Clay-induced DNA breaks as a path for genetic diversity, antibiotic resistance, and asbestos carcinogenesis.

Natural clays and synthetic nanofibres can have a severe impact on human health. After several decades of research, the molecular mechanism of how asbestos induces cancer is not well understood. Different fibres, including asbestos, can penetrate cell membranes and introduce foreign DNA in bacterial and eukaryotic cells. Incubating Escherichia coli under friction forces with sepiolite, a clayey material, or with asbestos, causes double-strand DNA breaks. Antibiotics and clays are used together in animal husbandry, the mutagenic effect of these fibres could be a pathway to antibiotic resistance due to the friction provided by peristalsis of the gut from farm animals in addition to horizontal gene transfer. Moreover, we raise the possibility that the same mechanism could generate bacteria diversity in natural scenarios, playing a role in the evolution of species. Finally, we provide a new model on how asbestos may promote mutagenesis and cancer based on the observed mechanical genotoxicity.

Effect of Clinoptilolite and Sepiolite Nanoclays on Human and Parasitic Highly Phagocytic Cells.

Nanoclays have potential applications in biomedicine raising the need to evaluate their toxicity in in vitro models as a first approach to its biocompatibility. In this study, in vitro toxicity of clinoptilolite and sepiolite nanoclays (NC) was analyzed in highly phagocytic cultures of amoebas and human and mice macrophages. While amebic viability was significantly affected only by sepiolite NC at concentrations higher than 0.1 mg/mL, the effect on macrophage cultures was dependent on the origin of the cells. Macrophages derived from human peripheral blood monocytes were less affected in viability (25% decrease at 48 h), followed by the RAW 264.7 cell line (40%), and finally, macrophages derived from mice bone marrow monocytes (98%). Moreover, the cell line and mice macrophages die mainly by necrosis, whereas human macrophages exhibit increased apoptosis. Cytokine expression analysis in media of sepiolite NC treated cultures showed a proinflammatory profile (INFγ, IL-1α, IL-8, and IL-6), in contrast with clinoptilolite NC that induced lees cytokines with concomitant production of IL-10. The results show that sepiolite NC is more toxic to amoebas and macrophages than clinoptilolite NC, mostly in a time and dose-dependent manner. However, the effect of sepiolite NC was comparable with talc powder suggesting that both NC have low cytotoxicity in vitro.

[Clinical strategies for prevention of drug-induced urinary calculi].

Drug-induced urinary calculi, although they account for only 1-2% of urinary calculi, deserve consideration because most of them are preventable. In the drug-containing calculi resulting from the crystallization of a certain drug and its metabolites in the urine, stone analysis can identify the responsible drug. While, in the drug-induced metabolic calculi caused by interference with calcium, oxalate and purine metabolism, careful clinical inquiry is necessary to reveal involvement of a certain drug in stone formation. Better awareness of the possible drugs with lithogenic potential and close surveillance of patients on long-term treatment with these drugs are necessary. Especially, in patients with a history of urolithiaisis, prescription of lithogenic drugs deserve careful consideration.

Pulmonary exposures to Sepiolite nanoclay particulates in rats: resolution following multinucleate giant cell formation.

Sepiolite is a magnesium silicate-containing nanoclay mineral and is utilized as a nanofiller for nanocomposite applications. We postulated that lung exposures to Sepiolite clay samples could produce sustained effects. Accordingly, the pulmonary and extrapulmonary systemic impacts in rats of intratracheally instilled Sepiolite nanoclay samples were compared with quartz or ultrafine (uf) titanium dioxide particle-types at doses of 1mg/kg or 5mg/kg. All particulates were well characterized, and dedicated groups were evaluated by bronchoalveolar lavage, lung cell proliferation, macrophage functional assays and full body histopathology at selected times postexposure (pe). Bronchoalveolar lavage results demonstrated that quartz particles produced persistent, dose-dependent lung inflammatory responses measured from 24h through 3 months pe. Exposures to uf TiO(2) particles or Sepiolite samples produced transient neutrophilic responses at 24-h pe; however, unlike the other particle-types, Sepiolite exposures produced macrophage-agglomerates or multinucleate giant cells at 1 week, 5 weeks and 3 months pe. In vitro alveolar macrophage functional studies demonstrated that mononuclear cells recovered from quartz but not Sepiolite or uf TiO(2)-exposed rats were deficient in their chemotactic capacities. Moreover, lung parenchymal cell proliferation rates were increased in rats exposed to quartz but not Sepiolite or uf TiO(2) particles. Histopathological evaluation of lung tissues revealed that pulmonary exposures to Sepiolite nanoclay or quartz samples produced inflammation in centriacinar regions at 24-h pe but the effects decreased in severity over time for Sepiolite and increased for quartz-exposed rats. The quartz-induced lesions were progressive and were characterized at 3 months by acinar foamy alveolar macrophage accumulation and septal thickening due to inflammation, alveolar Type II cell hyperplasia and collagen deposition. In the Sepiolite nanoclay group, the finding of multinucleated giant cell accumulation associated with minor collagen deposition in acinar regions was rarely observed. Exposures to ultrafine TiO(2) produced minimal effects characterized by the occurrence of phagocytic macrophages in alveolar ducts. Full body histopathology studies were conducted at 24h and 3 months post particle exposures. Histopathological evaluations revealed minor particle accumulations in some mediastinal or thoracic lymph nodes. However, it is noteworthy that no extrapulmonary target organ effects were observed in any of the particle-exposed groups at 3 months postexposure.

[Silica-containing urinary stones--clinical issues to keep in mind]. / Silikathaltige Harnsteine im Klinikalltag. Was gibt es zu beachten?

Formation of calculi in efferent urinary passages is always due to supersaturation of urinary calculi substances and associated increased crystallization. Apart from the typical calculi, consisting of calcium oxalate, inorganic phosphates, uric acid or cystine, there are occasional signs of rare substance classes. Although more than 50 silicate stones have already been reported internationally, this stone entity remains relatively unknown. In particular, the occurrence of silicate stones in the absence of magnesium trisilicate abuse is extremely rare. A medium-sized left-sided ureterolith was removed from a 54-year-old male patient using a ureteroscope. X-ray diffraction showed it to be a compound stone consisting of 40% silicate. The patient, who in 1986 was living close to the nuclear reactor accident in Chernobyl, showed no signs of a constant uptake of magnesium trisilicate. However, he had undergone partial (2/3) gastrectomy 4 months before for a drug-refractory gastric ulcer, which had been diagnosed at the end of the 1980s and treated with excessive dosages of a magnesium trisilicate antacid preparation until the time of the operation. The patient had also been suffering from unstable angina pectoris since 1986 and treated with Pentalong (pentaerythrityltetranitrate) for 17 years. We were also able to detect silicium dioxide in components of this drug using X-ray diffraction. Silicate uroliths are extremely rare but they can be clearly identified by X-ray diffraction or infrared spectroscopy and distinguished from artifacts or quartz pebbles. Formation of calculi can be prevented by increasing diuresis as well as switching to a different drug and reducing the dosage.

Talcose pulmonar associada ao uso endovenoso de medicamentos orais: relato de caso / Pulmonary talcosis associated with intravenous use of oral medications: a case report

Neste trabalho são apresentados os achados observados na tomografia computadorizada de alta resolução de um paciente com talcose pulmonar, com a doença adquirida pelo uso de drogas orais injetadas por via venosa. O principal aspecto observado na tomografia computadorizada de alta resolução foi o de nódulos centrolobulares, associados a massas conglomeradas. Havia também enfisema e áreas de atenuação em vidro fosco. Estes achados são bastante sugestivos de talcose pulmonar

We report the findings of the high-resolution computed tomography of the chest of a patient with pulmonary talcosis related to intravenous injection of diluted oral medicine. The most important high-resolution computed tomography findings were small centrilobular nodules associated with conglomerated masses. Areas of emphysema and ground glass attenuation were also seen. These high-resolution computed tomography findings are highly suggestive of pulmonary talcosis.

Kinetics of in vivo degradation of sepiolite-collagen complexes: effect of glutaraldehyde treatment.

A kinetic study of the in vivo degradation of sepiolite-collagen complexes after subcutaneous implantation in rats was performed. A foreign-body reaction was the characteristic host tissue response against the implants. The resorption of the implanted materials was analyzed by measuring both the weight and the collagen persistences. This last was measured by using (14C)acetylated collagen, which was revealed to be not modified upon radioactive labeling, in terms of its ability to form a complex with sepiolite. The persistence of the implants is controllable by treatment of the collagen component with glutaraldehyde. Thus, for 1% glutaraldehyde-treated collagen complexes, 100% of persistence was observed after several months of implantation, this value decreasing to a few days for nontreated collagen samples. The collagen-sepiolite complex showed a low immunological response, almost null for 1% glutaraldehyde-treated collagen complexes, which was analyzed by measuring anti-collagen antibodies levels. Based on the performed studies, sepiolite-collagen complexes can be considered a resorbable material.

In vitro biological effects of clay minerals advised as substitutes for asbestos.

We studied one sample of commercial sepiolite and two samples of commercial vermiculite--clay minerals proposed as replacements for asbestos--and tested in vitro their abilities to activate complement, to lyse erythrocytes, and to elicit the production of reactive oxygen species (ROS) with human polymorphonuclear leukocytes (PMN) or bovine alveolar macrophages (AM); their behavior was compared with that of asbestos fibers obtained from the Union International Contra Cancer (UICC) as reference standards, as well as with kaolinite and illite, main members of the clay mineral family. Since in short-term in vitro tests the biological activity of mineral particles seems especially related to the active sites on their surface, we first measured the specific surface area of each mineral. Sepiolite was unreactive in two of the three tests we used (complement activation and ROS production) and able to lyse a minimal percentage of red blood cells. Vermiculite was shown to be incapable of activating complement, to have a moderate hemolytic activity and a high ability to elicite ROS production, although lower than that of chrysotile. Sepiolite, therefore, might be of more interest than vermiculite, given the low level of biological effects detected during the tests used to compare both clay minerals with asbestos fibres. The ROS production does not seem to require phagocytosis. A high ROS production was observed with kaolinite: this result casts doubt on the ability of pathogenic mineral dusts in vitro to induce a greater release of ROS than nonpathogenic mineral dusts.

Implantation of sepiolite-collagen complexes in surgically created rat calvaria defects.

The response of osseous tissue to the implantation of sepiolite-collagen complexes has been studied. Sepiolite, sepiolite-collagen complex and 0.5% glutaraldehyde-treated sepiolite-collagen complex were implanted in created circular defects in rat calvaria. The tissue reactions were analysed using light, transmission and scanning electron microscopies. The patterns of bone growth were radiographically analysed and the bone activity was indirectly quantified by using a point-count method. The reaction against the three implanted materials is characteristic of a foreign body reaction with abundant macrophages and giant cells. Implanted products have been detected in macrophages, which suggest the involvement of phagocytosis in the resorptive process. Bone grew at the implantation sites originating excrescences or sometimes a thin bridge at the defect margins. The studied materials, after implantation in contact with bone tissue, did not produce any toxic effect or necrosis, allowing bone activity.

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)