Time interval between self-expandable metal stent placement or creation of a decompressing stoma and elective resection of left-sided obstructive colon cancer

Background The optimal timing of resection after decompression of left-sided obstructive colon cancer is unknown. Revised expert-based guideline recommendations have shifted from an interval of 5-10 days to approximately 2 weeks following self-expandable metal stent (SEMS) placement, and recommendations after decompressing stoma are lacking. We aimed to evaluate the recommended bridging intervals after SEMS and explore the timing of resection after decompressing stoma.Methods This nationwide study included patients registered between 2009 and 2016 in the prospective, mandatory Dutch ColoRectal Audit. Additional data were collected through patient records in 75 hospitals. Only patients who underwent either SEMS placement or decompressing stoma as a bridge to surgery were selected. Technical SEMS failure and unsuccessful decompression within 48 hours were exclusion criteria.Results 510 patients were included (182 SEMS, 328 decompressing stoma). Median bridging interval was 23 days (interquartile range [IQR] 13-31) for SEMS and 36 days (IQR 22-65) for decompressing stoma. Following SEMS placement, no significant differences in post-resection complications, hospital stay, or laparoscopic resections were observed with resection after 11-17 days compared with 5-10 days. Of SEMS-related complications, 48% occurred in patients operated on beyond 17 days. Compared with resection within 14 days, an interval of 14-28 days following decompressing stoma resulted in significantly more laparoscopic resections, more primary anastomoses, and shorter hospital stays. No impact of bridging interval on mortality, disease-free survival, or overall survival was demonstrated.Conclusions Based on an overview of the data with balancing of surgical outcomes and timing of adverse events, a bridging interval of approximately 2 weeks seems appropriate after SEMS placement, while waiting 2-4 weeks after decompressing stoma further optimizes surgical conditions for laparoscopic resection with restoration of bowel continuity.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Regulation of CCL2 Expression by an Upstream TALE Homeodomain Protein-Binding Site That Synergizes with the Site Created by the A-2578G SNP

CC Chemokine Ligand 2 (CCL2) is a potent chemoattractant produced by macrophages and activated astrocytes during periods of inflammation within the central nervous system. Increased CCL2 expression is correlated with disease progression and severity, as observed in pulmonary tuberculosis, HCV-related liver disease, and HIV-associated dementia. The CCL2 distal promoter contains an A/G polymorphism at position -2578 and the homozygous -2578 G/G genotype is associated with increased CCL2 production and inflammation. However, the mechanisms that contribute to the phenotypic differences in CCL2 expression are poorly understood. We previously demonstrated that the -2578 G polymorphism creates a TALE homeodomain protein binding site (TALE binding site) for PREP1/PBX2 transcription factors. In this study, we identified the presence of an additional TALE binding site 22 bp upstream of the site created by the -2578 G polymorphism and demonstrated the synergistic effects of the two sites on the activation of the CCL2 promoter. Using chromatin immunoprecipitation (ChIP) assays, we demonstrated increased binding of the TALE proteins PREP1 and PBX2 to the -2578 G allele, and binding of IRF1 to both the A and G alleles. The presence of TALE binding sites that form inverted repeats within the -2578 G allele results in increased transcriptional activation of the CCL2 distal promoter while the presence of only the upstream TALE binding site within the -2578 A allele exerts repression of promoter activity

Anaerobic digestion and gasification of seaweed

The potential of algal biomass as a source of liquid and gaseous biofuels is a highly topical theme, with over 70 years of sometimes intensive research and considerable financial investment. A wide range of unit operations can be combined to produce algal biofuel, but as yet there is no successful commercial system producing such biofuel. This suggests that there are major technical and engineering difficulties to be resolved before economically viable algal biofuel production can be achieved. Both gasification and anaerobic digestion have been suggested as promising methods for exploiting bioenergy from biomass, and two major projects have been funded in the UK on the gasification and anaerobic digestion of seaweed, MacroBioCrude and SeaGas. This chapter discusses the use of gasification and anaerobic digestion of seaweed for the production of biofuel

Mitochondrial affinity for ADP is twofold lower in creatine kinase knock-out muscles - Possible role in rescuing cellular energy homeostasis

Adaptations of the kinetic properties of mitochondria in striated muscle lacking cytosolic (M) and/or mitochondrial (Mi) creatine kinase (CK) isoforms in comparison to wild-type (WT) were investigated in vitro. Intact mitochondria were isolated from heart and gastrocnemius muscle of WT and single- and double CK-knock-out mice strains (cytosolic (M-CK-/-), mitochondrial (Mi-CK-/-) and double knock-out (MiM-CK-/-) respectively). Maximal ADP-stimulated oxygen consumption flux (State3 V-max; nmol O-2.mg mitochondrial protein(-1).min(-1)) and ADP affinity (K-50(ADP); muM) were determined by respirometry. State 3 V-max and K-50(ADP) of M-CK-/- and MiM-CK-/- gastrocnemius mitochondria were twofold higher than those of WT, but were unchanged for Mi-CK-/-. For mutant cardiac mitochondria, only the K-50(ADP) of mitochondria isolated from the MiM-CK-/- phenotype was different (i.e. twofold higher) than that of WT. The implications of these adaptations for striated muscle function were explored by constructing force-flow relations of skeletal muscle respiration. It was found that the identified shift in affinity towards higher ADP concentrations in MiM-CK-/- muscle genotypes may contribute to linear mitochondrial control of the reduced cytosolic ATP free energy potentials in these phenotypes

A novel hypertonicity-induced cation channel in primary cultures of human hepatocytes

AbstractIn whole-cell recordings on primary cultures of human hepatocytes, we observe the hypertonic activation of a novel type of cation channel with a permeability ratio for Na+:Li+:K+:Cs+:NMDG+ of 1:1.2:1.3:1.2:0.6. With a PCa/PNa of 0.7 the channel is also clearly permeable to Ca++. Most likely, the channel is Cl− impermeable but its activity critically depends on the extracellular Cl− concentration (with the half maximal effect at 88mmol/l). With a 64% inhibition by amiloride and a complete block by flufenamate and Gd3+ (at 100μmol/l each), the channel may represent a molecular link between the amiloride-sensitive and insensitive channels reported so far