Carvedilol is an antihypertensive and antianginal compound that combines nonselective beta-adrenoceptor blocking and vasodilation properties and is devoid of intrinsic sympathomimetic activity. The purpose of the present study was to evaluate the bioequivalence of two carvedilol tablets, $Dilatrend^{TM}$ (Chong Kun Dang Pharmaceutical Co., Ltd.) and $Carvelol^{TM}$ (Dae Won Pharmaceutical Co., Ltd.), according to the prior and revised guidelines of Korea Food and Drug Administration (KFDA). The carvedilol release from the two carvedilol tablets in vitro was tested using KP VII Apparatus II method with various different kinds of dissolution media (pH 1.2, 4.0, 6.8 buffer solution, water and blend of PSB80 into water). Eighteen normal male volunteers, $24.22{\pm}1.86$ years in age and $64.81{\pm}4.56\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 25 mg of carvedilol was orally administered, blood was taken at predetermined time intervals and the concentrations of carvedilol in serum were determined using HPLC method with fluorescence detector. The dissolution profiles of two carvedilol tablets were very similar at all dissolution media. Besides, the pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using non-transformed and logarithmically transformed $AUC_t$ and $C_{max}$. The results showed that the differences in $AUC_t$, $C_{max}$ and $T_{max}$ between two tablets based on the $Dilatrend^{TM}$ were 2.23%, -2.00% and 0.00%, respectively. Minimum detectable differences $({\Delta})$ at ${\alpha}=0.05$ and $1-{\beta}=0.8$ were less than 20% (e.g., 13.55% and 17.61% for $AUC_t$ and $C_{max}$, respectively). The powers $(l-{\beta})$ at ${\alpha}=0.05$, ${\Delta}=0.2$ for $AUC_t$ and $C_{max}$ were 98.08% and 88.81%, respectively. The 90% confidence intervals were within ${\pm}20%$ (e.g., $-5.69{\sim}10.16$ and $-12.30{\sim}8.30$ for $AUC_t$ and $C_{max}$, respectively). There were no sequence effect between two tablets in logarithmically transformed $AUC_t$ and $C_{max}$. The 90% confidence intervals using logarithmically transformed were within the acceptance range of log(0.8) to log(1.25) (e.g., $0.95{\sim}1.11$ and $0.89{\sim}1.09$ for $AUC_t$ and $C_{max}$, respectively). Two parameters met the criteria of prior and revised KFDA guideline for bioequivalence, indicating that $Carvelol^{TM}$ tablet is bioequivalent to $Dilatrend^{TM}$ tablet.
Background : Chronic cough, defined as a cough persisting for three weeks or longer, is a common symptom for which outpatient care is sought. The most common etiologies of chronic cough are postnasal drip, asthma, and gastroesophageal reflux. Methacholine challenge is a useful diagnostic study in the evaulation of chronic cough, particularly useful in chronic cough patients with asthmatic symptom. Patients with chronic cough may have dysfunction of bronchial and extrathoracic airways. To evaluate if dysfunction of the bronchial and extrathoracic airways causes chronic cough, we assessed bronchial (BHR) and extrathoracic airway (EAHR) responsiveness to inhaled methacholine in patients with chronic cough. Method : 111 patients with chronic cough were enrolled in our study. Enrolled patients had no recorded diagnosis of asthma, bronchopulmonary disease, hypertension, heart disease or systemic disease and no current treatment with bronchodilator or corticosteroid. Enrolled patients consisted of 46 patients with cough alone, 24 patients with wheeze, 22 patients with dyspnea, 19 patients with wheeze and dyspnea. The inhaled methacholine concentrations causing a 20% fall in forced expiratory volume in 1s($PC_{20}FEV_1$) and 25% fall in maximal mid-inspiratory flow ($PC_{25}MIF_{50}$) were used as bronchial and extra thoracic hyperresponsiveness. Results : There were four response patterns to methacholine challenge study : BHR in 27 patients, EAHR in 16 patients, combined BHR and EAHR in 8 patients, and no hyperresponsiveness in 60 patients. In patients with cough alone, there were BHR in 3 patients, EAHR in 9 patients, and combined BHR and EAHR in 2 patients. In patients with wheeze and/or dyspnea, there were BHR in 24 patients, EAHR in 7 patients, and BHR and EAHR in 6 patients. Compared with patients with wheeze and/or dyspnea, patients with cough alone had more common EAHR than BHR. In patients with wheeze and/or dyspnea, BHR was more common than EAHR. Conclusion : These results show that among patients with hyperresponsiveness to methacholine, those with dyspnea and/or wheezing had mainly bronchial hyperresponsiveness, whereas those with chronic cough alone had mainly extrathoracic airway hyperresponsiveness.
Experimental transportations of the olive flounder (Paralichthys olivaceus) seedlings (body weight $2.1\pm0.39g$) with polyethylene vinyl bag were Performed to study the change of dissolved oxygen (DO) during transportation, survival rate and feeding activity of seedlings after transportation. The distance and time required for the transportations were 272 km and 11 hours, respectively. DO was rapidly decreased within 3 hours (P<0.05) during the transportation of seedlings of 40 fish in 10l of sea water at $15.6\~17.8^{\circ}C$ of initial water temperature with 5 ml/l of initial DO. The decreasing tendency of DO (Y) according to elapsed time (X) was expressed an equation of $Y\;=\;2.7444X^{-0.4780}$ (r=0.8071). Feeding activity of the seedlings after transportation supplemented with oxygen and icepack besides above transport conditions was significantly higher than that of fish supplemented with icepack only (P<0.05). It was desirable to starve the seedlings for 36 hours before transportation. Survival rate of seedlings was greatly reduced, when the dissolved oxygen concentration was lowered below the range of $0.7\~0.94ml/l$ just after transportation.
Parcina, Marijo;Brune, Maik;Kaese, Vareska;Zorn, Markus;Spiegel, Rainer;Vojvoda, Valerija;Fleming, Thomas;Rudofsky, Gottfried;Nawroth, Peter Paul
Nutrition Research and Practice
/
v.9
no.2
/
pp.165-173
/
2015
BACKGROUND/OBJECTIVES: This study addressed the question whether the composition of supposedly 'healthy' or 'unhealthy' dietary regimes has a calorie-independent short-term effect on biomarkers of metabolic stress and vascular risk in healthy individuals. SUBJECTS/METHODS: Healthy male volunteers (age $29.5{\pm}5.9years$, n = 39) were given a standardized baseline diet for two weeks before randomization into three groups of different dietary regimes: fast food, Mediterranean and German cooking style. Importantly, the amount of calories consumed per day was identical in all three groups. Blood samples were analyzed for biomarkers of cardiovascular risk and metabolic stress after two weeks of the baseline diet and after two weeks of the assigned dietary regime. RESULTS: No dietary intervention affected the metabolic or cardiovascular risk profile when compared in-between groups or compared to baseline. Subjects applied to the Mediterranean diet showed a statistically significant increase of uric acid compared to baseline and compared to the German diet group. Plasma concentrations of urea were significantly higher in both the fast food group and the Mediterranean group, when compared to baseline and compared to the German diet group. No significant differences were detected for the levels of vitamins, trace elements or metabolic stress markers (8-hydroxy-2-deoxyguanosine, malondialdehyde and methylglyoxal, a potent glycating agent). Established parameters of vascular risk (e.g. LDL-cholesterol, lipoprotein(a), homocysteine) were not significantly changed in-between groups or compared to baseline during the intervention period. CONCLUSIONS: The calorie-controlled dietary intervention caused neither protective nor harmful short-term effects regarding established biomarkers of vascular or metabolic risk. When avoiding the noxious effects of overfeeding, healthy individuals can possess the metabolic capacity to compensate for a potentially disadvantageous composition of a certain diet.
Four hundred and fifty tilapias ($6.77{\pm}0.23$ g) were assigned randomly to six groups to evaluate the feasibility of the tested antibacterial peptides (ABPs) and oligosaccharides as substitutes for antibiotics. The control group was fed with a commercial tilapia diet; other five groups were fed with the same commercial diet supplemented with konjac glucomannan (KGLM), cluster bean galactomannan (CBGAM), and three animal intestinal ABPs derived from chicken, pig and rabbit at 100 mg/kg respectively. After 21 days of feeding, growth, disease resistance, and in vivo anti-adherence were determined. Furthermore, the inhibitory effect of tested agents on adhesion of Aeromonas veronii biovar sobria (A.vbs) strain BJCP-5 to tilapia enteric epithelia in vitro was assessed by cell-ELISA system. As a result, the tested agents supplemented at 100 mg/kg show significant benefit to tilapia growth and disease resistance (p<0.05), and the benefit may be correlated with their interfering in the contact of bacteria with host mucosal surface. Although none of the tested agents did inhibit the growth of BJCP-5 in tryptic soy broth at $100{\mu}g/ml$, all of them did inhibit the adhesion of A.vbs to tilapia enteric epithelia in vivo and in vitro. In vitro mimic assays show that three ABPs at low concentrations of $25{\mu}g/ml$ and $2.5{\mu}g/ml$ have the reciprocal dose-dependent anti-adherence effect. The inhibition of ABPs may be correlated with a cation bridging and/or receptor-ligand binding, but not with hydrophobicity. The KGLM and CBGAM inhibited the adherence of BJCP-5 to tilapia enteric epithelia with dose-dependent manner in vitro, and this may be through altering bacterial hydrophobicity and interfering with receptor-ligand binding. Our results indicate that the anti-adherence of the tested ABPs and oligosaccharides may be one of the mechanisms in promoting tilapia growth and resistance to A.vbs.
Objective: The objective of this study was to investigate effects of mixed organic acids (MOA) on nutrient digestibility, volatile fatty acids composition and intestinal microbiota in growing-finishing pigs fed high wheat bran diet. Methods: Six crossbred barrows ($Duroc{\times}Landrace{\times}Yorkshire$), with an average body weight $78.8{\pm}4.21kg$, fitted with T-cannulas at the distal ileum, were allotted to a double $3{\times}3$ Latin square design with 3 periods and 3 diets. Each period consisted of a 5-d adjustment period followed by a 2-d total collection of feces and then a 2-d collection of ileal digesta. The dietary treatments included a corn-soybean-wheat bran basal diet (CTR), mixed organic acid 1 diet (MOA1; CTR+3,000 mg/kg OA1), mixed organic acid 2 diet (MOA2; CTR+2,000 mg/kg OA2). Results: Pigs fed MOA (MOA1 or MOA2) showed improved (p<0.05) apparent total tract digestibility (ATTD) of gross energy, dry matter and organic matter, and pigs fed MOA2 had increased (p<0.05) ATTD of neutral detergent fiber compared to CTR. Dietary MOA supplementation decreased (p<0.05) pH value, and improved (p<0.01) concentrations of lactic acid and total volatile fatty acids (TVFA) in ileum compared to CTR. Pigs fed MOA showed higher (p<0.05) concentration of acetic acid, and lower (p<0.05) content of formic acid in feces compared to CTR. Pigs fed MOA1 had increased (p<0.05) concentration of TVFA and butyric acid in feces. Pigs fed MOA1 showed higher concentration of Lactobacillus and lower concentration of Escherichia in feces compared to CTR. Conclusion: Dietary supplementation of MOA 1 or 2 could improve nutrients digestibility, TVFA concentration and intestinal flora in growing-finishing pigs fed high fiber diet.
Park, Youngcheon;Kim, Kang-in;Lee, Jeongho;Lee, Dong Hwan
Journal of The Korean Society of Inherited Metabolic disease
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v.16
no.2
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pp.86-92
/
2016
Purpose: The $BH_4$ loading test is an important test that distinguishes PKU from $BH_4$ deficiency and identifies the $BH_4$ reactivity of PKU patients. Phenylalanine and $BH_4$ loading tests are useful methods that can shorten the length of hospital stay while improving patients' convenience. However, sufficient research on the dose of phenylalanine loading and $BH_4$ administration time after the loading has not been carried out. The present study investigates the effectiveness of the existing phenylalanine loading method by analyzing the medical records of six patients who underwent the $BH_4$ loading test after taking 100 mg/kg of phenylalanine patients. Methods: The medical records of six patients who underwent the $BH_4$ load test after taking 100 mg/kg of phenylalanine were examined out of 207 patients who were followed up in the Genetic Metabolic Clinic in Soonchunhyang University Hospital. All of the six patients had a low phenylalanine diet. First, they were taking 100 mg/kg of phenylalanine. 3 hours later, 20 mg/kg of $BH_4$ were loaded. The phenylalanine levels in the blood were continuously measured at 1, 2, 4, 6, 8, 12, and 24 hours by setting the time the $BH_4$ was loaded as the basal. Results: The average of the highest phenylalanine concentrations of six patients was $20.0{\pm}11.70mg/dL$. One reached the highest concentration seven hours after taking phenylalanine; another reached it five hours after that, and the remaining three reached it four hours after that. Only one patient reached the highest concentration within three hours. The phenylalanine levels of four out of six patients (66%) rose above $400{\mu}mol/L$ after being loaded with phenylalanine. The phenylalanine levels of the remaining two were 6.1 mg/dL ($366{\mu}mol/L$) and 5 mg/dL ($300{\mu}mol/L$), respectively. Conclusion: One of six patients (16%) reached the highest concentration three hours after taking 100 mg/kg of phenylalanine and four patients (66%) reached $400{\mu}mol/L$ or higher phenylalanine levels. There were patients whose phenylalanine levels did not rise above $400{\mu}mol/L$ using a commonly known test method; moreover, this method had the disadvantage of reaching the highest concentration after more than three hours. Therefore, it is considered that taking 200 mg/kg or more of phenylalanine and performing $BH_4$ loading four to six hours after taking phenylalanine are helpful in proper diagnosis.
Due to the development of industry, interest in air pollutants has increased. Air pollutants have affected various fields such as environmental pollution and global warming. Among them, environmental diseases are one of the fields affected by air pollutants. Air pollutants can affect the human body's skin or respiratory tract due to their small molecular size. As a result, various studies on air pollutants and environmental diseases have been conducted. Asthma, part of an environmental disease, can be life-threatening if symptoms worsen and cause asthma attacks, and in the case of adult asthma, it is difficult to cure once it occurs. Factors that worsen asthma include particulate matter and air pollution. Asthma is an increasing prevalence worldwide. In this paper, we study how air pollutants correlate with the number of emergency room admissions in asthma patients and predict the number of future asthma emergency patients using highly correlated air pollutants. Air pollutants used concentrations of five pollutants: sulfur dioxide(SO2), carbon monoxide(CO), ozone(O3), nitrogen dioxide(NO2), and fine dust(PM10), and environmental diseases used data on the number of hospitalizations of asthma patients in the emergency room. Data on the number of emergency patients of air pollutants and asthma were used for a total of 5 years from January 1, 2013 to December 31, 2017. The model made predictions using two models, Informer and LTSF-Linear, and performance indicators of MAE, MAPE, and RMSE were used to measure the performance of the model. The results were compared by making predictions for both cases including and not including the number of emergency patients. This paper presents air pollutants that improve the model's performance in predicting the number of asthma emergency patients using Informer and LTSF-Linear models.
This study was conducted to investigate the applicability of lignocellulosic fiber and coconut shell activated carbon (CSA) for the production of a particulate matter (PM)-reducing air-filter as raw materials to solve the environmental problems of non-woven fabrics. CSA had a good potential to use as a raw material of air-filter for reducing volatile organic compounds as well as noxious metals, and reduction capability of the CSA was 5 times higher than that of wood fiber. Natural adhesives formulated with proteinaceous wastes mostly were applied successfully to fabricate air-filters with the shape of fiberboard. The air-filter fabricated with the minimum target density of 200 kg/m3 and the maximum CSA-content of 40 wt% in fiberboard had a good manageable strength. However, the fiberboard filters was required to make vent-holes for improving an air-permeability of the filters. Size of the CSA particles was adjusted to greater than 2 mesh with the consideration of strength and formability of the fiberboard. Three-layers fiberboard that only wood fiber and the mixture of wood fiber and CSA were formed in the surface and middle layers, respectively, was determined to the optimal condition for the production of air-filters. In addition, traditional Korean paper handmade from mulberry trees (TKP) showed a good PM-reducing property as an air-filter. It is concluded that air-filtering set composed of fiberboard with vent-holes and TKP instead of conventional air-filters made with non-woven fabrics can be used as a filter for reducing the concentrations of PM, VOC and noxious metals existed in indoor and outdoor spaces.
Methane production during anaerobic fermentation in the rumen represents an energy loss to the host animal and induces emissions of greenhouse gases in the environment. Our study focused on comparison in methane production from growing Korean native steers fed different grain sources. Six Hanwoo steers (BW = $180.6{\pm}3.1$ kg) were fed, on a DM basis (TDN 2.80 kg), 40% timothy and 60% barley concentrate (Barley) or corn concentrate (Corn), respectively, based on the Korean Feeding Standards. Each period lasted 18 days including a 14-day adaptation and a 4-day measuring times. The steers were in the head hood chamber system (one cattle per chamber) during each measuring time to measure heat and methane production per day. Different grain sources did not affect digestibilities of dry matter, crude protein, crude fiber, crude fat, NDF, ADF and nitrogen-free extract. The mean methane concentrations per day were 202.0 and 177.1 ppm for Barley and Corn, respectively. Methane emission averaged 86.8 and 77.7 g/day for Barley and Corn, respectively. Methane emission factor by maintenance energy requirement for the growing steers fed barley based concentrate was higher than the steers fed corn based concentrate (Barley vs. Corn, 31.7 kg $CH_4\;head^{-1}\;yr^{-1}$ vs. 28.4 kg $CH_4\;head^{-1}\;yr^{-1}$). Thus, methane conversion rate was 0.065 (6.5%) and 0.055 (5.5%) for Barley and Corn, respectively.
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