Calcium Carbonate Suppresses Haem Toxicity Markers without Calcium Phosphate Side Effect on Colon Carcinogenesis

Red meat intake is associated with increased risk of colorectal cancer. We have previously shown that haemin, haemoglobin and red meat promote carcinogen-induced preneoplastic lesions, aberrant crypt foci, in the colon of rats. We have also shown that dietary calcium phosphate inhibits haemin-induced promotion, and normalizes faecal lipoperoxides and cytotoxicity. Unexpectedly, high-calcium phosphate control diet-fed rats had more preneoplastic lesions in the colon than low-calcium control diet-fed rats. The present study was designed to find a calcium supplementation with no adverse effect, by testing several doses and types of calcium salts. One in vitro study and two short-term studies in rats identified calcium carbonate as the most effective calcium salt to bind haem in vitro and to decrease faecal biomarkers previously associated with increased carcinogenesis: faecal water cytotoxicity, thiobarbituric acid reactive substances. A long term carcinogenesis study in dimethylhydrazine-injected rats demonstrated that a diet containing 100 µmol/g calcium carbonate did not promote aberrant crypt foci, in contrast with previously tested calcium phosphate diet. The results suggest that calcium carbonate, and not calcium phosphate, should be used to reduce haem-associated colorectal cancer risk in meat-eaters. They support the concept that the nature of the associated anion to a protective metal ion is important for chemoprevention

Gut microbiota facilitates dietary heme-induced epithelial hyperproliferation by opening the mucus barrier in colon

Colorectal cancer risk is associated with diets high in red meat. Heme, the pigment of red meat, induces cytotoxicity of colonic contents and elicits epithelial damage and compensatory hyperproliferation, leading to hyperplasia. Here we explore the possible causal role of the gut microbiota in heme-induced hyperproliferation. To this end, mice were fed a purified control or heme diet (0.5 μmol/g heme) with or without broad-spectrum antibiotics for 14 d. Heme-induced hyperproliferation was shown to depend on the presence of the gut microbiota, because hyperproliferation was completely eliminated by antibiotics, although heme-induced luminal cytotoxicity was sustained in these mice. Colon mucosa transcriptomics revealed that antibiotics block heme-induced differential expression of oncogenes, tumor suppressors, and cell turnover genes, implying that antibiotic treatment prevented the heme-dependent cytotoxic micelles to reach the epithelium. Our results indicate that this occurs because antibiotics reinforce the mucus barrier by eliminating sulfide-producing bacteria and mucin-degrading bacteria (e.g., Akkermansia). Sulfide potently reduces disulfide bonds and can drive mucin denaturation and microbial access to the mucus layer. This reduction results in formation of trisulfides that can be detected in vitro and in vivo. Therefore, trisulfides can serve as a novel marker of colonic mucolysis and thus as a proxy for mucus barrier reduction. In feces, antibiotics drastically decreased trisulfides but increased mucin polymers that can be lysed by sulfide. We conclude that the gut microbiota is required for heme-induced epithelial hyperproliferation and hyperplasia because of the capacity to reduce mucus barrier function

Transformation einer Vorlesung durch E-Learning-Elemente

Die Veranstaltungsform Vorlesung ist vor allem in geistes- und sozialwissenschaftlichen Studienrichtungen umstritten: mangelnde Aktivierung der Studierenden, kaum Dialog und Diskurs, wenig Möglichkeiten zum Feedback. In diesem Beitrag soll an einem Beispiel aus der Lehrpraxis des Studienfachs Pädagogik an der TU Darmstadt gezeigt werden, dass und wie es möglich ist, eine Vorlesung durch Einsatz von E-Learning-Elementen so zu transformieren, dass das aktive und diskursive Arbeiten mit den Vorlesungsinhalten erfolgreich angeregt wird

Heme iron from meat and risk of colorectal cancer: a meta-analysis and a review of the mechanisms involved

Red meat and processed meat intake is associated with a risk of colorectal cancer, a major cause of death in affluent countries. Epidemiological and experimental evidence supports the hypothesis that heme iron present in meat promotes colorectal cancer. This meta-analysis of prospective cohort studies of colon cancer reporting heme intake included 566,607 individuals and 4,734 cases of colon cancer. The summary relative risk of colon cancer was 1.18 [95%C.I.: 1.06-1.32] for subjects in the highest category of heme iron intake compared with those in the lowest category. Epidemiological data thus show a suggestive association between dietary heme and risk of colon cancer. The analysis of experimental studies in rats with chemically-induced colon cancer showed that dietary hemoglobin and red meat consistently promote aberrant crypt foci, a putative pre-cancer lesion. The mechanism is not known, but heme iron has a catalytic effect on (i) the endogenous formation of carcinogenic N-nitroso compounds and (ii) the formation of cytotoxic and genotoxic aldehydes by lipoperoxidation. A review of evidence supporting these hypotheses suggests that both pathways are involved in heme iron toxicit

Газоаналитические средства системы контроля утечек хлора на основе электрохимических сенсоров

Созданы и внедряются газоаналитические средства контроля и сигнализации утечек хлора на основе электрохимических сенсоров с улучшенными характеристиками

Meat processing and colon carcinogenesis: Cooked, nitrite-treated and oxidized high-heme cured meat promotes mucin depleted foci in rats

Processed meat intake is associated with colorectal cancer risk, but no experimental study supports the epidemiologic evidence. To study the effect of meat processing on carcinogenesis promotion, we first did a 14-day study with 16 models of cured meat. Studied factors, in a 2 × 2 × 2 × 2 design, were muscle color (a proxy for heme level), processing temperature, added nitrite, and packaging. Fischer 344 rats were fed these 16 diets, and we evaluated fecal and urinary fat oxidation and cytotoxicity, three biomarkers of heme-induced carcinogenesis promotion. A principal component analysis allowed for selection of four cured meats for inclusion into a promotion study. These selected diets were given for 100 days to rats pretreated with 1,2-dimethylhydrazine. Colons were scored for preneoplastic lesions: aberrant crypt foci (ACF) and mucin-depleted foci (MDF). Cured meat diets significantly increased the number of ACF/colon compared with a no-meat control diet (P = 0.002). Only the cooked nitrite-treated and oxidized high heme meat significantly increased the fecal level of apparent total N-nitroso compounds (ATNC) and the number of MDF per colon compared with the no-meat control diet (P < 0.05). This nitrite-treated and oxidized cured meat specifically increased the MDF number compared with similar non nitrite-treated meat (P = 0.03) and with similar non oxidized meat (P = 0.004). Thus, a model cured meat, similar to ham stored aerobically, increased the number of preneoplastic lesions, which suggests colon carcinogenesis promotion. Nitrite treatment and oxidation increased this promoting effect, which was linked with increased fecal ATNC level. This study could lead to process modifications to make non promoting processed meat

Freeze-Dried Ham Promotes Azoxymethane-Induced Mucin-Depleted Foci and Aberrant Crypt Foci in Rat Colon

Processed and red meat consumption is associated with the risk of colorectal cancer. Meta-analyses have suggested that the risk associated with processed meat is higher. Most processed meats are cured and cooked, which leads to formation of free nitrosyl heme. We speculated that free nitrosyl heme is more toxic than native myoglobin. The promoting effect of a freeze-dried, cooked, cured ham diet was looked for in a 100-day study. Colon carcinogenesis endpoints were aberrant crypt foci and mucin depleted foci (MDF). A second study (14 days) was designed 1) to compare the effect of ham, hemoglobin, and hemin; and 2) to test the effect of sodium chloride, nitrite, and phosphate in diet on early biomarkers associated with heme-induced promotion. In the 100-day study, control and ham-fed rats had 3.5 and 8.5 MDF/colon, respectively (P < 0.0001). Promotion was associated with cytotoxicity and lipid peroxidation. In the short-term study, cytotoxicity and lipid peroxidation of fecal water, and the urinary marker of lipid peroxidation, increased dramatically in ham- and hemin-fed rat. In contrast, the hemoglobin diet, sodium chloride, nitrite, phosphate diet had no effect. Freeze-dried cooked ham can promote colon carcinogenesis in a rodent model. Hemin, but not hemoglobin, mimicked ham effect on early biochemical markers associated with carcinogenesis

Editorial: Medien in der Erziehungswissenschaft II

Im Juli 2004 fand in Darmstadt die zweite MEWISS-Tagung («Medien in der Erziehungswissenschaft») statt, organisiert vom Arbeitsbereich «Bildung und Technik» des Instituts für Allgemeine Pädagogik und Berufspädagogik der TU Darmstadt in Zusammenarbeit mit der Kommission Medienpädagogik der Deutschen Gesellschaft für Erziehungswissenschaft. Fortgesetzt wurde damit der 2003 am Duisburg Learning Lab der Universität Duisburg-Essen begonnene Erfahrungs- und Gedankenaustausch zum Einsatz computer- und netzwerkgestützter Medien in der erziehungswissenschaftlichen Hochschullehre. Damit wurde das Ziel verfolgt, die Diskussion in der erziehungswissenschaftlichen Community über Medienfragen im deutschsprachigen Raum anzuregen, den Austausch über entsprechende Aktivitäten zu fördern, zu einer Verbreitung verfügbarer Lösungen beizutragen, Anknüpfungspunkte für die gemeinsame Fortführung entsprechender Aktivitäten zu finden und vorliegende Kompetenzen zu vernetzen. Dem Tagungsziel entsprechend stellten die Autorinnen und Autoren der Beiträge sich insbesondere der Frage, worin der pädagogische Sinn des Einsatzes Neuer Medien in der Hochschullehre liegt und wie die zur Verfügung stehenden medialen Formen und Mittel für eine pädagogisch verantwortete Praxis zur Wirkung gebracht werden können. C. Swertz führt in das Konzept einer «Web-Didaktik» ein, indem er seinen Beitrag selbst webdidaktisch organisiert. W. Sesink und Mitarbeiter zeigen an einem Beispiel aus dem Studienfach Pädagogik an der TU Darmstadt, dass und wie es möglich ist, eine Vorlesung durch Einsatz eines «interaktiven Skripts» so zu transformieren, dass das aktive und diskursive Arbeiten mit den Vorlesungsinhalten erfolgreich angeregt wird. Entlastung von «überflüssiger Präsenzlehre», um Kapazitäten freizusetzen für aktivierende Lehrformen, ist ein an der TU Kaiserslautern im Lehrbereich Berufs- und Wirtschaftspädagogik verfolgter Ansatz, von dem M. Lermen berichtet. Eine «Lern-, Studier- und Forschungswerkstatt» für die Entwicklung eigener Projekte im Bereich innovativen Medieneinsatzes im Unterricht durch Studierende der Medieninformatik und der Lehrämter stellt die Arbeitsgruppe Hendrik Bunke, Sandra Ostermann, Elin-Birgit Berndt von der Universität Bremen vor. Friederike Siller und Stefan Aufenanger berichten von der Entwicklung einer «Lernanwendung» zum «fallbasierten Erwerb medienpädagogischer Kompetenz» in Lehramtsstudiengängen an der Universität Hamburg. Auch mit dieser Ausgabe verbindet sich die Hoffnung, weitere Impulse und Anregungen zum Medieneinsatz in der erziehungswissenschaftlichen Lehre geben zu können

Calcium Inhibits Promotion by Hot Dog of 1,2-Dimethylhydrazine-Induced Mucin-Depleted Foci in Rat Colon

Epidemiology suggests that processed meat is associated with colorectal cancer risk, but few experimental studies support this association. We have shown that a model of cured meat made in a pilot workshop promotes preneoplastic lesions, mucin-depleted foci (MDF) in the colon of rats. This study had two aims: to check if real store-bought processed meats also promote MDF, and to test if calcium carbonate, which suppresses heme-induced promotion, can suppress promotion by processed meat. A 14-day study was done to test the effect of nine purchased cured meats on fecal and urinary biomarkers associated with heme-induced carcinogenesis promotion. Fecal water from rats given hot dog or fermented raw dry sausage was particularly cytotoxic. These two cured meats were thus given to rats pretreated with 1,2-dimethylhydrazine, to evaluate their effect on colorectal carcinogenesis. After a 100-d feeding period, fecal apparent total N-nitroso compounds (ATNC) were assayed and colons were scored for MDF. Hot dog diet increased fecal ATNC and the number of MDF per colon compared with the no-meat control diet (3.0±1.7 vs. 1.2±1.4, P<0.05). In a third study, addition of calcium carbonate (150 µmol/g) to the hot dog diet decreased the number of MDF/colon and fecal ATNC compared with the hot dog diet without calcium carbonate (1.2 ± 1.1 vs. 2.3 ± 1.4, respectively, P<0.05). This is the first experimental evidence that a widely consumed processed meat promotes colon carcinogenesis in rats. It also shows that dietary prevention of this detrimental effect is possible

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