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A comparative study of iodine and potassium perchlorate metabolism in the laying hen. 2. Uptake, distribution, and excretion of potassium perchlorate.

The concentrations of 36Cl-labeled potassium perchlorate (K36CiO4) and previously reported iodide (131I) in the ova, thyroid gland, and blood of the laying hen were compared in this investigation. Radioperchlorate concentration and deposition properties showed a remarkable resemblance to those of iodide (131I). The topographic distribution of radioperchlorate in ova followed a peripheral and concentric ring deposition identical to that observed in the 131I investigation. The studies of the distribution of radioperchlorate showed that about 10.3, 2.0, and 1.4% of a single intramuscular injection of K36CiO4 was retained in the body at 3, 24, and 48 hours, respectively. The largest total concentration in the 3-hour group was found in the blood (2.9%), followed by muscles (2.4%), internal organs (1.1%), and the 10 largest ova (1.0%). The 24 and 48-hour hens' ova showed the largest concentrations with values of 1.5 and 1.2% of the dose, respectively. This represented 76.9 and 81.3% of the total activity retained in the body at these times. The excreta in the 3 and 24-hour experiments accounted for most of the radioperchlorate dose.

Animals

Perchlorate ion enhances mouse thyroid responsiveness to thyrotropin, human chorionic gonadotropin and long acting thyroid stimulator.

Perchlorate treatment of mice increased by 1.5-2-fold the thyroid secretory response to TSH, hCG and LATS, in the McKenzie bioassay. Perchlorate alone did not increase basal plasma radioactivity. Perchlorate augmentation of the secretory response index was roughly proportional to the level of stimulation; it was similar for all three stimulators despite their different time courses of action which were unaltered by perchlorate; it was the same whether perchlorate administration preceded, coincided with or shortly followed injection of the stimulator, a finding in keeping with the slow clearance of this ion. The perchlorate effect was dose-related, although within a narrow range (6.25-12.5 microng/mouse). Near-maximal per chlorate effect was obtained with a dose (12.5 microng) which, when tested in different experimental conditions (MMI-blocked thyroid), discharged 80% of intrathyroidal radioiodide. Perchlorate exerted its augmenting effect by enhancing thyroid secretion: it increased plasma radioiodothyronines and radioiodide concentrations without decreaseing the blood disappearance rates of iodide and iodothyronines. The potentiating effect of perchlorate probably takes place at a step prior to cyclic AMP action since it did not affect dbcAMP-stimulated secretion. The perchlorate effect may be indirect, through mobilization of minute amounts of intrathyroidal iodide.

Animals

Extraction of CEA from tumour tissue, foetal colon and patients' sera, and the effect of perchloric acid.

The use of perchloric acid and water for the extraction of CEA from tumour and foetal tissues has been investigated. In the case of tumour, lower recoveries of CEA were obtained from perchloric acid extracts than from aqueous extracts of the same tissue. CEA has also been extracted with 3M KCl solution from insoluble perchloric acid residues of tumour homogenates and cancer patients' serum. Whilst a large proportion of CEA activity recovered from tumour was associated with the perchloric acid residue, the corresponding amounts from serum were very small. CEA elution volumes for each extract, obtained by assay of Sephadex G-200 column fractions, showed significant heterogeneity in molecular size. The purified CEA pools also showed quantitative variations in the binding profiles on Con A-Sepharose. It has been shown that perchloric acid modifies the carbohydrate in CEA, thus altering its Con A-binding properties. Preliminary experiments with foetal colon have demonstrated that, unlike colorectal CEA, a significant proportion of foetal CEA was not bound to ConA. Comparative immunodiffusion showed immunological identity of CEA from the various extracts, although the purified aqueous extract produced an additional precipitin reaction, indicating a second antigen which is relatively unstable or less soluble in perchloric acid.

Bronchial Neoplasms

Stability of aqueous perchlorate formulations.

The stability of three aqueous perchlorate formulations used in nuclear medicine was studied as a function of the formulation and storage temperature. The formulations were intravenous potassium perchlorate solution, oral sodium perchlorate-sorbitol solution and oral potassium perchlorate in cherry syrup solution. The assays were conducted gravimetrically by precipitation with tetra-n-pentylammonium bromide. All formulations were found to be stable at least nine months. It is recommended that any formulation containing potassium perchlorate be kept at room temperature since precipitation of the active ingredient may occur if refrigerated. Sodium perchlorate formulations, however, may be refrigerated if desired because of their greater solubility.

Drug Stability

Accelerated fall in serum bromide level after administration of perchlorate to man.

Five patients intoxicated with bromoureide showed accelerated elimination of bromide from serum after a single dose of perchlorate. It was probably due to increased renal excretion of bromide. Perchlorate has been reported to increase the renal clearance of other monovalent anions by inhibiting their tubular reabsorption and a similar interaction between perchlorate and bromide is suggested. Although perchlorate effectively eliminates bromide it should not replace chloride in the treatment of bromide intoxication, because of the side effects of its repeated administration.

Adult

[Dose-time effects of competitive displacement of radiopertechnetate by sodium perchlorate following oral and intravenous administration].

The effect of various doses of sodium perchlorate in several dose fractions on the extent and the time scale of displacement of radiopertechnetate, in dependence on application mode, was studied. An intravenous dose of 50 mg perchlorate was in respect of competitive suppression of organs actively concentrating pertechnetate as effective as intravenous 1000 mg ClO-4- simultaneously or 1000 mg orally 30 min before the injection of radiopertechnetate. An intravenous injection of perchlorate given later also produces a complete and immediately beginning depletion of pertechnetate already accumulated in the thyroid, within a period of 195 min after 99m-TcO-4-injection with a corresponding increase in blood levels. 20 mg result in incomplete depletion which becomes complete after a second additional dose. The intravenous application of perchlorate offers advantages in clinical use.

Administration, Oral

Immunization against experimental Chagas' disease by using culture forms of Trypanosoma cruzi killed with a solution of sodium perchlorate.

Protection against infection with virulent blood (trypomastigote) forms of Trypanosoma cruzi was accomplished in mice by immunization with culture (mainly epimastigote) forms killed by treatment with sodium perchlorate. Sodium chloride, used instead of sodium perchlorate, with all other conditions kept the same, failed to kill all the organisms, indicating that the effects of the perchlorate anion were not simply ionic or osmotic, suggesting that they might be chaotropic. A single dose of the immunogen, without adjuvants, was sufficient to significantly protect against the infection. Protection was achieved by either intraperitoneal, intramuscular, or subcutaneous immunization, though the first two routes appeared to be more effective. After challenge, parasitemias were negative in 25, 29, and 17% of the animals immunized intraperitoneally, intramuscularly, and subcutaneously, respectively.

Animals

[Effect of potassium iodide and perchlorate on the process of thyroid hormone secretion].

The influence of potassium iodide and perchlorate on the parameters characterizing the thypoid hormones secretion, such as the cAMP level in the gland tissue and the number of intracellular colloid droplets under condition of stimulation by thyrotropic hormone was studied. It was shown that the abovementioned parameters were depressed by an excess of iodide, but perchlorate administration prevented the inhibitory effect of iodide. The results obtained favour the conception on the sensitivity of the thyroid adenylate cyclase system to the organic iodine concentration. Apparently and excess of iodide depressed the capacity of perchlorate to influence its concentration in the gland, and thereby the process of iodine organification and of the thyroid hormone secretion maintained at the optimal leve.

Animals

Loss of ATP in micromolar amounts after perchloric acid treatment.

Treatment of fluid samples containing known amounts of ATP with 6.0 N perchloric acid (PCA) results in a total loss of 65-71% when the initial concentrations of ATP ranged between 0.5 to 50 muM. Half of this loss was attributed to desensitization of firefly extract (luciferin-luciferase reaction) while the remaining loss was presumably due to adsorption of ATP to perchlorate precipitate upon neutralization. Similar treatment of solutions with higher initial concentrations (100-1000 muM) resulted in apparent total losses averaging 22%. These losses were due solely to desensitization of firefly extract by neutralized PCA. Both the adsorption and desensitization phenomena must be taken into account when the ATP content is measured from tissue extracts and fluid samples subjected to this procedure.

Adenosine Triphosphate

Rapid radioimmunoassay of carcinoembryonic antigen (CEA) in ultrafiltered perchloric acid extracts: results of a clinical survey.

Perchloric acid treatment of the carcinoembryonic antigen (CEA) results in subunits of approximate mol. wt 40 000 to 50 000 with different electrophoretic mobilities and amtogenic deficiences as demonstrated by immunoelectrophoresis. An improved radioimmunoassay is described for the quantitation of CEA using rapid ultrafiltration of serum or plasma extracts. The assay was designed to take into account the changes CEA undergoes during perchloric acid extraction. Absorption of antibodies against a crossreacting non-specific antigen from CEA antiserum did not improve the specificity of the radioimmunoassay as was shown by clinical use of the test in almost 1800 patients.

Animals

Effect of pentagastrin, histalog, glucagon, secretin, and perchlorate on the gastric handling of 99mTc pertechnetate in mice.

Pentagastrin, histalog, glucagon, secretin, and perchlorate were intravenously injected into mice in order to investigate the hormonal regulation of 99mTc pertechnetate uptake by gastric mucosa. Pentagastrin significantly increased uptake; the effect of histalog was weaker. Secretin did not alter the uptake. Glucagon produced some diminution, and perchlorate significantly inhibited gastric uptake. Hormones may play a role in improving the sensitivity and specificity of diagnostic tests for Meckel's diverticulum.

Animals

Kinetic analysis of iodide transport in dog thyroid slices: perchlorate-induced discharge.

Dog thyroid slices were incubated with methimazole (2 mM) and radioiodide. The medium radioactivity was continuously recorded for 8 h. Multiple data were collected for individual glands to calculate simultaneously by compartmental analysis the influx and efflux rates of iodide from the slices. A two-compartment thyroid model was necessary and sufficient to simulate the transport of inorganic iodide. The two compartments could be defined as the cellular and the luminal spaces, but interferences due to slice thickness, nonuniform follicle sizes, and open follicles were not excluded. Sodium perchlorate (1 mM) inhibited the influx of iodide into the follicles and discharged the trapped radioiode into the medium with increased efflux rates. Our data suggest that perchlorate decreases the inward influx rates by competition and enhances the outward efflux rates by countertransport and support the hypothesis of mobile iodide carriers at the basal and apical membranes of the thyroid cells.

Animals

Rat mammary gland atypia produced by iodine blockade with perchlorate.

Prior published work from our laboratory concluded that there was a need for appropriate metabolic activity of iodine in breast tissue for normal growth and development. Results from studies in rats that were made iodine deficient showed histological changes in the breasts that were atypical and dysplastic. These tissue findings were further affected by the presence of estrogen and thyroxine. These changes parallel the iodine uptake of the tissues, thus representing a difference in the utilization of iodine by the mammary glands. Using an ion blockade agent, sodium perchlorate, breast tissues lacking iodine were evaluated by both endocrine and histological techniques. A dose-response series was completed that showed that perchlorate therapy for 8 weeks at 400 mg/100 ml produced breast blockade by a reduction in iodine uptake of greater than 52% of the control. At these levels, the histological experimentation showed atypia and some pleomorphism of the cells, particularly in the glands of the lobules. Blockade was less effective in estrogen-treated groups. It is especially notable that both histological changes and uptake reduction were greatest in those breasts that had been rendered euthyroid by thyroxine replacement, thus clearly indicating the necessity of iodine itself for maintenance of normal breast development. By this blockade the responses of iodine inadequacy in the breast were shown to cause abnormal tissue changes relative to the percentage of the block obtained.

Animals

Rectal perchlorate for unconscious patients prior to brain scintigraphy with pertechnetate: concise communication.

Patients undergoing brain scintigraphy with pertechnetate are frequently premedicated with oral perchlorate. However, the oral route is difficult to employ in unconscious or uncooperative patients or when oral intake is restricted. In such situations, rectal administration of sodium perchlorate dissolved in water is an effective alternative to oral administration.

Brain Diseases

Kinetics and mechanism of oxidation of promazine and promethazine by ferric perchlorate.

The equilibrium constants, kinetics, and mechanism of promazine and promethazine oxidation by ferric perchlorate were investigated at different temperatures and acidities using a stopped-flow spectrophotometric technique. The overall reaction can be represented as follows: (formula: see text) where P+ represents the radical cation corresponding to the phenothiazine derivative. The equilibrium quotients were evaluated at 1.00 M HClO4, 25.0 degrees, and ionic strength 1.0 M. The kinetics of reaction follow the equation: -d[P] divided by dt = k1[Fe3+][P]-k-1[Fe2+][P+] The rate constants k1 and k-1 are independent of acidity and are related to the corresponding equilibrium quotients.

Chemical Phenomena

Kinetic studies on the formation of nitrosamines I. Formation of dimethylnitrosamine in aqeous solution of perchloric acid.

The kinetics of nitrosation of dimethylamine (DMA) in aqueous perchloric acid solution have been studied using a differential spectrophotometric technique. The rate law is Initial rate = e[DMA]0 [nitrite]2 0 [H+]/(f + [H+])2 where [DMA]0 and [nitrite]0 represent initial stoichiometric concentrations. At 310.0 K and mu = 2.0 M, e = (2.2 +/- 0.2) X 10(-5) M-1 s-1 and f = (1.28 +/- 0.02) X 10(-3) M. The associated activation energy is 56 +/- 3 kJ mol-1. A clear inhibition of the nitrosation rate by ionic strength has been observed in which only the kinetic parameter (f) has an effective change. It is concluded that under the experimental conditions of this work only the dinitrogen trioxid is the effective carrier for the nitrosation.

Dimethylnitrosamine

Comparison of whole plasma and perchloric acid-extracted plasma assays for carcinoembryonic antigen.

A direct, paired, comparison was made of two plasma radioimmunoassays for carcinoembryonic antigen (CEA), between a perchloric acid-extracted, ammonium sulphate precipitation method; and a whole-plasma, double-antibody method. For both assays the same preparations of standard CEA, 125I-labelled CEA, and anti-CEA serum were used. Plasma samples were taken from young healthy subjects (24), cancer-free hospital inpatients (44) and cancer-proven untreated patients (94). Within-batch and between-batch variation were both greater for the extracted-plasma method. Cancer discriminatory ability was assessed by probabilistic means. With cancer-free inpatients as the reference group, no difference between the assay methods was revealed. With young healthy subjects as the reference group the whole-plasma assay was superior.

Adult