• Title/Summary/Keyword: non-linear dose-effect

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Preparation and Characterization of Self-assembled Glycol Chitosan Hydrogels Containing Palmityl-acylated Exendin-4 for Extended Hypoglycemic Action

  • Lee, Ju-Ho;Lee, Chang-Kyu;Bae, Sung-Ho;Yoon, Jeong-Hyun;Choi, Eun-Joo;Oh, Kyung-Taek;Lee, Eun-Seong;Lee, Kang-Choon;Youn, Yu-Seok
    • Journal of Pharmaceutical Investigation
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    • v.41 no.3
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    • pp.173-178
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    • 2011
  • Injectable chitosan hydrogels have attracted great potential due to sustained-release property and safety. Here, palmityl-acylated glycol chitosan (Pal-GC) was used to generate physically cross-linked hydrogels by virtue of hydrophobic attraction of linear fatty carbons. Glycol chitosan was chemically modified with N-hydroxysuccinimide-activated palmitic acid in dimethylsulfoxide (DMSO) containing dimethylaminopyridine. Through a series of preparation steps of (i) dialysis with DMSO, (ii) addition of palmityl-acylated exendin-4 (Ex4-C16), and (iii) dialysis with water, Pal-GC was self-assembled to form physically cross-linked hydrogels entrapped with Ex4-C16. The Pal-GC derivative was analyzed by using 1H NMR, and the surface morphology of Pal-GC hydrogels formed was examined by scanning electron microscopy. Also, the hypoglycemic effect induced by Pal-GC hydrogels containing Ex4-C16 (250 nmol/kg) was evaluated in non-fasted type 2 diabetic db/db mice and compared with GC hydrogels containing native Ex4 at the same dose. Results showed that palmityl group was successfully conjugated with the amines of glycol chitosan, and that Pal-GC efficiently generated the hydrogels formation. Moreover, Pal-GC hydrogels containing Ex4-C16 was found to greatly prolong the hypoglycemia duration (~ 4 days). This was due to the dual-functions of the palmityl groups present in both GC and exendin-4 such as hydrophobic attraction and plasma albumin-binding. We consider this new type of self-assembled GC hydrogels loaded with Ex4-C16 would be a promising long-acting sustained-release system with anti-diabetic property.

Sleep Duration and Cancer Risk: a Systematic Review and Meta-analysis of Prospective Studies

  • Zhao, Hao;Yin, Jie-Yun;Yang, Wan-Shui;Qin, Qin;Li, Ting-Ting;Shi, Yun;Deng, Qin;Wei, Sheng;Liu, Li;Wang, Xin;Nie, Shao-Fa
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7509-7515
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    • 2013
  • To assess the risk of cancers associated with sleep duration using meta-analysis of published cohort studies, we performed a comprehensive search using PubMed, Embase and Web of Science through October 2013. We combined hazard ratios (HRs) from individual studies using meta-analysis approaches. A random effect dose-response analysis was used to evaluate the relationship between sleep duration and cancer risk. Subgroup analyses and sensitivity analyses were also performed. Publication bias was evaluated using Funnel plots and Begg's test. A total of 13 cohorts from 12 studies were included in this meta-analysis, which included 723, 337 participants with 15, 156 reported cancer outcomes during a follow-up period ranging from 7.5 to 22 years. The pooled adjusted HRs were 1.06 (95% CI: 0.92, 1.23; P for heterogeneity =0.003) for short sleep duration, 0.91 (95% CI: 0.78, 1.07; P for heterogeneity <0.0001) for long sleep duration. In subgroup analyses stratified by cancer type, long duration of sleep showed an inverse relation with hormone-related cancer (HR=0.79; 95% CI: 0.65, 0.97; P for heterogeneity =0.009) and a greater risk of colorectal cancer (HR=1.29; 95% CI: 1.09, 1.52; P for heterogeneity =0.346). Further meta-analysis on dose-response relationships showed that the relative risks of cancer were 1.00 (95% CI: 0.99, 1.01; P for linear trend=0.9151) for one hour of sleep increment per day, and 1.00 (95% CI: 0.98, 1.01; P for linear trend=0.7749) for one hour of sleep increment per night. No significant dose-response relationship between sleep duration and cancer was found on non-linearity testing (P=0.5053). Our meta-analysis suggests a positive association between long sleep duration and colorectal cancer, and an inverse association with incidence of hormone related cancers like those in the breast. Studies with larger sample size, longer follow-up times, more cancer types and detailed measure of sleep duration are warranted to confirm these results.

The Effects of the Combined Use of Haloperidol and Nimodipine on Plasma HVA, 5-HIAA in Male Chronic Schizophrenics (남자 만성 정신분열병환자에서 Haloperidol과 Nimodipine의 병합사용이 혈장 HVA와 5-HIAA에 미치는 영향)

  • Kim, Hyeong-Seob;Choi, Ai-Kyung;Jee, Sung-Hak;Kim, Soo-Dong;Park, Sung-Deok;Kim, Kwang-Hyeon
    • Korean Journal of Biological Psychiatry
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    • v.3 no.1
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    • pp.88-95
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    • 1996
  • In an open labeled study, two fixed doses of nimodipine(45mg and 90mg daily) were added to the usual antipsychotic drug treatment (Haloperidol : mean dose=25mg/day) in 20 male chronic schizophrenics for 5 weeks. The purposes of this study were to evaluate the therapeutic effects and the effect an the changes of plasma homovanillic acid(HVA) and 5-hydroxyindoleacetic acid(5-HIAA) levels. The results were as follows : 1) Total BPRS score and thought cluster, paranoid cluster subscores showed linear decreasing trend over the course of the study(P<0.05). Especially the thought cluster and paranoid cluster subscores were significant difference between 45mg and 90mg dose of nimodipine(P<0.05). The improvement rates were 45,45% of 90mg and 11.11% of 45mg, but there was no significant difference between the 45mg and 90mg dose of nimodipine. 2) The scores of extrapyramidal symptoms and adverse events-somatic symptoms showed a linear decreasing trends over the course of study. 3) The changes in the mean plasma HVA and 5-H1AA concentrations by the dosages and durations of combining of nimodipine were not statistically significant. 4) There was no statistical significance in plasma HVA and 5-HIAA of the improved, non-improved goroup. Nimodipine has a possibility os on adjunctive agent for treatment resistant schizophrenics, elderly patients and liable patients for the Side effects to usual antipsychotic drugs. So we suggest that the dosage of nimodipine must be above 90mg/day in the treatment of schizophrenia.

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Effect of Inhomogeneity correction for lung volume model in TPS (Lnug Volume을 모델로 한 방사선치료계획 시 불균질 조직 보정에 따른 효과)

  • Chung SeYoung;Lee SangRok;Kim YoungBum;Kwon YoungHo
    • The Journal of Korean Society for Radiation Therapy
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    • v.16 no.1
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    • pp.57-65
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    • 2004
  • Introduction : The phantom that includes high density materials such as steel was custom-made to fix lung and bone in order to evaluation inhomogeneity correction at the time of conducting radiation therapy to treat lung cancer. Using this, values resulting from the inhomogeneous correction algorithm are compared on the 2 and 3 dimensional radiation therapy planning systems. Moreover, change in dose calculation was evaluated according to inhomogeneous by comparing with the actual measurement. Materials and Methods : As for the image acquisition, inhomogeneous correction phantom(Pig's vertebra, steel(8.21g/cm3), cork(0.23 g/cm3)) that was custom-made and the CT(Volume zoom, Siemens, Germany) were used. As for the radiation therapy planning system, Marks Plan(2D) and XiO(CMS, USA, 3D) were used. To compare with the measurement value, linear accelerator(CL/1800, Varian, USA) and ion chamber were used. Image, obtained from the CT was used to obtain point dose and dose distribution from the region of interest (ROI) while on the radiation therapy planning device. After measurement was conducted under the same conditions, value on the treatment planning device and measured value were subjected to comparison and analysis. And difference between the resulting for the evaluation on the use (or non-use) of inhomogeneity correction algorithm, and diverse inhomogeneity correction algorithm that is included in the radiation therapy planning device was compared as well. Results : As result of comparing the results of measurement value on the region of interest within the inhomogeneity correction phantom and the value that resulted from the homogeneous and inhomogeneous correction, gained from the therapy planning device, margin of error of the measurement value and inhomogeneous correction value at the location 1 of the lung showed $0.8\%$ on 2D and $0.5\%$ on 3D. Margin of error of the measurement value and inhomogeneous correction value at the location 1 of the steel showed $12\%$ on 2D and $5\%$ on 3D, however, it is possible to see that the value that is not correction and the margin of error of the measurement value stand at $16\%$ and $14\%$, respectively. Moreover, values of the 3D showed lower margin of error compared to 2D. Conclusion : Revision according to the density of tissue must be executed during radiation therapy planning. To ensure a more accurate planning, use of 3D planning system is recommended more so than the 2D Planning system to ensure a more accurate revision on the therapy plan. Moreover, 3D Planning system needs to select and use the most accurate and appropriate inhomogeneous correction algorithm through actual measurement. In addition, comparison and analysis through TLD or film dosimetry are needed.

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