Traditional medicine and herbal remedies are gaining popularity worldwide, comprising a significant portion of healthcare research, advancements, and market demand. Growing scientific evidence supports their substantial efficacy as pharmaceutical ingredients and dietary supplements in preventive healthcare. When developing pharmaceuticals, it is crucial to ensure that ingredients are free from side effects and toxicity in order to prioritize safety. Geckos, known as shou gong, are a diverse group of lizards that are widely utilized for treating various diseases in Korean Medicine. This study was conducted to assess the potential acute toxicity of a water extract Gekko gecko by a single oral dose in Sprague-Dawley rats. Twenty rats of each sex were randomly assigned to four groups (5 rats each). Test articles were administrated once by oral gavage to rats at dose levels of 0, 500, 1,000, or 2,000 mg/kg body weight. Mortality, changes of body weight, and clinical signs of gross observation were monitored for 14 days after dosing. At the end of a 14-day observation period, all animals were sacrificed and complete macroscopic and hematological examinations were performed. There was no dead animal or test article-related effect on clinical signs, body weight, or gross finding. Other specific changes were not found between control and treated groups in hematology. Results showed no adverse effect at a dose of 500, 1,000, or 2,000 mg/kg in rats. The minimal lethal dose was considered to be over 2,000 mg/kg body weight in rats.
In this study, we examined the effects of gamma irradiation dosage on the mycelial growth of Auricularia auriculajudae and performed analyses of fruiting body yield, growth characteristics, taste, fragrance, and mineral composition. Assessments of mycelial growth in response to gamma irradiation at different intensities revealed an enhancement in the growth of fungi exposed to irradiation at 200 Gy. Fruiting body yield was also highest at 200 Gy, followed by 800 Gy and the control group. On the basis of these observations, we subsequently applied gamma ray doses of 200 and 800 Gy to examine the effects of irradiation on fungal quality characteristics. In terms of the taste of fruiting bodies, we detected no significant differences among the control, 200 Gy, and 800 Gy groups. Contrastingly, with respect to fragrance, we found that fungi treated with 200 Gy were characterized by a pattern that differed from those of the control and other treatment groups. Furthermore, whereas we detected no significant difference among treatments with respect total dietary fiber content, calcium content was found to be higher in the treatment groups compared with the control group, with the highest content being measured in fungi exposed to 800 Gy irradiation. Copper content was confirmed to be higher in the control group, whereas there were no significant differences between the fungi irradiated with 200 and 800 Gy. Contrastingly, the highest levels of zinc were detected in response to 200 Gy irradiation, followed by 800 Gy. Collectively, our findings thus indicate that gamma irradiation can contribute to promoting increases in the fruiting body yield and mineral contents of mushrooms.
Collagen peptides have garnered significant attention as functional foods across multiple fields due to their capacity to regulate physiological and hormonal processes, offering numerous advantages. However, despite their broad range of applications, comprehensive research on the potential toxicity of these substances remains lacking. Therefore, this study sought to assess the acute oral toxicity of a collagen peptide derived from skate (Raja kenojei) skin (CPSS) in both rats and dogs. In the rat model, CPSS was orally administered at doses of 300 and 2,000 mg/kg to Sprague-Dawley rats. An escalating single-dose oral toxicity assessment at doses of 500, 1,000, and 2,000 mg/kg was carried out in beagle dogs with 3-day intervals between doses. Throughout the 14-day post-administration assessment period, clinical signs, mortality rates, changes in body weight, and necropsy observations were closely monitored. After oral administration, no signs of toxicity associated with CPSS were observed in either rats or dogs. Therefore, the oral LD50 (approximate lethal dose for 50% mortality) for CPSS in rats was determined to exceed 5,000 mg/kg, and the maximum tolerated dose for dogs was estimated to be above 2,000 mg/kg. Consequently, this study offers safety data on the use of CPSS in functional foods and medicinal applications.
The emergence of micropollutants in natural water sources due to the overuse of anthropogenic chemicals in industry and households has threatened the production of clean and safe tap water in drinking water treatment plants. Conventional physicochemical processes such as coagulation/flocculation followed by sand filtration are not effective for the control of micropollutants, whereas chemical oxidation processes (applying chlorine, permanganate, ozone, etc.) are known to be promising alternatives. Determining the optimum oxidant dose is important issue related to the production of disinfection by-products as well as unnecessary operating cost, and is made possible by simulations of target-micropollutant abatement based on kinetic model equation consisting of second-order rate constant (between the oxidant and the target) and oxidant exposure. However, the difficulty in determining oxidant exposure as a function of complex water quality parameters limits the field application of kinetic model equation. With respect to representative oxidants used in drinking water treatment plants, this article reviews two main approaches for determining oxidant exposure: i) direct measurement in situ and ii) prediction by empirical models based on key water quality parameters. In addition, we discussed research requirements to improve the predictive accuracy of the empirical models for oxidant exposure and to develop a rational algorithm to determine optimal oxidant dose by considering the priority of the target pollutants to be treated.
Iron deficiency is known to be a common nutritional disorder in many countries, especially among children, women of childbearing age and pregnant women. SUNACTIVE Fe-P80 is a new type of iron supplement that applies nanotechnlateology for the purpose of overcoming the disadvantages of food supplements. This study was conducted to investigate the potential adverse effects of a 28-day repeated oral dose of SUNACTIVE Fe-P80 in rats. SUNACTIVE Fe-P80 was administered once daily by gavage to Sprague-Dawley rats for 28 days at doses of 0, 500, 1,000, and 2,000 mg/kg/day. Additional recovery groups from the control and highdose groups were observed for a 14-day recovery period. At the scheduled termination, the animals were sacrificed, their organs weighed, and blood samples collected. There were no treatment-related effects in the context of clinical signs, body weight, food intake, ophthalmoscopy, urinalysis, necropsy findings, organ weights, and hematologic, serum biochemical and histopathological parameters at any dose tested. Under the present experimental conditions, the no-observed-adverse-effect level of SUNACTIVE Fe-P80 was ≥ 2,000 mg/kg/day in both the sexes, and no target organs were identified. Thus, the results suggest that SUNACTIVE Fe-P80 is relatively safe, as no treatment-related adverse effects were observed following a 28-day repeated oral dose experiment.
Bovine mammary epithelial (MAC-T) cells are commonly used to study mammary gland development and mastitis. Lipopolysaccharide is a major bacterial cell membrane component that can induce inflammation. Autophagy is an important regulatory mechanism participating in the elimination of invading pathogens. In this study, we evaluated the mechanism underlying bacterial mastitis and mammary cell death following lipopolysaccharide treatment. After 24 h of 50 μg/mL lipopolysaccharide treatment, a significant decrease in the proliferation rate of MAC-T cells was observed. However, no changes were observed upon treatment of MAC-T cells with 10 μg/mL of lipopolysaccharide for up to 48 h. Thus, upon lipopolysaccharide treatment, MAC-T cells exhibit dose-dependent effects of growth inhibition at 10 μg/mL and death at 50 μg/mL. Treatment of MAC-T cells with 50 μg/mL lipopolysaccharide also induced the expression of autophagy-related genes ATG3, ATG5, ATG10, ATG12, MAP1LC3B, GABARAP-L2, and BECN1. The autophagy-related LC3A/B protein was also expressed in a dose-dependent manner upon lipopolysaccharide treatment. Based on these results, we suggest that a high dose of bacterial infection induces mammary epithelial cell death related to autophagy signals.
Artemisia annua (AA) is a well-known as a source of antimalarial drug (artemisinin), which also has been traditionally used as an antipyretic and hemostatic agent in Korea and China. In preclinical effective study, a water extract of Artemisia annua (WEAA) ameliorated weight gain and hepatic lipid accumulation in high-fat diet-fed mice. The plasma levels of triglyceride, AST, and ALT were reduced in the WEAA-treated group. Based on these results, the safety of WEAA as a functional ingredient for liver health was evaluated in this repeated dose oral toxicity study before the clinical trial. Sprague- Dawley (SD) rats were treated by gavage with 20 times (1,000 mg/kg) more than the effective dose for 13 weeks. All rats had survived at the end of the study, and there were no changes indicating obviously abnormal clinical sign and behavior. The treatment of WEAA were also observed no obvious toxicities in the body weights, urine, hematological, serum biochemical, ophthalmic and histopathological examinations. Based on the results of this study, the NOAEL (no-observed-adverse-effect level) of WEAA in SD rats was estimated to be 1,000 mg/kg. In conclusion, WEAA could be used as a safe functional ingredient for the improvement of liver health in individuals with hepatic diseases including nonalcoholic steatohepatitis.
폐경은 여성비만의 중요한 원인이다. 본 연구는 폐경여성의 동물모델인 난소절제 암컷 쥐에서 몸무게와 혈청 속 지질 성분의 조절에 대한 제니스테인의 농도 의존적 영향을 수영운동과 비교함으로써, 비만 조절에 대한 제니스테인의 효과적인 농도를 조사하였다. 난소절제 암컷 쥐는 대조군, 수영 운동군, 제니스테인 농도별(0.005%, 0.05%, 0.1% wt/wt) 처리군으로 나누고, 모든 쥐는 고지방식 사료를 8주 동안 섭취하였다. 고지방식 사료를 섭취한 대조군에 비해 수영운동을 실시한 군과 제니스테인이 농도별로 처리된 군 모두 몸무게, 백색지방조직의 무게, 혈청 속 지질 성분 농도 및 간조직의 지질 성분 축적이 감소되었다. 이러한 몸무게, 백색지방조직의 무게, 혈청 속 지질 성분 농도 및 간조직의 지질 성분 축적에 대한 제니스테인의 감소효과는 제니스테인 처리농도에 의존적이었고 제니스테인 농도 0.1%에서 가장 효과적이었으며 1시간 수영운동을 실시한 경우와 유사한 효과를 나타내었다. 본 연구결과들은 난소가 절제된 암컷 쥐에서 적정농도의 제니스테인 처리는 비만개선에 대해 수영운동과 유사한 효과를 나타낸다는 것을 제시한다. 제니스테인 보충제 식이의 섭취는 페경기 여성의 비만예방에 도움을 줄 것이다.
51세 여자가 갑자기 발생한 심한 복통으로 응급실에 내원하였다. 환자는 1년 전 유방암으로 수술을 시행받았고 6개월 전부터 저용량(하루에 10 mg)의 타목시펜을 복용하기 시작했다. 환자의 복통은 중증의 궤사성 췌장염이 원인으로 밝혀졌다. 환자는 특별한 기저질환이나 약물 복용력은 없었으며 음주도 하지 않았다. 내시경 초음파에서 담석은 보이지 않았다. 환자의 6개월 전 중성지방의 수치는 정상이었으나 응급실 내원 당시의 수치는 2,534 mg/dL로 확인되었다. 고중성지방혈증과 췌장염의 원인으로 타목시펜이 가장 의심되었기에 타목시펜 중단 후 보존적 치료를 시행하였고 회복되어 퇴원하였다. 퇴원시 환자의 중성지방 수치는 정상이었다. 타목시펜은 유방암 치료에 효과적인 약이나 처방 후 지질대사에 대한 추적관찰과 관심이 반드시 필요하다.
솔껍질깍지벌레는 남부지방의 곰솔을 가해하는 주요 해충으로 최근 그 분포범위가 확산되고 있다. 현재 솔껍질깍지 벌레의 모니터링은 난낭의 조사를 통해 이뤄지고 있으나, 이는 매우 많은 인력이 필요하며 부정확하다. 따라서 페로몬을 이용한 솔껍질깍지벌레의 모니터링이 새로운 대안으로 제시되고 있다. 하지만 이 역시 적절한 가이드라인이 없어 현장적용에 큰 어려움이 있다. 본 연구 에서는 페로몬을 이용한 솔껍질깍지벌레의 효율적인 모니터링 기법 개발을 위하여 최적 페로몬 방출농도 및 트랩설치 방법을 규명하였으며, 페로몬의 새로운 합성기법의 개발 통하여 경제적 효율성을 기하였다. 성 페로몬에 대한 수컷 솔껍질깍지벌레의 유인효과는 100 μg부터 1,600 μg 까지의 처리에서 용량의존적인 관계를 나타내었으며 이 이상으로 처리할 경우 페로몬 처리 증가에 따른 유인개체수가 증가하지 않았다. 트랩의 설치 높이를 지표면으로부터 50cm, 100cm 150 cm로 구분하여 조사한 결과 지상부로부터 50cm에 설치한 트랩에 가장 많은 개체가 포획되었다. 새로운 방법으로 합성한 페로몬 역시 기존 페로몬과 마찬가지로 페로몬 처리량과 유인 개체수 간 용량의존적인 관계가 나타났다.
Mosquitoes are the most important medical species by transmitting some of deadly infectious diseases to human. Established vector control methods involving the elimination of larval habitats, the use of physical barriers, or those involving insecticides are not sufficient to maintain the populations of these species below the epidemic risk threshold. The sterile insect technique (SIT) is a species-specific, non-polluting and environmentally benevolent method of insect control. This technique involves the release of massive numbers of artificially-reared sterile male insects that, due to their abundance, outcompete fertile wild males for mating opportunities with wild female insects. In this study we discuss optimization of the sterilization process and present a simple model and procedure for determining the optimum dose.
Purpose: This study examined the effects of α-lipoic acid in diluted solvents on cell growth in 3T3-L1 cells according to the treated concentration and times. Methods: Adipocyte 3T3-L1 cell were cultured. Confluent cells underwent starvation with SFM for 1 day and then were cultured in a medium containing various concentrations 0, 100, 200, and 400 μmol/L of α-lipoic acid. The cell viability was measured using the EZ Cytox assay kit. In addition, the effect of α-lipoic acid of diluted solvents on the cell growth in 3T3-L1cells was examined according to the treated concentration and times. Results: The α- lipoic acid diluted ethanol inhibited cell proliferation in a dose and time dependent manner. The α-lipoic acid diluted ethanol induced adipocyte 3T3-L1 cells proliferation with an adipocyte inducer. In addition, α-lipoic acid inhibited adipocyte 3T3- L1 growth in a dose and time dependent manner (p<0.05). Conclusion: This study showed that a treatment with α-lipoic acid diluted ethanol inhibits cell growth of, adipocyte 3T3-L1 cells induced with an adipocyte inducer, (200 μmol/L of α- lipoic acid) treated for 48 hr.
Effective phytosanitary fumigation can prevent the introduction of exotic insects into new areas where they become pests. Traditionally Probit 9 level control (99.9968%) was considered as a stand-alone quarantine treatment. However, unacceptable phytotoxic damage often associated with high-dose treatment to realize Probit 9 level control of a large number of pests has often restricted its practical application. Therefore, quarantine security is being achieved for some commodities using a “systems approach”, where quarantine pests are cumulatively reduced to acceptable levels using independent, pre- and postharvest measures that comprise a systems that effectively mitigate the pest. Preharvest reductions in population through the study and application of chemical ecology involving insect behavior modifying chemicals can be an integral part of systems approach. This results in low pest prevalence prior to end point treatment, where pests may be effectively controlled using a less-than-Probit 9 level, low-dose treatment. In this talk, I discuss the chemical ecology of invasive quarantine pests including Drosophila suzukii and its perspective in the effective end point fumigation treatment using ethyl formate.
박물관, 기록원 등의 주요 소독약제인 메틸브로마이드(MB)와 Ethylene Oxide(EO)는 오존층 파괴 물질 및 1급 발암물질로 규제가 되고 있어 대체 훈증제 개발이 필요한 실정이다. 따라서, 친환경 약제인 검역훈증제 에틸포메이트 (베이퍼메이트®)의 적용가능성을 확인하고자 주요 해충인 독일바퀴(Blatella germanica) 및 흰개미(Reticulitermes speratus)를 대상으로 Dose response 실험을 실시하였다. 공시충은 팜한농 작물보호연구센터 곤충사육실에서 누대사육중인 개체를 사용하였으며, 데시게이터(6.9L)에 농도별로 24시간동안 밀폐 훈증처리하여 약효를 조사하였다. 통계분석은 Probit analysis 통해 L(Ct) (Lethal Concentration x Time, gꞏhꞏm3)값을 산출하였다. 시험결과 L(Ct)50 및 L(Ct)99 값은 독일바퀴(혼합태)의 경우 48.38 및 346.34 gꞏhꞏm3 흰개미(성충)은 14.91및 660.94 gꞏhꞏm3로 나타났다. 모두 방제가 가능한 L(Ct)99 값은 660.94 gꞏhꞏm3으로 이는 에틸포메이 트 28.2 g/m3(베이퍼메이트® 170 g/m3)를 24시간 처리시 완전 방제가 가능할 것으로 판단된다.
Lysophosphatidic acid (LPA) is an important signaling molecule. Here, the effect and mechanism of LPA on the preimplantation development of porcine embryos during in vitro culture (IVC) was examined. Porcine embryos were cultured in porcine zygote medium (PZM-3) supplemented with 30 μM LPA during different days. There was a significantly higher cleavage rate in Day 1-7 and significantly higher total cell number of blastocysts in Day 1-3 and Day 4-7. It was also found that messenger RNA (mRNA) expression level of PCNA, BCL2 and BAX in blastocysts obtained from D1-7 group were significantly higher and BCL2/BAX mRNA ratio in D1-3 group was significantly lower than control group but Day 4-7 and Day 1-7 groups were comparable with control group. Treatment with 20 μM PLC inhibitor significantly decreased the embryo cleavage rate and blastocyst formation rate. Moreover, LPA as an activator of PLCs, enhanced the 30 μM LPA + 20 μM U73122 group embryo cleavage rate which similar with control group. In conclusion, the results suggest that treatment with LPA during IVC improves the porcine early embryo cleavage by activation of PLC signaling pathway and regulate the mRNA expression that contribute to total cell number of blastocysts during blastocyst formation.
This study examined the acute toxicity of Vital-Shoot containing reduced glutathione in male and female ICR mice. Mice were intraperitoneally injected the drug at dose levels of 0, 250, 500, 1,000 and 2,000 mg/kg body weight (BW) for single-dose toxicity test. There were no statistical differences in BW changes between the control and all treated groups. Based on hematological and blood biochemical analyses, the drug did not affect all parameters. In addition, markers for liver and kidney functions did not meaningfully change in all treated groups. Since there were no adverse effects from the drug in a single-dose intraperitoneal toxicity test, it was concluded that the lethal dose 50 (LD50) of Vital-Shoot is estimated to be >2,000 mg/kg BW.
종래 판례는 의약발명에 대해 산업상 이용가능 성이 없어 특허를 받을 수 없다고 판시해 왔다. 그런데 의약발명에는 오랜 시간이 소요될 뿐만 아니라 막대한 자본과 인력, 그리고 축적된 기술력을 필요로 한다. 의약 분야에 있어서 물질의 속성이 다면적이어서 특정의 약리효과라는 새로운 속성의 발견도 의학적으로 중요한 의미를 가지는데, 이러한 의약용도발명도 특허 보호의 필요성이 인정된다.
현재 의약용도발명에 대해 특허대상성을 인정 하는 것이 일반적인데, 의약의 투여용법과 투여용량의 특허대상성에 대해서는 견해의 대립이 있다. 원래 의도한 효과를 위해 적절한 투여용법과 투여용량이 필요하고 새로운 쓰임새를 제공한다는 점에서 의약용도발명과 본질을 같이 하므로 특허대 상성을 인정함이 타당하고, 최근 우리 대법원도 종래 입장을 변경하여 특허대상성을 인정하였다.
그런데 유럽이나 일본과 달리 미국에서는 특허 대상을 넓게 규정하되 자연법칙의 예외 이론을 도입하여 ‘발명’의 개념에서 배제하는 구조를 취하고 있고, 미국 연방대법원은 Mayo 판결에서 투여 용법⋅투여용량에 대한 특허대상성을 부인한 바 있다. 이러한 판례의 취지는 ‘특허로써 보호할 만 한 가치가 있는지’의 판단에서 비롯된 것일 뿐 일반적으로 투여용법⋅투여용량에 대한 특허대상성을 부인한 것으로는 보기 어려워 우리 대법원의 태도와 배치된다고 단언할 수는 없다.
우리 실무에서도 ‘특허로써 보호할 만한 가치가 있는지’에 대한 판단이 실질적으로 더 중요한 문제로 부각될 것인데 이에 대한 기준 정립이 앞으로 다루어야 할 과제가 될 것이다.