Ischemic acute kidney injury (AKI) is a common medical problem with significant mortality and morbidity, affecting a large number of patients globally. Ischemic AKI is associated with intrarenal inflammation as well as systemic inflammation; thus, the innate and adaptive immune systems are implicated in the pathogenesis of ischemic AKI. Among various intrarenal immune cells, T cells play major roles in the injury process and in the repair mechanism affecting AKI to chronic kidney disease transition. Importantly, T cells also participate in distant organ crosstalk during AKI, which affects the overall outcomes. Therefore, targeting T cell-mediated pathways and T cell-based therapies have therapeutic promise for ischemic AKI. Here, we review the major populations of kidney T cells and their roles in ischemic AKI.

Purpose: Recently, high-protein diets have become highly popular, and the market for protein products has steadily increased in Korea together with the development of various types of such products. However, there is limited information on the consumption of protein supplements (PS) or protein-fortified foods (PF). Thus, this study aimed to evaluate the use of PS/PF among young adults in Jeju. Methods: A total of 350 adults (140 men and 210 women) aged 19–39 years voluntarily participated in this study from June 2022 to May 2023. PS/PF use was measured using a questionnaire. Dietary intake was assessed using a 24-hour dietary recall. Results: Approximately 31.4% of the participants (n = 110) had consumed PS/PF for more than 2 weeks during the past year and 71.8% of them (n = 79) were still consuming these products (PS/PF consumers). The PS/PF consumers tended to be male and physically active (p < 0.05 for all). The most frequent reason for PS/PF use was muscle gain (59.5%), followed by protein supplementation (19.0%) and body fat loss (13.9%), and the most frequent type of PS/PF consumed was powders (70.6%), followed by drinks (17.7%) and bars (8.8%). The PS/PF consumers tended to consume a high-protein low-carbohydrate diet compared to the non-consumers. The prevalence of consuming dietary protein less than the estimated average requirement (EAR) was significantly lower in PS/PF consumers (13.9%) compared to non-consumers (25.4%; p = 0.0316). Conclusion These findings indicate that the necessity of protein supplementation should be determined based on the current dietary protein intake and individual requirements. The study also provides the basic information for establishing guidelines for appropriate protein intake.

BACKGROUND: Voglibose is an alpha-glucosidase inhibitor. The purpose of this study was to evaluate the pharmacodynamic characteristics of voglibose for determining the appropriate study design and parameters for a pharmacodynamic equivalence study of voglibose. METHODS: This study consisted of two studies. The single dose study had an open and single sequence design. Nineteen subjects received placebo and then one tablet of voglibose on two consecutive days with sucrose. The multiple dose study was performed with the similar design, except that it was a multiple dose of the single dose study. Nine subjects who showed an effective response in the single dose study received placebo three times and then voglibose 4 times on two consecutive days. Serial blood samples for pharmacodynamic parameters were taken until 180 mins after each administration. The baseline adjusted maximum serum glucose level (G(max)) and area under the serum glucose level-time profiles were determined and compared. RESULTS: In the single dose study, the difference in G(max) was -10.6 +/- 28.7 mg/dL. The area under the serum glucose concentration-time curve (AUGC(0-1h)) of placebo and voglibose were 7825.0 +/- 1145.3 mg.min/dL, 7907.5 +/- 917.2 mg.min/dL, respectively. In the multiple dose study, the difference in G(max) was 46.6 +/- 16.1 mg/dL. The AUGC(0-1h) of placebo and voglibose were 8138.6 +/- 721.9 mg.min/dL and 6499.7 +/- 447.2 mg.min/dL, respectively. The G(max) and AUGC(0-1h) of the multiple dose study was significantly different between placebo and voglibose in paired t-test. CONCLUSION: The differences in G(max) and AUGC(0-1h) are suitable for pharmacodynamic parameters to evaluate bioequivalence of voglibose.
alpha-Glucosidases ; Glucose ; Inositol ; Sucrose ; Therapeutic Equivalency

Levofloxacin is a broad-spectrum antibiotic with activity against gram-positive and -negative bacteria. This study compared the pharmacokinetics (PK) and evaluated the bioequivalence of two levofloxacin 100-mg tablet formulations. An open, randomized, two-way crossover study was conducted in 28 healthy volunteers. The reference (Cravit Tab 100-mg, Jeil) or test (Levobacter Tab, Seoul) formulation was administered and serial blood samples were collected over 24 h for PK analysis. Levofloxacin plasma concentrations were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The correlation of levofloxacin concentration at various time points with the area under the concentration time-curve over the time interval from 0 extrapolated to infinity (AUCinf) was estimated to determine the best reflected time point. The average half-life, maximum plasma concentration (Cmax), and AUClast were comparable. The 90% confidence intervals (CIs) of the geometric mean ratio (GMR test/reference) of AUClast and Cmax were 0.8200-1.0633 and 0.9474-1.0643 respectively. Both formulations were tolerated with no clinically relevant safety issues. Plasma levofloxacin concentrations at various time points correlated well with the AUCinf, and showed high correlation coefficients (r > 0.7, P < 0.001) for both drugs 8 and 12 h after administration. Both formulations showed similar PK profiles while levofloxacin plasma levels after administration indicated their bioequivalence. The Cmax and AUClast GMR 90% CIs were 0.80-1.25. Moreover, 12 h was the best time point to predict the AUCinf and therefore suitable for therapeutic drug monitoring.
Bacteria ; Cross-Over Studies ; Drug Monitoring ; Half-Life ; Healthy Volunteers ; Levofloxacin* ; Mass Spectrometry ; Pharmacokinetics ; Plasma ; Therapeutic Equivalency

Simvastatin is used to reduce plasma cholesterol by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and is primarily used to treat hypercholesterolemia. This study was conducted to assess the bioequivalence between the generic formulation of simvastatin 20 mg and the branded formulation of simvastatin 20 mg. A generic formulation of simvastatin 20 mg tablet was developed and the pharmacokinetics of the generic formulation were compared with those of the branded formulation of simvastatin 20 mg tablet in 33 healthy male volunteers after a single oral dose in a randomized, open-label, two-period, two-sequence, crossover study. The reference (Zocor®, MSD Korea LTD.) and test (Simvarotin®, Korea Arlico Pharm Co., Ltd.) formulations, two 20 mg tablets each, were administered to all subjects in fasting status. The serial blood samples for pharmacokinetic analysis were collected before dosing and up to 24 hours post-dose, and plasma concentrations of simvastatin were determined by liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters including T(max), C(max), AUC(last), AUC(inf) and t½ were calculated for both formulations by non-compartmental method, and the log-transformed C(max) and AUC(last) were compared statistically. Geometric mean ratios (90% confidence intervals) of the test to the reference formulation in C(max) and AUC(last) were 0.9652 (0.8302–1.1223) and 0.9891 (0.8541–1.1455), respectively. No significant differences in tolerability profiles were noted between the two formulations. The two formulations of simvastatin 20 mg tablets exhibited comparable pharmacokinetic profiles and 90% confidence intervals were within the acceptable range of bioequivalence criteria.
Cholesterol ; Coenzyme A ; Cross-Over Studies ; Fasting ; Humans ; Hypercholesterolemia ; Korea ; Male* ; Mass Spectrometry ; Methods ; Oxidoreductases ; Pharmacokinetics ; Plasma ; Simvastatin* ; Tablets ; Therapeutic Equivalency ; Volunteers*

BACKGROUND: Molecular imaging such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) can provide the crucial pharmacokinetic-pharmacodynamic information of a drug non-invasively at an early stage of clinical drug development. Nevertheless, not much has been known how molecular imaging has been actually used in drug development studies. METHODS: We searched PubMed using such keywords as molecular imaging, PET, SPECT, drug development, and new drug, or any combination of those to select papers in English, published from January 1, 1990, to December 31, 2015. The information about the publication year, therapeutic area of a drug candidate, drug development phase, and imaging modality and utility of imaging were extracted. RESULTS: Of 10,264 papers initially screened, 208 papers met the eligibility criteria. The more recent the publication year, the bigger the number of papers, particularly since 2010. The two major therapeutic areas using molecular imaging to develop drugs were oncology (47.6%) and the central nervous system (CNS, 36.5%), in which efficacy (63.5%) and proof-of-concept through either receptor occupancy (RO) or other than RO (29.7%), respectively, were the primary utility of molecular imaging. PET was used 4.7 times more frequently than SPECT. Molecular imaging was most frequently used in phase I clinical trials (40.8%), whereas it was employed rarely in phase 0 or exploratory IND studies (1.4%). CONCLUSIONS The present study confirmed the trend that molecular imaging has been more actively employed in recent clinical drug development studies although its adoption was rather slow and rare in phase 0 studies.

BACKGROUND: Molecular imaging such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) can provide the crucial pharmacokinetic-pharmacodynamic information of a drug non-invasively at an early stage of clinical drug development. Nevertheless, not much has been known how molecular imaging has been actually used in drug development studies.METHODS: We searched PubMed using such keywords as molecular imaging, PET, SPECT, drug development, and new drug, or any combination of those to select papers in English, published from January 1, 1990, to December 31, 2015. The information about the publication year, therapeutic area of a drug candidate, drug development phase, and imaging modality and utility of imaging were extracted.RESULTS: Of 10,264 papers initially screened, 208 papers met the eligibility criteria. The more recent the publication year, the bigger the number of papers, particularly since 2010. The two major therapeutic areas using molecular imaging to develop drugs were oncology (47.6%) and the central nervous system (CNS, 36.5%), in which efficacy (63.5%) and proof-of-concept through either receptor occupancy (RO) or other than RO (29.7%), respectively, were the primary utility of molecular imaging. PET was used 4.7 times more frequently than SPECT. Molecular imaging was most frequently used in phase I clinical trials (40.8%), whereas it was employed rarely in phase 0 or exploratory IND studies (1.4%).CONCLUSIONS: The present study confirmed the trend that molecular imaging has been more actively employed in recent clinical drug development studies although its adoption was rather slow and rare in phase 0 studies.
Central Nervous System ; Clinical Trials, Phase I as Topic ; Molecular Imaging ; Positron-Emission Tomography ; Publications ; Tomography, Emission-Computed ; Tomography, Emission-Computed, Single-Photon

Volumetric absorptive microsampling (VAMS) is a novel sampling technique that allows for the collection of an accurate volume of blood by dipping a microsampler tip. The purpose of this study is to compare the requirement of a stabilizing reagent for the conventional venous blood sampling method versus VAMS in the analytical measurement of the concentration of acetylsalicylic acid. A high-performance liquid chromatography with mass spectrometry (LC-MS/MS) method was developed and validated for the accurate determination of acetylsalicylic acid in human blood. The blood samples spiked with acetylsalicylic acid with and without stabilizing reagent were absorbed into VAMS tips. In the whole blood sample, the same concentration was shown regardless of the addition of the stabilizing reagent, but the concentration decreased when the stabilizing reagent was not added to the VAMS sample. To apply the VAMS technology as a new blood sampling method, stabilizing reagents should be added before the analysis of acetylsalicylic acid concentration.
Aspirin ; Chromatography, Liquid ; Humans ; Indicators and Reagents ; Mass Spectrometry ; Methods

A clinical trial management system (CTMS) is a comprehensive program that supports an efficient clinical trial. To improve the environment of clinical trials and to be competitive in the global clinical trials market, an advanced and integrated CTMS is necessary. However, there is little information about the status of CTMSs in Korea. To understand the utilization of current CTMSs and requirements for a future CTMS, we conducted a survey on the subjects related to clinical trials. The survey was conducted from July 27 to August 16, 2017. The total number of respondents was 596, and 531 of these responses were used. Almost half of the respondents were from hospitals (46%). The proportion of respondents who are currently using a CTMS was the highest for contract research organizations at 59%, whereas the proportion used by investigators was 39%. The main reason for not using a CTMS was that it is unnecessary and expensive, but it showed a difference between workplaces. Many respondents frequently used CTMSs to check the clinical trial schedule and progress status, which was needed regardless of workplace. While two-thirds of users tended to be satisfied with their current CTMS, there were many users who felt their CTMS was inconvenient. The most requested function for a future CTMS was one that could be used to manage the project schedule and subject enrollment status. Additionally, a systematic linkage to electronic medical records, including prescription and laboratory test results, and a function to confirm the participation history of subjects in other hospitals were requested.
Appointments and Schedules ; Electronic Health Records ; Humans ; Korea ; Prescriptions ; Research Personnel ; Surveys and Questionnaires