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Introduction: Hyperkalemia is a common finding in patients with advanced kidney disease for multiple reasons. Renin-Angiotensin-Aldosterone-System Inhibitors (RAASi) that are indicated for slowing down progression of kidney disease are often associated with hyperkalemia which becomes a limiting factor in their use and titration to the maximum dose. Having a safe, effective, tolerable, and affordable potassium binder can help optimize RAAS inhibition in the setting of kidney disease., Areas Covered: Although sodium polystyrene sulfonate has been a mainstay of acute management of hyperkalemia for decades, evidence regarding its efficacy is limited, and its chronic use is not routinely recommended for concerns regarding toxicity. The concern of gastrointestinal (GI) adverse effects with sodium polystyrene sulfonate has spurred the development of alternatives. Sodium zirconium cyclosilicate (SZC) is a promising agent that selectively binds potassium in the gut and eliminates it, while being safe for chronic use based on 1 year of data. Even though we do not have head-to-head studies among the three currently available binders, SZC stands out in rapidity of onset and efficacy., Expert Opinion: In this review, we summarize the general management of hyperkalemia, including new agents. We review the pre-clinical and clinical data relating to sodium zirconium cyclosilicate.

The efficient dehydration of fructose to 5-hydroxymethylfurfural (HMF) was developed in ionic liquids (ILs) with acidic ion-exchange resins as catalyst. By screening different resins and ILs respectively, it was found that the structure of resins and ILs had a prominent effect on the dehydration of fructose. In 1-butyl-3-methylimidazolium chloride ([Bmim]Cl), D001-cc resin showed a high activity. And then the effects of reaction temperatures, dosages of D001-cc, and different initial fructose loadings on the dehydration of fructose were studied in detail. The system of D001-cc resin and [Bmim]Cl exhibited a constant activity at 75°C for 20 min and a 86.2% yield of HMF was obtained after seven recycles. At 75°C for 20 min, a 93.0% yield of HMF from the dehydration of fructose was obtained., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

A highly efficient and stable biocatalyst (denoted D201_Lac) was fabricated by encapsulating Trametes versicolor laccase within a macroporous and strongly basic exchange resin D201 through a simple adsorption process. Transmission electron micrographs and Fourier transform infrared spectra of the resultant D201_Lac proved that nanosized laccase clusters were embedded into the inner nano-pores/channels of D201. As compared to the free laccase, D201_Lac showed enhanced resistance in the pH range of 3-7 or at temperature of 30-60°C. Besides, negligible laccase was leached out from the host polymer D201 in solution of pH 3-7 and NaCl concentration up to 0.5M, which might be attributed to the electrostatic attraction and the possible twining between long-chain laccase and the cross-linking host resin. Continuous seven-cycle batch decoloration of malachite green demonstrates that decoloration efficiency of D201_Lac kept constant for more than 320-h operation., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

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.)

We immobilized Candida sp. lipase onto seven kinds of industrial adsorption and ion exchange resins. By determining the activity of each immobilized enzyme, the weakly basic anionic exchange resin of D301 showed the best results for the immobilization of Candida sp. lipase. Comparing the scanning electron micrographs of D301 with Novozym 435 (immobilized Candida antarctica lipase B from Novo Nordisk Corp.), we selected D301 as a carrier for the immobilization of Candida sp. lipase. And we pretreated the resin D301 with the bifunctional agent glutaraldehyde and crosslinked it with Candida sp. lipase. The optimal conditions for the immobilization of Candida sp. lipase were as follows: 8 mL of the amount of 5% glutaraldehyde solution, five hours of the time pretreated D301 with glutaraldehyde, 1.0 g/L the concentration of Candida sp. lipase used, pH of the phosphate buffered, 6.0 and 10 hours of time for immobilization, respectively. The activity of immobilized enzyme was over 35 U/mg and the efficiency of immobilization was around 3.5 Ul(mg x h).

Hyperphosphatemia is highly prevalent in patients with chronic kidney disease (CKD), particularly in those with advanced or end-stage renal disease. Sevelamer hydrochloride is an ion-exchange resin that reduces serum phosphorus concentrations. The agent also produces favorable lipid profile effects and does not cause hypercalcemia. However, reported drawbacks of this agent are metabolic acidosis, high pill burden, and a relatively low affinity and selectivity for phosphate anions. Sevelamer carbonate is a new buffered formulation that does not increase the risk of metabolic acidosis. To determine the roles of these two agents in the treatment of hyperphosphatemia in patients with CKD, we performed a MEDLINE search (June 1995-June 2008) focusing on the mechanism of action of resin binding with phosphate and the development of metabolic acidosis. We also reviewed studies that evaluated the effects of sevelamer hydrochloride or sevelamer carbonate on serum bicarbonate concentrations. Several studies in patients with CKD and hyperphosphatemia who received hemodialysis or peritoneal dialysis found decreases in serum bicarbonate concentrations with the use of sevelamer hydrochloride, whereas sevelamer carbonate did not have this negative effect on bicarbonate concentrations. Both drugs appear to be equivalent in their abilities to lower serum phosphorus concentrations. However, as sevelamer carbonate does not decrease serum bicarbonate levels, it may be more appropriate for patients at risk for metabolic acidosis who require phosphate binders that do not contain calcium or aluminum.

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.

Mammals dispose of cholesterol mainly through 7alpha-hydroxylated bile acids, and the enzyme catalyzing the 7alpha-hydroxylation, cholesterol 7alpha-hydroxylase (CYP7A1), has a deep impact on cholesterol homeostasis. In this review, we present the study of regulation of CYP7A1 as a good exemplification of the extraordinary contribution of molecular biology to the advancement of our understanding of metabolic pathways that has taken place in the last 2 decades. Since the cloning of the gene from different species, experimental evidence has accumulated, indicating that the enzyme is mainly regulated at the transcriptional level and that bile acids are the most important physiological inhibitors of CYP7A1 transcription. Multiple mechanisms are involved in the control of CYP7A1 transcription and a variety of transcription factors and nuclear receptors participate in sophisticated regulatory networks. A higher order of transcriptional regulation, stemming from the so-called histone code, also applies to CYP7A1, and recent findings clearly indicate that chromatin remodelling events have profound effects on its expression. CYP7A1 also acts as a sensor of signals coming from the gut, thus representing another line of defence against the toxic effects of bile acids and a downstream target of agents acting at the intestinal level. From the pharmacological point of view, bile acid binding resins were the first primitive approach targeting the negative feed-back regulation of CYP7A1 to reduce plasma cholesterol. In recent years, new drugs have been designed based on recent discoveries of the regulatory network, thus confirming the position of CYP7A1 as a focus for innovative pharmacological intervention.

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.

Different chromatographic methods have been used to purify bacterially expressed single chain antibodies in soluble or insoluble form. Here, we compared two methods for purification of anti-CD19-c-myc-His6-Cys scFv expressed in Escherichia coli as soluble protein. The protein-L-agarose purification method is a one step purification method that yielded significant amounts of pure protein compared to the two-step Ni-NTA-agarose plus Resource 15S purification method. However, the protein-L purification method exhibited an additional lower molecular weight protein contaminant. Based on results from in vitro gel digestion, mass spectrometry and database search results, we confirmed that the lower molecular weight protein contaminant, which could not be purified by Ni-NTA-agarose and 15S column method, is a degraded product of the full length scFv construct.

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.

The effect on the urinary excretion of calcium of an oral cation exchange resin without phosphorus was studied in healthy control subjects and patients with recurrent calcium lithiasis under out-patient conditions. An immediate reduction of intestinal calcium absorption and urinary calcium excretion was found in five control subjects and in one patient after ingestion of resin, whereas calcium excretion remained unchanged in all other patients during long-term treatment. In addition, signs of mild transitory hyperparathyroidism together with an increase in intestinal calcium transport were observed during treatment. It is suggested that intraluminal binding of calcium ions to the resin leads to substantial changes in calcium metabolism with the result that urinary calcium excretion returns to pre-treatment values.

13 patients who had undergone a haemoperfusion therapy with Amberlite XAD-4 resin (Haemoresin, Braun, F.R.G.) because of acute intoxication were examined for adsorption of biological material from the blood. Treatment lasting on average 4 hours at a blood-circulation rate of 200 ml/min resulted in a 43% reduction of thrombocytes and in changes in the concentrations of proteins, complement factors, triglycerides, aldosterone and testosterone. Low-molecular substances and electrolytes were however, except for sodium, only slightly influenced. Thus this haemoperfusion system is only suitable for shortterm application and cannot be used without substitution for chronic treatment of terminal renal insufficiency.

Studies on the uptake and storage of sodium and biogenic amines (phenylethylamine, noradrenaline, histamine) by two weak cation-exchangers, IRC-50 and Sephadex C-50, and by biogenic granule-enriched preparations demonstrated that the synthetic and biogenic materials had several common characteristics. They showed similar concentration- and pH-dependence and fitted the same cation-exchange and receptor-binding equations. The observations were taken to support the view that the matrices of amine-storing granules have the properties of weak cation-exchangers, with carboxyls as the cation-binding groups.

The influence of calcium carbonate, aluminium oxyhydrate (Andursil) and an anion exchanger (Colestid) on the absorption of oxalate from the intestine in rats was investigated. The animals were administered daily doses of 15mg oxalate as a 14C-sodium-oxalate solution by means of a throat probe, and the substances of interest were mixed with the food. The intake of food and the 14C-activity in the urine were measured during four urine-collecting periods of 3 days each. The quantity of the enterally administered oxalate excreted with urine has a negative correlation to the amount of the investigated test substances ingested with food.

The possibility of optimizing the processes of B. pertussis cultivation carried out in liquid semisynthetic culture media with strong-base anion-exchange resins is shown. The use of strong-base ionites enhances the reproducibility of cultivation processes, increases the activity of microbial populations and the concentration of microorganisms. B. pertussis cultures grown in the media with anion-exchange resins are characterized by pronounced biological activity.

A new anion exchange resin with an imidazolium salt on a epoxide polymer skeleton was synthesized. This white powder material was odorless and tasteless. The in vitro sodium cholate binding of this resin was much more potent than that of cholestyramine. The hypocholesterolemic activity of this resin in cholesterol-fed rabbits proved to be 4.3 times more potent than that of cholestyramine. These results suggest that effective reduction of plasma cholesterol may be achieved with lower doses of this resin.

Sorption of aminoglycoside antibiotics close by their chemical structures such as gentamicin, sisomicin and kanamycin by polyacrylic and polymetaacrylic cation exchange resins was studied. The generality of the sorption process (kinetics and statics) on the carboxylic cation exchange resins with participation of the ions of the aminoglycoside antibiotics was shown.

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.

The properties of immobilized penicillinamidases prepared by different methods were studied. Immobilization of penicillinamidase was achieved by using the covalend binding ion exchange sorption, incorporation into gel and other procedures. The effect of the carrier type, purification level of the native enzyme and other factors on stability of the immobilized preparations was studied. In 4 cases significant stabilization of the enzyme in the immobilized state was observed, while in 3 cases destabilization was registered.

The process of reactivation of acid-inactivated alpha-amylase of Bacillus subtilis in weakly alkaline media was examined. The reactivation of alpha-amylase immobilized on carboxyl polyelectrolytes developed in a larger measure than that of the native enzyme. The stabilizing effect of the cross polymer decreased as its porosity increased.

Sodium oxalate (402 mg) was administered in a single dose to 10 healthy volunteers receiving a controlled diet. Half the group received 3 times 10 g Colestid and the other half 4 times 2 g Andursil. On the 5th day the oxalate load was repeated. Urine was collected within 32 hours following oxalate application in 8 fractions. In each fraction the levels of oxalate, calcium, phosphate and uric acid were determined. The amount of oxalate, phosphate and uric acid measured in the group receiving Colestid was lower in all fractions. Peak excretions of oxalate found in unmedicated volunteers were suppressed following oxalate load. In the group receiving Andursil, only the excretion of phosphate was decreased. The results presented suggest that Colestid may be promising in the prevention of calcium-oxalate-urolithiasis.

Experiments were carried out to clarify the effect of swelling coefficients of various samples of the polycondensation anion exchange resin FAF in the C1 form on its sorption properties. The anion exchange resin was used to eliminate contaminating proteins and low molecular weight agents from the allantois fluid and liver cultured cells of pigs. Thermal treatment of the anion exchange resin increased the coefficient of its swelling, leaving the structure unchanged. The resin structure was controlled by electron microscopy and X-ray scattering of low angle. When the resin samples with the swelling coefficients of 3.5 and 4.0 were used, 30-40% of proteins, 50% of reducing agents and neutral carbohydrates and a small quantity of phosphorus were adsorbed.

Although the primary and direct action of the bile acid sequestrants is to bind bile acids in the gut, their interruption of the enterohepatic recirculation of bile acids has important effects on hepatic lipoprotein metabolism. Three key enzyme systems are affected: phosphatidic acid phosphatase, cholesterol 7 alpha-hydroxylase, and 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase. Activation of phosphatidic acid phosphatase promotes hepatic triglyceride (TG) synthesis, induces secretion of TG-rich, very low density lipoprotein particles, and consequently, increases plasma TG levels. The activation of hepatic cholesterol 7 alpha-hydroxylase promotes the conversion of intracellular cholesterol to bile acids. The decrease in intracellular cholesterol stores, in turn, increases low-density lipoprotein (LDL) receptor expression on hepatocyte surface membranes and, consequently, receptor-mediated fractional catabolism of LDL. Reduction of intracellular cholesterol may also increase the synthesis of cholesterol through activation of HMG CoA reductase. The potential loss of the sequestrant's cholesterol-lowering efficacy can be overcome by adding a drug to the regimen that inhibits HMG CoA reductase. Finally, bile acid sequestrants promote apoprotein AI synthesis by an unknown mechanism and tend to raise high-density lipoprotein (HDL) cholesterol levels, primarily by increasing plasma HDL-2 concentrations.

It has been suggested that cation exchange resins might be helpful in urinary stone prophylaxis. The effect of the cation exchange resin Dowex 50 WX8 upon calcium absorption and urinary excretion in guinea pigs was investigated. The mean fecal calcium concentration was very close in the Dowex-treated and control animals and the urinary calcium concentration was not reduced in the resin-treated animals. These findings suggest that Dowex was ineffective in binding calcium in the gastrointestinal tract.

A mitochondrial fraction was isolated from durum wheat seedlings via differential centrifugation using three different tissue grinding buffers. One buffer contained bovine serum albumin (BSA), a protein proven effective in protecting mitochondria from damage during isolation. The other two buffers contained either polyethyleneglycol of M.W. 20,000D (PEG-20), a phenolic binding compound or PEG-20 plus XAD-2, a non-ionic adsorbent material. Organelles isolated with the BSA exhibited an average ADP/O ratio of 2.3 and an average respiratory control ratio of 5.1, substantially higher than those obtained with the other media. Addition of the XAD-2 to a buffer containing PEG-20 resulted in an increase in the respiratory control ratio to an average value of 3.7 vs 2.7 for organelles isolated with PEG-20 alone without causing a concomitant rise in the ADP/O ratio which remained an average of 1.9. Protein values for the mitochondrial fraction isolated with BSA ranged from 2.5 to 3 times greater than those obtained from the PEG-20 preparations. This difference in organelle protein is discussed in relation to the accurate measurement of mitochondrial respiration.

Further testing and evaluation of the thin-film adsorber (TFA) type of hemoperfusion device is reported here to complement an earlier paper describing the development of these devices and clearance tests performed with them. The present paper describes the results of pressure drop tests, flow uniformity tests, and detailed studies of the mass transfer characteristics of the components of the TFA units. The TFA units consist of powdered activated charcoal embedded in thin films of cellulose nitrate. These films are sprinkled with small particles of granular charcoal and then wound into spools, which are then placed in a plastic housing. The use of powdered charcoal exploits the enormous rate-of-uptake advantage of powdered charcoal over the granular sorbents used in other hemoperfusion devices. The present tests showed that the pressure drops in the TFA devices are intrinsically low, but that their priming volumes are only marginally acceptable. Significant flow nonuniformities also exist. Despite this, the overall mass transfer resistance values for the TFA devices are lower than those for available commercial hemoperfusion units. Measurements of diffusion coefficients in the carbon and in the carbon-loaded polymer film showed that in the carbon-loaded film, the slowest diffusion step involves the carbon particles themselves. Other tests disclosed that the liquid external to the film (i.e., in the flow spaces) offers even greater mass transfer resistance than does the carbon-loaded film. Further evaluations of the TFA type of device are suggested, particularly concerning its thrombogenic properties.

The culture of Bacillus subtilis 21 was subjected to the action of nonuniform electric field, and the effect of the latter on the bacterial survival and biochemical activity was studied. The action of the field on the cells was shown to depend on the material of a load on which the culture was immobilized. The studied properties of Bac. subtilis 21 did not change when the culture was immobilized on cellulose fiber. About 50--60% of the cells died on silica gel under the action of field; the respiration activity and the rate of hexamethylene diamine destruction did not change. Almost all of the bacterial cells lost their viability upon electroimmobilization on ion-exchange resins. The destructive properties of the culture retained by the field exceed the activity of the control variants.

The cation exchange resin BioRex-70 was able to activate the classical complement pathway in human serum at 37 degrees C over the resin concentration range 0-5% (v/v). Using zymosan-treated human serum, it was found that the activation proceeded as far as complement protein C3.

In the presence of concentration gradient of metal ions on bilayer lipid membrane (BLM) the addition of non-electrogenic carriers results in a formation of concentration gradient of hydrogen ions in the unstirred layers near membrane. Addition of protonophore under these conditions brings about the formation of diffusion potential of hydrogen ions. This effect underlies the method of measuring non-electrogenic fluxes on BLM initiated in the presence of Men+/nH+ - exchangers. The proposed method was tested on the following Men+/nH+ - exchangers: nigericin, monensin and A23187. The order of cationic selectivity of the given carriers obtained by measuring the potentials on BLM in the presence of protonophores agrees with literature data, which were obtained by direct measurements of ionic fluxes.

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.

The mechanism of the antibacterial effect of monocarboxyl cellulose (MCC) and other ion exchange derivatives of cellulose was studied. It was shown that MCC, cellulose phosphate and aminocellulose had a pronounced antibacterial effect due to the presence of the ionogenic group H+ or OH- in the initial drugs. A certain role in this process was played by sorption. The level of the antibacterial activity of MCC depended on the number of the carboxylic groups. MCC is promising as a dressing material.

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.

The first step in developing a bladder infection is attachment of bacteria to the bladder epithelium. Removing the bladder mucin increases bacterial adherence up to a thousand-fold, and this increase can be prevented by pretreating the mucin-deficient bladder with heparin. To develop a rapid, in vitro antiadherence screening assay, we studied the adherence of Escherichia coli to various chromatography resins and the ability of heparin and other agents to antagonize this attachment. The results can be summarized as follows: Although E. coli attached to all resins, only the adherence to the anion exchange resin was inhibited by heparin (up to 95%). Agents which did not effect E. coli adherence to the resin did not affect attachment to the bladder. Agents which inhibited E. coli adherence to the bladder also inhibited E. coli adherence to the resin. Similar to the effect of heparin on E. coli attachment, the adherence of Klebsiella ozaene, Proteus mirabilis, and Streptococcus fecalis to both bladder epithelium and anion exchange resin were also antagonized. These studies indicate that the adherence of E. coli (as well as other bacterial species) to anion exchange resin responds to heparin and other chemical agents in a similar manner as does adherence to the mucin-deficient rabbit urinary bladder. Because of the ease and rapid nature of this in vitro assay, it serves as a useful screen for potential bacterial antiadherence agents and could be used to help elucidate mechanisms of bacterial attachment.