The occurrence and the further spread of high-level glycopeptide-resistant, vanA-positive Enterococcus faecium strains outside of hospitals have been investigated. We could isolate such bacteria directly from thawing liquids of commercially produced frozen poultry (chickens, turkeys; no further data on previous feeding with avoparcin were available). In 5 of 13 samples of raw minced meat of pigs originating from 13 different butcher's shops, glycopeptide-resistant E. faecium (VanA type) could be detected after overnight broth cultivation of these samples. No glycopeptide-resistant enterococci could be isolated from meat samples of chickens that were fed without avoparcin. VanA type E. faecium strains were also identified in 12 fecal samples recovered from 100 nonhospitalized humans in the rural area of Saxony-Anhalt federal county. These results suggest a possible role of the food chain in the spread of glycopeptide-resistant E. faecium. Molecular typing (macrorestriction and multilocus enzyme analysis) reveal a wide dissemination of the vanA gene among strains of different ecological origins.

The fermented extract of wheat germ, trade name Avemar, is a complex mixture of biologically active molecules with potent anti-metastatic activities in various human malignancies. Here we report the effect of Avemar on Jurkat leukemia cell viability, proliferation, cell cycle distribution, apoptosis, and the activity of key glycolytic/pentose cycle enzymes that control carbon flow for nucleic acid synthesis. The cytotoxic IC 50 concentration of Avemar for Jurkat tumor cells is 0.2 mg/ml, and increasing doses of the crude powder inhibit Jurkat cell proliferation in a dose-dependent fashion. At concentrations higher than 0.2 mg/ml, Avemar inhibits cell growth by more than 50% (72 h of incubation), which is preceded by the appearance of a sub-G 1 peak on flow histograms at 48 h. Laser scanning cytometry of propidium iodideand annexin V-stained cells indicated that the growthinhibiting effect of Avemar was consistent with a strong induction of apoptosis. Inhibition by benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone of apoptosis but increased proteolysis of poly(ADP-ribose) indicate caspases mediate the cellular effects of Avemar. Activities of glucose-6-phosphate dehydrogenase and transketolase were inhibited in a dose-dependent fashion, which correlated with decreased 13 C incorporation and pentose cycle substrate flow into RNA ribose. This decrease in pentose cycle enzyme activities and carbon flow toward nucleic acid precursor synthesis provide the mechanistic understanding of the cell growth-controlling and apoptosis-inducing effects of fermented wheat germ. Avemar exhibits about a 50-fold higher IC 50 (10.02 mg/ml) for peripheral blood lymphocytes to induce a biological response, which provides the broad therapeutic window for this supplemental cancer treatment modality with no toxic effects.The preventive and therapeutic potential of two natural wheat products, wheat bran and fermented wheat germ (Avemar), in experimental carcinogenesis has recently been described (1, 2). Although no chemical constituents are yet isolated and tested experimentally, it is likely that benzoquinones and wheat germ agglutinin in wheat germ and fiber and lipids and phytic acid in wheat bran play a significant role in exerting anti-carcinogenic effects. In a recent report utilizing intracellular carbon flow studies with a 13 C-labeled isotope of glucose and biological mass spectrometry (GC/MS), 1 it was demonstrated that the crude powder of fermented wheat germ dosedependently inhibits nucleic acid ribose synthesis primarily through the nonoxidative steps of the pentose cycle while increasing direct glucose carbon oxidation and acetyl-CoA utilization toward fatty acid synthesis in pancreatic adenocarcinoma cells (3). These metabolic changes indicate that fermented wheat germ exerts its anti-proliferative action through altering metabolic enzyme activities, which primarily control glucose carbon flow toward nucleic acid synthesis.In vivo, Avemar has a marked inhibitory effect on metastasis formation in tumor-bearing animals (4), an...

Metabolomic characteristics in boar spermatozoa were studied using [1,2-13 C 2 ]glucose and mass isotopomer analysis. In boar spermatozoa, glycolysis was the main pathway of glucose utilization producing lactate/pyruvate, whereas no gluconeogenesis was seen. Slight glycogen synthesis through the direct pathway and some incorporation of pyruvate into the Krebs cycle also took place. Neither RNA ribose-5-phosphate nor fatty acid synthesis from glucose occurred despite the detection of pyruvate dehydrogenase activity. In contrast to the known metabolic activities in dog sperm, boar spermatozoa have low levels of energy production and biosynthetic activities suggesting two di¡erent metabolic pro¢les for the two di¡erent phenotypes.

Metabolomics has become a crucial phenotyping technique in a range of research fields including medicine, the life sciences, biotechnology and the environmental sciences. This necessitates the transfer of experimental information between research groups, as well as potentially to publishers and funders. After the initial efforts of the metabolomics standards initiative, minimum reporting standards were proposed which included the concepts for metabolomics databases. Built by the community, standards and infrastructure for metabolomics are still needed to allow storage, exchange, comparison and re-utilization of metabolomics data. The Framework Programme 7 EU Initiative ‘coordination of standards in metabolomics’ (COSMOS) is developing a robust data infrastructure and exchange standards for metabolomics data and metadata. This is to support workflows for a broad range of metabolomics applications within the European metabolomics community and the wider metabolomics and biomedical communities’ participation. Here we announce our concepts and efforts asking for re-engagement of the metabolomics community, academics and industry, journal publishers, software and hardware vendors, as well as those interested in standardisation worldwide (addressing missing metabolomics ontologies, complex-metadata capturing and XML based open source data exchange format), to join and work towards updating and implementing metabolomics standards.

In solid tumors, cancer stem cells (CSCs) can arise independently of epithelial-mesenchymal transition (EMT). In spite of recent efforts, the metabolic reprogramming associated with CSC phenotypes uncoupled from EMT is poorly understood. Here, by using metabolomic and fluxomic approaches, we identify major metabolic profiles that differentiate metastatic prostate epithelial CSCs (e-CSCs) from non-CSCs expressing a stable EMT. We have found that the e-CSC program in our cellular model is characterized by a high plasticity in energy substrate metabolism, including an enhanced Warburg effect, a greater carbon and energy source flexibility driven by fatty acids and amino acid metabolism and an essential reliance on the proton buffering capacity conferred by glutamine metabolism. An analysis of transcriptomic data yielded a metabolic gene signature for our e-CSCs consistent with the metabolomics and fluxomics analysis that correlated with tumor progression and metastasis in prostate cancer and in 11 additional cancer types. Interestingly, an integrated metabolomics, fluxomics and transcriptomics analysis allowed us to identify key metabolic players regulated at the post-transcriptional level, suggesting potential biomarkers and therapeutic targets to effectively forestall metastasis.