Analysis of particles from hamster lungs following pulmonary talc exposures: implications for pathogenicity.

BACKGROUND: Talc, a hydrous magnesium silicate, often used for genital hygiene purposes, is associated with ovarian carcinoma in case-control studies. Its potential to cause inflammation, injury, and functional changes in cells has been described. A complication of such studies is that talc preparations may be contaminated with other materials. A previous study by (Beck et al. Toxicol Appl Pharmacol 87:222-34, 1987) used a hamster model to study talc and granite dust exposure effects on various biochemical and cellular inflammatory markers. Our current study accessed key materials used in that 1987 study; we re-analyzed the original talc dust with contemporary scanning electron microscopy and energy dispersive x-ray analysis (SEM/EDX) for contaminants. We also examined the original bronchoalveolar lavage (BAL) cells with polarized light microscopy to quantify cell-associated birefringent particles to gain insight into the talc used. RESULTS: SEM/EDX analyses showed that asbestos fibers, quartz, and toxic metal particulates were below the limits of detection in the original talc powder. However, fibers with aspect ratios ≥3:1 accounted for 22% of instilled material, mostly as fibrous talc. Talc (based on Mg/Si atomic weight % ratio) was the most abundant chemical signature, and magnesium silicates with various other elements made up the remainder. BAL cell counts confirmed the presence of acute inflammation, which followed intratracheal instillation. Measurements of cell associated birefringent particles phagocytosis revealed significant differences among talc, granite, and control exposures with high initial uptake of talc compared to granite, but over the 14-day experiment, talc phagocytosis by lavaged cells was significantly less than that of granite. Phagocytosis of talc fibers by macrophages was observed, and birefringent particles were found in macrophages, neutrophils, and multinucleate giant cells in lavaged cells from talc-exposed animals. CONCLUSION: Our data support the contention that talc, even without asbestos and other known toxic contaminants, may elicit inflammation and contribute to lung disease. Our findings support the conclusions of (Beck et al. Toxicol Appl Pharmacol 87:222-34, 1987) study. By analyzing particulate exposures with polarized light microscopy and SEM/EDX, fibrous talc was identified and a distinctive pattern of impaired particulate ingestion was demonstrated.

Sepiolite as a New Nanocarrier for DNA Transfer into Mammalian Cells: Proof of Concept, Issues and Perspectives.

Sepiolite is a nanofibrous natural silicate that can be used as a nanocarrier for DNA transfer thanks to its strong interaction with DNA molecules and its ability to be naturally internalized into mammalian cells through both non-endocytic and endocytic pathways. Sepiolite, due to its ability to bind various biomolecules, could be a good candidate for use as a nanocarrier for the simultaneous vectorization of diverse biological molecules. In this paper, we review our recent work, issued from a starting collaboration with Prof. Ruiz-Hitzky, that includes diverse aspects on the characterization and main features of sepiolite/DNA nanohybrids, and we present an outlook for the further development of sepiolite for DNA transfer.

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.

Acute myocardial injury caused presumably by coronary spasm after magnesium fluoro-silicate ingestion.

A patient who developed magnesium fluoro-silicate poisoning is described. This condition was manifest by the findings of acute chest pain, dysphagia, diarrhea, metabolic acidosis, hypocalcemia and hypomagnesemia and was complicated by acute myocardial injury-a phenomenon not previously described. Coronary cineangiography showed normal coronary arteries. The physiopathologic mechanisms of this electrocardiographic finding are discussed.

Increased levels of surgical adhesions in TGFbeta1 heterozygous mice.

Adhesion formation and fibrosis represent a major complication of surgical intervention. Reducing the morbidity associated with adhesions requires an understanding of the mechanisms underlying their formation. Since increased levels of transforming growth factor-beta1 (TGFbeta1) have been associated with inflammation and adhesion production, we investigated the requirement of TGFbeta1 in peritoneal adhesion formation utilizing mice carrying a targeted disruption of the TGFbeta1 allele. Mice that were either wild-type (+/+), containing two normal alleles of TGFbeta1, or heterozygous (+/-) for the TGFbeta1 null allele received injections of magnesium silicate (talc), and the extent of abdominal adhesions was determined utilizing a standard grading score. Wild-type (+/+) animals had at least twofold more TGFbeta1 protein in peritoneal fluids at 2 h posttrauma compared to heterozygous (+/-) mice (727 vs. 243 pg TGFbeta1/mg protein by enzyme-linked immunosorbent assay (ELISA) in +/+ and +/- mice, respectively), and had significantly less scar and adhesion formation (p < .05) at 7 days posttrauma (1.8 +/- 0.8 vs. 3.4 +/- 1.4, graded from 0 to 5, in +/+ and +/- mice, respectively). These results demonstrate that haploid insufficiency in TGFbeta1 levels can lead to inappropriate matrix and adhesion production during inflammation, and together with previous studies suggest that any perturbation of normal TGFbeta1 levels can modulate the injury response that regulates the extent of adhesion formation.

Preparation and characteristics of antibacterial sepiolite containing povidone-iodine as a useful pharmaceutical product for patient care.

Povidone-iodine (PVP-I), an antibacterial medicine, was infiltrated in sepiolite (SPL). The available iodine content in this new pharmaceutical product, a sepiolite preparation containing povidone-iodine (PVP-I-SPL), was retained at 98.9 and 98.3% during storage at 40 degrees C for 3 and 6 months, respectively. The effective removal of various gasses, including ammonia, hydrogen sulfide, ethylmercaptan and acetaldehyde, was achieved by use of PVP-I-SPL. Especially, the concentration of ammonia gas was reduced more than half after 30 min of exposure, suggesting that PVP-I-SPL has excellent ability to adsorb ammonia gas. The satisfactory antibacterial effect of PVP-I-SPL was also obtained by testing its minimum bactericidal concentration (MBC). No irritation reactions to the rabbit auricle or ophthalmic mucosa or to human skin were observed by the skin irritation test. The PVP-I-SPL preparation has bactericidal activity and gas-adsorbing ability; therefore, this pharmaceutical product should be useful for the prevention of infections and deodorization in hospital rooms and houses, as well as in nursing homes for elderly people.

Investigations on health-related properties of two sepiolite samples.

Published i.p. injection studies have shown different biological behavior of different sepiolite samples. There was no evidence for carcinogenic potential of sepiolite from Vicalvaro, Spain, whereas a high tumor incidence was reported for sepiolite from Finland. The low biological activity of the sepiolite from Vicalvaro, compared to the Finnish sample, could be caused by low in vivo persistence or by the short length of the fibers, or both. In this study a further sepiolite sample, obtained as a commercial sample originating from China, was investigated. This sample contained a higher fraction of fibers longer than 5 microns, comparable to the Finnish sepiolite sample. The fraction of fibers with a length > 5 microns was 0.12 and 2.2% for the Vicalvaro and Chinese sepiolite, respectively. For the fiber fraction longer than 8 microns, the corresponding values were 0.0045 and 0.82%. The in vivo persistence of the sepiolite samples from China and Vicalvaro was analyzed after intratracheal instillation of 2 mg in female Wistar rats. Fiber retention in the lungs was analyzed by transmission electron microscopy at different sacrifice dates up to 12 months after application. For the Vicalvaro sepiolite, a splitting of fiber bundles was found during retention time in the lung. Therefore, no half-time of the fiber clearance could be calculated from the number of fibers. The decrease of the calculated retained fiber mass was faster for the Vicalvaro sepiolite (T1/2 = 89 days) compared to the Chinese sepiolite (T1/2 = 129 days). For 2 or 3 rats per group, at sacrifice date 12 months after i.p. injection, the lung was investigated by histopathology. The main difference between both treatment groups was a more pronounced fibrotic response in the Chinese sepiolite-treated rats compared to those treated with Vicalvaro sepiolite. It is concluded that both the higher fraction of long sepiolite fibers and the slower elimination rate of the fiber mass in the Chinese sample were important factors for the different biological reaction in comparison with Vicalvaro sepiolite.