A pilot randomised controlled trial to reduce colorectal cancer risk markers associated with B-vitamin deficiency, insulin resistance and colonic inflammation

Colorectal cancer risk is associated with biochemical markers for B-vitamin deficiency, insulin resistance and colonic inflammation, suggesting that these three conditions are each involved in colon carcinogenesis. We expected that dietary supplements of folic acid, n-3 fatty acids and calcium would reduce the markers and thus possibly cancer risk. We therefore randomised 98 participants, with previous colonic polyps or intramucosal carcinomas, to a combined treatment of supplementary folic acid, fish oil and calcium carbonate, or placebos for 28 days. Blood and faecal samples were obtained prior to and at the conclusion of the intervention and analysed for plasma folate, homocysteine, insulin, free fatty acids, triglycerides and faecal calprotectin. In addition, plasma vitamin B12, thiamin, glucose and C-reactive protein were assessed. Our supplemental strategy modestly affected some of the biomarkers associated with folate metabolism and insulin resistance, but had no effect on those associated with colonic inflammation. This pilot study demonstrates the feasibility and practicality of clinical trials aimed at reducing diet-related biochemical risk markers for colon cancer. We suggest that long-term intervention studies with tumour-related end points should be undertaken when the intervention agents used are found effective in short-term biochemical risk marker trials

Shaping Skeletal Growth by Modular Regulatory Elements in the Bmp5 Gene

Cartilage and bone are formed into a remarkable range of shapes and sizes that underlie many anatomical adaptations to different lifestyles in vertebrates. Although the morphological blueprints for individual cartilage and bony structures must somehow be encoded in the genome, we currently know little about the detailed genomic mechanisms that direct precise growth patterns for particular bones. We have carried out large-scale enhancer surveys to identify the regulatory architecture controlling developmental expression of the mouse Bmp5 gene, which encodes a secreted signaling molecule required for normal morphology of specific skeletal features. Although Bmp5 is expressed in many skeletal precursors, different enhancers control expression in individual bones. Remarkably, we show here that different enhancers also exist for highly restricted spatial subdomains along the surface of individual skeletal structures, including ribs and nasal cartilages. Transgenic, null, and regulatory mutations confirm that these anatomy-specific sequences are sufficient to trigger local changes in skeletal morphology and are required for establishing normal growth rates on separate bone surfaces. Our findings suggest that individual bones are composite structures whose detailed growth patterns are built from many smaller lineage and gene expression domains. Individual enhancers in BMP genes provide a genomic mechanism for controlling precise growth domains in particular cartilages and bones, making it possible to separately regulate skeletal anatomy at highly specific locations in the body

Common Genetic Denominators for Ca++-Based Skeleton in Metazoa: Role of Osteoclast-Stimulating Factor and of Carbonic Anhydrase in a Calcareous Sponge

Calcium-based matrices serve predominantly as inorganic, hard skeletal systems in Metazoa from calcareous sponges [phylum Porifera; class Calcarea] to proto- and deuterostomian multicellular animals. The calcareous sponges form their skeletal elements, the spicules, from amorphous calcium carbonate (ACC). Treatment of spicules from Sycon raphanus with sodium hypochlorite (NaOCl) results in the disintegration of the ACC in those skeletal elements. Until now a distinct protein/enzyme involved in ACC metabolism could not been identified in those animals. We applied the technique of phage display combinatorial libraries to identify oligopeptides that bind to NaOCl-treated spicules: those oligopeptides allowed us to detect proteins that bind to those spicules. Two molecules have been identified, the (putative) enzyme carbonic anhydrase and the (putative) osteoclast-stimulating factor (OSTF), that are involved in the catabolism of ACC. The complete cDNAs were isolated and the recombinant proteins were prepared to raise antibodies. In turn, immunofluorescence staining of tissue slices and qPCR analyses have been performed. The data show that sponges, cultivated under standard condition (10 mM CaCl2) show low levels of transcripts/proteins for carbonic anhydrase or OSTF, compared to those animals that had been cultivated under Ca2+-depletion condition (1 mM CaCl2). Our data identify with the carbonic anhydrase and the OSTF the first two molecules which remain conserved in cells, potentially involved in Ca-based skeletal dissolution, from sponges (sclerocytes) to human (osteoclast)

Postmenopausal vaginal atrophy: evaluation of treatment with local estrogen therapy

Minkin MJ, Maamari R, Reiter S. Int J Womens Health. 2014;6:281–288. On page 281, the year of publication was incorrectly listed as 2013, it should have been 2014. The year for the copyright notice was also listed as 2013 in error, the correct notice is © 2014 Minkin et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php.Read the original articl