Antimicrobial gelatin-based elastomer nanocomposite membrane loaded with ciprofloxacin and polymyxin B sulfate in halloysite nanotubes for wound dressing.

Bacterial infection is a major problem world-wide, especially in wound treatment where it can severely prolong the healing process. In this study, a double drug co-delivery elastic antibacterial nanocomposite was developed by combining ciprofloxacin (CPX) and polymyxin B sulfate-loaded halloysite clay nanotubes (HNTs-B) into a gelatin elastomer. CPX nanoparticles which act against both gram positive and gram-negative bacterium were dispersed directly in the matrix, and polymyxin B sulfate was loaded in HNTs and then distributed into the matrix. The effect of CPX and HNTs-B content on the physical properties, cytotoxicity, fibroblast adhesion and proliferation, in vitro drug release behavior and anti-bacterial properties were systematically investigated. The ciprofloxacin crystals and HNT-B were distributed in the matrix uniformly. The HNTs in the drug loading system not only enhanced the matrix' tensile strength but also slowed down the release rate of the high dissoluble polymyxin B sulfate. When the amount of HNT in the matrix increased, the thermal stability and tensile strength also increased but the polymyxin B sulfate release rate decreased because the HNTs prevented the drug release inside. All the nanocomposites exhibited antimicrobial activity against both gram-negative and gram-positive bacteria with the dual combination of drugs released from the nanocomposites. Furthermore, this kind of gelatin-based nanocomposites possesses higher water-absorbing quality, low cytotoxicity, adaptable biodegradability and good elasticity which can satisfy the requirements for an ideal biomaterial for use in wound healing applications.

Halloysite nanotubes-induced Al accumulation and oxidative damage in liver of mice after 30-day repeated oral administration.

Halloysite (Al2 Si2 O5 (OH)4 ·nH2 O) nanotubes (HNTs) are natural clay materials and widely applied in many fields due to their natural hollow tubular structures. Many in vitro studies indicate that HNTs exhibit a high level of biocompatibility, however the in vivo toxicity of HNTs remains unclear. The objective of this study was to assess the hepatic toxicity of the purified HNTs in mice via oral route. The purified HNTs were orally administered to mice at 5, 50, and 300 mg/kg body weight (BW) every day for 30 days. Oral administration of HNTs stimulated the growth of the mice at the low dose (5 mg/kg BW) with no liver toxicity, but inhibited the growth of the mice at the middle (50 mg/kg BW) and high (300 mg/kg BW) doses. In addition, oral administration of HNTs at the high dose caused Al accumulation in the liver but had no marked effect on the Si content in the organ. The Al accumulation caused significant oxidative stress in the liver, which induced hepatic dysfunction and histopathologic changes. These findings demonstrated that Al accumulation-induced oxidative stress played an important role in the oral HNTs-caused liver injury.

PEG-PE/clay composite carriers for doxorubicin: Effect of composite structure on release, cell interaction and cytotoxicity.

A novel drug delivery system for doxorubicin (DOX), based on organic-inorganic composites was developed. DOX was incorporated in micelles (M-DOX) of polyethylene glycol-phosphatidylethanolamine (PEG-PE) which in turn were adsorbed by the clay, montmorillonite (MMT). The nano-structures of the PEG-PE/MMT composites of LOW and HIGH polymer loadings were characterized by XRD, TGA, FTIR, size (DLS) and zeta measurements. These measurements suggest that for the LOW composite a single layer of polymer intercalates in the clay platelets and the polymer only partially covers the external surface, while for the HIGH composite two layers of polymer intercalate and a bilayer may form on the external surface. These nanostructures have a direct effect on formulation stability and on the rate of DOX release. The release rate was reversely correlated with the degree of DOX interaction with the clay and followed the sequence: M-DOX>HIGH formulation>LOW formulation>DOX/MMT. Despite the slower release from the HIGH formulation, its cytotoxicity effect on sensitive cells was as high as the "free" DOX. Surprisingly, the LOW formulation, with the slowest release, demonstrated the highest cytotoxicity in the case of Adriamycin (ADR) resistant cells. Confocal microscopy images and association tests provided an insight into the contribution of formulation-cell interactions vs. the contribution of DOX release rate. Internalization of the formulations was suggested as a mechanism that increases DOX efficiency, particularly in the ADR resistant cell line. The employment of organic-inorganic hybrid materials as drug delivery systems, has not reached its full potential, however, its functionality as an efficient tunable release system was demonstrated. STATEMENT OF SIGNIFICANCE: DOX PEG-PE/clay formulations were design as an efficient drug delivery system. The main aim was to develop PEG-PE/clay formulations of different structures based on various PEG-PE/clay ratios in order to achieve tunable release rates, to control the external surface characteristics and formulation stability. The formulations showed significantly higher toxicity in comparison to "free" DOX, explained by formulation internalization. For each cell line tested, sensitive and ADR resistant, a different formulation structure was found most efficient. The potential of PEG-PE/clay-DOX formulations to improve DOX administration efficacy was demonstrated and should be further explored and implemented for other cancer drugs and cells.

Safety Assessment of Synthetic Fluorphlogopite as Used in Cosmetics.

The Cosmetic Ingredient Review Expert Panel (the Panel) reviewed the safety of synthetic fluorphlogopite as used in cosmetics. Synthetic fluorphlogopite functions as a bulking agent and a viscosity-increasing agent. The Panel reviewed available animal and human data related to this ingredient along with a previous safety assessment of other magnesium silicates. The Panel concluded that synthetic fluorphlogopite was safe as cosmetic ingredients in the practices of use and concentration as given in this safety assessment.

Levels of lead, arsenic, mercury and cadmium in clays for oral use on the Dutch market and estimation of associated risks.

Pregnant women in Africa, Asia and Suriname, and some immigrants in Western societies, traditionally consume clay products known by a variety of names such as mabele, calabash chalk, sikor and pimba. Furthermore, clay is used for health purposes in Western societies. Because certain clays can contain high levels of metals and metalloids, the aim of this study was to determine lead, arsenic, mercury and cadmium in clay products for oral use available on the Dutch market. Traditional clays originating from Africa (n = 10) and Suriname (n = 26), and health clays (n = 27) were sampled from 2004 up to and including 2012. Total metal and metalloid contents were measured by ICP-MS and showed maximum levels of lead, arsenic, mercury and cadmium of 99.7, 45.1, 2.2 and 0.75 mg kg⁻¹, respectively. In the absence of maximum limits for these type of clays, the potential exposure was estimated from the determined concentration, the estimated daily use level of the clays, and the estimated bioaccessibility of the different metals and arsenic. The intake estimates were compared with existing health-based guidance values. For lead, the use of 34 of the 36 traditional clays and two of the 27 health clays would result in intake levels exceeding the toxicological limit by up to 20-fold. Use of 15 of the 35 traditional clays and 11 of the 27 health clays would result in intake levels exceeding the toxicological limit for inorganic arsenic by up to 19-fold. Although limited bioaccessibility from the clay may limit the exposure and exceedance of the health-based guidance values, it was concluded that lead and arsenic intakes from some clay products could be of concern also because of their use by pregnant women and the potential developmental toxicity. As a result the use of these products, especially by pregnant women, should be discouraged.

Soil consumed by chacma baboons is low in bioavailable iron and high in clay.

Despite widespread consumption of soil among animals, the role of geophagy in health maintenance remains an enigma. It has been hypothesized that animals consume soil for supplementation of minerals and protection against toxins. Most studies determine only the total elemental composition of soil, which may not reflect the amount of minerals available to the consumer. Our aim was to test these hypotheses by evaluating the bioavailability of iron in soil consumed by chacma baboons, using a technique that simulates digestion and adsorption. Our results indicate that, despite variation in absolute iron concentration of soil samples, actual iron bioavailability was low while clay content was quite high. This suggests that iron supplementation is unlikely to be the primary motivation for geophagy in this population, and that detoxification is a plausible explanation. This study demonstrates that more research on bioavailability and clay composition is needed to determine the role geophagy plays in health maintenance.

In situ absorption and relative bioavailability studies of zaleplon loaded self-nanoemulsifying powders.

Self-nanoemulsifying drug delivery systems (SNEDDSs) offer potential as suitable carriers for improved oral delivery of poorly soluble and low bioavailable drugs. To derive self-nanoemulsifying powders (SNEPs), the optimized Z-SNEDDS formulation was adsorbed onto different carriers and based on micromeritics the formulation loaded onto neusilin US2 (SNEP-N) was selected for further characterization. The solid-state characterization (scanning electron microscopy, differential scanning calorimetry and powder X-ray diffraction) studies unravel the transformation of native crystalline state to amorphous and/or molecular state. The higher predictive effective permeability coefficient and fraction absorbed in humans extrapolated from in situ single-pass intestinal absorption study data in rats provide an insight on the potential of SNEPs for augment in absorption across gastrointestinal barrier. Overall a 3.5-fold enhancement in the extent of absorption of zaleplon from SNEP-N formulation proves the feasibility of SNEPs formulation for improved oral delivery of zaleplon.

Interaction between tylosin and bentonite clay from a pharmacokinetic perspective.

The interaction between bentonite and tylosin was investigated in broiler chickens, based on pharmacokinetic characteristics obtained in vivo. Simultaneous oral administration of bentonite and tylosin significantly lowered plasma levels of tylosin and reduced the area under the plasma concentration-time curve (AUC(0-inf)), maximal plasma concentration (C(max)), time to maximal plasma concentration (T(max)) and relative oral bioavailability. The results prove unambiguously the binding of tylosin by bentonite. Simultaneous administration of tylosin (in the drinking water or feed) and bentonite (mixed in the feed as a mycotoxin binder) should therefore be avoided.

Total allowable concentrations of monomeric inorganic aluminum and hydrated aluminum silicates in drinking water.

Maximum contaminant levels are used to control potential health hazards posed by chemicals in drinking water, but no primary national or international limits for aluminum (Al) have been adopted. Given the differences in toxicological profiles, the present evaluation derives total allowable concentrations for certain water-soluble inorganic Al compounds (including chloride, hydroxide, oxide, phosphate and sulfate) and for the hydrated Al silicates (including attapulgite, bentonite/montmorillonite, illite, kaolinite) in drinking water. The chemistry, toxicology and clinical experience with Al materials are extensive and depend upon the particular physical and chemical form. In general, the water solubility of the monomeric Al materials depends on pH and their water solubility and gastrointestinal bioavailability are much greater than that of the hydrated Al silicates. Other than Al-containing antacids and buffered aspirin, food is the primary source of Al exposure for most healthy people. Systemic uptake of Al after ingestion of the monomeric salts is somewhat greater from drinking water (0.28%) than from food (0.1%). Once absorbed, Al accumulates in bone, brain, liver and kidney, with bone as the major site for Al deposition in humans. Oral Al hydroxide is used routinely to bind phosphate salts in the gut to control hyperphosphatemia in people with compromised renal function. Signs of chronic Al toxicity in the musculoskeletal system include a vitamin D-resistant osteomalacia (deranged membranous bone formation characterized by accumulation of the osteoid matrix and reduced mineralization, reduced numbers of osteoblasts and osteoclasts, decreased lamellar and osteoid bands with elevated Al concentrations) presenting as bone pain and proximal myopathy. Aluminum-induced bone disease can progress to stress fractures of the ribs, femur, vertebrae, humerus and metatarsals. Serum Al ≥100 µg/L has a 75-88% positive predictive value for Al bone disease. Chronic Al toxicity is also manifest in the hematopoietic system as an erythropoietin-resistant microcytic hypochromic anemia. Signs of Al toxicity in the central nervous system (speech difficulty to total mutism to facial grimacing to multifacial seizures and dyspraxia) are related to Al accumulation in the brain and these symptoms can progress to frank encephalopathy. There are four groups of people at elevated risk of systemic Al intoxication after repeated ingestion of monomeric Al salts: the preterm infant, the infant with congenital uremia and children and adults with kidney disease. There is a dose-dependent increase in serum and urinary Al in people with compromised renal function, and restoration of renal function permits normal handling of systemically absorbed Al and resolution of Al bone disease. Clinical experience with 960 mg/day of Al(OH)(3) (~5 mg Al/kg-day) given by mouth over 3 months to men and women with compromised renal function found subclinical reductions in hemoglobin, hematocrit and serum ferritin. Following adult males and females with reduced kidney function found that ingestion of Al(OH)(3) at 2.85 g/day (~40 mg/kg-day Al) over 7 years increased bone Al, but failed to elicit significant bone toxicity. There was one report of DNA damage in cultured lymphocytes after high AlCl(3) exposure, but there is no evidence that ingestion of common inorganic Al compounds presents an increased carcinogenic risk or increases the risk for adverse reproductive or developmental outcomes. A number of studies of Al exposure in relation to memory in rodents have been published, but the results are inconsistent. At present, there is no evidence to substantiate the hypothesis that the pathogenesis of Alzheimer's Disease is caused by Al found in food and drinking water at the levels consumed by people living in North America and Western Europe. Attapulgite (palygorskite) has been used for decades at oral doses (recommended not to exceed two consecutive days) of 2,100 mg/day in children of 3-6 years, 4,200 mg/day in children of 6-12 years, and 9,000 mg/day in adults. Chronic ingestion of insoluble hydrated Al silicates (in kg) can result in disturbances in iron and potassium status, primarily as a result of clay binding to intestinal contents and enhanced fecal iron and zinc elimination. Sufficiently high doses of ingested Al silicates (≥50 g/day) over prolonged periods of time can elicit a deficiency anemia that can be corrected with oral Fe supplements. There is essentially no systemic Al uptake after ingestion of the hydrated Al silicates. Rats fed up to 20,000 ppm Ca montmorillonite (equivalent to 1,860 ppm total Al as the hydrated Al silicate) for 28 weeks failed to develop any adverse signs. The results of dietary Phase I and II clinical trials conducted in healthy adult volunteers over 14 days and 90 days with montmorillonite found no adverse effects after feeding up to 40 mg/kg-day as Al. Since the Al associated with ingestion of hydrated Al silicates is not absorbed into the systemic circulation, the hydrated Al silicates seldom cause medical problems unless the daily doses consumed are substantially greater than those used clinically or as dietary supplements. A no-observable-adverse-effect-level (NOAEL) of 13 mg/kg-day as total Al can be identified based on histologic osteomalacia seen in adult hemodialysis patients given Al hydroxide for up to 7 years as a phosphate binder. Following U.S. EPA methods for calculation of an oral reference dose (RfD), an intraspecies uncertainty factor of 10x was applied to that value results in a chronic oral reference dose (RfD) of 1.3 mg Al/kg-day; assuming a 70-kg adult consumes 2 L of drinking water per day and adjusting for a default 20% relative source contribution that value corresponds to a drinking water maximum concentration of 9 mg/L measured as total Al. A chronic NOAEL for montmorillonite as representative of the hydrated Al silicates was identified from the highest dietary concentration (20,000 ppm) fed in a 28-week bioassay with male and female Sprague-Dawley rats. Since young rats consume standard laboratory chow at ~23 g/day, this concentration corresponds to 56 mg Al/kg-day. Application of 3x interspecies uncertainty factor and a 3x factor to account for study duration results in a chronic oral RfD of 6 mg Al/kg-day. Of note, this RfD is 5-10 fold less than oral doses of Al silicates consumed by people who practice clay geophagy and it corresponds to a maximum drinking water concentration of 40 mg Al/L. To utilize the values derived here, the risk manager must recognize the particular product (e.g., alum) or source (e.g., groundwater, river water, clay or cement pipe) of the Al found in tap water, apply the appropriate analytical methods (atomic absorption, energy dispersive X-ray diffraction, infrared spectral analysis and/or scanning transmission electron microscopy) and compare the results to the most relevant standard. The drinking water concentrations derived here are greater than the U.S. EPA secondary maximum contaminant level (MCL) for total Al of 0.05-0.2 mg/L [40 CFR 143.3]. As such, domestic use of water with these concentrations is likely self-limiting given that its cloudy appearance will be greater than the maximum permitted (0.5-5.0 nephalometric turbidity units; 40 CFR Parts 141 and 142). Therefore, the organoleptic properties of Al materials in water determine public acceptance of potable water as contrast to any potential health hazard at the concentrations ordinarily present in municipal drinking water.

Drug intercalation in layered double hydroxide clay: application in the development of a nanocomposite film for guided tissue regeneration.

It has been proposed that localized and controlled delivery of alendronate and tetracycline to periodontal pocket fluids via guided tissue regeneration (GTR) membranes may be a valuable adjunctive treatment for advanced periodontitis. The objectives of this work were to develop a co-loaded, controlled release tetracycline and alendronate nanocomposite plasticized poly(lactic-co-glycolic acid) (PLGA) film that would form a suitable matrix supporting osteoblast proliferation and differentiation. Alendronate release was successfully controlled, with complete suppression of the burst phase of release by intercalation of alendronate anions in magnesium/aluminum layered double hydroxide (LDH) clay nanoparticles and dispersed in the PLGA film matrix. Tetracycline, loaded as free drug into the film together with alendronate-LDH clay complex released more rapidly than alendronate, but showed evidence of intercalation in the LDH clay particles. The dual drug loaded nanocomposite films were biocompatible with osteoblasts and after 5 week incubations, significant increase in alkaline phosphatase activity and bone nodule formation were observed.

Influence of clay content on bioavailability of copper in the earthworm Eisenia fetida.

We investigated the effect of clay content on the bioavailability of copper to the earthworm Eisenia fetida, in the laboratory for 28 days using OECD artificial soil adjusted to 5%, 20% and 40% clay. Mortality, growth, cocoon production and internal copper concentrations were assessed in worms, and total, DTPA and CaCl(2) extractable copper in the substrates were also determined. The results showed that with increased clay content, there was significant reduction in internal Cu concentration of worms as well as toxicity of copper as shown by data for growth and mortality. However, internal copper concentrations of worms could not explain fully the observed toxicity in this study probably because of Cu regulation. Among the three extraction methods, DTPA extraction revealed the strongest relationship between partitioning and toxicity of Cu in this study. DTPA extract is thus a promising surrogate measure of bioavailability of Cu to earthworms. It is concluded that clay content has significant influence on the bioavailability of copper to earthworms and other similar species.

Role of food and clay particles in toxicity of copper and diazinon using Daphnia magna.

Toxicity changes in copper and diazinon were investigated in the presence of food, clay, and their mixture by using Daphnia magna. In sorption equilibrium experiments, copper was significantly attracted (>34% sorbed) to food, clay, and food-clay mixture due to their negative zeta potential, while diazinon was less sorbed (<11%). In the exposure test with food and clay particles, it was revealed that copper was remarkably reduced in the presence of clay particles indicating the change in bioavailability of copper by sorption to clay. This was considered as the primary mechanism for toxicity reduction whereas diazinon toxicity was food dependent in the analysis of toxicity using toxicity change index (TCI). It was also shown that certain foods could not only act as a sorbent to copper and diazinon, but also as a material of energy source to alleviate the toxic damage. Meanwhile, clay can be considered as a prominent sorbent to copper but not to diazinon and can inhibit the sorption interaction between foodstuffs and toxicants through the aggregation and sedimentation processes. Furthermore, clay particles, as shown in TCI analysis, may be a potentially risky material as a physiological stressor or a toxicant carrier in contaminated environments.

Interactions between ingested kaolinite and the intestinal mucosa in rat: proteomic and cellular evidences.

Although some of the effects of clay ingestion by humans and animals, such as gastrointestinal wellness and the increase in food efficiency are well known, the underlying mechanisms are not yet fully understood. Therefore, the interactions between the intestinal mucosa and kaolinite particles and their effects on mucosal morphology were observed using light microscopy (LM), transmission electron microscopy (TEM), conventional (CSEM) and environmental (ESEM) scanning electron microscopy combined with an EDX micro-analysis system. Kaolinite consumption, given with free access to rats, varied considerably from one animal to the other but was regular through time for each individual. Some kaolinite particles appeared chemically dissociated in the lumen and within the mucus barrier. Aluminium (Al) originating from ingested clay and present in the mucus layer could directly cross the intestinal mucosa. A significant increase in the thickness of the villi with large vacuoles at the base of the mucosal cells and a decrease in the length of enterocyte microvilli characterized complemented animals. The proteomic analyses of the intestinal mucosa of complemented rats also revealed several modifications in the expression level of cytoskeleton proteins. In summary, kaolinite particles ingested as food complement interact with the intestinal mucosa and modify nutrient absorption. However, these data, together with the potential neurotoxicity of Al, need further investigation.

Fate of prions in soil: trapped conformation of full-length ovine prion protein induced by adsorption on clays.

Studying the mechanism of retention of ovine prion protein in soils will tackle the environmental aspect of potential dissemination of scrapie infectious agent. We consider the surface-induced conformational changes that the recombinant ovine prion protein (ovPrP) may undergo under different pH conditions when interacting with soil minerals of highly adsorptive capacities such as montmorillonite. The conformational states of the full-length ovine prion protein adsorbed on the electronegative clay surface are compared to its solvated state in deuterated buffer in the pD range 3.5-9, using FTIR spectroscopy. The in vitro pH-induced conversion of the alpha-helical monomer of ovPrP into oligomers of beta-like structure prone to self-aggregation does not occur when the protein is adsorbed on the clay surface. The conformation of the trapped ovPrP molecules on montmorillonite is pH-independent and looks like that of the ovPrP solvated state at pD higher than 7, suggesting the major role of Arg and Lys residues in the electrostatic origin of adsorption. The uneven distribution of positively and negatively charged residues of the ovPrP protein would promote a favored orientation of the protein towards the clay, so that not only the basic residues embedded in the N-terminal flexible part but also external basic residues in the globular part of the protein might participate to the attractive interaction. From these results, it appears unlikely that the interaction of normal prions (PrP(C)) with soil clay surfaces could induce a change of conformation leading to the pathogenic form of prions (PrP(Sc)).

Formulation and preliminary in vivo dog studies of a novel drug delivery system for the treatment of periodontitis.

A novel drug delivery system for the treatment of periodontitis was developed using two components. The first was tetracycline base loaded into the microtubular excipient halloysite, which was coated with chitosan to further retard drug release. Encapsulation efficiencies of 32.5% were achieved with the loading procedure, with tetracycline base showing in vitro release for up to 50 days in simulated gingival crevicular fluid. The second component developed was a vehicle for the drug loaded coated halloysite, which was primarily based on the thermoresponsive polymer, poloxamer 407. A concentration of 20% was chosen with the thermoresponsivity of the system modified using PEG 20,000 so that the mobile product at room temperature would gel by temperature rise following syringing into a periodontal pocket. Retention of the overall system in the pocket was further improved by the addition of octyl cyanoacrylate (OCA). The thermoresponsivity of the poloxamer 407 system proved to be sensitive to the presence of added excipients with the levels of PEG 20,000 and OCA requiring modification in the presence of the halloysite component. A final formulation was developed which consisted of 200 mg of halloysite double loaded with tetracycline base and coated with chitosan, suspended in 1 ml of poloxamer 407 20% (w/w), PEG 20,000 0.5% (w/w), OCA 1.0% (w/w), water to 100%, adjusted to pH 4. The syringeability of this formulation at various temperatures was evaluated to ensure ease of delivery to the periodontal pocket. A stability study was performed to examine the change in thermoresponsivity over time, with the final formulation found to be stable for at least 9 months when stored at room temperature (approximately 20 degrees C). This formulation offered ease of delivery to the periodontal pocket and sustained release of the antibiotic for up to 6 weeks. The formulation had preliminary in vivo testing performed in dogs to determine levels of drug release, antimicrobial activity and retentive ability of the product. A wound pocket creation model was developed for the purposes of the trial. The product was easy to deliver to the pockets with application times of less than 1 min. Results showed the product was retained in the pocket for up to 6 weeks with effective tetracycline levels released locally over this time period, which achieved good antibacterial activity.

Modeling and experimental comparison of the differential adsorption of B1 and G1 aflatoxins on mineral aluminosilicate surfaces.

Aflatoxins produced by Aspergillus fungus are secondary metabolites undergoing biotransformation rates in hepatic tissues and lipid peroxidation. Although the use of adsorbent materials became a common practice for feed grain detoxification, fundamental studies are needed to clarify the interaction occurring between mineral surfaces and organic molecules. We evaluated the differential adsorption of B1 and G1 on 10 adsorbent materials and compared it in vitro by means of fluorescence emission from solution. Three aluminosilicates showed no adsorption of B1 at all, whereas only one was inactive for G1 adsorption and seven of them showed 15.2 to 77.9% adsorption for B1 and 8.3 to 78% for G1. All these adsorbents were more selective toward G1 rather than B1 aflatoxins. This behavior can be explained by the presence of an additional cyclic ester in G1, which provides a higher electronic density to G1 molecules, thus forming more stable hydrogen bridges with respect to the cyclopentanone ring present in B1.

Effects of inorganic adsorbents and cyclopiazonic acid in broiler chickens.

Previous studies with cyclopiazonic acid (CPA) have indicated that this mycotoxin strongly adsorbs onto the surface of a naturally acidic phyllosilicate clay (AC). The objective of this study was to determine whether AC (and similar adsorbents) could protect against the toxicity of CPA in vivo. Acidic phyllosilicate clay, neutral phyllosilicate clay (NC, or hydrated sodium calcium aluminosilicate), and a common zeolite (CZ, or clinoptilolite) were evaluated. One-day-old broiler chicks consumed diets containing 0 or 45 mg/kg CPA alone or in combination with 1% AC, NC, or CZ ad libitum from Day 1 to 21. Body weight, feed consumption, feed:gain, hematology, serum biochemical values, and enzyme activities were evaluated. Compared to controls, CPA alone reduced body weight at Day 21 by a total of 26% and resulted in a significantly higher feed:gain ratio. Toxicity of CPA was also expressed through increased relative weights of kidney, proventriculus, and gizzard. Also, there were some alterations in hematology, serum biochemical values, and enzyme activities. Treatment with inorganic adsorbents did not effectively diminish the growth-inhibitory effects of CPA or the increased weights of organs, although there was some protection from hematological, serum biochemical, and enzymatic changes produced by CPA. The results of this study suggest that in vitro binding of CPA to clay does not accurately forecast its efficacy in vivo; the reasons for this discrepancy are not clear, but they may be related to differences in clay binding capacity and ligand selectivity for CPA in vitro vs in vivo. Predictions about the ability of inorganic adsorbents to protect chickens from the adverse effects of mycotoxins should be approached with caution and should be confirmed in vivo, paying particular attention to the potential for nutrient interactions.

Pharmacokinetic study of zeolite A, sodium aluminosilicate, magnesium silicate, and aluminum hydroxide in dogs.

Zeolite A is a synthetic zeolite which may have therapeutic utility in osteoporotic individuals because of its ability to stimulate bone formation. A study of Zeolite A (30 mg/kg), sodium aluminosilicate (16 mg/kg), magnesium trisilicate (20 mg/kg), and aluminum hydroxide (675 mg) was designed in beagle dogs. The purpose of this study was to compare the oral bioavailability of silicon and aluminum from Zeolite A, sodium aluminosilicate, magnesium trisilicate, and aluminum hydroxide in dogs. Twelve female dogs received each compound as a single dose separated by one week in a randomized, 4-way, crossover design. Plasma samples were drawn at time 0 and for 24 hours after dosing. The concentrations of silicon and aluminum were determined by graphite furnace atomic absorption. The mean plasma silicon AUC values (+/- S.D.) were 9.5 +/- 4.5, 7.7 +/- 1.6, 8.8 +/- 3.0, 6.1 +/- 1.9 mg.hr/L and the mean plasma silicon Cmax values (+/- S.D.) were 1.07 +/- 1.06, 0.67 +/- 0.27, 0.75 +/- 0.31, 0.44 +/- 0.17 mg/L for Zeolite A, sodium aluminosilicate, magnesium trisilicate, and aluminum hydroxide respectively. Although mean silicon AUC and Cmax values were elevated when compared to baseline after administration of the silicon containing compounds, only the AUC from Zeolite A reached statistical significance (p = 0.041). The mean plasma silicon Tmax values (+/- S.D.) were 7.9 +/- 6.4, 5.8 +/- 4.6, 6.9 +/- 6.3 and 8.5 +/- 3.4 hrs for Zeolite A, sodium aluminosilicate, magnesium trisilicate and aluminum Hydroxide respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of bronchopulmonary lavage on lung retention and clearance of particulate material in hamsters.

Hamsters were exposed to an aerosol of fused aluminosilicate particles (FAP) labeled with 57Co. Three groups of animals were given bronchopulmonary lavage, beginning at either 1 week, 1 month, or 6 months after exposure. Each treated group was lavaged eight times over a period of 25 days. Each lavage involved 10 saline washes of the lungs. For each group, about 60-70% of the body content of 57Co at the start of lavage treatment was removed; nearly half of this was recovered in the first two lavages. A positive correlation was demonstrated between the macrophage content and 57Co activity of the washings. The subsequent fractional clearance rate of 57Co from lavaged animals was not significantly different from that in a group of untreated control animals.

[Adsorption of dyes as an indicator of the biological activity of mineral dust]. / Adsorbtsiia na bagrila kato pokazatel za biologichnata aktivnost na mineralni prakhove.

A study is made on the adsorption capacity of several types silicates and quartz dusts, prepared from pure mineral standards with respect to methylene blue and fuchsin. There are differences in the adsorption capacity of the minerals referring to unit surface. The quantity of the adsorption for samples of the same mineral, broken to pieces of different dispersity, also differs. However, between the adsorption capacity of test samples, divided into 3 groups--quartz, zeolite and mixed from the work environment, with respect to methylene blue, and their biological aggressiveness, tested "in vivo" after intratracheal test and the subcutaneous pocket method and the zeolite dusts on diploid culture, an inverse dependence is established. The adsorption capacity of the test dusts from the work environment is many times higher than the examined quartz and zeolite dusts, because of the presence of mineral components in them, especially argillaceous, which have high affinity toward the dye. The inverse dependence established between the adsorption capacity with respect to methylene blue and the biological effect of the tested dusts give grounds to propose the adsorption capacity as one of the induces for studying and hygienic evaluation of different types dusts, which have no components manifesting specific affinity to the dye.