Parallels between Pathogens and Gluten Peptides in Celiac Sprue

Pathogens are exogenous agents capable of causing disease in susceptible organisms. In celiac sprue, a disease triggered by partially hydrolyzed gluten peptides in the small intestine, the offending immunotoxins cannot replicate, but otherwise have many hallmarks of classical pathogens. First, dietary gluten and its peptide metabolites are ubiquitous components of the modern diet, yet only a small, genetically susceptible fraction of the human population contracts celiac sprue. Second, immunotoxic gluten peptides have certain unusual structural features that allow them to survive the harsh proteolytic conditions of the gastrointestinal tract and thereby interact extensively with the mucosal lining of the small intestine. Third, they invade across epithelial barriers intact to access the underlying gut-associated lymphoid tissue. Fourth, they possess recognition sequences for selective modification by an endogenous enzyme, transglutaminase 2, allowing for in situ activation to a more immunotoxic form via host subversion. Fifth, they precipitate a T cell–mediated immune reaction comprising both innate and adaptive responses that causes chronic inflammation of the small intestine. Sixth, complete elimination of immunotoxic gluten peptides from the celiac diet results in remission, whereas reintroduction of gluten in the diet causes relapse. Therefore, in analogy with antibiotics, orally administered proteases that reduce the host's exposure to the immunotoxin by accelerating gluten peptide destruction have considerable therapeutic potential. Last but not least, notwithstanding the power of in vitro methods to reconstitute the essence of the immune response to gluten in a celiac patient, animal models for the disease, while elusive, are likely to yield fundamentally new systems-level insights

ÚDRŽBA JAKO NÁSTROJ ZVYŠOVÁNÍ VÝKONNOSTI CHEMICKO-TECHNOLOGICKÉHO VÝROBNÍHO PROCESU

Reliability, flexibility and speed belong among particularly valued parameters of contractor. In manufacturing companies, the achievement thereof is significantly limited by the reliability of production equipment. The aim of the article is to analyse an applied production equipment maintenance system with heavily utilized production equipment, and to define guidelines for its improvement. A content analysis of information obtained in a primary qualitative research and a comparison with theoretical approaches made it possible to define an adequate combination of various types of maintenance, including methods and tools that are not primarily intended for the examined type of manufacturing processes.Mimořádně ceněnými parametry dodavatele jsou spolehlivost, flexibilita a rychlost. Jejich dosažení je ve výrobních podnicích významně limitováno spolehlivostí výrobního zařízení. Zejména u velmi vytíženého výrobního zařízení je proto třeba věnovat trvalou pozornost managementu údržby a neustále hledat cesty jeho zlepšování, a to se zohledněním specifik konkrétního výrobního procesu. Cílem článku proto je analyzovat reálně aplikovaný systém údržby výrobního zařízení (v podniku chemického průmyslu), jehož kapacita je využívána na více než 95 % a na základě identifikovaných nedostatků vymezit hlavní směry jeho zlepšení. Obsahová analýza informací získaných primárním kvalitativním výzkumem a komparace s teoretickými přístupy k údržbě výrobního zařízení umožnila vymezit, že adekvátní systém údržby zkoumaného výrobního zařízení musí být založen na vhodné kombinaci jednotlivých typů údržby. Jako vhodné se jeví i využití metod a nástrojů, které nejsou primárně určeny pro zkoumaný typ výrobních procesů

Novel vancomycin–peptide conjugate as potent antibacterial agent against vancomycin-resistant Staphylococcus aureus

Pavlina Jelinkova,1 Zbynek Splichal,1,2 Ana Maria Jimenez Jimenez,1,2 Yazan Haddad,1,2 Aninda Mazumdar,1,2 Vishma Pratap Sur,1,2 Vedran Milosavljevic,1,2 Pavel Kopel,1,2 Hana Buchtelova,1 Roman Guran,1,2 Ondrej Zitka,1,2 Lukas Richtera,1,2 Dagmar Hegerova,1,2 Zbynek Heger,1,2 Amitava Moulick,1,2 Vojtech Adam1,2 1Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska, Brno, Czech Republic; 2Central European Institute of Technology, Brno University of Technology, Purkynova, Brno, Czech Republic Background: Increase in vancomycin (Van)-resistant bacterial strains including vancomycin-resistant Staphylococcus aureus (VRSA) and lack of new effective antibiotics have become a formidable health problem. Materials and methods: We designed a new conjugate composed of Van and a peptide Hecate (Hec; Van/Hec), and its potential antimicrobial activity was evaluated. Results: Results from disk diffusion test, time-kill assay, determination of minimum inhibitory concentration (MIC), microscopy, and comet assay showed strong antimicrobial effects of Van/Hec against wild-type, methicillin-resistant Staphylococcus aureus (MRSA) and VRSA. Microscopy revealed that the exposure to Van/Hec results in disruption of bacterial cell integrity in all tested strains, which was not observed in case of Van or Hec alone. Conclusion: Overall, we showed that the preparation of conjugates from antibiotics and biologically active peptides could help us to overcome the limitation of the use of antibiotic in the treatment of infections caused by multidrug-resistant bacteria. Keywords: vancomycin, antibacterial, Staphylococcus aureus, antibiotic resistance, peptid