroids in a porcine sepsis model

BACKGROUND: INO also has an anti-inflammatory effect and inhibits the expression of many genes th... more BACKGROUND: INO also has an anti-inflammatory effect and inhibits the expression of many genes thought to be involved in inflammatory diseases. Another group of anti-inflammatory agents are the glucocorticoids(GCs). We hypothesized that there may be an interaction between inhalation of NO (INO) and systemic

Research paper thumbnail of Inhalde Nitric Oxide Therapy. Non-response Rebound Response

Therapeutic inhaled nitric oxide (INO) has proved beneficial in patients with pulmonary hypertens... more Therapeutic inhaled nitric oxide (INO) has proved beneficial in patients with pulmonary hypertension. However, around 30-40% of the patients are non-responders to this therapy, and a life-threateni ...

Research paper thumbnail of Gastrointestinal manifestations and possible mechanisms of COVID ‐19 in different periods

Journal of Digestive Diseases, 2021

Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (S... more Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, has become a pandemic worldwide. Although COVID‐19 mainly affects the respiratory system, gastrointestinal (GI) manifestations have been frequently reported in such cases, even as initial symptoms. There have been several studies on different GI manifestations in patients with mild and severe disease or in remission. In this review article we summarized different GI manifestations of COVID‐19 at various disease stages and the possible mechanisms based on published literatures, as well as the significance of GI manifestations in systemic inflammatory injury.

Research paper thumbnail of No redistribution of lung blood flow by inhaled nitric oxide in endotoxemic piglets pretreated with an endothelin receptor antagonist

Journal of applied physiology (Bethesda, Md. : 1985), Jan 30, 2014

Inhaled nitric oxide (INO) improves ventilation-perfusion matching and alleviates pulmonary hyper... more Inhaled nitric oxide (INO) improves ventilation-perfusion matching and alleviates pulmonary hypertension in patients with acute respiratory distress syndrome. However, outcome has not yet been shown to improve, and non-response is common. A better understanding of the mechanisms by which INO acts, may guide in improving treatment with INO in patients with severe respiratory failure. We hypothesized that INO may act not only by vasodilation in ventilated lung regions, but also by causing vasoconstriction via endothelin (ET-1) in atelectatic, non-ventilated lung regions. This was studied in 30 anesthetized, mechanically ventilated piglets. The fall in oxygenation and rise in pulmonary artery pressure during a sepsis-like condition (infusion of endotoxin) were blunted by INO 40ppm. Endotoxin infusion increased serum ET-1, and INO almost doubled the ratio between mRNA expression of endothelin receptor A (mediating vasoconstriction) and B (mediating vasodilation and clearance of ET-1) (E...

Research paper thumbnail of Integrative medicine for subacute stroke rehabilitation: a study protocol for a multicentre, randomised, controlled trial

BMJ open, Jan 4, 2014

Many patients with stroke receive integrative medicine in China, which includes the basic treatme... more Many patients with stroke receive integrative medicine in China, which includes the basic treatment of Western medicine and routine rehabilitation, in conjunction with acupuncture and Chinese medicine. The question of whether integrative medicine is efficacious for stroke rehabilitation is still controversial and very little research currently exists on the integrated approach for this condition. Consequently, we will conduct a multicentre, randomised, controlled, assessor-blinded clinical trial to assess the effectiveness of integrative medicine on stroke rehabilitation. 360 participants recruited from three large Chinese medical hospitals in Zhejiang Province will be randomly divided into the integrative medicine rehabilitation (IMR) group and the conventional rehabilitation (CR) group in a 1:1 ratio. Participants in the IMR group will receive acupuncture and Chinese herbs in addition to basic Western medicine and rehabilitation treatment. The CR group will not receive acupuncture...

Research paper thumbnail of Inhalation of nitric oxide in the treatment of SARS in Beijing

BACKGROUND: Patients with severe acute respiratory syndrome (SARS) frequently suffer from hypoxem... more BACKGROUND: Patients with severe acute respiratory syndrome (SARS) frequently suffer from hypoxemia despite supplemental oxygen and mechanical ventilator support. Inhalation of nitric oxide (INO) could improve oxygenation in intubated ARDS patients. However, whether INO has similar effect in the patients with severe acute respiratory syndrome (SARS), and whether INO could be administrated in adults with non-invasive ventilator support is not known yet. METHOD: Fourteen patients with severe SARS (in two ICU units) were studied. Six patients received INO (30 ppm, 3-7 d), and eight patients served as controls. Oxygen saturation, hemodynamic index, inspired oxygen fraction, and chest x-ray were studied. A 4-week follow up was made. RESULTS: In the INO group, oxygen index (.P_(aO_2)/F_(iO_2)) increased from 94 till 250 mmHg. CPAP/BiPAP could be discontinued in all four patients and PEEP lowered in the intubated patient with no decrease of arterial oxygenation. The effects were remained after INO was discontinued, and chest x-ray showed reduced lung infiltrates in all patients but one. Four weeks after INO, one patients remained in the ICU and one died. In the controls, no improvement was seen over a similar study period. Four weeks later, four patients remained in the ICU and two patients had died. CONCLUSION: INO improved oxygenation both in intubated and non- intubated SARS patients. The possibility to leave ventilator pressure support may reduce the risk for lung damage, and also reduce exposure of SARS virus to the nursing staff. The improvement in chest X-ray and the remaining in the effect can hardly be explained by the vasorelaxant properties of INO. It may suggest that INO may also change the disease itself.

Research paper thumbnail of Treatment of COVID-19 by Inhaled NO to Reduce Shunt?

American Journal of Respiratory and Critical Care Medicine

Research paper thumbnail of Inhaled Nitric Oxide Therapy : Non-response and Rebound Response

Research paper thumbnail of Cyclooxygenase inhibitor blocks rebound response after NO inhalation in an endotoxin model

American journal of physiology. Heart and circulatory physiology, 2003

This study addressed the possible role of cyclooxygenase (COX) and its products in the rebound re... more This study addressed the possible role of cyclooxygenase (COX) and its products in the rebound response to inhaled nitric oxide (INO). Anesthetized, mechanically ventilated piglets were exposed to endotoxin alone, endotoxin combined with INO, or endotoxin with INO plus the COX inhibitor diclofenac (3 mg/kg iv) (n = 8 piglets/group). A control group of healthy pigs (n = 6) was also studied. Measurements were made of blood gases, hemodynamic parameters, lung tissue COX expression, and plasma concentrations of thromboxane B(2) (TxB(2)), PGF(2alpha), and 6-keto-PGF(1alpha). Endotoxin increased lung inducible COX (COX-2) expression and circulating prostanoids concentrations. Inhalation of NO during endotoxemia increased the constitutive COX (COX-1) expression, and the circulating TxB(2) and PGF(2alpha) increased further after INO withdrawal. The combination of COX inhibitor with INO blocked all these changes and eliminated the rebound reaction to INO withdrawal, which otherwise was seen ...

Research paper thumbnail of Endothelin-1 and nitric oxide synthase in short rebound reaction to short exposure to inhaled nitric oxide

American journal of physiology. Heart and circulatory physiology, 2001

On withdrawal of inhalation of nitric oxide (INO) administered after lung injury, pulmonary arter... more On withdrawal of inhalation of nitric oxide (INO) administered after lung injury, pulmonary artery pressure (PAP) and arterial oxygen tension (Pa(O(2))) may deteriorate more than before INO (rebound response). In this study, we investigated the possible roles of endothelin (ET)-1 and nitric oxide (NO) synthase (NOS) activity in the short rebound reaction to short-term inhalation of NO. Twenty-six anesthetized mechanically ventilated piglets were given endotoxin infusion. Twelve animals then received INO (30 parts per million) for two 30-min periods. Nine controls were not given NO. Measurements were made of blood gases and hemodynamic parameters, lung tissue ET-1 expression and NOS activity, and plasma ET-1 concentration. INO decreased PAP and increased Pa(O(2)), but INO withdrawal caused a short rebound reaction with an increase in PAP. Lung tissue expression and plasma concentration of ET-1 increased during INO, and plasma ET-1 increased further after its withdrawal. Activity of c...

Research paper thumbnail of Inhibition of SARS Coronavirus Infection In Vitro with Clinically Approved Antiviral Drugs

Emerging Infectious Diseases, 2004

Severe acute respiratory syndrome (SARS) is an infectious disease caused by a newly identified hu... more Severe acute respiratory syndrome (SARS) is an infectious disease caused by a newly identified human coronavirus (SARS-CoV). Currently, no effective drug exists to treat SARS-CoV infection. In this study, we investigated whether a panel of commercially available antiviral drugs exhibit in vitro anti-SARS-CoV activity. A drugscreening assay that scores for virus-induced cytopathic effects on cultured cells was used. Tested were 19 clinically approved compounds from several major antiviral pharmacologic classes: nucleoside analogs, interferons, protease inhibitors, reverse transcriptase inhibitors, and neuraminidase inhibitors. Complete inhibition of cytopathic effects of SARS-CoV in culture was observed for interferon subtypes, β-1b, α-n1, α-n3, and human leukocyte interferon a. These findings support clinical testing of approved interferons for the treatment of SARS.

Research paper thumbnail of Nitric oxide up-regulates the glucocorticoid receptor and blunts the inflammatory reaction in porcine endotoxin sepsis*

Critical Care Medicine, 2007

Nitric oxide inhibits the expression of many genes involved in inflammatory diseases. Glucocortic... more Nitric oxide inhibits the expression of many genes involved in inflammatory diseases. Glucocorticoids inhibit similar transcription factors. We hypothesized that there may be an interaction between nitric oxide and glucocorticoids, with the potential to enhance the anti-inflammatory effect when administered simultaneously. Prospective, randomized, controlled study. Animal research laboratory. A total of 45 anesthetized and mechanically ventilated pigs. Lung and systemic injury was induced by intravenous infusion of endotoxin (lipopolysaccharide) for 6 hrs. After 2.5 hrs, one group received 3.5 mg/kg hydrocortisone, another group inhaled nitric oxide (30 ppm), and still another group received both steroid and nitric oxide. Control groups of healthy and endotoxin-exposed piglets were also studied. Central hemodynamics and gas exchange were measured. Detection of the glucocorticoid receptor and inflammatory markers in lung, liver, and kidney tissue were made by immunohistochemistry, and morphology was studied with light microscopy. Endotoxin infusion markedly reduced glucocorticoid receptor expression in lung, liver, and kidney and up-regulated activator protein-1 and the inflammatory markers nuclear factor-kappaB and tumor necrosis factor-alpha. When administered separately, steroids and nitric oxide had modest effect on the inflammatory response. However, nitric oxide up-regulated the glucocorticoid receptor expression. Simultaneous administration of steroids and nitric oxide attenuated the inflammatory response and almost preserved or restored normal histology of both lung and systemic organs. When the glucocorticoid receptor was blocked by a receptor antagonist (mifepristone, 600 mg) and inhaled nitric oxide was subsequently administered, no increase in the expression of the glucocorticoid receptor was seen. We suggest that up-regulation of glucocorticoid receptor expression by nitric oxide made steroid therapy more effective.

Research paper thumbnail of Effects of inhaled carbon monoxide and glucocorticoids in porcine endotoxin sepsis

Research paper thumbnail of Inhalation of Nitric Oxide in the Treatment of Severe Acute Respiratory Syndrome: A Rescue Trial in Beijing

Clinical Infectious Diseases, 2004

Research paper thumbnail of Pulmonary Vasoconstriction during Regional Nitric Oxide Inhalation

Anesthesiology, 2001

Background Inhaled nitric oxide (INO) is thought to cause selective pulmonary vasodilation of ven... more Background Inhaled nitric oxide (INO) is thought to cause selective pulmonary vasodilation of ventilated areas. The authors previously showed that INO to a hyperoxic lung increases the perfusion to this lung by redistribution of blood flow, but only if the opposite lung is hypoxic, indicating a more complex mechanism of action for NO. The authors hypothesized that regional hypoxia increases NO production and that INO to hyperoxic lung regions (HL) can inhibit this production by distant effect. Methods Nitric oxide concentration was measured in exhaled air (NO(E)), NO synthase (NOS) activity in lung tissue, and regional pulmonary blood flow in anesthetized pigs with regional left lower lobar (LLL) hypoxia (fraction of inspired oxygen [FIO2] = 0.05), with and without INO to HL (FIO2 = 0.8), and during cross-circulation of blood from pigs with and without INO. Results Left lower lobar hypoxia increased exhaled NO from the LLL (NO(E)LLL) from a mean (SD) of 1.3 (0.6) to 2.2 (0.9) parts ...

Research paper thumbnail of Nitric oxide dosed in short bursts at high concentrations may protect against Covid 19

Research paper thumbnail of in vitroでの一酸化窒素によるSARS-CoV-2の複製の緩和【JST・京大機械翻訳】

Research paper thumbnail of Effects of inhaled carbon monoxide and glucocorticoids in porcine endotoxin sepsis

International Journal of Clinical and Experimental Medicine, Feb 6, 2011

Recent animal studies have demonstrated that pre-treatment with inhaled carbon monoxide (iCO) exe... more Recent animal studies have demonstrated that pre-treatment with inhaled carbon monoxide (iCO) exert anti-inflammatory effects in various septic models. In all these models, there is no information whether iCO might act therapeutically after the onset of septic damage. The objective of this study was to investigate the potential anti-inflammatory effects of iCO to treat established injury in a model of porcine endotoxin sepsis. Five groups of pigs (n=6 in each group), were studied under anesthesia and mechanical ventilation: healthy control group (HC); lipopolysaccharide (LPS) groups, animals received continuous IV infusion of LPS for 6 hours; 2.5 hours after of LPS infusion treated groups received either: 250 ppm of iCO for 3.5 h, (LPS+CO group); 3 mg/Kg hydrocorti-sone bolus [Steroid (ST)], (LPS+ST group); or both steroid and iCO, (LPS+CO+ST group). Measurements of haemodynamics, blood gases, respiratory mechanics and biochemistry of organ function, were made. At the end of the exp...

Research paper thumbnail of and Göran Hedenstierna. Cyclooxygenase inhibitor blocks

rebound response after NO inhalation in an endotoxin model.

Research paper thumbnail of Inhaled nitric oxide

Use of nitric acid (NO) inhalable oxide in the form of gaseous nitric oxide or a nitric oxide don... more Use of nitric acid (NO) inhalable oxide in the form of gaseous nitric oxide or a nitric oxide donor, in combination with a cyclooxygenase inhibitor for the manufacture of a medicament for treating pulmonary vasoconstriction or constriction of the airways in a mammal, especially man, in order to counteract a hypo- or non-response to treatment with gaseous nitric oxide or a provider of nitric only oxide, and / or to counteract a rebound response in the case of withdrawal of treatment with nitric oxide gas or a donor of nitric oxide only.

Research paper thumbnail of Enhanced anti-inflammatory effects by steroids in a porcine sepsis model

BACKGROUND: INO also has an anti-inflammatory effect and inhibits the expression of many genes th... more BACKGROUND: INO also has an anti-inflammatory effect and inhibits the expression of many genes thought to be involved in inflammatory diseases. Another group of anti-inflammatory agents are the glucocorticoids(GCs). We hypothesized that there may be an interaction between inhalation of NO (INO) and systemic

Research paper thumbnail of Inhalde Nitric Oxide Therapy. Non-response Rebound Response

Therapeutic inhaled nitric oxide (INO) has proved beneficial in patients with pulmonary hypertens... more Therapeutic inhaled nitric oxide (INO) has proved beneficial in patients with pulmonary hypertension. However, around 30-40% of the patients are non-responders to this therapy, and a life-threateni ...

Research paper thumbnail of Gastrointestinal manifestations and possible mechanisms of COVID ‐19 in different periods

Journal of Digestive Diseases, 2021

Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (S... more Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, has become a pandemic worldwide. Although COVID‐19 mainly affects the respiratory system, gastrointestinal (GI) manifestations have been frequently reported in such cases, even as initial symptoms. There have been several studies on different GI manifestations in patients with mild and severe disease or in remission. In this review article we summarized different GI manifestations of COVID‐19 at various disease stages and the possible mechanisms based on published literatures, as well as the significance of GI manifestations in systemic inflammatory injury.

Research paper thumbnail of No redistribution of lung blood flow by inhaled nitric oxide in endotoxemic piglets pretreated with an endothelin receptor antagonist

Journal of applied physiology (Bethesda, Md. : 1985), Jan 30, 2014

Inhaled nitric oxide (INO) improves ventilation-perfusion matching and alleviates pulmonary hyper... more Inhaled nitric oxide (INO) improves ventilation-perfusion matching and alleviates pulmonary hypertension in patients with acute respiratory distress syndrome. However, outcome has not yet been shown to improve, and non-response is common. A better understanding of the mechanisms by which INO acts, may guide in improving treatment with INO in patients with severe respiratory failure. We hypothesized that INO may act not only by vasodilation in ventilated lung regions, but also by causing vasoconstriction via endothelin (ET-1) in atelectatic, non-ventilated lung regions. This was studied in 30 anesthetized, mechanically ventilated piglets. The fall in oxygenation and rise in pulmonary artery pressure during a sepsis-like condition (infusion of endotoxin) were blunted by INO 40ppm. Endotoxin infusion increased serum ET-1, and INO almost doubled the ratio between mRNA expression of endothelin receptor A (mediating vasoconstriction) and B (mediating vasodilation and clearance of ET-1) (E...

Research paper thumbnail of Integrative medicine for subacute stroke rehabilitation: a study protocol for a multicentre, randomised, controlled trial

BMJ open, Jan 4, 2014

Many patients with stroke receive integrative medicine in China, which includes the basic treatme... more Many patients with stroke receive integrative medicine in China, which includes the basic treatment of Western medicine and routine rehabilitation, in conjunction with acupuncture and Chinese medicine. The question of whether integrative medicine is efficacious for stroke rehabilitation is still controversial and very little research currently exists on the integrated approach for this condition. Consequently, we will conduct a multicentre, randomised, controlled, assessor-blinded clinical trial to assess the effectiveness of integrative medicine on stroke rehabilitation. 360 participants recruited from three large Chinese medical hospitals in Zhejiang Province will be randomly divided into the integrative medicine rehabilitation (IMR) group and the conventional rehabilitation (CR) group in a 1:1 ratio. Participants in the IMR group will receive acupuncture and Chinese herbs in addition to basic Western medicine and rehabilitation treatment. The CR group will not receive acupuncture...

Research paper thumbnail of Inhalation of nitric oxide in the treatment of SARS in Beijing

BACKGROUND: Patients with severe acute respiratory syndrome (SARS) frequently suffer from hypoxem... more BACKGROUND: Patients with severe acute respiratory syndrome (SARS) frequently suffer from hypoxemia despite supplemental oxygen and mechanical ventilator support. Inhalation of nitric oxide (INO) could improve oxygenation in intubated ARDS patients. However, whether INO has similar effect in the patients with severe acute respiratory syndrome (SARS), and whether INO could be administrated in adults with non-invasive ventilator support is not known yet. METHOD: Fourteen patients with severe SARS (in two ICU units) were studied. Six patients received INO (30 ppm, 3-7 d), and eight patients served as controls. Oxygen saturation, hemodynamic index, inspired oxygen fraction, and chest x-ray were studied. A 4-week follow up was made. RESULTS: In the INO group, oxygen index (.P_(aO_2)/F_(iO_2)) increased from 94 till 250 mmHg. CPAP/BiPAP could be discontinued in all four patients and PEEP lowered in the intubated patient with no decrease of arterial oxygenation. The effects were remained after INO was discontinued, and chest x-ray showed reduced lung infiltrates in all patients but one. Four weeks after INO, one patients remained in the ICU and one died. In the controls, no improvement was seen over a similar study period. Four weeks later, four patients remained in the ICU and two patients had died. CONCLUSION: INO improved oxygenation both in intubated and non- intubated SARS patients. The possibility to leave ventilator pressure support may reduce the risk for lung damage, and also reduce exposure of SARS virus to the nursing staff. The improvement in chest X-ray and the remaining in the effect can hardly be explained by the vasorelaxant properties of INO. It may suggest that INO may also change the disease itself.

Research paper thumbnail of Treatment of COVID-19 by Inhaled NO to Reduce Shunt?

American Journal of Respiratory and Critical Care Medicine

Research paper thumbnail of Inhaled Nitric Oxide Therapy : Non-response and Rebound Response

Research paper thumbnail of Cyclooxygenase inhibitor blocks rebound response after NO inhalation in an endotoxin model

American journal of physiology. Heart and circulatory physiology, 2003

This study addressed the possible role of cyclooxygenase (COX) and its products in the rebound re... more This study addressed the possible role of cyclooxygenase (COX) and its products in the rebound response to inhaled nitric oxide (INO). Anesthetized, mechanically ventilated piglets were exposed to endotoxin alone, endotoxin combined with INO, or endotoxin with INO plus the COX inhibitor diclofenac (3 mg/kg iv) (n = 8 piglets/group). A control group of healthy pigs (n = 6) was also studied. Measurements were made of blood gases, hemodynamic parameters, lung tissue COX expression, and plasma concentrations of thromboxane B(2) (TxB(2)), PGF(2alpha), and 6-keto-PGF(1alpha). Endotoxin increased lung inducible COX (COX-2) expression and circulating prostanoids concentrations. Inhalation of NO during endotoxemia increased the constitutive COX (COX-1) expression, and the circulating TxB(2) and PGF(2alpha) increased further after INO withdrawal. The combination of COX inhibitor with INO blocked all these changes and eliminated the rebound reaction to INO withdrawal, which otherwise was seen ...

Research paper thumbnail of Endothelin-1 and nitric oxide synthase in short rebound reaction to short exposure to inhaled nitric oxide

American journal of physiology. Heart and circulatory physiology, 2001

On withdrawal of inhalation of nitric oxide (INO) administered after lung injury, pulmonary arter... more On withdrawal of inhalation of nitric oxide (INO) administered after lung injury, pulmonary artery pressure (PAP) and arterial oxygen tension (Pa(O(2))) may deteriorate more than before INO (rebound response). In this study, we investigated the possible roles of endothelin (ET)-1 and nitric oxide (NO) synthase (NOS) activity in the short rebound reaction to short-term inhalation of NO. Twenty-six anesthetized mechanically ventilated piglets were given endotoxin infusion. Twelve animals then received INO (30 parts per million) for two 30-min periods. Nine controls were not given NO. Measurements were made of blood gases and hemodynamic parameters, lung tissue ET-1 expression and NOS activity, and plasma ET-1 concentration. INO decreased PAP and increased Pa(O(2)), but INO withdrawal caused a short rebound reaction with an increase in PAP. Lung tissue expression and plasma concentration of ET-1 increased during INO, and plasma ET-1 increased further after its withdrawal. Activity of c...

Research paper thumbnail of Inhibition of SARS Coronavirus Infection In Vitro with Clinically Approved Antiviral Drugs

Emerging Infectious Diseases, 2004

Severe acute respiratory syndrome (SARS) is an infectious disease caused by a newly identified hu... more Severe acute respiratory syndrome (SARS) is an infectious disease caused by a newly identified human coronavirus (SARS-CoV). Currently, no effective drug exists to treat SARS-CoV infection. In this study, we investigated whether a panel of commercially available antiviral drugs exhibit in vitro anti-SARS-CoV activity. A drugscreening assay that scores for virus-induced cytopathic effects on cultured cells was used. Tested were 19 clinically approved compounds from several major antiviral pharmacologic classes: nucleoside analogs, interferons, protease inhibitors, reverse transcriptase inhibitors, and neuraminidase inhibitors. Complete inhibition of cytopathic effects of SARS-CoV in culture was observed for interferon subtypes, β-1b, α-n1, α-n3, and human leukocyte interferon a. These findings support clinical testing of approved interferons for the treatment of SARS.

Research paper thumbnail of Nitric oxide up-regulates the glucocorticoid receptor and blunts the inflammatory reaction in porcine endotoxin sepsis*

Critical Care Medicine, 2007

Nitric oxide inhibits the expression of many genes involved in inflammatory diseases. Glucocortic... more Nitric oxide inhibits the expression of many genes involved in inflammatory diseases. Glucocorticoids inhibit similar transcription factors. We hypothesized that there may be an interaction between nitric oxide and glucocorticoids, with the potential to enhance the anti-inflammatory effect when administered simultaneously. Prospective, randomized, controlled study. Animal research laboratory. A total of 45 anesthetized and mechanically ventilated pigs. Lung and systemic injury was induced by intravenous infusion of endotoxin (lipopolysaccharide) for 6 hrs. After 2.5 hrs, one group received 3.5 mg/kg hydrocortisone, another group inhaled nitric oxide (30 ppm), and still another group received both steroid and nitric oxide. Control groups of healthy and endotoxin-exposed piglets were also studied. Central hemodynamics and gas exchange were measured. Detection of the glucocorticoid receptor and inflammatory markers in lung, liver, and kidney tissue were made by immunohistochemistry, and morphology was studied with light microscopy. Endotoxin infusion markedly reduced glucocorticoid receptor expression in lung, liver, and kidney and up-regulated activator protein-1 and the inflammatory markers nuclear factor-kappaB and tumor necrosis factor-alpha. When administered separately, steroids and nitric oxide had modest effect on the inflammatory response. However, nitric oxide up-regulated the glucocorticoid receptor expression. Simultaneous administration of steroids and nitric oxide attenuated the inflammatory response and almost preserved or restored normal histology of both lung and systemic organs. When the glucocorticoid receptor was blocked by a receptor antagonist (mifepristone, 600 mg) and inhaled nitric oxide was subsequently administered, no increase in the expression of the glucocorticoid receptor was seen. We suggest that up-regulation of glucocorticoid receptor expression by nitric oxide made steroid therapy more effective.

Research paper thumbnail of Effects of inhaled carbon monoxide and glucocorticoids in porcine endotoxin sepsis

Research paper thumbnail of Inhalation of Nitric Oxide in the Treatment of Severe Acute Respiratory Syndrome: A Rescue Trial in Beijing

Clinical Infectious Diseases, 2004

Research paper thumbnail of Pulmonary Vasoconstriction during Regional Nitric Oxide Inhalation

Anesthesiology, 2001

Background Inhaled nitric oxide (INO) is thought to cause selective pulmonary vasodilation of ven... more Background Inhaled nitric oxide (INO) is thought to cause selective pulmonary vasodilation of ventilated areas. The authors previously showed that INO to a hyperoxic lung increases the perfusion to this lung by redistribution of blood flow, but only if the opposite lung is hypoxic, indicating a more complex mechanism of action for NO. The authors hypothesized that regional hypoxia increases NO production and that INO to hyperoxic lung regions (HL) can inhibit this production by distant effect. Methods Nitric oxide concentration was measured in exhaled air (NO(E)), NO synthase (NOS) activity in lung tissue, and regional pulmonary blood flow in anesthetized pigs with regional left lower lobar (LLL) hypoxia (fraction of inspired oxygen [FIO2] = 0.05), with and without INO to HL (FIO2 = 0.8), and during cross-circulation of blood from pigs with and without INO. Results Left lower lobar hypoxia increased exhaled NO from the LLL (NO(E)LLL) from a mean (SD) of 1.3 (0.6) to 2.2 (0.9) parts ...

Research paper thumbnail of Nitric oxide dosed in short bursts at high concentrations may protect against Covid 19