Effects of high-amylose maize starch and butyrylated high-amylose maize starch on azoxymethane-induced intestinal cancer in rats

Colorectal cancer (CRC) is a major cause of death worldwide. Studies suggest that dietary fibre offers protection perhaps by increasing colonic fermentative production of butyrate. This study examined the importance of butyrate by investigating the effects of resistant starch (RS) and butyrylated-RS on azoxymethane (AOM)-induced CRC in rats. Four groups (n = 30 per group) of Sprague–Dawley rats were fed AIN-93G-based diets containing a standard low-RS maize starch (LAMS), LAMS + 3% tributyrin (LAMST), 10% high-amylose maize starch (HAMS) and 10% butyrylated HAMS (HAMSB) for 4 weeks. Rats were injected once weekly for 2 weeks with 15 mg/kg AOM, maintained on diets for 25 weeks and then killed. Butyrate concentrations in large bowel digesta were higher in rats fed HAMSB than other groups (P < 0.001); levels were similar in HAMS, LAMS and LAMST groups. The proportion of rats developing tumours were lower in HAMS and HAMSB than LAMS (P < 0.05), and the number of tumours per rat were lower in HAMSB than LAMS (P < 0.05). Caecal digesta butyrate pools and concentrations were negatively correlated with tumour size (P < 0.05). Hepatic portal plasma butyrate concentrations were higher (P < 0.001) in the HAMSB compared with other groups and negatively correlated with tumour number per rat (P < 0.009) and total tumour size for each rat (P = 0.05). HAMSB results in higher luminal butyrate than RS alone or tributyrin. This is associated with reduced tumour incidence, number and size in this rat model of CRC supporting the important protective role of butyrate. Interventional strategies designed to maximize luminal butyrate may be of protective benefit in humans

Low Concentration of Sodium Butyrate from Ultrabraid+NaBu suture, Promotes Angiogenesis and Tissue Remodelling in Tendon-bones Injury

Sodium butyrate (NaBu), a form of short-chain fatty acid (SCFA), acts classically as a potent anti-angiogenic agent in tumour angiogenesis models, some authors demonstrated that low concentrations of NaBu may contribute to healing of tendon-bone injury in part at least through promotion of tissue remodelling. Here, we investigated the effects of low-range concentrations of NaBu using in vitro and in vivo assays using angiogenesis as the primary outcome measure and the mechanisms through which it acts. We demonstrated that NaBu, alone or perfused from the UltraBraid+NaBu suture was pro-angiogenic at very low-range doses promoting migration, tube formation and cell invasion in bovine aortic endothelial cells (BAECs). Furthermore, cell exposure to low NaBu concentrations increased expression of proteins involved in angiogenic cell signalling, including p-PKCβ1, p-FAK, p-ERK1/2, p-NFκβ, p-PLCγ1 and p-VEGFR2. In addition, inhibitors of both VEGFR2 and PKCβ1 blocked the angiogenic response. In in vivo assays, low concentrations of NaBu induced neovascularization in sponge implants in mice, evidenced by increased numbers of vessels and haemoglobin content in these implants. The findings in this study indicate that low concentrations of NaBu could be an important compound to stimulate angiogenesis at a site where vasculature is deficient and healing is compromised

Antimicrobial potential of probiotic or potentially probiotic lactic acid bacteria, the first results of the international European research project PROPATH of the PROEUHEALTH cluster

The EU-funded PROPATH project addresses the important health issue of prevention of gastrointestinal disorders through probiotics and prebiotics. Seven European laboratories are co-operating in this project, which aims to isolate and characterize the relevant antimicrobial agents to combat Gram-negative bacteria including Helicobacter pylori and Salmonella enterica serovar Typhimurium. In this paper, the first results on the screening for probiotic or potentially probiotic lactobacilli that exhibit antimicrobial activity towards these Gram-negative pathogenic bacteria are presented. Spot-on-lawn assays, well-diffusion assays and time-kill studies were performed among the lactic acid bacteria strains that were either collected from fermented foods and faeces (breast-fed babies, infants and animals) or isolated from commercial products to investigate whether any of the collected strains were inhibiting growth of or were killing certain indicator bacteria. Strains inhibiting the gastrointestinal pathogens mentioned above were found. Evidence has been obtained that compounds different from organic acids are produced

Modulation of angiogenesis by dithiolethione-modified NSAIDs and valproic acid

Background and purpose: Angiogenesis involves multiple signaling pathways that must be considered when developing agents to modulate pathological angiogenesis. Because both cyclooxygenase inhibitors and dithioles have demonstrated antiangiogenic properties, we investigated the activities of a new class of anti-inflammatory drugs containing dithiolethione moieties (S-NSAIDs) and S-valproate. Experimental approach: Anti-angiogenic activities of S-NSAIDS, S-valproate, and the respective parent compounds were assessed using umbilical vein endothelial cells, muscle and tumor tissue explant angiogenesis assays, and developmental angiogenesis in Fli: EGFP transgenic zebrafish embryos. Key results: Dithiolethione derivatives of diclofenac, valproate, and sulindac inhibited endothelial cell proliferation and induced Ser 78 phosphorylation of hsp27, a known molecular target of anti-angiogenic signaling. The parent drugs lacked this activity, but dithiolethiones were active at comparable concentrations. Although dithiolethiones can potentially release hydrogen sulphide, NaSH did not reproduce some activities of the S-NSAIDs, indicating that the dithioles regulate angiogenesis through mechanisms other than release of H2S. In contrast to the parent drugs, S-NSAIDs, S-valproate, NaSH, and dithiolethiones were potent inhibitors of angiogenic responses in muscle and HT29 tumor explants assessed by 3-dimensional collagen matrix assays. Dithiolethiones and valproic acid were also potent inhibitors of developmental angiogenesis in zebrafish embryos, but the S-NSAIDs, remarkably, lacked this activity. Conclusions and implication: S-NSAIDs and S-valproate have potent anti-angiogenic activities mediated by their dithiole moieties. The novel properties of S-NSAIDs and S-valproate to inhibit pathological versus developmental angiogenesis suggest that these agents may have a role in cancer treatment