Sodium zirconium cyclosilicate for the management of chronic hyperkalemia in kidney disease, a novel agent.

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.

Contact-mediated reversible suppression of myogenesis. II. Reversal of suppression by bromodeoxyuridine.

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

Motor effects of copper in the caudate nucleus: reversible lesions with ion-exchange resin beads.

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.

The pharmacological exploitation of cholesterol 7alpha-hydroxylase, the key enzyme in bile acid synthesis: from binding resins to chromatin remodelling to reduce plasma cholesterol.

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.

[The in vitro effect of the addition of ion exchange resins on the bioavailability of electrolytes in artificial enteral feeding formulas]. / Efecto in vitro de la adición de resinas de intercambio iónico sobre la biodisponibilidad de electrolitos en fórmulas de nutrición enteral artificial.

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.

Enhanced production of human epidermal growth factor by a recombinant Escherichia coli integrated with in situ exchange of acetic acid by macroporous ion-exchange resin.

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.

Activation of the classical complement pathway by BioRex-70.

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.

Escherichia coli adherence to anion exchange resin. In vitro model for initial screening of potential antiadherence agents.

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.

Bile acid binding and hypocholesterolemic activity of a new anion exchange resin from 2-methylimidazol and epichlorohydrin.

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.

[Measurements of non-electrogenic fluxes through lipid bilayers induced by Men+/nH+-exchangers]. / Izmereniia neélektrogennykh potokov cherez bisloinye lipidnye membrany, indutsiruemye Men+/nH+-obmennikami.

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.

[Reversibility of the acid inactivation of immobilized alpha-amylase]. / Obratimost' kislotnoi inaktivatsii immobilizovannoi al'fa-amilazy.

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.

[Effect of FAF anionite swelling on its sorption properties]. / Vliianie nebukhaniia anionita FAF na ego sorbtsionnye svoistva.

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.

[Ion-exchange chromatography on cholesterol oxidase from Actinomyces lavendulae on a Biocarb-type carboxyl cationite]. / Ionoobmennaia khromatografiia kholesterinoksidazy iz Actinomyces lavendulae na karboksil'nom kationite tipa Biokarb.

Reversible sorption on the Biocarb-D carboxyl cationite of cholesterol oxidase extracted from the mycelium of Actinomyces lavendulae was examined. Sorption at pH 5.0 and desorption at pH 5.5 maintained 80% of the enzyme activity and increased seven-fold the specific activity as calculated per protein. By gel chromatography on Sephadex G-150 it was shown that the process was accompanied by a significant decrease in the number of inactive proteins.

[Sorption properties of carboxyl cation exchangers with a bacteriostatic effect]. / Sorbtsionnye svoistva karboksil'nykh kationitov, obladaiushchikh bakteriostaticheskim deistviem.

Sorption properties of new carboxyl cation exchangers containing components of salicylic acid (CST and CMTS) and benzoic acid (CBT and CMTB) were examined with respect to large organic ions. Such cation exchangers were shown to have greater permeability for high molecular weight proteins that sorbents of the Biocarb type. Bacteriostatic properties of the above cation exchangers were studied. With an increase in the content of the bactericidal component the bacteriostatic effect of the cation exchangers on Escherichia coli and Staphylococcus aureus enhanced. The cation exchangers CST and CMTS showed a greater bacteriostatic effect than those CBT and CMTB.

[Cultivation of Bordetella pertussis in liquid semisynthetic nutrient media with ion-exchange resins]. / Kul'tivirovanie kokliushnykh bakterii v zhidkikh polusinteticheskikh pitatel'nykh sredakh s ionoobmennymi smolami.

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.

The dehydration of fructose to 5-hydroxymethylfurfural efficiently catalyzed by acidic ion-exchange resin in ionic liquid.

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.

Contact activation of blood plasma and factor XII by ion-exchange resins.

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.

Simple fabrication of polymer-based Trametes versicolor laccase for decolorization of malachite green.

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.