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Radiation sterilization of medical products
Around
the Nucleur
World
165
Ionizing radiation can substitute in whole or in part for nitrites in cured meats while eliminating the hazard of production of Cl. botulinum toxin. No nitrosamines are detected in “No Nitrite” bacon, even after frying. Ionizing radiation can be used instead of mutagenic and potentially carcinogenic agents such as ethylene oxide, ethylene dibromide and other chemical food preserving agents. Nutritionally, even when the high doses required for radappertization are used, quality is equal to or better than foods made shelf-stable by other processes such as heat. The extended shelf-life through irradiation makes it possible to supply much animal protein, calories, and other essential nutrients to a hungry world. Bibliography JOSEPHXINE. S., BRYNJOLFS~~N A. and WIERBICKIE. In Radiation Research, Biomedical, Chemical and Physical Perspectives (Edited by NYGAARD0. F., ADLERH. I. and SINCLAIRW. K.), pp. 96-l 17. Academic Press, New York (1975). JOSEPHSON E. S., THOMASM. H. and CALHOUNW. K. J. Fd Process. Pres. 2,299-313 (1978). ROWLEYD. B., SULLIVANR. and J~~EPH~~NE. S. In Indicators of Viruses in Water and Food,
Chapter 14, pp. 355-382. Ann Arbor Science Publishers, Ann Arbor, Mich. (1978).
Radiation Sterilization of Medical Products F. J. LEY Irradiated Products Limited, Elgin Estate, Swindon, England The tremendous potential for the production of large radiation sources through the construction of nuclear reactors was recognised in the late 1950s. Cobalt-60 has become available in quantities which allows y-radiation processing on an industrial scale and radiation facilities are now operating all over the world. Almost all these plants are used for the sterilization of medical products, including devices, pharmaceuticals and biological .materials. Although the accent now is on the employment of a radioisotope source, the beginnings of the process were based on the use of electron-beam generators. The pioneering efforts of Ethicon Inc. and of Charles Artandi in particular, are well recognised. The lethal effect of y-radiation on microorganisms without causing a significant rise in temperature, combined with complete product penetration, makes the process particularly attractive for the sterilization of pre-packaged, single-use medical devices such as plastic syringes or catheters. The list of such products being commercially produced and sterilized is now extensive and includes drapes and hospital procedure packs. It is generally accepted that a 2.5 Mrad dose is the preferred choice for sterilization. This is based on the investigation of the inactivation of different microbial species taking into account the influence of environmental conditions on radiation resistance and the significance of initial population numbers on the margin of safety achieved. Not all materials are suitable for irradiation; polypropylene tends to embrittle and PVC to discolor, whilst cotton loses some tensile strength. In some instances health authorities approve the use of doses lower than 2.5 Mrad, depending on the use of the product; in this way radiation damage can be avoided. As far as pharmaceutical products are concerned, few are marketed and these are mainly antibiotic preparations particularly for ophthalmic use. So far, there has been no real need in this area since industry has solved many sterilization problems by investment in aseptic handling areas, many equipped with laminar flow systems. Furthermore, the application of radiation to individual pharmaceuticals normally requires approval from health authorities, and it is necessary to produce detailed experimental evidence of non-toxicity; this requirement applies to any change in the method of manufacture. Some biological tissues are radiation sterilized; there is considerable experience with bond grafts and some success with blood vessels, heart valves, nerves and tendons. The technique has been used in the preservation of human tissues in relation to the establishment of tissue banks. The rapid introduction of radiation processing in the medical field has been helped through the interest of the U.N. organisations, in particular by the International Atomic Energy Agency. Harmony of legislation between countries is a necessary step to encourage trade, which is very active in the area of pre-sterilized disposable “ready-to-use” medical equipment. A code of practice governing production methods and the operation of radiation facilities has been prepared. A number of publications are available covering in detail the broad areas of application which have been referred to as well as providing a description of the type of radiation facilities involved.~‘~z~3’
166
Around
the Nuclear
World
References 1. Radiosterilization of Medical Products and Recommended Code of Practice. Pub. No. ST],; PUB/157. IAEA, Vienna (1967). 2. Manual on Radiation Sterilization of Medical and Biological Materials IAEA Pub. No. ST11 DOG/149. IAEA, Vienna (1973). 3. Radiation Sterilization-Irradiated Tissues and their Potential Clinical Use. Proceedings of an IAEA Advisory Group, Athens, 1976 (Edited by PHILLIPSCi. O., TALLENTIREA. and TRIANTAFYLLOU N.). North E Wales Institute, Clwyd, U.K. (1978).
Application of Nuclear Technology to the Development of a Vaccine Against Sporozoite-induced Malaria ALAN H. COCHRANJZ Assistant Professor, New York University Medical Center, Division of Parasitology, Department Microbiology
of
The sporozoite stage of malaria parasites has been used in vaccination attempts involving a variety of mammalian hosts. Mice have been immunized and protected with radiation-attenuated sporozoites of Plasmodium berghei and P. chabaudi; a relatively small number of rhesus monkeys have been immunized with irradiated sporozoites of either P. cynomolgi or P. knowlesi; and finally, a small number of humans have been successfully immunized by the bites of irradiated P. vivax or P. falciparum-infected mosquitoes. Intact irradiated or viable sporozoites are, at present, the most effective sporozoite antigen preparation for vaccination purposes. They are highly immunogenic and when administered either intravenously or by the bites of infected mosquitoes, confer complete protection against sporozoiteinduced malaria infections without the need for immunopotentiation. In rodents complete protection can be obtained following immunization with a single dose of irradiated sporozoites. Induction of protective immunity in rhesus monkeys and humans, however, requires the administration of larger numbers of sporozoites in multiple immunizing doses. Successful vaccination against sporozoites is characterized by development of a sterile immunity which is strictly stage specific. Immunized hosts, while totally resistant to sporozoite challenge, are fully susceptible to challenge with blood stages of the malaria parasite. In sporozoite-vaccinated rhesus monkeys and humans, protection, as well as antisporozoite antibodies, is strictly species specific. Immunized primates are protected only against challenge with sporozoites of the plasmodial species used for immunization. These immunized hosts are however fully resistant to challenge with sporozoites of various strains of the homologous species. This protection is accompanied by the development of species-specific antibodies which show cross-strain reactivity for a given plasmodial species. In contrast, in sporozoite-immunized rodents, protection and antisporozoite antibodies appear to be less species specific. Both cell-mediated and humoral immune responses play a role in sporozoite-induced immunity. In rodents, the transfer of immune spleen cells confers protection to naive recipient mice, and, in addition, ~-suppressed mice have been successfully immunized. Following incubation with immune serum from sporozoite-immunized and protected simian or rodent hosts sporozoites lose their infectivity. The passive transfer of rodent immune serum decreases both the circulation time and the number of sporozoites which develop into exo-erythrocytic stages. A hybrid cell line, formed by the fusion of spleen cells of P. berghei sporozoite-immunized mice with a mouse plasmacytoma, secretes antisporozoite antibodies in vitro. These monospecific antibodies are directed against a functional, species-specific protective surface antigen. This antigen has been characterized by radiolabeling of the sporozoite surface membrane, or by metabolic labeling of the parasites, followed by immunoprecipitation of the parasite extract and acrylamide gel electrophoresis. Metabolically-labeled sporozoites in addition remain fully infective and are being used to follow early sporozoite-host cell interaction. The hybridoma tech&logy and labeling techniques, once fully developed in the rodent and simian malaria sysmms, should be applicable to human malaria sporozoites, and will hopefully solve the problems of antigen source for vaccination purposes.
the Nucleur
World
165
Ionizing radiation can substitute in whole or in part for nitrites in cured meats while eliminating the hazard of production of Cl. botulinum toxin. No nitrosamines are detected in “No Nitrite” bacon, even after frying. Ionizing radiation can be used instead of mutagenic and potentially carcinogenic agents such as ethylene oxide, ethylene dibromide and other chemical food preserving agents. Nutritionally, even when the high doses required for radappertization are used, quality is equal to or better than foods made shelf-stable by other processes such as heat. The extended shelf-life through irradiation makes it possible to supply much animal protein, calories, and other essential nutrients to a hungry world. Bibliography JOSEPHXINE. S., BRYNJOLFS~~N A. and WIERBICKIE. In Radiation Research, Biomedical, Chemical and Physical Perspectives (Edited by NYGAARD0. F., ADLERH. I. and SINCLAIRW. K.), pp. 96-l 17. Academic Press, New York (1975). JOSEPHSON E. S., THOMASM. H. and CALHOUNW. K. J. Fd Process. Pres. 2,299-313 (1978). ROWLEYD. B., SULLIVANR. and J~~EPH~~NE. S. In Indicators of Viruses in Water and Food,
Chapter 14, pp. 355-382. Ann Arbor Science Publishers, Ann Arbor, Mich. (1978).
Radiation Sterilization of Medical Products F. J. LEY Irradiated Products Limited, Elgin Estate, Swindon, England The tremendous potential for the production of large radiation sources through the construction of nuclear reactors was recognised in the late 1950s. Cobalt-60 has become available in quantities which allows y-radiation processing on an industrial scale and radiation facilities are now operating all over the world. Almost all these plants are used for the sterilization of medical products, including devices, pharmaceuticals and biological .materials. Although the accent now is on the employment of a radioisotope source, the beginnings of the process were based on the use of electron-beam generators. The pioneering efforts of Ethicon Inc. and of Charles Artandi in particular, are well recognised. The lethal effect of y-radiation on microorganisms without causing a significant rise in temperature, combined with complete product penetration, makes the process particularly attractive for the sterilization of pre-packaged, single-use medical devices such as plastic syringes or catheters. The list of such products being commercially produced and sterilized is now extensive and includes drapes and hospital procedure packs. It is generally accepted that a 2.5 Mrad dose is the preferred choice for sterilization. This is based on the investigation of the inactivation of different microbial species taking into account the influence of environmental conditions on radiation resistance and the significance of initial population numbers on the margin of safety achieved. Not all materials are suitable for irradiation; polypropylene tends to embrittle and PVC to discolor, whilst cotton loses some tensile strength. In some instances health authorities approve the use of doses lower than 2.5 Mrad, depending on the use of the product; in this way radiation damage can be avoided. As far as pharmaceutical products are concerned, few are marketed and these are mainly antibiotic preparations particularly for ophthalmic use. So far, there has been no real need in this area since industry has solved many sterilization problems by investment in aseptic handling areas, many equipped with laminar flow systems. Furthermore, the application of radiation to individual pharmaceuticals normally requires approval from health authorities, and it is necessary to produce detailed experimental evidence of non-toxicity; this requirement applies to any change in the method of manufacture. Some biological tissues are radiation sterilized; there is considerable experience with bond grafts and some success with blood vessels, heart valves, nerves and tendons. The technique has been used in the preservation of human tissues in relation to the establishment of tissue banks. The rapid introduction of radiation processing in the medical field has been helped through the interest of the U.N. organisations, in particular by the International Atomic Energy Agency. Harmony of legislation between countries is a necessary step to encourage trade, which is very active in the area of pre-sterilized disposable “ready-to-use” medical equipment. A code of practice governing production methods and the operation of radiation facilities has been prepared. A number of publications are available covering in detail the broad areas of application which have been referred to as well as providing a description of the type of radiation facilities involved.~‘~z~3’
166
Around
the Nuclear
World
References 1. Radiosterilization of Medical Products and Recommended Code of Practice. Pub. No. ST],; PUB/157. IAEA, Vienna (1967). 2. Manual on Radiation Sterilization of Medical and Biological Materials IAEA Pub. No. ST11 DOG/149. IAEA, Vienna (1973). 3. Radiation Sterilization-Irradiated Tissues and their Potential Clinical Use. Proceedings of an IAEA Advisory Group, Athens, 1976 (Edited by PHILLIPSCi. O., TALLENTIREA. and TRIANTAFYLLOU N.). North E Wales Institute, Clwyd, U.K. (1978).
Application of Nuclear Technology to the Development of a Vaccine Against Sporozoite-induced Malaria ALAN H. COCHRANJZ Assistant Professor, New York University Medical Center, Division of Parasitology, Department Microbiology
of
The sporozoite stage of malaria parasites has been used in vaccination attempts involving a variety of mammalian hosts. Mice have been immunized and protected with radiation-attenuated sporozoites of Plasmodium berghei and P. chabaudi; a relatively small number of rhesus monkeys have been immunized with irradiated sporozoites of either P. cynomolgi or P. knowlesi; and finally, a small number of humans have been successfully immunized by the bites of irradiated P. vivax or P. falciparum-infected mosquitoes. Intact irradiated or viable sporozoites are, at present, the most effective sporozoite antigen preparation for vaccination purposes. They are highly immunogenic and when administered either intravenously or by the bites of infected mosquitoes, confer complete protection against sporozoiteinduced malaria infections without the need for immunopotentiation. In rodents complete protection can be obtained following immunization with a single dose of irradiated sporozoites. Induction of protective immunity in rhesus monkeys and humans, however, requires the administration of larger numbers of sporozoites in multiple immunizing doses. Successful vaccination against sporozoites is characterized by development of a sterile immunity which is strictly stage specific. Immunized hosts, while totally resistant to sporozoite challenge, are fully susceptible to challenge with blood stages of the malaria parasite. In sporozoite-vaccinated rhesus monkeys and humans, protection, as well as antisporozoite antibodies, is strictly species specific. Immunized primates are protected only against challenge with sporozoites of the plasmodial species used for immunization. These immunized hosts are however fully resistant to challenge with sporozoites of various strains of the homologous species. This protection is accompanied by the development of species-specific antibodies which show cross-strain reactivity for a given plasmodial species. In contrast, in sporozoite-immunized rodents, protection and antisporozoite antibodies appear to be less species specific. Both cell-mediated and humoral immune responses play a role in sporozoite-induced immunity. In rodents, the transfer of immune spleen cells confers protection to naive recipient mice, and, in addition, ~-suppressed mice have been successfully immunized. Following incubation with immune serum from sporozoite-immunized and protected simian or rodent hosts sporozoites lose their infectivity. The passive transfer of rodent immune serum decreases both the circulation time and the number of sporozoites which develop into exo-erythrocytic stages. A hybrid cell line, formed by the fusion of spleen cells of P. berghei sporozoite-immunized mice with a mouse plasmacytoma, secretes antisporozoite antibodies in vitro. These monospecific antibodies are directed against a functional, species-specific protective surface antigen. This antigen has been characterized by radiolabeling of the sporozoite surface membrane, or by metabolic labeling of the parasites, followed by immunoprecipitation of the parasite extract and acrylamide gel electrophoresis. Metabolically-labeled sporozoites in addition remain fully infective and are being used to follow early sporozoite-host cell interaction. The hybridoma tech&logy and labeling techniques, once fully developed in the rodent and simian malaria sysmms, should be applicable to human malaria sporozoites, and will hopefully solve the problems of antigen source for vaccination purposes.