The prediction of brain lithium concentrations from plasma or erythrocyte measures

Fraser, A. C.; Mendels, J.; Secunda, Steven K.; Cochrane, Carl M.; Bianchi, C. Paul

doi:10.1016/0022-3956(73)90004-6

Cited by 94 publications

(21 citation statements)

References 16 publications

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“…This cannot be monitored and so it is usual to measure the concentration of the ions in the serum, which is the closest site in which repeated observations can be made safely. However, it has been shown in rats that when the lithium concentration in the serum changes rapidly, it does not correlate well with that found in the brain (Frazer, Mendels, Secunda, Cochrane & Bianchi, 1973).…”

Section: Introductionmentioning

confidence: 95%

The Pharmacokinetics of Lithium in the Brain, Cerebrospinal Fluid and Serum of the Rat

Wraae

1978

British J Pharmacology

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1 Addition of lithium carbonate (55 mmol/kg dry wt.) to the diet of rats for 4 days resulted in ratios between lithium in the brain and serum and between the cerebrospinal fluid (CSF) and serum of approx. 1 and 0.4, respectively. The relationships between the concentrations were linear. 2 After single intraperitoneal injections of lithium chloride (5 mmol/kg body wt.) the concentration of lithium in the CSF was greater than that of the brain for 2 h. 3 Repeated subcutaneous injections of lithium chloride (0.9 mmol/kg body wt.) resulted in steady state ratios corresponding to those .observed when lithium was given in the diet. The rate of elimination from the CSF was intermediate between that of the serum and cerebral tissue until a new equilibrium was reached after approx. 24 h. At that time the ratios between lithium in the brain and serum, and in the CSF and serum were increased to approx. 5 and 0.8, respectively. 4 These results are consistent with passive transfer kinetics of lithium in the CSF and elimination of lithium from the cerebral tissue via the CSF.5 The results may explain some of the phenomena observed in patients during intoxication with lithium.

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Section: Introductionmentioning

confidence: 95%

The Pharmacokinetics of Lithium in the Brain, Cerebrospinal Fluid and Serum of the Rat

Wraae

1978

British J Pharmacology

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“…The presence in the erythrocyte membrane of a transport mediating the exchange of intracellular lithium for extracellular sodium was first suggested after the finding that, in lithiumtreated patients who had affective disorders, lithium concentration was systematically lower in the erythrocytes than in the plasma (1,2). Since the first identification, sodium-lithium countertransport (SLC)-so called because sodium, at opposite with the sodium pump, is moved toward the intracellular compartment-was confirmed in the erythrocyte of humans and of a number of animal species (3,4).…”

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confidence: 99%

Increased Sodium-Lithium Countertransport Activity

Zerbini

Gabellini

Ruggieri

et al. 2004

Journal of the American Society of Nephrology

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Abstract. An increased activity of sodium-lithium countertransport (SLC) is a common finding in patients who have essential hypertension. The evidence that a similar dysfunction is shared also by patients with type 1 diabetes and nephropathy has suggested the hypothesis that a predisposition to essential hypertension may be the factor that, along with hyperglycemia, underlies the development of diabetic nephropathy. Despite the initial enthusiasm surrounding the potential use of SLC activity as a marker for the early detection and treatment of individuals who are predisposed to hypertension and diabetic nephropathy, its use has been so far restricted to epidemiologic studies, as specificity and sensitivity of the test are still too low to justify any clinical use. The recent finding, however, that the measurement of kinetic parameters of SLC can significantly increase the power to discriminate among individuals with and without hypertension or diabetic nephropathy could be of help toward a future clinical use of the measurement of this membrane transport. A second major point relates to the possibility that SLC per se might be directly involved in the pathogenesis of essential hypertension and diabetic nephropathy. This case has never been fully tested, as the gene responsible for this membrane transport has been, until recently, unknown. The recent identification of an alternative splicing of the first isoform of Na-H exchange that mediates SLC activity should allow for a rapid comprehension of the role of this transport in the pathophysiology of essential hypertension and diabetic nephropathy.The presence in the erythrocyte membrane of a transport mediating the exchange of intracellular lithium for extracellular sodium was first suggested after the finding that, in lithiumtreated patients who had affective disorders, lithium concentration was systematically lower in the erythrocytes than in the plasma (1,2). Since the first identification, sodium-lithium countertransport (SLC)-so called because sodium, at opposite with the sodium pump, is moved toward the intracellular compartment-was confirmed in the erythrocyte of humans and of a number of animal species (3,4).SLC gained widespread reputation in 1980 after the demonstration by Canessa et al. (5) that elevated activity rates of this transport are a consistent concomitant of essential hypertension. It is interesting that although SLC activity rate can be affected by several environmental factors (6,7), family and genetic epidemiology studies have shown that the effect of polygenic inheritance and/or of recessive major gene is nonetheless a major determinant in the interindividual variability of SLC (8 -10).Since the original finding, an increased activity of SLC has always been considered an established marker of essential hypertension. For this reason, after the demonstration that hyperglycemia by itself is not sufficient to explain the development of diabetic nephropathy (11) and the discovery that arterial BP is higher in parents of patients with type 1 dia...

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“…Merely from the fact that RBC and CSF lithium concentrations rise and fall more slowly following a dose of lithium, than does plasma lithium concentration (4,6), one might predict a closer corre spondence of CSF with RBC than with plasma lithium, especially in a study where the time factor varied from subject to subject. That this failed to occur, together with the fact that RBC lithium proved significantly higher than CSF lithium, supports the hypothesis that transfer of lithium into and out of the CSF and RBC takes place by different mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…The basis for this practice derives partly from a study by Frazer et al (6), who, after administering acute and chronic courses of lithium to rats, found that RBC lithium correlated with brain lithium more closely than did plasma lithium. Comparable data for humans, understandably difficult to obtain, appear nonexistent.…”

mentioning

confidence: 99%

Relationship between Plasma, RBC, and CSF Lithium Concentrations in Human Subjects

White¹,

Cohen²,

Boyd³

et al. 1979

Int Pharmacopsychiatry

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Simultaneous measurement of plasma, RBC, and plasma lithium concentrations took place with 17 inpatients chronically treated with lithium, at various times after the last lithium dose. RBC lithium levels were significantly higher than CSF lithium levels. Specimens drawn 10 or more hours after the last dose showed higher RBC and CSF lithium and lower plasma lithium than specimens drawn 4 or less hours after the last lithium dose. None of the lithium measurements differentiated manic-depressives from schizophrenics or schizoaffectives. Plasma, RBC, and CSF lithium all intercorrelated highly and equally.

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The prediction of brain lithium concentrations from plasma or erythrocyte measures

Cited by 94 publications

References 16 publications

The Pharmacokinetics of Lithium in the Brain, Cerebrospinal Fluid and Serum of the Rat

The Pharmacokinetics of Lithium in the Brain, Cerebrospinal Fluid and Serum of the Rat

Increased Sodium-Lithium Countertransport Activity

Relationship between Plasma, RBC, and CSF Lithium Concentrations in Human Subjects

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