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Gentamicin의 투여방법에 따른 정상가토 수정체의 Calcium 이동에 미치는 영향

Other Titles
 (The) effect of gentamicin on calcim transport in normal rabbit lenses according to the route of administration 
Issue Date
1992
Description
의학과/박사
Abstract
[한글] 안내 수술이나 천공성 안외상을 받은 후 세균의 안내 침투로 인하여 초자체내에 염증을 일으키는 세균성 안내염은 수일내에 안구에 치명적인 손상을 줄 수 있다. 최근에는 녹농균을 포함한 그람 음성 간균들에 의한 경우가 증가하는 추세로, 이런 경우 병의 진행이 빠르고 심하며 예후가 대단히 불량하여 안구가 소실되기도 한다. 이의 치료시 점안, 경구투여, 근육주사, 정맥주사 및 결막하주사 등의 일반적인 항생제 투여 방법으로는 혈액망막책이나 혈액방수책등의 안구의 해부생리학적 특징으로 인해 초자체내로 약물의 침투가 쉽게 이루어지지 않아 치료 효과를 기대할 수 없다. 세균성 안내염의 치료에는 광범위 항생제를 초자체내로 직접 주사하는 방법이 가장 유효하고 적합하다고 알려져 왔다. 특히 녹농균에 대해 유효한 aminoglycoside 계열의 gentamicin은 가장 널리 사용되고 있는 수용성의 광범위 항생물질로서 그람 양성균과 음성균 모두에 효과가 있는데, gentamicin을 전방이나 초자체내로 주사함으로써 세균성 안내염에 대한 치료 효과를 기대할 수 있게 되었다. 그러나 gentamicin을 이와 같은 여러 경로를 통해 투여하는 경우 gentamicin이 주위 안구조직에 침투하여 세포기능에 이상을 초래할 수 있으며, 그중 수정체혼탁이나 망막에 독성을 일으키는 경우가 가장 문제가 된다. 이것은 gentamicin이 세포내의 calcium농도를 증가시켜 독성을 일으키기 때문인데, 수정체에서는 calcium transport system이 억제되어 수정체내의 calcium농도가 증가되어 백내장이 유발된다고 한다. 최근의 연구에서는 적출된 정상가토의 수정체를 (45)**Ca이 포함된 용액내에서 incubation시킨 후 gentamicin을 투여할 때 (45)**Ca의 능동적 유출을 감소시키고 gentamicin이 Ca**++-ATPase의 활성도를 억제시키며, Ca**++이 수정체내에 축적된다는 것이 보고되었다. 이에 저자는 정상가토안에 gentamicin을 전방 및 초자체내로 주사하고, 1, 3 및 7일 후에 수정체를 적출하여 수정체의 Ca**++-activated ATPase 활성도와 수정체낭을 통한 Ca** ++ 유출, 수정체내의 Ca**++ 농도를 측정하여, 세균성 안내염의 치료시 gentamicin 투여 방법에 따른 수정체에서 calcium 이동을 비교하여 다음과 같은 결과를 얻었다. 1. 수정체의 Ca**++-ATPase 활성도는 생리식염수 주사군에시는 주사후 시간이 경과하여도 변화가 없었으나, gentamicin 주사군에서는 주사후 시간이 경과함에 따라 대조군에 비해 의의 있게 억제됨을 알 수 있었다. 2. 수정체에서의 Ca**++ 유출은 gentamicin 주사군이 생리식염수 주사군에 비해 의의있게 감소되어 있음을 알 수 있었다. 3. 수정체내의 Ca**++ 농도는 생리식염수 주사군에서는 주사후 시간이 경과하여도 변화가 없었으나, gentamicin 주사군에서는 주사후 시간이 경과함에 따라 의의있게 증가함을 알 수 있었다. 4. 수정체의 Ca**++-ATPase 활성도의 억제, 수정체에서의 Ca**++ 유출의 감소 및 수정체내 Ca**++ 농도의 증가는 gentamicin을 전방내 주사한 경우보다 초자체내 주사한 경우에 더 심하였다. 이상의 결과로 보아 gentamicin주사시 수정체내의 Ca**++ 농도의 증가는 수정체 Ca**++-ATPase 활성도의 억제로 인한 수정체낭을 통한 Ca**++ 유출의 감소에 기인하는 것으로 생각되며, 이런 현상은 초자체내 주사군에서 전방내 주사군보다 더 현저하였다. The effect of gentamicin on calcium transport in normal rabbit lenses according to the route of administration Byung Joo Cho Department of Medical Science, The Graduate School, Yonsei University (Directed by Professor Hong Bok Kim) Endophthalmitis is one of the most catastrophic complications in intraocular surgery and penetrating injuries of the eye. Recently, gram-negative rods including pseudomonas have been found to be the major causative organisms of bacterial endophthalmitis. Gentamicin has been the conventional treatment for pseudomonas infection and therefore its use for eye infections was evaluated. Because of poor penetration of antibiotics into the eye and particularly into the vitreous via the conventional route of administration, the method of injection of antibiotics directly into either the anterior chamber or the vitreous employed. Although higher concentration of intraocular gentamicin were obtained, sight-limiting complications such as cataract and retinal toxicity secondary to toxic effects on adjacent ocular tissues resulted. The mechanism of cataract formation have not been proven definitively but the transparency of the lens is known to depend on its ^^Ca++ level, and many researchers have proven experimentally that cataracts may occur in cases of increased lens calcium levels. Recently, in vitro studies with rabbit lenses have showed that increased calcium levels in cataracts were the results of decreased active Ca**++ efflux from the lens secondary to inhibition of Ca**++ -activated ATPase activity in the lens. In this experiment, gentamicin and normal saline were administrated into the anterior chamber and into the vitreous. Ca**++-activated ATPase activity in the lens, active Ca**++ efflux from the lens and calcium concentration in the lens were measured at day 1, day 3 and 7 days after injection of gentamicin or saline solution into the anterior chamber or vitreous to compare the effect on calcium transport in the rabbit lenses according to the route of administration between four different groups. They included normal saline injection group(control group) and gentamicin injection group(experimental group), intracameral gentamicin injection group and intravitreal gentamicin injection group. The results are summarized as follows; 1. The Ca**++-activated ATPase activity of the lens showed no interval change in the control group, but progressively inhibited in the experimental group. 2. The active efflux of Ca**++ from the lens was significantly decreased in the experimental group compared to the control group. 3. The calcium concentration in the lens showed no interval change in the control group, but progressively increased in the experimental group. 4. The inhibition of Ca**++-activated ATPase activity of the lens, decreased active Ca**++ efflux from the lens and increased calcium concentration in the lens were more severe in the intravitreal injection group than intracameral injection group. From the above results, it may be speculated that the decreased active efflux of Ca**++ from the lens induced by gentamicin is related to inhibiting Ca**++-activated ATPase activity of the lens and this makes the accumulation of calcium in the lens. These effects were more severe in the intravitreal gentamicin injection group than in the intracameral gentamicin injection group.
[영문] Endophthalmitis is one of the most catastrophic complications in intraocular surgery and penetrating injuries of the eye. Recently, gram-negative rods including pseudomonas have been found to be the major causative organisms of bacterial endophthalmitis. Gentamicin has been the conventional treatment for pseudomonas infection and therefore its use for eye infections was evaluated. Because of poor penetration of antibiotics into the eye and particularly into the vitreous via the conventional route of administration, the method of injection of antibiotics directly into either the anterior chamber or the vitreous employed. Although higher concentration of intraocular gentamicin were obtained, sight-limiting complications such as cataract and retinal toxicity secondary to toxic effects on adjacent ocular tissues resulted. The mechanism of cataract formation have not been proven definitively but the transparency of the lens is known to depend on its ^^Ca++ level, and many researchers have proven experimentally that cataracts may occur in cases of increased lens calcium levels. Recently, in vitro studies with rabbit lenses have showed that increased calcium levels in cataracts were the results of decreased active Ca**++ efflux from the lens secondary to inhibition of Ca**++ -activated ATPase activity in the lens. In this experiment, gentamicin and normal saline were administrated into the anterior chamber and into the vitreous. Ca**++-activated ATPase activity in the lens, active Ca**++ efflux from the lens and calcium concentration in the lens were measured at day 1, day 3 and 7 days after injection of gentamicin or saline solution into the anterior chamber or vitreous to compare the effect on calcium transport in the rabbit lenses according to the route of administration between four different groups. They included normal saline injection group(control group) and gentamicin injection group(experimental group), intracameral gentamicin injection group and intravitreal gentamicin injection group. The results are summarized as follows; 1. The Ca**++-activated ATPase activity of the lens showed no interval change in the control group, but progressively inhibited in the experimental group. 2. The active efflux of Ca**++ from the lens was significantly decreased in the experimental group compared to the control group. 3. The calcium concentration in the lens showed no interval change in the control group, but progressively increased in the experimental group. 4. The inhibition of Ca**++-activated ATPase activity of the lens, decreased active Ca**++ efflux from the lens and increased calcium concentration in the lens were more severe in the intravitreal injection group than intracameral injection group. From the above results, it may be speculated that the decreased active efflux of Ca**++ from the lens induced by gentamicin is related to inhibiting Ca**++-activated ATPase activity of the lens and this makes the accumulation of calcium in the lens. These effects were more severe in the intravitreal gentamicin injection group than in the intracameral gentamicin injection group.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/117033
Appears in Collections:
2. 학위논문 > 1. College of Medicine (의과대학) > 박사
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