The goal of this study was to determine if a multi-mineral natural product derived from red marine algae, could reduce colon polyp formation in mice on a high fat diet. C57BL/6 mice were maintained for up to 18 months either on a high-fat “Western-style” diet or on a low-fat diet (AIN 76A), with or without the multi-mineral-supplement. To summarize, colon polyps were detected in 22 of 70 mice (31%) on the high-fat diet, but in only 2 of 70 mice (3%) receiving the mineral-supplemented high-fat diet (p<0.0001). Colon polyps were detected in 16 of 70 mice (23%) in the low-fat group; not significantly different from high-fat group but significantly higher than the high-fat-supplemented group (p=0.0006). This was in spite of the fact that the calcium level in the low-fat diet was comparable to the level of calcium in the high-fat diet containing the multi-mineral-product. Supplementation of the low-fat diet reduced the incidence to 8 of 70 mice (11% incidence). Taken together, these findings demonstrate that a multi-mineral natural product can protect mice on a high-fat diet against adenomatous polyp formation in the colon. These data suggest that increased calcium alone is insufficient to explain the lower incidence of colon polyps.

C57BL/6 mice were maintained for up to 18-months on high-fat and low-fat diets with or without a multi-mineral-supplement derived from the skeletal remains of the red marine algae Lithothamnion calcareum. Numerous grossly observable liver masses were visible in animals on the “western-style” high-fat diet sacrificed at 12 and 18 months. The majority of the masses were in male mice (20 out of 100 males versus 3 out of 100 females; p=0.0002). There were more liver masses in animals on the high-fat diet than on the low-fat diet (15 out of 50 on high-fat versus 5 out of 50 on low-fat; p=0.0254). The multi-mineral supplement reduced the number of liver masses in mice on both diets (3 out of 25 male mice in the low-fat diet group without the supplement versus 1 out of 25 mice with supplement; 12 of 25 male mice in the high-fat diet group without the supplement versus 3 of 25 mice with supplement [p=0.0129]). Histological evaluation revealed a total of 17 neoplastic lesions (9 adenomas and 8 hepatocellular carcinomas), and 18 pre-neoplastic lesions. Out of 8 hepatocellular carcinomas, 7 were found in unsupplemented diet groups. Steatosis was widely observed in livers with and without grossly observable masses, but the multi-mineral supplement had no effect on the incidence of steatosis or its severity. Taken together, these findings suggest that a multi-mineral-rich natural product can protect mice against neoplastic and pre-neoplastic proliferative liver lesions that may develop in the face of steatosis.

MDI 301 is a picolinic acid-substituted ester of 9-cis retinoic acid. It has been shown in the past that MDI 301 increases epidermal thickness, decreases matrix metalloproteinase (MMP) activity, and increases procollagen synthesis in organ-cultured human skin. Unlike all-trans retinoic acid (RA), MDI 301 does not induce expression of proinflammatory cytokines or induce expression of leukocyte adhesion molecules in human skin. In the present study we examined topical MDI 301 treatment for ability to improve the structure and function of skin in three models of skin damage in rodents and for ability to improve abrasion wound healing in these models. MDI 301 was applied daily to the skin of rats treated with the potent corticosteroid, clobetasol propionate, to the skin of diabetic rats (8 weeks posttreatment with streptozotocin) and to the skin of aged (14-16-month-old) rats. In all three models, subsequently induced abrasion wounds healed more rapidly in the retinoid-treated animals than in vehicle-treated controls. Immediately after complete wound closure, tissue from the wound site (as well as from a control site) was put into organ culture and maintained for 3 days. At the end of the incubation period, culture fluids were assessed for soluble type I collagen and for MMPs-2 and -9. In all three models, the level of type I collagen was increased and MMP levels were decreased by MDI 301. In all three models, skin irritation during the retinoid-treatment phase was virtually nonexistent.Minor abrasions that occur in healthy skin are expected to heal without incident. Interventions are designed primarily to prevent infection and to provide support for the body's own regenerative mechanisms. In contrast, wounds in chronically damaged and atrophic skin often go on to form nonhealing ulcers with devastating consequences. Diabetes alone is a contributing factor in up to 70% of the > 55,000 amputations that occur annually. [1][2][3][4] Skin that has become atrophic as a consequence of the aging process also demonstrates impaired wound healing, 5-7 as does skin that has been damaged as a result of extended corticosteroid use. [8][9][10] The majority of wound-healing research is directed toward understanding the pathophysiology of impaired wound healing and identifying interventions that can mitigate the critical patho-physiological events.Several past studies have demonstrated the efficacy of all-trans retinoic acid (RA) and its parent compound all-trans retinol (ROL, vitamin A) in wound healing. Although most studies have focused on wounds in the skin, [11][12][13][14][15][16][17] retinoid efficacy has also been demonstrated in healing of wounds in other tissues (bone, cornea, respiratory tract, upper digestive system, and gut). 27 Likewise, skin irritation is also a complication with synthetic retinoidal agents currently on the market. 28 Irritation is a major cause of non-compliance among retinoid users. In addition, excessive irritation may counteract the beneficial effects of retinoid use or actually predispo...

The purpose of this study was to assess insoluble salts containing gadolinium (Gd3+) for effects on human dermal fibroblasts. Responses to insoluble Gd3+ salts were compared to responses seen with Gd3+ solubilized with organic chelators, as in the Gd3+-based contrast agents (GBCAs) used for magnetic resonance imaging. Insoluble particles of either Gd3+-phosphate or Gd3+-carbonate rapidly attached to the fibroblast cell surface and stimulated proliferation. Growth was observed at Gd3+ concentrations between 12.5 and 125 μM, with toxicity at higher concentrations. Such a narrow window did not characterize GBCA stimulation. Proliferation induced by insoluble Gd3+ salts was inhibited in the presence of antagonists of mitogen-activated protein kinase and phosphatidylinositol 3-kinase signaling pathways (similar to chelated Gd3+) but was not blocked by an antibody to the platelet-derived growth factor receptor (different from chelated-Gd3+). Finally, high concentrations of the insoluble Gd3+ salts failed to prevent fibroblast lysis under low-Ca2+ conditions while similar concentrations of chelated-Gd3+ were effective. In conclusion, while insoluble Gd3+ salts are capable of stimulating fibroblast proliferation, one should be cautious in assuming that GBCA dechelation must occur in vivo to produce the profibrotic changes seen in association with GBCA exposure in the subset of renal failure patients that develop nephrogenic systemic fibrosis.

Progressive bone mineral loss and increasing bone fragility are hallmarks of osteoporosis. A combination of minerals isolated from the red marine algae, Lithothamnion sp. was examined for ability to inhibit bone mineral loss in female mice maintained on either a standard rodent chow (control) diet or a high-fat western diet (HFWD) for 5-, 12- and 18-months. At each time-point, femora were subjected to μ-CT analysis and biomechanical testing. A subset of caudal vertebrae was also analyzed. Following this, individual elements were assessed in bones. Serum levels of the 5b isoform of tartrate-resistant acid phosphatase (TRAP) and procollagen type I propeptide (P1NP) were also measured. Trabecular bone loss occurred in both diets (evident as early as 5-months). Cortical bone increased through month-5 and then declined. Cortical bone loss was primarily in mice on the HFWD. Inclusion of the minerals in the diet reduced bone mineral loss in both diets and improved bone strength. Bone mineral density (BMD) was also enhanced by these minerals. Of several cationic minerals known to be important to bone health, only strontium was significantly increased in bone tissue from animals fed the mineral diets, but the increase was large (5–10 fold). Serum levels of TRAP were consistently higher in mice receiving the minerals but levels of P1NP were not. These data suggest that trace minerals derived from marine red algae may be used to prevent progressive bone mineral loss in conjunction with calcium. Mineral supplementation could find use as part of an osteoporosis - prevention strategy.