Genomic variation landscape of the human gut microbiome

While large-scale efforts have rapidly advanced the understanding and practical impact of human genomic variation, the latter is largely unexplored in the human microbiome. We therefore developed a framework for metagenomic variation analysis and applied it to 252 fecal metagenomes of 207 individuals from Europe and North America. Using 7.4 billion reads aligned to 101 reference species, we detected 10.3 million single nucleotide polymorphisms (SNPs), 107,991 short indels, and 1,051 structural variants. The average ratio of non-synonymous to synonymous polymorphism rates of 0.11 was more variable between gut microbial species than across human hosts. Subjects sampled at varying time intervals exhibited individuality and temporal stability of SNP variation patterns, despite considerable composition changes of their gut microbiota. This implies that individual-specific strains are not easily replaced and that an individual might have a unique metagenomic genotype, which may be exploitable for personalized diet or drug intake

Influence of lipid metabolism disorder on the formation of experimental gastric ulcer

The article is devoted to lipid metabolism and role in mucosal protection and local resistance of gastric tissue in an experimental ulcer model. The experiments were carried out in rats (n = 34). Conclusion: small size of ulcer is associated with a significant increase of triglycerides level and decrease of fatty acids, phospholipids level in stomach tissue. Such lipid composition of stomach tissue increases its local resistance

Minimale Hemm-Konzentration (MHK) und minimale bakterizide Konzentration (MBK) von Polihexanid und Triclosan gegen Antibiotika-empfindliche und resistente Staphylococcus aureus- und Escherichia coli-Stämme

Background: An in-vitro study was conducted investigating the antim icrob ial efficacy of polihexanide and triclosan against clinical isola tes and reference laboratory strains of Staphylococcus aureus and E scherich ia coli .Methods: The minimal inhibitory concentration (MIC) and the minimal microbicidal concentration (MMC) were determined following DIN 58940-81 using a micro-dilution assay and a quantitative suspension test following EN 1040. Polihexanide was tested in polyethylene glycol 4000, triclosan in aqueous solutions.Results: Against all tested strains the MIC of polihexanide ranged between 1-2 µg/mL. For triclosan the MICs varied depending on strains ranging between 0.5 µg/mL for the reference strains and 64 µg/mL for two clinical isolates. A logRF >5 without and logRF >3 with 0.2% album in burden was achieved at 0.6 µg/mL triclosan. One exception was S. aureus strain H-5-24, where a triclosan concentration of 0.6 µg/mL required 1 minute without and 10 minutes with albumin burden to achieve the same logRFs. Polihexanide achieved a logRF >5 without and logRF >3 with albumin burden at a concentration of 0.6 µg/mL within 30 sec. The exception was the North-German epidemic MRSA strain, were an application time of 5 minutes was required. Conclusion: The clinical isolates of E. coli generally showed higher MICs against triclosan, both in the micro-dilution assay as well in the quantit ativ e suspension test than comparable reference laboratory strains. For polihexanide and triclosan strain dependant susceptibility was shown. However, both antimicrobial compounds are effective when used in concentrations common in practice.Hintergrund: In einer quantitativen in-vitro Studie wurde der antimikrobielle Effekt von Polihexanid und Triclosan unter identischen Verhältnissen gegen Referenzstämme sowie klinische Isolate von Staphylococcus aureus und Escherichia coli bestimmt.Methoden: Die minimale Hemmkonzentration (MHK) und die minimale mikrobiozide Konzentration (MMK) wurden gemäß DIN 58940-81 mittels Mikro-Verdünnungs-Essay und eines quantitativen Verdünnungstests gemäß EN 1040 bestimmt. Polihexanid wurde in einer Polyethylene-Glykol 4000 Lösung, Triclosan in wässriger Lösung angesetzt. Ergebnisse: Die MHK von Polihexanid gegen alle getesteten Stämme lag zwischen 1-2 µg/mL. Die MHK von Triclosan war stammabhängig und lag bei 0,5 µg/mL für die getesteten Referenzstämme und bei 64 µg/mL für zwei klinischen Isolate. Gegen alle Stämme erreichte Triclosan bei einer Konzentration von 0,6 µg/mL einen logRF >5 ohne und logRF >3 mit 0,2% Albuminbelastung. Als Ausnahme erwies sich S. aureus -Stamm H-5-24, für den eine Triclosan-Konzentration von 0,6 µg/mL bei einer Einwirkungszeit von 1 min ohne bzw. 10 min mit Albuminbelastung erforderlich war, um dieselben logRF zu erreichen. Polihexanid erreichte bei einer Konzentration von 0,6 µg/mL einen logRF >5 ohne und logRF >3 mit Belastung bei einer Einwirkungszeit von 30 s . Hier erwies sich als Ausnahme der Norddeutsche MRSA Epidemiestamm, gegen den bei selber Konzentration eine Einwirkungszeit von 5 min erforderlich war. Schlussfolgerungen: Die klinischen E. coli -Isolate erforderten höhere MHKs bei Triclosan als die untersuchten Referenzstämme. Für Polih exan id und Triclosan konnte eine stammabhängige Empfindlichkeit gezeigt werden. Beide Antiseptika werden im klinischen Einsatz jedoch regelhaft bei weit höheren Konzentrationen eingesetzt, womit die unterschiedlichen Empfindlichkeiten klinisch keine Rolle spielen sollten

Psoriasis: from Pathogenesis to Targeted Therapies

Over the last decade, the management of psoriasis has witnessed a paradigm shift. Thanks to the increasing knowledge about the pathogenesis of psoriasis, targeted treatments with monoclonal antibodies have been developed. These antibodies, which target the pathogenic TNF/IL-23/IL-17-pathway, were shown to be safe and efficacious in the management of most patients with moderate to severe chronic plaque psoriasis. Recently, molecular and genetic studies in pustular and erythrodermic psoriasis have identified additional inflammatory pathways, providing evidence that psoriasis is a heterogeneous disease and highlighting the requirement for personalized disease characterization for treatment optimization. In this article, we will review these advances and provide an update on the currently available treatment arsenal. We discuss the efficacy and safety profile of these individual therapeutic agents and describe their use in special indications. We will also describe the current understanding of psoriasis as a systemic disease associated with multiple comorbidities and illustrate its impact in the management of psoriatic patients. Finally, we discuss ongoing therapeutic developments as well as unmet needs and future perspectives in the field of psoriasis