Resistance of Saccharomyces to high concentrations of lithium chloride.
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Effects of lithium chloride on growth, differentiation and respiration of Herpetomonas samuelpessoai, cultivated in a synthetic medium were studied both at 28 and 37 degrees C. Low concentration of lithium chloride (15 mM) stimulated growth at 37 degrees C. In addition, the protozoon tolerated high concentrations (60-150 mM) of the salt at both incubation temperatures. In general, 15 mM lithium chloride increased and 150 mM decreased oxygen uptake when glucose, glutamic acid and proline were used as substrates. However, at 28 degrees C after incubation for 96 h, the highest concentration increased oxygen uptake in the presence of glucose. Sodium butyrate induced cell differentiation in H. samuelpessoai both at 28 and 37 degrees C. High concentration (150 mM) of lithium chloride inhibited cell differentiation of H. samuelpessoai induced by both controlled growth conditions and butyrate addition. The results obtained are described in this paper.
OBJECTIVE: To investigate the effects of lithium chloride on the proliferation and apoptosis of human leukemia cell line (K562). METHODS: The effects of lithium chloride on the proliferation of K562 leukemia cells were evaluated by liquid culture assay, MTT assay, and colony formation assay. The effects of lithium chloride on the apoptosis of K562 leukemia cell were verified by cellular morphology and the agarose gel electrophoresis of DNA fragments. RESULTS: 1. The proliferation of K562 leukemia cells was inhibited by lithium chloride (10-50 mmol/L) in a dose-dependent manner. 2. With lithium chloride (30 mmol/L), the apoptosis cells could be observed in cellular morphology, and DNA ladder was also observed in agarose gel electrophoresis. CONCLUSION: Lithium chloride can inhibit the proliferation of K562 cells and cause the apoptosis of K562 cells.
The preexposure paradigm was utilized to evaluate the similarity of ionizing radiation, lithium chloride and ethanol as unconditioned stimuli for the acquisition of a conditioned taste aversion. Three unpaired preexposures to lithium chloride (3.0 mEq/kg, IP) blocked the acquisition of a taste aversion when a novel sucrose solution was paired with either the injection of the same dose of lithium chloride or exposure to ionizing radiation (100 rad). Similar pretreatment with radiation blocked the acquisition of a radiation-induced aversion, but had no effect on taste aversions produced by lithium chloride (3.0 or 1.5 mEq/kg). Preexposure to ethanol (4 g/kg, PO) disrupted the acquisition of an ethanol-induced taste aversion, but not radiation- or lithium chloride-induced aversions. In contrast, preexposure to either radiation or lithium chloride attenuated an ethanol-induced taste aversion in intact rats, but not in rats with lesions of the area postrema. The results are discussed in terms of relationships between these three unconditioned stimuli and in terms of implications of these results for understanding the nature of the proximal unconditioned stimulus in taste aversion learning.
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OBJECTIVE: We have previously described an indicator dilution technique of measuring cardiac output in which lithium chloride is injected as a bolus via a central venous catheter and cardiac output derived from the arterial lithium dilution curve recorded from a lithium-selective electrode, which we have developed for this purpose. It would be an advantage if the lithium could be injected via the basilic vein (in the antecubital fossa) in those patients who do not need central venous catheterisation for other reasons. We have therefore compared cardiac output measurements made using these two routes of lithium chloride administration. METHODS: Lithium dilution cardiac output was measured 10 times in each of 10 patients, injecting the lithium chloride alternately via the basilic or central venous catheter. RESULTS: The mean difference was 0.8 +/- 5.2% (SD) (range -8.5 to +7.0%) over a range of cardiac output of 4.5-13 l/min. CONCLUSIONS: Injection of lithium chloride via the basilic vein in the antecubital fossa allows accurate lithium dilution cardiac output measurements to be made in patients who do not have central venous catheters in place.
Chronic treatment with lithium chloride produced significant involution of the thymus gland with histological evidence of reduced cellularity due to loss of thymic lymphocytes and a significant reduction in the weight of the gland in normal and adrenalectomized mice. Lithium also increased corticosterone levels in normal mice without changes in adrenal weights. The involution of the thymus gland is most likely due to an effect of lithium on the gland, and it is not mediated by adrenocortical mechanisms or stress.
Lithium chloride was injected subcutaneously to mice (in amounts of 500 and 300 mg/kg) once a day for 10 and 15 days, and to rabbits in single doses via a tube into the stomach (in amounts of 400 and 850 mg/kg). After different time intervals following a single or course-wise administration of the compound the level of total lipids was determined in the muscles and liver of the mice, and of the total lipids, beta-lipoproteins, phospholipids, cholesterol, fatty acids and 11-oxycorticosteroids levels in the blood serum of rabbits and of the bile acids content in the vesical bile of these animals. Hyperlipemia that developed under the effect of lithium was caused by mobilization of fat from fat depots and by deranged interstitial lipids metabolism.
A nutrient medium containing 0.7 per cent of lithium chloride was tested and Yersinia pestis inhibitor was detected in 83.3 per cent of the strains on the growth tufts of 8 indicator strains isolated from a homologous focus. Lowering the lithium chloride concentration in the medium up to 0.6 per cent promoted detection of the inhibitor in a larger number of the tested strains (93.3 per cent). But even on this medium none of the indicator strains formed overall growth tufts. The subcultures of the indicator strains resistant to lithium chloride formed overall growth tufts on agar plates with lithium chloride and were sensitive to the inhibitor of the tested strains from the central Caucasus. However, during storage they lost their sensitivity to the inhibitor which did not permit their use as the test cultures.
Previously we reported that lithium chloride (LiCl) potentiates tumor necrosis factor (TNF)-mediated cytotoxicity in vitro and in vivo. Here, using a murine normal skin model, it is shown that a subcutaneous injection of TNF plus LiCl induces acute dermal and subcutaneous inflammation and necrosis. Histology showed a marked initial dermal and subcutaneous neutrophil infiltrate by approximately 2 hours, followed by a predominantly mononuclear infiltrate by 24 hours, which remained present for several days. Tumor necrosis factor or LiCl alone induced negligible inflammation, disappearing after 6 hours; furthermore there was never necrosis or ulceration of the overlying skin in case of single-agent application. In vitro studies showed that the combination of TNF and LiCl, but not either agent alone, was directly cytotoxic to fibroblastic cells of murine skin. No inflammatory infiltration was visible in tumors treated intratumorally or perilesionally with TNF plus LiCl, although the latter treatment resulted in a perilesional leukocyte infiltration. Furthermore the combination of TNF and LiCl had no effect on macrophage cytotoxicity to L929 tumors.
These experiments were designed to determine whether treatment with two subthreshold doses of radiation or lithium chloride, either alone or in combination, could lead to taste aversion learning. The first experiment determined the thresholds for a radiation-induced taste aversion at 15-20 rad and for lithium chloride at 0.30-0.45 mEq/kg. In the second experiment it was shown that exposing rats to two doses of 15 rad separated by up to 3 hr produced a taste aversion. Treatment with two injections of lithium chloride (0.30 mEq/kg) did not produce a significant reduction in preference. Combined treatment with radiation and lithium chloride did produce a taste aversion when the two treatments were administered within 1 hr of each other. The results are discussed in terms of the implications of these findings for understanding the nature of the unconditioned stimuli leading to the acquisition of a conditioned taste aversion.
The possible effect of lithium chloride, a compound which reduces the incidence of infection in cancer patients, was investigated on murine melanoma. C57 BL syngeneic mice were inoculated i.p. with B16 melanoma cells. The animals were divided into 4 groups, receiving daily i.p. treatment with saline--group 1, controls; lithium chloride--group 2, bleomycin and vinblastine--group 3, and lithium chloride with bleomycin and vinblastine--group 4. Animals in group 4 had a significant delay in tumour appearance, a higher degree of tumour necrosis, and a longer survival rate. In addition a significant reduction of serum lithium concentration was noted in animals of this group in comparison with animals in group 2, treated with lithium chloride alone. There was no lithium-induced leukocytosis.
Immunohistochemistry was used to map c-fos expression in rats to investigate the neural substrates that mediate the emetic action of lithium chloride and the effect of osmotic pressure. Solutions of 3% lithium chloride or 4.14% saline, isotonic to each other, as well as 0.65% lithium chloride or 0.9% saline, also isotonic to each other, were administered intraperitoneally (3 ml/kg) in rats. Both lithium chloride and osmotic pressure enhanced c-fos expression in the nuclei of the solitary tract, the paraventricular nuclei and supraoptic nuclei of the hypothalamus, and in the amygdala. This suggests that these brain structures might be the sites where the autonomic, neuroendocrine and behavioral responses elicited by lithium chloride and osmotic pressure are integrated.
Studies in human embryo fibroblasts infected with measles or herpes simplex virus showed a reduction in virus yield when cultures were pretreated with 1-10 mM lithium chloride doses. Maximum effect was obtained by a 1 h treatment with 10 mM lithium chloride, preceding viral infection by 19-24 hours. A specific antiviral effect against measles virus was manifest immediately after culture pretreatment. Intermittent treatment with 10 mM lithium chloride of cultures persistently infected with measles or herpes virus obtained from human myeloid K-562 cell line shows a reduction in the extracellular virus yield. In the K-562/herpes virus system, the culture treatment with lithium chloride and acyclovir (10 microM) has an additive inhibitory effect on virus production. The paper is focused on the mechanism of lithium chloride antiviral action and the expediency of lithium therapy in SSPE (subacute sclerosing panencephalitis).
Lithium salt has been widely used as a treatment for mania, but the mechanism of its effect remains unknown. Previously, by studying c-fos expression, we showed that the striatum was a possible target region for the antimanic effects of lithium salt. The present study focused on the effect of subchronic lithium chloride treatment on G-proteins (Golf, Ggamma7) and adenylyl cyclase type V, which are expressed specifically in the rat striatum. Subchronic lithium chloride treatment significantly increased the level of Golf protein, a stimulant alpha-subunit of G-protein, by 53.5% (P<0.01), but the levels of Ggamma7 and adenylyl cyclase type V did not change. This increased level of Golf protein was found after 2 weeks of lithium chloride treatment, but not after 1 week, and the level returned to the basal level 1 week after withdrawal of lithium chloride. This result suggests that the level of Golf protein increases to compensate for the suppression of the adenylyl cyclase system by lithium, and that this increase may account for the "rebound" phenomenon, which is the relapse observed after abrupt discontinuation of lithium salt treatment.
Denaturation of ribonuclease-A by lithium chloride has been studied using difference spectral, circular dichroic and viscometric measurements. The difference spectral results were interpreted in the light of our observations that the solvent effect of the denaturant on the tyrosyl residue is non-linear. It has been observed that (1) the lithium chloride-denatured protein contains 3% alpha-helix and 18% beta-structure, and (2) only two of the three buried tyrosyl residues are normalized in the denatured protein.
Male inbred rats were used to determine the lethal dose of lithium chloride. The rats were 3 weeks, 6 weeks, 3 months and 6 months old, and lithium chloride was given intraperitoneally, subcutaneously and orally. In relation to age, LD50 was significantly higher in rats of 6 weeks after oral administration than LD50 in rats of 3 and 6 months. No differences were found following intraperitoneal and subcutaneous administration. In relation to route of administration, LD50 was significantly higher in rats of 3 and 6 weeks after oral administration than LD50 after intraperitoneal and subcutaneous administration. This difference was not found in rats of 3 and 6 months. It is concluded that age and route of administration are of significance for LD50 of lithium chloride in the rat.