Analgesic Mechanism of Electroacupuncture in an Arthritic Pain Model of Rats: A Neurotransmitter Study

Yonsei University College of Medicine 2011 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Licens

Pharmacokinetic study of meropenem in healthy beagle dogs receiving intermittent hemodialysis

Meropenem, a second carbapenem antimicrobial agent with a broad spectrum of activity, is used to treat sepsis and resistant-bacterial infections in veterinary medicine. The objective of this study was to identify the pharmacokinetics of meropenem in dogs receiving intermittent hemodialysis (IHD) and to determine the proper dosing in renal failure patients receiving IHD. Five healthy beagle dogs were given a single i.v. dose of 24 mg/kg of meropenem and received IHD. The blood flow rate, dialysate flow, and ultrafiltration rate were maintained at 40 mL/min, 300 mL/min, and 40 mL/h, respectively. Blood samples were collected for 24 h from the jugular vein and from the extracorporeal arterial and venous line. Urine samples and dialysate were also collected. The concentrations of meropenem were assayed using HPLC/MS/MS determination. The peak plasma concentration was 116 +/- 37 mu g/mL at 15 min. The systemic clearance was 347 +/- 117 mL/h/kg, and the steady-state volume of distribution was 223 +/- 67 mL/kg. Dialysis clearance was 71.1 +/- 34.3 mL/h/kg, and the extraction ratio by hemodialysis was 0.455 +/- 0.150. The half-life (T-1/2) in dogs with IHD decreased compared with those without IHD, and the reduction in T1/2 was greater in renal failure patients than in normal patients. Sixty-nine percent and 21% of the administered drug were recovered by urine and dialysate in the unchanged form, respectively. In conclusion, additional dosing of 24 mg/kg of meropenem after dialysis could be necessary according to the residual renal function of the patient based on the simulated data.OAIID:RECH_ACHV_DSTSH_NO:T201621129RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:A003050CITE_RATE:1.279FILENAME:Byun_et_al-2016-Journal_of_Veterinary_Pharmacology_and_Therapeutics.pdfDEPT_NM:수의학과EMAIL:[email protected]_YN:YFILEURL:https://srnd.snu.ac.kr/eXrepEIR/fws/file/eb2b2d93-6cb2-4420-a374-90eb43215957/linkCONFIRM:

Efficacy and Safety of Nivolumab Plus Ipilimumab in Patients With Advanced Hepatocellular Carcinoma Previously Treated With Sorafenib The CheckMate 040 Randomized Clinical Trial

IMPORTANCE Most patients with hepatocellular carcinoma (HCC) are diagnosed with advanced disease not eligible for potentially curative therapies; therefore, new treatment options are needed. Combining nivolumab with ipilimumab may improve clinical outcomes compared with nivolumab monotherapy. OBJECTIVE To assess efficacy and safety of nivolumab plus ipilimumab in patients with advanced HCC who were previously treated with sorafenib. DESIGN, SETTING, AND PARTICIPANTS CheckMate 040 is a multicenter, open-label, multicohort, phase 1/2 study. In the nivolumab plus ipilimumab cohort, patients were randomized between January 4 and September 26, 2016. Treatment group information was blinded after randomization. Median follow-up was 30.7 months. Data cutoff for this analysis was January 2019. Patients were recruited at 31 centers in 10 countries/territories in Asia, Europe, and North America. Eligible patients had advanced HCC (with/without hepatitis B or C) previously treated with sorafenib. A total of 148 patients were randomized (50 to arm A and 49 each to arms B and C). INTERVENTIONS Patients were randomized 1:1:1 to either nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, administered every 3 weeks (4 doses), followed by nivolumab 240 mg every 2 weeks (arm A); nivolumab 3 mg/kg plus ipilimumab 1 mg/kg, administered every 3 weeks (4 doses), followed by nivolumab 240 mg every 2 weeks (arm B); or nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks (arm C). MAIN OUTCOMES AND MEASURES Coprimary end points were safety, tolerability, and objective response rate. Duration of response was also measured (investigator assessed with the Response Evaluation Criteria in Solid Tumors v1.1). RESULTS Of 148 total participants, 120 were male (81%). Median (IQR) age was 60 (52.5-66.5). At data cutoff (January 2019), the median follow-up was 30.7 months (IQR, 29.9-34.7). Investigator-assessed objective response rate was 32% (95% CI, 20%-47%) in arm A, 27% (95% CI, 15%-41%) in arm B, and 29% (95% CI, 17%-43%) in arm C. Median (range) duration of response was not reached (8.3-33.7+) in arm A and was 15.2 months (4.2-29.9+) in arm B and 21.7 months (2.8-32.7+) in arm C. Any-grade treatment-related adverse events were reported in 46 of 49 patients (94%) in arm A, 35 of 49 patients (71%) in arm B, and 38 of 48 patients (79%) in arm C; there was 1 treatment-related death (arm A; grade 5 pneumonitis). CONCLUSIONS AND RELEVANCE In this randomized clinical trial, nivolumab plus ipilimumab had manageable safety, promising objective response rate, and durable responses. The arm A regimen (4 doses nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks then nivolumab 240 mg every 2 weeks) received accelerated approval in the US based on the results of this study. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0165887

Correlation between Geometrically induced oxygen octahedral tilts and multiferroic behaviors in BiFeO3 films

The equilibrium position of atoms in a unit cell is directly connected to crystal functionalities, e.g., ferroelectricity, ferromagnetism, and piezoelectricity. The artificial tuning of the energy landscape can involve repositioning atoms as well as manipulating the functionalities of perovskites (ABO3), which are good model systems to test this legacy. Mechanical energy from external sources accommodating various clamping substrates is utilized to perturb the energy state of perovskite materials fabricated on the substrates and consequently change their functionalities; however, this approach yields undesired complex behaviors of perovskite crystals, such as lattice distortion, displacement of B atoms, and/or tilting of oxygen octahedra. Owing to complimentary collaborations between experimental and theoretical studies, the effects of both lattice distortion and displacement of B atoms are well understood so far, which leaves us a simple question: Can we exclusively control the positions of oxygen atoms in perovskites for functionality manipulation? Here the artificial manipulation of oxygen octahedral tilt angles within multiferroic BiFeO3 thin films using strong oxygen octahedral coupling with bottom SrRuO3 layers is reported, which opens up new possibilities of oxygen octahedral engineering

Reversibly controlled ternary polar states and ferroelectric bias promoted by boosting square???tensile???strain

Interaction between dipoles often emerges intriguing physical phenomena, such as exchange bias in the magnetic heterostructures and magnetoelectric effect in multiferroics, which lead to advances in multifunctional heterostructures. However, the defect-dipole tends to be considered the undesired to deteriorate the electronic functionality. Here, we report deterministic switching between the ferroelectric and the pinched states by exploiting a new substrate of cubic perovskite, BaZrO3, which boosts square-tensile-strain to BaTiO3 and promotes four-variants in-plane spontaneous polarization with oxygen vacancy creation. First-principles calculations propose a complex of an oxygen vacancy and two Ti3+ ions coins a charge-neutral defect-dipole. Cooperative control of the defect-dipole and the spontaneous polarization reveals ternary in-plane polar states characterized by biased/pinched hysteresis loops. Furthermore, we experimentally demonstrate that three electrically controlled polar-ordering states lead to switchable and non-volatile dielectric states for application of non-destructive electro-dielectric memory. This discovery opens a new route to develop functional materials via manipulating defect-dipoles and offers a novel platform to advance heteroepitaxy beyond the prevalent perovskite substrates

Cranioplasty Using Three-Dimensional–Printed Polycaprolactone Implant and Free Latissimus Dorsi Musculocutaneous Flap in a Patient with Repeated Wound Problem following Titanium Cranioplasty

Titanium mesh is an alloplastic material widely used for the reconstruction of moderate-to-large skull defects. Repeated wound problems or infection following these reconstructions inevitably lead to the replacement of the cranioplasty material. Among the various alloplastic materials, polycaprolactone implants are usually used for the coverage of small defects such as burr holes. 1 Herein, we present a case of a large cranial defect successfully reconstructed with three-dimensional-printed polycaprolactone implant and a free latissimus dorsi musculocutaneous flap. Until 1-year follow-up, the patient showed a favorable esthetic outcome with no complications or wound relapse

Electrical properties and oxygen sensing ability of Zn1-xCoxO epitaxial films

While Co-doped ZnO has been much studied from the viewpoint of dilute magnetic semiconductors, we offer a new perspective by shedding light on the oxygen sensing ability of Co-doped ZnO. Epitaxial Zn1 xCoxO (x ¼ 0.0,0.05,0.1,0.15) thin films are grown on a-Al2O3 (0001) by pulsed laser deposition. We successfully optimize growth conditions of Zn1 xCoxO films to prevent Co clustering and also to obtain high crystallinity. As Co content (x) increases, the c-axis lattice constant of Zn1 xCoxO films linearly increases. We particularly pay attention to the effect of oxygen annealing and dynamic response under reduction gas (2% hydrogen in Ar) and oxygen gas environment in electrical properties of Zn1 xCoxO. It is shown that the resistance of Zn0.85Co0.15O changes more than two orders of magnitude reversibly as it is reduced and oxidized alternatively. Thus, the present work demonstrates a potential of Zn1 xCoxO as an oxygen sensor at high temperatures. Oxygen (oxygen vacancy and/or oxygen interstitial) and Co in the system appear to play a role cooperatively in determining the electrical properties of Zn1 xCoxO.1122Nsciescopuskc