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[Molecular Adsorbent Recirculating System in liver function replacement therapy].

The molecular adsorbent recirculating system (MARS) method removes from the blood catabolites either free in the plasma water such as uremic toxins and ammonia, taking advantage of dialysis or free albumin bound ones, like hepatic toxins, transferring them from the albumin in the blood to the albumin circulating in a closed loop where toxins are removed by adsorbtion on resins (charcoal and ion exchange resin). The efficacy of the method in removing the hepatic toxins either in the acute or in the acute on chronic liver failure is demonstrated in numerous studies. Based on these findings, 10 patients affected by acute on chronic liver failure were treated. The results demonstrated that the method, powerfully removing ammonia, bilirubin and bile acids (taken as method efficacy markers), reduced the blood concentrations of these molecules remarkably; allowing the elimination of the refractory pruritus (due to the lowering of plasma bile acid levels), an almost constant symptom in chronic liver diseases, especially with cholestasis, and improves other parameters (cholinesterase, alkaline phosphatase and prothrombin activity). These results agree with those reported in the literature concerning the efficacy of MARS in the replacement of the liver detoxifying function.

Adsorption↗
PubMed1986

A modification of the saccharine test for nasal mucociliary clearance.

The saccharine test for assessing mucociliary clearance in the nose is the most practicable method. As the used sodium salt of saccharine is well water soluble, there is suspicion of interference with the very delicate two-layer-system of mucus or transport merely in the periciliary fluid, thus bringing about methodical errors. This is avoided by using inert tracers such as radioactively tagged ion exchange resin particles, which on the other hand must be observed with expensive equipment. A synthesis of both methods is demonstrated by using saccharine loaden ion exchange resin particles. The validity of the test is proven in vitro and in vivo.

Animals↗
PubMed2002

Gastrointestinal transit times in mice and humans measured with 27Al and 19F nuclear magnetic resonance.

Gastric emptying and gastrointestinal (GI) transit times in mice and humans were monitored noninvasively by using 27Al and 19F nuclear magnetic resonance (NMR). Al(3+) bound to ion-exchange resin and perfluorononane were administered orally as selective and specific markers for the stomach and the entire GI tract, respectively. 27Al- and 19F-MR spectroscopy (MRS) was employed to follow quantitatively boli of the mixed markers in awake, fed mice over a period of 48 hr. The selectivity of the markers was confirmed by whole-body 1H-, 27Al-, and 19F-MRI of anesthetized mice. Gastric emptying in humans was also monitored with 27Al-MRS of aluminum-loaded ion exchange resin. GI transit was assessed by 19F projection imaging of pharmaceutical capsules tagged with perfluorononane. Quantitative analysis of the MR data revealed that gastric emptying in humans proceeded linearly, whereas in mice an exponential decay was observed. This difference is explained by the respective feeding patterns of humans and mice. Humans usually achieve nearly complete gastric emptying before each meal. In contrast, very short delays between successive food intakes in small animals result in successive dilution of the stomach contents. For stomach emptying in mice the exponential decay constant was 74 min, whereas the half-time of the linear gastric emptying in humans was 30 min.

Aluminum↗
PubMed2006

Modeling film-coat non-uniformity in polymer coated pellets: a stochastic approach.

The objective of the present study is to include coating thickness non-uniformity in the development of a drug release model using coated ion-exchange pellets through the use of stochastic approaches. Drug release from ion-exchange resins was described using a Nernst-Plank model. Complexes of a model drug (dextromethorphan) and Dowex 50WX4-200 were prepared using a modified batch method and coated with Kollicoat SR 30D polymer. The deterministic model, validated using experimental drug release profiles for different coating thicknesses at 0%, 10%, 15%, 20% (w/w), was in agreement with the experimental data with a maximum root mean square error (RMSE) of 2.4%. An arbitrary Lagrangian-Eulerian approach was pursued to develop models of spherical pellets with non-uniform coating thicknesses. The Monte Carlo method was used to simulate the effect of the level of coating deformity on the cumulative drug release profile. Considering the co-existence of equal percentages of deformed and undeformed pellets in a batch, the cumulative release profile can vary by approximately +/-6% as a result of coating non-uniformity. The release profile obtained for a model of an arbitrary pellet with an actual non-uniform coating profile was in good agreement with the average release profile for the models of the theoretical randomly deformed pellets. The developed mathematical model is a useful tool to evaluate and predict release profiles of polymer coated ion-exchange resin complexes.

Algorithms↗
PubMed1980

Sorption of cholesterol and other bile components on ion-exchangers in vitro, and their influence on the cholesterol level in human serum in vivo.

The sorption of bile acids, bilirubin, bilirubin glucuronates and cholesterol on ion-exchange resin is described. After some successful attempts of sorption of these substances from human and animal bile in vitro, this exchanger has been used in human therapy. Positive results obtained showed the usefulness of the method. The purpose of the experiments was to study the usefulness of ion-exchangers for sorption of bile components of bile acids, bilirubin, bilirubin glucuronates and cholesterol. First sorption was carried out on human and animal bile, on Zerolit-FS-ip, in cycles (OH-) and (Cl-), by passing through glass columns downwards and some of them by mixing the bile with ion-exchange resin. Zerolit FS-ip is an organic sorbent, a scavenger, a strongly basic macroporous, anion exchanger. Positive results of these sorptions indicated the possibility of using this method in therapy of disturbed lipid conditions.

Adult↗
PubMed1987

Serial section method for cytofluorometric determinations of the DNA content of component cells of the human cochlea.

We describe a method for measuring the DNA content of the component cells of the organ of Corti using serial sections of human cochleae obtained at autopsy. Cochleae were fixed in Carnoy's solution and embedded in Acrytron E, a water-miscible methacrylate resin. A procedure was developed to reduce the background fluorescence in methacrylate-embedded sections; the resin was pretreated with ion-exchange resin (Amberlite IRA-410). Experiments showed that pretreatment reduce the background fluorescence practically to zero. Seventy 3 microns-thick serial sections were prepared on fluorescence free glass slides and stained with azocarmin G and acriflavine-Feulgen. After postirradiation using blue excitation light, the amount of Feulgen-DNA present in the target nucleus in each section was determined using a microfluorometer. The amount of DNA in the entire nucleus was determined by adding together the DNA content of the segments of the nucleus. The characteristic appearance of the organ of Corti made it easy to detect these cells; under green excitation light the cells of this organ exhibited red cytoplasmic azocarmin-G fluorescence. Due to the relatively wide internuclear spaces, cytofluorometry fo individual nuclei could be performed without interference from the neighboring cells. Our technique using serial sections allowed us to measure the DNA content of individual cells and obtain histological information about particular cells and their neighboring cells. Several polyploid cells were found among the Hensen's cells in the cochlea, while all other component cells of the organ of Corti were diploid.

Cell Nucleus↗
PubMed2001

Galactomannans as a sieving matrix in capillary electrophoresis.

Purification of galactomannans including guaran, tara gum, and locust bean gum is described as well as their use as a sieving matrix in DNA sequencing by capillary electrophoresis (CE). Three methods of galactomannan purification were developed and tested using guaran. The first method is based on hydrolysis of proteins using alkali treatment and precipitation of guaran with acetone. The second method uses ion-exchange resins QAE Sephadex A-25 and SP Sephadex C-25 together with acetone precipitation. The third method is similar to the second one, except that it uses ion-exchange resins based on polystyrene, Source 30Q and Source 30S. Capillary zone electrophoresis of acetonitrile extracts from guaran revealed 4-5 characteristic major peaks and several minor peaks. Guar gum from different suppliers differed in the content of proteins. In purified guaran, protein peaks were detectable only using a 300-fold concentrate of extract. The content of proteins in the guaran purified using the third method was 0.001% m/m as determined by CE. The weight average molecular mass of purified guaran can be as large as 2.2 x 10(6). The purified galactomannans were used as a sieving matrix in DNA sequencing by CE. M13 DNA was sequenced to read lengths of about 600 bases in less than 90 min. Separation efficiencies exceeded 1 million theoretical plates for DNA fragments shorter than about 600 bases.

Acetonitriles↗
PubMed1992

Dose response and toxicity of doxorubicin microspheres in a rat tumor model.

The therapeutic response and toxic effects of chemotherapy using several doses of doxorubicin in conventional solution form or bound to an ion-exchange resin were compared in a rat tumor model, to assess the relationship of drug dose to therapeutic efficacy and associated toxicity. Single bolus injections of 3.0, 4.5, 6.0, 7.5 and 9.0 mg/kg were administered via the abdominal aorta to rats bearing hindlimb tumors. Tumor size was measured serially and the growth rates of treated groups were compared with a control growth curve. In addition, the effect of empty microspheres on tumor growth rate was assessed. The levels of circulating white blood cells were measured and compared to control levels to provide an indication of the severity of bone marrow toxicity experienced by each form of treatment. Finally, any difference in the distribution of doxorubicin to tumor, hindlimb and cardiac tissue following administration of doxorubicin as free drug or on microspheres was ascertained. Empty ion-exchange resin exerted a small although significant detrimental effect on tumor growth which may be explained by the embolization of microspheres in the precapillary blood vessels of the tumor resulting in a transient delay in tumor growth rate. The lowest dose of doxorubicin produced a significantly better therapeutic response when administered in the free drug form, but higher doses elicited an equivalent delay in tumor growth for both drug microsphere and free drug groups in a dose-dependent manner, with the maximum anti-tumor response occurring at the highest dose. Treatment with free doxorubicin at high doses resulted in significant reductions of circulating white blood cells suggesting the occurrence of bone marrow toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1967

Polonium-210: removal from smoke by resin filters.

Use of a mixed ion-exchange resin as a filter for cigarettes markedly reduces both the total amount of polonium-210 in mainstream smoke and the picocuries per milligram of smoke. This procedure effectively minimizes exposure of the lungs of smokers to alpha irradiation.

Alpha Particles↗
PubMed1999

A method for the determination of glucose synthesis in isolated bovine hepatocytes.

A simple method for determining glucose synthesis from radiolabeled precursors in isolated bovine hepatocytes using ion exchange resins is presented. This method allows processing of multiple small volume samples using suspensions of anion and cation exchange resins rather than traditional stacked column separation methods. Hepatocytes were isolated from calf liver by collagenase perfusion of the caudate lobe and were incubated with (14)C-labeled lactate or propionate as gluconeogenic substrates. Glucose synthesis was determined in an aliquot of cell suspension that was vortexed with a slurry of anion exchange (acetate form) resin, followed by a slurry of cation exchange resin. Newly synthesized, labeled glucose was recovered in the supernatant after centrifugation and quantitated by scintillation counting. Using this procedure, more than 98% of the unused labeled precursor was bound to the ion exchange resin and essentially 100% of a labeled glucose tracer was recovered in the supernatant. Pretreatment of hepatocyte suspensions with glucose oxidase was shown to eliminate the accumulation of radioactivity in the supernatant, thus confirming the specificity of this technique for measurement of newly synthesized glucose. This method was sensitive to changes in the rate of hepatic gluconeogenesis that resulted from changes in substrate concentration or the addition of glucagon or fatty acids to the hepatocyte incubations.

Journal Article↗
PubMed1979

Detection of staphylococcal enterotoxin in foods.

A method has been developed for the detection of staphylococcal enterotoxin A in the boiled rice extract. The procedure utilized was the batch adsorption of enterotoxin from the cell-free culture supernatant by CG-50 ion exchange resin at pH 5.6. The enterotoxin was eluted by various concentrations of elution solution with different pH values. The lyophilized eluate was dissolved in Phosphate Buffer Saline (PBS) solution and analyzed with a quantitative double diffusion method. The desorption of enterotoxin from ion exchange resin appeared to be less effective by increasing the concentration of elution solution than by elevating the pH value of elution solution. The pH below 6.2 seemed to lose the ability to elute the enterotoxin from ion exchanger but enough to elimate non-specific extra proteins. The quantitative double diffusion method was able to detect enterotoxin in food with approximation in quantitation.

Chromatography, Ion Exchange↗
PubMed1986

Influence of thyroid hormones on rat cerebellar cell aggregation and survival in culture.

In order to study the effect of thyroid hormones on rat cerebellar granule cells, cerebellar perikarya isolated from 5-7-day-old rats were cultured in the presence of normal fetal calf serum, fetal calf serum treated with Dowex-2 ion exchange resin to remove thyroid hormones, or ion exchange-treated serum resupplemented with physiological concentrations of T4 and T3. Granule cells grown under hypothyroid conditions showed abnormal cellular aggregation, neurite fasciculation and cell survival. Cell aggregation, which may be an in vitro correlate of cerebellar granule cell migration to the internal granule layer, was reduced by over 50% under hypothyroid conditions. The rate of protein synthesis in hypothyroid cultures was stimulated by as much as 3-fold compared to thyroid hormone-containing cultures consistent with a proposal that the normal developmental pattern of diminishing protein synthesis specific activity is delayed or prevented under hypothyroid conditions. In addition ultrastructural studies revealed abnormalities in the density of cold-stable microtubules in thyroid hormone-deficient cultures. These results demonstrate that thyroid hormones can influence granule neuron behavior in the absence of Purkinje cells. Furthermore, the observed defects bear numerous similarities to documented abnormalities within the hypothyroid cerebellum, suggesting that this in vitro culture system may serve as a useful model for studying the mechanism of action of thyroid hormones on the cells of the cerebellum.

Animals↗
PubMed1978

Qualitative detection of placidyl (ethchlorvynol) alone or in combination with poly-drugs in drug abuse urine screening programs using ion-exchange paper and/or liquid-liquid extraction.

Two procedures for the detection of ethchlorvynol are presented. Procedure I involves the use of SA-2-cation-exchange resin loaded paper. The use of multiple ion-exchange resin papers is proposed in a sequence that enables the detection of amphetamines, barbiturates, phenothiazines, propoxyphene (Darvon), phencyclidine, cocaine (benzoyl ecgonine), pentazocine (Talwin) and benzodiazepines in addition to ethchlorvynol. This procedure discusses the details of detecting ethchlorvynol in combination with the entire array of drugs of abuse depending on the needs of a clinical program. Procedure II involves the principle of liquid-liquid extraction using either raw or spent urines.

Chromatography, Ion Exchange↗
PubMed2006

The synergistic effect between hydrophobic and electrostatic interactions in the uptake of amino acids by strongly acidic cation-exchange resins.

The goal of this work was to investigate the synergistic effect between the electrostatic and hydrophobic interactions upon the uptake of organic ions with hydrophobic moieties by ion-exchange resins with hydrophobic matrixes. The uptake of neutral amino acids by a macroporous polystyrene-based strongly acidic cation-exchange resin (D001) and two strongly acidic cation-exchange resins (poly(2-acrylamido-2-methyl propanesulfonic acid) and poly(vinylsulfonic acid)) with much less hydrophobic matrixes essentially follow an ion exchange stoichiometry. However, the thermodynamic parameters of the uptakes indicate that besides electrostatic interaction, hydrophobic interaction also contributes to the affinity of the amino acids with hydrophobic side chains for D001. No detectable uptake capacities for the amino acids by D001AM, which was obtained by amidation of the sulfonic acid groups of D001, can be determined. Thus, it is deduced that the hydrophobic interaction alone contributes little to the uptake of these amino acids by D001, of which hydrophobicity is the same with or lower than that of D001AM. These results indicate that synergistic effect exists between the electrostatic and hydrophobic interactions when the two interactions exist in a chelate manner and the hydrophobic interaction contributes to the uptake even if the hydrophobic interaction is so weak that it contributes little to the uptake when it acts alone.

Amino Acids↗
PubMed2003

Recovery of lactic acid from simultaneous saccharification and fermentation media using anion exchange resins.

The physicochemical properties (capacity, kinetics and selectivity) of the ion exchange resins Amberlite IRA900, IRA400, IRA96 and IRA67 were determined to evaluate their comparative suitability for lactic acid recovery. Both the kinetics of lactic acid sorption from aqueous solutions and the equilibrium were assessed using mathematical models, which provided a close interpretation of the experimental results. The best resins (Amberlite IRA96 and IRA67) were employed in further fixed-bed operation using aqueous lactic acid solutions as feed. In this set of experiments, parameters such as capacity, regenerant consumption, percentage of lactic acid recovery and product concentration were measured. Amberlite IRA67, a weak base resin, was selected for lactic acid recovery from SSF (simultaneous saccharification and fermentation) broths. Owing to the presence of nutrients and ions other than lactate, a slightly decreased capacity was determined when using SSF media instead aqueous lactic acid solutions, but quantitative lactic acid recoveries at constant capacities were obtained in four sequential load/regeneration cycles.

Journal Article↗