Low iron availability in continuous in vitro colonic fermentations induces strong dysbiosis of the child gut microbial consortium and a decrease in main metabolites

Iron (Fe) deficiency affects an estimated 2 billion people worldwide, and Fe supplements are a common corrective strategy. The impact of Fe deficiency and Fe supplementation on the complex microbial community of the child gut was studied using in vitro colonic fermentation models inoculated with immobilized fecal microbiota. Chyme media (all Fe chelated by 2,2′-dipyridyl to 26.5 mg Fe L−1) mimicking Fe deficiency and supplementation were continuously fermented. Fermentation effluent samples were analyzed daily on the microbial composition and metabolites by quantitative PCR, 16S rRNA gene 454-pyrosequencing, and HPLC. Low Fe conditions (1.56 mg Fe L−1) significantly decreased acetate concentrations, and subsequent Fe supplementation (26.5 mg Fe L−1) restored acetate production. High Fe following normal Fe conditions had no impact on the gut microbiota composition and metabolic activity. During very low Fe conditions (0.9 mg Fe L−1 or Fe chelated by 2,2′-dipyridyl), a decrease in Roseburia spp./Eubacterium rectale, Clostridium Cluster IV members and Bacteroides spp. was observed, while Lactobacillus spp. and Enterobacteriaceae increased consistent with a decrease in butyrate (−84%) and propionate (−55%). The strong dysbiosis of the gut microbiota together with decrease in main gut microbiota metabolites observed with very low iron conditions could weaken the barrier effect of the microbiota and negatively impact gut healt

The Synthesis of Some Disubstituted Derivatives of p,p\u27-bis- (Pyrimidyl-2-sulphamyl)-carbanilide. II

In an earlier paper1 we\u27 describ ed the preparation of some disub stitutedderivatives of p,p\u27-bis-(sulphamyl)-carbanilide by the condensation of carbanilide- p,p\u27-disulphbnic acid dichloride with various heterocyclic amines, and their hydrolysis to the corresponding sulphonamides. This paper reports our work <:oncerned with the synthesis of p,p\u27-bis-(pyrimidyl-2-sulphamyl)-carbanilides by condensation of p,p\u27-bis-(N-guanylsulphamyl)-carbanUide with various appropriate s ub stituted aliphatic carbonyl compounds. The preparation was performed according to the standard procedures for the synthesis of substituted .sulphapyrimidines2- 4 and pyrimidines

The Synthesis of Some Disubstituted Derivatives of p,p\u27-bis- (Pyrimidyl-2-sulphamyl)-carbanilide. II

In an earlier paper1 we\u27 describ ed the preparation of some disub stituted derivatives of p,p\u27-bis-(sulphamyl)-carbanilide by the condensation of carbanilide- p,p\u27-disulphbnic acid dichloride with various heterocyclic amines, and their hydrolysis to the corresponding sulphonamides. This paper reports our work <:oncerned with the synthesis of p,p\u27-bis-(pyrimidyl-2-sulphamyl)-carbanilides by condensation of p,p\u27-bis-(N-guanylsulphamyl)-carbanUide with various appropriate s ub stituted aliphatic carbonyl compounds. The preparation was performed according to the standard procedures for the synthesis of substituted .sulphapyrimidines2- 4 and pyrimidines

Modulation of Myocardial Mitochondrial Mechanisms during severe Polymicrobial Sepsis in the Rat

Background: We tested the hypothesis that 5-Hydroxydecanoic acid (5HD), a putative mitoKATP channel blocker, will reverse sepsis-induced cardiodynamic and adult rat ventricular myocyte (ARVM) contractile dysfunction, restore mitochondrial membrane permeability alterations and improve survival. Methodology/Principal Findings: Male Sprague-Dawley rats (350-400 g) were made septic using 400 mg/kg cecal inoculum, ip. Sham animals received 5% dextrose water, ip. The Voltage Dependent Anion Channels (VDAC1), Bax and cytochrome C levels were determined in isolated single ARVMs obtained from sham and septic rat heart. Mitochondria and cytosolic fractions were isolated from ARVMs treated with norepinephrine (NE, 10 µmoles) in the presence/absence of 5HD (100 µmoles). A continuous infusion of 5HD using an Alzet pump reversed sepsis-induced mortality when administered at the time of induction of sepsis (-40%) and at 6 hr post-sepsis (-20%). Electrocardiography revealed that 5HD reversed sepsis-induced decrease in the average ejection fraction, Simpsons+m Mode (53.5±2.5 in sepsis and 69.2±1.2 at 24 hr in sepsis+5HD vs. 79.9±1.5 basal group) and cardiac output (63.3±1.2 mL/min sepsis and 79.3±3.9 mL/min at 24 hr in sepsis+5HD vs. 85.8±1.5 mL/min basal group). The treatment of ARVMs with 5HD also reversed sepsis-induced depressed contractility in both the vehicle and NE-treated groups. Sepsis produced a significant downregulation of VDAC1, and upregulation of Bax levels, along with mitochondrial membrane potential collapse in ARVMs. Pretreatment of septic ARVMs with 5HD blocked a NE-induced decrease in the VDAC1 and release of cytochrome C. Conclusion: The data suggest that Bax activation is an upstream event that may precede the opening of the mitoKATP channels in sepsis. We concluded that mitoKATP channel inhibition via decreased mitochondrial membrane potential and reduced release of cytochrome C provided protection against sepsis-induced ARVM and myocardial contractile dysfunction. © 2011 Chopra et al

Full characterization of vibrational coherence in a porphyrin chromophore by two-dimensional electronic spectroscopy

In this work we present experimental and calculated two-dimensional electronic spectra for a 5,15-bisalkynyl porphyrin chromophore. The lowest energy electronic Qy transition couples mainly to a single 380 cm–1 vibrational mode. The two-dimensional electronic spectra reveal diagonal and cross peaks which oscillate as a function of population time. We analyze both the amplitude and phase distribution of this main vibronic transition as a function of excitation and detection frequencies. Even though Feynman diagrams provide a good indication of where the amplitude of the oscillating components are located in the excitation-detection plane, other factors also affect this distribution. Specifically, the oscillation corresponding to each Feynman diagram is expected to have a phase that is a function of excitation and detection frequencies. Therefore, the overall phase of the experimentally observed oscillation will reflect this phase dependence. Another consequence is that the overall oscillation amplitude can show interference patterns resulting from overlapping contributions from neighboring Feynman diagrams. These observations are consistently reproduced through simulations based on third order perturbation theory coupled to a spectral density described by a Brownian oscillator model

'Treatment of the Sportsman's groin': British Hernia Society's 2014 position statement based on the Manchester Consensus Conference

&lt;b&gt;Introduction&lt;/b&gt; The aim was to produce a multidisciplinary consensus to determine the current position on the nomenclature, definition, diagnosis, imaging modalities and management of Sportsman's groin (SG).&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; Experts in the diagnosis and management of SG were invited to participate in a consensus conference held by the British Hernia Society in Manchester, UK on 11–12 October 2012. Experts included a physiotherapist, a musculoskeletal radiologist and surgeons with a proven track record of expertise in this field. Presentations detailing scientific as well as outcome data from their own experiences were given. Records were made of the presentations with specific areas debated openly.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; The term ‘inguinal disruption’ (ID) was agreed as the preferred nomenclature with the term ‘Sportsman's hernia’ or ‘groin’ rejected, as no true hernia exists. There was an overwhelming agreement of opinion that there was abnormal tension in the groin, particularly around the inguinal ligament attachment. Other common findings included the possibility of external oblique disruption with consequent small tears noted as well as some oedema of the tissues. A multidisciplinary approach with tailored physiotherapy as the initial treatment was recommended with any surgery involving releasing the tension in the inguinal canal by various techniques and reinforcing it with a mesh or suture repair. A national registry should be developed for all athletes undergoing surgery.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; ID is a common condition where no true hernia exists. It should be managed through a multidisciplinary approach to ensure consistent standards and outcomes are achieved

Effects of iron supplementation on dominant bacterial groups in the gut, faecal SCFA and gut inflammation: a randomised, placebo-controlled intervention trial in South African children

Fe supplementation is a common strategy to correct Fe-deficiency anaemia in children; however, it may modify the gut microbiota and increase the risk for enteropathogenic infection. In the present study, we studied the impact of Fe supplementation on the abundance of dominant bacterial groups in the gut, faecal SCFA concentration and gut inflammation in children living in rural South Africa. In a randomised, placebo-controlled intervention trial of 38 weeks, 6- to 11-year-old children with Fe deficiency received orally either tablets containing 50mg Fe as FeSO4 (n 22) for 4d/week or identical placebo (n 27). In addition, Fe-sufficient children (n 24) were included as a non-treated reference group. Faecal samples were analysed at baseline and at 2, 12 and 38 weeks to determine the effects of Fe supplementation on ten bacterial groups in the gut (quantitative PCR), faecal SCFA concentration (HPLC) and gut inflammation (faecal calprotectin concentration). At baseline, concentrations of bacterial groups in the gut, faecal SCFA and faecal calprotectin did not differ between Fe-deficient and Fe-sufficient children. Fe supplementation significantly improved Fe status in Fe-deficient children and did not significantly increase faecal calprotectin concentration. Moreover, no significant effect of Fe treatment or time×treatment interaction on the concentrations of bacterial groups in the gut or faecal SCFA was observed compared with the placebo treatment. Also, there were no significant differences observed in the concentrations of any of the bacterial target groups or faecal SCFA at 2, 12 or 38 weeks between the three groups of children when correcting for baseline values. The present study suggests that in African children with a low enteropathogen burden, Fe status and dietary Fe supplementation did not significantly affect the dominant bacterial groups in the gut, faecal SCFA concentration or gut inflammatio

The effects of iron fortification on the gut microbiota in African children: a randomized controlled trial in Cote d'Ivoire.

BACKGROUND: Iron is essential for the growth and virulence of many pathogenic enterobacteria, whereas beneficial barrier bacteria, such as lactobacilli, do not require iron. Thus, increasing colonic iron could select gut microbiota for humans that are unfavorable to the host. OBJECTIVE: The objective was to determine the effect of iron fortification on gut microbiota and gut inflammation in African children. DESIGN: In a 6-mo, randomized, double-blind, controlled trial, 6-14-y-old Ivorian children (n = 139) received iron-fortified biscuits, which contained 20 mg Fe/d, 4 times/wk as electrolytic iron or nonfortifoed biscuits. We measured changes in hemoglobin concentrations, inflammation, iron status, helminths, diarrhea, fecal calprotectin concentrations, and microbiota diversity and composition (n = 60) and the prevalence of selected enteropathogens. RESULTS: At baseline, there were greater numbers of fecal enterobacteria than of lactobacilli and bifidobacteria (P < 0.02). Iron fortification was ineffective; there were no differences in iron status, anemia, or hookworm prevalence at 6 mo. The fecal microbiota was modified by iron fortification as shown by a significant increase in profile dissimilarity (P < 0.0001) in the iron group as compared with the control group. There was a significant increase in the number of enterobacteria (P < 0.005) and a decrease in lactobacilli (P < 0.0001) in the iron group after 6 mo. In the iron group, there was an increase in the mean fecal calprotectin concentration (P < 0.01), which is a marker of gut inflammation, that correlated with the increase in fecal enterobacteria (P < 0.05). CONCLUSIONS: Anemic African children carry an unfavorable ratio of fecal enterobacteria to bifidobacteria and lactobacilli, which is increased by iron fortification. Thus, iron fortification in this population produces a potentially more pathogenic gut microbiota profile, and this profile is associated with increased gut inflammation. This trial was registered at controlled-trials.com as ISRCTN21782274

Iron supplementation promotes gut microbiota metabolic activity but not colitis markers in human gut microbiota-associated rats

The global prevalence of Fe deficiency is high and a common corrective strategy is oral Fe supplementation, which may affect the commensal gut microbiota and gastrointestinal health. The aim of the present study was to investigate the impact of different dietary Fe concentrations on the gut microbiota and gut health of rats inoculated with human faecal microbiota. Rats (8 weeks old, n 40) were divided into five (n 8 each) groups and fed diets differing only in Fe concentration during an Fe-depletion period (12 weeks) and an Fe-repletion period (4 weeks) as follows: (1) Fe-sufficient diet throughout the study period; (2) Fe-sufficient diet followed by 70mg Fe/kg diet; (3) Fe-depleted diet throughout the study period; (4) Fe-depleted diet followed by 35mg Fe/kg diet; (5) Fe-depleted diet followed by 70mg Fe/kg diet. Faecal and caecal samples were analysed for gut microbiota composition (quantitative PCR and pyrosequencing) and bacterial metabolites (HPLC), and intestinal tissue samples were investigated histologically. Fe depletion did not significantly alter dominant populations of the gut microbiota and did not induce Fe-deficiency anaemia in the studied rats. Provision of the 35mg Fe/kg diet after feeding an Fe-deficient diet significantly increased the abundance of dominant bacterial groups such as Bacteroides spp. and Clostridium cluster IV members compared with that of an Fe-deficient diet. Fe supplementation increased gut microbial butyrate concentration 6-fold compared with Fe depletion and did not affect histological colitis scores. The present results suggest that Fe supplementation enhances the concentration of beneficial gut microbiota metabolites and thus may contribute to gut healt