• Biomolecules & Therapeutics
• /
• v.10 no.2
• /
• pp.129-135
• /
• 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.

• Biomolecules & Therapeutics
• /
• v.4 no.4
• /
• pp.334-338
• /
• 1996

Antigenicity of DA-3285, human recombinant erythropoietin which was produced from mammalian cells, was examined in guinea pigs and mice. In active systemic anaphylactic test, mild anaphylactic signs were observed in guinea pigs sensitized subcutaneously with DA-3285 or DA-3285 incorporated with complete Freund's adjuvant(CFA) when challenged with high dose(1000 IU/Kg) of DA-3285. Other groups showed negative responses. In mouse-rat passive cutaneous anaphylaxis test, 20% sera of mice immunized with DA-3285 or DA-3285 mixed with aluminum hydroxide(alum) showed mild positive responses. In the case of indirect haemagglutination reaction(IHA) test, when sheep red blood cells coated with DA-3285 was incubated with mouse serum, all the serum samples were showed negative responses. These results suggest that DA-3285 has a very weak antigenic potential and probably would not induce systemic allergic reactions in clinical uses.

• Toxicological Research
• /
• v.14 no.3
• /
• pp.307-313
• /
• 1998

Dimethyl dimethoxy biphenylate (DDB) is an agent used to treat hepatits. DDB-S (DDB-soluble), a new DDB derivative, was synthsized to increase water solubility of the original DDB. In the present study, the antigenic potential of DDB-S was examined by active systemic anaphylaxis (ASA), passive cutaneous anaphylaxis (PCA) and passive hemagglutination (PHA) tests. The experimental groups consist of a low dosage group, a high dosage group, he group emulsified with Freund's complete adjuvant (FCA, ASA test) or an alum (PCA and PHA tests) and the macromolecule conjugate group emulsified with FCA or an alum. In the ASA test, all experimental groups showed negative responses whereas the positive control group given ovalbumin plus FCA showed severe anaphylactic responses. In the heterologous PCA test using mice and rats, positive responses were not detected in any of the experimental groups. In the PHA test, all experimental groups showed negative responses whereas the positive control group given ovalbumin plus an alum showed 512~2048 PHA titers. These results demonstrated that DDB-S does not have any antigenic potential. These can be utilized as a part of preclinical data for the development of DDB-S as an intravenous injection.

• Toxicological Research
• /
• v.14 no.3
• /
• pp.459-463
• /
• 1998

The antigenicity of intralipidos was investigated in guinea pig, mice and rats. Antigenicity tests-active systemic anaphylaxis (ASA), passive systemic anaphylaxis (PSA), passive cutaneous anaphylaxix (PCA) of this materials were performed. The results were followed: 1. After sensitizaion with YPL, YPL+intralipidos, and intralipidos, emulsified with complete Freund's adjuvant (CFA), guinea pigs didn's show any anaphylatic shock symptom in the ASA test, 2. These materials didn't show any anaphylatic shock symptom in the PSA test, 3. After sensitization with antisera of YPL, YPL+intralipidos, and intralipidos sensitized mice, blue spots were not observed on the hypodermis of back of rats in the PCA test. From the results of this investigation, the antigenicity of YPL, intralipidos was negative under the present experimental condition.

• Biomolecules & Therapeutics
• /
• v.3 no.4
• /
• pp.251-255
• /
• 1995

DA-3002 is a genuine human growth hormone produced by Dong-A Pharm. Co. Ltd. research laboratory using recombinant DNA technic. In this study, antigenic potential of DA-3002 was examined by active systemic anaphyaxis(ASA) in guinea pigs, mouse-rat passive cutaneous anaphylaxis(PCA) and passive hemagglutination(PHA) test as a part of safety research. DA-3002 induced anaphylactic shock in ASA test using guinea pigs Immunized with DA-3002 alone or DA-3002 incoporated into Freund's complete adjutant(FCA) when challenged with 10 times higher dose of anticipated clinical dose of DA-3002. In the mouse-rat PCA and PHA test, DA-3002 also showed positive results. DA-3002, therfore, was considered to produce IgE, IgG, and/or IgM in mice. The results of this study were similar to those of the other human growth hormones and these positive results were thought to be caused due to the fact that both DA-3002 and the other human growth hormones were heterogenous proteins to guinea pigs and mice. Considering the fact that DA-3002 is a genuine human growth hormone of which structure is identical with indigenous human growth hormone, DA-3002 is thought not to cause immunological problems in clinical use.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.21 no.5
• /
• pp.1118-1126
• /
• 2007

The purpose of this study was to examine the anti allergic effect in vivo and in vitro, and to observe single and four weeks repeated toxicity in mice of Bangpung-galgeun-tang (BGT). We investigated anti DNP IgE-mediated passive cutaneous anaphylaxis in rodents and compound 48/80-induced active systemic anaphylatic shock in mice after oral administration with BGT of 0.4 g/kg and 0.8 g/kg for 8 days, and also examined MTT assay, ${\beta}-hexosaminidase$ activity, IL-4 and $TNF-{\alpha}$ from RBL-2H3 and $TNF-{\alpha}$ from Raw264.7 after pre-treatment with BGT of 0.25 mg/ml, 0.5 mg/ml, 1 mg/ml and 2 mg/ml. To ascertain safety and toxicity of BGT, we divided into single and four weeks repeated administration test. In single test, three groups were administrated different dosages and routes (2 g/kg/i.p., 4 g/kg/i.p. and 15 g/kg /p.o.) of BGT, and in four weeks repeated test, 0.8 g/kg BGT was administrated. Control groups were administrated with only saline according to on Korean Food and Drug Administration, respectively. We observed attentively motality, abnormal clinical sign, body weight change, organ weight, AST and ALT of mice after BGT administration. BGT inhibited passive cutaneous anaphylaxis and active systemic anaphylatic shock by oral administration. All the concentrations of BGT from 0.25 to 2 mg/ml didn't have an effect on cell viability and cytotoxicity. In RBL-2H3, ${\beta}-hexosaminidase$ release, IL-4 and $TNF-{\alpha}$, and in Raw264.7, $TNF-{\alpha}$ were significantly reduced by treated all concentrations of BGT. During toxicity experiment period, there was no difference in body weight change, organ weight, AST and ALT among different dose groups. Death were found 3 mice from day 2 to day 3 in single test i.p. group. (2 g/kg, 4 g/kg). Several individuals of single test i.p. group were observed that decreased locomotor activity, exophthalmos, bloodshot eyes, loss of eyesight and so on in early period after administration. But there was no difference in clinical signs among p.o. group. These results indicate that BGT have inhibition effects on allergy and suggest that no observable effect level of the test orally administration was considered to be more than 2 g/kg in mice under the conditions employed in this study.

• Toxicological Research
• /
• v.12 no.1
• /
• pp.81-86
• /
• 1996

Antigenicity of recombinant human interferon $\beta$(LB00013), a newly developed drug for anti-cancer and anti-viral therapeutic use, was investigated in mice and guinea pigs. The following results were obtained: 1. Mice showed no production of antibodies against LB00013 sensitized with aluminum hydroxide gel (Alum) as an adjuvant, when judged by the heterologous passive cutaneous anaphylaxis (PCA) test in rats. Meanwhile, antibodies against ovalbumin (OVA) sensitized with Alum were clearly detected. 2. In guinea pigs, the sensitization of neither LB00013 only nor LB00013 with complete Freund's adjuvant (CFA) produced positive reactions in the homologous active systemic anaphylaxis (ASA) and the PCA tests. Meanwhile, the sensitization of OVA with CFA produced positive reactions in both PCA and ASA. 3. A LB00013-specific reaction was not observed in an indirect hemagglutination(IHA) assay using sera isolated from LB00013 sensitized mice. The present results suggested that LB00013 may have no antigenic potential in mice and guinea pigs.

• Biomolecules & Therapeutics
• /
• v.7 no.1
• /
• pp.14-21
• /
• 1999

The immunogenicity of the recombinant human basic fibroblast growth factor (rh-bFGF) was investigated by tests for active systemic anaphylaxis (ASA), passive cutaneous anaphylaxis (PCA), passive hemagglutination (PHA) and guinea pig maximization test (GPMT) in mice or guinea pigs. Guinea pigs were sensitized with rh-bFGF ($100-1000\;\mu\textrm{g}/kg$) or rh-bFGF-CFA mixture ($1000\;\mu\textrm{g}/kg$). All animals sensitized with rh-bFGF alone or mixture with CFA showed symptoms of anaphylactic shock. IgE antibodies to rh-bFGF were detected in sera obtained from rh-bFGF and rh-bFGF-Alum ($1000\;\mu\textrm{g}/kg$) sensitized mice, indicating that rh-bFGF has immunogenicity eliciting potential. IgG and/or IgM antibodies to rh-bFGF were also detected in all the sera obtained from sensitized mice by PHA. In the GPMT for delayed type skin reaction, no skin reaction was observed in sensitized guinea pigs after intradermal injection and dermal application of 0.01% rh- bFGF. However, these positive reactions were consistent with the results of another rh-bFGF, showing that rh- bFGF is a heterogenous protein to rodents. Considering the fact that rh-bFGF is a genuine human protein of which structure is identical to the endogenous human bFGF, it is thought that rh-bFGF is rarely associated with immunological problems in clinical use.

• Proceedings of the PSK Conference
• /
• 2003.10b
• /
• pp.125.3-126
• /
• 2003

Effect of Compound-A, a phenylpropanoid isolated from Arctium lappa fruit, on heterologous passive cutaneous anaphylaxis (HPCA), the release of histamine, and Phospholipase $A_2$ (PLA2) and phosphadiesterase (PDE) activities were studied by the method of Levine and Vaz. Anti-serum was prepared from ovalbumin (OA)-sensitized male Balb/c mouse at two weeks after the last challenge of OA and alumina gel. Heterologous PCA test in rats were carried out to determine the contents of leakaged pigment in the dorsal skin 30 minutes after i.v. injection of 0.2 ml of 1 % OA and 1 % Evans blue mixture (1:1). (omitted)

• Biomolecules & Therapeutics
• /
• v.10 no.2
• /
• pp.124-128
• /
• 2002

Hantaan (HTN) and Puumala (PUU) viruses are major etiological agents of hemorrhagic fever with renal syndrome (HFRS), an important public health problem in Korea after the Korean War. The objective of present study was to determine allergenic potency of an inactivated combination vaccine against HTN and PUU viruses inflection. As a series of allergenicity assessment, a homologous active systemic anaphylaxis (ASA) and homologous/heterologous passive cutaneous anaphylaxis (PCA) tests using the mice and guinea pigs were carried out. In the ASA test, no anaphylactic symptoms were observed in the guinea pigs sensitized with the vaccine alone as well as the vaccine emulsified with an adjuvant. By homologous PCA test, the vatscine did not induced the potential IgE antibody production in the sera obtained from the sensitized guinea pigs. In addition, IgE against the vaccine was not significantly enhanced from the mice inoculated with the vaccine, which was judged by the heterologous PCA test in rats. On the other hand, the inoculation of ovalbumin appeared to allergenic reactions both in the ASA and PCA tests. The results suggest that a combination vaccine against HW and PUU viruses have no allergenic potential in mice or guinea pigs.