Pre-clinical animal studies precede the majority of clinical trials. While the clinical definitions of sepsis and recommended treatments are regularly updated, a systematic review of pre-clinical models of sepsis has not been done and clear modeling guidelines are lacking. To address this deficit, a Wiggers-Bernard Conference on pre-clinical sepsis modeling was held in Vienna in May 2017. The goal of the conference was to identify limitations of pre-clinical sepsis models and to propose a set of guidelines, defined as the “Minimum Quality Threshold in Pre-Clinical Sepsis Studies” (MQTiPSS), to enhance translational value of these models. A total of 31 experts from 13 countries participated and were divided into 6 thematic working groups (WG): (1) study design, (2) humane modeling, (3) infection types, (4) organ failure/dysfunction, (5) fluid resuscitation, and (6) antimicrobial therapy endpoints. As basis for the MQTiPSS discussions, the participants conducted a literature review of the 260 most highly cited scientific articles on sepsis models (2002–2013). Overall, the participants reached consensus on 29 points; 20 at “recommendation” (R) and 9 at “consideration” (C) strength. This executive summary provides a synopsis of the MQTiPSS consensus (Tables 1 , 2 , and 3 ). Detailed commentaries to all Rs and Cs are simultaneously published in three separate full-length papers. We believe that these recommendations and considerations will serve to bring a level of standardization to pre-clinical models of sepsis and ultimately improve translation of pre-clinical findings. These guideline points are proposed as “best practices” for animal models of sepsis that should be implemented. In order to encourage its wide dissemination, this article is freely accessible in Shock, Infection and Intensive Care Medicine Experimental.

Biological methane formation is associated with anoxic environments and the activity of anaerobic prokaryotes (Archaea). However, recent studies have confirmed methane release from eukaryotes, including plants, fungi, and animals, even in the absence of microbes and in the presence of oxygen. Furthermore, it was found that aerobic methane emission in plants is stimulated by a variety of environmental stress factors, leading to reactive oxygen species (ROS) generation. Further research presented evidence that molecules with sulfur and nitrogen bonded methyl groups such as methionine or choline are carbon precursors of aerobic methane formation. Once generated, methane is widely considered to be physiologically inert in eukaryotes, but several studies have found association between mammalian methanogenesis and gastrointestinal (GI) motility changes. In addition, a number of recent reports demonstrated anti-inflammatory potential for exogenous methane-based approaches in model anoxia-reoxygenation experiments. It has also been convincingly demonstrated that methane can influence the downstream effectors of transiently increased ROS levels, including mitochondria-related pro-apoptotic pathways during ischemia-reperfusion (IR) conditions. Besides, exogenous methane can modify the outcome of gasotransmitter-mediated events in plants, and it appears that similar mechanism might be active in mammals as well. This review summarizes the relevant literature on methane-producing processes in eukaryotes, and the available results that underscore its bioactivity. The current evidences suggest that methane liberation and biological effectiveness are both linked to cellular redox regulation. The data collectively imply that exogenous methane influences the regulatory mechanisms and signaling pathways involved in oxidative and nitrosative stress responses, which suggests a modulator role for methane in hypoxia-linked pathologies.

This study was designed to follow the time course of inflammatory activation in a rodent model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)–induced colitis. We hypothesized that oral phosphatidylcholine (PC) pretreatment regimens may influence leukocyte-mediated microcirculatory reactions in this condition. In series I, Wistar rats were monitored 1 day after colitis induction (n = 24), and in series II (n = 24) on day 6 following a TNBS enema. The PC-pretreated animals received a 2% PC-enriched diet for 6 days before the TNBS enema (series I), or for 3 days before and 3 days after TNBS treatment (series II). The macrohemodynamics, serosal microcirculation (visualized by intravital videomicroscopy), colonic xanthine oxidoreductase, myeloperoxidase and nitric oxide end products, and changes in proinflammatory cytokine levels in plasma were measured. The mucosal structural injury was monitored in vivo by means of confocal laser scanning endomicroscopy. The TNBS enema induced a systemic hyperdynamic circulatory reaction with increased serosal capillary blood flow and significantly elevated colonic inflammatory enzyme activities, levels of nitric oxide production, and cytokine concentrations. Acute colitis caused disruption of the capillary network, whereas the morphologic damage was less severe in series II. The PC pretreatment protocols led to significant decreases in the serosal hyperemic reaction, the cytokine levels, and the inflammatory enzyme activities. The objective signs of tissue damage were reduced in both series, and the number of mucus-producing goblet cells in the resolving phase of colitis was increased. Dietary PC efficiently decreases the cytokine-mediated progression of inflammatory events and preserves the microvascular structure in the large intestine.

Optimized biocompatibility of new materials is a major requirement for transvaginal meshes for pelvic organ prolapse (POP) repair. Polyvinylidene fluoride (PVDF) presented good characteristics in prior animal experiments and clinical use in humans. Between 01/2012 and 04/2016 37 women underwent transvaginal repair of symptomatic prolapse of the anterior vaginal wall (cystocele) with PVDF-mesh in a single institution. A chart review for recurrence, continence, peri- and early postoperative complications was performed. Referring practitioners were interviewed by telephone and mail. Additionally patient reported outcome and satisfaction were measured by Patient Global Improvement Inventory (PGI-I) scale. 34 women were eligible for a mean follow up of 19 months. The functional outcome improved significantly. One symptomatic vault prolapse (2.9%) and two reoperations for incontinence (5.9%) occurred. Two mesh exposures (5.9%) occurred and were treated conservatively. No other severe complications were registered. 87.5% of treated women felt very much better or much better and would undergo the surgery again. A cohort study including development steps in accordance with the IDEAL system is presented. For the first time we report on effectivity and safety of transvaginal application of PVDF-mesh in real-life practice. A prospective long-term evaluation in a registry is justified.

Mammalian methanogenesis is regarded as an indicator of carbohydrate fermentation by anaerobic gastrointestinal flora. Once generated by microbes or released by a non-bacterial process, methane is generally considered to be biologically inactive. However, recent studies have provided evidence for methane bioactivity in various in vivo settings. The administration of methane either in gas form or solutions has been shown to have anti-inflammatory and neuroprotective effects in an array of experimental conditions, such as ischemia/reperfusion, endotoxemia and sepsis. It has also been demonstrated that exogenous methane influences the key regulatory mechanisms and cellular signalling pathways involved in oxidative and nitrosative stress responses. This review offers an insight into the latest findings on the multi-faceted organ protective activity of exogenous methane treatments with special emphasis on its versatile effects demonstrated in sepsis models.