A collaborative study to establish the second national standard for hepatitis B immunoglobulin in Korea.

This study aimed to establish a second national standard for hepatitis B immunoglobulin (HBIG) that can be used for potency assays of hepatitis B and normal immunoglobulin. The candidate material was manufactured using a process approved as Good Manufacturing Practice. The freeze-dried candidate preparation was tested for physicochemical and biological properties, including pH, residual moisture, molecular size distribution, and potency. A collaborative study was performed involving four laboratories, including the National Institute of Food and Drug Safety Evaluation, as an official national control laboratory in Korea and manufacturers. The potency was calibrated against the second international standard for HBIG using two enzyme immunoassays: enzyme-linked immunosorbent assay and electrochemiluminescence immunoassay. Results from 240 assays were obtained from four laboratories, and combined potency estimates were obtained by calculating the geometric means. Intra- and inter-laboratory variability showed acceptable geometric coefficients of variation of 1.3-6.0 and 3.2-3.6%, respectively. The candidate preparation showed satisfactory stability in accelerated thermal degradation and real-time stability tests. Based on these results, the potency value of 105 IU/vial was assigned (95% confidence intervals: 100.0-109.2 IU/vial), and it was deemed suitable to serve as the Korean national standard for HBIG.

Stability Evaluation of National Reference Standards for Blood Products in Korea.

National reference standards (NRSs) for biologics are established through potency estimation by a multicenter joint study of standard materials used in the approval process for national lot release and quality control of vaccines, blood products, and other biologics. In this study, a stability evaluation was conducted to determine whether the potency of NRSs for six blood products was being maintained at a consistent level in Korea. The present study conducted real-time stability tests via in-vivo/in-vitro bioassay on NRSs for blood coagulation factor VIII concentrate (2nd standard), antithrombin concentrate, prekallikrein activator, anti-hepatitis B immunoglobulin, blood coagulation factor IX concentrate, and anti-tetanus human immunoglobulin, as well as a trend analysis using cumulative annual results. The real-time stability test results showed that the mean potency of six NRSs was all within the control limit. In the trend analysis, the potency of NRS for blood coagulation factor VIII concentrate (2nd standard) showed a decreasing trend, while the potency of all other products had been stably maintained. The present study confirmed that the mean potency of NRSs for six blood products had been stably maintained in Korea. The findings of the present study establish a foundation that can ensure the quality of NRSs for biologics in Korea, and it is expected to make a major contribution to the supply of high-quality biologics.

Aerosol delivery of spermine-based poly(amino ester)/Akt1 shRNA complexes for lung cancer gene therapy.

Polyethylenimine (PEI) has been commonly used as a cationic polymeric gene carrier due to high transfection efficiency, however, its cytotoxicity has hindered the practical application. In this study, we report the development of poly(amino ester) (PAE) based on glycerol propoxylate triacrylate (GPT) and spermine (SPE) as an alternative gene carrier for lung cancer therapy. GPT-SPE copolymer was prepared by Michael addition reaction between GPT and SPE, and the efficacy was evaluated using shAkt1 as a model therapeutic gene. The molecular weight and composition were characterized using gel permeability chromatography (GPC) and (1)H-nuclear magnetic resonance ((1)H-NMR), respectively. The GPT-SPE could effectively condense DNA with about 163 nm size and protect the DNA from nucleases. GPT-SPE/DNA complexes showed excellent transfection with low toxicity both in vitro and in vivo. Furthermore, aerosol delivery of GPT-SPE/Akt1 shRNA complexes significantly suppressed lung tumorigenesis in K-ras(LA1) lung cancer model mice. These results suggest that GPT-SPE can be used in shRNA-based lung cancer gene therapy.

[The formation and background of Claude Bernard's general physiology].

Claude Bernard, a French physiologist in the nineteenth century, strove to establish experimental physiology as a medical branch and scientific field. In 1854, he started his lecture series on general physiology at the Paris Faculty of Sciences, which was continued at the National Museum of Natural History since 1869 when Bernard's chair was transferred from the Faculty to the Museum. At the Museum, Bernard titled his lecture series the"Phenomena of Life Common to Animals and Plants," which revealed the main characteristic of his general physiology. At that time, physiology was generally considered a medical science which dealt only with the human body. Bernard, on the other hand, came to have the idea that physiology could study the functions of plant, animal, and human bodies in the same manner. Bernard's lectures on general physiology had two distinct phases. At Sorbonne, general physiology was a rather speculative theoretical system. It was mainly because of the fact that he did not have a laboratory at the Faculty of Sciences. There, the lecture dealt only with animal functions, and he had no concern for plant physiology at all. After he moved to the Museum, significant changes occurred. In the new laboratory, general physiology was transformed into a truly experimental science, which dealt with both animals and plants. Protoplasm, a physiological basic unit, replaced tissue, which was basically an anatomical unit that fell short of explaining physiological phenomena. The Museum of Natural History played an important role in this transformation. At the museum, zoologists, botanists, and physiologists worked together, and the peculiar natural history tradition of the institution enabled scientists to study animals and plants at the same time. Although there existed some conflicts between experimentalists and naturalists, Bernard could wisely figure out the problem by asserting that the role of a physiologist was to disclose, by experimentation, the fundamental principles that lay behind the superficial facts of life that were already discovered by natural historians. At the Museum, Bernard could break down the distinction between the animal and plant kingdoms in the domain of experimental physiology, and it can perhaps be considered a step toward the formation of the general science of biology.

Assessment of estimated daily intakes of benzoates for average and high consumers in Korea.

A study was performed to evaluate the estimated daily intakes (EDI) of benzoates for the average and high (90th percentile) consumers by age and sex categories in Korea. The estimation of daily intakes of benzoates was based on individual dietary intake data from the National Health and Nutrition Survey in 1998 and on the determination of benzoates in eight food categories. The EDI of benzoates for average consumers of different age groups ranged from 0.009 to 0.025 mg kg(-1) bw day(-1). For high consumers, the range of EDI of benzoates was 0.195-1.878 mg kg(-1) bw day(-1). The intakes represented 0.18-0.50% of the acceptable daily intake (ADI) of benzoates for average consumers and 3.9-37.6% of the ADI for high consumers. Foods that contributed most to the daily intakes of benzoates were mixed beverages and soy sauce in Korea.