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Short term administration of potassium perchlorate restores euthyroidism in amiodarone iodine-induced hypothyroidism.

We studied the effect of potassium perchlorate (KClO4) in patients with hypothyroidism due to amiodarone. The short term administration of KClO4 to six such patients led to prompt restoration of euthyroidism, while the three untreated patients remained hypothyroid for 2-6 months. Since KClO4 inhibits thyroid iodide transport, thereby blocking further entrance of iodide into the thyroid and decreasing intrathyroidal iodide content, amiodarone-associated hypothyroidism is probably secondary to the inhibitory effect of excess intrathyroidal iodine on thyroid hormone synthesis.

Adult↗

The iodine perchlorate discharge test before and after one year of methimazole treatment of hyperthyroid Graves' disease.

We have recently reported that many euthyroid patients with a history of Graves' disease treated years earlier with methimazole (MMI) have a positive iodide (500 micrograms)-perchlorate discharge test (I-ClO4 test), suggesting a permanent thyroid iodide organification defect. We now report the results of the I-ClO4 test in patients with hyperthyroid Graves' disease before beginning a 1-yr course of MMI therapy and 40 days after MMI was discontinued. Twenty-nine patients (25 women and 4 men; mean age, 38 +/- 1.7 yr) with their first episode of hyperthyroid Graves' disease were studied. Before MMI therapy, I-ClO4 tests were carried out, and serum T4, T3, and TSH were measured to confirm the diagnosis of hyperthyroidism. A positive I-ClO4 test is defined as more than 15% 131I discharged from the thyroid 1 h after the administration of 1 g KClO4. Patients were then treated with 20 mg MMI for the first 2 months and variable doses thereafter for the next 10 months to maintain euthyroidism. Serum T4, T3, and TSH were measured monthly. Forty days after MMI was discontinued, I-ClO4 tests were repeated, and serum T4, T3, and TSH were measured every 2 months thereafter. Before MMI treatment, the I-ClO4 test was positive in 20 of 29 patients (69%) and negative in 9. The favorable responses (normal serum T4 and T3 values) to MMI therapy were similar in both groups. We have thus far studied 16 patients after MMI was discontinued and 9 of 12 patients (75%) with a negative I-ClO4 test after MMI therapy, and 1 of 4 patients (25%) with a positive test remained in remission for a mean of 7 months. We conclude that the I-ClO4 test is frequently positive in patients with untreated hyperthyroid Graves' disease, suggesting either an inability to organify the increased iodide concentrated by the hyperfunctioning gland or the concomitant presence of Hashimoto's thyroiditis, which almost always is associated with a positive I-ClO4 test. The former hypothesis is more likely, because many patients with a positive I-ClO4 test before MMI therapy had a negative test after MMI was discontinued.

Adult↗

[Some chemical and serological properties of perchloric acid-soluble glycoproteins separated from ascitic fluid of a patient with metastatic omentum tumor from ovarian cancer].

One mol perchloric acid-soluble fraction (PASF) obtained from ascitic fluid of a patient (blood group B) with metastatic omentum tumor from ovarian cancer was a glycoprotein fraction containing 35.4% carbohydrate and exhibited A, B and Thomsen-Friedenreich (T) activities. This fraction was separated into three fractions, Frs. 1-3, by a gel filtration with Bio-Gel A-1.5 m column. Among these fractions, Fr. 1 which was obtained in a 5.5% yield to PASF, was a glycoprotein fraction with a high molecular weight, 23.3% carbohydrate and A, B and T activities. Other minor fraction, Fr. 2, and the major fraction, Fr. 3, contained 43.2% and 43.9% carbohydrate, but did not show A, B and T activities, respectively.

ABO Blood-Group System↗

[Separation of Thomsen-Friedenreich (T) antigen and N antigen precursor glycoproteins from perchloric acid-soluble fraction of cyst fluid of human ovarian clear cell carcinoma and their some chemical and serological properties].

One M perchloric acid-soluble fraction separated from cyst fluid of a patient (blood group AB) with ovarian clear cell carcinoma in malignant was subjected to Sephacryl S-200 gel filtration and Fraction 1 which was eluted at void volume, reacted with both of the lectins of Vicia unijuga and Arachis hypogaea. This fraction was then separated into 6 fractions (DEAE-Frs. 1-6) in a DEAE-Sephacel column chromatography. DEAE-Frs. 3-6 were sugar-rich glycoprotein fractions which contained galactose and N-acetylglucosamine in remarkably high percentages, respectively. Reactivities against various hemagglutinins of these four fractions suggest that DEAE-Fr. 3 is a Thomsen-Friedenreich (T) glycoprotein fraction with AB activity and weak N antigen precursor activity and DEAE-Fr. 4 is an N antigen precursor glycoprotein fraction with AB activity and weak T activity.

Adenocarcinoma↗

[Serological property of perchloric acid-soluble glycoprotein fractions of human meconium].

Perchloric acid-soluble fractions (PASFs) were separated, in yields of 87.0-151.9 mg per 1.0 g of wet meconium sample, from six samples of human meconium, and identified as glycoproteins having 41.2-74.1% carbohydrate by chemical composition analysis. Six PASFs reacted with anti-A, -B, -Lea and -Leb sera, but did not react with anti-M and -N sera. These PASFs alos reacted with many lectins such as DBA, UEA-I, Vicia graminea lectin (VGA), Vicia unijuga lectin (VUA), Con A, WGA, RCA-I, PHA-E, SBA, SJA, and influenza A and B viruses. The serological results show that six PASFs contained VGA or VUA-binding (Vgu) glycoproteins as new oncofetal substances, but did not contain M and N blood group substances.

Amino Acids↗

Thyroid function and perchlorate in drinking water: an evaluation among California newborns, 1998.

Perchlorate (ClO4-) has been detected in groundwater sources in numerous communities in California and other parts of the United States, raising concerns about potential impacts on health. For California communities where ClO4- was tested in 1997 and 1998, we evaluated the prevalence of primary congenital hypothyroidism (PCH) and high thyroid-stimulating hormone (TSH) levels among the 342,257 California newborns screened in 1998. We compared thyroid function results among newborns from 24 communities with average ClO4- concentrations in drinking water>5 microg/L (n=50,326) to newborns from 287 communities with average concentrations 5 microg/L were observed, with 20.4 expected [adjusted prevalence odds ratio (POR)=0.71; 95% confidence interval (CI), 0.40-1.19]. Although only 36% of all California newborns were screened before 24 hr of age in 1998, nearly 80% of newborns with high TSH were screened before 24 hr of age. Because of the physiologic postnatal surge of TSH, the results for newborns screened before 24 hr were uninformative for assessing an environmental impact. For newborns screened>or=24 hr, the adjusted POR for high TSH was 0.73 (95% CI, 0.40-1.23). All adjusted odds ratios (ORs) were controlled for sex, ethnicity, birth weight, and multiple birth status. Using an assessment of ClO4- in drinking water based on available data, we did not observe an association between estimated average ClO4- concentrations>5 microg/L in drinking water supplies and the prevalence of clinically diagnosed PCH or high TSH concentrations.

California↗

Raman spectroscopic detection for perchlorate at low concentrations.

Perchlorate (ClO4-) has recently emerged as a widespread environmental contaminant found in groundwater and surface water, and there is a great need for rapid detection and monitoring of this contaminant. In this study, we explore the use of surface-enhanced (SERS) and normal Raman spectroscopy for detecting ClO4- at low concentrations. We found that ClO4- is SERS active and, for the first time, were able to detect ClO4- at concentrations as low as 10(-6)-10(-7) M (or 10-100 microg/L) through the application of silver SERS substrates or selective sorbents such as bifunctional anion-exchange resins. The use of selective sorbents greatly enhanced the reproducibility and sensitivity of ClO4- detection by normal Raman spectroscopy. Further exploration and research may allow application of these techniques for in situ, real-time detection and monitoring of ClO4- in environmental samples at even lower concentrations.

Perchlorates↗

New surface-enhanced Raman spectroscopy substrates via self-assembly of silver nanoparticles for perchlorate detection in water.

Perchlorate (ClO4-) has recently emerged as a widespread contaminant in drinking water and groundwater supplies in the United States, and a need exists for rapid detection and monitoring of this contaminant. In this study, surface-enhanced Raman spectroscopy (SERS) was studied as a means of ClO4- detection, and new sol-gel-based SERS substrates were developed by self-assembly of silver colloidal nanoparticles with various functionalized silane reagents. These substrate materials were tailored to allow detection of ClO4- in water with improved sorptivity, stability, and sensitivity and with the ability to detect ClO4- at concentrations as low as 10(-6) M (or 100 microg/L) with good reproducibility. Similar techniques were used to fabricate capillary SERS flow cells by assembling functionalized silver nanoparticles capable of attracting ClO4- to the SERS surface or the internal wall of glass capillaries. These capillary flow cells could be readily configured to allow for in situ, nondestructive detection of ClO4- via fiber optics.

Crystallization↗

Simultaneous spectrophotometric calibration of wavelength and absorbance in an interlaboratory survey using holmium oxide (Ho2O3) in perchloric acid as reference, compared with p-nitrophenol and cobaltous sulphate solutions (1978-1984).

The wavelength accuracy of ten different types of spectrophotometer was tested with holmium perchlorate solutions. It was found to be good, with mean deviations from the literature values of maximally 0.3 nm. Standard deviations over the entire spectral range were within 0.75 nm. The absorbance accuracy for different types of instruments was generally within 5%, except in the 287 nm range where higher deviations were found. The sharpness of the holmium peaks, in combination with band width and sensitivity of the instruments, troubled the majority of the participants. 150 spectrophotometers were involved in the surveys. Linearity of the spectrophotometers was tested with p-nitrophenol and cobaltous sulphate and found to be satisfactory.

Chemical Phenomena↗

Inhibition of iodide accumulation by perchlorate and thiocyanate in a model of the thyroid iodide transport system.

The manner of inhibition of thyroid I- accumulation by perchlorate (CIO4-) and thiocyanate (SCN-) was studied using a newly developed biological model of the I- transport system. CIO4- inhibited I- accumulation in phospholipid vesicles made from thyroid plasma membrane and soybean phospholipids by decreasing Na+-dependent I- influx. The anion did not at all induce I- leakage from the vesicles. On the basis of Lineweaver-Burk plot analysis, it did not change Vmax for I- concentration. These results suggest that CIO4- is a competitive inhibitor of thyroid I- transport. In contrast, SCN- did increase I- leakage from the phospholipid vesicles to diminish I- accumulation. This anion might cause only slight depression of Na+-dependent I- entry, if any. The results do not support the idea that SCN- may be a competitive inhibitor, in spite of the fact that the anion did not change Vmax for I- transport on the basis of Lineweaver-Burk plot analysis.

Cell Membrane↗

Endotoxemia in liver diseases: detection by a quantitative assay using chromogenic substrate with perchloric acid pretreatment.

With a quantitative blood endotoxin assay using a chromogenic substrate with a perchloric acid pretreatment (PCA-LCT), endotoxemia in various liver diseases was studied. With PCA-LCT, recovery of added endotoxin in human plasma was nearly 90%, as evidenced by an intra- and inter-assay coefficients of variation of 5.7% and 11%, respectively. Because the recovery of endotoxin was not affected in severely icteric plasmas, PCA-LCT proved to be applicable to patients with liver diseases where various degree of jaundice exist. In none of the plasmas from patients with chronic hepatitis, acute hepatitis without hepatic failure or liver cirrhosis without ascites did the endotoxin level exceed the normal range of less than 5 pg/ml. With the presence of ascites, however, endotoxemia became detectable, but at low levels and not in all cases. At the stage of hepatic failure complicated with renal failure or disseminated intravascular coagulation, endotoxemia was more frequent and endotoxin concentration greater. It is uncertain, at present, whether endotoxemia itself is deteriorating factor in hepatic failure or is merely concomitant phenomenon resulting from Kupffer cell failure.

Ascites↗

Influence of sodium perchlorate on thiourylene antithyroid drug accumulation in mice.

Radiolabelled [35S]propylthiouracil and [35S]methimazole were shown to accumulate in mouse thyroid gland in vivo, with maximal tissue/plasma ratios and maximal intrathyroidal levels of 35S-labelled drug being seen at the lowest dose of drug studied (0.1 micrograms/animal). Pretreatment with sodium perchlorate (10 mg) abolished iodide trapping by the thyroid and caused a fall in accumulation of both [35S]methimazole and [35S]propylthiouracil, although this effect was not seen at higher doses of drug, when tissue/plasma ratios approached unity. These data suggest that thiourylene antithyroid drug accumulation by the thyroid gland does not depend directly on the anion trap, and it is suggested that this accumulation might depend on subsequent intrathyroidal drug metabolism.

Animals↗

[Analysis of iodine compounds in young rat skin in the period of suckling and in the adult. Effect of perchlorate].

In the suckling and adult rats equilibrated or no by 125I, cutaneous iodine analysed by dialysis and chromatography techniques (Dowex and Sephadex) was the purpose of this study. Dialysis studies had shown that most of steady or labelled skin iodine had an iodide form (90 to 95% of the total iodine). There were at least two intracellular iodide pools: the first one was quickly dialysable, in fact about 60 percent of initial radioactivity represented the intracellular iodide equilibrated with extracellular fluid. The other one wasn't or was little dialysable representing probably the cutaneous iodide storage compartment. Chromatography studies (Dowex or Sephadex) demonstrated that the skin of the young and adult rat contained T4 and T3 hormones in a small percentage. The iodide represented a value more than 90% of initial total radioactivity. Results concerning kinetic skin iodine, eight and twenty four hours after LT4(125)I injected to adults and to control and iodine deficient ten day old rats, confirmed those obtained here by Dowex chromatography and previous ones. Triiodothyronine (T3) might have an origin either in thyroid synthesis or in deiodination of T4. Consequently we may say that the skin of the 10 day and 14 day old rats presented a great accumulation of iodide. The perchlorate inhibited this storage. Indeed, in young deficient iodine rats at birth, cutaneous iodide concentrations were reduced whereas those of T4 and T3 as well as the ratio T3/T4 haven't been modified. Therefore the iodine deficiency seemed to have a few effects on the skin deiodinating activity. Indeed the skin of iodine deficient immature rat became unable to accumulate iodide. The main effect of the skin iodine deficiency was the inhibition of iodide transport from the extracellular fluid to the intracellular one, but not inside cellular structures.

Animals↗

Isolation of perchloric acid soluble, heat stable, ethanol extractable protein from Mycobacterium tuberculosis.

The perchloric acid soluble, heat stable, and ethanol insoluble antigen of M. tuberculosis (TB-PBE) was prepared, and antigenicity of this antigen was studied in vivo and in vitro. TB-PBE showed a single band of 60 kDa by SDS-PAGE. Sera from the patients with active pulmonary tuberculosis did not react with this antigen by ELISA. A delayed hypersensitivity skin reaction was induced with this antigen and was correlated with the reaction with PPD. Skin biopsy was performed in this skin lesion induced by TB-PBE and stained by H-E and immunohistochemical methods. TB-PBE induced an inflammatory lesion similar to a lesion induced by PPD. Blastogenic activity of the peripheral blood mononuclear cells stimulated by TB-PBE increased, and showed a peak reaction at 7 days after stimulation. The blastogenic activity changed in a dose-dependent manner. After stimulation with TB-PBE, mononuclear cells were analyzed by FACS. DR+ T cells and CD4/CD8 ratio increased after stimulation by TB-PBE. These cells secreted IL-2, not IL-4 after stimulation with TB-PBE. In the immunofluorescence test, mouse antiserum against TB-PBE showed a positive reaction with M. tuberculosis and showed cross-reactivity with M. bovis and other atypical mycobacteria, but not with S. aureus. With these results, it is evident that TB-PBE is an antigen which can induce cell mediated immunity in vivo and in vitro.

Animals↗

[The role of scintigraphy with dual tracer and potassium perchlorate (99mTcO4 & KClO4/ MIBI) in primary hyperparathyroidism].

BACKGROUND: The diagnostic value of scintigraphy using a dual tracer and high-resolution neck ecotomography in the preoperative localisation of parathyroid enlargements was evaluated in a group of consecutive patients suffering from primary hyperparathyroidism (HPT) who were uniformly studied and subsequently operated by the same surgical team. METHODS: Scintigraphic imaging and high-resolution neck ecotomography were carried out in a single session on 143 patients. Scintigraphic imaging was performed using a dual tracer, 99mTc-pertechnetate/99mTc-MIBI), modified by the addition of potassium perchlorate (KCL04) to achieve a rapid washout of 99mTc04 from the thyroid and, consequently, to achieve good quality and rapid MIBI images. In a limited number of patients (21 cases) SPECT was also performed. Limited surgery was planned in patients with evidence of single parathyroid lesions and with normal thyroid parameters, in the form of either unilateral or with mini-invasive surgery (91 cases). Patients with eco-scintigraphic evidence of multiglandular parathyroid pathology or the coexistence of a nodular thyroid goitre, or in patients suffering from MEN or familial HPT, or lastly those with negative eco-scintigraphic results under-went more extensive surgery with bilateral exploration of the neck (52 cases). A single parathyroid lesion was diagnosed during surgery in 90 out of 91 patients undergoing planned unilateral or mini-invasive exploration of the neck. Therefore, in our experience, the predictive value of preoperative imaging as a mean of identifying single parathyroid lesions was 98.9% with a clear impact on the choice of conservative surgery. After the removal of the parathyroid to which preoperative imaging referred, it was only necessary in one patient to extend surgical exploration to the other side of the neck to remove another enlarged parathyroid owing to persistent high PTH. RESULTS: The sensitivity of scintigraphy and high-resolution neck ecotomography in pa-tients with a single adenoma was 94% and 83.7% respectively, whereas it was 76.9% and 64.5% respectively in the group of patients with multiglandular pathology. It is worth underlining that in all 31 patients with associated nodular thyroid pathology, the evaluation of thyroid scintigraphic imaging using 99mTc04 and high-resolution neck ecotomography enabled the preoperative diagnosis of thyroid pathology, therefore guiding the surgeon towards more extensive surgery. SPECT enabled the parathyroid adenoma to be correctly localised in a deep site in 5 patients, in the neck in 3 cases and at the mediastinum in 2 patients, providing additional data that helped the surgeon to plan surgery. CONCLUSIONS: In conclusion, in our experience: a) an integrated diagnostic approach based on scintigraphy 99mTc04 & KCLO4/MIBI and high-resolution neck ecotomography was an extremely accurate mean of identifying patients with single parathyroid lesions before surgery, enabling them to undergo limited surgery, b) scintigraphy with a dual tracer might be the elective methods for studying patients with HPT because it allows the contemporary diagnosis of possible thyroid diseases. This aspect is extremely important in geographical areas with a high predominance of nodular thyroid pathology, c) SPECT scintigraphic analysis may be useful in some patients with suspected parathyroid adenoma localised in a deep seat, allowing a more precise identification of the latter and better surgical planning.

Adenoma↗

Semipreparative scale enantioseparation of racemic amine and amino ester hydrogen perchlorate salts using a silica gel-bound optically active di-tert-butylpyridino-18-crown-6 ligand.

We report herein results on the enantioseparation of selected racemic amine and amino ester hydrogen perchlorate salts using a silica gel-bound optically pure chiral di-tert-butylpyridino-18-crown-6 ligand (R,R)-1. The effect of solvent composition was studied using appropriate binary and ternary solvent mixtures as eluents. We found that acetonitrile/ methanol/ dichloromethane (MeCN/MeOH/CH2 Cl2 ) ternary solvent mixtures gave better enantioseparations for the racemic salts using chiral stationary phase (R,R)-1 than any of the binary ones. In the present paper we also describe the studies of chromatographic parameters such as loading, flow rate and eluent polarity.

Ethers, Cyclic↗

[Propythiouracil and perchlorate effects on thyroid function in young and lactating mice].

We have studied the effects of propythiouracil (PTU) or perchlorate (CIO(4)(-)), given to the mothers' drink from the 15(th) day of pregnancy until the day of sacrifice, on thyroid function of suckling mice. Antihyroid drugs (PTU or CIO(4)(-)) provoked growth perturbations of young mice during studied ages from 6 to 18 days. A decrease of body weight was respectively as follows: 14 and 22% in 6 day-old mice; 16 and 23% in 10 day-old mice; 18 and 18% in 14 day-old mice; 19 and 11% in 18 day-old mice. We have noticed an hypertrophy of thyroid glands of pups and their mothers caused by an increase of pituitary TSH. Thyroid follicles presented the aspect of hypothyroid animals with an increase of follicular number and vascularisation. Structural modifications confirmed biochemical results. In fact thyroid iodine contents decreased strongly in young as follow: 40 and 43% in 6 day-old mice; 51 and 50% in 10 day-old mice; 66 and 84% in 14 day-old mice; 54 and 89% at 18 day-old mice and in their mothers (50, 37%; 59, 54%; 75, 65% and 85, 72%) respectively after PTU or CIO(4)(-) treatment. A decrease of iodine thyroid gland was accompanied by an important fall of free thyroid hormones levels (FT3 and FT4) in young and adult mice. A decrease of thyroid hormonemia could explain the pups' growth perturbations.

Aging↗