sodium-perchlorate and thiocyanate

Topics: Humans; Iodine Radioisotopes; Perchlorates; Radionuclide Imaging; Sodium Compounds; Sodium Pertechnetate Tc 99m; Thiocyanates; Thyroid Diseases; Thyroid Function Tests; Thyroid Gland; Triiodothyronine

Thyroid destruction leading to endemic myxoedematous cretinism is highly prevalent in central Africa, where iodine (I) and selenium (SE) deficiencies as well as thiocyanate (SCN) overload are combined. All three factors have been studied experimentally in the etiology of the disease, but they have never been studied in combination. In a model using rats, we have previously shown that combining I and SE deficiencies increases the sensitivity of the thyroid to necrosis after iodide overload, an event unlikely to occur in the African situation. To develop a model that would more closely fit with the epidemiological findings, we have determined whether an SCN overload would also result in thyroid necrosis as does the I overload. The combination of the three factors increased by 3.5 times the amount of necrotic cells, from 5.5 +/- 0.3% in the I-SE+ thyroids to 18.9 +/- 1.6% in the I-SE-SCN-overloaded ones. Methimazole administration prevented the SCN-induced necrosis. SE- thyroids evolved to fibrosis, whereas SE+ thyroids did not. TGFbeta was prominent in macrophages present in SE- glands. Thyroid destruction in central Africa might therefore originate from the interaction of three factors: I and SE deficiencies by increasing H(2)O(2) accumulation, SE deficiency by decreasing cell defense and promoting fibrosis, and SCN overload by triggering follicular cell necrosis.

Topics: Africa, Central; Animals; Antithyroid Agents; Congenital Hypothyroidism; Disease Models, Animal; Endemic Diseases; Female; Fibrosis; Hydrogen Peroxide; Inflammation; Iodine; Macrophages; Methimazole; Myxedema; Necrosis; Perchlorates; Rats; Rats, Wistar; Selenium; Sodium Compounds; Thiocyanates; Thyroid Gland; Transforming Growth Factor beta

It has been previously argued that the use of the one-electron oxidants (SCN)2(*-) and Br2(*-) with plasmid DNA leads to the formation of DNA guanyl radicals. These guanyl radical species are intermediates in the DNA damage produced by processes such as photo-ionization and ionizing irradiation. The present paper evaluates the use of thallium(II) ions (Tl(II)OH(+)) as the one-electron oxidant, and also determines rate constants for the reduction (repair) of guanyl radicals in plasmid DNA by a variety of reducing agents including the biologically important compounds ascorbate and glutathione.. Aqueous solutions of plasmid DNA containing 10(-3) mol dm(-3) thiocyanate or thallous ions and a reducing agent (azide, nitrite, ferrocyanide, hexachloroiridate(III), iodide, ascorbate, glutathione, glutathione disulphide, methionine, tyrosine, 5-hydroxyindole-3-acetic acid, 10(-7)-10(-4) mol dm(-3)) were irradiated with 137Cs gamma-rays (662 keV). After irradiation, the plasmid was incubated with the E. coli base excision repair endonuclease formamidopyrimidine-DNA N-glycosylase (FPG). Strand break yields after incubation were quantified by means of agarose gel electrophoresis.. High yields of FPG-sensitive sites produced by the oxidants (SCN)2(*-) and Tl(II)OH(+) were strongly attenuated by the presence of the reducing agents.. From the results, it is possible to arrive at estimates of the rate constants for the reduction of the DNA guanyl radical by the reducing agents. Values lie in the range 10(4)-10(7) dm(3) mol(-1) s(-1). Using the values for ascorbate and glutathione, it is possible to estimate an upper limit on the order of milliseconds for the lifetime of DNA guanyl radicals under cellular conditions. The implication is that there may well be a significant chemical repair of DNA base damage by the direct effect of ionizing radiation.

Topics: DNA; DNA Damage; DNA Repair; DNA-Formamidopyrimidine Glycosylase; DNA, Single-Stranded; Ferrocyanides; Free Radical Scavengers; Free Radicals; Kinetics; N-Glycosyl Hydrolases; Oxidation-Reduction; Perchlorates; Plasmids; Radiation, Ionizing; Sodium Compounds; Thallium; Thiocyanates; Tyrosine

In this study, we compared the effects of different chloride (Cl(-)) substitutes - methane sulfonate (CH(3)SO(-)(3)), bromide (Br(-)), nitrate (NO(-)(3)), thiocyanate (SCN(-)) and perchlorate (ClO(-)(4)) - on the secretory activity and calcium current activation of rat lactotropes in primary culture. We observed that CH(3)SO(-)(3) decreased basal prolactin (PRL) secretion. Br(-) had no effect, whereas the more lyotropic anions, such as NO(-3), SCN(-) and C1O(-4), increased basal PRL secretion. The latter three substitutes induced a significant shift in the voltage dependence of T-type calcium channel activation towards hyperpolarized values. However, this shift alone cannot explain the increase in secretion. Anion permeability studies also demonstrated that the organic anion CH(3)SO(-3) was less permeant than Cl(-), whereas monovalent inorganic anions were more permeant, with the following anion permeability sequence: SCN(-) > ClO(-4) > NO(-3) > Br(-). In conclusion, deprivation of Cl(-) ions has converse consequences on basal and induced secretion; permeating anions result in a transient increase in intracellular Ca(2+) ions. This process involves voltage-dependent Ca(2+) channels. We propose that an alteration in intracellular anion concentrations may influence the activation of internal effectors such as G proteins or channel proteins and, therefore, interfere with exocytosis. These effects are correlated with an external action of lyotropic anions, particularly NO(-3), ClO(-4) and SCN(-), on the gating properties of T-type calcium channels, probably through changes in cell surface charges. The results demonstrate the modulatory effect of anions on the secretory activity of rat lactotropes and underline the specific role played by chloride in stimulus-secretion coupling.

Topics: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; Animals; Bromides; Calcium; Calcium Channel Agonists; Calcium Channels, T-Type; Cells, Cultured; Chlorides; Female; In Vitro Techniques; Ion Channel Gating; Mesylates; Nitrates; Patch-Clamp Techniques; Perchlorates; Pituitary Gland; Prolactin; Rats; Rats, Wistar; Sodium Compounds; Thiocyanates

The transport of iodide into the thyroid, catalyzed by the Na+/I- symporter (NIS), is the initial and rate-limiting step in the formation of thyroid hormones. To study the basic characteristics of the human (h) NIS, we have established a Chinese hamster ovary cell line stably expressing the hNIS (CHO-NIS9). In agreement with previous work on the rat NIS, iodide uptake in these cells was initiated within 2 min of the addition of 131I, reaching a plateau after 30 min. Both perchlorate and thiocyanate inhibited iodide uptake in a dose-dependent manner, with inhibition evident at concentrations of 0.01 and 0.1 micromol/L, respectively, and reaching complete inhibition at 20 micromol/L and 500 micromol/L, respectively. Ouabain, which blocks the activity of the Na+/K+ adenosine triphosphatase, also inhibited iodide uptake in a dose-dependent manner, starting at concentrations of 100 micromol/L and reaching maximum inhibition at 1600 micromol/L, indicating that iodide uptake in these cells is sodium dependent. CHO-NIS9 cells were further used to study 88 sera from patients with Graves' disease, for iodide uptake inhibitory activity, which were compared with sera from 31 controls. Significant iodide uptake inhibition was taken as any inhibition in excess of the mean + 3 SD of the results with the control sera. On this basis, 27 (30.7%) of the Graves' sera, but none of the controls, inhibited iodide uptake in CHO-NIS9. IgGs from these patients also inhibited iodide uptake, indicating that this inhibitory activity was antibody mediated. In summary, we have established a CHO cell line stably expressing the hNIS and shown that antibodies in GD sera can inhibit iodide uptake in these cells. This further emphasizes the role of NIS as a novel autoantigen in thyroid immunity.

Topics: Animals; Antibodies; Carrier Proteins; Case-Control Studies; CHO Cells; Cricetinae; Graves Disease; Humans; Iodides; Membrane Proteins; Ouabain; Perchlorates; Recombinant Proteins; Sodium Compounds; Symporters; Thiocyanates; Transfection

Membrane-bound acetylcholinesterase (AChE) from mosquito showed the characteristic substrate inhibition of this enzyme, but 105,000 x g supernatants of freshly extracted enzyme did not. Addition of chaotropic anions, a freeze-thaw cycle and autolysis of the amphiphilic acetylcholinesterase to its non-amphiphilic derivatives resulted in return of the substrate inhibition feature along with an apparent increment in the enzyme activity. These results suggested that the lipidic environment of the mosquito AChE is temporarily perturbed when extracted. The enzyme is probably trapped in non-sedimenting mixtures composed of endogenous amphiphilic molecules. The occurrence of this phenomenon was not affected by the presence of Triton X-100 and other detergents, either alone or in combination with sodium chloride. Freezing in the presence of strong chaotropic anions (perchlorate, iodide and thiocyanate) caused the irreversible inactivation of the mosquito AChE. Crude and incomplete purified fractions of the enzyme were more sensitive than a more purified preparation. With both the purified AChE and the non-purified AChE, amphiphilic AChE was more freeze labile. Freezing at -10 degrees C enhanced inactivation of non-purified fractions. At this temperature, even weak chaotropic anions (fluoride, chloride and nitrate), while in combination with non-ionic detergents that solubilized mosquito AChE efficiently, reduced the enzyme activity of these fractions. In this case, recovery of the enzyme activity by incubation at 25 degrees C was inversely correlated with the effectiveness of the chaotropic anion. Gel filtration failed to show any change in the hydrodynamic radius of the freezing-inactivated AChE. Therefore, this phenomenon is explained as different degrees of denaturation of the enzyme in direct association with the chaotropic strength. Thus, antichaotropic anions, such as sulfate, should improve the stability of the mosquito acetylcholinesterase during extraction, purification and storage.

Topics: Acetylcholinesterase; Animals; Anions; Chemical Phenomena; Chemistry, Physical; Chlorides; Cholinesterase Inhibitors; Culicidae; Detergents; Enzyme Activation; Fluorides; Freezing; Hot Temperature; Iodides; Kinetics; Nitrates; Perchlorates; Sodium Chloride; Sodium Compounds; Solubility; Thiocyanates

The effect of methimazole (MMI) and 2-mercaptoethanol (ME) on I-transport was studied using phospholipid vesicles (P-vesicles) made from porcine thyroid plasma membranes and soybean phospholipids by sonication. 1. When buffer solutions contained either 1 mM MMI or 2 mM ME, I-uptake by P-vesicles in the presence of external Na+ was apparently higher than that in the absence of external Na+. Na+-dependent I- uptake was inhibited by both C1O4- and SCN- added externally. 2. When PM was treated with 4 mM N-ethylmaleimide prior to preparation of P-vesicles, the activity of Na+-dependent I- transport was completely lost even when P-vesicles were incubated in the presence of ME. 3. When neither MMI nor ME was added to buffers, I- uptake in the presence of external Na+ was not at all higher than that in the absence of external Na+. In these instances, however, I- uptake was much higher compared than the baseline uptake in the presence of MMI or ME, and was inhibited by external SCN- and not by C1O4- without relation to external Na+. These data indicate that MMI or ME has two distinct effects on our model system of I- transport. The one is preservation of the Na+-dependent I- transport activity by protecting a sulfhydryl group, and the other is reduction of nonspecific I- binding to P-vesicles. In addition, C1O4- is a more specific inhibitor of thyroid I- transport than SCN-, when non-specific I- oxidation is imperfectly prevented.

Topics: Animals; Biological Transport; Cell Membrane; Iodine; Mercaptoethanol; Methimazole; Perchlorates; Phospholipids; Sodium; Sodium Compounds; Thiocyanates; Thyroid Gland

The effects of twitch potentiators at physiologically effective concentrations on intramembrane charge movements were examined in voltage-clamped frog skeletal muscle in the presence and absence of tetracaine. Caffeine, even at high concentrations (2.5 mM) did not alter the potential dependence of either tetracaine-sensitive or tetracaine-resistant portions of non-linear charge through a voltage range that included the mechanical threshold. Perchlorate (8 mM) altered the form and shifted the potential dependence of the non-linear charge by about -25 mV in the hyperpolarizing direction, but did not alter the total available charge. Comparing charge movements in the presence and absence of 4 mM-tetracaine demonstrated that perchlorate shifted the threshold and voltage dependence of the delayed ('q gamma') transients but had no action on the steady-state tetracaine-resistant charge. Thiocyanate (10 mM) shifted the voltage dependence of charge movements by about 20 mV in the hyperpolarizing direction. Experiments employing 4 mM-tetracaine demonstrated that this was the result of effects on both tetracaine-sensitive and tetracaine-resistant charge movements. On the basis of their effects on contractile activation reported on earlier occasions, these differential effects of twitch potentiators are explicable in terms of tetracaine-sensitive and tetracaine-resistant charge components being causally separate and not requiring a direct participation of tetracaine-resistant charge in contractile activation.

Topics: Action Potentials; Animals; Caffeine; In Vitro Techniques; Muscle Contraction; Muscles; Perchlorates; Rana temporaria; Sodium Compounds; Tetracaine; Thiocyanates

Effects of KSCN on thyroidal iodine metabolism were studied in weanling mice fed a low iodide diet (LID) labeled continuously with 125I as iodide. The addition of KSCN (0.3 and 0.6 mg/g diet) resulted in the accumulation of an unusual iodinated protein within the follicles of the mouse thyroids. After 60 days, total thyroidal iodine was 4 times greater than in controls without thiocyanate. The iodinated protein was essentially insoluble at pH 8.0 and was very slowly released from the thyroids; it contained more MIT than DIT and little thyroid hormone. By use of three isotopes (125I, 127I, and 131I) and auto-radiographs, there were shown different iodinated proteins synthesized during high and low iodine intakes and coexistent but segregated in the colloid. Low doses of perchlorate or iodide inhibited or prevented accumulation of the essentially insoluble iodinated protein. It is suggested that when mouse thyroids are iodine depleted, thiocyanate increases the formation of an essentially insoluble iodinated thyroglobulin within the thyroid. Only a small fraction of the iodination may have occurred by this route, but the rate of formation exceeded the rate of release, so the product continuously accumulated.

Topics: Animals; Diet; Iodides; Iodine; Male; Mice; Perchlorates; Proteins; Sodium Compounds; Thiocyanates; Thyroglobulin; Thyroid Gland