• 한국식품과학회지
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• 제11권4호
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• pp.224-231
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• 1979

감미(甘味) 식물(植物) stevia의 추출물(抽出物)(주(主) 감미(甘味) 성분(成分),stevioside)을 흰쥐에 투여함으로써 본 감미 성분의 안전성(安全性)을 검토하였다. 복강내(腹腔內) 주사(注射)로 치사(致死)를 $LD_{50}$를 측정한 결과 추출물(抽出物)로 보아서는 3,400 mg/Kg이고 stevioside로 보면 1,700 mg/Kg이었으며, stevia 추출물의 56일간에 걸친 다량(多量) 구광(口腔) 투여(投與)$(2.5{\sim}5.0\;g/Kg{\cdot}day)$에도 실험 동물의 성장(成長)에 아무 장애(障碍)가 초래되지 않았다. 56일간 구강 투여 후의 전혈(全血) 검사(檢査)(RBC, WBC, Hb 및 Hct), 혈청(血淸) 성분(成分) 분석(分析)(총 단백질, 혈당(血糖), 콜레스테롤 및, GOT 등 17개 조사 항목) 및 간(肝) 조직(組織) 검사(檢査)(간 세포 핵퇴폐(核頹廢)), Kupffer 세포의 증식(增殖), 문맥성(門脈城) 섬유화(纖維化) 등 11개 소견(所見))는 총 33개 항목인데, 그 중 lactate dehydrogenase (LDH) 활성을 제외하고는 모두 대조군(對照群)과 시험군(試驗群) 사이에 유의차(有意差)를 볼수 없었다. 상기한 실험 결과에 입각하여 stevia 추출물 및 stevioside는 흰쥐에 대하여 급성(急性) 및 아급성(亞急性) 독성(毒性)을 발현(發現)하지 아니하는 것으로 사료(思料)된다.

• Molecules and Cells
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• 제41권8호
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• pp.742-752
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• 2018

Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive degeneration of dopaminergic (DAergic) neurons, particularly in the substantia nigra (SN). Although circadian dysfunction has been suggested as one of the pathophysiological risk factors for PD, the exact molecular link between the circadian clock and PD remains largely unclear. We have recently demonstrated that $REV-ERB{\alpha}$, a circadian nuclear receptor, serves as a key molecular link between the circadian and DAergic systems. It competitively cooperates with NURR1, another nuclear receptor required for the optimal development and function of DA neurons, to control DAergic gene transcription. Considering our previous findings, we hypothesize that $REV-ERB{\alpha}$ may have a role in the onset and/or progression of PD. In the present study, we therefore aimed to elucidate whether genetic abrogation of $REV-ERB{\alpha}$ affects PD-related phenotypes in a mouse model of PD produced by a unilateral injection of 6-hydroxydopamine (6-OHDA) into the dorsal striatum. $REV-ERB{\alpha}$ deficiency significantly exacerbated 6-OHDA-induced motor deficits as well as DAergic neuronal loss in the vertebral midbrain including the SN and the ventral tegmental area. The exacerbated DAergic degeneration likely involves neuroinflammation-mediated neurotoxicity. The $REV-erb{\alpha}$ knockout mice showed prolonged microglial activation in the SN along with the over-production of interleukin $1{\beta}$, a pro-inflammatory cytokine, in response to 6-OHDA. In conclusion, the present study demonstrates for the first time that genetic abrogation of $REV-ERB{\alpha}$ can increase vulnerability of DAergic neurons to neurotoxic insults, such as 6-OHDA, thereby implying that its normal function may be beneficial for maintaining DAergic neuron populations during PD progression.

• 대한약침학회지
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• 제16권4호
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• pp.22-29
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• 2013

Objectives: This study was performed to analyze the toxicity of the test substance, anti-inflammatory pharmacopuncture (AIP), when used as a single intramuscular-dose in 6-week-old, male and female Sprague-Dawley rats and to find the lethal dose. Methods: The experiment was conducted at Biotoxtech according to Good Laboratory Practices. Twenty (20) female and 20 male Spague-Dawley rats were divided into 4 groups of five 5 female and 5 male animals per group. The rats in the three experimental groups received single intramuscular injections with 0.1-$m{\ell}$, 0.5-$m{\ell}$ and 1.0-$m{\ell}$/animal doses of AIP, Groups 2, 3, and 4, respectively, and the control group, Group 1, received a single intramuscular injection with a 1.0-$m{\ell}$ dose of normal saline. Clinical signs were observed and body weight measurements were carried out for 14 days following the injections. At the end of the observation period, hematology, clinical chemistry, histopathological tests and necropsy were performed on the injected parts. Results: No deaths occurred in any of the groups. Also, histopathological tests showed that AIP had no effect on the injected parts in terms of clinical signs, body weight, hematology, clinical chemistry, and necropsy. Conclusions: As a result of single intramuscular-dose tests of the test substance AIP in 4 groups of rats, the lethal dose for both males and females exceeded $1.0m{\ell}$/animal. Therefore, AIP is a relatively safe pharmacopuncture that can be used for treatment, but further studies should be performed.

• 대한약침학회지
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• 제18권1호
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• pp.79-85
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• 2015

Objectives: A vertebral compression fracture (VCF) is characterized by back pain and fracture of a vertebral body on spinal radiography. VCFs of the thoraco lumbar spine are common in the elderly. In general, appropriate analgesics should be prescribed to reduce pain and, thus, promote early mobilization. The ideal treatment approach for VCFs has not been determined. In Korea, acupuncture and herbal medication have been used to treat VCFs for many years. There is empirical evidence that acupuncture might benefit patients with a VCF. However, no randomized, controlled, clinical trials evaluating the efficacy and the safety of acupuncture for treating a VCF have been published. Therefore, we designed a randomized, controlled, pilot, clinical trial to obtain information for the design of a further full scale trial. Methods: A five week protocol for a randomized, controlled, pilot, clinical trial is presented. Fourteen patients will be recruited and randomly allocated to two groups: a control group receiving interlaminar epidural steroid injections once a week for three weeks, and an experimental group receiving interlaminar epidural steroid injections plus acupuncture treatment (three acupuncture sessions per week for three weeks, nine sessions in total). The primary outcomes will be the pain intensity (visual analogue scale and PainVision$^{TM}$ system). The secondary outcome measurements will be the answers on the short form McGill pain questionnaire and the oswestry disability index. Assessments will be made at baseline and at one, three, and five weeks. The last assessment (week five) will take place two weeks after treatment cessation. This study will provide both an indication of feasibility and a clinical foundation for a future large scale trial. The outcomes will provide additional resources for incorporating acupuncture into existing treatments, such as nonsteroidal anti-inflammatory medications, narcotics and vertebral augmentation. This article describes the protocol.

• 대한약침학회지
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• 제18권1호
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• pp.36-43
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• 2015

Objectives: Water-soluble carthami flos (WCF) is a new mixture of Carthami flos (CF) pharmacopuncture. We conducted a 4-week toxicity test of repeated intramuscular injections of WCF in Sprague-Dawley rats. Methods: Forty male and 40 female rats were divided into 4 groups of 10 male and 10 female SD rats: The control group received 0.5 mL/animal/day of normal saline whereas the three experimental groups received WCF at doses of 0.125, 0.25, and 0.5 mL/animal/day, respectively. For 4 weeks, the solutions were injected into the femoral muscle of the rats alternating from side to side. Clinical signs, body weights, and food consumption were observed; opthalmological examinations and urinalyses were performed. On day 29, blood samples were taken for hematological and clinical chemistry analyses. Then, necropsy was conducted in all animals to observe weights and external and histopathological changes in the bodily organs. All data were tested using a statistical analysis system (SAS). Results: No deaths were observed. Temporary irregular respiration was observed in male rats of the experimental group for the first 10 days. Body weights, food consumptions, opthalmological examinations, urinalyses, clinical chemistry analyses, organ weights and necropsy produced no findings with toxicological meaning. In the hematological analysis, delay of prothrombin time (PT) was observed in male rats of the 0.25- and the 0.5-mL/animal/day groups. In the histopathological test, a dose-dependent inflammatory cell infiltration into the fascia and panniculitis in perimuscular tissues was observed in all animals of the experimental groups. However, those symptoms were limited to local injection points. No toxicological meanings, except localized changes, were noted. Conclusion: WCF solution has no significant toxicological meaning, but does produce localized symptoms. No observed adverse effect level (NOAEL) of WCF in male and female rats is expected for doses over 0.5 mL/animal/day.

• 한국발생생물학회지:발생과생식
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• 제8권2호
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• pp.85-89
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• 2004

본 연구는 임신한 생쥐에 DEHP의 투여가 분만 후 생쥐의 번식기능과 태아의 성비에 미치는 영향을 검토하였다. 임신한 자성 생쥐에 DEHP을 투여한 후 임신 19일째에 임신한 자성의 체중, 태아의 체중, 태아수 및 태아성비를 조사한 결과, 실험개시시와 실험종료시 임신한 자성의 체중은 각 투여구간에 차이가 없었으며, 자${\cdot}$웅성태아의 체중, 평균 태아수 및 태아의 자${\cdot}$웅성 성비는 투여구간에 커다란 차이가 없었다. 임신기에 DEHP의 투여가 분만한 후 어미의 번식기관무게와 혈구화학치에 미치는 효과를 검사한 결과, 각 투여구간에 커다란 차이는 없었다. 임신기에 DEHP의 투여가 분만한 후 난소와 자궁의 조직에 미치는 영향을 조사한 결과, 난소에서는 모든 투여구간에 커다란 차이는 없었으나, 자궁에서는 0.5mg 투여구가 대조구에 비해 자궁내막층과 부종이 감소했으며, 1.0mg 투여구와 10.0mg 투여구는 일부에서 자궁내막층이 감소했지만 0.5mg 투여구에서의 감소보다는 적었다. 임신중인 생쥐에 저농도의 DEHP의 투여는 임신중인 모체와 태어난 자손의 번식 특성과 혈구화학치에 영향을 미치지 않았다.

• Journal of Microbiology and Biotechnology
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• 제16권10호
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• pp.1529-1536
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• 2006

We cloned a gene of ompH(D:4) from pigs infected with P. multocida D:4 in Korea [16]. The gene is composed of 1,026 nucleotides coding 342 amino acids (aa) with a signal peptide of 20 aa (GenBank accession number AY603962). In this study, we analyzed the ability of the ompH(D:4) to induce protective immunity against a wild-type challenge in mice. To determine appropriate epitope(s) of the gene, one full and three different types of truncated genes of the ompH(D:4) were constructed by PCR using pET32a or pRSET B as vectors. They were named ompH(D:4)-F (1,026 bp [1-1026] encoding 342 aa), ompH(D:4)-t1 (693 bp [55-747] encoding 231 aa), ompH(D:4)-t2 (561 bp [187-747] encoding 187 aa), and ompH(D:4)-t3 (540 bp [487-1026] encoding 180 aa), respectively. The genes were successfully expressed in Escherichia coli BL21(DE3). Their gene products, polypeptides, OmpH(D:4)-F, -t1, -t2, and -t3, were purified individually using nickel-nitrilotriacetic acid (Ni-NTA) affinity column chromatography. Their $M_rs$ were determined to be 54.6, 29, 24, and 23.2 kDa, respectively, using SDS-PAGE. Antisera against the four kinds of polypeptides were generated in mice for protective immunity analyses. Some $50{\mu}g$ of the four kinds of polypeptides were individually provided intraperitoneally with mice (n=20) as immunogens. The titer of post-immunized antiserum revealed that it grew remarkably compared with pre-antiserum. The lethal dose of the wild-type pathogen was determined at $10{\mu}l$ of live P. multocida D:4 through direct intraperitoneal (IP) injection, into post-immune mice (n=5, three times). Some thirty days later, the lethal dose ($10{\mu}l$) of live pathogen was challenged into the immunized mouse groups [OmpH(D:4)-F, -t1, -t2, and -t3; n=20 each, two times] as well as positive and negative control groups. As compared within samples, the OmpH(D:4)-F-immunized groups showed lower immune ability than the OmpH(D:4)-t1, -t2, and -t3. The results show that the truncated-OmpH(D:4)-t1, -t2, and -t3 can be used for an effective vaccine candidate against swine atrophic rhinitis caused by pathogenic P. multocida (D:4) isolated in Korea.

• Journal of Microbiology and Biotechnology
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• 제18권7호
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• pp.1326-1334
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• 2008

The prime-boost vaccination with DNA vaccine and recombinant viral vector has emerged as an effective prophylactic strategy to control infectious diseases. Here, we compared the protective immunities induced by multiple alternating immunizations with DNA vaccine (pCIgB) and replication-incompetent adenovirus (Ad-gB) expressing glycoprotein gB of pseudorabies virus (PrV). The platform of pCIgB-prime and Ad-gB-boost induced the most effective immune responses and provided protection against virulent PrV infection. However, priming with pCIgB prior to vaccinating animals by the DNA vaccine-prime and Ad-boost protocol provided neither effective immune responses nor protection against PrV. Similarly, boosting with Ad-gB following immunization with DNA vaccine-prime and Ad-boost showed no significant responses. Moreover, whereas the administration of Ad-gB for primary immunization induced Th2-type-biased immunity, priming with pCIgB induced Th1-type-biased immunity, as judged by the production of PrV-specific IgG isotypes and cytokine IFN-$\gamma$. These results indicate that the order and injection frequency of vaccine vehicles used for heterologous prime-boost vaccination affect the magnitude and nature of the immunity. Therefore, our demonstration implies that the prime-boost protocol should be carefully considered and selected to induce the desired immune responses.

• Journal of Animal Science and Technology
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• 제46권2호
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• pp.183-192
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• 2004

급성 기 반응중인 육계에서 사료 중 크릴 밀의 생산성과 SOD 활성에 미치는 영향을 조사하기 위하여 크릴 밀 A와 B를 이용한 실험 1과 크릴 밀 A를 이용한 확인 실험 2가 실시 되었다. 실험사료는 옥수수 대두박 위주의 기초 사료 와 기초 사료 중 대두박과 2.0%의 크릴 밀 A(수입) 또는 크릴 밀 B(수입)를 대치한 사료이다. 실험 사료를 1 일령 육계 병아리에 급여하여 Salmonella typhymurium lipopolysaccharide (LPS)를 복강 내 주입하여 급성 기 반응을 발생시킨 2 주령 육계의 생산성과 Superoxide dismu- tase(SOD) 활성에 미치는 영향을 Saline을 주입한 대조와 비교하였다. 증체량, 사료 섭취량 및 사료효율은 크릴 밀 A와 크릴 밀 B 사료를 급여한 육계사이에 차이가 있었다. 크릴 밀 사료를 급여한 육계에서 급성기 반응은 간장과 비장 무계를 높였다. 그리고 급성기 반응은 크릴 밀 사료를 급여한 육계 병아리의 간장과 적혈구 세포액의 MnSOD와 Cu/ZnSOD 활성을 높였다. PHA-p 반응에 미치는 크릴 밀 사료의 영향은 없었다. 크릴 밀 B는 면역반응 후 회복중인 육계의 생산성을 향상시켰으나 크릴 밀 A에서는 이러한 영향이 없었다. 이상과 같이 크릴 밀의 종류에 따라 급성기반응시 와 회복시의 생산성은 SOD 활성의 변화로부터 산화 스트레스의 영향을 받고 있다는 것을 시사하고 있다.

• The Korean Journal of Physiology and Pharmacology
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• 제5권3호
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• pp.223-230
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• 2001

Melatonin, a pineal gland hormone, is believed to act as an antioxidant via the stimulation of radical detoxifying enzymes and scavenging of free radicals. In this study, effects of in vitro and in vivo treatments of melatonin on the cisplatin-induced lipid peroxidation, LDH release and plasma creatinine were determined in rabbit renal cortical cells. The level of malondialdehyde (MDA) was assayed as an index of lipid peroxidation and the level of LDH release as an indicator of cellular damage. In in vitro studies, cisplatin increased the levels of MDA and LDH release in a concentration-and time-dependent manner. Melatonin inhibited the cisplatin-induced lipid peroxidation and LDH release in a concentration-dependent manner. The minimal effective concentration of melatonin that significantly reduced the $300\;{\mu}M$ cisplatin-induced lipid peroxidation and LDH release was 1 mM. In in vivo studies, the levels of lipid peroxidation and LDH release in renal cortical cells increased significantly 24 or 48 hours after a single injection of cisplatin (6 mg/kg). When the cisplatin-injected rabbits were pretreated with 10 mg/kg of melatonin, a significant reduction in both lipid peroxidation and LDH release was observed. The plasma creatinine level increased from $0.87{\pm}0.07$ mg/dl in control to $6.33{\pm}0.54$ mg/dl in cisplatin-injected rabbits (P＜0.05). Melatonin partially prevented the increase in serum creatinine level $(1.98{\pm}0.11\;mg/dl)$ by cisplatin (P＜0.05). In the proximal tubules from cisplatin-treated group, tubular cells had microvilli of variable heights. Necrotic debris was seen in tubular lumens. In most of cells, the mitochondria and lysosomes were increased in frequency. The endocytic vacuoles were not prominent and distribution of the brush border was irregular and shortened. These cisplatin-induced morphological changes were moderate in the melatonin-pretreated group. These results suggest that the toxicity of cisplatin is associated with the generation of reactive oxygen free radicals and that melatonin is a powerful antioxidant, which prevents some of the adverse effects of cisplatin.