Are ate complexes true intermediates in lithium-metalloid exchange? Subtle effects of ion-pair structure in lithium-tellurium and lithium-selenium exchange reactions.
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The solvation parameter model has been applied to the characterization of micellar electrokinetic chromatographic (MEKC) systems with mixtures of lithium dodecyl sulfate and lithium perfluorooctanesulfonate as surfactant. The variation in MEKC surfactant composition results in changes in the coefficients of the correlation equation, which in turns leads to information on solute-solvent and solute-micelle interactions. Lithium perfluorooctanesulfonate is more dipolar and hydrogen bond acidic but less polarizable and hydrogen bond basic than lithium dodecyl sulfate. Therefore mixtures of lithium dodecyl sulfate and lithium perfluorooctanesulfonate cover a very wide range of polarity and hydrogen bond properties, which in turn results in important selectivity changes for analytes with different solute properties.
The lithium ion phase-transfer reaction between the spinel lithium manganese oxide electrode and a nonaqueous electrolyte was investigated by the ac impedance spectroscopic method. The dependence of the impedance spectra on the electrochemical potential of the lithium ion in the electrode, the lithium salt concentration in the electrolyte, the kind of solvent, and the measured temperature were examined. Nyquist plots, obtained from the impedance measurements, consist of two semicircles for high and medium frequency and warburg impedance for low frequency, indicating that the reaction process of two main steps for high and medium frequency obey the Butler-Volmer type equation and could be related to the charge-transfer reaction process accompanied with lithium ion phase-transfer at the interface. The dependency on the solvent suggests that both steps in the lithium ion phase-transfer at the electrode/electrolyte interface include the desolvation process and have high activation barriers.
The distribution of RBC lithium ratios in vitro in a recently hospitalized psychiatric population was found to be multimodal. Psychotic patients who had an antipsychotic response during open trials of lithium carbonate alone were identified with high sensitivity (89%), but low specificity (51%) before drug treatment, by lithium ratios that were in the extreme modes of the distribution (less than 0.30 or greater than 0.38). Diagnostic efficiency of the test was 61%. The DSM-III diagnosis of schizophreniform disorder demonstrated 90% diagnostic efficiency in predicting response/nonresponse during treatment with lithium carbonate alone. A subgroup of the psychotic disorders was similar to affective disorders with respect to course of illness, biological characteristics, and response to lithium carbonate.
The cyclotron resonance equation predicts that the frequency of an applied magnetic field that might optimally interact with a single ion species may be computed as a function of the charge-to-mass ratio of the ion and the strength of the background static magnetic field. The present study was undertaken to discern the applicability of this equation for optimizing lithium ion utilization in the rat, as inferred by the predicted magnetic "ion resonance "field-induced shift of lithium's dose-dependent curve for seizure onset times (SOTs) when combined with the cholinergic agent pilocarpine. Groups of rats were administered 1.5 thru 3 mEq/kg lithium chloride (in 0.5 mEq/kg increments) and exposed to reference conditions or to one of three intensities (70 nanoTesla, 0.8 microTesla, or 25 microTesla) of a 85 Hz magnetic field calculated to resonate with lithium ions given the background static geomagnetic field of approximately 38,000 nanoTesla (0.38 Gauss). A statistically significant quadratic relationship for SOT as a function of magnetic field intensity (irrespective of lithium dose) was noted: this U-shaped function was characterized by equal SOTs for the reference and 25 microTesla groups, with a trend toward shorter SOTs for the 70 nanoTesla and 0.8 microTesla groups. Although not predicted by the equations, this report extends other findings suggestive of discrete intensity windows for which magnetic field frequencies derived from the cyclotron ion resonance equation may affect ion activity.
The serum lithium concentration was determined around the clock in patients treated with conventional tablets given once daily, in the evening, and in patients treated with slow-release tablets given twice daily, in the morning and in the evening. Curve shapes differed markedly in the two groups, with much wider variation of serum concentrations in the former than in the latter. The data were used to calculate for the two patient groups the ratio of the mean serum lithium concentration over the 24-h day to the serum lithium concentration in blood samples drawn 12 h after the last intake of lithium. Around-the-clock determinations of the patients' renal lithium clearance showed about 20% lower values during the night than during the day.
To examine the relations between erythrocyte sodium-lithium countertransport and renal proximal tubular sodium handling, we measured countertransport, and then subjected 30 normal and 32 hypertensive subjects, both white and black, to provocative maneuvers of volume expansion and contraction. The fractional excretions of sodium and lithium were measured simultaneously. In agreement with previous studies, we found that countertransport in erythrocytes was elevated in hypertensive patients compared with normal subjects. We also observed that whites have a higher level of countertransport than blacks. In the basal state, we found that fractional sodium excretion of hypertensive patients was no different than in normal subjects, whereas the fractional lithium excretion of hypertensive persons was increased compared with normotensive values. Volume expansion with 2 1 0.9% saline administered intravenously during a 4-hour period provoked an exaggerated natriuresis and a greater increase in fractional lithium clearance in hypertensive patients compared with the control group. With volume expansion and contraction, fractional lithium clearance and countertransport were directly correlated. Our data suggest that hypertensive persons do not have increased proximal tubular sodium reabsorption compared with normal subjects. Further, the exaggerated natriuresis of hypertension is, in part, the result of increased distal solute delivery. The fact that our hypertensive patients were older may partially explain the discrepancies between this report and previous observations.
The utility and side effects of sustained-release lithium carbonate (Priadel) in a once-per-day dose regimen was investigated with 66 male delinquents, ages 17-24 years, in a double-blind study comparing the antiaggressive effect of lithium carbonate with placebo. Serum lithium levels and symptoms were determined weekly for up to eight drug-free and 12 on-medication weeks. Average daily doses of 1500-1700 mg Priadel gave 24-hour serum lithium levels in the range 0.7-0.9 mEq/liter. Principal side effects were polyuria and shakiness, with other important side effects bring hand tremor, dryness of mouth, nausea, and weakness. No lithium toxicity was observed, and diarrhea was reported infrequently. Placebo response data are presented.
KEYWORDS: The structures of substituted (aminomethyl)lithium and (thiomethyl)lithium compounds have been examined. Geometric parameters, charge densities, bond orders, dipole moments and heats of formation for all the members of the two series of monomers and dimers of the units LiCN(R)2 and LiCSR where R=H, CH3(Me), C6H5(Ph) have been calculated. The structures of the three complex compounds containing the same units; [[Li(CH2SMe)(THF)]X], [Li2(CH2SPh)2(THF)4] and [Li2(CH2NPh2)2(THF)3] have also been modeled. Geometry optimizations have been performed with the semiempirical PM3 method. The molecular orbital calculations have been carried out by a self-consistent field method using the restricted Hartree-Fock formalism. Comparisons have been made with the corresponding properties of methyl lithium monomer and dimer. The results show that in all of the nitrogen-containing monomers, the C-Li bonds weaken and the Li-C-H(N) angles decrease due to the coordination of lithium with nitrogen. Substitution of hydrogen atoms by methyl or phenyl groups decreases the Li-N coordination. In the sulfur-containing compounds, sulfur behaves similarly to nitrogen but the changes are smaller because the 3p lone-pair orbital of sulfur is higher in energy than the 2p lone-pair of nitrogen. All the dimers of nitrogen/sulfur-containing methyl lithium derivatives form six-membered rings in which the Li-N(S) coordination is greater than the one in the corresponding monomers. Dimerization reactions have been found to be exothermic and the formation of all the dimers is favored. The results obtained for the three complex structures are comparable to the experimental results reported in the literature.
It has been proposed that lithium's antimanic action is due to an effect on phosphoinositide metabolism. Second messengers generated by this pathway regulate calcium mobilization and the activity of the serine and threonine kinase, protein kinase C (PKC). Included among the targets of PKC is activation of fos protooncogene expression, a well-established component of the AP-1 transcription factor. Because of these interactions, we investigated the effect of lithium on fos gene expression in PC12 pheochromocytoma cells. We find that lithium increases the level of fos mRNA that occurs in response to receptor and postreceptor activation of PKC. Treatment with lithium also leads to an augmentation of muscarinic cholinergic-mediated fos gene expression in cells that are down-regulated as a result of excessive cholinergic stimulation. The ability of lithium to enhance the response of a down-regulated cholinergic system suggests a model for its therapeutic efficacy in affective disorders.
Psychiatric life histories of 218 first degree family members of 16 lithium responsive and 33 lithium non-responsive psychotic (mood incongruent) probands were contrasted. While the morbid risk of schizophrenic spectrum disorder was 9.8% in the 142 relatives of lithium nonresponsive probands, no cases of schizophrenic spectrum disorder were found among the 76 first degree relatives of lithium responsive psychotics (p less than 0.03). Lithium responsive psychotic illnesses appear to be familially, and perhaps genetically distinct from the bulk of the schizophrenias.
Six offspring of manic-depressive patients, whose parents were lithium responders, were selected on the basis of their incapacitating psychopathology for treatment with lithium. The children ranged in age from 6 to 12. A double-blind, crossover design was used over 16-18 weeks. Weekly ratings were done, and average evoked potentials (EPs) were measured at each crossover. Two children diagnosed as having a bipolar affective disorder had a clear-cut response to lithium and were strong augmenters on the EP. This, taken together with the similarity of the EP changes on lithium to those occurring in adult patients treated with lithium, supports a physiological parallel between bipolar affective illness in adults and children.
In the particular case of boron and lithium we examine the possibilities of using stable isotopes for experiments of isotopic labelling and microlocalization, as no radioisotopes exist. The detection is made with the help of a specific nuclear reaction, using homogeneous detectors. The first experimental applications are given: transepithelial fluxes of lithium (frog skin) have shown Liefflux values larger than the influx ones. Detailed microlocalization of lithium have been made on histological preparations of mice having received lithium treatment: particularly important contents are found in the hypophysis, the salivary glands, the bladder, the kidney (especially the pelvis), the intestinal system and certain parts of the brain (particularly the hippocampus); the liver, however remains very poor in lithium. Physiological implications are examined.
BACKGROUND: This study aims to investigate whether the risk of recurrence following lithium discontinuation is less than reported in discontinuation of a successful, long-term prophylaxis in bipolar patients. METHODS: A total of 32 bipolar patients discontinued lithium according to the controlled lithium discontinuation (CLD) protocol following a definite good response to lithium maintenance of at least 5 years. Subjects were followed for up to 9 years. RESULTS: The total rate of recurrence was 7% in the first week, 32% in the first month, 62% in the first year, and 81% at the end of the 9th year following discontinuation. Only six of the 32 patients (19%) did not have a recurrence during the follow-up period. CONCLUSIONS: Discontinuation of lithium seems to be followed by a high rate of recurrence in bipolar patients even after good response to a long-duration illness-free period. A controlled discontinuation protocol can reduce the risks of morbidity.
Lithium treatment, initially considered specific for bipolar disorder, has since been shown to provide additional benefits in affective and other disorders. This variety of benefits should be taken into account when interpreting recently reported lower efficacy during lithium prophylaxis, as well as early relapses and loss of efficacy after lithium discontinuation. There are particularly striking parallels between these recent reports and earlier observations of "antipsychotic" lithium effects. Other factors, such as the accumulation of atypical, treatment-resistant patients in academic centers and, in particular, the broadening of diagnoses of affective disorders, further complicate the interpretation of the recent reports. Lithium, however, continues working well for patients with typical bipolar disorders, for whom it was originally proved effective.
Clinical and biochemical factors related to the activity of the erythrocyte lithium-sodium countertransport (LSC) system were investigated during lithium prophylaxis in 27 patients (13 male, 14 female) with bipolar affective illness. No relationship was found between erythrocyte LSC and such factors as age, gender, duration of lithium prophylaxis, quality of prophylactic lithium response, and family history of affective illness. There was a significant negative correlation between the activity of LSC and the magnitude of the erythrocyte lithium ratio both in whole group and in female patients. In seven patients with concomitant hypertension, the relationship between high activity of LSC and hypertension was not demonstrated. The levels of total cholesterol, HDL cholesterol, triglycerides, and potassium related neither to LSC activity nor to hypertension. Erythrocyte LSC in patients with lower TSH levels were significantly reduced compared to patients with higher TSH. The values of TSH were negatively correlated with T4 but not with T3. Concentrations of T3 were positively correlated with plasma total cholesterol levels. These results are discussed in the view of recent findings on erythrocyte LSC.
In a cross-sectional study of 237 patients treated with lithium for more than six months, 10 patients had serum thyroid stimulating hormone (TSH) values above 35 mU/l and concomitantly low triiodothyronine (T3) and abnormally low serum thyroxine (T4). Eight patients had TSH values of 10.0-34.9 mU/l, while T3 and T4 were within or close to the normal ranges. Most of the patients had TSH values of 0.9-9.9 mU/l and normal or close to normal T3 and T4 values. Three male patients had TSH below 0.9 mU/l, but normal T3 and T4 values. A retrospective investigation three years later showed that all patients with TSH above 35 mU/l had clinically diagnosed overt hypothyroidism and treated accordingly with either replacement therapy with thyroxine or discontinuation of the lithium treatment. The thyroid parameters normalized spontaneously in 2 out of 3 patients who had their lithium treatment discontinued, while one still needed replacement therapy 1 1/2 years after withdrawal of lithium. Five patients had been put on replacement therapy before the cross-sectional study. The frequency of overt hypothyroidism thus indicated a prevalence about ten times as high as should be expected. An overrepresentation of women was found in the group with TSH values above 10 mU/l, whereas the group with TSH values of 0.9-10.0 mU/l showed no such sex predomination. The age distribution was equal in all groups. TSH appeared to be the most efficient parameter in revealing undetected hypothyroidism in the present investigation of patients in long-term lithium treatment.
The possible presence of lithium transport beyond the proximal tubule was examined by measuring lithium excretion after administration of triamterene, a potassium-sparing diuretic, exclusively acting in the cortical collecting tubule. Eight young and healthy volunteers were studied on two occasions during maximal water diuresis. After obtaining baseline values triamterene (100 mg orally) or placebo was administered, and measurements continued for 4 hours. Creatinine clearance was used as a marker of glomerular filtration rate, and phosphate excretion was used as an additional marker of proximal sodium transport. Compared to placebo (P), triamterene (T) caused a significant increase in fractional excretion of sodium (P, 0.74 +/- 0.08%; T, 1.73 +/- 0.24%, mean +/- SEM; P less than 0.01), and lithium (P, 21.2 +/- 1.3%; T, 27.5 +/- 1.5%; P less than 0.01), whereas fractional excretion of phosphate remained unchanged (P, 9.8 +/- 1.3%; T, 9.4 +/- 1.5%; P = NS). These results indicate that lithium is transported in the cortical collecting tubule, and provide further evidence that the use of lithium as a marker of purely proximal tubular sodium transport is of limited value.