This review updates earlier work addressing the epidemiology and toxicity of wollastonite. Earlier chronic animal bioassay and human mortality data were inadequate (IARC term) or negative and no new studies of these types have been published. Wollastonite has been determined to have low biopersistence in both in vivo and in vitro studies, which probably accounts for its relative lack of toxicity. Earlier morbidity studies of mining/mineral processing facilities in Finland and New York State indicated that exposure to wollastonite might result in pleural plaques (Finland) or decrements in certain measures of lung function (New York). More recent analysis of data from an ongoing health surveillance program at one facility (New York) indicates that there are no pleural plaques or interstitial lung disease or decrements in lung function among never smokers or former smokers occupationally exposed to wollastonite. This result probably reflects continued reduction in exposures as part of an ongoing product stewardship program at this facility and suggests that wollastonite has relatively low toxicity as currently managed.
In July 2002, NYCO Minerals, Inc., discovered a heretofore unknown contaminant in its wollastonite ore. The contaminant was first believed to be tremolite asbestos. Immediate efforts were made to eliminate this material. Additional studies were initiated to fully characterize the contaminant and its distribution in the ore body. Subsequent study by NYCO and their consultants led to the identification of the contaminant as a transition material (TM) intermediate between tremolite and talc. In vitro dissolution rate measurements indicated that the TM dissolved much more rapidly than tremolite asbestos. This article provides background information on wollastonite mineralogy and NYCO's product stewardship program (PSP). At present, NYCO Minerals uses selective mining to control the trace levels of TM in the ore and finished product verified by periodic monitoring of workplace air and finished product.NYCO Minerals, Inc., developed a product stewardship program (PSP) to identify, manage, and control occupational risks associated with the production and use of wollastonite. This article presents a short case history of the discovery, identification, and control of what was initially considered to be a potentially
MicroRNA-29 is an anti-fibrotic miRNA whose expression is downregulated in multiple fibrotic indications including in cutaneous scars and keloids. Its target genes include numerous collagens and other extracellular matrix molecules, suggesting that restoration of miR-29 expression in a skin wound or at the site of an excised scar could have a therapeutic benefit by reducing scarring and/or preventing scar regrowth. An oligonucleotide mimic of miR-29b (MRG-201) was studied in vivo in mouse, rats and rabbits as well as in vitro in human skin fibroblasts to identify a set of conserved pharmacodynamic biomarkers in the skin. MRG-201 was then evaluated in a Phase 1 double-blinded within-patient randomized clinical trial in 53 normal healthy volunteers (NCT02603224). Expression of miR-29b and its pharmacodynamic biomarkers was assessed in untreated skin incisions and following single or multiple administrations of MRG-201 at the site of a sutured skin incision. miR-29b expression was significantly decreased and direct miR-29 target genes were significantly upregulated with incision alone. Intradermal administration of MRG-201 resulted in a high local concentration of miR-29b with low systemic exposure and good safety/tolerability at all doses tested. Pharmacodynamic activity was seen after MRG-201 treatment: single and multiple doses of MRG-201 reduced collagen mRNA expression as compared to a placebo injected incision in the same subject. Additionally, multiple administrations of MRG-201 reduced fibroplasia as assessed by histopathology (p < 0.01). These findings support further investigation of MRG-201 as a novel therapeutic to inhibit scar formation or prevent hypertrophic scar or keloid recurrence following excision.
Cutaneous neurofibromas (cNF) are complex tumors of the skin in individuals with neurofibromatosis type 1 (NF1), a syndrome affecting approximately 1:3,000 persons worldwide. There are no drug therapies for these tumors, and current treatment is limited to various procedure-based approaches. A critical need in conducting meaningful translational studies of these tumors is to have high quality tissue samples representing the diversity of human cutaneous tumors. Multiple challenges exist, including a lack of standardized sample collection or analysis protocols, non-universal terminology for cNF, different methods for the removal of tumors, and varied patient privacy requirements across countries. Investigators and field experts engaged in an initiative towards targeting cNF have identified criteria for prospective tissue collection, including the use of uniform terminology, sample collection methods, and clinical datasets that are compliant with international requirements for future cNF translational studies. These recommendations now provide clinical and translational scientists with a common set of guidelines to collect and study cNF biospecimens to enable more meaningful translational studies with increased clinical impact.
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