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131.
Sohyun Park Youn Woo Lee Jaeseong Oh Su Jin Kim Sukmook Lee HoYoung Lee 《CTS Clinical and Translational Science》2022,15(12):2938
Anti‐angiogenic antibodies are widely used in the treatment of neovascular macular degeneration. Human antibody targeting C‐type lectin domain family 14 member A (CLEC14a) is potential therapeutic agents owing to its antiangiogenic activity. In the present study, we aimed to predict the human intraocular pharmacokinetic (PK) properties of an anti‐CLEC14a antibody. I‐125 labeled aflibercept and anti‐CLEC14a antibody were intravitreally injected into mice, rats, and rabbits. Single photon emission computed tomography/computed tomography imaging was performed, and the intraocular radioactivity concentration (%ID/ml) was obtained. The PK parameters in those three animal species were obtained by compartmental analysis. The PK parameters in humans were estimated by allometric scaling of the animal PK parameters with consideration of the hydrodynamic radius of the antibody. The mean half‐life values of intraocular I‐125‐labeled aflibercept in mice, rats, and rabbits were 1.13 days, 1.25 days, and 4.91 days, respectively, by analysis with a one‐compartment model. The predicted human half‐life of intraocular aflibercept was 5.75 days based on vitreal volume by allometric scaling. The half‐life values of intraocular I‐125‐labeled anti‐CLEC14a in mice, rats and rabbits were 1.05 days, 1.84 days, and 6.37 days, respectively, by analysis with a one‐compartment model. The predicted human half‐life of intraocular anti‐CLEC14a was 10.29 days based on vitreal volume. According to the hydrodynamic volume of the anti‐CLEC14a, the predicted human half‐life of intraocular anti‐CLEC14a was 9.81 days. The PK characteristics of the intraocular anti‐CLEC14a antibody were evaluated noninvasively in animals using I‐125 labeling, and the intraocular PK characteristics in humans were predicted using these animal data. This methodology can be applied for the development of new antiangiogenic antibodies to treat macular degeneration.Study Highlights
- WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?
- WHAT QUESTION DID THIS STUDY ADDRESS?
- WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?
- HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?
132.
Gyu Man Oh Kyoungwon Jung Jae Hyun Kim Sung Eun Kim Won Moon Moo In Park Seun Ja Park 《Medicine》2022,101(30)
Among the plethora of foreign body impactions, fish bones are common examples that patients may struggle to properly disclose in clinical situations. This study investigated whether patients could pinpoint where the ingested fish bone was lodged. In addition, we investigated the differences between fish bone and other foreign bodies, the usefulness of computed tomography (CT), and the related risk factors for hospitalization. The cases of patients who underwent an endoscopic removal of fish bone between April 2008 and April 2020 were retrospectively reviewed. The clinical outcomes, X-ray scan, CT, and complications of each patient were investigated. A total of 96 patients were included in this study. The mean size of the impacted fish bone was 23.78 mm, and most were found in the upper esophagus (n = 38). There was a weak correlation between pain location and the actual lesion location (r = 0.419, P < .001). Compared to those of other foreign bodies, the location of impacted fish bones was different (P < .001), the X-ray detection rate of fish bones was lower (P < .001), and the complication incidence was higher (P = .030). CT (95.89%) showed higher sensitivity than X-ray scanning (11.24%) (P < .001). Foreign body size (P = .004) and door-to-endoscopy time (P = .029) were related to admission. Patients only managed to point out the approximate location of the ingested fish bone. CT detected fish bones well, but scans should include at least the entire esophagus instead of solely the area where pain is felt. Fish bone impaction has different clinical characteristics from other foreign bodies. Endoscopic removal without delay can reduce the admission rates. 相似文献
133.
Subramanyam Vankadara Monique Danielle Dawson Jia Yi Fong Qin Yao Oh Qi An Ang Boping Liu Hong Yun Chang Judice Koh Xiaoying Koh Qian Wen Tan Joma Joy Cheng San Brian Chia 《ACS medicinal chemistry letters》2022,13(8):1345
The SARS-CoV-2 pandemic is currently causing an unprecedented global health emergency since its emergence in December 2019. In December 2021, the FDA granted emergency use authorization to nirmatrelvir, a SARS-CoV-2 main protease inhibitor, for treating infected patients. This peptidomimetic is designed with a nitrile warhead, which forms a covalent bond to the viral protease. Herein, we investigate nirmatrelvir analogs with different warheads and their inhibitory activities. In addition, antiviral activities against human alphacoronavirus 229E was also investigated along with a cell-based assay. We discovered that the hydroxymethylketone and ketobenzothiazole warheads were equipotent to the nitrile warhead, suggesting that these analogs can also be used for treating coronavirus infections. 相似文献
134.
135.
136.
Jun-Pil Jang Gil Soo Kim Tae Hoon Oh Beomcheol Park Minhee Kim Gwi Ja Hwang Hyeok-Won Lee Jin-Gyeom Lee Young-Soo Hong Jong Seog Ahn Sung-Kyun Ko Jae-Hyuk Jang 《RSC advances》2022,12(35):22360
Two new polyketide glycosides jejuketomycins A (1) and B (2), were isolated from a culture of Streptomyces sp. KCB15JA151. Their chemical structures including the absolute configurations were determined by detailed analyses of the NMR and HRMS data and ECD calculations and spectral data. Compounds 1 and 2 possess an unusual 6/6/8 tricyclic ring system. Biological evaluation with the wound healing assay and time-lapse cell tracking analysis revealed that compounds 1 and 2 have significant inhibitory activities against cancer cell migration with low cytotoxicity.Two new polyketide glycosides jejuketomycins A (1) and B (2), were isolated from a culture of Streptomyces sp. KCB15JA151. 相似文献
137.
An allergic reaction ensues after antigen binds to mast cell or basophil high affinity IgE receptor, Fc epsilonRI, resulting in degranulation of various inflammatory mediators that produce various allergic symptoms. In this study, i) we isolated the active component for the inhibition of mast cell degranulation from the extract of leaves of Castanea crenata and identified it as quercetin; ii) we established the total synthesis procedure of quercetin; iii) using quercetin as positive control, we excavated some lead compounds that possess inhibitory activities for mast cell degranulation by screening the chemical libraries of 1,3-oxazolidine derivatives prepared by solid phase combinatorial chemistry. Some of 1,3-oxazolidine compounds possessing acetyl and 3',4'-dichlorophenyl group displayed strong inhibitory activities on Fc epsilonRI-mediated mast cell degranulation, suggesting that they can be used as lead compounds for the development of anti-allergic agents. 相似文献
138.
Preparation and evaluation of immediate release ibuprofen solid dispersions using polyethylene glycol 4000 总被引:2,自引:0,他引:2
Newa M Bhandari KH Li DX Kim JO Yoo DS Kim JA Yoo BK Woo JS Choi HG Yong CS 《Biological & pharmaceutical bulletin》2008,31(5):939-945
To improve its dissolution, ibuprofen solid dispersions (SDs) were prepared in a relatively easy and simple manner, characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR), and evaluated for solubility, in-vitro drug release and oral bioavailability of ibuprofen in rats. Loss of individual surface properties during melting and resolidification as revealed by SEM micrographs indicated the formation of effective SDs. Absence or shifting towards the lower melting temperature of the drug peak in SDs and physical mixtures in DSC study indicated the possibilities of drug-polymer interactions. FT-IR spectra showed the presence of drug crystalline in SDs. Quicker release of ibuprofen from SDs in rat intestine resulted in a significant increase in AUC and Cmax, and a significant decrease in Tmax over pure ibuprofen. Preliminary results from this study suggested that the preparation of fast dissolving ibuprofen SDs by low temperature melting method using polyethylene glycol 4000 (PEG 4000) as a meltable hydrophilic polymer carrier could be a promising approach to improve solubility, dissolution and absorption rate of ibuprofen. 相似文献
139.
Kook-Hwan Oh Sue K. Park Jayoun Kim Curie Ahn Representing the KNOW-CKD Study Investigators 《Yebang Ŭihakhoe chi》2022,55(4):313
The KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) was launched in 2011 with the support of the Korea Disease Control and Prevention Agency. The study was designed with the aim of exploring the various clinical features and characteristics of chronic kidney disease (CKD) in Koreans, and elucidating the risk factors for CKD progression and adverse outcomes of CKD. For the cohort study, nephrologists at 9 tertiary university-affiliated hospitals participated in patient recruitment and follow-up. Biostatisticians and epidemiologists also participated in the basic design and structuring of the study. From 2011 until 2016, the KNOW-CKD Phase I recruited 2238 adult patients with CKD from stages G1 to G5, who were not receiving renal replacement therapy. The KNOW-CKD Phase II recruitment was started in 2019, with an enrollment target of 1500 subjects, focused on diabetic nephropathy and hypertensive kidney diseases in patients with reduced kidney function who are presumed to be at a higher risk of adverse outcomes. As of 2021, the KNOW-CKD investigators have published articles in the fields of socioeconomics, quality of life, nutrition, physical activity, renal progression, cardiovascular disease and outcomes, anemia, mineral bone disease, serum and urine biomarkers, and international and inter-ethnic comparisons. The KNOW-CKD researchers will elaborate a prediction model for various outcomes of CKD such as the development of end-stage kidney disease, major adverse cardiovascular events, and death. 相似文献
140.