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PubMed1998

Growth inhibitory effect of lithium gammalinolenate on pancreatic cancer cell lines: the influence of albumin and iron.

Essential fatty acids, especially gamma linolenic (GLA) and eicosapentaenoic acids, have been proposed as potential anticancer drugs. Our aim was to study the effect of the lithium salt of gamma linolenic acid (LiGLA) on the growth of two human pancreatic cancer cell lines (MIA PaCa2 and Panc 1) and primary human fibroblasts (HFF 5) in vitro. Cell growth was assessed by a microculture tetrazolium (MTT) assay. LiGLA had a selective growth inhibitory effect on pancreatic cancer cell lines with 50% growth inhibition (IC50) at approximately 6-16 mumol/l compared with approximately 111 mumol/l for the fibroblasts. The degree of growth inhibition increased with the time of exposure to LiGLA. Special attention was paid to the influence of albumin and iron on LiGLA-mediated growth inhibition. Albumin incorporated into essentially serum-free culture medium inhibited the effect of LiGLA in a dose-dependent manner, associated with reduced GLA uptake by cancer cells. Ferric ions were confirmed as potentiators of the growth inhibitory effect of LiGLA but more physiologically relevant transferrin-bound iron was ineffective. With further improvements in the fatty acid delivery mechanism, LiGLA may become a useful adjunct in the management of pancreatic cancer patients.

Albumins↗
PubMed1994

Toxicity, uptake, and mutagenicity of particulate and soluble nickel compounds.

Toxicity testing in AS52 cells (24-hr exposures) gave LC50 values of 2 to 130 micrograms Ni/ml for particulate nickel compounds and 45 to 60 micrograms Ni/ml for water-soluble salts (NiCl2, NiSO4, Ni(CH3COO)2). The Ni(OH)2, NiCO3, and sulfides (Ni3S2, Ni7S6, "amorphous NiS") exhibited similar toxicities (LC50's of 2 to 8 micrograms Ni/ml), while three nickel oxides were more variable and less toxic (LC50's of 18 to 130 micrograms Ni/ml). Most compounds displayed nuclear to cytoplasmic nickel ratios of approximately 1:1.5 to 1:5 (except approximately 1:20 for nickel salts). At the LC50's, a 75-fold range in exposure levels occurred compared to a 10-fold range in cytoplasmic and nuclear nickel concentrations, [Ni]. Cellular nickel distribution indicated three groupings: inert compounds (green NiO, lithium nickel oxide, relatively low nuclear and cytosolic [Ni]); water-soluble salts (very low nuclear [Ni]; high cytosolic [Ni]), and slightly soluble compounds (relatively high cytosolic and nuclear [Ni]). Nickel compounds are considered to be only weak or equivocal mutagens. In this study, a low but significant increase in mutation rate at the gpt locus was shown. Although the results would not be sufficient to deem nickel compounds mutagenic by traditional criteria, characterization by PCR analysis indicated that the spontaneous and nickel-induced mutants exhibited different and compound-specific mutational spectra (thus confirming nickel compound involvement). The results reported illustrate some of the methodologic problems involved in testing "weak" mutagens and indicate that alternative approaches may be necessary in classifying the mutagenicity of nickel and other compounds.

Animals↗
PubMed1982

Acute and chronic effects of lithium in therapeutically relevant concentrations on potassium uptake into astrocytes.

Potassium uptake into astrocytes in primary cultures was measured by the aid of 42K. Acute application of lithium in concentrations of 1 and 5 mM, but not 0.5 und 0.25 mM, exerted a significant inhibition of the potassium uptake rates. This effect is due to a partial impairment of the ouabain-sensitive part of the uptake into the cells caused by a lithium interaction with the extracellular K+-activated site of the Na+, K+-ATPase. After 14 days of exposure of the astrocytes to 1 mM lithium, the potassium uptake remained lower in the presence of lithium than in its absence. However, the cells had adjusted to the chronic presence of lithium by increasing their potassium uptake to such an extent that, during the exposure to 1 mM lithium, it was indistinguishable from that in cultures from the same batches grown in the absence of lithium and measured in the absence of this compound. The interference by lithium with potassium uptake into astrocytes may well be related to the inhibition of potassium clearance in the CNS described in the literature.

Astrocytes↗
PubMed2003

High lithium ionic conductivity in the lithium halide hydrates Li3-n(OHn)Cl (0.83 < or = n < or = 2) and Li3-n(OHn)Br (1 < or = n < or = 2) at ambient temperatures.

Lithium ionic conductivity and phase transitions in a series of lithium halides hydrates and hydroxides with general formula Li3-n(OHn)X (0.83 < or = n < or = 2; X = Cl,Br) were studied using impedance measurements and 1H and 7Li NMR spectroscopy. All compounds studied in this work crystallize in the antiperovskite structure or are closely related to this structure type. With the exception of LiCl. H2O, all compounds with integer lithium content exhibit good lithium ionic conductivity in their high temperature cubic phases above T = 33 degrees C. Lithium doping of samples LiX.H2O and Li2(OH)X leads to a suppression of the phase transition into the noncubic phases and the good ionic conductivity is extended down to lower temperatures (T < 0 degree C). Thus, lithium doping of the lithium halide hydrates provides a promising tool for tailoring the ionic conductivity at ambient temperatures to its optimum value.

Journal Article↗
PubMedDate not supplied

Effect of human chorionic gonadotrophin coadministration on the activities of ovarian Delta5-3beta-hydroxysteroid dehydrogenase, and 17beta-hydroxysteroid dehydrogenase, and ovarian and uterine histology in lithium chloride-treated albino rats.

Lithium chloride, a compound with clinical use in bipolar disorder, produces adverse effects on ovarian function in amphibian and rodent models. This study examined the effect of human chorionic gonadotrophin coadministration on ovarian steroidogenic and gametogenic activities in lithium chloride-treated rats. Relative ovarian and uterine weights, ovarian Delta(5)-3beta-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid dehydrogenase activities, folliculogenesis, uterine diameter, endometrial and myometrial thickness, and uterine luminal epithelial height were decreased significantly after lithium chloride treatment for 28 days at 1.6 mg/kg/day, the human therapeutic dose. These parameters were unchanged from the control level when subcutaneous (s.c.) human chorionic gonadotrophin (hCG) at 25 microg/kg/day was coadministered with the lithium chloride. The duration of the oestrous cycle was increased in lithium chloride-treated rat with longer metestrous and diestrous phases. Administration of hCG with lithium chloride prevented these estrous cycle alterations. We conclude that hCG can protect ovarian steroidogenic and gametogenic function after lithium chloride treatment.

17-Hydroxysteroid Dehydrogenases↗
PubMed1983

The effect of lithium chloride on tumour appearance and survival of melanoma-bearing mice.

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.

Animals↗
PubMed2002

[P,P-Di-tert-butyl-N-trimethylsilyl-P-(trimethylsilylamino)phosphine imidato-kappa2N,N']bis(pyridine-kappaN)lithium(I).

In the title compound, [Li(C(14)H(36)N(2)PSi(2))(C(5)H(5)N)(2)], the bulky chelating monoanionic P,P-di-tert-butyl-N-trimethylsilyl-P-(trimethylsilylamino)phosphine imidate ligand and two pyridine ligands bind to Li in a pseudo-tetrahedral arrangement with twofold symmetry. The Li-N(phosphine) distance is 2.048 (5) A, while the Li.P distance is 2.520 (6) A.

Journal Article↗
PubMed2004

Tris(oxalato)phosphorus acid and its lithium salt.

The conversion of three equivalents of anhydrous oxalic acid with phosphorus pentachloride yields tris(oxalato)phosphorus acid 1, which crystallizes from diethyl ether solutions as protonated diethyl ether complex [(Et2O)2H](+)[P(C2O3)3)]-. The superacidic compound can be used as catalyst for Friedel-Crafts-type reactions. Upon neutralization with lithium hydride, the lithium salt Li[P(C2O3)3] 2 is obtained, which is highly soluble in aprotic solvents and which exhibits a wide voltage window. Thus, the lithium compound is a promising candidate as electrolyte for high performance non-aqueous batteries.

Journal Article↗
PubMed2004

Formation of benzynes from 2,6-dihaloaryllithiums: mechanistic basis of the regioselectivity.

The key elimination step for the formation of 3-chloro- and 3-fluorobenzyne from 2-chloro-6-fluorophenyllithium displays a pronounced solvent-dependent regioselectivity. 6Li and 13C NMR spectroscopic studies on 2-chloro-6-fluorophenyllithium reveal a single monomeric aryllithium, suggested by DFT computational studies to be a trisolvate. Rate studies indicate that the elimination of LiCl and LiF proceeds via trisolvated and disolvated monomers, respectively.

Benzene Derivatives↗
PubMed1995

Norepinephrine metabolism and psychoactive drugs in the endogenous depressions. 1968.

After intraventricular injection of norepinephrine-H3, the concentration of norepinephrine, of normetanephrine and of the deaminated catechols in rat brains was determined, following action of imipramine, desmethylimipramine, chlorpromazine, lithium chloride or cocaine. Following administration of imipramine, desmethylimipramine, and chlorpromazine, norepinephrine concentration decreased significantly at first, had distinctly increased 4.5 hours after imipramine and desmethylimipramine but was normal once again after chlorpromazine. Normetanephrine concentration increased after imipramine and desmethylimipramine but was unchanged after chlorpromazine. Under the effect of these drugs, the deaminated catechols showed no changes compared with control values. Cocaine resembled the antidepressants, but the amount of deaminated compounds was reduced. Lithium chloride, on the other hand, increased the concentration of deaminated catechols under certain conditions, reduced normetanephrine concentration but did not influence norepinephrine concentration. In addition to the animal experiments, the following data of six patients with an "endogenous" depression were recorded over a period of several weeks: the clinical findings by means of the Hamilton Depression Rating Scale, and the excretion of normetanephrine and of vanillylmandelic acid (VMA) in the urine before, during and after treatment with imipramine. The therapy led to a significant reduction of VMA; however, this reduction cannot be correlated with an improvement in the clinical findings. On the other hand, excretion of normetanephrine is apparently not dependent on the administration of imipramine but seems to reflect the clinical state, since improvement of the depression was regularly combined with an increased excretion of normetanephrine.

Animals↗
PubMedDate not supplied

[Effect of the enteric sorbent noolit on the psychoemotional status in mice].

The enterosorbent noolit (representing a mineral matrix base with immobilized lithium and silicon compounds) significantly affects the psychoemotional state of mice with depression model induced by prolonged social emotional stress. Noolit administration produces a pronounced anxiolytic and antidepressant effect and reduced the level of behavioral deficiency in the test animals.

Animals↗
PubMed2006

Application of the lithium and magnesium initiators for the synthesis of glycolide, lactide, and epsilon-caprolactone copolymers biocompatible with brain tissue.

The subject of this work is new method of the synthesis of biodegradable copolymers compatible with brain tissue. Copolymerization of glycolide with lactide was conducted in solution or in bulk in the presence of LiBu, LiAcac, MgBu(2), Mg(acac)(2) as initiators. In all cases, copolymers with molecular weight of 20000-40000 were obtained, which enables to use them as drug carriers. During the reactions of copolymer chain growth, the intermolecular transesterification occurs, changing the distribution of comonomeric units in copolymer chain. Magnesium initiators showed a lower contribution to transesterification in comparison with lithium and calcium compounds. The copolymerization of glycolide with epsilon-caprolactone using magnesium compounds as initiators was also described. The random glycolide/epsilon-caprolactone copolymer (10/90) obtained with MgBu(2) was used in in vivo study in the forms of microspheres and foils. Complete degradation of microspheres during 6 weeks was observed after the implantation to brain tissue. All implanted copolymers are compatible with brain tissue.

Absorbable Implants↗