Lactoperoxidase-catalyzed oxidation of thiocyanate ion: a carbon-13 nuclear magnetic resonance study of the oxidation products.

Products formed from the lactoperoxidase (LPO) catalyzed oxidation of thiocyanate ion (SCN-) with hydrogen peroxide (H2O2) have been studied by 13C-NMR at pH 6 and pH 7. Ultimate formation of hypothiocyanite ion (OSCN-) as the major product correlates well with the known optical studies. The oxidation rate of SCN- appears to be greater at pH < or = 6.0. At [H2O2]/[SCN-] ratios of < or = 0.5, OSCN- is not formed immediately, but an unidentified intermediate is produced. At [H2O2]/[SCN-] > 0.5, SCN- appears to be directly oxidized to OSCN-. Once formed, OSCN- slowly degrades over a period of days to carbon dioxide (CO2), bicarbonate ion (HCO3-), and hydrogen cyanide (HCN). An additional, previously unrecognized product also appears after formation of OSCN-. On the basis of carbon-13 chemical shift information this new species is suggested to result from rearrangement of OSCN- to yield the thiooxime isomer, SCNO- or SCNOH.     

Iodine-Induced Thyroid Blockade: Role of Selenium and Iodine in the Thyroid and Pituitary Glands

The purpose of this study was to determine the content of iodine and selenium in the thyroid and pituitary glands of rats under iodine-induced blockade of the thyroid gland. Electron probe microanalysis, wavelength-dispersive spectrometry, and point analysis were used in this investigation. We also determined the expression of sodium iodide symporter and caspase 32 in the thyroid and pituitary glands and the expression of thyroid-stimulating hormone in the pituitary. The samples for iodine analysis must be thoroughly dehydrated, and for this purpose, we developed a method that produced samples of constant mass with minimal loss of substrate (human thyroid gland was used for the investigation). Normal levels of iodine and selenium were found in the thyroid, pituitary, ovaries, testes hypothalamus, and pancreas of healthy rats. The levels of iodine and selenium in I- or Se-positive points and the percentage of positive points in most of these organs were similar to those of controls (basal level), except for the level of iodine in the thyroid gland and testes. Blockade of the thyroid gland changed the iodine level in iodine-positive points of the thyroid and the pituitary glands. On the sixth day of blockage, the iodine level in iodine-positive points of the thyroid gradually decreased to the basal level followed by an abrupt increase on the seventh day, implying a rebound effect. The opposite was found in the pituitary, in which the level of iodine in iodine-positive points increased during the first 6 days and then abruptly decreased on the seventh day. Expression of the thyroid-stimulating hormone in the pituitary decreased during the first 5 days but sharply increased on the sixth day, with a minimum level of iodine in the thyroid and maximum in the pituitary, before normalization of the iodine level in both glands preceding the rebound effect. The expression of sodium iodide symporter increased during the first 4 days of blockage and then decreased in both glands. The fluctuations of the thyroid-stimulating hormone in the pituitary gland reflected the changes of iodine in the thyroid gland more precisely than the changes of sodium iodide symporter. The selenium level in the selenium-positive points changed only in the pituitary, dropping to zero on the second and fifth day of the blockade. Simultaneously, the maximum induction of caspase 32 was observed in the pituitary gland. We believe that these results may help to clarify a role of the pituitary gland in the thyroid blockade.     

Evidence for cigarette smoke-induced calcitonin secretion from lungs of man and hamster

In hamsters, acute cigarette smoke inhalation increased serum levels of the hormone calcitonin; and, in humans, smoking of two high-nicotine content cigarettes increased serum and urine levels of this hormone. The source of this immunoreactive calcitonin (iCT) does not appear to be the thyroid gland, since previously thyroidectomized patients demonstrated a similar response. In the hamster, the increased serum iCT levels were accompanied by a decreased lung tissue iCT content and hypocalcemia. It is suggested that the source of the cigarette smoke-induced hypercalcitonemia is the lung, possibly from the iCT-containing pulmonary neuroendocrine (PNE) cells. Moreover, this response appears to be dependent on the nicotine content of the cigarettes.     

Thiocyanate catalyzes myeloperoxidase-initiated lipid oxidation in LDL

There is evidence that LDL oxidation may render the lipoprotein atherogenic. The myeloperoxidase-hydrogen peroxide (MPO/H2O2) system of activated phagocytes may be involved in this process. Chloride is supposed to be the major substrate for MPO, generating reactive hypochlorous acid (HOCl), modifying LDL. The pseudo-halide thiocyanate (SCN-) has been shown to be a suitable substrate for MPO, forming reactive HOSCN/SCN*. As relatively abundant levels of SCN- are found in plasma of smokers--a well-known risk group for cardiovascular disease--the ability of SCN- to act as a catalyst of LDL atherogenic modification by MPO/H2O2 was tested. Measurement of conjugated diene and lipid hydroperoxide formation in LDL preparations exposed to MPO/H2O2 revealed that SCN- catalyzed lipid oxidation in LDL. Chloride did not diminish the effect of SCN- on lipid oxidation. Surprisingly, SCN inhibited the HOCl-mediated apoprotein modification in LDL. Nitrite--recently found to be a substrate for MPO--showed some competing properties. MPO-mediated lipid oxidation was inhibited by heme poisons (azide, cyanide) and catalase. Ascorbic acid was the most effective compound in inhibiting the SCN- -catalyzed reaction. Bilirubin showed some action, whereas tocopherol was ineffective. When LDL oxidation was performed with activated human neutrophils, which employ the MPO pathway, SCN- catalyzed the cell-mediated LDL oxidation. The MPO/H2O2/SCN- system may have the potential to play a significant role in the oxidative modification of LDL--an observation further pointing to the link between the long-recognized risk factors of atherosclerosis: elevated levels of LDL and smoking.     

Skeletal manifestations of hypothyroidism from Switzerland

Hypothyroidism is caused by a deficiency in the synthesis of thyroid hormone. Dwarfism is the most obvious skeletal manifestation, but most people with hypothyroidism do not have any skeletal evidence of the disease. When the skeleton is affected, the severity of this manifestation depends on the degree of the deficiency and age of onset. Endemic hypothyroidism typically is linked to specific ecological settings such as the high mountains where iodine is absent, or else it occurs with very low concentrations in water and soil. In these areas, the prevalence may be as high as 8%. The disease can be expected to occur in archaeological human skeletal samples from endemic regions. Sporadic hypothyroidism is caused by a deficiency in the thyroid gland itself, and is not linked to any specific environmental context. The disease may be the result of a genetic defect, but can also be caused by other pathological conditions that may affect the thyroid gland, including infection and cancer. The skeletal abnormalities of the two variants will be indistinguishable in archaeological human remains. In order to identify hypothyroidism in archaeological skeletal samples, one must be aware of the differences in pathological skeletal changes seen in hypothyroidism in comparison with other diseases, such as achondroplasia, that can cause similar abnormalities. Twelve clinically documented cases of hypothyroidism provide data for understanding the skeletal abnormalities associated with this disease. All 12 are modern documented cases from Switzerland, where endemic hypothyroidism occurred in the iodine-deficient Alpine regions. However, at least one case in the sample was caused by a defect in the thyroid gland itself.     

Fine structural aspects of the black thyroid induced by minocycline, and the effects of a low iodine diet, propylthiouracil, thyroxine tablet and TSH, on the black discoloration of the rat thyroid

Fine structural aspects of the effect of minocycline, an antibiotic of the tetracycline group, on the rat thyroid were studied. In all the rats administered minocycline (100 mg/kg/day) for 21 days, diffuse black discoloration of the thyroid gland occurred. However, when the rats were fed on a low iodine diet, given propylthiouracil (PTU) or thyroxine tablet with minocycline the black pigmentation of the thyroid gland did not take place. On the other hand, black discoloration of the thyroid was accelerated in the rats administered TSH and minocycline simultaneously. Ultrastructurally, numerous dense bodies containing highly electron-dense deposits were seen in the supranuclear region of the follicular epithelial cells of the black thyroid. These dense bodies, which showed positive acid phosphatase activity, are considered to be lysosomes containing minocycline or its derivatives. It is speculated that minocycline is taken up into follicular epithelial cells with iodine, and that the black discoloration of the thyroid gland is intimately related to iodine metabolism.     

Recent Canadian court decisions on consent.

A 51-year-old woman presented with a painful, rapidly enlarging thyroid gland. The serum concentrations of the thyroid hormones were initially at the upper limit of normal, and the uptake of radioactive iodine by the thyroid was completely depressed. Although subacute thyroiditis was suspected, a biopsy specimen from the thyroid showed malignant disease and no evidence of inflammation. At the time of right subtotal lobectomy metastatic breast carcinoma was diagnosed. Thus, primary or secondary malignant disease of the thyroid can simulate thyroiditis and present a serious problem in differential diagnosis.     

Effect of increased bromide intake on iodine excretion in rats

The time course of iodine excretion in adult male rats substantially differs from bromine excretion. Bromine is excreted at a single rate, whereas iodine evinces two excretion rates. Even a strong increase in bromide intake in experimental animals failed to affect the rate of iodine excretion but it lowered the fraction of iodine accumulated increase in bromide intake in experimental animals failed to affect the rate of iodine excretion but it lowered the fraction of iodine accumulated in the thyroid gland by 20% probably by affecting the transport of iodide into the thyroid gland.     

Iodine metabolism in the thyroid gland in chronic uranium poisoning]

The exchange of radioactive and stable iodine was studied for 21 days after the I131 injection in the thyroid gland and the blood of rats against the background of chronic uranium intoxication. The latter was accompanied by a decrease in the number of iodine-transport loci of the gland, as well as of the value of the intrathyroid iodine pool and of the stable iodine concentration in the thyroid tissue. The compensatory reaction of the thyroid gland was expressed in the increase of its mass and the rate of the thyroid metabolism as well.     

THE USE OF RADIOACTIVE IODINE IN THE TREATMENT OF GRAVES' DISEASE

Fifty patients with uncomplicated Graves'' disease were treated with radioactive iodine (I₁₃₁). Twenty-six patients who were followed for one year or longer are the basis of this report. Twenty-five are now euthyroid; only one is not completely well.The total dose of radioiodine administered varied from 0.5 to 10 millicuries. The average length of time necessary for return to a euthyroid state was from three to four months.Hypometabolism developed in three patients, and in one the signs and symptoms of myxedema developed. No other complications ensued. One patient who apparently relapsed had complete return to normal after further iodine administration.The determination of the uptake of radioactive iodine by the thyroid gland is a useful diagnostic procedure in differentiating conditions simulating hyperthyroidism.Following treatment with radioactive iodine, the thyroid gland becomes smaller, the uptake of iodine by the gland is reduced, and the level of organic iodine in the plasma becomes normal.In acute thyroiditis, in spite of a high basal metabolic rate, high content of organic iodine in the plasma and other evidences of “hyperthyroidism,” the uptake of I₁₃₁ has been very low.     

Molecular and cellular mechanisms of transepithelial iodide transport in the thyroid

Thyroid hormone is an essential regulator of developmental growth and metabolism in vertebrates. Iodine is a necessary constituent of thyroid hormone. Due to the scarcity and uneven distribution of iodine on the Earth's crust, the structure of the thyroid gland is adjusted to collect and store this element in order to secure a continuous supply of thyroid hormone throughout life. Still, disease resulting from hypothyroidism due to iodine deficiency is a global health problem, illustrating the great biological significance that iodine saving mechanisms have evolved. Iodide is accumulated together with prohormone (thyroglobulin) in the lumen of the thyroid follicles. The rate-limiting step of this transport is the sodium/iodide symporter located in the basolateral plasma membrane of the thyroid follicular cells. Iodide is also transferred across the apical plasma membrane into the lumen where hormonogenesis takes place. In this review, recent progress in the understanding of transepithelial iodide transport in the thyroid is summarized.     

Effect of radish (Raphanus sativus Linn.) on thyroid status under conditions of varying iodine intake in rats

Cruciferous plants viz. cabbage, cauliflower, turnip, radish, mustard etc. that contain goitrogenic/antithyroid substances, constitute a portion of regular human diet. The effect of chronic feeding of fresh and cooked radish, R. sativus under varying state of iodine intake on morphological and functional status of thyroid in albino rats was evaluated by thyroid gland morphology and histology, thyroid peroxidase activity, serum triiodothyronine, thyroxine and thyrotropin levels. The consumption pattern of iodine and goitrogens of cyanogenic origin was evaluated by measuring urinary iodine and thiocyanate levels respectively. After chronic radish feeding, increased weight of thyroid gland, decreased thyroid peroxidase activity, reduced thyroid hormone profiles and elevated level of thyrotropin were observed resembling a relative state of hypoactive thyroid gland in comparison to control even after supplementation of adequate iodine.     

Iodinated phospholipids and the iodination of proteins of dog thyroid gland in vitro

Slices of dog thyroid gland were incubated with liposomes consisting of (125)I-labelled phosphatidylcholine (the iodine was covalently linked to unsaturated fatty acyl chains). The (125)I label of (125)I-labelled liposomes was incorporated into thyroid protein and/or thyroglobulin at a higher rate than was the (131)I label of either Na(131)I or (131)I(2). The iodine was shown to be protein-bound by the co-migration of the labelled iodine with protein under conditions where free iodine, iodide and lipid-bound iodine were removed from protein. The uptake of iodine from the iodinated phospholipid was probably due to phospholipid exchange between the iodinated liposomes and the thyroid cell membrane, since (a) (14)C-labelled phospholipid was metabolized to (14)CO(2) and (b) many lipids in the tissue slice became (14)C-labelled. A very strong inhibition of iodide ;uptake' from Na(131)I, caused by thiosulphate, produced only a minor inhibition of the incorporation of (125)I from (125)I-labelled liposomes into thyroid protein and/or thyroglobulin. This implies that free iodide may not necessarily be formed from the iodinated phospholipids before their entrance or utilization in the cell. Synthetic polytyrosine polypeptide suspensions showed some iodination by (131)I-labelled liposomes. In tissues with low tyrosine contents, such as liver and kidney, only a trace uptake was observed. Salivary gland showed some uptake. Endoplasmic reticulum of thyroid gland showed a higher iodine uptake than that of the corresponding plasma membranes. These experiments, together with the demonstration of the diet-dependent presence of iodinated phospholipids in dog thyroid, leads us to suggest that iodination of the membrane phospholipids of thyroid cells may be directly or indirectly involved at some stage in the synthesis of thyroglobulin, or exists as a scavenger mechanism, to re-utilize and/or recover released iodine from unstable compounds inside the thyroid cell.     

IODINE AND THE THYROID : III. THE SPECIFIC ACTION OF IODINE IN ACCELERATING AMPHIBIAN METAMORPHOSIS.

1. Amphibian metamorphosis depends upon the amount of iodine secured by the larvæ; the greater the quantity the more rapid the differentiation. 2. Bromine is physiologically inert when fed even in large quantities to frog larvæ, hence it cannot be substituted for iodine. Bromine feeding has no effect on the thyroid. 3. Iodine is the active constituent of the thyroid gland, in the Anura at any rate, and functions within the body by stimulating intracellular oxidations; it is apparently specific in its action. 4. The basal metabolism of patients suffering from athyreosis, whose metabolism is 40 per cent below normal, is very likely held at this figure and prevented from sinking lower to the death point by the introduction of iodine into the body through food and water. 5. The thyroid gland is an organ the function of which is the extraction from the circulation, storage, and supplying to the organism, under the pressure of its needs, the small quantities of iodine taken into the body. The chief function of this gland then is the utilization of iodine in small quantities.     

Iodide excess exerts oxidative stress in some target tissues of the thyroid hormones

Environmental iodine deficiency continues to be a significant public health problem worldwide. On the other hand, iodide excess results principally from the use of iodine-containing medicinal preparations or radiographic contrast media. For this reason we intended to explore iodide excess impairment on prooxidant/antioxidant balance of the thyroid gland, hepatic tissue and in blood and the effect of selenium administration on oxidative stress markers under the same circumstances. Experiments were performed for 10 days with white, male, Wistar rats, as follows: group 1: control-normal iodine supply group; 2: high iodine diet, group; 3: high iodine diet and selenium; group 4: high iodine diet and Carbimasole. Oxidative stress markers such as lipid peroxides were determined in thyroid gland, hepatic tissue and in blood. Measuring H+ donor ability of the sera and catalase activity in thyroid gland and in hepatic tissue assessed antioxidant defense. Iodide excess had prooxidant effects, leading to an increased lipid peroxides level and catalase activity in target tissues and in blood and to a decreased H+ donor ability of the sera. Selenium supplementation had opposite effects. Present data allow us to conclude that the alterations due to iodide excess in thyroid gland, hepatic tissue and in blood are mediated through oxidative stress.     

Compartmental models for human iodine metabolism

Compartmental models for the various aspects of human iodine metabolism are reviewed, emphasizing the role of Mones Berman in the development of this field. The review first presents published submodels for the peripheral distribution of inorganic iodine, for the thyroidal iodide trapping function, and for the peripheral distribution and metabolism of the thyroid hormones. Approaches to improving understanding of the physiology of the thyroid gland itself through compartmental modeling techniques are then discussed in more detail. The three submodels described above are incorporated into overall models of thyroid iodine metabolism after being simplified to various degrees. Previously published models for thyroid-gland radioiodine metabolism, as well as current work in progress, are illustrated by attempting to fit the models to data from a single (previously unpublished) detailed prolonged ¹²⁵I feeding experiment in a normal human subject. Published thyroid gland models reviewed include: (1) the usual presentation, where the thyroid is a single homogeneous iodine compartment; (2) the model of DeGroot and colleagues, where thyroidal iodine is presented as MIT, DIT, T3, and T4, each with an active and linked storage compartment; (3) the thyroid model developed by Berman and colleagues, with less chemical subcategorization but incorporating a delay compartment, in which a fraction of the iodinated material in the thyroid is partially or completely inaccessible to secretion during the delay; and the later updating of Berman's model to include a thyroidal iodide recirculation pool. The experimental data presented fits most of these models for the first 1–2 weeks, but the fit could not be extended to longer data collection times. To overcome this shortcoming, a new thyroid gland model is introduced. It is based on the latest Berman model but describes thyroglobulin metabolism as incorporating multiple delay compartments of various time periods. The overall fit of the long term data is better with this model construct than with any of the published models. It appears that a complex thyroidal substructure, such as that of the multidelay model under development, will be required to account for overall thyroid iodine metabolism as isotopic equilibrium in man is approached.     

Effects of Iodine-131 in sheep depending on the content of stable iodine in the diet]

The biological effect of 131I was studied in sheep kept on a diet deficient in stable iodine. An increased capture and accretion of iodine in the thyroid gland and in the whole body were observed. The disturbances in the structure and function of the thyroid gland, liver and haemopoietic organs were more pronounced in the animals kept on the iodine deficient diet.     

Surgical correction of exophthalmos secondary to Graves' disease

Graves' disease has been recorded in the medical literature for more than 150 years. Despite introduction of iodine into the diet, Graves' disease still remains the most important disorder of the thyroid gland. Clinically, Graves' disease is a multisystem disorder of unknown etiology characterized by the clinical triad of infiltrative pretibial dermopathy, thyroid glandular hyperplasia, and ophthalmopathy. Expansion of the bony orbital volume is an effective method of treating moderate to severe exophthalmos. Our experience with a simplified version of a three-wall orbital decompression to correct exophthalmos secondary to Graves' disease is presented.     

The use of radioactive iodine in the treatment of Graves disease

Fifty patients with uncomplicated Graves' disease were treated with radioactive iodine (I(131)). Twenty-six patients who were followed for one year or longer are the basis of this report. Twenty-five are now euthyroid; only one is not completely well. The total dose of radioiodine administered varied from 0.5 to 10 millicuries. The average length of time necessary for return to a euthyroid state was from three to four months. Hypometabolism developed in three patients, and in one the signs and symptoms of myxedema developed. No other complications ensued. One patient who apparently relapsed had complete return to normal after further iodine administration. The determination of the uptake of radioactive iodine by the thyroid gland is a useful diagnostic procedure in differentiating conditions simulating hyperthyroidism.Following treatment with radioactive iodine, the thyroid gland becomes smaller, the uptake of iodine by the gland is reduced, and the level of organic iodine in the plasma becomes normal. In acute thyroiditis, in spite of a high basal metabolic rate, high content of organic iodine in the plasma and other evidences of "hyperthyroidism," the uptake of I(131) has been very low.