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PubMed1987

Assay of sodium-lithium countertransport rate by direct measurement of erythrocyte lithium concentrations.

A method is described for the in-vitro measurement of erythrocytic sodium-lithium countertransport rate (SLC) by direct assay of intra-erythrocytic lithium (Li) concentrations in Li loaded cells during controlled Li efflux. Bicarbonate stimulated erythrocytic Li loading to an approximate intracellular concentration of 3 mmol/l can be achieved within 4 min. Maximum SLC rates are achieved at intra-erythrocytic concentrations greater than 2.5 mmol/l. Lithium efflux is linear over 0-60 min, and independent of pH change. The within-batch coefficient of variation for positive displacement pipetting of Li loaded erythrocytes is 2.8%. Storage of erythrocytes in isosmotic MgCl2 for 24 h had no effect on the SLC. Intra-individual coefficient of variation for SLC was less than 6%. The reference range for Caucasian subjects (n = 43) was 0.14-0.49 mmol Li +/l erythrocytes/h.

Antiporters↗

PubMed1995

Monitoring of lithium levels in human serum after therapy with lithium preparations by capillary isotachophoresis.

An isotachophoretic method for the evaluation of the level of lithium salts in serum samples was optimized. Use of operating systems containing polyethylene glycol permitted the separation of cationically migrating components from Li (i.e., Na, K and Ca). The pretreatment of serum samples involves only appropriate dilution with demineralized water depending on the concentration of the major components such as sodium. The lithium levels were studied both in model samples and serum from patients treated with lithium preparations.

Electrophoresis, Capillary↗

PubMed1995

An electron microscopic study of collagen fibril structure after lithium treatment--II. The effects of low lithium dose and short treatment on mouse skin collagen.

The structure of mouse skin collagen fibrils, after treatment with lithium chloride at a dose of 0.7 meq/kg of body weight, was studied by electron microscopy. Animals were sacrificed 1-day, 1-, 2- and 6-months after the end of 30 consecutive days experimental period. Fibrils in disarray interspersed with normal ones were seen, although there were areas where the normal parallel packing of fibrils was completely replaced by a random arrangement. In some regions this packing was interrupted by fibrils forming a 'hairpin loop' and in some others helical twisting was apparent. Lithium treated collagen fibrils had a marked decrease in mean diameter compared to normal with a high variability in width. Clusters of abnormal fibrils were found when viewed in cross-sections, constituted approximately 10% of the whole population with an irregular outline. A shorter experimental period (7 days) leads to the same features in collagen disorganization as with the longer experimental period (30 periods). However, in short lithium treatment, there is no high variability in fibril width and although fibrils are smaller than the control, the decrease in mean diameter is not so pronounced as with longer treatment. In general, fibril diameter becomes altered progressively with experimental time. Lower dose, 0.3 meq Li/kg, in short treatment (7 days), leads to a normal collagen organization although in some areas fibril twisting is observed. Fibril diameter is not considerably affected.

Animals↗

PubMed1994

Lithium-induced alterations in parathyroid cell function: insight into the pathogenesis of lithium-associated hyperparathyroidism.

BACKGROUND: Reduced parathyroid sensitivity to changes in calcium (Ca2+) has been observed in patients treated with lithium (Li+). In order to investigate this desensitization phenomenon, the effect of Li+ on cytosolic calcium (Cai2+) regulation was examined. METHODS: Transmembrane signal transduction and Ca2+ sequestration were investigated in bovine parathyroid cells by measuring changes in [Cai2+] in response to 5 mmol/L magnesium (Mg2+), 0.5 to 2.5 mmol/L Ca2+, 25 mumol/L adenosine triphosphate (ATP), and 1 mumol/L ionomycin in cells pretreated with 1 to 10 mmol/L lithium chloride (LiCl) and control cells. Measurement of Cai2+ was made using fura-2. RESULTS: Increases in [Cai2+] in response to Ca2+ and Mg2+ were blunted following overnight culture with as low as 1 mmol/L LiCl. In normocalcemic medium, 1 mmol/L Ca2+ produced an 81% increase in [Cai2+] in control cells compared with a 58% increase in cells pretreated with LiCl (P < 0.01), whereas in hypocalcemic medium, increases in [Cai2+] were similar in lithium-treated and control cells (78% versus 82%, P > 0.1). The ATP produced increases in [Cai2+] from 225 +/- 9 nmol/L to 366 +/- 10 nmol/L in control cells, compared with 221 +/- 7 nmol/L to 308 +/- 10 nmol/L in cells pretreated with 5 mmol/L LiCl (P < 0.01). Ionomycin-induced increases in [Cai2+] were unaffected by Li+. CONCLUSIONS: We concluded that the in vitro desensitizing effects of Li+ occur at therapeutic concentrations, but only in the presence of Ca2+ in concentrations that induce transmembrane signaling; and that Li+ blunts increases in [Cai2+] related to cation and ATP-induced transmembrane signal transduction without affecting ionomycin-releasable Ca2+ stores.

Animals↗

PubMed2002

Lithium concentrations in plasma of lithium-treated psychiatric patients in the Netherlands: commentary on Cusin et al.

Seasonal variations in 68 psychiatric patients receiving prophylactic lithium treatment in the Netherlands between 1974 and 1994 were analyzed and compared with findings from Italy. Although lithium doses remained stable, there was a significant change in plasma levels of lithium, with values in spring and summer tending to exceed those in autumn and winter. These findings are similar to those reported in Italy, although the maximal seasonal change was approximately 5% in the Netherlands compared with approximately 10% in Italy. The difference could reflect the hotter summer climate in Italy, associated with increased perspiration. Future studies should measure perspiration levels directly.

Adult↗

PubMed1998

Behavioral reversal of lithium effects by four inositol isomers correlates perfectly with biochemical effects on the PI cycle: depletion by chronic lithium of brain inositol is specific to hypothalamus, and inositol levels may be abnormal in postmortem brain from bipolar patients.

The inositol depletion hypothesis of lithium (Li) action has been criticized, because depletion of inositol after chronic Li treatment has not been reproducible, effects of inositol to reverse Li-induced behaviors occurred also with epi-inositol, a unnatural isomer, and because inositol is ubiquitous in brain and hard to relate to the pathogenesis of affective disorder. Therefore, we review our studies showing that lithium depletion of brain inositol occurs chronically in the hypothalamus, a region not previously examined; that behavioral effects of four different inositol isomers including epi-inositol correlate perfectly with their biochemical effects; and that inositol in postmortem human brain is reduced by 25% in frontal cortex of bipolars and suicides as compared with controls. Because inositol in postmortem brain is reduced and not increased in bipolar patients, the relationship between inositol, lithium, and affective disorder is complex.

Aged↗

PubMed2002

Lithium-sulfoxide-lithium exchange for the asymmetric synthesis of atropisomers under thermodynamic control.

Ortholithiation and reaction with (-)-menthyl p-toluenesulfinate introduces a sulfoxide substituent ortho to the stereogenic Ar-CO axis of an aromatic amide. The sulfoxide exerts a powerful conformational bias on the axis, such that after rapid equilibration at ambient temperature essentially only one of two diastereoisomeric Ar-CO atropisomers is populated. Sulfoxide-lithium exchange by treatment with t-BuLi regenerates the ortholithiated amide in an enantiomerically pure and conformationally stable form. Rapid electrophilic trapping of the organolithium therefore generates highly enantiomerically enriched atropisomeric tertiary aromatic amides. The overall process, involving temporary substitution of lithium to sulfoxide to lithium, amounts to a dynamic resolution under thermodynamic control.

Amides↗

PubMed1981

Monitoring lithium dose levels: estimation of lithium in blood and other body fluids.

The theoretical basis and practical application of the analytical procedures used to quantitate lithium in biological fluids, i.e., flame emission and atomic absorption, are described in their most simple form in nontechnical language. The clinical relevance of the erythrocyte to plasma ratio, saliva, urine, and spinal fluid lithium measures is discussed. Other topics include acute treatment plasma lithium levels and maintenance treatment plasma levels, pitfalls in sample collection, availability of micro (finger prick) procedures, and laboratory accuracy and evaluation.

Blood Specimen Collection↗

PubMed1990

Pharmacokinetics of lithium in patients treated with controlled release lithium formulations.

There has long been discussion as to the relative merits of the lithium formulations available in the UK. Two of these have been shown to exhibit similar pharmacokinetics in normal volunteers and both are now marketed as controlled release formulations. In this study the serum lithium profiles of these formulations were compared in patients at two centres during the first 4 h after the dose, and at 24 h. We were unable to show any significant difference between the formulations in respect of maximum serum lithium concentrations or the concentration at each time point.

Adult↗

PubMed1977

"Lithium non-responders" in a lithium clinic.

The present study is concerned with the outcome of long-term lithium maintenance therapy administered to 107 manic-depressive patients after more than 12 months. Nine patients failed to respond despite having met the criteria for maintenance within the therapeutic range of lithium. This group, termed "lithium non-responders", had all shown bipolar illness with gross morbidity with frequent cycles, greater than 4 per year, seven had a family history of affective illness (six bipolar). The study did not demonstarte any other clear factors common to the "non-responders" group.

Adult↗

PubMed1977

Comparison of side effects with coated lithium carbonate tablets and lithium sulphate preparations giving medium-slow and slow-release.

Side effects with coated, rapidly dissolving lithium carbonate tablets, medium-slow-release and slow release lithium sulphate tablets, all administered twice a day, were compared in a double-blind, cross-over study in 27 patients who had only used lithium carbonate tablets. The relation between medication and meals was not standardized. The repidly dissolving tablets and the medium-slow-release tablets had a similar tendency to produce side effects, while slow-release tablets more often produced purgative side effects than the other two preparations did.

Adult↗

PubMed1989

Acute antidepressant effect of lithium is associated with fluctuation of calcium and magnesium in plasma. A double-blind study on the antidepressant effect of lithium and clomipramine.

In a double-blind study on 22 patients with major depressive disorder the effects of lithium and clomipramine on signs and symptoms and on calcium and magnesium in plasma were compared. Ratings of antidepressant and side effects were performed by 2 psychiatrists at the end of a placebo period of 5-7 days and after treatment for 2 and 4 weeks. Psychopathology was rated by 15 reported and 4 observed items from the Comprehensive Psychopathological Rating Scale (CPRS). Eleven items present in 72-100% of the patients were used to evaluate the effect of the two drugs. After 2 weeks of treatment the rated scores dropped for more than half of the CPRS items. After 4 weeks the scores for all but one item were reduced in both groups. The sums of scores were significantly reduced after 2 weeks in both groups and after 4 weeks global scores were reduced as well. The drugs had notable and similar antidepressant effects. Lithium treatment was associated with fluctuations in calcium and magnesium levels in plasma not seen during clomipramine treatment. Serum prolactin increased during clomipramine treatment but was unaffected by lithium treatment. No correlations were found between the sum of rating scores and blood levels of drugs, prolactin, calcium or magnesium.

Adult↗

PubMed1996

Mortality of patients who dropped out from regular lithium prophylaxis: a collaborative study by the International Group for the Study of Lithium-treated patients (IGSLI).

Excess mortality has repeatedly been found in patients with recurrent affective disorders. In previous studies our group has shown that during long-term lithium treatment the mortality of such patients is not significantly higher than that of the general population. In the present study, we extended our investigation to 273 patients from the earlier IGSLI cohort who subsequently dropped out from regular lithium prophylaxis. The standardized mortality ratio (SMR) for the whole group was 2.5, significantly higher (P < 0.01) than 1.0, which is the SMR of the general population. Furthermore, the SMR of the patients from each of the participating countries, namely Denmark, Germany and Austria, was significantly higher than 1.0. These findings strengthen the evidence accumulated in previous investigations that regular long-term lithium treatment does in fact markedly reduce the excess mortality of patients with recurrent affective disorders.

Antimanic Agents↗

PubMed1973

Lithium and pregnancy. II. Hazards to women given lithium during pregnancy and delivery.

The renal lithium clearance of a manic-depressive woman rose when she became pregnant and fell to the prepregnancy level when she gave birth. The lithium clearances of four healthy women were higher during pregnancy than after delivery. This emphasizes the need for frequent determinations of the serum lithium concentration and appropriate dosage adjustments during pregnancy and delivery.

Bipolar Disorder↗

PubMed1981

Course and relationship of lithium side effects to plasma lithium levels.

49 patients with primary affective disorders maintained on lithium were evaluated over a 6-month course and the pattern of 10 well-known innocuous side effects of lithium therapy was closely evaluated. The patients had significantly more side effects in the 1st month as opposed to the 4th through 6th months. The difference was statistically significant (with p less than 0.05). There was no difference in plasma lithium levels among individuals having no side effects, 1-2 side effects or 3 or more side effects at any point during the 6-month period.

Adult↗

PubMed1979

Lithium side effects in a routine lithium clinic.

Approximately two thirds of a group of bipolar patients attending the routine lithium clinic suffered sid effects. These patients tended to have a lower plasma and erythrocyte lithium concentration and a lower erythrocyte/plasma lithium ratio than those who had no side effects. Explanations of this unexpected finding are discussed.

Bipolar Disorder↗

PubMed1978

Use of saliva lithium determinations for monitoring lithium therapy.

During acute and chronic administrations of lithium, 25 patients were studied to determine the effect of other psychotropic drugs on the plasma-saliva lithium concentration correlations. Changes, even discontinuation, in either tricyclic antidepressants or neuroleptics did not affect the plasma-saliva ratio which had an overall correlation coefficient of r = 0.79 (p less than 0.01). The relationship using linear regression analysis was described by the equation, y = 2.27x--0.45. Individual patients' plasma-salivary relations were described by this equation in 87% of cases. The study extends the usefulness of these determinations to include patients on lithium and neuroleptics or tricyclic antidepressants.

Antidepressive Agents, Tricyclic↗

PubMed1979

Prospective use of saliva lithium determinations to monitor lithium therapy.

A mathematical equation (y = 2.27x -0.45) relating saliva (y) to plasma (x) lithium concentrations was previously determined by one of the authors. A prospective study is reported here in which the correlation coefficient between the predicted and the observed plasma concentrations in a new group of 25 patients was r = 0.89 (p less than 0.001). The study demonstrates that saliva lithium determinations can be safely used to monitor lithium therapy.

Bipolar Disorder↗