Clostridioides difficile (C. difficile) infection is a major public health problem worldwide. The current treatment of C. difficile-associated diarrhea relies on the use of antibacterial agents. However, recurrences are frequent. The main virulence factors of C. difficile are two secreted cytotoxic proteins toxin A and toxin B. Alternative research exploring toxin binding by resins found a reduced rate of recurrence by administration of tolevamer. Hence, binding of exotoxins may be useful in preventing a relapse provided that the adsorbent is innocuous. Here, we examined the toxin binding capacity of G-PUR®, a purified version of natural clinoptilolite-tuff. Our observations showed that the purified clinoptilolite-tuff adsorbed clinically relevant amounts of C. difficile toxins A and B in vitro and neutralized their action in a Caco-2 intestinal model. This conclusion is based on four independent sets of findings: G-PUR® abrogated toxin-induced (i) RAC1 glucosylation, (ii) redistribution of occludin, (iii) rarefaction of the brush border as visualized by scanning electron microscopy and (iv) breakdown of the epithelial barrier recorded by transepithelial electrical resistance monitoring. Finally, we confirmed that the epithelial monolayer tolerated G-PUR® over a wide range of particle densities. Our findings justify the further exploration of purified clinoptilolite-tuff as a safe agent in the treatment and/or prevention of C. difficile-associated diarrhea.

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Various gluten-related diseases (celiac disease, wheat allergy, gluten sensitivity) are known and their incidence is growing. Gluten is a specific type of plant storage protein that can impair the health of gluten-prone persons following consumption, depending on the origin. The most severe effects are induced by wheat, barley, and rye. The only treatment is based on the absolute avoidance of those foods, as even traces might have severe effects on human well-being. With the goal of binding gluten impurities after ingestion, an in vitro setting was created. A special processed kind of zeolite, purified clinoptilolite-tuff (PCT), was implemented as an adsorber of gluten derived from different origins. Zeolites are known for their excellent sorption capacities and their applications in humans and animals have been studied for a long time. Tests were also performed in artificial gastric and intestinal fluids, and the adsorption capacity was determined via a certified validated method (ELISA). Depending on the kind of gluten source, 80–130 µg/mg of gluten were bound onto PCT. Hence, purified clinoptilolite-tuff, which was successfully tested for wheat, barley, and rye, proved to be suitable for the adsorption of gluten originating from different kinds of crops. This result might form the basis for an expedient human study in the future.

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BACKGROUND: Yielding and shear elasticity of blood are merely discussed within the context of hematocrit and erythrocyte aggregation. However, plasma might play a substantial role due its own viscoelasticity. OBJECTIVE: If only erythrocyte aggregation and hematocrit would determine yielding, blood of different species with comparable values would present comparable yield stresses. METHODS: rheometry (SAOS: amplitude and frequency sweep tests; flow curves) of hematocrit-matched samples at 37°C. Brillouin Light Scattering Spectroscopy at 38°C. RESULTS: Yield stress for pig: 20mPa, rat: 18mPa, and human blood: 9mPa. Cow and sheep blood were not in quasi-stationary state supporting the role of erythrocyte aggregation for the development of elasticity and yielding. However, pig and human erythrocytes feature similar aggregability, but yield stress of porcine blood was double. Murine and ruminant erythrocytes both rarely aggregate, but their blood behavior was fundamentally different. Pig plasma was shear-thinning and murine plasma was platelet-enriched, supporting the role of plasma for triggering collective effects and gel-like properties. CONCLUSIONS: Blood behavior near zero shear flow is not based solely on erythrocyte aggregation and hematocrit, but includes the hydrodynamic interaction with plasma. The shear stress required to break down elasticity is not the critical shear stress for dispersing erythrocyte aggregates, but the shear stress required to fracture the entire assembly of blood cells within their intimate embedding.

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