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Sepharose ion-exchange particles bearing strong Lewis acid/base functional groups (sulfopropyl, carboxymethyl, quaternary ammonium, dimethyl aminoethyl, and iminodiacetic acid) exhibiting high plasma protein adsorbent capacities are shown to be more efficient activators of blood factor XII in neat-buffer solution than either hydrophilic clean-glass particles or hydrophobic octyl sepharose particles (FXII (activator)→(surface) FXIIa; a.k.a autoactivation, where FXII is the zymogen and FXIIa is a procoagulant protease). In sharp contrast to the clean-glass standard of comparison, ion-exchange activators are shown to be inefficient activators of blood plasma coagulation. These contrasting activation properties are proposed to be due to the moderating effect of plasma-protein adsorption on plasma coagulation. Efficient adsorption of blood-plasma proteins unrelated to the coagulation cascade impedes FXII contacts with ion-exchange particles immersed in plasma, reducing autoactivation, and causing sluggish plasma coagulation. By contrast, plasma proteins do not adsorb to hydrophilic clean glass and efficient autoactivation leads directly to efficient activation of plasma coagulation. It is also shown that competitive-protein adsorption can displace FXIIa adsorbed to the surface of ion-exchange resins. As a consequence of highly-efficient autoactivation and FXIIa displacement by plasma proteins, ion-exchange particles are slightly more efficient activators of plasma coagulation than hydrophobic octyl sepharose particles that do not bear strong Lewis acid/base surface functionalities but to which plasma proteins adsorb efficiently. Plasma proteins thus play a dual role in moderating contact activation of the plasma coagulation cascade. The principal role is impeding FXII contact with activating surfaces, but this same effect can displace FXIIa from an activating surface into solution where the protease can potentiate subsequent steps of the plasma coagulation cascade., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: To determine in vitro free ion concentration in three standard artificial enteral feeding formulas following the addition of ion exchange resins., Method: Three standard types of AEF were chosen: Osmolite HN, Nutrison Standard and Isosource Standard. The ion exchange resins used were: Sodium Polystyrene Sulfonate and Calcium Polystyrene Sulfonate. 100 ml of AEF were mixed in a beaker with 1.5 g or 3 g of ion exchange resins for 48 hours at 37 masculineC. Subsequently, the samples were precipitated and the supernatant obtained was used for determining the concentrations of calcium, magnesium, sodium and potassium ions., Results: The addition of Sodium Polystyrene Sulfonate to different types of enteral feeding formulas reduced the concentrations of potassium, calcium and magnesium ions by 70%. 78.2%, and 77.6% in the case of Osmolite HN; by 72.3%, 69.2% and 63.5% in the case of Nutrison Standard, and by 78.3%, 80.5% and 74.5% in the case of Isosource Standard. In contrast, the addition of Calcium Polystyrene Sulfonate reduced the concentration of potassium and magnesium by 50.5% and 55.5% in the case of Osmolite HN; by 49.8% and 43% in the case of Nutrison Standard and by 42.6% and 37.7% in the case of Isosource Standard., Conclusions: The addition of ion exchange resins to different types of enteral feeding formulas, allows the in vitro free ion content of these to be reduced.

A macroporous ion-exchange resin was adopted for the in situ exchange of acetic acid during human epidermal growth factor (hEGF) production by recombinant Escherichia coli JM101. The results of this study suggest that in situ exchange by macroporous resin can improve E. coli growth, decrease acetate accumulation and enhance hEGF production.

The effect of a new polystyrene-based, strongly basic, anion-exchange resin possessing an omega-oxobutyl chain as a spacer arm on the fecal bile acid excretion was investigated in rats and compared with that of Dowex 1-X2, chemically equivalent to cholestyramine. The new resin did produce a significant rise in the total fecal bile acid excretion with its ingestion for a period of 4 weeks. Its promoting activity proved to be 2.0- and 1.8-fold more potent than that of Dowex 1-X2 at the 3rd and 4th week, respectively. These results suggest that the introduction of a spacer arm between the polymer backbone and a functional group would lead to an improvement in the in vivo adsorptive efficiency of the resin.

1. The interference of resins and activated charcoal with the absorption of digoxin, carbamazepine and frusemide was studied. 2. In a cross-over study consisting of four phases, single doses of colestipol hydrochloride (10 g), cholestyramine (8 g), activated charcoal (8 g) or water only were given to six healthy volunteers immediately after the simultaneous ingestion of digoxin (0.25 mg), carbamazepine (400 mg) and frusemide (40 mg). Plasma and urine concentrations of the test drugs and the urine volumes were determined up to 72 h. 3. The absorption of digoxin was not reduced by colestipol, moderately (30-40%, P less than 0.05) reduced by cholestyramine and greatly (96%) by charcoal. 4. The absorption of carbamazepine was not decreased by cholestyramine, slightly (10%) by colestipol and greatly (90%) by activated charcoal. 5. The absorption and the diuretic effect of frusemide were significantly diminished by all agents. The bioavailability was reduced by colestipol 80%, by cholestyramine 95% and by activated charcoal 99.5%. 6. The interference with the gastrointestinal absorption of most of the basic drugs by colestipol and cholestyramine seems to be minimal. On the other hand, the resins may seriously impair the absorption of certain acidic drugs, for example frusemide.

The resin-I5 column developed in our laboratories rendered aqueous suspensions containing up to 5 X 10(4) cysts of Giardia muris or Giardia lamblia per ml incapable of excystation. The inhibition of excystation was effective at both 4 and 25 degrees C. The addition of Na2S2O3 to column eluates containing cysts appeared to partially reverse the disinfectant action, and the reversal was more pronounced at 4 degrees C than at 25 degrees C. In contrast, the rapid removal of cysts from the column eluates by centrifugation and filtration or the use of other reductants, notably cysteine and glutathione, did not similarly reverse the disinfectant properties of the column. Based on these data, we suggest that the disinfecting agent is acquired by the cyst in its passage through the resin column and that either the disinfecting agent or its reaction can be partially and specifically neutralized by Na2S2O3. We hypothesize that the time between disinfectant acquisition and activity is a function of the thickness of the Giardia cyst wall and consequently takes longer at the lower temperature. Nevertheless, resin-I5 appears to inactivate a larger number of cysts in a shorter period of time with lower residual halogen levels than do agents of other published methods.

Ammonia excretion was studied in rat ileal segments during perfusion of the animal through the saphenous vein. In the first 10 min during and after intravenous infusion of L-glutamine (116 mg/kg to double arterial glutamine concentration) average net change in lumenal ammonia was 13 +/- 8 (S.E.) nmole NH3/min/g ileum; average net change in ileal venous ammonia was 28 +/- 9 nmole NH3/min/g ileum; and average net change in total ammonia (lumen + ileal vein) was 41 +/- 13 compared to -5 +/- 10 nmole/min/g ileum for animals infused with saline P less than 0.025. These data suggest that ileal metabolism of arterial glutamine liberates ammonia to both ileal venous blood and intestinal lumen. When a cation-exchange resin which binds ammonia was infused intralumenally, average net change in lumenal ammonia in the first 10 min during and after intravenous infusion of 116 mg/kg L-glutamine was 415 +/- 156 nmole NH3/min/g ileum (p less than 0.01 compared to value during perfusion of Earle's solution alone). During the first 10 min during and after glutamine infusion net change in ileal venous plasma ammonia was -8 +/- 14 when resin was being perfused through the lumen compared to +28 +/- 9 nmole/min/g ileum during perfusion of Earle's solution alone without resin P less than 0.05. Thus resin in the small intestine can trap very large amounts of ammonia.

Effects of feeding cottonseed meal and anion-exchange resin on iodine absorption and excretion by calves were investigated. Each additional amount of resin fed from .3 to 3.5 g/kg body weight further increased fecal excretion from single oral iodine-131 and intravenous iodine-125 doses. By feeding 3 to 10 g cottonseed meal/kg body weight, excretion of oral iodine-131 given daily was increased 7 to 94% in feces and reduced as much as 35% in urine, but plasma iodine-131 was not changed. Introducing 1 g resin/kg body weight daily into the diet increased fecal iodine-131 excretion three to five times that with cottonseed meal alone and reduced both plasma and urinary iodine-131. The same amount of resin fed daily had similar effects on excretion of iodine-131 injected subcutaneously each day. Although iodine depletion by a highly efficient iodine binder (resin) in the gastrointestinal tract is probable, iodine binding by a natural feed constituent (cottonseed meal) was relatively inefficient.

Platelet concentrates were prepared at twice the normal concentration and stored at room temperature for 7 days in either standard bags (controls) or bags to which 1 or 2 g of Amberlite resin beads charged with dibasic phosphate had been added. The resin beads served as a buffer system by providing a "slow release" form of phosphate ions as well as by binding CO2 produced during platelet metabolism. Control platelets demonstrated rapid falls in pH, ATP content, morphology score, and thrombin-induced nucleotide release after 24 hr of storage with a fall in pH to less than 6.0 by day 3. Profound ultrastructural changes and a rise in pO2, suggesting loss of platelet viability, accompanied these changes. In contrast, the resin-stored platelets remained near normal after 24 hr of storage, with preservation of discoid morphology, 95% of ATP levels, excellent ultrastructural appearance, and evidence of continued oxygen consumption after 3 days of storage. Even after 7 days of storage, ATP levels remained greater than 50% of baseline and ultrastructurally intact platelets were seen. In the 1-g resin bags the pH remained at baseline levels (6.9-7.0), while there was a rise in pH in the 2-g resin bags. These results demonstrate the beneficial effects of maintaining a higher pH during platelet storage and provide a new approach to studying the metabolic changes that occur during longer term storage.

Strongly basic anion-exchange resins form stable, water-insoluble combinations with triiodide ions. The combinations have remarkable antibacterial properties: 3.0 x 10(5)Escherichia coli cells per ml were killed when passed through a 3.8-g column of commercially available resin treated with triiodide (volume 4 ml after treatment). In an attempt to deplete the resin-triiodide complex, 1.14 x 10(9)E. coli cells in 15 liters were passed through the column with no significant loss of effectiveness. The antibacterial capabilities of the resin-triiodide columns ranged from 10(6)Salmonella typhimurium per ml to 1.1 x 10(4)Streptococcus faecalis per ml. Staphylococcus aureus and Pseudomonas aeruginosa were also tested and killed at concentrations of 1.8 x 10(4) and 1.3 x 10(5) per ml, respectively. The cells were not filtered from the water. They emerged from the column in nonviable form. This was demonstrated by using (14)C-labeled bacteria. The irreversible nature of the antibacterial action was revealed when attempts to wash the damaged cells did not restore viability.

Doak, G. O. (University of North Carolina, Chapel Hill), Leon D. Freedman, and John W. Clark, Jr. Ionic requirements of Treponema pallidum. III. Divalent ions. J. Bacteriol. 82:909-912. 1961.-Suspensions of Treponema pallidum, prepared by extracting the testes of syphilitic rabbits with normal rabbit serum or with a culture medium, were shaken with Amberlite IRC-50 resin in the sodium ion form. This procedure did not noticeably reduce the number of motile organisms, but markedly decreased their ability to survive in vitro. The addition of calcium, strontium, or barium ions to the treated suspensions largely restored this loss of motility. These same ions, when added to suspensions of T. pallidum not treated with the ion exchange resin, were without effect. Magnesium ion also had a beneficial effect, but considerably less than that produced by calcium ion. Cobaltous, manganous, ferrous, and zinc ions gave no beneficial effect, and, except for manganous ion, were toxic to the organisms at 5 x 10(-3)m.

Chondrocytes from the vertebral columns of 11-day chick embryos were cultured in the continuous presence of 5-bromodeoxyuridine (BUdR) Under these conditions the cells form multilayers but synthesize little extracellular matrix as determined by toluidine blue metachromasia or sulfate-(35)S incorporation into polysaccharide. Myogenic cells from the breast muscles of 11-day chick embryos formed myotubes when plated into BUdR-treated chondrocyte cultures. When plated on untreated chondrocyte multilayers or on multilayers which had been permitted to recover from BUdR treatment for 3 days, myogenic cells failed to form myotubes Since extracellular matrix is present in untreated chondrocyte cultures and reappears in multilayers recovering from BUdR treatment, it is suggested that extracellular matrix is the active agent in the suppression of myogenesis An attempt was made to duplicate the suppressing activity of multilayer cultures by using ion exchange resins as substrates for myogenic cells Myotubes formed on acidic and basic resin particles If extracellular matrix is the active suppressing agent, it may have to fulfill certain spatial distributional requirements before its activity is expressed

The antiviral activity of the double-stranded complex poly(rI) . poly(rC) in cell culture was restored or even surpassed if the constituent homopolymers were administered separately. Poly(rI) primed the cells for the antiviral activity of poly(rC) and poly(rC) primed for poly(rI), but neither poly(rI) nor poly(rC) primed the cells for the antiviral activity of noncomplementary homopolynucleotides. The priming effect of poly(rI) was significantly reduced if the poly(rI)-primed cells were treated with either T(1) ribonuclease or diethylaminoethyl (DEAE)-dextran before addition of poly(rC), and the priming effect of poly(rC) was significantly reduced if the poly(rC)-primed cells were treated with either pancreatic ribonuclease or DEAE-dextran before addition of poly(rI). (3)H-labeled poly(rC) bound more rapidly to poly(rI)-treated cells than to control cells. Cell-associated poly(rC) was markedly more resistant to pancreatic ribonuclease treatment if the cells had been incubated with poly(rI) before exposure to poly(rC). Our results clearly indicate that poly(rI) and poly(rC) added successively to cell cultures do not act independently but reunite at the cellular level, most likely at the outer cell membrane.

The infectivity of trachoma-inclusion conjunctivitis (TRIC) organisms (TW-5) was enhanced by pretreatment of HeLa cell monolayers before inoculation with diethylaminoethyl (DEAE)-dextran (30 mug/ml) and poly-l-lysine (10 mug/ml) and inhibited by dextran sulphate (250 mug/ml), fetuin (4%), ovomucoid (5%), N-acetyl neuraminic acid (0.5%), and Cholera vibrio neuraminidase (100 U/ml). The infectivity of lymphogranuloma venereum organisms (434) was not affected by DEAE-dextran, fetuin, and neuraminidase, was slightly inhibited by poly-l-lysine, and was inhibited by dextran-sulphate, ovomucoid, and N-acetyl neuraminic acid. The study suggested that sialic acid residues on the cell surface may be specific receptors for TRIC organisms. The receptors for TRIC organisms (TW-5 and TW-3) could be specifically blocked with inactivated (56 C for 30 min) TRIC organisms at the ratio of one live to 100 inactivated TRIC organisms, but not by inactivated lymphogranuloma venereum (434) or influenza virus (A(2)/Jap 305).

It has been demonstrated experimentally that small numbers of a variety of different bacteria fail to survive or multiply in normal cow or human blood or in a mixture of blood and a suitable culture medium, owing to the binding of the magnesium ion and a protein component of the antimicrobial system. However, a satisfactory and simple method has now been evolved for the rapid multiplication of Gram-negative and Gram-positive bacteria in blood without the addition of a liquid culture medium. This method involves the addition to blood of optimum amounts of hydrogen and magnesium ion exchange resins and sodium citrate.

A method employing the use of ion-exchange resin beads is described for the punctate introduction of discrete amounts of various anions, cations, or zwitterions into given brain regions. A series of experiments utilizing the method to introduce ionic copper into the caudate nucleus with the resulting motor manifestations are discussed.

1. Effects of starvation or treatment with a cation exchange resin, dowex 50, parallel in some respects those seen earlier on the respiration and fermentation of bakers' yeast receiving 90,000 r of 250 kv. x-rays. Starvation increased the radiosensitivity of cell division processes whether measured by colony formation or by turbidimetric determination of growth in a liquid medium. The dowex 50 enhanced the radiation effect by the latter measure but appeared to increase colony formation of irradiated yeast. 2. The effects on growth differ from those on respiration and fermentation in that the exchange resin treatment did not inhibit colony formation further, and neither starvation nor resin appreciably altered the growth of non-irradiated yeast. 3. Two effects of radiation are seen in these experiments: (a) a permanent inhibition of growth, and (b) a temporary inhibition of the remaining cells resulting in delay of growth. 4. The irradiated cell is more dependent on certain aspects of its environment in terms of growth responses as well as in terms of metabolism (i.e. respiration and fermentation). Whether or not potassium plays a role in the growth response as it does in the metabolic response cannot be ascertained from the present data.