[EFFECT OF COMPLEXONS ON THE EXCRETION OF TOXIC METALS AND TRACE ELEMENTS AND ON THE STATUS OF BIO-COMPLEXONS].
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Chelating Agents↗
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Interference by haemoglobin with the cresolphthalein complexone method for serum calcium measurement.
The spectral interference caused by haemoglobin in the calcium-cresolphthalein complexone reaction was investigated. The results show that the nature of the haemoglobin derivative in the reaction mixture influences the degree of interference; in turn, the derivative formed depends on the order in which the sample and reagents are added. Methods using a single, alkaline cresolphthalein complexone reagent are most seriously affected by haemolysis due to persistence of oxyhaemoglobin. If the sample is added to an acid cresolphthalein complexone reagent then acid haematin is formed, this being converted to a different derivative on the addition of alkali, producing less pronounced interference. The addition of the sample to a buffer, followed by addition of complexone, appears to offer a means to correct for moderate haemolysis in the sample.
Buffers↗
A novel series of complexones with bis- or biazole structure as mixed ligands of paramagnetic contrast agents for MRI.
We describe the syntheses, physicochemical properties and biological evaluation of a novel series of complexones containing bis- or biazoles moieties and two iminodiacetic acid units as novel ligands for paramagnetic lanthanides. The complexones were prepared by reaction of the corresponding 1,1'-bishaloethylbi- or bispyrazoles with methyl iminodiacetate and subsequent NaOH hydrolysis. 1,1'-Bisbromoethyl precursors were obtained by direct alkylation with an excess of 1,2-dibromoethane, or by heating the corresponding alcohol in HCl. Sigmoidal binding isotherms and MO calculations supported as most stable structures in solution, those containing two Gd(III) atoms bound per molecule of complexone with half saturation values S(0.5) (M(-1), 22 degrees C, pH 7.2) in the range 6.5 10(-6)<S(0.5)<36.1 10(-6). Relaxivity properties [r(1), r(2), s(-1) mM(-1) Gd(III)] determined at 1.5 Tesla gave values (12.0<r(1)<17.7, 12.2<r(2)<20), improving significantly the relaxivities of reference compounds such as Gd(III)EDTA (5.2, 5.6) or Gd(III)DTPA (4.30, 4.30). These improvements involve mainly increased hydration and slower rotational motions. In vitro toxicity experiments are reported.
Animals↗
Some observations on the nature of the calcium-cresolphthalein complexone reaction and its relevance to the clinical laboratory.
The reasons for the non-linearity of the standard curve for the calcium-cresolphthalein complexone reaction have been investigated. Calcium forms both 1:1 and 2:1 complexes with cresolphthalein complexone; at low calcium concentrations the 1:1 complex predominates and causes non-linearity. At high calcium concentrations the cresolphthalein complexone concentration becomes limiting, resulting in flattening of the calibration curve. It is recommended that two-point calibration of the assay be performed using a low calcium standard rather than setting on the baseline.
Calcium↗
[Effectiveness of the therapeutic use of complexones in various diseases of the extrapyramidal system in children].
The article is devoted to therapy of some extrapyramidal diseases related to accumulation of biomicroelements in the basal ganglia. Two clinical observations (Fahr's disease and Hallervodren-Spatz' disease) in children are described. In both cases therapy with complexones (xydifon, penicillamine, deferoxamine) combined with antioxidants, calcium antagonists, drugs improving the microcirculation, etc., produced a marked positive effect. This was the first case of using complexones for treating Fahr's disease. Possible ways of correcting the metabolism of trace elements in diseases affecting the central nervous system, in particular perspectives of wider application of complexones are discussed.
Adolescent↗
Gadolinium-phthalein complexone as a contrast agent for hepatobiliary MR imaging.
Gadolinium-phthalein complexone (Gd-PC) was developed as a hepatobiliary magnetic resonance (MR) contrast agent. Phthalein complexone is one of the iminodiacetic acid derivatives and a structural analogue of bromosulfophthalein. Gadolinium-PC substantially enhanced signal intensity of normal functioning livers on T1-weighted MR images. Contrast enhancement of rabbit liver and gradual accumulation of high intensity bile in the gallbladder were observed after intravenous injection of 0.05 and 0.1 mmol/kg Gd-PC. However, 0.1 mmol/kg of Gd-DTPA caused little effect on liver MR.
Animals↗
[Biological action of 239Pu during intake by inhalation and complexon therapy with Zn or Ca DTPA under experimental conditions].
The authors described the effect of substantial amounts of plutonium nitrate administered to rats by inhalation in the presence of Zn- or CaDTPA-complexon therapy for 2 months. A 2-fold decrease of absorbed doses in the lung, a 3-fold decrease in the skeleton and a 4-fold decrease in the liver were shown. The mean life of the treated animals was considerably raised. A significant reduction of the frequency of development of severe pneumosclerosis and an increase in the frequency of lung tumor development were noted. In view of the above, complexon therapy should be necessarily recommended during inhalation of radionuclides in substantial amounts.
Administration, Inhalation↗
[Effect of antioxidants and complexons on the stability of the microbiological standard for mycoheptin].
Stability is one of the most important indices of the quality of antibiotic microbiological standards. At present the expiry date of the mycoheptin standard (a specially purified preparation) is 1 year when stored in sealed ampoules in an inert gas at a temperature of -20 degrees C. To prolong the expiry date of the standard the effect of various antiohidants and complexons on its stability was studied with the method of "accelerated aging". Sodium hexametaphosphate and Trilon B were tested as complexing agents and propyl gallate, ionol, N-phenyl-2-napththyl amine, mannitol and their mixtures were tested as antioxidants. The substances were applied in an amount of 3 per cent of the antibiotic weight. The favourable effect of the complexons on mycoheptin stability was shown. Their stabilizing effect was potentiated by addition of certain antioxidants.
Antibiotics, Antineoplastic↗
[Effect of polymer complexons based on vinylpyrrolidone copolymers with vinyliminodiacetic acid and methacrtloylacetone on the antibiotic sensitivity of antibiotic-resistant bacterial strains].
Polymer complexons, such as copolymers of vinylpyrrolidone with vinyliminodiacetic acid and metacryloilacetone changed the permeability of the bacterial cell wall due to chelating of the metalic ions contained in the cell wall. An increase in the bacterial sensitivity to chloretracycline, methicillin, ampicillin and methicillin was observed in the presence of the above complexons.
Anti-Bacterial Agents↗
Spectral shifts of cytochrome c oxidase induced by complexons.
Ca2+-chelating agents, such as EDTA and ATP, are shown to bring about a rapid spectral response of the oxidized cytochrome c oxidase due to reversal of the Ca2+-induced red shift of the gamma- and alpha-absorption bands of the ferric enzyme. In addition, complexons are found to bring about Ca2+-independent, slow irreversible spectral changes indicative of a conformational transition of cytochrome oxidase. 1 mol EDTA per mol enzyme is sufficient to produce the maximal effect even in the presence of excess Ca2+, indicating high specificity of interaction. It is suggested that the conformation of cytochrome c oxidase may be regulated by the tightly bound "non-redox' metal ions (Mg, Zn, Cux) known to be present in the enzyme. These ions might be involved in specific binding of physiological effectors with chelating properties, such as ATP.
Adenosine Triphosphate↗
Rhizoferrin: a complexone type siderophore of the Mucorales and entomophthorales (Zygomycetes).
The present investigation presents evidence that rhizoferrin, a novel polycarboxylate or complexone-type siderophore, originally isolated from Rhizopus microsporus, represents the common siderophore within the Zygomycetes. Thus, rhizoferrin could be detected by HPLC analysis in various families of the Mucorales, e.g., Rhizopus microsporus var. rhizopodiformis, Mucor mucedo and Phycomyces nitens (Mucoraceae), Chaetostylum fresenii and Cokeromyces recurvatus (Thamnidiaceae), Cunninghamella elegans and Mycotypha africana (Choanephoraceae) and Mortierella vinacea (Mortierellaceae) and in Basidiobolus microsporus (Entomophthorales). The function of rhizoferrin as a siderophore in the fungus R. microsporus var. rhizopodiformis was demonstrated by time- and concentration-dependent uptake of [55Fe]-labelled rhizoferrin, yielding saturation kinetics with values of Km = 8 microM and V(max) = 1.2 nmol min-1 (mg dry wt)-1.
Fungi↗
Evaluation of the ASTRA o-cresolphthalein complexone calcium method.
An automated calcium method based on o-cresolphthalein complexone chemistry and designed to be used in conjunction with the Beckman ASTRA systems (Beckman Instruments, Inc., Brea, CA) was evaluated. Day-to-day reproducibility studies yielded coefficients of variation ranging from 1.2 to 3.1%. Linearity was 5.0-15.5 mg/dL, and recovery of calcium averaged 98%. Bilirubin, creatinine, hemoglobin, and turbidity did not cause significant interference while there was a positive interference due to magnesium. The throughput is 70 samples per hour, and a single stat result can be obtained in 9 minutes from the standby mode. Very little sample (12 microL) or reagent (150 microL) is required. There was excellent correlation between the ASTRA calcium method and atomic absorption spectrophotometry (Y = 1.047x - 0.39, r = 0.9941). Analytic performance was judged acceptable according to Westgard's medical usefulness criteria of the observed total analytic errors being less than the limit of allowable error.
Autoanalysis↗
[Measurement of calcium content in the blood and other biological fluids by Arsenazo III complexone].
A method of photometric measurement of total calcium in the serum and other biological liquids using Arsenazo III color complexone is offered. Physicochemical characteristics of Arsenazo III (mol extinction, affinity for other ions, spectral characteristics, and its complex with calcium) are described. Calcium was measured in 750 normal subjects, its reference value was 2.15-2.75 mmol/liter, the mean value 2.47 mmole/liter. In semiautomated measurement CV% was about 5%. The reagent is convenient, particularly for automated analyzers; no other reagent are needed, it can be stored for a long time at room temperature, and gives stable results.
Adult↗
[Structure of macrocyclic K+, Rb+-complexon of meso-valinomycin monohydrate, cyclo[-(D-Val-Hyi-Val-D-Hyi)3-].H2O, in a crystalline complex with dioxane by x-ray structural data].
The crystal structure of a valinomycin analogue, cyclo[-(D-Val-Hyi-Val-D-Hyi)3-]x(C60H102N6O18) crystallized with dioxane and water molecules, has been solved by X-ray direct methods. The conformation found is analogous to one established for free meso-valinomycin crystallized from other organic solvents. It is characterized by a centrosymmetric bracelet form, stabilized by six intramolecular 4----1 type hydrogen bonds between amide N-H and C = O groups. One water molecule is fixed asymmetrically by hydrogen bonds in the internal negatively charged cavity of the complexon. The meso-valinomycin molecule "bracelets" in the crystal form stacks alternatively with dioxane molecules.
Cations, Monovalent↗
[238Pu body distribution in dogs after intravenous administration and early complexon therapy].
The paper is concerned with the assessment of the level and concentration of 238Pu in different organs and tissues of dogs after iv injection of 238Pu-citrate at the amount of 92.5 kBq.kg-1 and during early complexon therapy. Ninety per cent of Pu detected in the body was shown to be deposited in the skeleton and liver in the ratio 4.5:1. The concentration of 238Pu in per cent to 1 g of tissue in the critical organs (the skeleton, liver, bone marrow) was (28.7--46.9) X 10(-3)%. The concentration of the radionuclide in the organs and tissues regarded as uncritical, was 1-2 orders lower: the endocrine organs--(0.7--7.5) X 10(-3)%, the lymph nodes--(3.8--5.4) X 10(-3)%, the G. I. tract portions--(1.05--1.5) X 10(-3)%, the CNS portions--(0.1--2.0) X 10(-3)%; the kidneys, muscles, heart, spleen and lungs--(0.63--8.8) X 10(-3)%. Early use of octacine or pentacine decreased Pu concentration in all investigated organs and tissues 2 +/- 0.06 times on an average. The efficacy of octacine was no inferior to that of pentacine.
Animals↗
[Mitigation of cisplatin toxicity by the complexon tetacin-calcium].
A possibility to decrease toxic properties of intraperitoneally injected platidiam (cis-platin, CSSR) administered by means of edtacal, a complexon (tetracinium-calcium, CSSR), administered per os is studied. It is established in intact mice that administration of edtacal simultaneously with platidiam or 1 h before decreases the mortality rate, diarrhea incidence and animal body mass loss. Edtacal is shown to have also an antiemetic action. Edtacal administered simultaneously with platidiam as well as 1 and 3 h before its injection does not decrease the antitumour activity of the preparation in (C57B1 X CBA)F1 mice with the Ehrlich ascite carcinoma.
Animals↗
[Behavior and biological action of 239Pu administered intramuscularly during complexon therapy].
With intramuscular injection of 239Pu nitrate the radionuclide content of the rat skeleton was higher, and at the site of injection, lower, than with injection of a polymer plutonium. The animals developed osteosarcomas (nitrate greater than polymer), and at the site of trauma, fibrosarcomas (nitrate less than polymer). After a complexon therapy the dose accretion in the skeleton and liver diminished, the life span increased, and the incidence of sarcomas decreased.
Absorption↗
Spectrophotometric micro method for measurement of dialyzable calcium by use of cresolphthalein complexone and continuous-flow analysis.
We adapted a method for dialyzable calcium from fluorometric detection by use of calcein to a more specific spectrophotometric determination with cresolphthalein complexone. The reagents are available commercially and perform satisfactorily with respect to noise level, drift, stability, and sensitivity. Construction of the continuous-flow manifold with commercially available components (injection blocks, coils, and dialyzer) and the use of a 9-mm pathlength flow cell in an AutoAnalyzer I colorimeter have permitted a sampling rate of 70/h, and decreased the volume of serum required to 130 microL. A comparison of 71 sera analyzed by the present and the calcein method gave means of 1.39 (SD 0.14) and 1.39 (SD 0.13) mmol/L, respectively. The regression equation was: present method = 1.016 calcein--0.022 mmol/L (r = 0.97). The CV for the new method, as determined from 46 randomized duplicate analyses, was < 1%. The reference interval, as evaluated from results for 93 different individuals, was 1.26-1.43 mmol/L. We conclude that our methods is an improvement with respect to noise level, drift, specificity, detectability, and more general availability of instrumentation. Moreover, the smaller sample volume required makes possible the routine measurement of dialyzable calcium in pediatric samples.
Adult↗