• Title/Summary/Keyword: time in therapeutic range

Search Result 115, Processing Time 0.023 seconds

Effects of Baicalein on Neuroinflammation in Lipopolysaccharide-treated Mice (Baicalein이 Lipopolysaccharide에 의한 생쥐의 Neuroinflammation에 미치는 영향)

  • Ha, Gyung-Woon;Kim, Youn-Sub
    • The Korea Journal of Herbology
    • /
    • v.28 no.2
    • /
    • pp.93-101
    • /
    • 2013
  • Objects : Baicalein is a major bioactive flavonoid component of Scutellaria baicalensis Georgi that shows a wide range of biological activities, including neuroprotections and anti-inflammatory actions. Hence it is a potential therapeutic material for the treatment of neuroinflammation. In this study, we investigated the modulatory effect of baicalein on neuroinflammation. Method : Pro-inflammatory cytokines (TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 mRNA), COX-2 mRNA expression and microglial activation in the brain tissue is induced by systemic lipopolysaccharide (LPS) treatment in C57BL/6 mice. Baicalein was treated orally with 10, 20, and 30 mg/kg 1 hour prior to the LPS (3 mg/kg, i.p.) injection. TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and COX-2 mRNA expression in the brain tissue was measured by the quantitative real-time polymerase chain reaction(PCR) method. Iba1 expression in the brain was measured by western blotting method. Microglia was observed with immunohistochemistry. Results : Baicalein 30 mg/kg significantly attenuated the expression of TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and COX-2 mRNA in the brain tissue. Baicalein 20 mg/kg significantly attenuated the expression of IL-6 mRNA in the brain tissue. Baicalein 30 mg/kg significantly attenuated the expression of Iba1 protein expression in the brain tissue. Baicalein 30 mg/kg significantly decreased the number and cell size of microglia in the cerebral cortex and hypothalamic region and the area percentage of Iba1-expressed microglia in the hippocampus. Conclusion : These results demonstrated that baicalein attenuates LPS induced neuroinflammation in the mice via reduction of pro-inflammatory cytokines (TNF-${\alpha}$, IL-$1{\beta}$, IL-6), COX-2 mRNA expression and microglial activation.

Quercetin Prevents Hydrogen Peroxide-induced Necrotic and Apoptotic Cell Death in Human Colonic Epithelial Cells

  • Jung, Soon-Hee
    • Korean Journal of Clinical Laboratory Science
    • /
    • v.43 no.4
    • /
    • pp.161-170
    • /
    • 2011
  • Quercetin is one of the most distributed flavonoids in the plant kingdom and occurs naturally in a wide range of fruits and vegetables. This study was undertaken to determine whether quercetin exerts beneficial effect against necrotic and apoptotic cell death induced by hydrogen peroxide ($H_2O2$) in intestinal cells using the human-derived cultured T84 colonic epithelial cell line. Necrotic cell death was induced by exposing cells to 0.5 mM $H_2O_2$ for 2 h and apoptosis was induced by incubating cells in normal culture medium for 18 h following exposure of cells to 0.5 mM $H_2O2$ for 2 h. Cell viability was evaluated by the trypan blue exclusion assay and apoptosis was assessed by Hoechst 33258 staining and flow cytometry. $H_2O_2$ induced necrotic cell death in a time and dose-dependent fashion. Both necrotic and apoptotic cell deaths were not prevented by the antioxidants N,N'-diphenyl-p-phenylenediamine(DPPD) and Trolox, whereas both cell deaths induced by the organic hydroperoxide t-butylhydroperoxide (tBHP) were prevented by DPPD, suggesting that $H_2O_2$ induces cell death through a lipid peroxidation-independent mechanism. $H_2O2$-induced necrotic death was prevented by deferoxamine and 3-aminobenzamide, while the apoptotic cell death was not affected by these agents. Quercetin prevented both necrotic and apoptotic cell deaths induced by $H_2O_2$ in a dose-dependent manner. $H_2O_2$ caused activation of poly (ADP-ribose) polmerase (PARP), which was inhibited by deferoxamine, 3-aminobenzamide, and quercetin, but not DPPD. These results indicate that quercetin inhibits both necroticand apoptotic deaths of T84 cells. The anti-necrotic effect of quercetin may be attributed to its iron chelator activity rather than a direct $H_2O_2$ scavenging capacity and antioxidant. The present study suggests that quercetin may play a therapeutic role in the treatment of human gastrointestinal diseases mediated by oxidants.

  • PDF

Development of Polymeric Nanopaclitaxel and Comparison with Free Paclitaxel for Effects on Cell Proliferation of MCF-7 and B16F0 Carcinoma Cells

  • Yadav, Deepak;Anwar, Mohammad Faiyaz;Garg, Veena;Kardam, Hemant;Beg, Mohd Nadeem;Suri, Suruchi;Gaur, Sikha;Asif, Mohd
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.15 no.5
    • /
    • pp.2335-2340
    • /
    • 2014
  • Paclitaxel is hydrophobic in nature and is recognized as a highly toxic anticancer drug, showing adverse effects in normal body sites. In this study, we developed a polymeric nano drug carrier for safe delivery of the paclitaxel to the cancer that releases the drug in a sustained manner and reduces side effects. N-isopropylacrylamide/vinyl pyrrolidone (NIPAAm/VP) nanoparticles were synthesized by radical polymerization. Physicochemical characterization of the polymeric nanoparticles was conducted using dynamic light scattering, transmission electron microscopy, scanning electron microscopy and nuclear magnetic resonance, which confirmedpolymerization of formulated nanoparticles. Drug release was assessed using a spectrophotometer and cell viability assays were carried out on the MCF-7 breast cancer and B16F0 skin cancer cell lines. NIPAAm/VP nanoparticles demonstrated a size distribution in the 65-108 nm range and surface charge measured -15.4 mV. SEM showed the nanoparticles to be spherical in shape with a slow drug release of ~70% in PBS at $38^{\circ}C$ over 96 h. Drug loaded nanoparticles were associated with increased viability of MCF-7 and B16F0 cells in comparison to free paclitaxel. Nano loaded paclitaxel shows high therapeutic efficiency by sustained release action for the longer period of time, i increasing its efficacy and biocompatibility for human cancer therapy. Therefore, paclitaxel loaded (NIPAAm/VP) nanoparticles may provide opportunities to expand delivery of the drug for clinical selection.

Extrapulmonary Small Cell Carcinoma - a Case Series of Oropharyngeal and Esophageal Primary Sites Treated with Chemo-Radiotherapy

  • Sahai, Puja;Baghmar, Saphalta;Nath, Devajit;Arora, Saurabh;Bhasker, Suman;Gogia, Ajay;Sikka, Kapil;Kumar, Rakesh;Chander, Subhash
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.16 no.16
    • /
    • pp.7025-7029
    • /
    • 2015
  • Background: The optimal sequence and extent of multimodality therapy remains to be defined for extrapulmonary small cell carcinoma because of its rarity. The purpose of our study was to assess the response to neoadjuvant chemotherapy followed by chemoradiation/radiation in patients with extrapulmonary small cell carcinoma. Materials and Methods: Four consecutively diagnosed patients were included in this study. The primary tumor site was oropharynx in three patients and esophagus in one. The patients with the limited disease were treated with chemotherapy followed by concurrent chemoradiation (n=2) or radiotherapy (n=1). The patient with the extensive disease with the primary site in vallecula was treated with chemotherapy and palliative radiotherapy to the metastatic site. Results: The median follow-up was 22.5 months (range, 8-24 months). Three patients with the limited disease (base of tongue, n=2; esophagus, n=1) were in complete remission. The patient with the extensive disease died of loco-regional tumor progression at 8 months from the time of diagnosis. Conclusions: The combination of chemotherapy and radiotherapy is the preferred therapeutic approach for patients with extrapulmonary small cell carcinoma. Induction chemotherapy followed by concurrent chemoradiation or radiation provides a good loco-regional control in patients with limited disease.

Feasibility of Early Definitive Internal Fixation of Pelvic Bone Fractures in Therapeutic Open Abdomen

  • Choi, Kyunghak;Jung, Kwang-Hwan;Keum, Min Ae;Kim, Sungjeep;Kim, Jihoon T;Kyoung, Kyu-Hyouck
    • Journal of Trauma and Injury
    • /
    • v.33 no.1
    • /
    • pp.18-22
    • /
    • 2020
  • Purpose: Damage control laparotomy has contributed to improved survival rates for severe abdominal injuries. A large part of severe abdominal injury occurs with a concomitant pelvic bone fracture. The safety and effectiveness of internal fixation of pelvic bone fracture(s) has not been established. The aim of the present study was to evaluate infection risk in the pelvic surgical site in patients who underwent emergent abdominal surgery. Methods: This single-center retrospective observational study was based on data collected from a prospectively maintained registry between January 2015 and June 2019. Patients who underwent laparotomy and pelvic internal fixation were included. Individuals <18 and ≥80 years of age, those with no microbiological investigations, and those who underwent one-stage abdominal surgery were excluded. Comprehensive statistical comparative analysis was not performed due to the small number of enrolled patients. Results: A total of six patients met the inclusion criteria, and the most common injury mechanism was anterior-posterior compression (67%). The average duration of open abdomen was 98 hours (range, 44-98), and the time interval between abdominal closure and pelvic surgery was 98 hours. One patient (16.7%) died due to multi-organ dysfunction syndrome. Micro-organisms were identified in the abdominal surgical site in five patients (83%), with no micro-organisms in pelvic surgical sites. There was no unplanned implant removal. Conclusions: Internal fixation of pelvic bone fracture(s) could be performed in the state of open abdomen, and the advantages of early fixation may countervail the risks for cross contamination.

Cytotoxic and Apoptotic Activites of Echinomycin Derivative (Echinomycin-7) on P388 Murine Leukemia Cells

  • Jeon, Hyang;Kim, Sung-Su;Kim, Yoon-Suk;Park, Yil-Sung;Kim, Yong-Hae;Choi, Sun-Ju;Kim, Soo-Kie;Kim, Tae-Ue
    • BMB Reports
    • /
    • v.31 no.6
    • /
    • pp.560-564
    • /
    • 1998
  • Echinomycin-7 is an echinomycin derivative, Smethylated sulfonium perchlorate of echinomycin. We studied the in vitro cytotoxicity and in vivo antitumor activity of echinomycin-7 against P388 leukemia cells and compared the results with echinomycin. With respect to the cytotoxic effects, echinomycin-7 had cell line-dependent $IC_{50}$ values while echinomycin had similar values to several tumor cell lines. Also, in vivo antitumor activities were observed in tumor-bearing mice treated with both agents, which showed that echinomycin-7 had a broad therapeutic dose range. We also observed the apoptosis on leukemia cells treated with echinomycin-7 which exihibited the ladder pattern of DNA on electrophoresis. In addition to apoptosis, echinomycin-7 arrested $G_1/S$ phases of the cell cycle at the same time. We then examined the signaling pathway of echinomycin-7-induced apoptosis and showed that ERK of the MAP kinase family was activated and translocated into the nucleus by echinomycin-7 stimulation. This study suggests that echinomycin-7 acts as an antitumor agent through in vitro cytotoxicity and has in vivo antitumor activity against leukemia cells, and that the echinomycin-7- induced apoptosis might involve signal transduction via MAP kinases.

  • PDF

Arm Cortex S3C2440 Microcontroller Application for Transcranial Magnetic Stimulation's Pulse Forming on Bax Reactive Cells and Cell Death in Ischemia Induced Rats

  • Tac, Han-Ho;Kim, Whi-Young
    • Journal of Magnetics
    • /
    • v.21 no.2
    • /
    • pp.266-272
    • /
    • 2016
  • Transcranial magnetic stimulation devices has been used mainly for diagnostic purposes by measuring the functions of the nervous system rather than for treatment purposes, and has a problem of considerable energy fluctuations per repeated pulse. The majority of strokes are caused by ischemia and result in brain tissue damage, leading to problems of the central nervous system including hemiparesis, dysfunction of language and consciousness, and dysfunction of perception. Control is difficult and the size is large due to the difficulty of digitalizing the energy stored in a capacitor, and there are many heavy devices. In addition, there are many constraints when it is used for a range of purposes such as head and neck diagnosis, treatment and rehabilitation of nerve palsy, muscle strengthening, treatment of urinary incontinence etc. Output stabilization and minimization of the energy variation rate are required as the level of the transcranial magnetic stimulation device is dramatically improved and the demand for therapeutic purposes increases. This study developed a compact, low cost transcranial magnetic stimulation device with minimal energy variation of a high repeated pulse and output stabilization using a real time capacitor charge discharge voltage. Ischemia was induced in male SD rats by closing off the common carotid artery for 5 minutes, after which the blood was re-perfused. In the cerebrum, the number of PARP reactive cells after 24 hours significantly decreased (p < 0.05) in the TMS group compared to the GI group. As a result, TMS showed the greatest effect on necrosis-related PARP immuno-reactive cells 24 hours after ischemia, indicating necrosis inhibition, blocking of neural cell death, and protection of neural cells.

Correlations Between Hand Dexterity and Visual-Motor Skills of the Preschooler (취학 전 아동의 손 기민성과 시각-운동 기술과의 상관성에 대한 연구)

  • Kang, Hyun-Jin;Ko, Kyoung-Hye;Park, Su-Jung;Park, Ju-Yeoun;Chang, Moon-Young
    • The Journal of Korean Academy of Sensory Integration
    • /
    • v.3 no.1
    • /
    • pp.13-21
    • /
    • 2005
  • Objective : The purpose of this study was to investigate the correlation between hand dexterity and visual-motor skills of preschoolers. We searched for the correlation between two test results, which were the 9-Hole Peg Test performance time and the visual motor integration test(VMI) performance score. Then, we also compared the 9-Hole Peg Test performance times with the VMI performance scores according to sex and age. Method : The participants were fifty normal children ranging in age from four to six years living in Busan. We used two test methods which have high reliability and validity. One was the 9-Hole Peg Test to evaluate hand dexterity, and the other was the VMI to the evaluate visual-motor skills of these young children. Results : First, over the entire range of the participating children, there was a high correlation between the performance times from the 9-Hole Peg Test and the VMI performance scores(r=-.682). Second, there was not a statistically significant difference between the performance times from the 9-Hole Peg Test and the VMI scores according to sex. Third, there were significant differences between the hand dexterity and visual-motor skills according to the children's age(p<.001). Conclusion : This study proved that there is high correlation between hand dexterity and visual-motor skills of the preschooler. Occupational therapists in preschool service should consider that visual-motor skills need to be compatible with hand dexterity in both evaluation and therapy. In addition, hand dexterity and visual-motor skills improved according to advances in age, so we must give graded tasks to proper age groups through concrete analysis of activity. By doing this, children can get the better therapeutic effects.

  • PDF

Development of Transdermal Delivery Systems Containing Clenbuterol (클렌부테롤 경피흡수제제의 개발)

  • Choi, Han-Gon;Quan, Qi-Zhe;Jung, Si-Young;Rhee, Jong-Dal;Yong, Chul-Soon
    • Journal of Pharmaceutical Investigation
    • /
    • v.30 no.4
    • /
    • pp.247-252
    • /
    • 2000
  • The advantages of transdermal administration are avoiding hepatic first pass effect, minimizing inter- and intra-patient variation, maintaining steady-state plasma level to provide long-term therapy from a single dose, and allowing a rapid termination of drug input. Clenbuterol, a selective ${\beta}_2-adrenergic$ receptor stimulant, has been introduced as a potent bronchodilator for patients with bronchial asthma, chronic obstructive bronchial disease. For the development of transdermal systems containing clenbuterol, two limiting factors - long lag time and low flux - must be overcome. In this study, we attempted to select optimal formulation for preparation of clenbuterol patch using hairless mouse skin and flow-through diffusion cell. The flux of clenbuterol increased as the percent of clenbuterol dose dependently in the concentration range of 5-15%. Based on this result, we fixed the concentration of clenbuterol as 15%. The effect of various penetration enhancers on percutaneous absorption of clenbuterol through hairless mouse skin was investigated. Labrafil was the most effective enhancer, which increased the permeability of clenbuterol approximately 4-fold compared with the control without penetration enhancer. Optimal enhancer concentration was 3%. The effect of various adhesives on penetration of clenbuterol was also investigated. Among the adhesives studied, MA-31 was the most effective adhesive. Furthermore, the clenbuterol patch composed of 15% clenbuterol, 3% Labrafil and 82% MA-31, which gave most excellent penetration of drug in in vitro penetration study, maintained therapeutic plasma levels in in vivo study using S.D. rats. These studies demonstrated a good feasibility of clenbuterol administration through the intact skin using a transdermal patch, and show a possibility of the development of clenbuterol patches.

  • PDF

A Monte Carlo Simulation Study of a Therapeutic Proton Beam Delivery System Using the Geant4 Code (Geant4 몬테카를로 코드를 이용한 양성자 치료기 노즐의 전산모사)

  • Shin, Jungwook;Shim, Hyunha;Kwak, Jungwon;Kim, Dongwook;Park, Sungyong;Cho, Kwan Ho;Lee, Se Byeong
    • Progress in Medical Physics
    • /
    • v.18 no.4
    • /
    • pp.226-232
    • /
    • 2007
  • We studied a Monte Carlo simulation of the proton beam delivery system at the National Cancer Center (NCC) using the Geant4 Monte Carlo toolkit and tested its feasibility as a dose verification framework. The Monte Carlo technique for dose calculation methodology has been recognized as the most accurate way for understanding the dose distribution in given materials. In order to take advantage of this methodology for application to external-beam radiotherapy, a precise modeling of the nozzle elements along with the beam delivery path and correct initial beam characteristics are mandatory. Among three different treatment modes, double/single-scattering, uniform scanning and pencil beam scanning, we have modeled and simulated the double-scattering mode for the nozzle elements, including all components and varying the time and space with the Geant4.8.2 Monte Carlo code. We have obtained simulation data that showed an excellent correlation to the measured dose distributions at a specific treatment depth. We successfully set up the Monte Carlo simulation platform for the NCC proton therapy facility. It can be adapted to the precise dosimetry for therapeutic proton beam use at the NCC. Additional Monte Carlo work for the full proton beam energy range can be performed.

  • PDF