• Natural Product Sciences
• /
• 제27권2호
• /
• pp.128-133
• /
• 2021

The Coumarin (1,2-benzopyrone) is the main secondary metabolite of Mikania laevigata Sch. Beep ex Baker and Mikania glomerata Spreng., which are popularly known as guaco. These plants have been used mainly in traditional medicine in the treatment of respiratory diseases because their bronchodilator effect. However, there are around 200 species of Mikania, which are quite similar in appearance. From these, only M. leavigata and M. glomerata have high concentrations of coumarins. In this line, the falsification of products Mikania based has been frequent. In this sense, this work demonstrated the application of the easy, fast, e not destructive method based in Nuclear Magnetic Resonance in quantitative mode (qNMR) for the determination of coumarin in both commercial and homemade guaco products. Thus, in the first step the compounds were extract from guaco leaves and syrups using chloroform (CHCl₃), with or without ultrasound. About the method, was linear with a R² = 0.9947 for 1,2-benzopyrone, with detection and quantification limits with were 0.11 and 0.36 mg mL^-1 respectively. In the same line, the method was safe with RSD <0.3% and with recovery ranging from 93-101%. To confirm the applicability of the method, in the last step was applied to 10 real samples (6 from leaves and 4 from syrups). The content of the coumarin in the leaf extract ranged from 0.62 to 1.30 mg mL^-1. For syrups I, II and IV, the content of coumarin was in accordance with the manufacturers. However, for de Syrup III, the concentration was 155% higher. In summary, the qNMR is a rapid method with minimal sample preparation that can be used to quantify coumarin in home-made plant extracts as well as in commercial samples as syrup for instance. This method is applicable for quality control of different plants-based products.

• Tuberculosis and Respiratory Diseases
• /
• 제85권1호
• /
• pp.18-24
• /
• 2022

Background: Neutrophilic asthma (NeuA) is usually resistant to corticosteroids. Tiotropium bromide (TIO) is a bronchodilator that is used as an add-on therapy to inhaled corticosteroid and long-acting β2 agonist in asthma treatment. However, the role of TIO in NeuA is not fully known. Thus, the aim of this study was to evaluate the effect of TIO on NeuA compared to that of corticosteroids. Methods: C57BL/6 female mice were sensitized with ovalbumin and lipopolysaccharide to induce neutrophilic inflammation. Dexamethasone (DEX) was administered on days 14, 17, 20, and 23. TIO was inhaled on days 21, 21, and 23. On day 24, mice were sacrificed. Airway hyper-responsiveness, levels of cytokines in bronchoalveolar lavage (BAL) and lung homogenates, and lung tissue histopathology were compared between the two groups. Results: Neutrophil counts, T helper 2 cells (T_H2)/T_H17 cytokines, and pro-inflammatory cytokine in BAL fluids were elevated in the NeuA group. TIO group showed lower total cells, neutrophil counts, and eosinophil counts in BAL fluids than the DEX group (p<0.001, p<0.05, and p<0.001, respectively). Airway resistance was attenuated in the TIO group but elevated in the NeuA group (p<0.001). Total protein, interleukin (IL)-5, and IL-17A levels in BAL fluids were lower in the TIO group than in the NeuA group (all p<0.05). Conclusion: TIO showed more potent effects than DEX in improving airway inflammation and attenuating airway resistance in NeuA.

• Tuberculosis and Respiratory Diseases
• /
• 제86권1호
• /
• pp.33-46
• /
• 2023

Background: Umeclidinium/vilanterol (UMEC/VI; ANORO ELLIPTA, GSK) is a commonly used dual bronchodilator. This study evaluated the safety and effectiveness of UMEC/VI in Korean patients with chronic obstructive pulmonary disease (COPD) over a 6-year period. Methods: This was an open-label, multicentre, observational, post-marketing surveillance study. A total of 3,375 patients were enrolled consecutively in 52 hospitals, by 53 physicians, between July 2014 and July 2020. Patients who were administered UMEC/VI (fixed-dose 62.5 ㎍/25 ㎍) at least once and were monitored for safety and effectiveness were included in the analysis. Incidence and severity of adverse events (AEs) reported after administrating at least one dose of UMEC/VI were monitored, including unexpected adverse events (UAEs) and adverse drug reactions (ADRs). Effectiveness of UMEC/VI after 24 weeks of administration was also assessed using physician's evaluation (effective, ineffective/no change, worsening, indeterminable) and lung function improvement. Results: Of 3,375 patients, 3,086 were included in the safety assessment group (mean age±standard deviation: 69.76±8.80 years; 85.9% male [n=2,652]; 73.1% aged ≥65 years [n=2,255]). The overall incidence of AEs was 28.8% (n=890), of which 2.2% (n=67) were ADRs. Serious AEs and UAEs were reported in 181 (5.9%) and 665 (21.6%) patients, respectively, and two patients (<0.1%) reported unexpected severe ADR. Of the 903/3,086 patients analysed for effectiveness, most (82.8%, n=748) showed overall disease improvement after UMEC/VI treatment. Conclusion: This study confirmed UMEC/VI administered to Korean patients according to the prescribing information was well-tolerated and can be considered an effective option for COPD treatment.

• Tuberculosis and Respiratory Diseases
• /
• 제86권3호
• /
• pp.158-165
• /
• 2023

Asthma is a chronic inflammatory airway disease that is characterized by variable airflow obstruction. The Korean Asthma Study Group of the Korean Academy of Tuberculosis and Respiratory Diseases has recently updated the Korean Asthma Guideline. This review summarizes the updated Korean Asthma Guideline. Asthma prevalence is increasing worldwide, and in Korea. Variable airflow obstruction can be confirmed by bronchodilator response or other tests, and should be established prior to the controller medication. A low-dose inhaled corticosteroid-formoterol is used to alleviate symptoms in all treatment step, and it can be used as a controller as well as reliever in steps 3-5. This approach is preferred, because it reduces the risk of severe exacerbations, compared to the use of short-acting β2-agonist as reliever. In severe asthma, phenotype/endotype based on the underlying inflammation should be evaluated. For type 2 severe asthma, the biologics should be considered.

• Tuberculosis and Respiratory Diseases
• /
• 제47권5호
• /
• pp.629-641
• /
• 1999

연구배경: 스테로이드는 천식의 장기적인 치료에 사용하는 약물로 치료효과는 기도에 대한 항염증작용을 통해 이루어지는 것으로 알려져 있다. fluticasone propionate(FP)는 치료효과가 크고 주로 폐에 국소적으로 작용하는 약물로서 beclomethasone dipropionate(BDP)에 비해 2배 정도의 역가를 가지고 있다고 알려져 있다. 이 연구를 통해 FP와 BDP의 치료효과를 비교하고자 하였다. 방 법: 50명의 천식환자를 대상으로 하여 연구를 진행하였다. 환자에게 무작위적으로 FP 혹은 BDP를 4주 동안 투여하였다. 처음 2주간의 Run-in period에는 $\beta_2$-기관지확장제반을 투여하였고 그 후 무작위적으로 FP 또는 BDP를 투여하였다. FP는 diskhaler를 이용하여 하루 2 회 $250{\mu}g$씩 총 $500{\mu}g$을 투여하였고, BDP는 reservoir dry-power device-RPD 를 이용하여 하루 2회 $400{\mu}g$씩 총 $800{\mu}g$을 투여하였다. Run-in period 및 치료 기간 종에 매일 아침과 저녁의 최고호기유량과 주간과 야간의 천식증상점수, 주간과 야간의 응급 & 기관지확장제 사용횟수 등을 측정하였다. $FEV_{1.0}$과 FVC는 치료시작전과 치료 후 2주 간격으로 3 회 측정하였다. 결 과: FP를 투여한 환자 중 3 명과 BDP를 투여한 환자 중 7명이 탈락되어, 총 40명의 천식환자를 대상으로 결과를 분석하였다. FP 및 BDP 투여 후에 아침과 저녁의 최고호기유량이 유의하게 증가하고, 최고호기유량의 일중변이는 유의하게 감소하였다. 폐기능 검사 결과 $FEV_{1.0}$은 FP를 투여한 군에서 증가하고, FVC는 양 군에서 모두 증가하지 않았다. 주간 및 야간의 천식증상 점수가 호전되고, 응급 $\beta_2$-기관지확장제 사용횟수는 유의하게 감소하였다. 그러나 두 군 사이의 치료효과에는 유의한 차이가 없었다. 최고호기유량의 증가, 일중변이의 감소, 증상의 호전 및 응급 $\beta_2$-기관지확장제 사용횟수의 감소는 FP를 투여한 군에서 더 빨리 나타났다. 결 론: 천식환자에게 매일 FP $500{\mu}g$과 BDP $800{\mu}g$을 투여하였을 때, 두 군간의 치료효과는 유사하였다. 효과는 FP를 투여한 군에서 더 빨리 나타났고 부작용으로 치료를 중단한 경우는 없었다.

• Tuberculosis and Respiratory Diseases
• /
• 제72권1호
• /
• pp.8-14
• /
• 2012

Background: Although airway obstruction in chronic obstructive pulmonary disease (COPD) is due to pathologic processes in both the airways and the lung parenchyma, the contribution of these processes, as well as other factors, have not yet been evaluated quantitatively. We therefore quantitatively evaluated the factors contributing to airflow limitation in patients with COPD. Methods: The 213 COPD patients were aged >45 years, had smoked >10 pack-years of cigarettes, and had a post-bronchodilator forced expiratory volume in one second ($FEV_1$)/forced vital capacity (FVC) <0.7. All patients were evaluated by medical interviews, physical examination, spirometry, bronchodilator reversibility tests, lung volume, and 6-minute walk tests. In addition, volumetric computed tomography (CT) was performed to evaluate airway wall thickness, emphysema severity, and mean lung density ratio at full expiration and inspiration. Multiple linear regression analysis was performed to identify the variables independently associated with $FEV_1$ - the index of the severity of airflow limitation. Results: Multiple linear regression analysis showed that CT measurements of mean lung density ratio (standardized coefficient ${\beta}$=-0.46; p<0.001), emphysema severity (volume fraction of the lung less than -950 HU at full inspiration; ${\beta}$=-0.24; p<0.001), and airway wall thickness (mean wall area %; ${\beta}$=-0.19, p=0.001), as well as current smoking status (${\beta}$=-0.14; p=0.009) were independent contributors to $FEV_1$. Conclusion: Mean lung density ratio, emphysema severity, and airway wall thickness evaluated by volumetric CT and smoking status could independently contribute to the severity of airflow limitation in patients with COPD.

• Tuberculosis and Respiratory Diseases
• /
• 제56권6호
• /
• pp.670-676
• /
• 2004

유독성 물질의 흡인은 화학성 폐렴을 유발하며 이는 직업성 폐질환의 한 원인이다. 질산은 흔한 대기 오염물질의 한가지이고 작업장에서 사용되는 강력한 산화제로 직업적 노출의 가능성이 있다. 52세 남자 환자가 질산을 이용한 에어컨 도관 세척작업 중에 발생한 증기의 흡입 후 기침, 호흡곤란을 호소하며 병원에 방문하였다. 내원 당시 호흡수 분당 26회였고, 산소 투여 없이 시행한 동맥혈 가스분석에서 $PaO_2$ 42.6 mmHg, $SaO_2$ 80.2%로 저산소혈증이 나타났으며, 흉부 방사선 검사에서 양측폐야에 미만성 폐침윤과 젖빛유리 음영이 나타났다. 환자는 전신적인 스테로이드를 사용하지 않고, 보존적인 치료만으로 입원 2일째부터 임상적인 증상과 방사선 사진의 호전이 있었고 퇴원 후 폐기능의 손상 없이 호전되었기에 이를 보고하는 바이다.

• Clinical and Experimental Pediatrics
• /
• 제63권3호
• /
• pp.104-109
• /
• 2020

Background: It is challenging to diagnose asthma in preschool children. The asthma predictive index (API) has been used to predict asthma and decide whether to initiate treatment in preschool children. Purpose: This study aimed to investigate the association between questionnaire-based current asthma with API, pulmonary function, airway hyperreactivity (AHR), fractional expiratory nitric oxide (FeNO), and atopic sensitization in preschool children. Methods: We performed a population-based cross-sectional study in 916 preschool children aged 4-6 years. We defined current asthma as the presence of both physician-diagnosed asthma and at least one wheezing episode within the previous 12 months using a modified International Study of Asthma and Allergies in Childhood questionnaire. Clinical and laboratory parameters were compared between groups according to the presence of current asthma. Results: The prevalence of current asthma was 3.9% in the study population. Children with current asthma showed a higher rate of positive bronchodilator response and loose and stringent API scores than children without current asthma. The stringent API was associated with current asthma with 72.2% sensitivity and 82.0% specificity. The diagnostic accuracy of the stringent API for current asthma was 0.771. However, no intergroup differences in spirometry results, methacholine provocation test results, FeNO level, or atopic sensitization rate were observed. Conclusion: The questionnaire-based diagnosis of current asthma is associated with API, but not with spirometry, AHR, FeNO, or atopic sensitization in preschool children.

• 한국임상수의학회지
• /
• 제29권6호
• /
• pp.483-487
• /
• 2012

심장에 발생하는 원발성 그리고 전이성 종양은 개에서는 흔치 않다. 우리는 본 연구에서 심장초음파적 진단을 이용하여 요크셔테리어 2마리에서 발생한 심장내 종괴를 확인하였다. 첫째 증례에서의 종괴는 상행 대동맥과 폐동맥 사이에 위치하고 있었으며, 중증도의 대동맥 역류와 좌심실의 확장을 유발하고 있었다. 이 증례의 환자등급은 ISACHC II 등급의 심부전으로 분류되었다. 환자에 대한 심장처방으로는 furosemide, enalapril, pimobendan 그리고 경구적인 화학요법으로는 lomustine가 처방되었다. 둘째 증례에서의 종괴는 좌심방의 2/3를 차지하고 있었으며, 좌심방의 확연한 확장과 심각한 이첨판 역류 (~5 m/s) 를 유발하고 있었으나, 환자의 심부전 등급은 ISACHC Ib 등급으로 심각한 울혈성 심부전은 나타나지 않았다. 종괴의 성상은 cardiac myxoma로 추정되었으나, 조직생검검사는 보호자의 거절로 인하여 수행되지 않았다. 환자에 대한 심장처방으로는 ramipril, clopidogrel 그리고 기관지 확장제는 aminophylline이 처방되었다. 본 증례의 두 환자들은 여전히 생존해 있으며, 정기적인 검진을 받고 있다.

• Journal of Pharmaceutical Investigation
• /
• 제27권4호
• /
• pp.303-311
• /
• 1997

Proliposomal patch of clenbuterol, ${\beta}_2-agonist$ bronchodilator, was prepared and its feasibility as a novel transdermal drug delivery system was examined. Proliposomal granules containing clenbuterol was prepared by a standard method using sorbitol and lecithin with (Rx 2) or without cholesterol (Rx 1). The porous structure of sorbitol in the proliposomes was maintained allowing tree flowability of the granules. Following contact with water, the granules were converted probably to liposomes almost completely within several minutes. It indicates that proliposomes may be hydrated, when they are applied on the skin under occlusive condition in vivo, by the sweat to form liposomes. Clenbuterol release from Rx 1 and Rx 2 proliposomes to pH 7.4 isotonic phospate buffer (PBS) across cellulose membrane (mol. wt. cut-off of 12000-14000) was retarded significantly compared with that from the mixture of clenbuterol powder and blank proliposomes. Interestingly, proliposomes prepared with lecithin and cholesterol (i.e., Rx 2 proliposomes) showed much more retarded release of clenbuterol than proliposomes prepared only with lecithin (i.e.. Rx 1 proliposomes), indicating that clenbuterol release from proliposomes can be controlled by the addition of cholesterol to the proliposomes. Proliposomal patches were prepared using PVC film as an occlusive backing sheet, two sides adhesive tape (urethane, 1.45 mm thickness) as a reservoir for proliposome granules and Millipore MF-membrane (0.45 mm pore size) as a drug release-controlling membrane. Rx 1 or Rx 2 proliposomes containing 4.6 mg of clenbuterol were loaded into the reservoir of the patch. Clenbuterol release from the patches to pH 7.4 PBS was determined using USP paddle (50 rpm)-over-disc release method. Clenbuterol release from the proliposomal patches was much more retarded even than from a matrix type clenbuterol patch (Boehringer Ingelheim ltd). Being consistent with clenbuterol release from the proliposomal granules, the release from the patches was highly dependent on the presence of cholesterol in the proliposomes : Patches containing Rx 2 proliposomes showed several fold slower drug release than patches containing Rx 1 proliposomes. When the patch containing Rx 1 proliposomes was applied on to the back of a hair-removed rat, clenbuterol concentration in the rat blood was maintained during 6-72 hrs. Transdermal absorption of clenbuterol from the patch was accelerated when the patch was prehydrated with 50 ml of pH 7.4 PBS before topical application. Above results indicate that sustained transdermal delivery of clenbuterol is feasible using proliposomal patches if the cholesterol content and pore size of the release rate-controlling membrane of patches, for example, are appropriately controlled.