Role of Intestinal Microbiota in Metabolism of Voglibose In Vitro and In Vivo

BackgroundVoglibose, an α-glucosidase inhibitor, inhibits breakdown of complex carbohydrates into simple sugar units in intestine. Studies showed that voglibose metabolism in the liver might be negligible due to its poor intestinal absorption. Numerous microorganisms live in intestine and have several roles in metabolism and detoxification of various xenobiotics. Due to the limited information, the possible metabolism of voglibose by intestinal microbiota was investigated in vitro and in vivo.MethodsFor the in vitro study, different concentrations of voglibose were incubated with intestinal contents, prepared from both vehicle- and antibiotics-treated mice, to determine the decreased amount of voglibose over time by using liquid chromatography-mass spectrometry. Similarly, in vivo pharmacodynamic effect of voglibose was determined following the administration of voglibose and starch in vehicle- and antibiotic-pretreated non-diabetic and diabetic mice, by measuring the modulatory effects of voglibose on blood glucose levels.ResultsThe in vitro results indicated that the remaining voglibose could be significantly decreased when incubated with the intestinal contents from normal mice compared to those from antibiotic-treated mice, which had less enzyme activities. The in vivo results showed that the antibiotic pretreatment resulted in reduced metabolism of voglibose. This significantly lowered blood glucose levels in antibiotic-pretreated mice compared to the control animals.ConclusionThe present results indicate that voglibose would be metabolized by the intestinal microbiota, and that this metabolism might be pharmacodynamically critical in lowering blood glucose levels in mice.

Role of Intestinal Microbiota in Metabolism of Voglibose In Vitro and In Vivo

BackgroundVoglibose, an α-glucosidase inhibitor, inhibits breakdown of complex carbohydrates into simple sugar units in intestine. Studies showed that voglibose metabolism in the liver might be negligible due to its poor intestinal absorption. Numerous microorganisms live in intestine and have several roles in metabolism and detoxification of various xenobiotics. Due to the limited information, the possible metabolism of voglibose by intestinal microbiota was investigated in vitro and in vivo.MethodsFor the in vitro study, different concentrations of voglibose were incubated with intestinal contents, prepared from both vehicle- and antibiotics-treated mice, to determine the decreased amount of voglibose over time by using liquid chromatography-mass spectrometry. Similarly, in vivo pharmacodynamic effect of voglibose was determined following the administration of voglibose and starch in vehicle- and antibiotic-pretreated non-diabetic and diabetic mice, by measuring the modulatory effects of voglibose on blood glucose levels.ResultsThe in vitro results indicated that the remaining voglibose could be significantly decreased when incubated with the intestinal contents from normal mice compared to those from antibiotic-treated mice, which had less enzyme activities. The in vivo results showed that the antibiotic pretreatment resulted in reduced metabolism of voglibose. This significantly lowered blood glucose levels in antibiotic-pretreated mice compared to the control animals.ConclusionThe present results indicate that voglibose would be metabolized by the intestinal microbiota, and that this metabolism might be pharmacodynamically critical in lowering blood glucose levels in mice.

Influence of Hospitalization Recognition and Hospital-Related Fear on the Adjustment to Hospital Life by Hospitalized School-Aged Children

PURPOSE: This study was done to identify the level of adjustment to hospital life, hospitalization recognition and hospital-related fear by school-aged children, and investigate the influence of hospitalization recognition and hospital-related fear on the hospital life of these children. METHODS: Participants were 112 three to six grade students who were hospitalized from 3 to 7 days at one of two children's hospital. Date were collected from September 2015 to March 2016. Data were analyzed using frequency, percentage, mean, standard deviation, multiple regression. RESULTS: The mean score for adjustment to hospital life was 3.43±0.40 of 5, for hospitalization recognition, 2.98±0.46 of 4 and for hospital-related fear, 1.37±0.28 of 3. Factors affecting adjustment to hospital life were hospital-related fear (β=-.28, p=.002) and hospitalization recognition (β=.27, p=.003). These factors explained 17% of the variance in adjustment to hospital life. CONCLUSION: Results indicate that adjustment to hospital life by school-aged children is not sufficient enough for them to cope with illnesses and hospitalization. Therefore, to improve adjustment to hospital life by school-aged children, nursing interventions that focus on increasing hospitalization recognition and decreasing hospital-related fear need to be developed.

Pharmacokinetic Interaction of Chrysin with Caffeine in Rats

Pharmacokinetic interaction of chrysin, a flavone present in honey, propolis and herbs, with caffeine was investigated in male Sprague-Dawley rats. Because chrysin inhibited CYP1A-selective ethoxyresorufin O-deethylase and methoxyresorufin O-demethylase activities in enriched rat liver microsomes, the pharmacokinetics of caffeine, a CYP 1A substrate, was studied following an intragastric administration with 100 mg/kg chrysin. In addition to the oral bioavailability of chrysin, its phase 2 metabolites, chrysin sulfate and chrysin glucuronide, were determined in rat plasma. As results, the pharmacokinetic parameters for caffeine and its three metabolites (i.e., paraxanthine, theobromine and theophylline) were not changed following chrysin treatment in vivo, despite of its inhibitory effect on CYP 1A in vitro. The bioavailability of chrysin was found to be almost zero, because chrysin was rapidly metabolized to its sulfate and glucuronide conjugates in rats. Taken together, it was concluded that the little interaction of chrysin with caffeine might be resulted from the rapid metabolism of chrysin to its phase 2 metabolites which would not have inhibitory effects on CYP enzymes responsible for caffeine metabolism.

Effects of Baicalin on Oral Pharmacokinetics of Caffeine in Rats

Scutellaria baicalensis is one of the most widely used herbal medicines in East Asia. Because baicalein and baicalin are major components of this herb, it is important to understand the effects of these compounds on drug metabolizing enzymes, such as cytochrome P450 (CYP), for evaluating herb-drug interaction. The effects of baicalin and baicalein on activities of ethoxyresorufin O-deethylase (EROD), methoxyresorufin O-demethylase (MROD), benzyloxyresorufin O-debenzylase (BROD), p-nitrophenol hydroxylase and erythromycin N-demethylase were assessed in rat liver microsomes in the present study. In addition, the pharmacokinetics of caffeine and its three metabolites (i.e., paraxanthine, theobromine and theophylline) in baicalin-treated rats were compared with untreated control. As results, EROD, MROD and BROD activities were inhibited by both baicalin and baicalein. However, there were no significant differences in the pharmacokinetic parameters of oral caffeine and its three metabolites between control and baicalin-treated rats. When the plasma concentration of baicalin was determined, the maximum concentration of baicalin was below the estimated IC50 values observed in vitro. In conclusion, baicalin had no effects on the pharmacokinetics of caffeine and its metabolites in vivo, following single oral administration in rats.

Protective Effects of Diallyl Sulfide against Thioacetamide-Induced Toxicity: A Possible Role of Cytochrome P450 2E1

Effects of diallyl sulfide (DAS) on thioacetamide-induced hepatotoxicity and immunotoxicity were investigated. When male Sprague-Dawley rats were treated orally with 100, 200 and 400 mg/kg of DAS in corn oil for three consecutive days, the activity of cytochrome P450 (CYP) 2E1-selective p-nitrophenol hydroxylase was dose-dependently suppressed. In addition, the activities of CYP 2B-selective benzyloxyresorufin O-debenzylase and pentoxyresorufin O-depentylase were significantly induced by the treatment with DAS. Western immunoblotting analyses also indicated the suppression of CYP 2E1 protein and/or the induction of CYP 2B protein by DAS. To investigate a possible role of metabolic activation by CYP enzymes in thioacetamide-induced hepatotoxicity, rats were pre-treated with 400 mg/kg of DAS for 3 days, followed by a single intraperitoneal treatment with 100 and 200 mg/kg of thioacetamide in saline for 24 hr. The activities of serum alanine aminotransferase and aspartate aminotransferase significantly elevated by thioacetamide were protected in DAS-pretreated animals. Likewise, the suppressed antibody response to sheep erythrocytes by thioacetamide was protected by DAS pretreatment in female BALB/c mice. Taken together, our present results indicated that thioacetamide might be activated to its toxic metabolite(s) by CYP 2E1, not by CYP 2B, in rats and mice.

Neonatal Systemic Candidiasis: Comparison of Albicans and Parapsilosis Infection

PURPOSE: Systemic Candidiasis has become an increasingly important cause of morbidity and mortality in NICU infants. Severe infections caused by non-albicans Candida species have been increasingly reported in NICU infants. The purpose of the present study was to compare relative severity, mortality rates for C albians(CA) and C parapsilosis(CP) infections in our NICU. METHODS: This study included 16 infants with systemic candidiasis who were admitted to the Neonatal Intensive Care Unit of Samsung Medical Center from Oct. 1, 1994 to Aug. 31, 1998. Systemic candidiasis was defined as candida recovery from blood with clinical symptoms and signs of infection. Systemic candidiasis was diagnosed in 16 infants, 11 with CA and 5 with CP. Retrospective analysis of the medical records of patients with systemic candidiasis was performed. The analysis included demographic findings, clinical feature, hospital course, morbidity and mortality. RESULTS: No differences were found between CA and CP for birth weight, sex, gestational age, age or weight at onset, presence of necrotizing enterocolitis, severe ROP, prior duration of antibiotics, endotracheal intubation, parenteral nutrition, steroids, or central line. Infants with CA were more likely to have antecedent thrush and perineal Candida derrnatitis(P<0.05). Infants with CP were more likely to have catheter-related infection(P<0.05) and treated with more curnulative dose of Amphotericin B and for a longer duration than those with CA(P<0.05). CONCLUSION: Though both pathogens occur in similar NICU infants and can cause severe disease, CA appears more likely to result in complications than CP.

Relationship Between Airway Inflammation Assessed by Induced Sputum and Airway Hyperresponsiveness in Asthmatic Patient / 결핵

BACKGROUND: Airway inflammation and hyperresponsiveness are recognized as major characteristics of bronchial asthma. Airway inflammation has usually been assessed by invasive methods, e.g. BAL or bronchial biopsy, but recent studies proposed induced sputum as another reliable and non- invasive tool to investigate airway inflammation in asthmatic patients. Thus, the relationship between airway inflammation assessed by induced sputum and airway hyperresponsiveness was investigated in asthmatic patient. METHOD: Airway responsiveness was determined by the concentration that caused a 20% decrease in FEV1(PC20) after inhaling incremental concentrations of methacholine. The numbers of inflammatory cells and the concentration of eosinophilic cationic protein(ECP) were assessed in induced sputum obtained by inhalation of hypertonic saline(3%). RESULT: We analyzed sputum induced in 15 stable asthmatic patients. 1. The differential cell count(%) of macrophages, neutrophils, eosinophils and lymphocytes in induced sputum were 39.1 +/- 27.0%, 29.6 +/- 21.0%, 28.8 +/- 18.8%, 1.3 +/- 3.1% respectively. 2. The mean value of baseline FEV1 (Predicted) and ECP were 76.3 +/- 30.3% and 1,101 +/- 833 micro gram/L respectively. The geometric mean value of PC20 was 0.56mg/mL. 3. The relationships between the sputum eosinophil and ECP in induced sputum, and between sputum eosinophil and degree of airway responsiveness(PC20) were found be significantly correlated (r=0.81, p<0.05 and r=-0.78, p<0.05, respectively). 4. Sputum neutrophils and PC20 were not correlated to each other (r=0.11, p=0.69) and a significant negative correlation was found between ECP and baseline FEV1(predicted) (r=-0.62, p<0.05). CONCLUSION: The results of this study suggest that an induced sputum via a inhalation of hypertonic saline is useful to determine a patient's status of airway inflammation, and airway inflammation is one of the major causal factors in the development of bronchial hyperresponsiveness in asthmatic patients.

A case of spontaneous hemothorax associated with von Recklinghausen's disease / 결핵

Spontaneous hemothorax may be developed as a complication of von Reckilnghausen's disease. It is rare but fatal. A 60 year old man with von Reckilnghausen's disease was admitted to our hospital because of left chest and shoulder pain. Radiograph of chest showed a massive left pleural effusion. Thoracentesis revealed gross blood. The peripheral angiography was done to determine the source of bleeding and its finding showed intercostal artery aneurysm in left 7th rib. No active bleeding from the aneurysm was seen. The source of the hemothorax was believed to be hemorrhage from rupture of intercostal artery aneurysm. He was inserted chest tube and treated embolization of intercostal artery aneurysm.

Autosomal Dominant Polycystic Kidney Disease Complicated by Aldosterone-producing Adrenal Adenoma / 대한신장학회잡지

We report the case of a 34-year-old woman with autosomal dominant polycystic kidney disease associated with primary aldosteronism due to left adrenal adenoma. Although autosomal dominant polycystic kidney disease could mask hypokalemia and hypertension, refractory hypertension and hypokalemia were the clues that led to this diagnosis. The diagnosis of primary hyperaldosteronism was based on the presence of hypokalemia with excessive urinary potassium excretion and characteristic hormonal changes. Under laparoscopy, left adrenalectomy was performed. After surgery, plasma renin activity, plasma aldosterone titer, and serum potassium level normalized with only partial correction of the blood pressure. This could be explained by the persisting underlying polycystic kidney disease. We conclude that extrarenal causes in a hypertensive and hypokalemic patient with polycystic kidney disease may be ruled out.

Correlation between Levels of Serum Creatinine and Erythrocytic Malondialdehyde(MDA) and Antioxidant Enzymes in Patients with Diabetic Nephropathy / 대한신장학회잡지

Oxygen free radical activity is elevated in diabetes mellitus and has been implicated in the etiology of vascular complications and diabetic nephropathy is a serious microvascular complication in patients with IDDM. Despite intensive investigation, the pathophysiology of diabetic renal disease has not been fully elucidated. However, several clinical and experimental studies have suggested that endothelial dysfunction and changes of peritubular microcirculation might deteriorate renal function in patients with IDDM. We performed this study to examine the oxidative stress and correlation between levels of serum creatinine and erythrocytic MDA, SOD, catalase, GPX in IDDM patients with diabetic nephropathy. Twenty one patients with IDDM(diabetic duration >5 years) and persistent albuminuria(albumin excretion>1000mg/day) and 15 normal healthy controls were investigated prospectively for erythrocytic MDA(thiobarbituric acid assay) and antioxidant enzymes[SOD(Hyland et al.), catalase(Nelson and Kiesow), GPX(Palgia and Valentine)] and correlation to serum creatinine levels. Levels of erythrocytic MDA were significantly higher in patients with diabetic nephropathy than in normal healthy controls(p0.05) and group 2(r=0.12,p>0.05) but there was significant correlation between serum levels of creatine and erythrocytic MDA in group 3(r=0.96, p0.05). We concluded that increased oxidative stress and decreased antioxidative defense mechanism might be factors in the initiation of diabetic nephropathy and the oxidative stress correlated with higher serum levels of creatinine(more than 5mg/dL)(p<0.05).

Recent Trend of Increasing Proportion of Interventional Catheterization in Congenital Heart Disease

PURPOSE: The proportion of interventional catheterization in congenital heart disease is being increased in Korea, especially in Sejong Heart Institute, so we performed statistical analysis on the cardiac catheterization cases. METHODS: Total 233 cases of congenital heart disease confirmed by cardiac catheterization at the Sejong Heart Institute between Jaunary 1995 and June 1995 were analyzed retrospectively. RESULTS: 1) The distribution of age has become more younger than that of previous reports that is, the proportion of the infant less than 1 year old was 34.8%. 2) The proportion of male sex was equal to that of female. TOF and TGA were observed predominantly in male patients, and PDA and UVH revealed female preponderance. 3) The relative frequencies of each individual congenital heart disease in order of frequency were as follows; TOF 37.3%, PDA 13.3%, VSD 8.2% and UVH 7.7%. 4) Among the 145 (62%) cases of hemodynamic study pre-operation and post-operation cases were 85 and 60 cases, respectively. The cases of interventional catheterization were 84 (36%), and those of endomyocardial biopsy were 4 (2%). 5) The frequencies of each interventional catheterization of 84 cases in order of frequency were as follows: defect closure 28 cases, balloon valvuloplasty 20 cases, balloon angioplasty 17 cases, coil embolization 15 cases, and balloon atrial septostomy 4 cases. 6) There were 2 cases of mortality associated with cardiac catheterization. CONCLUSIONS: The proportion of interventional catheterization in congenital heart disease is being increased in the Sejong Heart Institute, and this trend will spread to the other cardiac center in Korea.