Oral but Not Intravenous Glucose Acutely Decreases Circulating Interleukin-6 Concentrations in Overweight Individuals

Background

Plasma interleukin-6 (IL-6) concentrations decrease acutely 1 h after ingestion of a glucose load or mixed meals and this may be mediated by an anti-inflammatory effect of insulin. The aim of the present study was to compare the effect of higher versus lower insulin levels on plasma IL-6 concentrations following oral compared with intravenous glucose administration in overweight/obese subjects.

Methods and Findings

Fifteen subjects (12 women and 3 men) with BMI >28 kg/m² were given an oral glucose load (75g) followed a week later by an intravenous infusion of glucose aimed at matching plasma glucose concentrations during the oral glucose load. A week later, they drank a volume of water equivalent to the volume consumed with the oral glucose load. Plasma glucose, insulin, nonesterified fatty acids, and IL-6 concentrations and blood hematocrit were measured at 30 minute intervals for 2 h following each intervention. Plasma IL-6 decreased (13–20%) significantly (P = 0.009) at 30 min to 90 min following the oral glucose load and did not change significantly following the other two interventions. The incremental area under the curve for plasma IL-6 concentrations following oral intake of glucose was significantly lower compared with concentrations following intravenous glucose (P = 0.005) and water control (P = 0.02). Circulating insulin concentrations were significantly (P<0.001) and 2.8 fold higher following oral compared with intravenous glucose administration.

Conclusions

These data show that plasma IL-6 concentrations did not decrease during isoglycemic, intravenous glucose administration suggesting that the markedly higher circulating insulin levels and/or gut-related factors may mediate the acute decrease in plasma IL-6 after oral glucose intake in overweight/obese subjects.

Trial Registration

Australian New Zealand Clinical Trials Registry ACTRN12612000491864     

Pollen influx values measured in different sedimentary environments and their palaeoecological implications

Aspects which need to be considered when calculating pollen influx values in three sedimentary environments (pollen traps, peats and lake sediments) are reviewed. Examples of influx values (grains cm^-2 year^-1) in northern Fennoscandia for two arboreal taxa Betula and Pinus, calculated from these three different environments are presented. Such long term average pollen influx values can be used to indicate the presence/absence and density of the species within the vicinity of the sampling site. Contrary to expectations, conditions do exist in which numerically comparable values are obtained from all three environments. Using these pollen influx values to interpret forest and woodland history in tree-line situations, from both peats and lake sediments, a higher degree of precision can be obtained than through the more classical pollen percentage method alone.     

Regulation of Rac1 and Reactive Oxygen Species Production in Response to Infection of Gastrointestinal Epithelia

Generation of reactive oxygen species (ROS) during infection is an immediate host defense leading to microbial killing. APE1 is a multifunctional protein induced by ROS and after induction, protects against ROS-mediated DNA damage. Rac1 and NAPDH oxidase (Nox1) are important contributors of ROS generation following infection and associated with gastrointestinal epithelial injury. The purpose of this study was to determine if APE1 regulates the function of Rac1 and Nox1 during oxidative stress. Gastric or colonic epithelial cells (wild-type or with suppressed APE1) were infected with Helicobacter pylori or Salmonella enterica and assessed for Rac1 and NADPH oxidase-dependent superoxide production. Rac1 and APE1 interactions were measured by co-immunoprecipitation, confocal microscopy and proximity ligation assay (PLA) in cell lines or in biopsy specimens. Significantly greater levels of ROS were produced by APE1-deficient human gastric and colonic cell lines and primary gastric epithelial cells compared to control cells after infection with either gastric or enteric pathogens. H. pylori activated Rac1 and Nox1 in all cell types, but activation was higher in APE1 suppressed cells. APE1 overexpression decreased H. pylori-induced ROS generation, Rac1 activation, and Nox1 expression. We determined that the effects of APE1 were mediated through its N-terminal lysine residues interacting with Rac1, leading to inhibition of Nox1 expression and ROS generation. APE1 is a negative regulator of oxidative stress in the gastrointestinal epithelium during bacterial infection by modulating Rac1 and Nox1. Our results implicate APE1 in novel molecular interactions that regulate early stress responses elicited by microbial infections.     

Chronic Cocaine Administration Increases CNS Tyrosine Hydroxylase Enzyme Activity and mRNA Levels and Tryptophan Hydroxylase Enzyme Activity Levels

Cocaine is an inhibitor of dopamine and serotonin reuptake by synaptic terminals and has potent reinforcing effects that lead to its abuse. Tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) catalyze the rate-limiting steps in dopamine and serotonin biosynthesis, respectively, and are the subject of dynamic regulatory mechanisms that could be sensitive to the actions of cocaine. This study assessed the effects of chronic cocaine on brain TH and TPH activities. Cocaine was administered (0.33 mg/infusion, i.v.) to rats for 7 days every 8 min for 6 h per day. This administration schedule is similar to patterns of self-administration by rats when given ad libitum access to this dose. This chronic, response-independent administration increased TH enzyme activity in the substantia nigra (30%) and ventral tegmental area (43%). Moreover, TH mRNA levels were also increased (45 and 50%, respectively). In contrast to the enzymatic and molecular biological changes in the cell bodies, TH activity was unchanged in the terminal fields (corpus striaturn and nucleus accumbens). Similarly, TPH activity was increased by 50% in the raphe nucleus (serotonergic cell bodies). In summary, the chronic response-independent administration of cocaine produces increases in the expression of TH mRNA and activity in both the cell bodies of motor (nigrostriatal) and reinforcement (mesolimbic) dopamine pathways. These increases are not manifested in the terminal fields of these pathways.     

Reproductive success and clonal genetic structure of the rareArnica montana (Compositae) in The Netherlands

In a medium-sized population ofArnica montana, a threatened species in The Netherlands, the breeding system, reproductive success and genetic clonal structure were studied. Pollination experiments suggested thatA. montana is largely self-incompatible. Inbreeding depression was observed for seedling weight but not for fruit weight and germination rate. Although genetic variation is rather low in this population, the data suggest an outcrossing mating system. Analysis of the genotype of all mapped rosettes in a plot of 100 m² indicated that dense clusters often consist of identical genotypes, suggesting a clonal structure. Open clusters frequently contained several different genotypes. This may be caused by limited fruit dispersal, since seedlings were found mainly within or in the near surroundings of the clusters.     

DarkHorse: a method for genome-wide prediction of horizontal gene transfer

A new approach to rapid, genome-wide identification and ranking of horizontal transfer candidate proteins is presented. The method is quantitative, reproducible, and computationally undemanding. It can be combined with genomic signature and/or phylogenetic tree-building procedures to improve accuracy and efficiency. The method is also useful for retrospective assessments of horizontal transfer prediction reliability, recognizing orthologous sequences that may have been previously overlooked or unavailable. These features are demonstrated in bacterial, archaeal, and eukaryotic examples.     

Mortality in adult intensive care patients with severe systemic inflammatory response syndromes is strongly associated with the hypo-immune TNF −238A polymorphism

The systemic inflammatory response syndrome (SIRS) is associated with activation of innate immunity. We studied the association between mortality and measures of disease severity in the intensive care unit (ICU) and functional polymorphisms in genes coding for Toll-like receptor 4 (TLR4), macrophage migratory inhibitory factor (MIF), tumour necrosis factor (TNF) and lymphotoxin-alpha (LTA). Two hundred thirty-three patients with severe SIRS were recruited from one general adult ICU in a tertiary centre in the UK. DNA from patients underwent genotyping by 5′ nuclease assay. Genotype was compared to phenotype. Primary outcome was mortality in ICU. Minor allele frequencies were TLR4 +896G 7%, MIF 173C 16%, TNF ?238A 10% and LTA +252G 34%. The frequency of the hypoimmune minor allele TNF ?238A was significantly higher in patients who died in ICU compared to those who survived (p?=?0.0063) as was the frequency of the two haplotypes LTA +252G, TNF ?1031T, TNF ?308G, TNF ?238A and LTA +252G, TNF?1031T, TNF?308A and TNF?238A (p?=?0.0120 and 0.0098, respectively). These findings re-enforce the view that a balanced inflammatory/anti-inflammatory response is the most important determinant of outcome in sepsis. Genotypes that either favour inflammation or its counter-regulatory anti-inflammatory response are likely to influence mortality and morbidity.     

A propolis extract and the labeling of blood constituents with technetium-99m

Since ancient times propolis has been employed for many human purposes because to their favourable properties. Blood constituents labeled with technetium-99m (99mTc) have been used in nuclear medicine procedures. Some authors have reported that synthetic or natural drugs can interfere with the labeling of blood constituents with 99mTc. The aim of this work was to evaluate the action of a propolis extract on the labeling of blood elements with 99mTc. Samples of whole blood of male Wistar rats were incubated in sequence with an aqueous propolis extract at different concentrations, stannous chloride and 99mTc, as sodium pertechnetate. Blood samples were centrifuged to separate plasma and blood cells, soluble and insoluble fractions of plasma and blood cells were also separated after precipitation in trichloroacetic acid solution and centrifugation. The radioactivity was counted and the percentage of incorporated radioactivity (%ATI) for each fraction was calculated. The data obtained showed that the aqueous propolis extract used decreased significantly the %ATI in plasma proteins at higher concentration studied. Results suggest that at high concentration the constituents of this extract could alter the labeling of plasma proteins competing with same binding sites of the 99mTc on the plasma proteins or acting as antioxidant compounds.     

Behavioral phenotypes of Disc1 missense mutations in mice

To support the role of DISC1 in human psychiatric disorders, we identified and analyzed two independently derived ENU-induced mutations in Exon 2 of mouse Disc1. Mice with mutation Q31L showed depressive-like behavior with deficits in the forced swim test and other measures that were reversed by the antidepressant bupropion, but not by rolipram, a phosphodiesterase-4 (PDE4) inhibitor. In contrast, L100P mutant mice exhibited schizophrenic-like behavior, with profound deficits in prepulse inhibition and latent inhibition that were reversed by antipsychotic treatment. Both mutant DISC1 proteins exhibited reduced binding to the known DISC1 binding partner PDE4B. Q31L mutants had lower PDE4B activity, consistent with their resistance to rolipram, suggesting decreased PDE4 activity as a contributory factor in depression. This study demonstrates that Disc1 missense mutations in mice give rise to phenotypes related to depression and schizophrenia, thus supporting the role of DISC1 in major mental illness.