• 대한방사선치료학회지
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• 제31권1호
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• pp.75-81
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• 2019

목 적: 두피 악성종양의 치료에 광자선을 사용할 때 필요한 Bolus 재질들의 단점으로 인하여 3D Printer용 헬멧형 bolus가 제작되고 있다. 하지만 사용되는 재질인 PLA은 조직등가물질에 비해 높은 밀도를 가지고 있으며 환자가 착용할 경우 불편한 점들이 발생한다. 이에 본 연구에서는 3D Printer를 이용한 M3 wax 헬멧을 제작하여 악성 두피종양을 치료하는 방법을 시도해 보고자 한다. 대상 및 방법: 헬멧형 M3 wax의 모델링을 위해 두부인체모형팬텀을 CT로 촬영해 DICOM file로 획득하고, 두피 위에 헬멧이 위치할 부위를 Helmet contour로 제작하였다. M3 Wax 헬멧의 제작은 paraffin wax를 녹이고, 산화마그네슘, 탄산칼슘을 섞어 용해시킨 후 PLA 3D 헬멧의 내부에 넣고 표면의 PLA 3D 헬멧을 제거하였다. 치료계획은 총 10 Portal의 Intensity-Modulated Radiation Therapy(IMRT)로 세웠으며, 치료선량은 200 cGy로 eclipse의 Analytical Anisotropic Algorithm(AAA)를 사용하였다. 그 후 EBT3 film과 Mosfet(Metal Oxide Semiconductor Field Effect Transistor: USA)를 이용해 선량검증을 실시하였으며, CT 모의치료실과 동일한 조건으로 두부인체모형팬텀을 재현해 IMRT Plan을 측정하였다. 결 과: CT상에서 측정된 Bolus의 Hounsfield unit(HU)는 $52{\pm}37.1$으로 나타났다. M3 wax bolus 측정점 A, B, C에서 TPS의 선량은 186.6 cGy, 193.2 cGy, 190.6 cGy으로 확인되었고, Mostet으로 3회 측정한 선량은 $179.66{\pm}2.62cGy$, $184.33{\pm}1.24cGy$, $195.33{\pm}1.69cGy$, 오차율은 -3.71 %, -4.59 %, +2.48 %였다. EBT3 Film으로 측정된 선량은 $182.00{\pm}1.63cGy$, $193.66{\pm}2.05cGy$, $196{\pm}2.16cGy$이었으며, 오차율은 -2.46%, +0.23 %, +2.83 %로 확인되었다. 결 론: M3 wax bolus는 2 cm의 두께로 제작되어 뇌 부분의 선량을 보다 쉽게 낮추어 치료계획을 수립할 수 있었다. 치료선량 검증에서의 EBT3 Film과 Mosfet의 선량계의 A, B, C 측정값에서도 두피의 표면선량 최대 오차율은 5 % 이내로 측정되었으며, 일반적으로 3 % 이내로 정확하게 측정되었다. M3 wax bolus는 제작과정 기간이 3D Printer보다 빠르고 비용이 저렴하며, 재사용 가능하고, 인체조직 등가물질로서 두피 악성종양 치료에 매우 유용한 Bolus이다. 따라서 3D Printer의 대용량 Bolus, Compensator의 제작시간 및 비용이 비싼 단점을 극복하는 주조형 M3 wax bolus의 사용이 추후 확대될 것으로 사료된다.

• Journal of Ginseng Research
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• 제43권2호
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• pp.236-241
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• 2019

Background: Thromboxane A2 ($TXA_2$) induces platelet aggregation and promotes thrombus formation. Although ginsenoside Ro (G-Ro) from Panax ginseng is known to exhibit a $Ca^{2+}-antagonistic$ antiplatelet effect, whether it inhibits $Ca^{2+}-dependent$ cytosolic phospholipase $A_2$ ($cPLA_{2{\alpha}}$) activity to prevent the release of arachidonic acid (AA), a $TXA_2$ precursor, is unknown. In this study, we attempted to identify the mechanism underlying G-Ro-mediated $TXA_2$ inhibition. Methods: We investigated whether G-Ro attenuates $TXA_2$ production and its associated molecules, such as cyclooxygenase-1 (COX-1), $TXA_2$ synthase (TXAS), $cPLA_{2{\alpha}}$, mitogen-activated protein kinases, and AA. To assay COX-1 and TXAS, we used microsomal fraction of platelets. Results: G-Ro reduced $TXA_2$ production by inhibiting AA release. It acted by decreasing the phosphorylation of $cPLA_{2{\alpha}}$, p38-mitogen-activated protein kinase, and c-Jun N-terminal kinase1, rather than by inhibiting COX-1 and TXAS in thrombin-activated human platelets. Conclusion: G-Ro inhibits AA release to attenuate $TXA_2$ production, which may counteract $TXA_2-associated$ thrombosis.

• 생약학회지
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• 제38권3호통권150호
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• pp.277-280
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• 2007

In our continuing effort to investigate compounds having anti-inflammatory activity from natural products, Ailanthus altissima was examined. Among six compounds isolated from Ailanthus altissima, Luteolin-7-O-glucoside (L7G) along with ethanol extract of Ailnathus altissima (EAa) were chosen to determine their inhibitory activity on secretory recombinant phospholipase $A_2s$ enzyme activity in vitro. As a results, EAa inhibited human recombinant $sPLA_2-V$ ($IC_{50}$ of about 100 ${\mu}g/ml$) and $cPLA_2$, ($IC_{50}$ of about 59 ${\mu}g/ml$), while L7G showed strong inhibitory effect on $sPLA_2-A$, V and $cPLA_2$ with an $IC_{50}$ value of approximately 40 ${\mu}M$, respectively.

• The Korean Journal of Physiology and Pharmacology
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• 제5권4호
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• pp.287-297
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• 2001

Contraction of smooth muscle is initiated by an increase in cytosolic $Ca^{2+}$ leading to activation of $Ca^{2+}$/ calmodulin-dependnet myosin light chain (MLC) kinase and phosphorylation of MLC. The types of contraction and signaling mechanisms mediating contraction differ depending on the region. The involvement of these different mechanisms varies depending on the source of $Ca^{2+}$ and the kinetic of $Ca^{2+}$ mobilization. $Ca^{2+}$ mobilizing agonists stimulate different phospholipases $(PLC-{\beta},\;PLD\;and\;PLA_2)$ to generate one or more $Ca^{2+}$ mobilizing messengers $(IP_3\;and\;AA),$ and diacylglycerol (DAG), an activator of protein kinase C (PKC). The relative contributions of $PLC-{\beta},\;PLA_2$ and PLD to generate second messengers vary greatly between cells and types of contraction. In smooth muscle cell derived form the circular muscle layer of the intestine, preferential hydrolysis of $PIP_2$ and generation of $IP_3$ and $IP_3-dependent\;Ca^{2+}$ release initiate the contraction. In smooth muscle cells derived from longitudinal muscle layer of the intestine, preferential hydrolysis of PC by PLA2, generation of AA and AA-mediated $Ca^{2+}$ influx, cADP ribose formation and $Ca^{2+}-induced\;Ca^{2+}$ release initiate the contraction. Sustained contraction, however, in both cell types is mediated by $Ca^{2+}-independent$ mechanism involving activation of $PKC-{\varepsilon}$ by DAG derived form PLD. A functional linkage between $G_{13},$ RhoA, ROCK, $PKC-{\varepsilon},$ CPI-17 and MLC phosphorylation in sustained contraction has been implicated. Contraction of normal esophageal circular muscle (ESO) in response to acetylcholine (ACh) is linked to $M_2$ muscarinic receptors activating at least three intracellular phospholipases, i.e. phosphatidylcholine-specific phospholipase C (PC-PLC), phospholipase D (PLD) and the high molecular weight (85 kDa) cytosolic phospholipase $A_2\;(cPLA_2)$ to induce phosphatidylcholine (PC) metabolism, production of diacylglycerol (DAG) and arachidonic acid (AA), resulting in activation of a protein kinase C (PKC)-dependent pathway. In contrast, lower esophageal sphincter (LES) contraction induced by maximally effective doses of ACh is mediated by muscarinic $M_3$ receptors, linked to pertussis toxin-insensitive GTP-binding proteins of the $G_{q/11}$ type. They activate phospholipase C, which hydrolyzes phosphatidylinositol bisphosphate $(PIP_2),$ producing inositol 1, 4, 5-trisphosphate $(IP_3)$ and DAG. $IP_3$ causes release of intracellular $Ca^{2+}$ and formation of a $Ca^{2+}$-calmodulin complex, resulting in activation of myosin light chain kinase and contraction through a calmodulin-dependent pathway.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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• pp.182-182
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• 1996

Annexin I is a member of the annexin family of calcium dependent phospholipid binding proteins and has anti-inflammatory activity by inhibiting phospholipase A$_2$ (PLA$_2$). Recent X-ray crystallographic study of annexin I identified six Ca$\^$2+/ binding bites, which was different types (type II, III) from the well-known EF-hand motif (type I). In this work, the structure of annexin I was studied at atomic level by using $^1$H, $\^$15/N and $\^$l3/C NMR(nuclear magnetic resonance) spectroscopy, and the effect of Ca$\^$2+/ binding on the structure of annexin I was studied, and compared with that of Mg$\^$2+/ binding, When Ca$\^$2+/ was added to annexin I, NMR peak change was occured in high- and low-field regions of $^1$H-NMR spectra. NMR peak change by Ca$\^$2+/ binding was different from that by Mg$\^$2+/ binding. Because annexin I is a larger protein with 35 kDa molecular weight, site-specific (amide-$\^$15/N, carbonyl-$\^$l3/C) labeling technique was also used. We were able to detect methionine, tyrosine and phenylalanine peaks respectively in $\^$13/C-NMR spectra, and each residue was able to be assigned by the method of doubly labeling annexin I with [$\^$13/C] carbonyl-amino acid and [$\^$15/N] amide-amino acid. In $\^$l3/C-NMR spectra of [$\^$13/C] carbonyl-Met labeled annexin I, we observed that methionine residues spatially located near Ca$\^$2+/ binding Sites Were Significantly effected by Ca$\^$2+/ binding. From UV spectroscopic data on the effect of Ca$\^$2+/ binding, we knew that Ca$\^$2+/ binding sites of annexin I have cooperativity in Ca$\^$2+/ binding. The interaction of annexin I with PLA$_2$ also could be detected by using heteronuclear NMR spctroscopy. Consequently, we expect that the anti-inflammatory action mechanism of annexin I may be a specific protein-protein interaction. The residues involved in the interaction with PLA$_2$ can be identified as active site by assigning NMR peaks effected by PLA$_2$ binding.

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4627-4630
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• 2012

Purpose: Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms have been reported to be associated with pancreatic cancer, but the published studies have yielded inconsistent results. This study assessed the relationship between MTHFR gene polymorphisms and the risk for pancreatic cancer using a meta-analysis approach. Methods:A search of Google scholar, PubMed, Cochrane Library and CNKI databases before April 2012 was performed, and then associations of the MTHFR polymorphisms with pancreatic cancer risk were summarized. The association was assessed by odds ratios (ORs) with 95% confidence intervals (CIs). Publication bias was also calculated. Results: Four relative studies on MTHFR gene polymorphisms (C667T and A1298C) were included in this meta-analysis. Overall, C667T (TT vs. CC:OR=1.61,95%CI=0.78-3.34; TT vs. CT: OR=1.41,95%CI=0.88-2.25; Dominant model:OR=0.68,95%CI=0.40-1.17; Recessive model: OR=0.82,95%CI=0.52-1.30) and A1298C (CC vs. AA:OR=1.01,95%CI=0.47-2.17; CC vs. AC: OR=0.99,95%CI=0.46-2.14; Dominant model:OR=1.01, 95%CI=0.47-2.20; Recessive model: OR=1.01,95%CI=0.80-1.26) did not increase pancreatic cancer risk. Conclusions: This meta-analysis indicated that MTHFR polymorphisms (C667T and A1298C) are not associated with pancreatic cancer risk.

• Korean Chemical Engineering Research
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• 제49권2호
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• pp.206-210
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• 2011

다양한 방식의 등통로각압축공정으로 생분해성 고분자인 폴리젖산수지 시편을 가공하여 각 공정 방식에 따른 시편들의 열 및 기계적 물성의 변화를 조사하였다. 각각 A, BC, C 세 가지의 시편 재 주입 방식과 1, 2, 4의 가공 횟수를 조합한 7개의 시편들을 제작하고, 각 시편의 녹는점, 열분해온도와 같은 열물성을 시차주사열량분석기와 열무게분석기를 사용하여 측정하였다. 시편의 응력변형의 변화를 경도 시험기를 사용하여 측정하고, 각 시편 절단면의 내부 미세구조를 주사전자현미경을 사용하여 관찰하였다. 관찰된 내부 미세구조는 경도시험결과를 설명하는데 정성적인 뒷받침이 되었다. 그 결과 PLA-P2A의 내부 미세 구조가 가장 치밀하고 촘촘히 겹쳐져 있음으로 인하여 내부 응력변형도 가장 많이 관찰되었다.

• The Korean Journal of Physiology and Pharmacology
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• 제3권1호
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• pp.93-100
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• 1999

The present study was designed to assess the roles of $PLA_2$ activation and arachidonic acid (AA) metabolites in hypoxia-induced renal cell injury. Hypoxia increased LDH release in a dose-dependent manner in rabbit renal cortical slices, and this increase was significant after 20-min hypoxia. The hypoxia-induced LDH release was prevented by amino acids, glycine and alanine, and extracellular acidosis (pH 6.0). Buffering intracellular $Ca^{2+}$ by a chelator, but not omission of $Ca^{2+}$ in the medium produced a significant reduction in hypoxia-induced LDH release. The effect of hypoxia was blocked by $PLA_2$ inhibitors, mepacrine, butacaine, and dibucaine. A similar effect was observed by a 85-kD $cPLA_2$ inhibitor $AACOCF_3.$ AA increased hypoxia-induced LDH release, and albumin, a fatty acid absorbent, prevented the LDH release, suggesting that free fatty acids are involved in hypoxia-induced cell injury. These results suggest that $PLA_2$ activation and its metabolic products play important roles in pathogenesis of hypoxia-induced cell injury in rabbit renal cortical slices.

• Macromolecular Research
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• 제17권5호
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• pp.346-351
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• 2009

$TiCl(O-i-Pr)_3/SiO_2$ and $Ti(O-i-Pr)_4/SiO_2$ were prepared by immobilizing chlorotitanium (IV) isopropoxide ($TiCl(O-i-Pr)_3$) and titanium (IV) isopropoxide ($Ti(O-i-Pr)_4$), to pretreated silica. The effect of the polymerization reaction conditions on the catalytic activity and characteristics of the resulting PLA were investigated. The catalytic conversion, molecular weight and polydispersity index (PDI) of the PLA produced on the titanium alkoxide supported catalysts increased proportionally with the reaction temperature. When the PLA was synthesized in bulk polymerization, the PLA produced with the supported catalysts had higher molecular weight than those with homogeneous catalysts. The melting temperature of the polymer produced with silica supported alkoxide catalysts was approximately $170-180^{\circ}C$.

• 한국식품영양과학회지
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• 제41권7호
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• pp.936-942
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• 2012

본 연구에서는 흰쥐에 마이크로웨이브를 조사한 후 폐조직을 대상으로 폐조직 기능장애를 일으키는데 주된 역할을 하는 혈전생성능을 arachidonic acid(AA) cascade계를 통해 관찰하여 마이크로웨이브에 의한 폐혈관 기능장애와 그에 대한 녹차 catechin의 항혈전 효과를 규명하고자 하였다. 실험군은 마이크로웨이브를 조사하지 않은 정상군과 마이크로웨이브를 조사한 군으로 나누고 마이크로웨이브 조사 군은 다시 식이 중 catechin 공급수준에 따라 catechin을 넣지 않은 군(MW group), catechin을 0.25% 급여한 군(MW-0.25C group), catechin을 0.5% 급여한 군(MW-0.5C group)으로 나누었다. 식이와 음료는 자유 섭식시키면서 2주간 사육한 후 2.45 GHz 대역의 주파수를 15분간 1회 조사하였으며 마이크로웨이브 조사 후 6일째 동물을 희생시켜 본 실험에 사용하였다. 실험군의 실험동물 수는 각각 10마리로 실험하였다. $PLA_2$ 활성은 마이크로웨이브 조사로 30% 증가하였으며 MW-0.25C군은 15% 증가였으나 MW-0.5C군은 정상군 수준이었다. 인지질분자종의 변화를 관찰한 결과 lyso PE가 MW군에서 47% 증가되었으나 MW-0.25C군 및 MW-0.5C군에서는 각각 18%, 20% 증가되었다. $TXA_2$ 생성은 MW군에서 50%의 현저한 증가를 보였으나 catechin 공급군인 MW-0.25C군 및 MW-0.5C군은 정상군 수준이었다. $PGI_2$ 생성은 MW군에서 31%의 유의적인 감소를 보였으나 catechin 공급군인 MW-0.25C군 및 MW-0.5군은 정상군 수준이었다. 따라서 혈전생성지표인 $PGI_2/TXA_2$ ratio는 정상군에 비해 MW군에서 43% 유의적으로 감소되었으나 MW-0.25C군 및 MW-0.5C군은 정상군 수준이었다. 지질과산화물의 함량은 MW군에서 34% 유의적으로 증가하였으며 catechin 공급군은 정상군 수준이었다. 결론적으로 마이크로웨이브에 피폭된 흰쥐 폐조직에서는 AA cascade계의 율속 효소인 $PLA_2$ 활성의 증가와 혈전생성지표로 인식하는 $PGI_2/TXA_2$ ratio의 불균형이 초래되었으나 catechin은 TBARS 농도를 낮추면서 $PLA_2$ 활성을 저해시키고 AA cascade계를 개선시킴으로써 항혈전 작용을 나타내었다.