BACKGROUND Eosinophilic esophagitis(EoE)is an eosinophilic-predominant inflammation of the esophagus diagnosed by upper endoscopy and biopsies.A non-invasive and cost-effective alternative for management of EoE is bei...BACKGROUND Eosinophilic esophagitis(EoE)is an eosinophilic-predominant inflammation of the esophagus diagnosed by upper endoscopy and biopsies.A non-invasive and cost-effective alternative for management of EoE is being researched.Previous studies assessing utility of fractional exhaled nitric oxide(FeNO)in EoE were low powered.None investigated the contribution of eosinophilic inflammation of the stomach and duodenum to FeNO.AIM To assess the utility of FeNO as a non-invasive biomarker of esophageal eosinophilic inflammation for monitoring disease activity.METHODS Patients aged 6-21 years undergoing scheduled upper endoscopy with biopsy for suspected EoE were recruited in our observational study.Patients on steroids and with persistent asthma requiring daily controller medication were excluded.FeNO measurements were obtained in duplicate using a chemiluminescence nitric oxide analyzer(NIOX MINO,Aerocrine,Inc.;Stockholm,Sweden)prior to endoscopy.Based on the esophageal peak eosinophil count(PEC)/high power field on biopsy,patients were classified as EoE(PEC≥15)or control(PEC≤14).Mean FeNO levels were correlated with presence or absence of EoE,eosinophil counts on esophageal biopsy,and abnormal downstream eosinophilia in the stomach(PEC≥10)and duodenum(PEC≥20).Wilcoxon rank-sum test,Spearman correlation,and logistic regression were used for analysis.P value<0.05 was considered significant.RESULTS We recruited a total of 134 patients,of which 45 were diagnosed with EoE by histopathology.The median interquartile range FeNO level was 17 parts per billion(11-37,range:7-81)in the EoE group and 12 parts per billion(8-19,range:5-71)in the control group.After adjusting for atopic diseases,EoE patients had significantly higher FeNO levels as compared to patients without EoE(Z=3.33,P<0.001).A weak yet statistically significant positive association was found between the number of esophageal eosinophils and FeNO levels(r=0.30,P<0.005).On subgroup analysis within the EoE cohort,higher FeNO levels were noted in patients with abnormal gastric(n=23,18 vs 15)and duodenal eosinophilia(n=28,21 vs 14);however,the difference was not statistically significant.CONCLUSION After ruling out atopy as possible confounder,we found significantly higher FeNO levels in the EoE cohort than in the control group.展开更多
Bronchial asthma is a common chronic airway inflammatory disease. Asthma is associated with high mortality, especially in the elderly patients. Repeated exacerbations cause disease progression. Therefore, identifying ...Bronchial asthma is a common chronic airway inflammatory disease. Asthma is associated with high mortality, especially in the elderly patients. Repeated exacerbations cause disease progression. Therefore, identifying the onset of acute elderly asthma as soon as possible and giving the effective treatment is crucial to improve the prognosis. This study was to investigate the significance of fractional exhaled nitric oxide （FeNO） combined with serum procalcitonin （PCT） and C-reactive protein （CRP） in the evaluation of elderly asthma. A total of 120 elderly patients with an acute attack of asthma from July, 2010 to May, 2012 were studied. On presentation, FeNO, serum PCT and CRP concentrations were measured and sputum culture was also performed. The elderly patients were re-evaluated when they had returned to their stable clinical state. The elderly patients were classified into two groups： positive bac- terial culture group （A） and negative bacterial culture group （B）. The results showed that： （1） In patients with an acute exacerbation of asthma, 48 （40%） patients had positive sputum bacterial culture and 72 （60%） had negative sputum bacterial culture. （2） The levels of FeNO in patients with acute exacerbation of asthma were significantly higher than in those with no acute exacerbation state （63.8±24.6 vs. 19±6.5 ppb, P〈0.05）. There was no significant difference in FeNO between group A and group B （P〉0.05）. （3） The levels of PCT and CRP in group A patients with an acute exacerbation of asthma were significantly higher （P〈0.05） than in group B （for PCT： 27.46±9.32 vs. 7.85±3.52 ng/mL; for CRP： 51.25±11.46 vs. 17.11±5.87 mg/L, respectively）. When they had returned to stable clinical state, the levels of PCT and CRP in group A were decreased significantly （P〈0.05）, and those in group B had no significant change （P〉0.05） when compared with the exacerbation group. There were no significant differences in the levels of PCT and CRP between the two groups in non-acute exacerbation state （/9〉0.05）. These results suggest that the increase in FeNO indicates the acute exacerbation of asthma, and the elevation of serum PCT and CRP levels may be associated with bacterial infection.展开更多
Background: Some patients present clinical features of both asthma and chronic obstructive pulmonary disease (COPD), which has led to the recent proposal of asthma-COPD overlap (ACO) as a diagnosis. Fractional exhaled...Background: Some patients present clinical features of both asthma and chronic obstructive pulmonary disease (COPD), which has led to the recent proposal of asthma-COPD overlap (ACO) as a diagnosis. Fractional exhaled nitric oxide (FeNO) is a candidate biomarker to diagnose ACO. We assessed the effect of an add-on treatment with budesonide/formoterol (BUD/FM) combination in patients with ACO, which was diagnosed by FeNO. Methods: This was a prospective, single-arm, open-label, before and after comparison study. Subjects included 83 patients with COPD who attended outpatient clinics for routine checkups at Shizuoka General Hospital between June and November 2016. All patients fulfilled the GOLD definition of COPD and were receiving long-acting muscarinic antagonist (LAMA) or LAMA/long-acting β2 agonist (LABA) combinations. After an 8-week run-in period, BUD/FM was added to the patients with FeNO levels of ≥35 ppb, defined as having ACO. For patients receiving LAMA/LABA, BUD/FM was added after the discontinuation of LABA. The modified British Medical Research Council (mMRC) score, COPD assessment test (CAT) score, spirometric indices, forced oscillation parameters, and FeNO were assessed before and after 8 weeks of BUD/ FM add-on treatment. Results: Twenty-four patients (28.9%) had FeNO levels ≥ 35 ppb, and 17 patients completed the study (mean age: 73 years and GOLD I/II/III/IV, 5/10/1/1). The mean CAT scores significantly improved (9.2 to 5.4, p = 0.015) and 10 patients (58.8%) showed ≥2 points improvement, a minimal clinically important difference. The mean FeNO levels significantly decreased from 63.0 to 34.3 ppb (p Conclusions: FeNO-guided treatment with BUD/FM improves symptoms in patients with ACO.展开更多
Introduction:Heart failure is a major public health issue with a prevalence of about 26 million people worldwide.Reduced nitric oxide availability,lower soluble guanylate cyclase(sGC)activity,and decreased cyclic guan...Introduction:Heart failure is a major public health issue with a prevalence of about 26 million people worldwide.Reduced nitric oxide availability,lower soluble guanylate cyclase(sGC)activity,and decreased cyclic guanosine monophosphate(cGMP)production are the causes of HF's development.Vericiguat prescribed under the brand name Verquvo was approved by U.S.Food and Drug Administration(FDA)in January 2021.It is a novel agent and the first sGC stimulator which helps to treat patients suffering from heart failure with reduced ejection fraction(HFrEF).Objective:The mechanism of action(cGMP pathway)of vericiguat,its clinical trials,its use in the treatment of heart failure,and its possible future aspects in therapeutic recommendations are all covered in this review.It will also raise awareness amongst healthcare professionals about the pharmacokinetic and pharmacodynamic parameters,dosing,administration,and drug-related problems of this new drug.Methods:Various databases for drug review were used in this review like PubMed,Medline,Google scholar,Drug bank,U.s.FDA,Medscape,and European society of cardiology guidelines.A total of 58 articles were screened out of which 39 articles were included in this review.Results:This review discusses vericiguat's mechanism of action(cGMP pathway),clinical studies,application in the treatment of heart failure,and potential future considerations in therapeutic recommendations.It will also educate healthcare professionals about the new drug's pharmacokinetics and pharmacodynamics,dose,administration,and drug-related problems.Conclusion:After hospitalization for HFrEF,the 5-year survival rate is just 25%,and disease morbidity and death are stil significant.As adjunctive therapy for individuals with heart failure and a low ejection fraction,vericiguat has a moderate level of effectiveness.Vericiguat's efficacy as an adjunct therapy to different drugs used to cure HF has to be further investigated.Vericiguat's safety and dosage in patients who have severe renal or hepatic illness need to be studied further.展开更多
Objective:To examine the effects of hydroalcoholic extract and fractions of Hordeum vulgare Linn.(H.vulgare,Da Mai)on streptozotocin(STZ)-induced diabetic nephropathy in Sprague-Dawley rat models.Methods:The study inv...Objective:To examine the effects of hydroalcoholic extract and fractions of Hordeum vulgare Linn.(H.vulgare,Da Mai)on streptozotocin(STZ)-induced diabetic nephropathy in Sprague-Dawley rat models.Methods:The study involved preliminary phytochemical screening of extract and fractions,estimation of secondary metabolites,chromatographic studies using high performance liquid chromatography(HPLC),antioxidant potential using 1,1-diphenyl-2-picrylhydrazyl(DPPH),nitric oxide radical scavenging and reducing power methods along with the determination of potential against diabetic nephropathy in STZ-induced rat models.Results:The phytochemical evaluation of the hydroalcoholic extract of H.vulgare and fractions revealed the presence of various phytoconstituents such as alkaloids,saponins,tannins,flavonoids,and glycosides.The chromatographic analysis indicated the peak complementing marker compound epicatechin and significant antioxidant activity in the extract and aqueous fraction.STZ-induced rats showed abnormal levels of serum albumin,creatinine,total cholesterol,blood urea nitrogen(BUN),and triglycerides,and urine albumin and creatinine,which returned to normal after 8 weeks of treatment with hydroalcoholic extract(400 mg/kg)and aqueous fraction(50 mg/kg)of H.vulgare.Conclusion:Hydroalcoholic extract(400 mg/kg)and aqueous fraction(50 mg/kg)of H.vulgare have significant antioxidant potential and positive effects on diabetic nephropathy.The fractionation and optimization increase the concentration of polyphenols in aqueous extract,causing a decrease in the dose required for effects against diabetic nephropathy.展开更多
文摘BACKGROUND Eosinophilic esophagitis(EoE)is an eosinophilic-predominant inflammation of the esophagus diagnosed by upper endoscopy and biopsies.A non-invasive and cost-effective alternative for management of EoE is being researched.Previous studies assessing utility of fractional exhaled nitric oxide(FeNO)in EoE were low powered.None investigated the contribution of eosinophilic inflammation of the stomach and duodenum to FeNO.AIM To assess the utility of FeNO as a non-invasive biomarker of esophageal eosinophilic inflammation for monitoring disease activity.METHODS Patients aged 6-21 years undergoing scheduled upper endoscopy with biopsy for suspected EoE were recruited in our observational study.Patients on steroids and with persistent asthma requiring daily controller medication were excluded.FeNO measurements were obtained in duplicate using a chemiluminescence nitric oxide analyzer(NIOX MINO,Aerocrine,Inc.;Stockholm,Sweden)prior to endoscopy.Based on the esophageal peak eosinophil count(PEC)/high power field on biopsy,patients were classified as EoE(PEC≥15)or control(PEC≤14).Mean FeNO levels were correlated with presence or absence of EoE,eosinophil counts on esophageal biopsy,and abnormal downstream eosinophilia in the stomach(PEC≥10)and duodenum(PEC≥20).Wilcoxon rank-sum test,Spearman correlation,and logistic regression were used for analysis.P value<0.05 was considered significant.RESULTS We recruited a total of 134 patients,of which 45 were diagnosed with EoE by histopathology.The median interquartile range FeNO level was 17 parts per billion(11-37,range:7-81)in the EoE group and 12 parts per billion(8-19,range:5-71)in the control group.After adjusting for atopic diseases,EoE patients had significantly higher FeNO levels as compared to patients without EoE(Z=3.33,P<0.001).A weak yet statistically significant positive association was found between the number of esophageal eosinophils and FeNO levels(r=0.30,P<0.005).On subgroup analysis within the EoE cohort,higher FeNO levels were noted in patients with abnormal gastric(n=23,18 vs 15)and duodenal eosinophilia(n=28,21 vs 14);however,the difference was not statistically significant.CONCLUSION After ruling out atopy as possible confounder,we found significantly higher FeNO levels in the EoE cohort than in the control group.
基金supported by Fundation of Henan Provincial Medical Science and Technology Research(No.201003098)
文摘Bronchial asthma is a common chronic airway inflammatory disease. Asthma is associated with high mortality, especially in the elderly patients. Repeated exacerbations cause disease progression. Therefore, identifying the onset of acute elderly asthma as soon as possible and giving the effective treatment is crucial to improve the prognosis. This study was to investigate the significance of fractional exhaled nitric oxide （FeNO） combined with serum procalcitonin （PCT） and C-reactive protein （CRP） in the evaluation of elderly asthma. A total of 120 elderly patients with an acute attack of asthma from July, 2010 to May, 2012 were studied. On presentation, FeNO, serum PCT and CRP concentrations were measured and sputum culture was also performed. The elderly patients were re-evaluated when they had returned to their stable clinical state. The elderly patients were classified into two groups： positive bac- terial culture group （A） and negative bacterial culture group （B）. The results showed that： （1） In patients with an acute exacerbation of asthma, 48 （40%） patients had positive sputum bacterial culture and 72 （60%） had negative sputum bacterial culture. （2） The levels of FeNO in patients with acute exacerbation of asthma were significantly higher than in those with no acute exacerbation state （63.8±24.6 vs. 19±6.5 ppb, P〈0.05）. There was no significant difference in FeNO between group A and group B （P〉0.05）. （3） The levels of PCT and CRP in group A patients with an acute exacerbation of asthma were significantly higher （P〈0.05） than in group B （for PCT： 27.46±9.32 vs. 7.85±3.52 ng/mL; for CRP： 51.25±11.46 vs. 17.11±5.87 mg/L, respectively）. When they had returned to stable clinical state, the levels of PCT and CRP in group A were decreased significantly （P〈0.05）, and those in group B had no significant change （P〉0.05） when compared with the exacerbation group. There were no significant differences in the levels of PCT and CRP between the two groups in non-acute exacerbation state （/9〉0.05）. These results suggest that the increase in FeNO indicates the acute exacerbation of asthma, and the elevation of serum PCT and CRP levels may be associated with bacterial infection.
文摘Background: Some patients present clinical features of both asthma and chronic obstructive pulmonary disease (COPD), which has led to the recent proposal of asthma-COPD overlap (ACO) as a diagnosis. Fractional exhaled nitric oxide (FeNO) is a candidate biomarker to diagnose ACO. We assessed the effect of an add-on treatment with budesonide/formoterol (BUD/FM) combination in patients with ACO, which was diagnosed by FeNO. Methods: This was a prospective, single-arm, open-label, before and after comparison study. Subjects included 83 patients with COPD who attended outpatient clinics for routine checkups at Shizuoka General Hospital between June and November 2016. All patients fulfilled the GOLD definition of COPD and were receiving long-acting muscarinic antagonist (LAMA) or LAMA/long-acting β2 agonist (LABA) combinations. After an 8-week run-in period, BUD/FM was added to the patients with FeNO levels of ≥35 ppb, defined as having ACO. For patients receiving LAMA/LABA, BUD/FM was added after the discontinuation of LABA. The modified British Medical Research Council (mMRC) score, COPD assessment test (CAT) score, spirometric indices, forced oscillation parameters, and FeNO were assessed before and after 8 weeks of BUD/ FM add-on treatment. Results: Twenty-four patients (28.9%) had FeNO levels ≥ 35 ppb, and 17 patients completed the study (mean age: 73 years and GOLD I/II/III/IV, 5/10/1/1). The mean CAT scores significantly improved (9.2 to 5.4, p = 0.015) and 10 patients (58.8%) showed ≥2 points improvement, a minimal clinically important difference. The mean FeNO levels significantly decreased from 63.0 to 34.3 ppb (p Conclusions: FeNO-guided treatment with BUD/FM improves symptoms in patients with ACO.
文摘Introduction:Heart failure is a major public health issue with a prevalence of about 26 million people worldwide.Reduced nitric oxide availability,lower soluble guanylate cyclase(sGC)activity,and decreased cyclic guanosine monophosphate(cGMP)production are the causes of HF's development.Vericiguat prescribed under the brand name Verquvo was approved by U.S.Food and Drug Administration(FDA)in January 2021.It is a novel agent and the first sGC stimulator which helps to treat patients suffering from heart failure with reduced ejection fraction(HFrEF).Objective:The mechanism of action(cGMP pathway)of vericiguat,its clinical trials,its use in the treatment of heart failure,and its possible future aspects in therapeutic recommendations are all covered in this review.It will also raise awareness amongst healthcare professionals about the pharmacokinetic and pharmacodynamic parameters,dosing,administration,and drug-related problems of this new drug.Methods:Various databases for drug review were used in this review like PubMed,Medline,Google scholar,Drug bank,U.s.FDA,Medscape,and European society of cardiology guidelines.A total of 58 articles were screened out of which 39 articles were included in this review.Results:This review discusses vericiguat's mechanism of action(cGMP pathway),clinical studies,application in the treatment of heart failure,and potential future considerations in therapeutic recommendations.It will also educate healthcare professionals about the new drug's pharmacokinetics and pharmacodynamics,dose,administration,and drug-related problems.Conclusion:After hospitalization for HFrEF,the 5-year survival rate is just 25%,and disease morbidity and death are stil significant.As adjunctive therapy for individuals with heart failure and a low ejection fraction,vericiguat has a moderate level of effectiveness.Vericiguat's efficacy as an adjunct therapy to different drugs used to cure HF has to be further investigated.Vericiguat's safety and dosage in patients who have severe renal or hepatic illness need to be studied further.
基金supported by Rashtrsant Tukadoji Maharaj Memorial Fellowship from Rashtrasant Tukadoji Maharaj Nagpur University。
文摘Objective:To examine the effects of hydroalcoholic extract and fractions of Hordeum vulgare Linn.(H.vulgare,Da Mai)on streptozotocin(STZ)-induced diabetic nephropathy in Sprague-Dawley rat models.Methods:The study involved preliminary phytochemical screening of extract and fractions,estimation of secondary metabolites,chromatographic studies using high performance liquid chromatography(HPLC),antioxidant potential using 1,1-diphenyl-2-picrylhydrazyl(DPPH),nitric oxide radical scavenging and reducing power methods along with the determination of potential against diabetic nephropathy in STZ-induced rat models.Results:The phytochemical evaluation of the hydroalcoholic extract of H.vulgare and fractions revealed the presence of various phytoconstituents such as alkaloids,saponins,tannins,flavonoids,and glycosides.The chromatographic analysis indicated the peak complementing marker compound epicatechin and significant antioxidant activity in the extract and aqueous fraction.STZ-induced rats showed abnormal levels of serum albumin,creatinine,total cholesterol,blood urea nitrogen(BUN),and triglycerides,and urine albumin and creatinine,which returned to normal after 8 weeks of treatment with hydroalcoholic extract(400 mg/kg)and aqueous fraction(50 mg/kg)of H.vulgare.Conclusion:Hydroalcoholic extract(400 mg/kg)and aqueous fraction(50 mg/kg)of H.vulgare have significant antioxidant potential and positive effects on diabetic nephropathy.The fractionation and optimization increase the concentration of polyphenols in aqueous extract,causing a decrease in the dose required for effects against diabetic nephropathy.
