• 한국안광학회지
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• 제12권2호
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• pp.67-78
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• 2007

시판중인 렌즈 보존액 중 가장 흔히 사용 또는 유통되고 있는 CLIWELL$^{TM}$에 대한 안점막자극성 시험을 식품의약품 안전청 고시에 따라 Draize법을 이용하여 그 자극성의 정도를 평가하고, 눈에 가해질 수 있는 잠재적인 독성을 평가하기 위하여, 배출물에 대한 도말표본 상에서 염증세포 및 비 염증성 유상피세포가 차지하는 비율과 함께 점안 14일 후 안구 중, 각막, 홍채, 망막 및 공막의 조직병리학적 관찰을 실시한 결과 다음과 같은 결과를 얻었다. 비 세척군에서는 점안 후 1, 2 및 3일에 국한하여, 각막과 결막에 경미한 자극이 관찰되어, 이 기간 동안의 평균 안점막 자극지수 MIOI가 각각 4.50, 1.67 및 0.67로 관찰되었으며, 세척군에서는 점안 후 1 및 2일에 국한하여, 결막에서 경미한 자극성이 인정되었고, 이때 MIOI는 각각 0.67로 관찰되었다. 따라서 CLIWELL$^{TM}$은 세척군 및 비 세척군 모두에서 MIOI가 모든 관찰 기간에서 4.50이하로 관찰되었으며, IAOI 역시 점안 1일 후 4.50으로 관찰되어 무자극성 물질로 판단되었다. 한편 배출물에 대한 염증성 세포의 비율은 무처치 대조군과 비교하여 점안 1일 후 유의성 있는 염증세포 비율의 증가가 비세척군에 국한하여 인정된 이외에 의미 있는 변화는 인정되지 않았다. 또한 안구의 조직병리학적 검사에서 각막, 홍채, 망막 및 공막 모두에서 무처치 대조군과 비교하여 의미 있는 변화는 인정되지 않았다.

• Toxicological Research
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• 제12권2호
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• pp.203-211
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• 1996

Methanol has been widely used as an industrial solvent and environmental exposure to methanol would be expected to be increasing. In humans, methanol causes metabolic acidosis and damage to ocular system, and can lead to death in severe and untreated case. Clinical symptoms are attributed to accumulation of forrnic acid which is a metabolic product of methanol. In humans and primates, formic acid is accumulated after methanol intake but not in rodents due to the rapid metabolism of methanol. Neverthless, the developmental and reproductive toxicity were reported in rodents. Previous reports showed that perinatal exposure to ethanol produces a variety of damage in human central nervous system by direct neurotoxicity. This suggests that the mechanism of toxic symptoms by methanol in rodents might mimic that of ethanol in human. In the present study I hypothesized that methanol can also induce toxicity in neuronal cells. For the study, primary culture of rat hippocampal neurons and glias were empolyed. Hippocampal cells were prepared from the embryonic day-17 fetuses and maintained up to 7 days. Effect of methanol (10, 100, 500 and 1000 mM) on neurite outgrowth and cell viability was investigated at 0, 18 and 24 hours following methanol treatment. To study the changes in proliferation of glial cells, protein content was measured at 7 days. Neuronal cell viability in culture was not altered during 0-24 hours after methanol treatment. 10 and 100 mM methanol treatment significantly enhanced neurite outgrowth between 18-24 hours. 7-day exposure to 10 or 100 mM methanol significantly increased protein contents but that to 1000 mM methanol decreased in culture. In conclusion, methanol may have a variety of effects on growing and differentiation of neurons and glial cells in hippocampus. Treatment with low concentration of methanol caused that neurite outgrowth was enhanced during 18-24 hours and the numbers of glial cell were increased for 7 days. High concentration of methanol brought about decreased protein contents. At present, the mechanism responsible for the methanol- induced enhancement of neurite outgrowth is not clear. Further studies are required to delineate the mechanism possibly by employing molecular biological techniques.

• Biomolecules & Therapeutics
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• 제2권3호
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• pp.247-255
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• 1994

As a series of safety studies of DA-3030, a new rhO-CSF, its local irritancy was examined in the rabbits after the following treatment; application into the conjunctival sac of the eye(single), subcutaneous injection(single), intramuscular injection(single), and intravenous injection(8-day repeated). In addition, paravenous irritation of DA-3030 was investigated in mice. The results obtained were as follows. 1. In the result of ocular irritation test, 0.03% solution of DA-3030 could be considered as a non-irritating material. 2. The local irritation of DA-3030 by an injection of 0.5mι of its solution subcutaneously or intramuscularly was negligible and not so much different from that of saline. 3. In the vascular irritancy test, macro- and microscopic observations revealed that the irritating activity of DA-3030 in blood vessels was not different from that of saline when they were injected once a day into vein retroauricularis of rabbits for 8 days.4. The paravenous administration of DA-3030 did not induce any abnormal changes at injection sites except mild swelling in 1 mouse at 3 hours after injection which was thought to be due to slow absorption. The above-mentioned results suggest that DA-3030 has no irritating activity when injected through intravenous or subcutaneous route for clinical practice as 0.03% solution.

• 생명과학회지
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• 제32권9호
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• pp.712-720
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• 2022

비록 PM_2.5 노출과 다양한 안구 표면 질환과 관련성이 많은 선행 연구에서 알려졌지만, PM_2.5 가 각막에 미치는 세포 독성에 대한 연구는 거의 수행되지 않았다. 본 연구의 목적은 PM에 의한 각막 상피세포의 유해성을 평가하기 위한 in vitro 모델로서 쥐의 각막유래 상피세포(primary rat corneal epithelial cells, RCE cells)의 효능을 조사하는 것이다. 이를 위하여 쥐의 눈에서 분리한 1차 배양 세포가 각막 상피세포임을 pan-cytokeratin 염색을 통하여 확인하였으며, PM_2.처리에 의한 각막 상피세포의 형태학적 변화를 동반한 생존율의 억제는 세포사멸 유도와 관련이 있었다. 또한 PM_2.가 처리된 각막 상피세포에서는 ROS의 생성이 증가되었으며, 이는 미토콘드리아 기능 장애와 연관성이 있었다. 이와 함께 PM_2.는 각막 상피세포에서 NO, TNF-α, IL-1β 및 IL-6를 포함한 염증 매개인자 및 사이토카인의 생성을 증가시켰다. 아울러 heatmap 분석을 통해 BLNK, IL-1RA, Itga2b, ABCb1a 및 Ptgs2가 미세먼지 유도 안구 질환의 임상 치료를 위한 잠재적인 표적 유전자로서 제시하였다. 결론적으로 본 연구의 결과는 1차 쥐의 각막 상피세포가 PM_2.에 의한 각막 상피세포 병리기전 연구에 유용한 모델일 수 있으며, 산화적 및 염증성 반응이 PM_2.유발 안구 표면 장애 유도에 핵심적인 역할을 함을 알 수 있었다.

• Toxicological Research
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• 제14권3호
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• pp.393-400
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• 1998

As a series of safety studies on DA-3585, a recombinant human erythropoietin, its local irritancy was examined in rabbits after the following treatments; application into the conjunctival sac of the eye(single), subcutaneous injection (single and -day repeated)and intravenous injection (7-day repeated.)In addition, perivascular irritation of DA-3585 was investigated in mice. In the result of ocular irritation test, 10,000IU/ml solution of DA-3585 could be considered as a non-irritating material. The local irritation of DA-3585 by a single and 7-day repeated subcutaneous injection was negligible and not so much different from that of saline. In the vascular irritancy test, macro-and microscopic observations revealed that local irritation of DA-3585 was comparable to that of saline when injected into retroauricular vein of rabbits for 7 consecutive days. Furthermore the perivascular administration of DA-3585 upto the concentration of 10,000 IU/ml did not induce any morphological abnormalities at injection sites. The results obtained from the present study suggest that the local irritancy of DA-3585 is not different from that of saline when injected through intravenous or subcutaneous route for clinical practice.

• Advances in nano research
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• 제13권1호
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• pp.87-96
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• 2022

Drug self-delivery systems can easily realize combination drug therapy and avoid carrier-induced toxicity and immunogenicity because they do not need non-therapeutic carrier materials. So, designing appropriate drug self-delivery systems for specific diseases can settle most of the problems existing in traditional drug delivery systems. Retinal pigment epithelium is very important for the homeostasis of retina. However, it is vulnerable to oxidative damage and difficult to repair. Worse still, the antioxidants can hardly reach the retina by non-invasive administration routes due to the ocular barriers. Herein, the targeted group (folic acid) and antioxidant (melatonin) have been grafted on the surface of ZnO quantum dots to fabricate a new kind of drug self-delivery systems as a protectant via eyedrops. In this study, the negative nanoparticles with size ranging in 4~6 nm were successfully synthesized. They could easily and precisely deliver drugs to retinal pigment epithelium via eyedrops. And they realized acid degradation to controlled release of melatonin and zinc in retinal pigment epithelium cells. Consequently, the structure of retinal pigment epithelium cells were stabilized according to the expression of ZO-1 and β-catenin. Moreover, the antioxidant capacity of retinal pigment epithelium were enhanced both in health mice and photic injury mice. Therefore, such new drug self-delivery systems have great potential both in prevention and treatment of oxidative damage induced retinal diseases.

• 한국식품영양과학회지
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• 제33권4호
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• pp.641-645
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• 2004

단회경구독성시험에서 미더덕 및 멍게 유래 crude콘드로이틴황산의 LD$_{50}$는 2g/kg 이상으로서 판명되어, 단회경구독성 측면에서 는 안전한 원료로 판단되었다. 비록 기니픽을 이용한 감작성시험은 미더덕 유래 crude 콘드로이틴황산만을 사용하여 실시하였고, 시험 농도는 GAGs의 임상 사용 예정량이 0.03∼0.15%임을 고려하여 inductiuon 농도는 임상사용 예정량의 10배인 3.0%, challenge 적용 농도를 0.3% 이하로 잠정 설정하여 3.0%, 0.3%, 0.03%농도에서 실시하였다. 그 결과 0.03% 및 0.15% 농도에서는 반응을 나타낸 개체가 없었으나, 양성대조군과 비교할 때 0.3% 농도에서는 24시간 후에는 10% 그리고 48시간 후에는 5%의 반응율을 나타냈지만 사용가능범위에 해당되어 미더덕의 GAGs은 감작성 측면에서 안전성이 높은 원료로 0.3%이하 농도에서는 사용 가능하다고 판단되었다. 토끼를 이용한 안점막 자극시험에서는 미더덕과 멍게 유래 crude 콘드로이틴황산 및 bovine trachea 콘드로이틴황산의 3.0% 적용 시 모두 A.O.I.가 기준치 이하로 나타나 실제 사용 시 눈에 자극성이 없음이 판명되었다. 토끼를 이용한 피부일차자극 시험에서는 미더덕 및 멍게 유래 crude 콘드로이틴황산을 3.0% 및 1.5%는 무자극을 보였지만, 멍게 유래 crude 콘드로이틴황산에서는 미약하게 보이던 피부반응이 미더덕 유래 crude 콘드로이틴황산에서는 3.0% 적용에서 다소 강한 반응을 보였다. 광독성 및 광감작성을 위한 UV 흡광 실험결과 미더덕 및 멍게 유래 crude 콘드로이틴황산과 대조군으로서 사용한 표품 콘드로이틴황산 모두 자외선영역(280∼420 nm)에서 흡광을 보이지 않아서 광독성 및 광감작성 시험을 시행하지 않았다. 실험동물을 사용하여 조사한 결과 화장품 원료로서의 미더덕 및 멍게 유래 crude 콘드로이틴황산은 3.0% 이내에서는 사용이 안전함이 증명되었고, 멍게가 미더덕 유래의 콘드로이틴황산에 비교하여 생체반응에 나은 것으로 나타났다.다.

• 대한약침학회지
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• 제4권3호
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• pp.109-117
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• 2001

Objective : There has been no known report on the pain shock after administering Korean bee-venom therapy. Three accounts of pain shock were observed at the Sangji university affiliated Oriental medicine clinic from July 2001 through September 2001. This thesis will inform clinical progression and cautions on administering Korean bee-venom therapy. Methods: We were able to witness different patterns of pain shock during the treatment of degenerative knee joint, progressive oral paralysis, and A.L.S. In order to reduce heat toxicity of the bee venom, needling points were first massaged with the ice for 10 minutes before injecting $0.1{\sim}0.2cc$ of the bee venom. Points of injection were ST36, LI11, LI4 and others. Pain shock occurred after injecting on inner xi-an, outer xi-an and LI4. The phenomena associated with pain shock was recorded in chronological order and local changes were examined. Results: Through examining 3 patients with the pain shock, we managed to observe clinical progression, duration, and time linked changes on specific regions. We also managed to determine sensitive needling points for the pain shock. Conclution: Following results were obtained from 3 patients with the pain shock caused by Korean bee-venom therapy from July 2001 to September 2001. 1. Either positive or negative responses were shown after the pain shock. For case 1, extreme pain was accompanied with muscular convulsion and tremble, ocular hyperemia, delirium, stiffening of extremities, and hyper ventilation which all suggest positive responses. For case 2 and 3, extreme pain was accompanied with facial sweating, asthenia of extremities, pallor face, dizziness, weak voice, and sleepiness which are the signs of negative responses. 2. The time required to recover to stable state took nearly an hour (including sleeping time) and there was no side effect. 3. Precautions required to prevent the pain shock includes full concentration from the practitioner, accurate point location, precise amount of injection, physiological condition and psychological stability of the patient 4. Coping with the pain shock should be similar with a needle shock, and since extreme pain is accompanied, sufficient psychological rest must be provided. 5. Pain shock occurs because the patient cannot tolerate stimulation on the needling point. Thus, symptoms were similar to the needle shock in addition to excruciating pain. Further investigation and research must be done to have better understanding of an immune response and the pain shock associated with Korean bee-venom therapy.