• The Korean Journal of Physiology and Pharmacology
• /
• 제20권1호
• /
• pp.63-67
• /
• 2016

Severe graft-versus-host disease (GVHD) is an often lethal complication of allogeneic hematopoietic stem cell transplantation (HSCT). The safety of clinical-grade mesenchymal stem cells (MSCs) has been validated, but mixed results have been obtained due to heterogeneity of the MSCs. In this phase I study, the safety of bone marrow-derived homogeneous clonal MSCs (cMSCs) isolated by a new subfractionation culturing method was evaluated. cMSCs were produced in a GMP facility and intravenously administered to patients who had refractory GVHD to standard treatment resulting after allogeneic HSCT for hematologic malignancies. After administration of a single dose ($1{\times}10^6cells/kg$), 11 patients were evaluated for cMSC treatment safety and efficacy. During the trial, nine patients had 85 total adverse events and the rate of serious adverse events was 27.3% (3/11 patients). The only one adverse drug reaction related to cMSC administration was grade 2 myalgia in one patient. Treatment response was observed in four patients: one with acute GVHD (partial response) and three with chronic GVHD. The other chronic patients maintained stable disease during the observation period. This study demonstrates single cMSC infusion to have an acceptable safety profile and promising efficacy, suggesting that we can proceed with the next stage of the clinical trial.

• Journal of Veterinary Science
• /
• 제22권6호
• /
• pp.78.1-78.10
• /
• 2021

Background: Recurrent subclinical mastitis (RScM) due to resistant bacteria has low clinical and bacteriological cure rates, often requiring the culling of cows. The sequential intramammary administration of enrofloxacin hydrochloride-dihydrate (enro-C) followed by ceftiofur HCl may be useful for treating these cases. Objectives: This study assessed the bacteriological and clinical cure-efficacies of the sequentially intramammary administration of enro-C, followed by ceftiofur HCl to treat RScM in Holstein/Friesian cows. Methods: This trial was conducted in a herd with a high prevalence of RScM, and 20 Holstein/Friesian cows were included: 45% suffering subclinical mastitis and 38.9% of the mammary quarters affected. Twenty-nine bacterial isolates in vitro resistant to enro-C were obtained (coagulase-negative Staphylococcus spp, 55.2%; Staphylococcus aureus, 27.6%; Escherichia coli, 6.9%; Streptococcus uberis, 6.9%; Corynebacterium bovis, 3.4%). Polymerase chain reaction-isolated the following genes linked to enro-C resistance: chromosomal (gyrA) and plasmid (aac(6')-lb-cr). The treatments were as follows: twice-daily intramammary infusions of enro-C (300 mg/10 mL) for 5 days. Cows clinically considered treatment failures were also treated with intramammary ceftiofur (125 mg/10 mL, twice daily for 5 days. The clinical and bacteriological cure rates were carried out when completing each treatment phase and at 14 and 21 days, aided by a California mastitis test, somatic cell count, and failure to identify the initially causative bacteria. Results: Enro-C achieved 65% clinical and bacteriological cure rates, and 100% cure rates were obtained after the rescue treatment with ceftiofur HCl. Conclusions: Outstanding clinical and bacteriological cure rates in cows affected by RScM were achieved with the consecutive intramammary infusions of enro-C, followed by ceftiofur HCl.

• 대한한방소아과학회지
• /
• 제33권1호
• /
• pp.17-33
• /
• 2019

Objectives The purpose of this study is to investigate the current status of registration of interventional studies focusing on children and adolescents in South Korea and the status of Korean medicine interventional studies through Clinical Research Information Service (CRIS). Methods CRIS was used to search interventional clinical researches which were registered from May, 2010 to October, 2018. Key words of 'child', 'children', 'adolescents', 'infant', 'toddler', 'elementary school student', 'middle and high school', 'middle school student', and 'high school student' were used. Results A total of 37 intervention clinical studies were selected. To identify the trends, years of registration in the CRIS, intervention types, disease categories, recruitment status, phase, institutions responsible for the research, consent, compensation and safety investigation were analyzed. Conclusions This study shows the current state of registration of interventional studies in children and adolescents in Korea. Since interventional studies in children and adolescents are essential for providing safe and effective treatment, further interventional studies, Korean medicine interventional studies and ethical considerations are needed.

• Bulletin of the Korean Chemical Society
• /
• 제34권11호
• /
• pp.3284-3288
• /
• 2013

This paper describes first development and validation of pentafluorophenylprophyl ligand-based liquid chromatography coupled to tandem mass spectrometry (PFPLC-MS/MS) method to determine metformin, a highly polar compound, in human plasma. Metformin and Phenformin (internal standard) were extracted from human plasma 50 ${\mu}L$ with a single-step protein precipitation. The chromatographic separation was performed using a linear gradient elution of mobile phase involving 5.0 mM ammonium formate solution with 0.1% formic acid (A) and acetonitrile (B) over 3.0 min of run time on a Phenomenex Luna PFP column. The detection was performed using a triple-quadrupole tandem mass spectrometer (Waters Quattro micro) with electrospray ionization in the mode of positive ionization and multiple-reaction monitoring (MRM). The developed method was validated with 5.0 ng/mL of lower limit of quantification (LLOQ). The calibration curve was linear over 5-3000 ng/mL of the concentration range ($R^2$ > 0.99). The specificity, selectivity, carry-over effect, precision, accuracy and stability of the method met the acceptance criteria. The method developed in this study had had rapidness, simplicity and ruggedness. The reliable method was successfully applied to high throughput analysis of real samples for a practical purpose of a pharmacokinetic study.

• Tuberculosis and Respiratory Diseases
• /
• 제73권1호
• /
• pp.1-10
• /
• 2012

Care of patients with sepsis has improved over the last decade. However, in the recent two years, there was no significant progress in the development of a new drug for critically ill patients. In January 2011, it was announced that the worldwide phase 3 randomized trial of a novel anti-Toll-like receptor-4 compound, eritoran tetrasodium, had failed to demonstrate an improvement in the mortality of patients with severe sepsis. In October 2011, Xigris (drotrecogin alfa, a recombinant activated protein C) was withdrawn from the market following the failure of its worldwide trial that had attempted to demonstrate improved outcome. These announcements were disappointing. The recent failure of 2 promising drugs to further reduce mortality suggests that new approaches are needed. A study was published showing that sepsis can be associated to a state of immunosuppression and loss of immune function in human. However, the timing, incidence, and nature of the immunosuppression remain poorly characterized, especially in humans. This emphasizes the need for a better understanding of sepsis as well as new therapeutic strategies. Many clinical experiences of the extracorporeal membrane oxygenator (ECMO) treatment for adult acute respiratory distress syndrome (ARDS) patients, which is caused by the H1N1 influenza A virus, were reported. The use of ECMO in severe respiratory failure, particularly in the treatment of adult ARDS, is occurring more commonly.

• Journal of the Korean Statistical Society
• /
• 제32권1호
• /
• pp.33-46
• /
• 2003

The continual reassessment method (CRM) provides a Bayesian estimation of the maximum tolerated dose (MTD) in phase I clinical trials. The CRM has been proposed as an alternative design of the standard design. The CRM has been modified to improve practical feasibility and, recently, the likelihood approach CRM has been proposed. In this paper we investigate the consistency and asymptotic normality of the modified likelihood approach CRM in which the maximum likelihood estimate is used instead of the posterior mean. Small-sample properties of the consistency is examined using complete enumeration. Both the asymptotic results and their small-sample properties show that the modified CRML outperforms the standard design.

• Journal of mucopolysaccharidosis and rare diseases
• /
• 제2권2호
• /
• pp.50-51
• /
• 2016

Combining basal insulin therapy with a glucagon-like peptide-1 receptor agonist (GLP-1 RA) has clear clinical advantages, and is supported by the latest EASD/ADA position statement (1). IDegLira is a once-daily combination of the basal insulin, degludec, and the GLP-1RA, liraglutide, in one pen. The DUAL phase 3 clinical trial program provides important evidence about the efficacy and safety of IDegLira in three different populations of patients with type 2 diabetes (T2D): insulin naïve subjects uncontrolled on oral antidiabetic drugs (OADs), subjects uncontrolled on OAD(s) and a GLP-1 RA, and subjects uncontrolled on OAD(s) and basal insulin. Treatment with IDegLira reduced mean HbA1c to below the EASD/ADA treatment target of 7.0% in all five trials. The mean reduction of HbA1c from baseline ranged from 1.3% and 1.9%. IDegLira resulted in weight loss for subjects uncontrolled on basal insulin, was weight neutral for subjects on OADs and weight gain was minimal (2 kg) for subjects previously treated with a GLP-1 RA. Rates of hypoglycaemia were low across all the trials, particularly considering the level of glycaemic control achieved.

• 대한치과교정학회지
• /
• 제54권1호
• /
• pp.16-25
• /
• 2024

Objective: To compare the effectiveness of laser-engineered copper-nickel titanium (SmartArch) and superelastic nickel-titanium (SENT) archwires in aligning teeth and inducing root resorption and pain experienced by patients. Methods: Two-arm parallel groups with a 1:1 allocation ratio were used. The participants were patients aged 11.5 years and older with 5-9 mm of mandibular anterior crowding who were indicated for non-extraction treatment. The primary outcome was alignment effectiveness, assessed using Little's irregularity index (LII) over 16 weeks with a single wire (0.016-inch) in the SmartArch group and 2 wires (0.014- and 0.018-inch) in the SENT group (8 weeks each). Secondary outcomes included root resorption evaluated by pre- and post-intervention periapical radiographs and pain levels recorded by the participants during the first week. Results: A total of 40 participants were randomly allocated into 2 groups; 33 completed the study and were analyzed (16 in the SmartArch group and 17 in the SENT group, aged 16.97 ± 4.05 years). The total LII decrease for the SmartArch and SENT groups was 5.63 mm and 5.29 mm, respectively, which was neither statistically nor clinically significant. Root resorption was not significantly different between the groups. The difference in pain levels was not statistically significant for the first 5 days following wire placement; however, there was a significant difference favoring the SENT group in the final 2 days. Conclusions: SmartArch and SENT archwires were similarly effective during the alignment phase of orthodontic treatment. Root resorption should be observed throughout the treatment with either wire. SmartArch wires demonstrated higher pain perception than SENT wires.

• The Korean Journal of Physiology and Pharmacology
• /
• 제28권2호
• /
• pp.153-164
• /
• 2024

This study aimed to identify metabolic biomarkers and investigate changes in intestinal microbiota in the feces of healthy participants following administration of Lactococcus lactis GEN-001. GEN-001 is a single-strain L. lactis strain isolated from the gut of a healthy human volunteer. The study was conducted as a parallel, randomized, phase 1, open design trial. Twenty healthy Korean males were divided into five groups according to the GEN-001 dosage and dietary control. Groups A, B, C, and D1 received 1, 3, 6, and 9 GEN-001 capsules (1 × 10¹¹ colony forming units), respectively, without dietary adjustment, whereas group D2 received 9 GEN-001 capsules with dietary adjustment. All groups received a single dose. Fecal samples were collected 2 days before GEN-001 administration to 7 days after for untargeted metabolomics and gut microbial metagenomic analyses; blood samples were collected simultaneously for immunogenicity analysis. Levels of phenylalanine, tyrosine, cholic acid, deoxycholic acid, and tryptophan were significantly increased at 5-6 days after GEN-001 administration when compared with predose levels. Compared with predose, the relative abundance (%) of Parabacteroides and Alistipes significantly decreased, whereas that of Lactobacillus and Lactococcus increased; Lactobacillus and tryptophan levels were negatively correlated. A single administration of GEN-001 shifted the gut microbiota in healthy volunteers to a more balanced state as evidenced by an increased abundance of beneficial bacteria, including Lactobacillus, and higher levels of the metabolites that have immunogenic properties.

• 지식경영연구
• /
• 제21권3호
• /
• pp.105-121
• /
• 2020

신약 개발과 관련하여 글로벌 판매망이 구축되지 않은 국내 바이오텍에게 가장 필요한 것은 신약의 기술이전과 관련된 의사 결정이다. 각 임상 단계별 성공 확률이 다르고, 어느 임상 단계에서 기술이전 계약을 하느냐에 따라서 총 계약금액과 로열티가 달라지게 된다. 이런 기술이전 계약의 특징과 바이오텍의 취약한 재무 구조 등으로 인하여, 바이오텍이 빅파마에게 기술 이전을 하는 시기를 정하는 것은 매우 중요한 의사 결정 문제가 된다. 이 연구에서는 '신약의 기술이전 최적시기 결정 문제'라는 연구모형을 제시하고, 의사결정트리 방법론으로 결과를 도출하였다. 사례 연구로, first-in-class 신약을 대상으로 FDA 글로벌 임상을 진행하고 있는 국내 바이오텍에 적용해 보았다. 타겟 질환의 시장 크기와 예상 시장 침투율은 알려져 있다고 가정하였을 때, 임상 1상이나 2상 이후에 기술이전을 하는 것이 이익을 최대화할 수 있는 대안임을 알 수 있었다. 본 연구는 제약 분야 문제에 경영과학 방법론을 사용할 수 있는 개념적인 틀을 제시하여 신약 기술이전에 대한 지식 및 연구의 기반이 될 수 있을 것으로 기대된다.