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At least 19 recordsLinked to original sources
PubMedDate not supplied

Alterations in the metabolism of choline-containing phospholipids by lithium and carbachol in SH-SY5Y neuroblastoma cells.

To investigate choline phospholipid metabolism in the human neuroblastoma cell line SH-SY5Y, cultures labeled with [14C-methyl]choline were incubated for up to 30 min in Krebs-Ringer-glucose-N-2-hydroxyethyl-piperazine-N1-2-ethane sulfonic acid (HEPES) buffer with or without 10 mmol/L LiCl. When desired, 1 mmol/L of the muscarinic agonist carbamoylcholine was present during the last minute of incubation. When cells were exposed for 10 min to lithium, radioactivity in phosphatidylcholine, lysophosphatidylcholine, and sphingomyelin was 40%-140% higher than in controls incubated in buffer only. This contrasted with the results from carbamoylcholine-containing incubations, which gave radioactivities lower than or equal to controls. Carbamoylcholine added to the LiCl-containing incubations yielded results only minimally different from LiCl alone. Phosphorylcholine radioactivity was also elevated by about 50% after 10 min incubation with LiCl with or without added carbamoylcholine, but was not increased in incubations with the agonist by itself. Similar changes were observed for intracellular choline but after only 5 min. These data suggest that carbamoylcholine does not stimulate phosphatidylcholine degradation, whereas LiCl can significantly affect its metabolism and may affect signal transduction via second messengers in human neuroblastoma cells.

Carbachol↗
PubMedDate not supplied

Diagnosis and treatment of Graves disease.

OBJECTIVE: To review the etiology, diagnosis, and clinical presentation of Graves disease and provide an overview of the standard and adjunctive treatments. Specifically, antithyroid drugs, beta-blockers, inorganic iodide, lithium, and radioactive iodine are discussed, focusing on current controversies. DATA SOURCES: Primary articles were identified through a MEDLINE search (1966-July 2000). Key word searches included beta-blockers, Graves disease, inorganic iodide, lithium, methimazole, and propylthiouracil. Additional articles from these sources and endocrinology textbooks were also identified. We agreed to include articles that would highlight the most relevant points, as well as current areas of controversy. DATA SYNTHESIS: Graves disease is the most common cause of hyperthyroidism. The 3 main treatment options for patients with Graves hyperthyroidism include antithyroid drugs, radioactive iodine, and surgery. Although the antithyroid drugs propylthiouracil (PTU) and methimazole (MMI) have similar efficacy, there are situations when 1 agent is preferred. MMI has a longer half-life than PTU, allowing once-daily dosing that can improve patient adherence to treatment. PTU has historically been the drug of choice for treating pregnant and breast-feeding women because of its limited transfer into the placenta and breast milk. Adjuvant therapies for Graves disease include beta-blockers, inorganic iodide, and lithium. beta-Blockers are used to decrease the symptoms of hyperthyroidism. Inorganic iodide is primarily used to prepare patients for thyroid surgery because of its ability to decrease the vascularity of the thyroid gland. Lithium, which acts in a manner similar to iodine, is not routinely used due to its transient effect and the risk of potentially serious adverse effects. In the US, radioiodine therapy has become the preferred treatment for adults with Graves disease. It is easy to administer, safe, effective, and more affordable than long-term treatment with antithyroid drugs. Hypothyroidism is an inevitable consequence of radioiodine therapy. Radioiodine is contraindicated in pregnant women because it can damage the fetal thyroid gland, resulting in fetal hypothyroidism. Bilateral subtotal thyroidectomy, which was once the only treatment available, is now performed only in special circumstances. In addition to the normal risks associated with surgery, laryngeal nerve damage, hypoparathyroidism, and hypothyroidism can occur following that procedure. CONCLUSIONS: Despite extensive experience with medical management, controversy prevails regarding choosing among the various drugs for treatment of Graves disease. None of the treatment options, including antithyroid drugs, radioiodine, and surgery, is ideal. Each has risks and benefits, and selection should be tailored to the individual patient.

Antithyroid Agents↗
PubMed2003

Tumour-specific activation of the sodium/iodide symporter gene under control of the glucose transporter gene 1 promoter (GTI-1.3).

Targeted transfer of a functionally active sodium iodide symporter (NIS) into tumour cells may be used for radioiodine therapy of cancer. Therefore, we investigated radioiodine uptake in a hepatoma cell line in vitro and in vivo after transfer of the sodium iodide symporter ( hNIS) gene under the control of a tumour-specific regulatory element, the promoter of the glucose transporter 1 gene (GTI-1.3). Employing a self-inactivating bicistronic retroviral vector for the transfer of the hNIS and the hygromycin resistance genes, rat Morris hepatoma (MH3924A) cells were infected with retroviral particles and hNIS-expressing cell lines were generated by hygromycin selection. (125)I(-) uptake and efflux were determined in genetically modified and wild type hepatoma cells. In addition, the iodide distribution in rats bearing wild type and genetically modified hepatomas was monitored. hNIS-expressing MH3924A cell lines accumulated up to 30 times more iodide than wild type hepatoma cells, with a maximal iodide uptake after 30 min incubation time. Competition experiments in the presence of sodium perchlorate revealed a decrease in the iodide uptake (80-84% decrease). Moreover, ouabain led to a loss of accumulated I(-) (81% decrease) whereas 4,4'-diisothiocyano-2,2'-disulphonic acid stilbene (DIDS) increased the I(-) uptake into cells (87% increase). However, a rapid efflux of the radioactivity (70%) was observed 20 min after (125)I(-)-containing medium had been replaced by non-radioactive medium. Lithium had no significant effect on iodide efflux. In rats, the hNIS-expressing tumours accumulated 22 times more iodide than the contralateral wild type tumour. In accordance with the in vitro data, we also observed a rapid efflux of the radioactivity out of the tumour in vivo. Dosimetric calculations resulted in an absorbed dose of 85 mGy in the wild type tumour and 830 mGy in the hNIS-expressing tumour after administration of 18.5 MBq (131)I. In conclusion, transduction of the hNIS gene under the control of the GLUT1 promoter element induces iodide transport in Morris hepatoma cells in vitro and in vivo. However, for therapeutic application additional conditions need to be defined which inhibit the iodide efflux out of the tumour cells.

Animals↗
PubMed2006

Comparison of tracer techniques for monitoring sewer losses.

Two different experimental techniques employing conservative tracers to determine exfiltration losses in a sewer system are reported. Both techniques compare the in-sewer responses measured along designated indicator and reference sections to assess the level of exfiltration although with different degrees of reliability. The experimental and interpretation errors associated with a pulse dosing technique, in which Rhodamine WT is used as the single tracer, are described. The estimation of exfiltration requires the comparison of indicator and reference peaks which need to be well resolved and reproducible in order to provide realistic results. A more consistent technique involves the continuous dosing of two different tracers with the objective of producing simultaneous downstream peak tracer concentrations. Any errors due to flow variations are eliminated and the longer measurement period allows both peak and background concentrations to be more accurately determined. Rhodamine WT, Li and Br were used in different combinations over the approximately 20 min duration of each continuous dosing experiment and were found to demonstrate conservative behaviours with measured recoveries of 97.6-100.6%, 97.3-101.4% and 108.4-109.2%, respectively. The analytical problems associated with the determination of the different tracers in sewage are described and are shown to be responsible for the reduced accuracy of the results associated with the use of Br. The preferred combination of tracers is Rhodamine WT as the indicator and Li as the reference and these are shown to be capable of estimating sewer losses to an accuracy of +/-1.0% using the continuous dosing approach.

Bromine↗
PubMedDate not supplied

[Pregnancy and breastfeeding. Side effects of drugs used in the treatment of thyroid diseases, on the fetus and the newborn].

The authors allude to the composed anti-thyroid drugs, blocking drugs, iodides, radioactive iodine, lithium carbonate and tyrosine side effects. The most common are composed anti-thyroid drugs and tyrosine. Anti-thyroid drugs risks are related to the tresspassing of the placenta barrier which can induce in goitre and hypothyroidism. Thyroid hormones are also very important for the fetus neural development during the first quarter when they cross the placenta.

Antithyroid Agents↗
PubMed1989

Dexamethasone treatment of amiodarone-induced thyrotoxicosis (AIT) with or without persistent administration of the drug.

Treatment of amiodarone-induced thyrotoxicosis (AIT) with thionamide, lithium or radioactive iodine is ineffective. This particular form of hyperthyroidism is long-lasting because of the slow elimination of amiodarone. Therefore, an alternative therapy is necessary, especially for patients who need to continue permanent administration of the drug. We report 2 cases of AIT: in one case, amiodarone was interrupted; in the other case, amiodarone was continued because of recurrent ventricular tachycardia resistant to classical antiarrhythmic drugs. Both patients were successfully treated with propylthiouracil (PTU) and dexamethasone (DXT).

Amiodarone↗
PubMed1992

Lithium enhances accumulation of [3H]inositol radioactivity and mass of second messenger inositol 1,4,5-trisphosphate in monkey cerebral cortex slices.

We previously reported that lithium, in the presence of acetylcholine, increased accumulations of inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate in brain cortex slices from the guinea pig, rabbit, rat, and mouse. In the mouse and rat, the Li(+)-induced increases required supplementation of the medium with inositol. This probably relates to the following facts: (a) Brain cortices of the mouse and rat contain in vivo concentrations of inositol half of that of the guinea pig. (b) Incubated rat brain cortex slices are depleted of inositol by 80%. (c) The slices require 10 mM inositol supplementation to restore in vivo concentrations. We now show that in monkey brain cortex slices, therapeutic concentrations of Li+ increase accumulation of inositol 1,4,5-trisphosphate. The inositol 1,3,4,5-tetrakisphosphate level is not increased. Neither inositol nor an agonist is required. The same effects are seen whether inositol 1,4,5-trisphosphate is quantified by the [3H]inositol prelabeling technique or by mass assay, although mass includes a pool of inositol 1,4,5-trisphosphate that is metabolically inactive. Thus, in a therapeutically relevant model for humans, Li+ increases inositol 1,4,5-trisphosphate levels in brain cortex slices, as was previously seen in lower mammals at non-rate-limiting concentrations of inositol.

Acetylcholine↗
PubMed1982

Management of hyper & hypo thyroid conditions.

In hyperthyroidism, the primary objective of therapy is to reduce secretion of thyroid hormone, which can be accomplished in various ways. The stimulus to hypersecretion can be removed in some causes of hyperthyroidism; in others, hormone synthesis and release can be inhibited by drugs such as thioamides, adrenergic blocking agents, or possibly lithium or glucocorticoids. Radioactive iodine is indicated for primary therapy of uncomplicated hyperthyroidism due to Graves' disease in persons over 30 years of age (myxedema may be a complication) and for treatment of autonomous thyroid adenoma in patients who are not suitable candidates for surgery. Surgical ablation is preferred for some causes of hyperthyroidism but may induce postoperative hypothyroidism. Hypothyroidism due to thyroid failure usually presents few therapeutic difficulties and can be managed simply by long-term hormone replacement. Before hormone replacement is prescribed for secondary or tertiary hypothyroidism, the other pituitary functions should be assessed.

Adult↗
PubMed2006

Cholestasis secondary to hyperthyroidism made worse by methimazole.

A 28-year-old man presented with weight loss, jaundice, and pruritus. This was diagnosed to be secondary to Graves disease and the patient was prescribed methimazole. He returned 2 weeks later with worsening of his jaundice. Further investigation, including liver biopsy, indicated that there was superimposed methimazole-induced cholestasis. Discontinuation of methimazole and treatment of hyperthyroidism with lithium followed by radioactive iodine therapy resulted in resolution of his symptoms. This case highlights the fact that worsening cholestasis after therapy for Graves disease should raise the possibility of thionamide-induced exaggeration of liver cholestasis.

Adult↗
PubMed1976

Lithium effects on magnesium, calcium, and phosphate metabolism in rats.

Rats were treated with lithium chloride for 8 weeks. At the last day of lithium administration, the animals were given radioactive calcium, magnesium, and phosphate. Electrolyte content and radioactivity were determined in serum, bone, muscle, liver and brain. Lithium led to an increase of inorganic phosphate in muscle and a decrease in serum. Uptake of radioactive phosphate was increased in muscle and liver but reduced in bone. The amount of magnesium in muscle and serum was increased in the lithium-treated rats, whereas the uptake of radioactive magnesium into bone was decreased. Uptake of radioactive calcium into bone was reduced, and radioactive calcium in serum was increased after lithium.

Animals↗
PubMed1976

Proteins of axonal transport: investigation of solubility characteristics and behaviour in gel filtration.

Rapid axonal transport of proteins in retinal ganglion cells of the rabbit was studied following intraocular injections of labelled amino acids. Approximately 10% of the transported radioactivity was found in the supernatant following homogenization and high-speed centrifugation of the nerve terminal region. Relatively simple manipulations with ionic strength, pH and the presence of a chelating agent could solubilize an equivalent amount of radioactivity from the pellet. Lithium diiodosalicylate solubilized most rapidly transported membrane proteins. Gel filtration of readily soluble rapidly transported radioactivity gave a main macromolecular radioactive peak with an approximate mol. wt. of 500,000 dalton as determined on Sephadex G-200. However, gel filtration on Sepharose CL-6B gave a mol. wt. of about 160,000 for the same radioactive peak. SDS polyacrylamide gel electrophoresis of rapidly transported soluble proteins and fractions derived from these proteins via gel filtration and ion exchange chromatography revealed in all cases a very complex picture of labelled polypeptides. Thus rapid axonal transport of soluble proteins in this system seems to involve many different macromolecules.

Animals↗
PubMed2001

Biodegradation of [(3)H]poly(epsilon-caprolactone) in the presence of active sludge extracts.

Poly(epsilon-caprolactone), PCL, is a commercial biodegradable and biocompatible polyester that can be bioassimilated by outdoor microorganisms. For biomedical and environmental applications, monitoring the fate of degradation products in vivo or under environmental conditions is one of the critical steps to evaluate degradation characteristics. [(3)H] radiolabeling is the best method to monitor the fate of degradable polymer chains in contact with complex living systems and to show bioassimilation. Therefore, tritiated PCL was synthesized by chemical modification using anionic activation by reaction with lithium diisopropylamide. The resulting radioactive polymer was characterized and allowed to degrade at 37 degrees C under aerobic conditions in the presence of active sludge. Comparison was made with abiotic hydrolytic degradation in pH = 7.4, 0.13 M phosphate buffer at 37 degrees C. Water-soluble degradation products were assessed by measuring radioactivity in the solution phase. It was shown that biodegradation of PCL started after a few hours and proceeded up to the ultimate stage over ca. 72 days, giving tritiated water (80-90%) and biomass. Radioactivity detection appeared much more sensitive than measurement of CO(2) production or consumption to monitor degradation phenomena. In particular, it showed that the onset of biodegradation occurs earlier than that reported using respirometry.

Bacteria, Aerobic↗
PubMedDate not supplied

Leukocytoclastic vasculitis: a rare manifestation of propylthiouracil allergy.

OBJECTIVE: To report a case of leukocytoclastic vasculitis as a manifestation of propylthiouracil allergy. METHODS: We present the history, findings on physical examination, and results of laboratory evaluation in a 25-year-old woman. Associated reports from the literature are reviewed. RESULTS: The patient, with a history of Graves' disease, was referred for evaluation of a purpuric rash on the pinnas and buttocks bilaterally. Findings included exophthalmos and bilateral goiter with neck bruits. She was biochemically hyperthyroid. Biopsy of the skin lesions revealed leukocytoclastic vasculitis. Propylthiouracil therapy was discontinued, and prednisone was prescribed. Treatment with radioactive iodine resulted in appreciably diminished skin lesions and reduction in the size of the thyroid gland, but thyroxine and triiodothyronine levels increased. Administration of a second, higher dose of radioactive iodine with concomitant lithium carbonate resulted in clinical and biochemical improvement. Six months after initial assessment, the rash had resolved, and the patient's free thyroxine value had normalized, although the thyrotropin level was still suppressed. CONCLUSION: Leukocytoclastic vasculitis, although rarely seen as a manifestation of propylthiouracil allergy, has been reported in the medical literature and should be considered in the differential diagnosis of patients with a vasculitic rash. Treatment consists of discontinuation of the offending medication and administration of a corticosteroid and, occasionally, cyclophosphamide or plasmapheresis.

Adult↗