ABSTRACT
BACKGROUND: Metformin is an effective oral antihyperglycaemic agent for type 2 diabetes mellitus, with a variety of metabolic effects. In addition to controlling blood glucose level, it has been appeared to decrease the long-period complications of diabetes, including macrovascular disease. Few reports have addressed the metabolite profiling of metformin. The study was to evaluate if targeted metabolic profiling approach is sensitive enough to predict the therapeutic effects of metformin after a single oral dose. METHODS: A randomized, open-label, single-dose study was conducted in twenty eight healthy Korean male volunteers. To determine the concentrations of endogenous metabolites in their pre-dose and post-dose plasma samples, blood samples were collected before and at 2 and 6 h after a single oral dose of 500 mg metformin. Both Modular P/Modular D analyzer and ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS)-based metabolic profiling was performed. RESULTS: We quantified pre-dose and post-dose creatinine, blood urea nitrogen (BUN), lactic acid, 7 amino acids (lysine, glutamic acid, alanine, valine, leucine, phenylalanine, tryptophan), and 5 lysophosphatidylcholines (14:0, 16:0, 17:0, 18:0, and 18:1) using autoanalyser and UPLC-MS/MS. The postdose levels of alanine, lactic acid, glutamic acid, lysine, valine, leucine, phenylalanine, tryptophan, and lysoPC (18:1) were slightly decreased with statistical significance, but there is no clinical significance. CONCLUSION: In order to explore the potential endogenous metabolites associated with the therapeutic effects of metformin, further study including non-targeted (global) metabolite profiling is needed.
Subject(s)
Humans , Male , Alanine , Amino Acids , Blood Glucose , Blood Urea Nitrogen , Chromatography, Liquid , Creatinine , Diabetes Mellitus, Type 2 , Glutamic Acid , Lactic Acid , Leucine , Lysine , Lysophosphatidylcholines , Metformin , Phenylalanine , Plasma , Tandem Mass Spectrometry , Tryptophan , ValineABSTRACT
BACKGROUND: Metformin is an effective oral antihyperglycaemic agent for type 2 diabetes mellitus, with a variety of metabolic effects. In addition to controlling blood glucose level, it has been appeared to decrease the long-period complications of diabetes, including macrovascular disease. Few reports have addressed the metabolite profiling of metformin. The study was to evaluate if targeted metabolic profiling approach is sensitive enough to predict the therapeutic effects of metformin after a single oral dose. METHODS: A randomized, open-label, single-dose study was conducted in twenty eight healthy Korean male volunteers. To determine the concentrations of endogenous metabolites in their pre-dose and post-dose plasma samples, blood samples were collected before and at 2 and 6 h after a single oral dose of 500 mg metformin. Both Modular P/Modular D analyzer and ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS)-based metabolic profiling was performed. RESULTS: We quantified pre-dose and post-dose creatinine, blood urea nitrogen (BUN), lactic acid, 7 amino acids (lysine, glutamic acid, alanine, valine, leucine, phenylalanine, tryptophan), and 5 lysophosphatidylcholines (14:0, 16:0, 17:0, 18:0, and 18:1) using autoanalyser and UPLC-MS/MS. The postdose levels of alanine, lactic acid, glutamic acid, lysine, valine, leucine, phenylalanine, tryptophan, and lysoPC (18:1) were slightly decreased with statistical significance, but there is no clinical significance. CONCLUSION: In order to explore the potential endogenous metabolites associated with the therapeutic effects of metformin, further study including non-targeted (global) metabolite profiling is needed.
Subject(s)
Humans , Male , Alanine , Amino Acids , Blood Glucose , Blood Urea Nitrogen , Chromatography, Liquid , Creatinine , Diabetes Mellitus, Type 2 , Glutamic Acid , Lactic Acid , Leucine , Lysine , Lysophosphatidylcholines , Metformin , Phenylalanine , Plasma , Tandem Mass Spectrometry , Tryptophan , ValineABSTRACT
BACKGROUND: In recent years, clinical trials have considerably increased and relevant education programs to clinical trials have been developed and implemented since 2008 in Korea. To enhance the quality as well as global competitiveness of clinical trial professionals (CTPs), a certification program of the human resource is needed. Accordingly, in Korea the first and the second certification examinations were implemented in February and October 2012, respectively. In this paper, introduction of the certification program of the human resource is described, and results of the certification examinations and questionnaire survey are presented. METHODS: Data including the examination results and questionnaire survey was collected by cooperative officials in Korea National Enterprise for Clinical Trials. Applicants who were selected eligible for examination by the steering committee were asked to complete questionnaires provided with the test papers on the day of the certification examination. RESULTS: In the first certification examination, a total of 221 eligible participants completed the examination. 99.5 % of the participants responded the questionnaire survey. In the second examination, a total of 223 applicants participated. The examination consisted of 50 multiple-choice questions with cut-off score of 70 per cent score.176 & 194 CTPs passed the first & second examinations respectively. CONCLUSION: This paper that described the results of the two certification tests and questionnaire surveys might be helpful in establishment and activation of the certification program in the future. Quality improvement of CTPs and international competitiveness of clinical trial in Korea can be anticipated by the certification program.
Subject(s)
Humans , Certification , Cytidine Triphosphate , Korea , Quality Improvement , Surveys and Questionnaires , SilanesABSTRACT
BACKGROUND: In recent years, clinical trials have considerably increased and relevant education programs to clinical trials have been developed and implemented since 2008 in Korea. To enhance the quality as well as global competitiveness of clinical trial professionals (CTPs), a certification program of the human resource is needed. Accordingly, in Korea the first and the second certification examinations were implemented in February and October 2012, respectively. In this paper, introduction of the certification program of the human resource is described, and results of the certification examinations and questionnaire survey are presented. METHODS: Data including the examination results and questionnaire survey was collected by cooperative officials in Korea National Enterprise for Clinical Trials. Applicants who were selected eligible for examination by the steering committee were asked to complete questionnaires provided with the test papers on the day of the certification examination. RESULTS: In the first certification examination, a total of 221 eligible participants completed the examination. 99.5 % of the participants responded the questionnaire survey. In the second examination, a total of 223 applicants participated. The examination consisted of 50 multiple-choice questions with cut-off score of 70 per cent score.176 & 194 CTPs passed the first & second examinations respectively. CONCLUSION: This paper that described the results of the two certification tests and questionnaire surveys might be helpful in establishment and activation of the certification program in the future. Quality improvement of CTPs and international competitiveness of clinical trial in Korea can be anticipated by the certification program.
Subject(s)
Humans , Certification , Cytidine Triphosphate , Korea , Quality Improvement , Surveys and Questionnaires , SilanesABSTRACT
BACKGROUND: Calcineurin-inhibitors have wide inter-individual variation in drug response. Although therapeutic drug monitoring has been conducted to optimize personalized regimen, toxicity or rejection may occur. In this study, pharmacologic effect was evaluated by measuring calcineurin activity in peripheral blood after administration of a single dose of cyclosporine in healthy volunteers. METHODS: 7 healthy Korean male subjects received cyclosporine 200 mg and blood samples were drawn immediately before and at 1, 1.5, 4, 6, 12 h after dosing to measure calcineurin activity. The blood concentrations of cyclosporine were determined for 24 hours. Calcineurin activity assay was done with Calcineurin cellular activity assay kit (Calbiochem, USA). Frozen whole blood samples in liquid N2 were thawed and lysed with lysis buffer. 50 microL of phosphate standard curve samples were added to each well of a 96-well plate and 10 microL of diluted lysate were added to the well with RII phosphopeptide substrate. After incubating for 30 min, reaction was terminated by adding 100 microL GREEN(TM) reagent. Absorbance was read at 620 nm using spectrophotometer. We evaluated percent change in calcineurin activity from baseline level in relation to the lowest level. RESULTS: Decrease of calcineurin activity was confirmed after cyclosporine administration (mean +/- SD: 58.9 +/- 48.6 (%)). Significant correlation was shown between calcineurin activity change and pharmacokinetic parameters (AUClast: r = 0.834, p value = 0.01, Cmax: r = 0.774, p value = 0.02). CONCLUSION: In this study, we confirmed the pharmacologic effect and its correlation with pharmacokinetics after administration of a single dose of cyclosporine by measuring calcineurin activity in peripheral blood in healthy volunteers.
Subject(s)
Humans , Male , Calcineurin , Cyclosporine , Drug Monitoring , Human Experimentation , Immunosuppressive Agents , Rejection, PsychologyABSTRACT
Insulinomas are the most common type of islet cell tumor. Generally, these tumors are benign (90%), intrapancreatic, solitary, and small. Moreover, hyperinsulinemia in infants and children can result in permanent damage to the central nervous system. Thus, early diagnosis and treatment are important. The principal challenge during anesthesia is the avoidance of hypoglycemia, which may occur during tumor manipulation, though hyperglycemia may follow after successful surgical removal of the tumor. Because symptoms of hypoglycemia (systemic hypertension, tachycardia, diaphoresis) may be masked during anesthesia, it is important to monitor blood glucose levels frequently during the perioperative period. Here we report up on the case of a 3 year old female with insulinoma. We monitored blood glucose levels intermittently (about every 15 minutes) using a glucometer (Medisense Optium, Abbott, USA). No hypoglycemic episode occurred during anesthesia. We report this clinical experience and review anesthetic choices and the management of this patient.
Subject(s)
Child , Child, Preschool , Female , Humans , Infant , Adenoma, Islet Cell , Anesthesia , Blood Glucose , Central Nervous System , Early Diagnosis , Hyperglycemia , Hyperinsulinism , Hypertension , Hypoglycemia , Insulinoma , Isoflurane , Masks , Pancreas , Perioperative Period , TachycardiaABSTRACT
Postoperative delirium in the intensive care unit is a serious problem that has recently attracted much attention. We present a 73-year-old female patient who was admitted by multiple fractures induced by an accident. We started general anesthesia for the operation of open reduction and internal fixation. After the discontinuation of general anesthesia, the patient was transported to the intensive care unit. The symptoms of delirium were developed and controlled with medications including haloperidols, benzodiazepines, and vitamins. The patient was recovered three weeks after the management and received two other operations, but delirium did not be developed again. She was discharged from the hospital without complications.
Subject(s)
Aged , Female , Humans , Anesthesia, General , Benzodiazepines , Delirium , Haloperidol , Intensive Care Units , VitaminsABSTRACT
BACKGROUND: Propofol (2,6-diisopropylphenol) is a widely used intravenous anesthetic, and the effects of propofol on several ion channels have been studied at the whole cell and single-channel levels. However, in general there is no report on the effect of propofol on outward K+ currents in canine colonic myocytes, in which there are two types of outward K+ currents, a large-conductance Ca2+-activated K+ current and a classical delayed rectifier K+ current. We examined the effects of propofol on the two types of outward K+ currents the kinetics involved. METHODS: Experiments were performed on freshly dispersed smooth muscle cells from the circular muscle layer of the proximal canine colon. Outward currents were recorded using the patch clamp technique in the whole cell configuration. RESULTS: The application of propofol (600 nM-600microM) decreased net outward current in a dose-dependent manner. Propofol (6-60microM) also decreased peak delayed rectifier K+ currents. Pretreatment with TEA abolished propofol effects on delayed rectifier K+ currents. However, propofol still decreased delayed rectifier K+ currents in the presence of 4-AP. CONCLUSIONS: These data suggest that propofol decrease net outward K+ currents primarily by inhibiting large-conductance Ca2+-activated K+ currents and 4-AP resistant delayed rectifier K+ currents. These results suggest that propofol action on outward currents may depend on the different blocking mechanisms of the different types of K+ channels. If propofol cannot induce contraction, Ca2+ currents in colonic myocytes warrant further study.