• 한국식품위생안전성학회지
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• 제21권2호
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• pp.113-117
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• 2006

돼지에게 실험물질을 투여후 4주령과 3개월령에서 뽑은 혈액에서의 면역 증강력을 측정하기 위하여 우선 선행되어야 할 건강한 개체여부를 판단하기 위하여 혈액분석을 실시하였다. 그 결과에서는 의뢰한 개체군에서 유의적인 차이가 없었으며, 이 결과로부터 본 실험에서의 면역 증강 수치 결과가 질병에 의한 결과가 아닌 개체 자체의 면역 증강성이 높아져있음을 판단 할 수 있는 근거가 되었다. 생체에서의 면역성은 크게 세포성 면역과 체액성 면역으로 나눌 수 있는데 세포성 면역의 대표적인 사이토카인인 IFN-r를 측정한 결과, 4주령에서는 대조군과 비교하여 유의적인 증가를 나타내는 군이 DIR-vitamineral 0.2%군이었으며, 다른 군에서는 유의적인 변화를 나타내지 않았다. 3개월령에서는 대조군농도인 38.5와 비교하였을 때 임뮤포르테알파, DIR-vita 0.1%, DIR-vitamineral 0.2%에서 유의적인 증가가 나타나는 것을 알 수 있었다. 이상의 결과로부터 DIR-vitamineral 0.2%는 4주령 및 3개월령에서 고른 면역 증강력을 확인 할 수 있었으며, 임뮤포르테알파, DIR-vita 0.1%는 3개월령에서 증강성이 확인된 결과를 나타내는 것으로 미루어보아 시간이 경과하면서 면역증강성을 나타내는것으로 사료된다. 또한, DIR-vita 0.2%의 경우에는 오히려 3개월령에서 면역 증강성에 있어서 유의적인 효능이 확인되지 않는 결과가 나타난것으로 미루어 그 적정농도를 DIR-vita 0.1%로 맞추는 것이 효과적일 것으로 판단된다. 한편, 체액성 면역에 있어서는 측정한 IgG, IgM, Total Ig모두에서 대조군과 비교하여 유의적인 변화를 나타내는 군은 관찰되지 않았다. 이러한 결과로부터 실험에 사용한 면역기능 증강물질들이 생체 내에서 면역방어기전을 세포성면역인 T 림파구와 관련하여 활성화되는 것을 알 수 있었으며, 실험에 사용된 물질 중 DIR-vitamineral 0.2%이 가장 효과적인 생체 내 면역기능 활성화를 나타내는 것으로 파악되었다. 실험에 사용된 물질 5가지의 생체내 면역기능활성화의 효과를 비교해 보면, 가장 효과적인 물질은 DIR-vitamineral 0.2%로 밝혀졌으며, 그 다음으로 DIR-vitamineral 0.1%, 임뮤포르테알파, DIR-vita 0.1% 순으로 효과적인 것으로 파악되었다. 이상의 결과를 종합하여 볼 때, 돼지에서 실험에 사용한 면역기능 신물질의 생체 면역증강 효과를 확인할 수 있었으며, 생산성 향상과 함께 세포성 면역증진에 따른 효과적인 질병방어기전 형성을 유도함이 인정되었다.

• Toxicological Research
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• 제19권2호
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• pp.141-146
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• 2003

A nonspecific immunostimulator $BARODON^{\circledR}$ was tested for mutagenicity using Ames Salmonella tester strains TA98, TA1 00, TA 102, TA 1535 and TA 1537 with or without metabolic activation (59 mix). None of the fresh species showed mutagenicity. In the reverse mutation test using Salmonella phimurium TA98, TA100, TA102, TA1535 and TA1537 did not increase the number of revertants at all doses tested (5, 2.5 or 1.25 mg/ml). Chromosome aberration test was carried out in Chinese hamster lung (CHL) cell line. The cells were treated with $BARODON^{\circledR}$ (1, 0.5 or 0.25 mg/ml), while positive control group was treated with Mitomycin C (0.1 mg/ml). The results show that there is no statistically significant difference between positive control and treatment groups. In mouse micronucleus test, there was significant increase in the ratio of micronucleated polychromatic erythrocyte (MNPCE) in the high dose group (10% $BARODON^{\circledR}$), while there is no significance between control and low (2.5% $BARODON^{\circledR}$) or middle (5% $BARODON^{\circledR}$ dose groups. Taken together, this results suggest that below 5% $BARODON^{\circledR}$ might not have mutagenic potential in vitro and vivo systems.

• Toxicological Research
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• 제19권1호
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• pp.39-44
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• 2003

Two local irritation and skin sensitization studies of nonspecific immunostimulator, $BARODON^{\circledR}$ were carried out with New Zealand White rabbits and Hartley guinea pigs. In skin irritation test of male New Zealand White rabbits, body weights were not significantly changed and there were no responses after treatment for 24 or 72 hours and the Primary irritation index (P.1.1.) was '0'. And, in the eye irritation test, there were chemosis in some of rabbits. One of 3 rabbits in washing group was detected chemosis after 24 and 72 h following treatment and 2 of 6 rabbits in non-washing group were detected chemosis after 24h and 7 days following treatment. Therefore, total score is '4' after 24 h and '2' after 72 h following treatment by conforming article "some blood vessel are clearly hyperemic" . However evaluation value is non-irritant because M.O.I. (Mean ocular irritation index) score is below during the all experimental period and no significance through individuals and exposure time. In skin sensitization, the score of skin reaction was graded 1 with 0% sensitization rate. Taken together, these results indicate that $BARODON^{\circledR}$ may be non-irritant material. material.

• 대한수의학회지
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• 제45권4호
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• pp.501-505
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• 2005

Immu-Forte composed of chitosan, ${\beta}-glucan$, manno-oligosaccharide and pangamic acid was evaluated for its effectiveness as a nonspecific immunostimulator in mice. The effects of Immu-Forte were determined by analysis of cytokines using ELISA and phenotype of leukocyte subpopulations using monoclonal antibodies specific to mouse leukocyte differentiation antigens and flow cytometry. All T cells, all B cells, CD4 T cells, CD8 T cells, macrophages, IL-2, IL-4, IL-12 and IFN-r in Immu-Forte A-treated group increased in 1 months posttreatment and were significantly higher (p < 0.05) than that of control at 1 months posttreatment. All T cells, all B cells, CD4 T cells, CD8 T cells, macrophages and IL-2 in Immu-Forte EX-treated low and middle dose groups increased in 1 months posttreatment and were significantly higher (p < 0.05) than that of control at 1 months posttreatment. In the Immu-Forte soybean-treated group, NK cells and IL-4 were significantly higher in middle dose-treated group, and IL-2, IL-4 and IFN-r were significantly higher in low dose-treated group. In the Immu-Forte F-treated group, all T cells, all B cells, CD4 T cells, CD8 T cells, macrophages, NK cells, IL-2, IL-4, IL-12 and IFN-r in high dose-treated group and all T cells, all B cells, CD4 T cells, CD8 T cells, macrophages, IL-2, IL-4, IL-12 and IFN-r in middle dose-treated group and NK cells, IL-2, IL-4, IL-12 and IFN-r in low dose-treated group were significantly higher (p < 0.05) than that of control at 1 months posttreatment. In conclusion, this study has demonstrated that Immu-Forte had an immunostimulatory effect on mice through proliferation and activation of mouse immune cells.

• 대한수의학회지
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• 제46권2호
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• pp.149-158
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• 2006

To determine the effects of ${\beta}$-carotene on the control of mastitis in dairy cows during the dry period, 38 dairy cows (18 mastitic cows and 20 healthy cows) were administered with 5 ml of ${\beta}$-carotene (30 mg/ml) intramuscularly twice (4 week intervals). Blood samples were taken from the cows before the injection and two weeks after the second injection, respectively, and were measured for the proportion of lymphocyte subpopulations and lymphocyte proliferation responses. With ${\beta}$-carotene injection, the proportion of cells expressing BoCD2, BoCD4 and B and N cells increased in healthy cows. In the presence of mitogens, lymphocytes from healthy cows showed significantly higher proliferation responses after ${\beta}$-carotene injection than before (p < 0.05), The somatic cell counts in ${\beta}$-carotene injected group decreased from 1,001,00 cells/ml at dry off to 647,000 cell/ml and 447 cells/ml at the stage of first and second weeks after calving, respectively (p < 0,05), This study indicated that ${\beta}$-carotene as a nonspecific immunostimulator could have a definite role for the prevention of intramammary infections in dairy cows at dry period.

• 대한수의학회지
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• 제43권2호
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• pp.255-261
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• 2003

The antigenicity of nonspecific immunostimulator BARODON$^{(R)}$, a newly developed drug, was investigated by tests for passive cutaneous anaphylaxis (PCA) and active systemic anaphylaxis (ASA) in mice and guinea pigs. In ASA test using guinea pigs, there were no significant clinical symptoms in all individuals of low(0.3%) and high(3%) dose of both groups treated with only BARODON$^{(R)}$ and cotreated with BARODON$^{(R)}$ and adjuvant group. In PCA test, blue spots of Evan's were observed from $2^6$ to $2^{10}$ in homologous group and from $2^2{\sim}2^5$ dilution rate in heterologous group of BSA treated positive control group. However, intradermal sensitization with antiserum obtained from low (0.3%) and high (3%) dose of BARODON$^{(R)}$ only treatment group and treated-with-adjuvant group, followed by intravenous injection of respective antigen and Evan's blue mixture (1:1) showed no blue spot observed. In conclusion, BARODON$^{(R)}$, as showed in ASA and PCA test, did not cause anaphylatic shock when treated 3 and 10 times higher than clinically intended dose, nor induce IgE, so that might not have antigenic properties in mice and guinea pigs.

• 한국가축번식학회지
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• 제25권2호
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• pp.131-138
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• 2001

생쥐 초기배의 배반포 발달율이 BSA첨가 배양액에 Barodon-FX(equation omitted) 첨가로 증가되지 않았으나 PVP 첨가 배양액에 0.25% 첨가에서는 부화배반포 발달율이 54.7%로 대조구(32.5%)보다 크게 향상 되었다(P ＜0.05). 1∼2% Barodon 첨가는 배발달을 월등히 저하시켰다. Barodon 첨가에 따른 체세포 증식율은 BOEC와 GC의 경우 0.25∼0.5%에서 대조구보다 각각 24∼40%와 17∼22%더 크게 증가되었다(P＜0.05). 그러나 GC와 CC에서는 1%이상 첨가시 세포증식이 크게 억제되었다(P ＜0.05). Barodon의 효과는 체세포간에 큰 차이가 있었다. 소 초기배에서 상실배이상의 배발달율은 BOEC와 GC 공배양조건에서 Barodon 0.5% 첨가에서 대조구보다 크게 향상되었다(P＜0.05). 그러나 다른 처리 수준에서는 배 발달율이 대조구와 차이가 없었다. 결론적으로 Barodon의 세포증식효과는 세포종류에 따라 차이가 많았으며 0.5% 수준의 첨가는 소 초기배의 배반포발달율을 향상시킬 수 있었다.

• 대한수의학회지
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• 제34권2호
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• pp.287-299
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• 1994

Plasma protein which has been known as one of nonspecific immunostimulators was added to feedstuff to examine its effect on the enhancement of cellular immune response in porcine immune system. A total of 40 piglets, 20 male and 20 female each, were fed for 30 days with or without plasma protein. The peripheral blood were collected and analyzed for the investigation of leukocyte subpopulations and their activities by using a panel of monoclonal antibodies specific to porcine leukocyte differentiation antigens and flow cytometry. The results obtained as follows. 1. Subpopulations expressing major histocompatibility complex(MHC) class I antigen were $96.2{\pm}3.1%$ and $86.6{\pm}3.8%$ in piglets fed with plasma protein and in piglets fed without plasma protein, respectively. 2. Proportion of leukocyte subpopulation expressing MHC class II antigens were significantly higher in the piglets fed with plasma protein than ones without plasma protein. The proportion was $27.6{\pm}3.6%$ and $16.6{\pm}2.2%$ in MHC class II DQ antigen, and $28.1{\pm}2.0%$ and $20.0{\pm}0.3%$ in MHC class II DR antigen, respectively. 3. A significant increase in the proportion of cells expressing poCD2 was not found in piglets fed plasma protein. 4. Proportion of subpopulation expressed porcine(Po) CD4 antigens which specific to helper T lymphocytes were not increased (18.3-19.1% vs. 25.6-28.8%), rather slightly decreased, in plasma protein-treated group. 5. The most important increase of proportion in plasma protein-treated group was the leukocyte subpopulation specific to $poCD8^+$ T cytotoxic/suppressor lymphocytes. The expression level was significantly higher up to 45.9-47.1% in plasma protein-treated group in comparing with 29.7-33.0% in non-plasma protein-treated group. 6. Lymphoblastogenetic responses using different concentrations of Con A mitogen and plasma protein has found that the responses of lymphocyte from piglets fed plasma protein was significantly activated (p<0.01). The activities measured by 3[H]-thymidine incorporation showed 3-6 times stronger in plasma protein-treated group than those in non-plasma protein-treated group. The study has concluded that plasma protein, which has known as a nonspecific immunostimulator, may have an immunoenhancing activities in porcine lymphoid system by increase the activated cell proportions and their blastogenetic properties which is critical to host immune responses.

• 한국식품위생안전성학회지
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• 제20권2호
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• pp.118-122
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• 2005

체내 면역 증강정을 관찰하기 위하여 체내 임파구의 활성 및 증가 여부를 3개월간 의뢰한 물질인 Immu-Forte EX, Immu-Forte 된장고추장, Immu-Forte A, Immu-Forte를 투여한 후, flowcyometry 및 sandwitch ELISA를 이용하여 측정하였다. 본 실험의 실험 기간 중에 동물의 질병이나 감염에 의한 면역학적인 변화가 있었는지를 확인하기 위하여 혈액학적인 검사를 실시하였으며, 혈액학적인 검사에서 Alkaline phosphatase, T protein, Albumin, Creatine, ALT, AST, Total bilirubin, Potasium을 검사해 본 결과 대조군과 비교 했을때 투여군 전군에서 정상적인 범위내 수치를 나타내는 것으로 나타났다. 이러한 결과로부터 본 실험에서 나온 결과는 질병이나 감염에 의한 것이 아닌 생체내에서의 면역성 증강에 의한 것으로 판단할수 있는 근거를 제공한다고 판단되어진다. 한편, 3개월간 장기 투여시 Immu-Forte EX, Immu-Forte 된장고추장, Immu-Forte A과 Immu-Forte 의 모든 물질은 전반적으로 면역 세포와 사이토카인의 수치를 유의적으로 증가시켰다 그러나, 3개월간 Immu-Forte EX를 투여 후 혈중콜레스테롤 수치를 검사해 본 결과 대조군$(118\pm24.4 mg/dL)$과 비교하였을때, 고용량$(126\pm7.7 mg/dL)$, 중간용량$(121\pm8.4 mg/dL)$, 저용량$(109\pm24.Smg/dL)$으로서 통계학적인 유의적 감소로는 보이지 않는다. 각각의 물질의 면역학적인 변화양상을 살펴보면 물질 동암 EX는 중간 농도군에서는 CD4 T 림파구, CD8 림파구, 대식세포, IL-12, IFN-r가 대조군에 비해서 유의적으로 증가했으며 떠농도에서는 전체 T 임파구, 전체 B 임파구, CD4 T 임파구, 대식세포, IL-2, IL4, IL-12가 대조군에 비해서 유의적으로 증가했다. 물질 Immu-Forte 된장고추장에서는 고농도에서는 CD4 T 임파구, IL-2, IL-4, IL-12가 유의적으로 증가했으며, 중간농도에서는 CD4 임파구, 대식세포, IL-2,IL-4,IL-12 가 유의적으로 증가했고, 저농도에서는 전체 T 임파구, CD4 T 임파구, IL-2, IL-4, IL-12가 유의적으로 증가했다. 물질 Immu-Forte A의 경우 고농도에서 대식세포,자연살해세포, IL-12가 중간농도에서는 전체 T임파구, CD4 T임파구, 대식세포, 자연살해세포, IL-2, IL-4, IL-12가 저농도에서는 자연살해세포가 유의적으로 증가했다. 물질 Immune-Forte f의 경우 고농도에서 전체 B 임파구, IL-4, IL-12가 중간농도에서 전체 T임파구, 전체 B임파구, CD4 T임파구, CD8 T 임파구, 대식세포, IL-2, IL-4, IL-12, IFN-r가 저농도에서는 자연살해세포, IL-12가 유의적으로 증가하였다. 이상과 같이 각각의 물질은 전반적으로 면역증강 효과가 있는 것으로 나타났으며 그 면역증강을 유도하는 세포나 사이토카인은 서로 정확히 일치하지 않는 것으로 보아 각각의 물질이 다른 기전을 통해서 면역증강을 유도하는 것으로 생각된다.

• 대한수의학회지
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• 제34권2호
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• pp.307-313
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• 1994

We have previously shown that crude water extract of Euonymus alatus (EA) had strong prophylactic effect against chemically induced-and tumor cell implanted-cancer, and that the mechanisms responsible for its antitumor effects were due to nonspecific enhancement of the NK cell activities and the cell mediated immunity. However, it was unknown that any components of crude extract did work so, since it consisted of several components. In this paper, we fractionated the crude watar EA-extract into several fraction such as hexane-, ethylether-, ethyl acetate-, n-butanol- and water soluble-fraction, and screened the immune regulating activities of each fraction by the evaluation of lymphokine production and activated lymphocyte proliferation. As a result of the component fraction of EA-extract, it was found that n-butanol fraction was a potent immunostimulator, and the remained water soluble fraction also contained some stimulator, But, other fraction did not showed any remarkable effect. It is therefore suggested that EA-glycosides in n-butanol fraction may be new one of the potent biological response modifiers. The present study was also undertaken in an efforts to investigate the effects of elm-bark(EB, Ulmus clavidiana var japonica), which has been used for curing ulcer and inflammation as a folk medicine without any kind of experimental evidence to support this, on the cellular- and humoral-immune responses, lymphocyte function and NK cell activities in mice. Regardless of time and duration of EB-treatment, Arthus reaction and antibody response to SRBC were not modified by EB, but delayed hypersensitivity to SRBC was significantly enhanced only when EB was treated prior to SRBC-sensitization. EB slightly inhibited the proliferation responses of splenocytes to PHA-stimulation, but it significantly augmented the responses of these cells to S aureus Cowan 1 and Con A-activation, and these effects were manifested only when EB was added at culture initiation. EB did not influence Ig secretion of spleen cells but it significantly augmented the Con A-induced 1L 2 and MIF production of splenocytes. NK cell activities of splenocytes were markedly riled when effector cells were pretreated with EB and this augmentation was dine to the increase of binding affinity of effector cells to target cells and the target cell lytic activities of effector cells. These results led to the conclusion that EB triggers increase of cellular immune responses, such as delayed hypersensitivitiy, lymphokine production and NK cell activities. Also these results suggested that EB contains potent immune stimulants, which may provide the rational basis for their therapeutic use as one of the new biological response modifiers.