급성신부전을 나타낸 Lithium 중독 1예

여성욱,정상근 대한정신약물학회 2013 대한정신약물학회지 Vol.24 No.3

We report a case of 48 years-old male bipolar disorder patient with acute kidney injury due to severe lithium intoxication. He was taking lithium 300 mg per day but suddenly ingested all 30 tablets of lithium 300 mg (total 9,000 mg) at one sitting to commit suicide. On his arrival at the emergency room, the serum lithium concentration was 12.47 mEq/L. Thereafter he was treated with hemodialysis four times for 4-4.5 hour per session and recovered without any prominent sequela. The serum lithium level checked 9 days after hemodialysis was 0.1 mEq/L. Therefore we suggest that clinicians should consider such a strategy as mandatory hemodialysis in a patient with severe kidney intoxication when serum lithium concentrations are very high or rapidly increasing. 저자들은 자살목적으로 lithium을 과량 복약하고 응급실로 내원한 환자의 혈액학적 검사 및 임상적 소견으로 급성신부전을 진단하여, 초기에 적극적으로 혈액 투석을 통해 lithium을배출시켜 유의한 후유증 없이 회복된 양극성 장애 환자의 사례를 보고하였다. 따라서, 정신건강의학과 의사는 lithium 복용 환자와 보호자에게 lithium 중독 가능성에 대한충분한 사전 설명과 교육을 실시하고, 심각한 lithium 중독 환자의 경우에 혈액투석과 같은 적극적인 내과적 치료를 시행해야 한다.

Differential Regulation of Neural Stem Cells in Normal Rat Brain After Chronic Lithium Treatment

Park, June Hyuk,Jung, Yong Wook 동국대학교 의학연구소 2006 東國醫學 Vol.13 No.2

Lithium은 오래 전부터 양극성 정서장애를 치료하는 약제로 알려져 왔다. 그러나 최근에는 그 작용기전을 알 수 없으나 여러 실험을 통해서 lithium의 신경세포증식 작용이 보고되어 왔다. 저자들은 본 실험에서 lithium의 전처치가 정상 뇌의 줄기세포가 위치하는 곳으로 알려진 외측뇌실의 뇌실아래지역과 치아이랑의 과립세포아래지역에서 뇌의 줄기세포들의 증식을 유도할 수 있는가를 알아보았다. 지속적인 lithium의 처치는 25일간 쥐 분말사료에 lithium citrate를 40 mM/dl 혹은 60 mM/dl을 섞어 투여하였다. 혈장에서 lithium의 농도는 40 mM/dl 투여군에서는 0.40土0.08 mEq/L 그리고 40 mM/dl과 60 mM/dl 투여군에서는 0.60土0.1 mEq/L으로 대조군에 비하여 증가하였다. 지속적 lithium 처리 후 줄기세포들의 증식여부는 BrdU를 이용한 면역조직화학법을 이용하여 조사하였다. 본 실험의 결과에 의하면 치료농도의 lithium처리 후 정상뇌의 치아이랑의 과립아래지역에서의 신경줄기세포들의 선택적 증식이 관찰되었으며 이는 뇌허혈 발생시 지속적인 lithium의 처치가 신경세포의 증식을 통하여 치료효과를 나타낼 수 있다는 가능성을 제시한다. Lithium has long been a primary drug used to treat bipolar mood disorder. Recently, in vivo and in vitro studies have demonstrated neuroproliferative actions of lithium, even though the drug's therapeutic mechanisms remain obscure. The present study was undertaken to examine the possibility whether chronic treatment with lithium in normal rats can induce neuroproliferation in subventricular zone (SVZ) of lateral ventricle (LV) and/or subgranular zone (SGZ) of dentate gyrus (DG). Chronic lithium treatment was produced by pellet of standard diet containing 40 mM/dl and/or 60 mM/dl lithium citrate for 25 days. The serum concentrations of Li^(+) were increased to 0.40±0.08 mEq/L in the 40 mM/dl lithium treated rats and 60±0.1 mEq/L in the 40 mM/dl plus 60 mM/dl lithium treated rats which is therapeutic dose of clinical practice. The numbers of BrdU—positive cells were determined using immunohistochemistry after chronic lithium treatment. There was a significant increase of BrdU-positive cells in the SGZ of the DG after therapeutic dose of lithium treatment. Selective enhancement of the proliferation in neural progenitors in subgranular zone (SGZ) of the dentate gyrus (DG) in normal adult rat hippocampus strongly suggest the possibility that chronic lithium treatment may have therapeutic potential for stroke via neuroproliferation.

Decreased Expression of NHE1 in Lithium Treated Rat Hippocampus

김중모,정용욱 동국대학교 의학연구소 2008 東國醫學 Vol.15 No.1

인간과 흰쥐에서 lithium의 장기적 복용은 온몸과 대뇌의 대사성산증을 초래하며 이는 H^(+)의 분비감소 혹은 HCO₃^(-)의 흡수증가에 기인한 것으로 생각된다. 그러나 낮은 농도에서의 lithium의 장기적투여가 뇌에서의 산 염기의 이상에 예민하게 반응하는 해마의 산-염기 운반자 단백질의 발현에 영향을 미치는가의 여부는 알려져 있지 않다. Lithium의 처치는 25일간 쥐 분말사료에 lithium 60 mmol/dl를 투여하였다. 혈장에서 lithium의 농도는 임상적으로 이용되는 치료농도의 범주에 해당하는 0.76 ± 0.2mEq/L으로 대조군에 비하여 증가하였다. Lithium처리 된 흰쥐에서 산 염기조절단백질인 Na^(+)/H^(+) exchanger isoform 1 (NHE1) 와 electrogenic Na^(+)/HCO₃^(-) cotransporter (eNBC) 의 발현변화는 흰쥐해마에서 조사하였다. Lithium처리 후 NHE1의 발현은 37 ± 8% (n=8, p<0.01)로 대조군에 비해 통계학적으로 의미있게 감소하였으나 eNBC의 발현에는 변화가 없었다. 이러한 결과들은 lithium의 장기적 투여가 해마내 산 염기조절운반자의 발현을 의미있게 변화시킬 수 있음을 의미한다. 이것은 흰쥐 해마에서 H^(+)의 분비를 감소하여 대사성산증을 방지하려는 직접적 혹은 보상적 효과의 하나로 생각된다. Prolonged lithium treatment of humans and rodents often results in systemic and cerebral metabolic acidosis. This is thought to be caused by diminished net H^(+) secretion and/or increased net uptake of bicarbonate. However, it is unclear that chronic treatment with lithium at a low dose is associated with changes in the expression of brain acid-base transporters in the hippocampus which is well known to response to brain acid-base imbalance. Chronic lithium treatment was produced by pellet of standard diet containing 60mmol /dl lithium citrate for 25 days. The serum concentrations of lithium were increased to 0.76 ± 0.2 mEq/L which is therapeutic dose of clinical practice. The changes of protein expression of acid-base transporters [Na^(+)/H^(+) exchanger isoform 1 (NHE1) and electrogenic Na^(+)HCO₃^(-) cotransporter (eNBC)] were examined in the lithium treated rat hippocampus. Immunoblott analyses revealed that the expression of NHE1 (37 ± 8% of controls, n=8, P<0.01) was significantly decreased. In contrast, the expression of eNBC was unchanged in lithium treated rat hippocampus compared with that of controls. These results demonstrate that the expression of hippocampus acid base transporter is markedly altered in response to long term lithium treatment. This is likely to represent direct or compensatory effects to decrease the H^(+) secretion to prevent the development of metabolic acidosis in the hippocampus.

Lithium Cabonate와 Chlorpromazine 병합 투여로 인한 급성 뇌증후군 : 유효 치료혈중 Lithium농도에서

李正浩 인제대학교 1984 仁濟醫學 Vol.5 No.2

조울 정신병 환자와 정동형 정신분열증 환자의 급성 상태에 있는 환자에게 Lithium Carbonate와 동시에 항정신병 약물을 병합 투여하여 치료하는 것이 바람직한 치료법으로 지금까지 널리 알려져 왔다. 그런데 최근에 Lithium Carbonate와 Halopendol을 동시에 투여함으로 인해서 신경 독성 증상이 발생할 수가 있다는 보고가 있는데. 본 저자는 Lithium Carbonate와 Chlorpromazine을 병합 투여함으로 인해서 유효 치료혈중 Lithium농도를 유지하였음에도 불구하고 급성 신경 독성 증상을 보인 경우를 치험하였고 부작용이 발생하였을 때 Lithium Carbonate의 투여를 중단함으로써 독성 신경 증상이 즉시 소실한 경우를 치험하였기에 이에 보고하고자 한다. Although lithium carbonate therapy is the treatment of choice for manic patients and useful treatment for schizoaffective patients, the 5 to 10 days delay befor lithium becomes clinically effective usually requires the addition of a neuroleptic to help control acutely and severely disturbed psychotic pstients. Extensive use of this combination has generally proved quite safe and effective. However, several reports have drawn attention to possible neurotoxic side reactions following the combined use of lithium and neuroleptics. The author experienced to treat a case of schizophrenia, affective type, who had develoed abrupt confusion and selective memory loss during combined use of lithium carbonate 1,200 mg and chlorpromazine 600 mg mg. When this patient developed confusion, her seam lithium concentration was 0.9 mEq/L which was therapeutic range of serum lithium concentration. The author immediatly discontinued the lithium carbonate, but continued chlorpromazine. Her confusion was started to resolve three days later and was resolved completly ten days later except selective memory loss around that time which was irreversible. The author is following this patient as an outpatient and is making her to take lithium carbonate 900 mg a day without any side reactions; Her serum lithium concentration remains in the 0.6 mEq/L and she is doing well. The author can not explain exactly the reason for neurotoxic side reaction of this patient. But I think the cause of side reaction in this patient is idiosyncratic drug interaction of lithium and chlorpromazine or abnormally elevation of the intracellular concentration of lithium by chlorpromazine. However combined use of lithium and neuroleptics in the treatment of acute manic or schizoaffective patients is generally safe and effective, the author think we have to carefully use combined therapy of lithium and chlorpromazine, especially in schizophrenic patients. Although it remains unclear whether such toxic reaction is secondary to lithium and neuroleptic interactions or secondary to be elevated the intracellular concentration of lithium by chlorpromazine, discontinuing lithium carbonate and reducing the dose of chlorpromazine should be an effective therapy when neurotoxic symptoms are developed by combined therapy with lithium carbonate and chlorpromazine.

혈액 및 소변의 Lithium치 측정에 있어서 AAS법과 ISE법의 비교

김정숙,이채훈,이수인,김경동 영남대학교 의과대학 1993 Yeungnam University Journal of Medicine Vol.10 No.2

이상에서와 같이 lithium치의 측정에 있어서 본 병원에서 기존 이용하던 AAS법이나 ISE법 모두 정밀도나 직선성 평가에 있어 비교적 좋았으나, 정밀도(재현성)에 있어서 ISE법이 AAS법보다 더 우수한 것으로 나왔고 ISE법의 경우 측정방법이 매우 간편하였다. 그러나 ISE법에 의한 혈중 측정치가 AAS법에 의한 것보다 다소 높게 나타났으며, ISE법이 AAS법에 비하여 분석 최하한치가 더 높아 예민도는 상대적으로 낮았다. In the method for lithium(Li) analysis, flame emission photometry and atomic absorption spectrophotometry (AAS) have been used most frequently. In addition, lithium can be analyzed by ion-selective electrode (ISE) or fluorscence polarization immunoassay. We evaluated the comparison between AAS method based on the principle of absorption of light at 670.8 ㎚ by Li and ISE method based on the principle of voltage difference generated by Li in contact with lithium ionophore. We compared with those obtained by AAS (AA/AE Spectrophotometer 551, Instrumentation Laboratory Co.) and ISE (SYNCHRON EL-ISE, Beckman Co.) in the serum and urine of 6 patients and evaluated time-related changes of serum lithium concentration after dosing in both methods. The results are summarized as follows : 1. In within-run precision study for lithium concentration, coefficient variations (CVs, %) ranged from 1.34 to 2.17 for AAS and from 0.34 to 0.85 for ISE method. In between-run precision study for lithium concentration, CVs ranged from 1.23 to 1.72 for AAS and from 0.61 to 1.38 for ISE method. 2. The correlation study between AAS and ISE method resulted in Y=0.946X+0.137 (N=32, r=0.933, X=AAS, Y=ISE) for serum lithium and Y=1.092X+0.977 (N=28, r=0.943, X=AAS, Y=ISE) for urine lithium. 3. Time-related changes of serum lithium concentration in both AAS and ISE method resulted in peak serum levels about 2 hours after dosing and then rapidly decreased after the peak serum level and finally arrived at nearly initial levels about 9 hours after dosing. 4. The reference range of serum lithium was found as undetectable level for both AAS and ISE method and the reference range of urine lithium to the urine creatinine was 0-0.00014 m㏖/㎎(mean 0.00002 m㏖/㎎) for AAS method.

온천수 내 리튬 분포

서현수(Hyunsoo Seo),이정환(Jeong-Hwan Lee),박선주(SunJu Park),오준섭(Junseop Oh),최재훈(Jaehoon Choi),이종태(Jong-Tae Lee),윤성택(Seong-Taek Yun) 대한자원환경지질학회 2023 자원환경지질 Vol.56 No.6

전기 자동차 및 배터리에 대한 수요가 증가함에 따라 리튬의 가치가 크게 증가하였다. 리튬은 주로 페그마타이트, 열수변질을 받은 응회암질 퇴적 점토 및 대륙성 염수에서 발견된다. 전 세계적으로 지하수로 공급되는 염호와 유전 염수는 세계 리튬 생산량의 약 70%를 차지하는 대륙 염수의 주요 리튬 공급원으로 주목받고 있다. 최근에는 심부 지하수, 특히 지열수도 리튬의 잠재적 공급원으로 연구되고 있다. 심부 지하수의 리튬 농도는 상당한 물-암석 반응과 염수와의 혼합을 통해 증가할 수 있다. 심부 지하수 중의 리튬 탐사를 위해서는 그 기원과 거동을 이해하는 것이 중요하다. 따라서 본 연구에서는 전국적인 규모에서 국내 온천지역 지열수의 수문지화학 특성과 진화에 관한 예비연구를 바탕으로, 심부 지하수 환경에서의 리튬의 분포를 평가하고 그 농도에 영향을 미치는 지구화학적 요인을 이해하고자 하였다. 총 555개의 온천 지하수 시료 자료는 수화학적 특성에 따라 뚜렷한 지화학 진화 특성을 갖는 5가지 유형으로 분류되었다. 또한, 리튬의 부화 기작을 평가하기 위해 리튬 농도가 90번째 백분위 수(0.94 mg/L)를 초과하는 시료(n = 56)에 대해 자세히 고찰하였다. 리튬의 농도는 수화학 유형에 따라 유의미한 차이를 보였는데, Na(Ca)-Cl유형, Ca(Na)-SO4유형, pH가 낮은 Ca(Na)-HCO3 유형 순이었다. Ca(Na)-Cl 유형에서 리튬 부화는 해수침투에 따른 역이온 교환으로 발생한다. 백악기 화산퇴적 분지에서 특징적으로 나타나는 Ca(Na)-SO4 유형 지하수에서 용존 리튬의 부화는 열수 변질 점토 광물의 산출 및 화산활동과 관련이 있는 반면, 낮은 pH의 Ca(Na)-HCO3 유형 지하수에서는 심부 CO2의 상승 혼입에 의한 기반암의 풍화 촉진으로 인해 리튬 부화가 일어난 것으로 해석된다. 본 광역 예비 지화학 연구 결과는 심부 지질환경에서의 수문지화학 진화에 대한 이해와 함께 향후 경제성 있는 리튬 탐사 지침과 관련하여 유용한 정보를 제공할 것이다. The value of lithium has significantly increased due to the rising demand for electric cars and batteries. Lithium is primarily found in pegmatites, hydrothermally altered tuffaceous clays, and continental brines. Globally, groundwater-fed salt lakes and oil field brines are attracting attention as major sources of lithium in continental brines, accounting for about 70% of global lithium production. Recently, deep groundwater, especially geothermal water, is also studied for a potential source of lithium. Lithium concentrations in deep groundwater can increase through substantial water-rock reaction and mixing with brines. For the exploration of lithim in deep groundwater, it is important to understand its origin and behavior. Therefore, based on a nationwide preliminary study on the hydrogeochemical characteristics and evolution of thermal groundwater in South Korea, this study aims to investigate the distribution of lithium in the deep groundwater environment and understand the geochemical factors that affect its concentration. A total of 555 thermal groundwater samples were classified into five hydrochemical types showing distinct hydrogeochemical evolution. To investigate the enrichment mechanism, samples (n = 56) with lithium concentrations exceeding the 90th percentile (0.94 mg/L) were studied in detail. Lithium concentrations varied depending upon the type, with Na(Ca)-Cl type being the highest, followed by Ca(Na)-SO4 type and low-pH Ca(Na)-HCO3 type. In the Ca(Na)-Cl type, lithium enrichment is due to reverse cation exchange due to seawater intrusion. The enrichment of dissolved lithium in the Ca(Na)-SO4 type groundwater occurring in Cretaceous volcanic sedimentary basins is related to the occurrence of hydrothermally altered clay minerals and volcanic activities, while enriched lithium in the low-pH Ca(Na)-HCO3 type groundwater is due to enhanced weathering of basement rocks by ascending deep CO2. This reconnaissance geochemical study provides valuable insights into hydrogeochemical evolution and economic lithium exploration in deep geologic environments.

Lithium 중독의 위험 요인에 대한 후향적 고찰

김상헌(Sang Heon Kim),손은희(Eun Hee Sohn),이준영(Joon Young Lee) 대한생물치료정신의학회 2006 생물치료정신의학 Vol.12 No.2

Lithium은 1970년도에 양극성 장애의 치료제로 승인을 받은 이후 정신과의 다양한 영역에서 치료제로 이용되고 있다. 하지만 lithium은 혈청 치료 농도의 범위가 매우 좁다는 약점 때문에 중독의 위험성이 높다. 본 연구에서는 2000년 1월부터 2006년 1월까지 경북대학병원 정신과에서 lithium이 포함된 처방을 받아 복용중인 환자들 중 혈청 lithium 농도 검사를 비롯한 기본적인 검사들을 완료한 72명을 대상으로 하여, lithium 중독의 위험 요인들이 중독 환자군과 비중독 환자군 간에 유의한 차이가 있는 지와 이 요인들이 lithium 중독환자군 내에서 혈액투석치료군과 비혈액투석치료군 사이에서도 차이가 존재하는지를 살펴보았다. 결과는 다음과 같다. 1) Lithium 중독 환자군과 비중독 환자군 간의 lithium 중독 위험 요인의 비교에서 혈청 lithium 수치, 신장 기능의 이상 유무, Gadallah의 증상 중증도 분류에서는 통계적으로 유의한 차이가 있었다. 2) 혈액투석치료군과 비혈액투석치료군 간의 lithium 중독 위험 요인의 비교에서는 혈청 lithium 농도, Gadallah의 증상 중증도 분류에서 통계적으로 유의한 차이를 보였다. 3) Lithium 중독 위험 요인들 사이의 상관관계 분석에서, 혈청 lithium 농도는 소디움 농도와는 음의 상관관계를 그리고 Gadallah의 중독 증상 단계와는 양의 상관관계를 보였다. 본 연구는 신장 문제가 lithium 중독과 관련성이 높다는 기존의 가설을 지지하였고, 높은 혈청 lithium 농도가 lithium 중독증의 치료 방법의 결정에 영향을 주며, 또한 혈청 lithium 농도가 높을수록 혈액투석법이 선택된다는 것을 밝혔다. 또한 lithium의 농도가 올라갈수록 부작용 Gadallah의 중독 증상 단계가 올라간다는 상관관계를 통해서 임상에서 lithium을 처방할 때 각 lithium 농도에 따른 부작용 증상을 숙지하는 것이 추적관찰 치료 시에 필요하며, 이는 자세한 이학적 검사와 문진을 통하여 미리 치명적인 부작용을 방지할 수 있다는 가능성을 시사한다. 향후 연구에서는 표본의 수를 확대하는 것이 필요하다고 본다. After lithium being approved for the treatment of bipolar affective disorder in 1970, it has been used for many psychiatric symptoms. But lithium has a very narrow therapeutic index which can sometimes be fatal to patients. In this study, retrospective analysis was done to 72 psychiatric patients who had taken lithium and completed serum lithium level test, complete blood cell count, liver function test, thyroid function test and serum renal function test. We compared the difference of lithium intoxication risk factors between lithium intoxication and non-intoxication group. And we also studied the difference of risk factors of lithium intoxication in relation to the treatment of hemodialysis. Current findings are as follows:1) Serum lithium levels, presence of renal problems and Gadallah's toxicity symptom stages were significantly higher in lithium intoxication group than in non-intoxication group. 2) Serum lithium levels and Gadallah's toxicity symptom stages were significantly higher in hemodialysis group than in nonhemodialysis group. 3) Serum lithium levels had negative correlations with serum sodium level and positive correlations with toxicity symptom stages. These results suggest that renal problems were related to lithium intoxication and the higher serum lithium levels and intoxication symptom stage were, the more physicians chose the method of hemodialysis. And we also found that Gadallah's toxicity symptom criteria might be very useful for the assessment of the side effects of lithium and helpful to prevent possible lithium intoxication. Further studies for verification of these facts will be necessary in the future.

탄산리튬으로부터 수산화리튬 전환을 위하여 탄산리튬의 열분해에 대한 연구

박재은,박민화,서형준,김태성,김대원,김보람,최희락,Park, Jae Eun,Park, Min Hwa,Seo, Hyeong Jun,Kim, Tae Seong,Kim, Dae Weon,Kim, Bo Ram,Choi, Hee Lack 한국결정성장학회 2021 한국결정성장학회지 Vol.31 No.2

현재 리튬이온 배터리에 사용되는 고니켈계 양극재의 수요 증대에 따라 수산화리튬(LiOH) 제조 연구가 활발히 진행되고 있다. 본 논문에서는 탄산리튬(Li2CO3)으로부터 수산화리튬의 제조를 위하여, 탄산리튬의 열분해를 통한 산화리튬(Li2O)의 전환 공정에 대해 연구하였다. 열처리 시 탄산리튬과 알루미나, 석영 그리고 흑연 도가니 사용에 따른 반응 메커니즘을 확인하였으며, 흑연 도가니를 사용했을 경우 온전한 산화리튬 분말을 얻었다. TG 분석 결과를 바탕으로 열처리 온도를 700℃, 900℃ 그리고 1100℃로 설정하였으며 유지시간 및 분위기를 제어하여 시약급 탄산리튬의 열처리를 진행하였다. XRD 분석 결과, 제조된 산화리튬은 질소 분위기에서 1시간 동안 1100℃의 온도로 열처리를 하였을 때 높은 결정성을 보였다. 또한 수산화리튬으로 전환하기 위해 시약급 산화리튬을 100℃에서 수반응하였다. XRD 분석을 통해 수산화리튬(LiOH)과 수산화리튬 일수화물(LiOH·H2O)이 생성됨을 확인하였다. Research on the production of lithium hydroxide (LiOH) has been actively conducted in response to the increasing demand for high nickel-based positive electrode materials for lithium-ion batteries. Herein we studied the conversion of lithium oxide (Li2O) through thermal decomposition of lithium carbonate for the production of lithium hydroxide from lithium carbonate (Li2CO3). The reaction mechanism of lithium carbonate with alumina, quartz and graphite crucible during heat treatment was confirmed. When graphite crucible was used, complete lithium oxide powder was obtained. Based on the TG analysis results, reagent-grade lithium carbonate was heat-treated at 700℃, 900℃ and 1100℃ for various time and atmosphere conditions. XRD analysis showed the produced lithium oxide showed high crystallinity at 1100℃ for 1 hour in a nitrogen atmosphere. In addition, several reagent-grade lithium oxides were reacted at 100℃ to convert to lithium hydroxide. XRD analysis confirmed that lithium hydroxide (LiOH) and lithium hydroxide monohydrate (LiOH·H2O) were produced.

Recovery of lithium from lithium aluminum silicate (LAS) glass-ceramics through a hydrometallurgical process

( Sung-ho Joo ),( Dong Ju Shin ),( Dongseok Lee ),( Shun Myung Shin ) 한국폐기물자원순환학회 2022 ISSE 초록집 Vol.2022 No.-

Among the global lithium reserve amount, more than 50% is distributed in Chile, Argentina, and Bolivia as brine sources, and 25% as ore sources in Australia, which shows the significantly poor distribution of lithium. Furthermore, the global recycling rate of lithium is less than 1%. Therefore, it is essential to find a new lithium raw material to solve the shortage of lithium supply due to the increase in demand for electric vehicles. The purpose of this study is to recover lithium from lithium aluminum silicate (LAS) glass-ceramics as a secondary source of lithium, through a hydrometallurgical process consisting of calcination, NaOH leaching, and solvent extraction. Before NaOH leaching experiments, the crystalline structure of LAS glass-ceramics was converted into a tetragonal structure from hexagonal by calcination at 1000°C for 3 h. NaOH leaching based on a 53 μm of particle undersize, 5M NaOH, a reaction temperature of 100°C, stirring speed of 250 rpm, and a reaction time of 5 h resulted in more than 99% lithium leaching efficiency from LAS glass-ceramics. The solvent extraction experiments were conducted using a cation exchange extractant following a purification process of the leachate to remove impurities such as aluminum and silica. The extraction behavior of lithium was investigated with an equilibrium pH, a concentration of extractant, a saponification ratio, and a McCabe-Thiele diagram. Finally, more than 99% lithium was extracted from the aqueous solution by a four-stage counter-current extraction using 15% saponified 1M PC-88A, and the content of lithium in the aqueous solution was concentrated at 5,280 mg/L by a single stripping stage with 1M H₂SO₄.

The Effect of Lithium on Adenylyl Cyclase: Thirty-Five Years of Research (1975∼2010)

RH Belmaker,G Agam 대한정신약물학회 2010 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.8 No.3

One of the first discovered effects of lithium was inhibition of adenylyl cyclase (AC). AC is linked to many brain receptors and transmits their message into the cell by catalyzing the formation of cyclic AMP from adenosine triphosphate. Since the original report found lithium inhibition at 2 mM we attempted to see whether this effect actually occurred in patients on lithium whose average blood levels are less than 1 mM. We were able to show this effect using subcutaneous adrenalin and measuring cyclic AMP in plasma over the course of 70 minutes. We then studied the specificity of the effect using the glucagon induced rise in plasma cyclic AMP and found no effect of lithium. In rat brain slices we could confirm the finding that lithium inhibition occurs only at 2 mM but we could show that chronic lithium treated rats had inhibition of cyclic AMP accumulation ex vivo. Since the AC system is complex we attempted to find the site of lithium action. Lithium inhibited G-protein function induced by isoproterenol or carbachol as measured by increases in rat brain homogenate radioactive GTP binding. However, lithium inhibited forskolin induced rises in cAMP accumulation and forskolin is thought to stimulate the AC system directly at the enzyme even in the absence of G-protein. More recently, 10 different isozymes of AC have been described, each the product of a different gene and with differential location throughout the brain or peripheral tissues. We were able to show that lithium preferentially inhibits AC5 and to a lesser extent AC2 and AC7. Since AC5 is located mostly in dopamine rich areas in the basal ganglia, this suggested that lithium’s specific behavioral effects might be related to AC5. The effect of lithium on AC5 is magnesium dependent, similar to the effect of lithium in many other biochemical systems. AC remains a candidate for the therapeutic mechanism of lithium and AC5 inhibitors under development may be brought to clinical trial in bipolar illness.