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Therapeutic Trial of an Endothelin Receptor Agonist for the Highly Pathogenic Avian Influenza A/H5N1 Virus Infection in Chicks

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Health 2014年第19期6卷 2553-2561页

作者： Kazuhide Adachi Retno Damajanti Soejoedono ekowati handharyani Marie Inai Yasuhiro Tsukamoto Department of Animal Hygiene Graduate School of Environmental & Biological Sciences Kyoto Prefecture University Kyoto Japan Faculty of Veterinary Medicine Bogor Agriculture University Bogor Indonesia

The rapid spread of the highly pathogenic A/H5N1 avian influenza virus among domestic birds and its transmission to humans has induced world-wide fears of a new influenza pandemic. A/H5N1 has infected over 300 people since 1997, and has shown a mortality rate of over 50%. The high mortality in human cases is thought to be enhanced by the excessive secretion of various endogenous factors, including cytokines and interleukins, stimulated by viral infections. Chickens infected with A/H5N1 viruses experience sudden death without showing severe clinical symptoms or inflammation. However, severe hemorrhage and congestion are seen in various tissues in sporadic chicken cases of A/H5N1-infections, especially in the pulmonary tissues, thus indicating that there is ischemia due to vascular abnormalities. Our previous studies have focused on the expression pattern of endothelin-1, which modulates the vascular tone via endothelin receptors. An Indonesian sporadic strain of A/H5N1 virus was intranasally administered to 10-day-old chicks, and the expression of endothelin was examined in the infected birds. All birds died within five days of inoculation, and had moderate inflammation accompanied by severe hemorrhage and congestion in the lungs. Immunohistochemical studies showed enhanced expression of endothelin-1 in the infected lungs. In addition, the real-time PCR analyses revealed that endothelin-1 and endothelin receptor A mRNA were significantly elevated in the birds with A/H5N1 infections. Subsequently, H5N1-infected birds were inoculated with bosentan hydrate, a competitive antagonist of endothelin receptors. Interestingly, the mortality rate of the infected birds was dramatically decreased in a dose-dependent manner by the administration of bosentan hydrate. The pathological lesions, including congestion and hemorrhage in the pulmonary tissues, were clearly inhibited. These findings are promising, and suggest that endothelin receptor antagonists are a potential treatment

关键词： Avian Influenza Virus A/H5N1 Endothelin Receptor Chicken

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Effects of the Soil-Derived Microorganism BX-1 on Chicken Newcastle Disease

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Advances in Infectious Diseases 2020年第1期10卷 1-10页

作者： Kiyotaka Murakami Kazuhide Adachi Retno Damajanti Soejoedono ekowati handharyani Yasuhiro Tsukamoto Department of Animal Hygiene Graduate School of Environmental & Biological Sciences Kyoto Prefecture University Kyoto Japan R&D Section Taiga Inc. Tokyo Japan Faculty of Veterinary Medicine Bogor Agriculture University Bogor Indonesia

In recent years, effective microorganisms (EMs) have been administered to humans and domestic animals, and their usefulness has been recognized for promoting health and enhancing immunity. For example, the preventative effects against flu are enhanced by ingestion of Lactobacillus by humans, and symptom relief of atopic dermatitis has been reported, with EMs actually used in commercial products. In addition, EM preparations are being used in livestock to prevent infections (e.g. Salmonella and Escherichia coli infection). In poultry, avian influenza and Newcastle disease are terrible and fatal infectious diseases that cause significant economic damage. Furthermore, countries designated as contaminated with these pathogens can experience major trade problems. Given the above, how to protect livestock from infections safely and at low cost without using disinfectants, antibiotics and vaccines is a major issue. In the present study, we examined whether or not Newcastle disease could be suppressed by feeding chickens BX-1 as an EM feed. A field strain of Newcastle virus was cloned from cloaca swabs of large numbers of dying chickens in a poultry farm in Indonesia by polymerase chain reaction (PCR) and hemaggregation assays. Chicken kidney cells and embryonated eggs were highly sensitive to this virus, and high titers of virus were able to be collected. The experimental viral inoculated to chickens showed a high mortality rate, with high pathogenicity in birds. Conventional chickens were also raised on a diet supplemented with BX-1 and directly infected with the Newcastle virus. The mortality was decreased in these infected birds. Even the low dose of BX-1 had an inhibitory effect on the lethality of the infection. These results suggest that BX-1 intake through an EM diet is effective in controlling Newcastle disease.

关键词： Newcastle Disease Effective Microorganisms BX-1 Chicken

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Suppression of Highly Pathogenic Avian Influenza A/H5N1 Infection Using Migratory Antibody Passed from Mother to Chick

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World Journal of Vaccines 2018年第4期8卷 89-97页

作者： Kazuhide Adachi Ganita Kurniasih Suryaman Retno Damajanti Soejoedono ekowati handharyani Yasuhiro Tsukamoto Department of Animal Hygiene Graduate School of Environmental & Biological Sciences Kyoto Prefecture University Kyoto Japan Faculty of Veterinary Medicine Bogor Agriculture University Bogor Indonesia

Avian influenza is the most contagious disease not only in poultry, but also in humans. Avian influenza in humans occurs mainly in Southeast Asia, but no human-to-human pandemic has occurred. Meanwhile, outbreaks of avian influenza in poultry occur on a global scale and cause a large economic loss. Migration antibodies passed from mother birds via eggs are said to be an important component of the immune system that protects birds from infection. Thus, the immunity status of mother birds can determine the ability of offspring to defend against infection. In this study, we investigated the presence of anti-avian influenza virus antibody in chickens hatched on a poultry farm in Indonesia and examined the involvement of migratory antibodies in protecting against virus infection by infectious experiments of highly pathogenic avian influenza in chickens. Blood was collected from randomly selected chicks, and antibodies against avian influenza virus were evaluated in all birds. Since these young birds had no history of vaccination, the antibodies were deemed to have been transferred from the mother birds. The enzyme-linked immunosorbent assay antibody titer in each bird varied. Infection of these birds with highly pathogenic avian influenza virus A/H5N1 intra-nasally resulted in a high mortality rate in chicks with low antibody titers but a low mortality rate in chicks with high antibody titers. These findings indicate that migratory antibody prevented highly pathogenic avian influenza A/H5N1 infection in chicks, suggesting that such a preventive effect could also be expected with outdoor natural infection.

关键词： Avian Flu Influenza Virus H5N1 Antibody Chicken

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Prevention of Highly Pathogenic Avian Influenza A/H5N1 Infection by Passive Immunotherapy Using Antiserum

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Advances in Microbiology 2018年第11期8卷 874-884页

The rapid epidemic of highly pathogenic A/H5N1 avian influenza virus by transmission from poultry to humans triggered global unrest in the pandemic of novel influenza. If a human trophic strain of avian influenza viruses replicates in livestock including pigs and chickens, it may have high infectivity and pathogenicity to humans. The most effective method of reducing the outbreaks of influenza would be prophylaxis with an effective vaccine as well as anti-viral drugs including Oseltamivir and Zanamivir hydrate. In this study, chicken antiserum against A/H5N1 virus was produced: the antisera from immunized adult chicken had a strong binding activity to A/H5N1 viral antigens by ELISA. Furthermore, the antiserum strongly inhibited hemaggregation of erythrocytes and cytopathic effects in MDCK cells, indicating a strong neutralization activity against A/H5N1 infections. Interestingly, the mortality rate of chicks inoculated with A/H5N1 virus was dramatically decreased with the antiserum injection. These results suggest that antiserum may be a potentially effective protective and therapeutic modality for A/H5N1 infection.

关键词： Avian Flu Influenza Virus H5N1 Antiserum Chicken

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