• Title/Summary/Keyword: recombinant Interferon-${\alpha}$

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Successful Management of Feline Infectious Peritonitis with Human Recombinant Interferon-alpha and Pentoxifylline in a Cat (재조합 인간 인터페론 알파와 Pentoxifylline을 이용한 고양이 전염성 복막염의 치료 증례)

  • Kang, Min-Hee;Park, Hee-Myung
    • Journal of Veterinary Clinics
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    • v.28 no.4
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    • pp.427-430
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    • 2011
  • A 6-month-old intact female, domestic short hair cat was presented with dyspnea and anorexia for 2 days. Physical examination revealed muffled heart sound with labored breaths. Hyperproteinemia and hyperglobulinemia with polyclonal gammapathy was revealed. Pleural effusion was non-septic exudates, it also had hyperglobulinemia with decreased albumin: globuline ration. In addition, effusion RT-PCR for feline coronavirus was positive in this cat. Feline infectious peritonitis (FIP) was strongly suspected and aggressive treatments with human interferon-alpha, pentoxifylline, and glucocorticoids were initiated. The cat remained healthy without recurrence of pleural effusion during 5 months follow-up periods. To the author's knowledge, this is the first case report describing successful management of FIP with human interferon-alpha and pentoxifylline in Korea.

Pharmacokinetics of DA-3021 (mono-PEGylated recombinant human interferon ($\alpha$-2a) after Subcutaneous Administrations to Experimental Animals

  • Jo, Yeong-Woo;Kim, Won-Geun;Choi, Yun-Kyu;Jeon, Hyun-Kyu;Kim, Dong-Hwan;Park, Beom-Soo;Lee, Sung-Hee;Kim, Won-Bae;Youn, Yu-Seok
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.424.1-424.1
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    • 2002
  • Interferon has therapeutic potential for a wide range of infectious and proliferative disorders such as chronic hepatitis C and malignant melanoma. However. it has some therapeutic problems as other protein therapeutics do. A variety of approaches have been developed to circumvent these problems. Among them. the attachment of a polyethylene glycol (PEG) moiety 10 interferon is considered as one of the most promising solutions for its ability of extending the plasma residence time. (omitted)

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Absorption of ${\alpha}-Interferon$ from Ointment after Topical Application to Nude Mice and Rats (연고제로부터 ${\alpha}$-인터페론의 흡수)

  • Shim, Chang-Koo;Kim, Dae-Duk;Jung, In-Whoan;Kim, Hyun-Su;Yoon, Moo-Yung
    • Journal of Pharmaceutical Investigation
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    • v.16 no.3
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    • pp.118-123
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    • 1986
  • Time-concentration curves of recombinant human interferon alpha$(rIFN-{\alpha}A)$ in the skin and serum of nude mice or rats were studied after topical application of IFN ointment. IFN appeared in the skin and serum in less than 30 minutes and lasted for more than 10-12 hours at high concentration level after the application to nude mice at a dose of $9.0{\times}10^5\;IU/g$ mouse. But in the rats, IFN was not detected in the serum even 7 hours after the application at a dose of $6.0{\times}10^5\;IU/g$ rat. Topical application of IFN might be useful for the topical and systemic treatment if the human skin resembles that of nude mouse in respect to transport characteristics.

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Effects of cytokines in the activation of peritoneal macrophages from mice infected with Toxopluma gondii (Cytokine이 Toxoplasma감염 마우스 복강대식세포의 활성화에 미치는 영향)

  • 이영하;신대환
    • Parasites, Hosts and Diseases
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    • v.32 no.3
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    • pp.185-194
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    • 1994
  • The present study was undertaken to assess the role of cytokines in the activation of peritoneal macrophages from Toxoplasma-infected mice. Peritoneal macrophages from Toxoplasma-infected mice (10 cysts of Beverley strain/mouse) were harvested 8 weeks after infection, and incubated with the mitogen-induced lymphokine, recombinant mouse $interferon-{\gamma}(IFN-{\gamma})$, recombinant mouse tumor necrosis $factor-{\alpha}{\;}(TNF-{\alpha})$ alone or in combination with 4$IFN-{\gamma}(IFN-{\gamma}/TNF-{\alpha})$ for 24hr at 37^{\circ}C$, 5% $CO_2$. Macrophage activation was measured by the amount of $H_20_2{\;}and{\;}N0_2^{-}$ production, and antiToxoplasma activities of macrophages. $IFN-{\gamma}{\;}or{\;}IFN-{\gamma}/TNF-{\alpha}-treated$ macrophages from Toxoplasma-infected mice revealed significantly higher $H_20_2$ production than resident macrophages from Toxoplasma-infected mice. The production of $N0_2^{-}{\;}by{\;}TNF-{\alpha}-,{\;}IFN-{\gamma}-{\;}or{\;}IFN-{\gamma}/TNF-{\alpha}-treated$ macrophages from Toxoplasma-infected mice were significantly higher than that by resident macrophages, whereas lymphokine-treated group produced similar amount as that produced by resident macrophages. Anti-Toxoplasma activities of cytokinetreated macrophages from Toxoplasma-infected mice were Significantly higher than those of resident macrophages. $IFN-{\gamma}-treated$ macrophages were significantly increased production of $H_20_2{\;}and{\;}N0_2^{-}$, and anti-Toxoplasma activities of macrophages between normal and Toxoplasma-infected mice, whereas the other cytokine-treated groups were not significant differences between them. These data suggested that IFN-{\gamma}was the only one of cytokines capable of significantly activating the peritoneal macrophages from Toxoplasmainfected mice.

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PERI-NATAL AND POST-NATAL STUDY OF THE RECOMBINANT HUMAN INTERFERON ${\alpha}A\;(rHuIFN-{\alpha}A)$ IN RATS

  • Lee, Yong-Soon;Kim, Yun-Bae;Kim, Hyun-Su;Cho, Nam-Jin;Yoo, Moo-Young
    • Toxicological Research
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    • v.3 no.1
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    • pp.55-63
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    • 1987
  • A Peri-and Postnatal Study was Carried out to examine the effects of rHuIFN-${\alpha}A$, produced by gene-manipulated E. coli, on offsprings of Wistar rats. The substance was administered intraperitoneally to dams at dose levels of $1{\times}10^5$, $4{\times}10^5$ and $1.2{\times}10^6$ I.U/kg/day during the period from day 17 of gestation to day 21 after delivery. All the pregnant dams were allowed to deliver naturally, and the postnatal development of the offsprings was observed. No noticeable toxic effects and pathological changes on dams were observed, and no detectable variations in postnatal development of offsprings occured.

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STUDIES OF RECOMBINANT HUMAN INTERFERON-${\alpha}A(rHuIFN-{\alpha}A)$ ON FERTILITY IN RATS

  • Lee, Yong-Soon;Park, Jae-Hak;Kang, Tae-Gyu;Kim, Hyun-Su;Cho, Nam-Sin;Yoo, Moo-Young
    • Toxicological Research
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    • v.3 no.1
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    • pp.33-44
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    • 1987
  • A fertility study was carried out in Sprague Daxley rats which have been given the intravenous or intraperitoneal injections of rHuIFN-${\alpha}$A, a commecially available therapeutic agent, at dose levels of $1{\times}10^5$, $4{\times}10^5$ and $1.2{\times}10^6$ I.U/kg/day. Male rats were treated with rHuIFN-${\alpha}$A from 60 days before pairing and until the completion of mating. Femal rats received rHuIFN-${\alpha}$A for 22days prior to mating and up to day of gestation. All pregnant females were sacrificed on day 20 of gestation and all fetuses were examined for abnormalities. Both the male and female animals treated with rHuIFN-${\alpha}$A did not show any abnormal responses. No abnormal signs were seen in reproducibility for the rats treated with rHuIFN-${\alpha}$A. No External, internal and skeletal anomalies attributable to rHuIFN-${\alpha}$A were observed in the fetuses. It was concluded that rHuIFN-${\alpha}A$ had no harmful effect on mating, fertilization, implantation, or embryonic development.

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TERATOLOGICAL STUDY OF THE RECOMBINANT HUMAN INTERFERON-${\alpha}A(rHuIFN-{\alpha}A)$ IN RATS

  • Lee, Yong-Soon;Kim, Yun-Bae;Ahn, Byoung-Ok;Kim, Hyun-Su;Cho, Nam-Jin;Yoo, Moo-Young
    • Toxicological Research
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    • v.3 no.1
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    • pp.45-53
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    • 1987
  • A teratogenicity study was carried out on Sprague-Dawley rats which have been given the intravenously or intraperitonealy injections of rHuIFN-${\alpha}$A, an available therapeutic agent, at dose levels of $1{\times}10^5$, $4{\times}10^5$ and $1.2{\times}10^6$ I.U/kg/day for a period of 11 days from day 7 to day 17 of gestation. Two-thirds of the pregnant females in each group were sacrificed on day 20 of gestation and their fetuses were examined. The remaining dams were allowed to litter naturally, and the postnatal development of the off springs was observed. No changes were observed in all aspects of parameters between the treated and the control dams. The incidence of external, internal, and skeletal anomalies were not significantly increased in the fetuses of any treated groups. The rHuIFN-${\alpha}A$ caused no effects on parturition, lactation, and postnatal growth.

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Purification and Characterization of the Functional Catalytic Domain of PKR-Like Endoplasmic Reticulum Kinase Expressed in Escherichia coli

  • Yun Jin-A;Chung Ho-Young;Kim Seong-Jun;Cho Hyun-Soo;Oh Jong-Won
    • Journal of Microbiology and Biotechnology
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    • v.16 no.9
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    • pp.1453-1458
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    • 2006
  • PKR-like endoplasmic reticulum (ER) kinase (PERK) is a type I transmembrane ER-resident protein containing a cytoplasmic catalytic domain with a Ser/Thr kinase activity, which is most closely related to the eukaryotic translation initiation factor-$2{\alpha}$ ($eIF2{\alpha}$) kinase PKR involved in the antiviral defense pathway by interferon. We cloned and expressed the PERK C-terminal kinase domain (cPERK) in Escherichia coli. Like PERK activation in cells under ER stress, wild-type cPERK underwent autophosphorylation when overexpressed in E. coli, whereas the cPERK(K621M) with a methionine substitution for the lysine at amino acid 621 lost the autophosphorylation activity. The activated form cPERK which was purified to near homogeneity, formed an oligomer and was able to trans-phosphorylate specifically its cellular substrate $eIF2{\alpha}$. Two-dimensional phosphoamino acids analysis revealed that phosphorylation of cPERK occurs at the Ser and Thr residues. The functionally active recombinant cPERK, and its inactive mutant should be useful for the analysis of biochemical functions of PERK and for the determination of their three-dimensional structures.

The Effects of Chelidonium majus on NO and $TNF-{\alpha}$ Production in Macrophages (백굴채가 대식세포의 NO 및 $TNF-{\alpha}$ 생성에 미치는 영향)

  • 김홍준;문석재;김동웅;문구;원경숙;윤준철;김유경;원진희
    • The Journal of Korean Medicine
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    • v.24 no.2
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    • pp.138-147
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    • 2003
  • Objectives : In this study, we investigated the mechanism by which Chelidonium majus (CM) regulates nitric oxide (NO) production. Methods : Using mouse peritoneal macrophages, the mechanism by which CM regulates NO or tumor necrosis $factor-{\alpha}(TNF-{\alpha})$ production was examined. NO release was measured by the Griess method. $TNF-{\alpha}$ production was measured by the ELISA method. The protein extracts were prepared and samples were analyzed for the inducible NOS(iNOS) expression and nuclear factor kappa $B(NF-{\kappa}B)$ activation by Western blotting. Results : When CM was used in combination with recombinant $interferon-{\gamma}{\;}(rIFN-{\gamma})$, there was a marked cooperative induction of NO production. CM had an effect on NO production by itself. The expression of the iNOS gene was increased in $rIFN-{\gamma}$ plus CM-stimulated peritoneal macrophages and almost completely inhibited by pre-treatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of $NF-{\kappa}B$. The $NF-{\kappa}B$ activation was increased in rIFN-{\gamma} plus CM-induced peritoneal macrophages. The increased production of NO from $rIFN-{\gamma}$ plus CM-stimulated peritoneal rnacrophages was decreased by the treatment with $N^{G}-monomethyl-{_L}-arginine{\;}(N^{G}MMA){\;}N^{\alpha}-Tosyl-Phe$ chloromethyl ketone (TPCK) , and was almost completely inhibited by pre-treatment with PDTC. Furthermore, treatment with CM alone or rIFN-{\gamma} plus CM in peritoneal macrophages caused a significant increase in $TNF-{\alpha}$ production. PDTC decreased CM-induced $TNF-{\alpha}$ production significantly. After CM treatment in HT-29 or AGS cells, cell viability decreased. Conclusions : These findings demonstrate that CM increases the production of NO and $TNF-{\alpha}{\;}by{\;}rIFN-{\gamma}-primed$ macrophages and suggest that NF-B plays a critical role in mediating these effects of CM.

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