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PubMed2006

Lithium as adjuvant to radioiodine therapy in differentiated thyroid carcinoma: clinical and in vitro studies.

OBJECTIVE: Lithium has been reported to increase radioactive iodine (RaI) doses in benign thyroid disease and in differentiated thyroid carcinoma (DTC). It is not known whether lithium influences the outcome of RaI therapy in DTC. We therefore studied the clinical effects of RaI without and with lithium carbonate in patients with proven metastatic DTC. Controversy also exists on the mechanism by which lithium increases RaI dose in DTC. We performed an in vitro study specifically aimed at examining the effects of lithium on the sodium iodide symporter (NIS). DESIGN: In a clinical study, 12 patients were selected with metastases of DTC who had received previous RaI therapy without lithium (control) that had not influenced tumour progression, despite RaI accumulation in metastases. The patients received 1200 mg lithium carbonate/day followed by 6000 MBq RaI. Outcome parameters were RaI uptake, serum thyroglobulin (Tg) levels and radiological dimensions of metastases compared between RaI with lithium and control. In an in vitro study, iodide uptake was studied in the benign rat thyroid cell line FRTL-5, in the polarized non-thyroid MDCK cell line, stably transfected with human sodium iodide symporter (hNIS) to study the effects of lithium on NIS in a non-thyroid background, and the human follicular thyroid carcinoma cell line FTC133-hNIS to study lithium effects in a background of DTC. Lithium chloride (LiCl) was added in concentrations up to 2 mM for 0-48 h. Both steady-state iodide uptake (30 min) and initial rate (2 min) were studied using a specific activity of 100 mCi/mmol I, the latter experiment to determine lithium effects on substrate dependency. Iodide efflux studies were performed as well. RESULTS: Despite an increased uptake of RaI in seven patients, no beneficial effect of RaI with lithium was observed on the clinical course as assessed by serum Tg measurements and radiographically. In the in vitro studies, no effects of LiCl on iodide uptake or efflux were observed. CONCLUSIONS: The addition of lithium to RaI did not have any beneficial effects on the clinical course in 12 patients with metastatic DTC. No beneficial effects of lithium on iodide uptake were observed in vitro. Therefore, the clinical value of lithium in DTC remains subject to debate.

Adjuvants, Pharmaceutic↗
PubMed1990

Thyrotrophin-releasing hormone stimulates polyphosphoinositide metabolism in the frog neurointermediate lobe.

Previous studies have demonstrated that TRH is a potent stimulator of alpha-MSH secretion from frog pituitary melanotrophs. In order to determine the intracellular events responsible for TRH-evoked alpha-MSH release, we have investigated the effect of TRH on polyphosphoinositide breakdown in frog pars intermedia. Neurointermediate lobes were labelled to isotopic equilibrium with myo-[3H]inositol. TRH stimulated the rate of incorporation of [3H]inositol into the phospholipid fraction. The effect of TRH was concentration-dependent; half-maximal stimulation of alpha-MSH release and inositol incorporation occurred at 12 and 28 nmol TRH/l respectively. In prelabelled neurointermediate lobes, lithium (10 mmol/l) enhanced the radioactivity in inositol monophosphate, bisphosphate (IP2) and trisphosphate (IP3). LiCl (10 mmol/l) induced a 38% inhibition of alpha-MSH release from perifused neurointermediate lobes but did not impair TRH-induced alpha-MSH secretion. In the presence of LiCl, TRH (1 mumol/l) induced a transient increase of the radioactivity in IP3, which was evident by 30 s and maximal by 1 min (+100%). TRH treatment also increased the radioactivity in IP2, which reached a plateau after 5 min (+100%). The increase in radioactivity in IP3 induced by TRH was closely paralleled by a rapid loss of [3H]phosphatidylinositol bisphosphate (PIP2), which was maximal by 1 min (-70%). These results indicate that, in frog pars intermedia, TRH-evoked alpha-MSH secretion is coupled to breakdown of PIP2. The data suggest that, in amphibian melanotrophs, as previously shown in GH3 tumour cells and in rat pituitary mammotrophs, TRH causes rapid stimulation of polyphosphoinositide-hydrolysing phospholipase C.

Animals↗
PubMed2004

Geochemical precursors to volcanic activity at Mount St. Helens, USA.

The importance of the interplay between degassing and crystallization before and after the eruption of Mount St. Helens (Washington, USA) in 1980 is well established. Here, we show that degassing occurred over a period of decades to days before eruptions and that the manner of degassing, as deduced from geochemical signatures within the magma, was characteristic of the eruptive style. Trace element (lithium) and short-lived radioactive isotope (lead-210 and radium-226) data show that ascending magma stalled within the conduit, leading to the accumulation of volatiles and the formation of lead-210 excesses, which signals the presence of degassing magma at depth.

Journal Article↗
PubMed1987

Stimulation of phosphoinositide hydrolysis in myelin by muscarinic agonist and potassium.

Slices of rat brainstem that had been prelabeled by in vivo injection of [3H]inositol were stimulated with carbachol in the presence of lithium and changes measured in the radioactivity of inositol lipids and water-soluble inositol phosphates. For the latter, significant increases were seen for inositol mono- and bisphosphate but not inositol trisphosphate. Analysis of whole tissue phosphoinositides revealed significantly reduced radioactivity in phosphatidylinositol and phosphatidylinositol 4-phosphate, whereas myelin showed decreases in those as well as phosphatidylinositol 4,5-bisphosphate. These effects were blocked by atropine. Stimulation of the tissue slices with elevated K+ resulted in increased formation of inositol phosphate and decreased radioactivity in phosphatidylinositol. The effect was not blocked by atropine and in the presence of this agent, which reduced background reaction, all 3 phosphoinositides showed significant K+-induced loss of label. Elevated K+ and carbachol thus function through different mechanisms in this system. Carbachol is believed to affect myelin phosphoinositides through direct interaction with muscarinic receptors which were recently shown to be present in this membrane.

Animals↗
PubMed1967

Ecological dosimetry: radiation levels influenced by plant growth.

The feasibility of using lithium-7-fluoride thermoluminescent dosimeters under field conditions for natural radiation at levels of 5 milliroentgens is demonstrated. Radiation dosages in tree trunks increased threefold from winter to spring and summer. This increase is attributed to the gamma radiation field resulting from relatively high levels of potassium-40 and other radionuclides present in the foliage and branches during the growing season.

Ecology↗
PubMed1982

Stable isotopes of lithium: in vivo differential distribution between plasma and cerebrospinal fluid.

Stable and radioactive isotopes of an element have been utilized to study a variety of complex phenomena including metabolic pathways and enzyme reactions. It is generally assumed that isotopes of an element are not treated in a differential manner. Nevertheless we have demonstrated that the two stable isotopes of lithium (Li), one of mass 6 and the other with a mass of 7, are differentially taken up by red blood cells with 6-8% higher quantities of 6-lithium (6Li) being accumulated. We report here on the in vivo pharmacokinetics of Li isotopes. Nineteen adult cats were given a single dose of either 6LiCl by gastric intubation (1 meq/kg) and 2 weeks later the treatment was crossed. Plasma concentrations of the two Li isotopes were determined. In another series of studies 19 adult cats were given either 6LiCl or 7LiCl by intubation, cerebrospinal fluid (CSF) and blood samples were collected simultaneously and isotropic Li concentrations of the spinal fluid and plasma were determined. The average plasma concentration of 6Li was higher than 7-lithium (7Li) between 2 and 9 hr postadministration. The elimination curve for both isotopes had an initial fast and later slow component. For the slow component 6Li had an average half-life of 12.9 and 7Li 15.9 hr. Comparison of the CSF/plasma ratio for 6Li and for 7Li indicated that the ratios were higher for 6Li than 7Li 2-6 hr after administration. These data suggest that factors in addition to concentration gradients influence the transport of Li isotopes across the blood-brain barrier. These studies demonstrate the acute pharmacokinetics of the two Li isotopes are not the same in compartmental distribution and rate of disappearance from plasma. It is conceivable 6Li may have a greater toxic or therapeutic effect than 7Li in the treatment of manic-depressive illness.

Administration, Oral↗
PubMed2004

Tracer diffusion measurements in solid lithium: a test case for the comparison between NMR in static and pulsed magnetic field gradients after upgrading a standard solid state NMR spectrometer.

This paper reports on the upgrading of a standard solid state NMR spectrometer, which has been used in combination with a field variable 7 T cryomagnet, to a low-cost combined SFG and PFG NMR spectrometer. Both methods are applied to solid lithium as a simple test case. The results show that under the given conditions SFG NMR and PFG NMR can provide tracer diffusion coefficients for 7 Li diffusion down to about 10(-14) and 10(-13) m2/s, respectively. SFG and PFG NMR are complementary methods. The paper demonstrates advantages and disadvantages of each method with a concrete example and why it is desirable to be able to apply both methods to the same sample.

Diffusion↗
PubMedDate not supplied

Transport of a reactive tracer in saturated alluvium described using a three-component cation-exchange model.

A weakly sorbing cation, lithium, will be used as a reactive tracer in upcoming field tracer tests in the saturated alluvium south of Yucca Mountain, Nevada. One objective of the field tests is to determine how well field-scale reactive transport can be predicted using transport parameters derived from laboratory experiments. This paper describes several laboratory lithium batch sorption and column transport experiments that were conducted using ground water and alluvium obtained from the site of the planned field tests. In the batch experiments, isotherms were determined over 2.5 orders of magnitude of lithium concentrations, corresponding to the range expected in the field tests. In addition to measuring equilibrium lithium concentrations, concentrations of other cations, namely Na(+), K(+), and Ca(2+), were measured in the batch tests to determine Li(+)-exchangeable equilibria. This information was used in conjunction with alluvium cation exchange capacity measurements to parameterize a three-component cation-exchange model (EQUIL) that describes lithium sorption in the alluvium system. This model was then applied to interpret the transport behavior of lithium ion in saturated alluvium column tests conducted at three different lithium bromide injection concentrations. The concentrations were selected such that lithium ion either dominated, accounted for a little over half, or accounted for only a small fraction of the total cation equivalents in the injection solution. Although tracer breakthrough curves differed significantly under each of these conditions, with highly asymmetric responses occurring at the highest injection concentrations, the three-component cation-exchange model reproduced the observed transport behavior of lithium and the other cations in each case with a similar set of model parameters. In contrast, a linear K(d)-type sorption model could only match the lithium responses at the lowest injection concentration. The three-component model will be used to interpret the field tests, with the expectation that it will help refine estimates of effective flow porosity, particularly if the lithium response curves are asymmetric.

Adsorption↗
PubMed1997

TFIIF, a basal eukaryotic transcription factor, is a substrate for poly(ADP-ribosyl)ation.

We have examined the susceptibility of some of the basal eukaryotic transcription factors as covalent targets for poly(ADP-ribosyl)ation. Human recombinant TATA-binding protein, transcription factor (TF)IIB and TFIIF (made up of the 30 and 74 kDa RNA polymerase II-associated proteins RAP30 and RAP74) were incubated with calf thymus poly(ADP-ribose) polymerase and [32P]NAD+ at 37 degrees C. On lithium dodecyl sulphate/PAGE and autoradiography, two bands of radioactivity, coincident with RAP30 and RAP74, were observed. No radioactivity co-migrated with TATA-binding protein or TFIIB. The phenomenon was dependent on the presence of nicked DNA, which is essential for poly(ADP-ribose) polymerase activity. Covalent modification of TFIIF increased with time of incubation, with increasing TFIIF concentration and with increasing NAD+ concentration. High-resolution PAGE confirmed that the radioactive species associated with RAP30 and RAP74 were ADP-ribose polymers. From these observations, we conclude that both TFIIF subunits are highly specific substrates for covalent poly(ADP-ribosyl)ation.

Animals↗
PubMed2006

The substrate specificity of a neuronal glutamate transporter is determined by the nature of the coupling ion.

Glutamate transporters are essential for terminating synaptic transmission. Glutamate is translocated together with three sodium ions. In the neuronal glutamate transporter EAAC1, lithium can replace sodium. To address the question of whether the coupling ion interacts with the 'driven' substrate during co-transport, the kinetic parameters of transport of the three substrates, L-glutamate and D- and L-aspartate by EAAC-1 in sodium- and lithium-containing media were compared. The major effect of the substitution of sodium by lithium was on Km. In the presence of sodium, the values for Km and Imax of these substrates were similar. In the presence of lithium, the Km for L-aspartate was increased around 13-fold. Remarkably, the corresponding increase for L-glutamate and D-aspartate was much larger, around 130-fold. In marked contrast, the Ki values for a non-transportable substrate analogue were similar in the presence of either sodium or lithium. The preference for L-aspartate in the presence of lithium was also observed when electrogenic transport of radioactive substrates was monitored in EAAC1-containing proteoliposomes. Our results indicate that, subsequent to substrate binding, the co-transported solutes interact functionally in the binding pocket of the transporter.

Amino Acids, Dicarboxylic↗
PubMedDate not supplied

Hyperthyroidism during lithium therapy for depression.

OBJECTIVE: To report three cases of hyperthyroidism encountered within a period of 32 months in patients receiving lithium therapy for depression. METHODS: Three detailed case reports are presented, and the related literature is discussed. RESULTS: Although hypothyroidism during lithium therapy is well recognized and documented, appearance of cases of hyperthyroidism during lithium therapy is considered uncommon. The antithyroid effect of lithium through inhibition of generation of cyclic adenosine monophosphate tends to mask the underlying hyperthyroidism. Nevertheless, during a 32-month period, three cases of hyperthyroidism were encountered in patients who had received lithium treatment (900 to 1,200 mg/day) for 7 months to 17 years. These patients had symptoms of heat intolerance, palpitations, and tremor, and they were subsequently treated successfully with radioactive iodine. CONCLUSION: Most likely, cases of hyperthyroidism that occur during lithium therapy may be under-diagnosed, underreported, or both.

Journal Article↗
PubMed1968

Occurrence of goitre during lithium treatment.

Of 330 patients given lithium for recurrent manic-depressive disorder 12 developed goitre after treatment periods of five months to two years. All the patients remained clinically euthyroid. Pressure symptoms necessitated subtotal thyroidectomy in two patients. In 9 out of 10 patients with goitre, and in two out of seven without goitre study with radioactive iodine showed abnormal findings in iodine metabolism. Discontinuance of lithium led to disappearance of goitres, while thyroid metabolism returned to normal. Thyroxine or desiccated thyroid produced shrinkage of the gland in spite of continued lithium medication.

Adolescent↗