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Evaluation of the medicinal use of clay minerals as antibacterial agents

aVivoPur Note: Blod empahsis added is ours. Read the full text at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2904249/

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Funding was made possible by the NIH-National Center for Complementary and Alternative Medicine.

"Traditionally, clay minerals are mixed with water for various periods of time (days to years) to form clay gels or pastes that can be applied externally for cosmetic or skin protective purposes (Carretero, 2002; Carretaro et al., 2007; Gomes et al., 2007). The high adsorption and absorption capacities, cation exchange capacity, as well as the extremely fine particle size of certain clays, e.g. smectites (expandable clay minerals) and kaolin group minerals are important reasons why these minerals are used to remove oils, secretions, toxins, and contaminants from the skin. By adsorbing and absorbing moisture and impurities from the skin, the clays also serve to cleanse and refresh the skin surface and to aid in the healing of topical blemishes, the major selling point for many cosmetics. Although consumers generally consider clays to be safe when applied topically, it is important to recognize that cosmetic firms must substantiate the safety of their products and that the U.S. Food and Drug Agency does not subject these products to pre-market approval."

"The ingestion of dried clay minerals or a clay suspension is commonly used as a source of dietary elements, as a detoxifying agent, and as an allopathic treatment of gastrointestinal illnesses and acute and chronic diarrhea (Carretero, 2002). For example in Ghana, the iron, copper, calcium, zinc, and manganese consumed in clays were in the range of 2 to 15 percent of recommended dietary allowances (Hunter, 1973) and it was concluded that moderate ingestion of clays lacking high cation-exchange capacities could serve as a nutritional supplement for these essential elements. In the acidic environment of the stomach, the clay minerals could bind to positively charged toxins and serve as detoxifying agents to reduce bioavailability interfering with gastrointestinal absorption of the toxin (Hladik and Gueguen, 1974; Johns and Duquette, 1991; Mahaney et al., 1996; Phillips, 1999; Phillips et al., 1995). Over-the-counter pharmaceuticals that originally contained kaolinite, attapulgite, or clay-like substances (i.e. Kaopectate®) represent classic examples of the use of clay minerals by human populations to treat diarrhea and intestinal illnesses (Vermeer and Ferrell, 1985) and soothe gastrointestinal ailments."

"Bentonite deposits are found worldwide wherever volcanic eruptions have taken place and preservation of the ash has exceeded erosion. Ten billion tons of bentonite are mined worldwide each year with about 35% produced in the western United States (primarily Wyoming). The second largest producer of bentonite is Greece (Grim and Güven, 1978), however, significant reserves are also found in many countries; Italy (Sardinia), India, China, and Australia to name a few. Many of the clays used in pelotherapy come from these deposits and localities (Cara et al., 2000; Veniale et al., 2007)."

"It is well known that metallic ions, such as silver, copper, and zinc, have strong inhibitory and bactericidal effects on a broad spectrum of bacteria (Berger et al., 1976; Domek et al., 1984; Gordon et al., 1994). Various forms of silver ions have been used to treat burn wound infections, osteomyelitis, urinary tract infections, and central venous catheter infections (Becker and Spadaro, 1978; Davenport and Keeley, 2005; Fox, 1968; Fox and Modak, 1974; Jansen et al., 1994; Liedberg and Lundeberg, 1990). In low concentrations (4 µg/ml), silver ions produced inhibitory and bactericidal effects with no obvious toxic effect on human blood cells (Berger et al., 1976). Although required by most living organisms at low concentrations, elevated levels of copper can inhibit the growth of some microorganisms and exhibit bactericidal activity (Domek et al., 1984; Gordon et al., 1994). The use of copper-coated products or copper alloys has been proposed for surfaces exposed to human contact to reduce the transmission of infectious microbial agents. Other metallic oxides, including zinc oxide, magnesium oxide, and calcium oxide, have antibacterial activity with demonstrated effectiveness against E. coli and S. aureus (Sawai, 2003). The nanometer particle size of these oxides, as well as titanium and silicon dioxide (Yamamoto et al., 2000; Yamamoto, 2001; Adams et al., 2006), have proven to be important for antibacterial activity. Zinc oxide has been used in a variety of dental composites to treat or prevent dental caries and as an endodontic sealer (Turkheim, 1955; Moorer and Genet, 1982; Siqueira and Goncalves, 1996). Nonetheless, the antibacterial mechanism has not been identified."

"The treatment of Buruli ulcer by Line Brunet de Courssou employed two clay samples provided by different suppliers of ‘French green clay’ (Brunet de Courrsou, 2002). These clays are thought to be altered volcanic ash deposits from Central France. The dry clay is mixed with water and applied as a paste directly to the ulcerated lesions and extended healthy skin of infected patients. The course of treatment is to remove and renew the clay packs at least once a day. Within days of initiating treatment with clay poultices, the therapeutic properties of the clay minerals were demonstrated, with the initiation of rapid, non-surgical debridement of the destroyed tissue. Extended treatment with the clay poultices resulted in continued debridement of the ulcer, regeneration of healthy tissue, and wound healing. After several months of daily clay applications, the Buruli ulcer wounds healed with soft, supple scarring, allowing return of normal motor function (Brunet de Courrsou, 2002; Williams et al., 2004). These observations are highly relevant since antibiotic treatment is only effective for small early lesions (nodules and plaques Chauty et al., 2007; van der Werf et al., 1999)."

"The extensive use of antibiotics has led to an increase in antibiotic resistance in many pathogenic and clinically-relevant bacteria, including Mycobacterium tuberculosis, S. aureus, Enterococcus faecalis, and Streptococcus pneumoniae (Menichetti, 2005; Shah, 2005; Sharma et al., 2005; Zetola et al., 2005). Therefore, modern and innovative research approaches are needed to identify and generate new antimicrobials for treating infections that are resistant to existing antibiotics or for which there is no known effective therapeutic agent. Using antibiotic-sensitive and antibiotic-resistant bacterial strains obtained from the American Type Culture Collection (ATCC) and a local diagnostic laboratory, we have been investigating the antibacterial properties of the two clays, CsAg02 and CsAr02, used to treat Buruli ulcer patients. The CsAr02 mineral promoted or had no effect on bacterial growth (Haydel et al., 2008). In contrast, CsAg02 exhibits an extraordinary ability to kill pathogenic E. coli, Salmonella enterica serovar Typhimurium, P. aeruginosa, ESBL E. coli (which is resistant to 11 antibiotics), and Mycobacterium marinum (a species genetically closely related to M. ulcerans that also causes a cutaneous infection) as well as inhibit the growth of pathogenic S. aureus, penicillin-resistant S. aureus (PRSA), methicillin-resistant S. aureus (MRSA; and also resistant to 10 antibiotics)"

"Evaluating the antibacterial effect of the coarse (1.0 –2.0 µm), medium (0.2–1.0 µm) and fine (E. coli allowed us to eliminate detrital minerals (quartz, carbonate, feldspar) from the clays as potential participants in the antibacterial effect. We found that only the finest fraction (E. coli, while the coarser fractions had no effect on bacterial growth (Haydel et al., 2008; Williams et al., 2007). Furthermore, X-ray diffraction analyses of the finest clay fraction confirmed that the coarser detrital mineral phases had been largely eliminated. Smectite dominated theFigure 5 shows two different morphologies of crystals in the

"During the past 25 years, approximately 70% of newly discovered drugs introduced in the U.S. have been derived from natural products (Newman and Cragg, 2007). Topical treatments by clay minerals have considerable advantages over surgery or generalized antibiotic therapy due to the practical simplicity of the application in the area specifically affected, rather than ingestion of drugs with potential side effects. The broad-reaching impacts of antimicrobial mineral research with applications in topical antimicrobial dressings, wound care management, personal care, and animal care markets are obvious. The discovery that natural minerals harbor antibacterial properties should provide impetus for exploring terrestrial sources for novel therapeutic compounds. Often natural products, such as clays, which are heterogeneous in chemical composition and physical character, are rejected as therapeutic agents by regulatory agencies. Nevertheless, in comparison to organic antimicrobial agents, inorganic minerals are likely to be considerably more stable and heat resistant, making the development and use of inorganic antimicrobial agents particularly advantageous."

"Clearly understanding the antibacterial mechanism of natural clay is complex, and it is possible that no single mechanism or set of reaction pathways is uniquely responsible for the observed bactericidal activity. Our future work will focus on identifying general themes displayed by the interaction presented herein between problematical human pathogens (e.g., MRSA) and the natural clay minerals that have now been shown to kill such bacteria (Williams et al., 2008). To progress towards understanding how antibacterial clays can be effective for treating bacterial infections will require integrated mineralogical, chemical, and microbial studies."