bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetic characterization of 14C-vascular endothelial growth factor controlled release microspheres using a rat model
Authors: Kim Tae-Kyoung , Burgess Diane J 
Published: October 2002

Abstract
The objectives of this study were to characterize the pharmacokinetics of vascular endothelial growth factor (VEGF) in poly(lactic-co-glycolic) acid (PLGA) microspheres using a rat model, and to develop a pharmacokinetic model for this controlled release formulation. 14C-VEGF was encapsulated using a solid-in-oil-in-water emulsification method. The microspheres were administered subcutaneously to rats and the pharmacokinetic parameters were compared with those of protein solutions. Intravenous administration of protein solutions resulted in short half-lives and subcutaneous administration resulted in rapid clearance from the subcutaneous tissue, with high plasma concentrations as expressed by rapid absorption and elimination. The subcutaneous administration of the VEGF microspheres produced low plasma concentrations and high subcutaneous concentrations over a period of 7 weeks. The area under the curve (AUC), the time required to achieve the maximum concentration (tmax), the maximum concentration (Cmax) in blood samples and the elimination rate constant (kel) values at the subcutaneous tissue site were selected to compare the pharmacokinetic characterization of VEGF microspheres with that of protein solutions. The in-vivo release profiles of the proteins were slower than the in-vitro release profiles and they followed the same trend as the in-vitro and in-vivo PLGA degradation rates. The PLGA microsphere degradation was the determinant step for VEGF release from the microspheres and its absorption at the subcutaneous site. Microspheres appear to be an attractive system for the localized rate-controlled delivery of VEGF. 14C-Methylation via reductive alkylation of VEGF did not affect its mitogenic activity, however approximately 25% activity was lost following release from PLGA microspheres. This loss of activity may be due to degradation in an acidic environment as a result of PLGA degradation.
Characterization of Ciclosporin A loaded poly (D,L lactide-co-glycolide) microspheres using modulated temperature differential scanning calorimetry
Authors: Passerini N , Craig D Q M 
Published: October 2002

Abstract
The aim of this study was to investigate the physical structure of poly (D,L lactide-co-glycolide) (PLGA) microspheres loaded with ciclosporin A in terms of the amorphous properties of the individual components and the phase separation characteristics of the binary systems. Microspheres were prepared using a standard oil-in-water emulsion technique. The thermal properties of the PLGA, ciclosporin A and loaded spheres were investigated using modulated temperature differential scanning calorimetry (MTDSC) using a TA Instruments MTDSC 2920, with scanning electron microscopy (SEM), X-ray powder diffraction (XRD) and high-performance liquid chromatography used as supportive techniques. MTDSC indicated a glass transition for ciclosporin A in the reversing heat flow signal at 107°C, supported by temperature cycling studies, while XRD showed clear evidence for diffraction peaks, thereby indicating that the material as received is semi-crystalline. The unloaded PLGA spheres showed a glass transition (Tg) at 43°C, with no reduction in Tg being observed on loading the peptide up to 50%, w/w. Similarly, no evidence for diffraction peaks were seen for the drug-loaded systems, although the glass transition corresponding to the peptide was observed for the loaded microspheres, suggesting that the drug is present as a separate amorphous phase. Similarly, SEM studies showed the appearance of distinct “islands” on the surface of the spheres that are suggested to correspond to the drug phase, with the size of the islands increasing with drug loading. Evidence is therefore presented that ciclosporin A may exist in a range of solid states, with the degree of crystallinity being altered by processing. In addition, there appears to be little or no miscibility between the drug and PLGA using the manufacturing protocol employed here. These findings may have implications for the choice of manufacturing protocol, the release of peptide drugs from PLGA microspheres and the chemical and physical stability of such drugs.
A pharmacokinetic model for analysis of drug disposition profiles undergoing enterohepatic circulation
Authors: Wajima Toshihiro , Yano Yoshitaka , Oguma Takayoshi 
Published: October 2002

Abstract
A new and simple pharmacokinetic model that can explain enterohepatic circulation profiles for both single and repeated dosing was developed, and its applicability and usefulness were assessed by an actual published data set and simulation study. The model is basically a conventional compartment model, and the transfer rate from the bile compartment to the central compartment is assumed to change periodically, with the sine function being used to describe this periodical change. Using this model, the effect of the parameter values on plasma time-course profiles was examined by simulation, and the applicability of the model was tested by curve fitting to obtain the parameter estimates using an actual published data set. These studies confirmed that our model can simulate the periodical increase of the concentration due to re-absorption. By averaging the sine function in the transfer rate from the bile compartment to the central compartment, a smoothed time-course profile in the elimination phase that is independent of the enterohepatic cycle can be obtained. Also, the apparent half-life in the elimination phase can be estimated, which is useful especially for evaluating drug accumulation during repeated dosing. It was suggested that the present model can be used to evaluate the drug disposition profile with enterohepatic circulation. The effects of sampling points and sampling time on parameter estimation are also discussed.
Structural requirements for the neuroprotective effects of aspirin analogues against N-methyl-D-aspartate and zinc ion neurotoxicity
Authors: Moon Ho-Sang , Nam Sung-Il , Kim Su-Dong , Kim Dong Yeon , Gwag Byoung Joo , Lee YoungAe , Yoon Sung-Hwa 
Published: October 2002

Abstract
In order to elucidate the structural requirements for the dual neuroprotective activity of aspirin against N-methyl-D-aspartate (NMDA) and zinc ion neurotoxicity, various aspirin analogues and derivatives, modified at the carboxylic group, the acetyl group, and the chain length between the carboxylic acid moiety and phenyl ring, were synthesized. Replacement of the carboxylic acid group with alkyl groups (compounds 2c and 2d) resulted in a dramatic increase in neuroprotective activity against NMDA neurotoxicity, while reduction of the carboxylic acid group to the alcohol (compound 2g) completely abolished this activity. In contrast to NMDA neurotoxicity, compounds that are devoid of the carboxylic acid group did not show any activity against zinc ion neurotoxicity. Replacement of the acetyl group with a propionyl (compound 5a) or butyryl group (compound 5b) did not significantly change the activity against NMDA neurotoxicity, but replacement of the acetyl group with a propionyl group (compound 5a) resulted in a slight decrease in activity against zinc ion neurotoxicity. Compound 12, which has ethylene units between the carboxylic acid moiety and phenyl ring in the structure of aspirin, exhibited greater neuroprotective activity against NMDA neurotoxicity than the compared compounds (aspirin, compound 9 and compound 17), which have different chain lengths. A similar trend was also observed in the neuroprotective activity against zinc ion neurotoxicity. These results indicate that the carboxylic acid group in aspirin is not indispensable for the inhibitory effect against NMDA neurotoxicity, but is essential for the inhibitory effect against zinc ion neurotoxicity. The acetyl group and ethylene unit's distance are favourable for the inhibitory effect against NM DA neurotoxicity as well as zinc ion neurotoxicity.
Synthesis and biological evaluations of brain-targeted chemical delivery systems of [Nva2]-TRH
Authors: Wu Jiaxiang , Yoon Sung-Hwa , Wu Whei-Mei , Bodor Nicholas 
Published: October 2002

Abstract
Various chemical delivery systems for [Nva2]-TRH were synthesized and their CNS activity was investigated and compared with that of a similar chemical delivery system of [Leu2]-TRH, previously studied. Sequential metabolism of the chemical delivery system delivered to the brain, starting with the conversion of the dihydrotrigonellyl (DHT) to the trigonellyl (T+) moiety, will provide the lock-in to the brain of the T+-chemical delivery system, which will undergo hydrolysis of the cholesteryl ester, formation of the Pr-amide and cleavage of the spacer-T+ part, allowing ultimately the sustained release of the active [Nva2]-TRH. The CNS activity was assessed by measuring the extent of antagonizing barbiturate-induced sleeping time in mice. The fully packaged DHT-Pro-Pro-Gln-Nva-Pro-Gly-OCh produced robust antagonism, reducing sleeping time from 89 min to 48 min, similar to the Leu2-analogue (49 min). However, the partially substituted [Nva2]-TRH analogues showed little or no CNS activity. The results indicate that the fully packaged delivery system is necessary to produce the successful brain targeting of the precursor construct and effective release of the Gln-Nva-ProNH2.
Ruscogenin glycoside (Lm-3) isolated from Liriope muscari inhibits lymphocyte adhesion to extracellular matrix
Authors: Liu Jianli , Chen Ting , Yu Boyang , Xu Qiang 
Published: October 2002

Abstract
We examined the effects of ruscogenin glycoside (Lm-3), isolated from Liriope muscari, on lymphocyte adhesion to extracellular matrix. Adhesion of Jurkat cells activated by anti-CD3 to type I collagen was inhibited by Lm-3 in a concentration- and time-dependent manner. Lm-3 also inhibited the cell attachment to fibronectin and laminin. However, the saponin did not influence anti-CD3-induced cell proliferation and Mn2+-induced adhesion. Protein kinase C activator, phorbol 12, 13-dibutyrate, significantly enhanced, while its inhibitor, chlorpromazine, almost completely blocked, the adhesion of anti-CD3-activated Jurkat cells to collagen. Against phorbol 12,13-dibutyrate-activated Jurkat cells, Lm-3 treatment, either before or after activation, significantly inhibited the cell adhesion to collagen. Lm-3 also inhibited the adhesion activated by both anti-CD3 and phorbol 12,13-dibutyrate. Similar inhibition by Lm-3 of the phorbol 12,13-dibutyrate-induced adhesion to collagen was also observed in lymphocytes freshly isolated from mice with contact dermatitis. Furthermore, Lm-3 significantly decreased the leucocyte accumulation in an animal model of experimental pleurisy. These results suggest that the blockade of lymphocyte adhesion to extracellular matrix through interference with the protein kinase C pathway may be one of the mechanisms by which Lm-3 exerts anti-inflammatory activity.
Effect of a potent cyclooxygenase inhibitor, 5-ethyl-4-methoxy-2-phenylquinoline (KTC-5), on human platelets
Authors: Liao Chang-Hui , Liao Cho-Hwa , Chang Ya-Ling , Guh Jih-Hwa , Kuo Shen-Chu , Huang Li-Jiau , Teng Che-Ming 
Published: October 2002

Abstract
Because the metabolites of arachidonic acid participate in many physiopathological responses, including inflammation and platelet aggregation, cyclooxygenase inhibitors are important in the treatment of associated diseases. A biologically active compound, 5-ethyl-4-methoxy-2-phenyl-quinoline (KTC-5), selectively and concentration dependently inhibited aggregation of platelets from man and ATP release caused by arachidonic acid (200 μM) and collagen (10 μ g mL−1) without affecting the aggregation caused by thrombin (0.1 U mL−1) and U46619 (2 μM). The IC50 value (drug concentration inhibiting maximum response by 50%) of KTC-5 for aggregation induced by arachidonic acid and collagen was 0.11 ± 0.04 μM and 0.20 ± 0.03 μM, respectively. This inhibitory effect of KTC-5 was reversible and time dependent. KTC-5 specifically inhibited intracellular calcium mobilization initiated by arachidonic acid or collagen without affecting that caused by thrombin or U46619 in human platelets. Furthermore, KTC-5 inhibited thromboxane B2 and prostaglandin D2 formation provoked by arachidonic acid. The IC50 value of KTC-5 for arachidonic-acid-induced thromboxane B2 formation was 0.07 ± 0.02 μM. Based on these observations, the data indicated that KTC-5 potently inhibited human platelet aggregation and ATP release mainly via the inhibition of the cyclooxygenase-1 activity. Moreover, KTC-5 inhibited lipopolysaccharide-induced prostaglandin E2 formation in RAW264.7 cells in the presence of external arachidonic acid with an IC50 value of 0.17 ± 0.06 μM. Immunoblot analysis showed that KTC-5 did not affect the cyclooxygenase-2 expression in the presence of lipopolysaccharide on RAW264.7 cells. This result indicated that KTC-5 affects the activity of cyclooxygenase-2. According to these data, we concluded that KTC-5 is a cyclooxygenase inhibitor for both subtypes.
Absorption characteristics of model compounds with different molecular weights from the serosal caecal surface in rats
Authors: Nishida Koyo , Nose Seiichi , Kuma Akiko , Mukai Takahiro , Kawakami Shigeru , Nakashima Mikiro , Sasaki Hitoshi , Sakaeda Toshiyuki , Nakamura Junzo 
Published: October 2002

Abstract
The purpose of this study was to clarify the absorption characteristics of drugs across the serosal caecal surface membrane, occupying a large absorption area in the peritoneal cavity in rats. Absorption of phenolsulfonphthalein (PSP) and fluorescein isothiocyanate dextrans (FDs) as model drugs after application to the rat serosal caecal surface was investigated using a cylindrical diffusion cell. PSP was absorbed from the rat serosal caecal surface, followed by appearance in the plasma and bile. The time course of the remaining PSP amount in the diffusion cell obeyed first-order kinetics, and the rate constant, Ka, was calculated to be 8.01 × 10−3min−1. No significant difference was seen in the absorption ratio of PSP, which was approximately 90% in 6 h for three doses (0.3, 0.5 and 1 mg), suggesting linear absorption. Moreover, the absorption ratios of FDs from the rat serosal caecal surface at 3 h decreased with an increase in the molecular weight (24.7 % for FD-4, 12.8% for FD-10 and 3.4% for FD-40).
Measuring Equity in Readmission as a Distinct Assessment of Hospital Performance
Authors: Nash Katherine A. , Weerahandi Himali , Yu Huihui , Venkatesh Arjun K. , Holaday Louisa W. , Herrin Jeph , Lin Zhenqiu , Horwitz Leora I. , Ross Joseph S. , Bernheim Susannah M. 
Published: January 2024

ImportanceEquity is an essential domain of health care quality. The Centers for Medicare &amp;amp; Medicaid Services (CMS) developed 2 Disparity Methods that together assess equity in clinical outcomes.ObjectivesTo define a measure of equitable readmissions; identify hospitals with equitable readmissions by insurance (dual eligible vs non–dual eligible) or patient race (Black vs White); and compare hospitals with and without equitable readmissions by hospital characteristics and performance on accountability measures (quality, cost, and value).Design, Setting, and ParticipantsCross-sectional study of US hospitals eligible for the CMS Hospital-Wide Readmission measure using Medicare data from July 2018 through June 2019.Main Outcomes and MeasuresWe created a definition of equitable readmissions using CMS Disparity Methods, which evaluate hospitals on 2 methods: outcomes for populations at risk for disparities (across-hospital method); and disparities in care within hospitals’ patient populations (within-a-single-hospital method).ExposuresHospital patient demographics; hospital characteristics; and 3 measures of hospital performance—quality, cost, and value (quality relative to cost).ResultsOf 4638 hospitals, 74% served a sufficient number of dual-eligible patients, and 42% served a sufficient number of Black patients to apply CMS Disparity Methods by insurance and race. Of eligible hospitals, 17% had equitable readmission rates by insurance and 30% by race. Hospitals with equitable readmissions by insurance or race cared for a lower percentage of Black patients (insurance, 1.9% [IQR, 0.2%-8.8%] vs 3.3% [IQR, 0.7%-10.8%], P &amp;lt; .01; race, 7.6% [IQR, 3.2%-16.6%] vs 9.3% [IQR, 4.0%-19.0%], P = .01), and differed from nonequitable hospitals in multiple domains (teaching status, geography, size; P &amp;lt; .01). In examining equity by insurance, hospitals with low costs were more likely to have equitable readmissions (odds ratio, 1.57 [95% CI, 1.38-1.77), and there was no relationship between quality and value, and equity. In examining equity by race, hospitals with high overall quality were more likely to have equitable readmissions (odds ratio, 1.14 [95% CI, 1.03-1.26]), and there was no relationship between cost and value, and equity.Conclusion and RelevanceA minority of hospitals achieved equitable readmissions. Notably, hospitals with equitable readmissions were characteristically different from those without. For example, hospitals with equitable readmissions served fewer Black patients, reinforcing the role of structural racism in hospital-level inequities. Implementation of an equitable readmission measure must consider unequal distribution of at-risk patients among hospitals.
Perinatal Depression and Risk of Suicidal Behavior
Authors: Yu Hang , Shen Qing , Bränn Emma , Yang Yihui , Oberg Anna Sara , Valdimarsdóttir Unnur Anna , Lu Donghao 
Published: January 2024

ImportanceSuicidal ideation is common among women with perinatal depression (PND). However, prospective data are limited on the risk, particularly long-term risk, of suicidal behavior (suicide attempt and completed suicide) among women with perinatal depression.ObjectiveTo examine the association between PND and risk of short- and long-term suicidal behavior.Design, Setting, and ParticipantsA nationwide population-matched cohort study was conducted in Sweden including 86 551 women with PND from 2001 to 2017 and 865 510 unaffected women individually matched on age and calendar year at delivery. Sibling comparison was used to account for familial confounding. Data were analyzed from January 2022 to November 2023.ExposurePND was identified through depression diagnosis or filled prescriptions of antidepressants from pregnancy to 1 year post partum in registers.Main Outcomes and MeasuresAll women were followed up for the first event of suicidal behavior recorded in registers. Hazard ratios (HR) of suicidal behavior were estimated using time-to-event analysis.ResultsWomen with PND (86 551 participants) received a diagnosis at a mean (SD) age of 30.67 (5.23) years. During a median (IQR) follow-up of 6.91 (3.62-10.88) years, 3604 events of suicidal behavior (incidence rate [IR], 5.62 per 1000 person-years) were identified among women with PND and 6445 (IR, 1.01 per 1000 person-years) among population-unaffected women. Women with PND had an elevated risk of suicidal behavior when compared with matched unaffected women (HR, 3.15; 95% CI, 2.97-3.35). Comparable, albeit somewhat attenuated, associations were yielded when comparing PND women with their PND-free sisters (HR, 2.75; 95% CI, 2.10-3.61). In the population-matched cohort, the association was greater for postnatal depression and among women without a history of psychiatric disorders. The excess risk was pronounced during the first year after diagnosis (HR, 7.20; 95% CI, 6.07-8.54), yet remained statistically significant during 5 to 18 years of follow-up (HR, 2.34; 95% CI, 2.12-2.57).Conclusions and RelevanceIn this nationwide cohort study, women with PND were at an increased risk of suicidal behavior, particularly within the first year after diagnosis with persistent risk elevations throughout the 18 years of follow-up, highlighting the need for vigilant clinical monitoring of this vulnerable group.
Total Knee Arthroplasty Versus Education and Exercise for Knee Osteoarthritis: A Propensity‐Matched Analysis
Authors: Young James J. , Zywiel Michael G. , Skou Søren T. , Chandran Vinod , Davey J. Rod , Gandhi Rajiv , Mahomed Nizar N. , Syed Khalid , Veillette Christian J. H. , Rampersaud Y. Raja , Perruccio Anthony V. 
Published: January 2024

ObjectiveWe estimate the treatment effect of total knee arthroplasty (TKA) versus an education and exercise (Edu+Ex) program on pain, function, and quality of life outcomes 3 and 12 months after treatment initiation for knee osteoarthritis (OA).MethodsPatients with knee OA who had undergone TKA were matched on a 1:1 ratio with participants in an Edu+Ex program based on a propensity score fitted to a range of pretreatment covariates. After matching, between‐group differences in improvement (the treatment effect) in Knee Injury and Osteoarthritis Outcome Score 12‐item version (0, worst to 100, best) pain, function, and quality of life from baseline to 3 and 12 months were estimated using linear mixed models, adjusting for unbalanced covariates, if any, after matching.ResultsThe matched sample consisted of 522 patients (Edu+Ex, n = 261; TKA, n = 261) who were balanced on all pretreatment characteristics. At 12‐month follow‐up, TKA resulted in significantly greater improvements in pain (mean difference [MD] 22.8; 95% confidence interval [95% CI] 19.7–25.8), function (MD 21.2; 95% CI 17.7–24.4), and quality of life (MD 18.3; 15.0–21.6). Even so, at least one‐third of patients receiving Edu+Ex had a clinically meaningful improvement in outcomes at 12 months compared with 75% of patients with TKA.ConclusionTKA is associated with greater improvements in pain, function, and quality of life, but these findings also suggest that Edu+Ex may be a viable alternative to TKA in a meaningful proportion of patients, which may reduce overall TKA need. Confirmatory trials are needed.
Tribotronic Vertical Field‐Effect Transistor Based on van der Waals Heterostructures
Authors: Wang Yifei , Lin Xiangde , Gao Guoyun , Yu Jinran , Wei Yichen , Gong Jie , Sun Jia , Wang Zhong Lin , Sun Qijun 
Published: January 2024

AbstractGraphene has attracted considerable interest for next‐generation electronics. However, the absence of natural bandgap has limited the current on/off ratio of graphene‐based transistors. Vertical integration of 2D heterostructures offers a promising approach to address this challenge, enabling high‐current‐density vertical field‐effect transistor (VFET) with large on/off ratio. Here, a triboelectric potential‐powered VFET with a vertical stacked graphene/MoS2 heterostructure and a sliding‐mode triboelectric nanogenerator (TENG) coupled with gate dielectrics are proposed. The tribotronic VFET has an ultrashort channel length in vertical direction, exhibiting excellent current driving capability with an ultrahigh on‐state current density of 950 A cm−2 and a good current on/off ratio of 630. It also demonstrates reconfigurable diode behavior with a rectification ratio over 102. Temperature‐dependent studies are applied to tribotronic devices for the first time, indicating an effective modulation on the Schottky barrier height of 150 meV by the triboelectric potential. A green LED pixel is driven by the tribotronic VFET as a demonstration to work as a tactile interactive light‐emitting device. The demonstrated tribotronic vertical device offers a promising strategy for integrating various 2D layered materials with TENG in vertical direction, enabling 3D integration of low‐power and interactive devices for next‐generation electronics.