754 research outputs found

    pH-responsive high-density lipoprotein-like nanoparticles to release paclitaxel at acidic pH in cancer chemotherapy

    Get PDF
    Jae-Yoon Shin,1,* Yoosoo Yang,1,* Paul Heo,1 Ji-Chun Lee,1 ByoungJae Kong,1 Jae Youl Cho,1 Keejung Yoon,1 Cheol-Su Shin,2 Jin-Ho Seo,3 Sung-Gun Kim,4 Dae-Hyuk Kweon11Department of Genetic Engineering, College of Biotechnology and Bioengineering, and Center for Human Interface Nano Technology, Sungkyunkwan University, 2APTech Research Center, Suwon, 3Department of Agricultural Biotechnology, Seoul National University, Seoul, 4Department of Biomedical Science, Youngdong University, Chungbuk, South Korea*These authors contributed equally to this workBackground: Nanoparticles undergoing physicochemical changes to release enclosed drugs at acidic pH conditions are promising vehicles for antitumor drug delivery. Among the various drug carriers, high-density lipoprotein (HDL)-like nanoparticles have been shown to be beneficial for cancer chemotherapy, but have not yet been designed to be pH-responsive.Methods and results: In this study, we developed a pH-responsive HDL-like nanoparticle that selectively releases paclitaxel, a model antitumor drug, at acidic pH. While the well known HDL-like nanoparticle containing phospholipids, phosphatidylcholine, and apolipoprotein A-I, as well as paclitaxel (PTX-PL-NP) was structurally robust at a wide range of pH values (3.8–10.0), the paclitaxel nanoparticle that only contained paclitaxel and apoA-I selectively released paclitaxel into the medium at low pH. The paclitaxel nanoparticle was stable at physiological and basic pH values, and over a wide range of temperatures, which is a required feature for efficient cancer chemotherapy. The homogeneous assembly enabled high paclitaxel loading per nanoparticle, which was 62.2% (w/w). The molar ratio of apolipoprotein A-I and paclitaxel was 1:55, suggesting that a single nanoparticle contained approximately 110 paclitaxel particles in a spherical structure with a 9.2 nm diameter. Among the several reconstitution methods applied, simple dilution following sonication enhanced the reconstitution yield of soluble paclitaxel nanoparticles, which was 0.66. As a result of the pH responsiveness, the anticancer effect of paclitaxel nanoparticles was much more potent than free paclitaxel or PTX-PL-NP.Conclusion: The anticancer efficacy of both paclitaxel nanoparticles and PTX-PL-NP was dependent on the expression of scavenger receptor class B type I, while the killing efficacy of free paclitaxel was independent of this receptor. We speculate that the pH responsiveness of paclitaxel nanoparticles enabled efficient endosomal escape of paclitaxel before lysosomal break down. This is the first report on pH-responsive nanoparticles that do not contain any synthetic polymer.Keywords: pH responsiveness, nanoparticle, apolipoprotein A-I, paclitaxe

    Design of the VISTA-ITL Test Facility for an Integral Type Reactor of SMART and a Post-Test Simulation of a SBLOCA Test

    Get PDF
    To validate the performance and safety of an integral type reactor of SMART, a thermal-hydraulic integral effect test facility, VISTA-ITL, is introduced with a discussion of its scientific design characteristics. The VISTA-ITL was used extensively to assess the safety and performance of the SMART design, especially for its passive safety system such as a passive residual heat removal system, and to validate various thermal-hydraulic analysis codes. The VISTA-ITL program includes several tests on the SBLOCA, CLOF, and PRHRS performances to support a verification of the SMART design and contribute to the SMART design licensing by providing proper test data for validating the system analysis codes. A typical scenario of SBLOCA was analyzed using the MARS-KS code to assess the thermal-hydraulic similarity between the SMART design and the VISTA-ITL facility, and a posttest simulation on a SBLOCA test for the shutdown cooling system line break has been performed with the MARS-KS code to assess its simulation capability for the SBLOCA scenario of the SMART design. The SBLOCA scenario in the SMART design was well reproduced using the VISTA-ITL facility, and the measured thermal-hydraulic data were properly simulated with the MARS-KS code

    Patterns of Using Complementary and Alternative Medicine by Stroke Patients at Two University Hospitals in Korea

    Get PDF
    This study measured the prevalence of complementary and alternative medicine (CAM) use among Korean stroke patients. Questionnaire-based 20-min interviews were conducted at the hospitals by a trained nurse after an outpatient visit. It included questions on demographic information, clinical information and the utilization of CAM. Of 304 stroke-patient respondents, 164 (54%) had used CAM, of which 66% had started taking CAM products following suggestions from family members and other relatives. Of the 57% of users who felt that CAM was effective, 84% considered that it improved the symptoms of stroke and 16% felt it was effective in achieving psychological relaxation. Of the eight CAM categories used by respondents, 92% used traditional Oriental medical treatments, 36% used plant- and animal-derived over-the-counter health care products, 24% used minerals and vitamins, and 11% used manual therapies. The majority of stroke patients (68%) were trying a new type of CAM, and half of the respondents (45%) relied on the knowledge of their general practitioner about CAMs when deciding whether to use them. Most of the stroke patients in this study used CAM, and a half of them reported beneficial effects. Despite the presence of adverse side effects, they tended to be used without discussion with chief physicians, and hence physicians should be actively involved in the usage of CAM

    Effects of education on low-phosphate diet and phosphate binder intake to control serum phosphate among maintenance hemodialysis patients: A randomized controlled trial.

    Get PDF
    Background:For phosphate control, patient education is essential due to the limited clearance of phosphate by dialysis. However, well-designed randomized controlled trials about dietary and phosphate binder education have been scarce. Methods:We enrolled maintenance hemodialysis patients and randomized them into an education group (n = 48) or a control group (n = 22). We assessed the patients' drug compliance and their knowledge about the phosphate binder using a questionnaire. Results:The primary goal was to increase the number of patients who reached a calcium-phosphorus product of lower than 55. In the education group, 36 (75.0%) patients achieved the primary goal, as compared with 16 (72.7%) in the control group (P = 0.430). The education increased the proportion of patients who properly took the phosphate binder (22.9% vs. 3.5%, P = 0.087), but not to statistical significance. Education did not affect the amount of dietary phosphate intake per body weight (education vs. control: -1.18 ± 3.54 vs. -0.88 ± 2.04 mg/kg, P = 0.851). However, the dietary phosphate-to-protein ratio tended to be lower in the education group (-0.64 ± 2.04 vs. 0.65 ± 3.55, P = 0.193). The education on phosphate restriction affected neither the Patient-Generated Subjective Global Assessment score (0.17 ± 4.58 vs. -0.86 ± 3.86, P = 0.363) nor the level of dietary protein intake (-0.03 ± 0.33 vs. -0.09 ± 0.18, P = 0.569). Conclusion:Education did not affect the calcium-phosphate product. Education on the proper timing of phosphate binder intake and the dietary phosphate-to-protein ratio showed marginal efficacy

    Assessment of serum biomarkers and coagulation/fibrinolysis markers for prediction of neurological outcomes of out of cardiac arrest patients treated with therapeutic hypothermia

    Get PDF
    Objective Despite increased survival in patients with cardiac arrest, it remains difficult to determine patient prognosis at the early stage. This study evaluated the prognosis of cardiac arrest patients using brain injury, inflammation, cardiovascular ischemic events, and coagulation/fibrinolysis markers collected 24, 48, and 72 hours after return of spontaneous circulation (ROSC). Methods From January 2011 to December 2016, we retrospectively observed patients who underwent therapeutic hypothermia. Blood samples were collected immediately and 24, 48, and 72 hours after ROSC. Neuron-specific enolase (NSE), S100-B protein, procalcitonin, troponin I, creatine kinase-MB, pro-brain natriuretic protein, D-dimer, fibrin degradation product, antithrombin-III, fibrinogen, and lactate levels were measured. Prognosis was evaluated using Glasgow-Pittsburgh cerebral performance categories and the predictive accuracy of each marker was evaluated. The secondary outcome was whether the presence of multiple markers improved prediction accuracy. Results A total of 102 patients were included in the study: 39 with good neurologic outcomes and 63 with poor neurologic outcomes. The mean NSE level of good outcomes measured 72 hours after ROSC was 18.50 ng/mL. The area under the curve calculated on receiver operating characteristic analysis was 0.92, which showed the best predictive power among all markers included in the study analysis. The relative integrated discrimination improvement and category-free net reclassification improvement models showed no improvement in prognostic value when combined with all other markers and NSE (72 hours). Conclusion Although biomarker combinations did not improve prognostic accuracy, NSE (72 hours) showed the best predictive power for neurological prognosis in patients who received therapeutic hypothermia

    Angiosarcoma of the Retroperitoneum: Report on a Patient Treated with Sunitinib

    Get PDF
    A 52 year-old woman presented with an incidentally detected retroperitoneal angiosarcoma and multiple hepatic metastases. After chemotherapy with weekly paclitaxel and doxorubicin, angiosarcoma had progressed rapidly. Because few chemotherapeutic options were available for her, sunitinib (37.5 mg/day, daily) as a salvage regimen was administered. Although sunitinib was interrupted after two weeks due to hematologic abnormalities, some metastatic nodules were regressed. Therefore, sunitinib was recommenced at a reduced dose (25 mg/day, daily). Serial computed tomography scans showed variable response in each tumor, however, sunitinib at least delayed tumor progression, compared to previous chemotherapy. With this case report, we suggest sunitinib may be effective against angiosarcomas. When sunitinib is administered to patients with angiosarcomas, hematologic abnormalities should be monitored frequently as severe hematologic toxicity may be caused either by sunitinib per se or angiosarcoma
    • …
    corecore