• Biomolecules & Therapeutics
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• 제10권2호
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• pp.129-135
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• 2002

HM10411 is a recombinant granulocyte-colony stimulating factor (rG-CSF) that has been developing as a drug for neutropenia. In this study, antigenic potential of HM10411 was examined by active systemic anaphylaxis (ASA) in guinea pigs and passive cutaneous anaphylaxis (PCA) in guinea pig-guinea pig system. HM10411 was subcutaneously administered at 0,5, and 50 mg/kg and also as a suspension with adjuvant (50 mg/kg+FCA). Ovalbumin (OVA) as a suspension with adjuvant was used to induce positive control responses. In the ASA test, no symptoms except urination and evacuation that were considered as physiological phenomena were observed at 0 and 5 mg/kg. Two of 5 animals at 50 mg/kg showed sneering, dyspnea, or cyanosis. All animals in the adjuvant mixture group showed severe symptoms of anaphylatic shock and 3 of them died. In the PCA test, no antibody against HM 10411 was detected in the sera from the animals sensitized with 0 or 5 mg/kg. Only 1 serum sample from the animals immunized with 50 mg/kg showed positive reaction against HM10411, while all 5 sera collected from the HM10411 and FCA mixture group contained the HM10411-specific antibodies. These results suggest HM10411 is considered to have antigenicity In guinea pig.

• 한국식품영양과학회지
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• 제33권7호
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• pp.1092-1097
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• 2004

큰느타리버섯의 기능성 식품으로서 활용도를 높이기 위해 동결 건조된 자실체에서 분리한 조다당체 추출물이 면역세포 활성에 미치는 효과를 조사한 결과는 다음과 같다. 조다당체 추출물은 300 및 1,000 $\mu$g/mL 농도에서 비장세포의 증식을 유도하였으며, 이 때 비장세포는 IL-6와 IFN-${\gamma}$ 분비를 유도하는 것으로 나타났다 조다당체 추출물은 농도 의존적으로B세포의 증식을 유도하였으며, 특히 100 $\mu$g/mL농도 이상에서는B세포의 증식이 현저히 증가하는 것으로 나타났다. 그리고 조다당체 추출물 1,000 $\mu$g/mL 농도에서 B세포가 생산하는 IgGl, IgG2a, IgG3의 분비량이 현저히 증가하였다. 또한 농도 의존적으로 대식세포주의 일산화질소 생산을 유도하였으며, 대식세포가 분비하는 IL-6, TNF-$\alpha$, GM-CSF의 생산도 현저히 증가하는 것을 확인할 수 있었다.

• Korean Journal of Acupuncture
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• 제27권3호
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• pp.109-118
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• 2010

Objectives : The purpose of this study is to investigate the effect of Bacillus-fermented Scutellariae Radix acupuncture solution (SB) on chemokine and growth factor production in RAW 264.7 mouse macrophages stimulated by lipopolysaccharide (LPS). Methods : Productions of chemokine and growth factor were measured by High-throughput Multiplex Bead based Assay with Bio-plex Suspension Array System based on xMAP$^{(R)}$ technology. Firstly, cell culture supernatant was obtained after treatment with LPS (1 ${\mu}g$/mL) and SB for 24 hours. Then, it was incubated with the antibody-conjugated beads for 30 minutes. Detection antibody was then added and incubated for 30 minutes. After incubated for 30 minutes, strepavidin-conjugated phycoerythrin (SAPE) was added. After another 30 minutes incubation, the level of SAPE fluorescence was analyzed in Bio-plex Suspension Array System. Results : The results of the experiment are as follows. 1. SB significantly inhibited the LPS-induced production of vascular endothelial growth factor (VEGF), interferon-inducible protein (IP)-10, and granulocyte-colony stimulating factor (G-CSF) at the concentration of 25, 50, 100, and 200 ${\mu}g$/mL in RAW 264.7 cells (P < 0.05). 2. SB significantly inhibited the LPS-induced production of Eotaxin at the concentration of 25, 100, and 200 ${\mu}g$/mL in RAW 264.7 cells (P < 0.05). 3. SB significantly inhibited the LPS-induced production of MIP-$1\alpha$ at the concentration of 25 and 100 ${\mu}g$/mL in RAW 264.7 cells (P < 0.05). Conclusions : These results suggest that SB has immuno-modulatory property related with its inhibition of VEGF, IP-10, G-CSF, and Eotaxin production in macrophages.

• Asian-Australasian Journal of Animal Sciences
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• 제13권11호
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• pp.1529-1535
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• 2000

The aim of the present study was to determine whether brain corticotropin-releasing factor (CRF) and a new peptide, urocortin (UCN) have a direct action in brain mechanisms controlling feed, water and salt intake in sheep. We gave a continuous intracerebroventricular (ICV) infusion of the peptide at a small dose of $5{\mu}g/0.2ml/hr$ for 98.5 hrs from day 1 to day 5 in sheep not exposed to stress. Feed and water intake during ICV infusion of CRF or UCN decreased significantly compared to those during artificial cerebrospinal fluid (CSF) infusion. NaCl intake during infusion of CRF or UCN was the same as that during CSF infusion. Mean carotid arterial blood pressure (MAP) and heart rate during ICV infusion of CRF or UCN were not significantly different from that during CSF infusion. On the other hand, the plasma glucose concentration during ICV infusion of CRF or UCN tended to be higher than that during CSF infusion. These observations indicate that decreased feed intake induced by CRF and UCN infusion is not mediated by the activation of both the pituitary-adrenal axis and the sympathetic nervous system. The results suggested that brain CRF and UCN act directly in brain mechanisms controlling ingestive behavior to decrease feed and water intake, but do not alter salt intake in sheep.

• IMMUNE NETWORK
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• 제20권6호
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• pp.49.1-49.15
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• 2020

C-C chemokine receptor type 5 (CCR5) regulates the trafficking of various immune cells to sites of infection. In this study, we showed that expression of CCR5 and its ligands was rapidly increased in the kidney after systemic Candida albicans infection, and infected CCR5^-/- mice exhibited increased mortality and morbidity, indicating that CCR5 contributes to an effective defense mechanism against systemic C. albicans infection. The susceptibility of CCR5^-/- mice to C. albicans infection was due to impaired fungal clearance, which in turn resulted in exacerbated renal inflammation and damage. CCR5-mediated recruitment of NK cells to the kidney in response to C. albicans infection was necessary for the anti-microbial activity of neutrophils, the main fungicidal effector cells. Mechanistically, C. albicans induced expression of IL-23 by CD11c⁺ dendritic cells (DCs). IL-23 in turn augmented the fungicidal activity of neutrophils through GM-CSF production by NK cells. As GM-CSF potentiated production of IL-23 in response to C. albicans, a positive feedback loop formed between NK cells and DCs seemed to function as an amplification point for host defense. Taken together, our results suggest that CCR5-mediated recruitment of NK cells to the site of fungal infection is an important step that underlies innate resistance to systemic C. albicans infection.

• Biomolecules & Therapeutics
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• 제6권4호
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• pp.400-405
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• 1998

The pharmacokinetics of CJ-50001 (recombinant human granulocyte-colony stimulating factor, developed by R&D center of Cheil Jedang Corp.) were investigated in rats and dogs. The serum concentrations of CJ-50001 were measured by a sandwich enzyme immunoassay. After single intravenous (iv) administration of Cf-50001 to rats at a dose of 5 $\mu$g/kg, the mean terminal half-life and area under the concentration-time curve (AUC) were 0.96 h and 124.497g . h/ml, respectively. After single subcutaneous (sc) administration at the same dose, maximum serum concentration was observed at about 2 hours after administration, and the mean terminal half-life, AUC and the bioavailability were 1.11 h,63.58$\mu$g . h/ml and 51.07%, respectively. In repeated dosing studies, CJ-50001 was administered iv and sc to rats at a daily dose of 5$\mu$g/kg for 7 days. The pharmacokinetic parameters, such as mean AUC and terminal half-life, were no significantly different from those of single administration. Following single iv and sc administration of CJ-50001 to dogs at a dose of 5 $\mu$g/kg, mean AUCs were much higher than those of rats, due to the decreased clearence (CL). After sc administration to dogs, maximum serum concentration was observed at 2~4 hours after administration and the bioavailability was 54.60%.

• Tuberculosis and Respiratory Diseases
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• 제48권6호
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• pp.922-931
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• 2000

배경 및 목적 : 기관지천식의 중요한 특징적인 병인인 기도의 만성염증 상태와 증상의 변화를 판단하는 객관적인 지표로서 여러 가지 방법이 시도되고 있는데 최근에는 비침습적이고 비교적 간단한 유도객담 검사로 침습적인 기관지 조직 검사나 기관지폐포세척술을 대신하려는 경향이 있다. 저자들은 기관지천식 환자의 유도객담에서 호산구, eosinophil cationic protein(ECP), interleukin(IL)-3, IL-5, granulocyte-macrophage colony-stimulating factor(GM-CSF), 그리고, nitric oxide(NO)의 유도체를 측정하고, 객담내 NO 및 호산구와 관계가 있다고 알려진 cytokine들의 농도가 증상 및 기도의 염증상태를 반영하는 지표로서 이용될 수 있는지를 알아보고자 하였다. 방법 : 기관지천식 환자 30명을 대상으로 2주간 경구용 프레드니솔론 30mg을 투여하고, 약제 투여 전후로 1초간 노력성 호기량($FEV_1$과 혈중 총 호산구수, 그리고 유도객담 검사를 시행하여 객담내 호산구 비율과 ECP, IL-3, IL-5, GM-CSF, 그리고, NO 유도체를 측정하였다. 결과 : 대상환자중 남자는 13a여(43.3%), 여자는 17명(56.7%)이었고 연령분포는 19세부터 64세까지였으며 평균연령은 41.8세였다. 30명중 2명은 두 번째 검사시 객담이 채취되지 않았고, 3명은 두 번째 방문을 하지 않았다. 프레드니솔론 투여후 평균 1초당 노력성 호기량(% of predicted value)은 78.1$\pm$27.2%에서 90.3$\pm$18.3%로 개선되었고(P<0.001), 유도객담내 평균 호산구비율은 56.1$\pm$27.2%에서 29.6$\pm$21.3%로 (P<0.001), 객담내 평균 ECP 농도는 $134.5\pm68.1{\mu}\;g/L$에서 $41.5\pm42.4\;{\mu}g/L$로 유의하게 감소하였고(P<0.001), 평균 혈중 총 호산구수는 425.7$\pm$265.9에서 287.7$\pm$294.7로 감소하는 경향을 보였지만 통계적으로 유의하지 않았다. 유도객담내 NO 유도체의 평균 농도는 프레드니솔론 투여 전호로 유의한 차이가 없었으며($70.4\pm44.6\;{\mu}mol/L$ vs $91.5\pm48.3\;{\mu}mol/L$) 평균 eotaxin 농도는 27.7$\pm$12.8 pg/ml에서 21.7$\pm$8.7 pg/ml로 감소하는 경향을 보였다. IL-3, IL-5, CSF는 대부분의 경우에서 측정되지 않았다. 치료전의 1초당 노력성 호기량과 객담내 ECP의 농도 사이에 의미있는 역상관관계가 있었고(r=0.369, P<0.05). 결론 : 유도객담내에서 측정 가능한 여러 인자중 eotaxin 및 ECP가 치료에 따른 기도염증 상태의 변화를 반영하는 지표로 이용될수 있을 것으로 생각된다. 그 외 유도객담내 호산구비율 측정도 치료에 따른 증상이나 염증의 변화를 손쉽게 관찰할수 있는 간단한 방법으로 생각되지만 유도객담에서 Griess reagent를 이용한 NO 유도체의 측정은 기관지천식의 증상이나 염증상태의 변화를 반영하는 지표로서 유용하지 않을 것으로 생각된다.

• 한국임상약학회지
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• 제25권2호
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• pp.80-93
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• 2015

Objective: Pegfilgrastim is recently introduced that is long acting G-CSF for prophylaxis of febrile neutropenia. Treatment of non-Hodgikin's lymphoma (NHL) with R-CHOP is classified with relative high risk of febrile neutropenia. The study evaluated the prophylactic effect of pegfilgrastim to reduce the incidence of febrile neutropenia associated with R-CHOP of patient in NHL. And the risk factors associated with the incidence of FN and related events were evaluated. Methods: This retrospective study reviews the Electronic Medical Record of 68 NHL patients who received R-CHOP chemotherapy in single center between September 2013 and August 2014. These patients were classified who receive prophylaxis pegfilgrastim or no prophylaxis. Results: Sixty eight patients received R-CHOP with NHL. In 144 cycles of patients receiving pegfilgrastim, compared with no prophylaxis 178 cycles, had a lower incidence of febrile neutropenia (5.5% vs. 23.6%, p = 0.001), grade 3 or grade 4 neutropenia (14.4% vs. 89.8%, p < 0.001) and neutropenia related events (p < 0.05). The risk of febrile neutropenia after prophylaxis was significantly associated with age ${\geq}65$ (OR: 5.87, 95% CI 1.07-32.27, p = 0.042), $IPI{\geq}3$ (OR: 7.2, 95% CI 1.31-39.6, p = 0.023), S.alb < 3.5 g/dL (OR: 31.01, 95% CI 6.32-152.17, p < 0.0001). In multiple logistic regression analysis, lower baseline serum albumin (OR: 21.1, 95% CI 3.8-116.98, p = 0.001) was significantly associated with occurrence of febrile neutropenia. Conclusion: The study recommends prophylactic pegfilgrastim through risk assessment of febrile neutropenia in patients with non-Hodgikin's lymphoma receiving R-CHOP.

• 한국식품영양학회지
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• 제30권6호
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• pp.1348-1358
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• 2017

To enhance the physiological activity of the Rhynchosia volubilis (RV), R. volubilis (RVHE-A) and R. volubilis-added herbal powder (RVHE-B) were fermented with a solid state culture of Hericium erinaceum mycelia (HE). The total isoflavone contents of the non-fermented RV-A ($489.9{\mu}g/g$) and RV-B ($571.1{\mu}g/g$) were remarkably increased in fermented RVHE-A ($1,836.4{\mu}g/g$) and RVHE-B ($1,276.7{\mu}g/g$). In particular, aglycone isoflavones such as daidzein and genistein were significantly higher in the RVHE-A than any other sample. When hot-water (HW) and EtOH extracts (E) were fractionated from the RV and RVHE, both extracts from the RVHE-A were higher than those from the RV-A in total polyphenol and flavonoid contents. However, the RVHE-B-HW showed a lower polyphenol and flavonoid content level than did RV-B-HW. RVHE-A-HW and -E also had more potent ABTS radical scavenging activity than any extract from the non-fermented RV and other ferments (RVHE-B). In the meanwhile, RVHE-A-HW potently stimulated the production of macrophage activation-related cytokines such as $TNF-{\alpha}$, IL-6 and IL-12 ($841.7{\pm}71.3pg/mL$, $3.9{\pm}0.1ng/mL$, $179.3{\pm}30.2pg/mL$) from peritoneal macrophage more than RV-A-HW ($92.5{\pm}1.5pg/mL$, $0.1{\pm}0.0ng/mL$, $37.4{\pm}5.4pg/mL$) as well as RVHE-B-HW ($557.0{\pm}21.3pg/mL$, $1.8{\pm}0.0ng/mL$, $90.0{\pm}10.0pg/mL$). However, all the EtOH extracts did not show significant activity. In addition, the RVHE-A-HW showed a significantly higher intestinal immune system modulating activity through Peyer's patch and GM-CSF production than did any other extract from RV and RVHE-B. In conclusion, these results suggest that the fermented R. volubilis with H. erinaceum mycelia possesses a possible use as an industrial application as functional food or material.

• Journal of Trauma and Injury
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• 제20권2호
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• pp.138-143
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• 2007

Purpose: $S100{\beta}$, a marker of traumatic brain injury (TBI), has been increasingly focused upon during recent years. $S100{\beta}$, is easily measured not only in cerebrospinal fluid (CSF) but also in serum. After TBI, serum S 10019, has been found to be increased at an early stage. The purpose of this study was to evaluate the clinical correlations between serum $S100{\beta}$, and neurologic outcome, and severity in traumatic brain injury. Methods: From August 2006 to October 2006, we made a protocol and studied prospectively 42 patients who visited the emergency room with TBI. Venous blood samples for $S100{\beta}$, protein were taken within six hours after TBI and vital signs, as well as the Glasgow Coma Scale (GCS), were recorded. The final diagnosis and the severity were evaluated using the Abbreviated Injury Score (AIS), and the prognosis of the patients was evaluated using the Glasgow Outcome Score (GOS). Results: Thirty-eight patients showed a favorable prognosis (discharge, recovery, transfer), and four showed an unfavorable prognosis. Serum $S100{\beta}$, was higher in patients with an unfavorable prognosis than in patients with a favorable prognosis, and a significant difference existed between the two groups ($0.74{\pm}1.50\;{\mu}g/L$ vs $7.62{\pm}6.53\;{\mu}g/L$ P=0.002). A negative correlation existed between serum $S100{\beta}$, and the Revised Traumatic Score (R2=-0.34, P=0.03), and a positive correlation existed between serum $S100{\beta}$, and the Injury Severity Score (R2=0.33, P=0.03). Furthermore, the correlation between serum $S100{\beta}$, and the initial GCS and the GCS 24 hours after admission to the ER were negative (R2=-0.62, P<0.001; R2=-0.47, P=0.005). Regarding the GOS, the mean serum concentration of $S100{\beta}$, was $7.62\;{\ss}{\partial}/L$ (SD=${\pm}6.53$) in the expired patients, $1.15\;{\mu}g/L$ in the mildly disable patient, and $0.727\;{\mu}g/L$ (SD=${\pm}0.73$) in the recovered patients. These differences are statistically significant (p<0.001). Conclusion: In traumatic brain injury, a higher level of serum concentration of $S100{\beta}$, has a poor prognosis for neurologic outcome.