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Extensive bowel resection can lead to short bowel syndrome and intestinal failure. Resection-induced dysbiosis may be related to the specific anatomic site of resection and influences the disease progression. Although patients with end-jejunostomy are at high risk for intestinal failure, preservation of the ileocecal valve and colon counteracts this risk. The present study investigated the role of the cecum in maintaining microbial homeostasis after different types of small bowel resection. Male C57BL6/J mice were anesthetized by intraperitoneal injection of ketamine-xylazine and received extended ileocecal resection (extended ICR), limited ileocecal resection (limited ICR), or mid-small bowel resection (SBR). Stool samples were collected before surgery and between postoperative days 2-7, for 16S rRNA gene sequencing. Only extended ICR, but neither limited ICR nor SBR, induced intestinal insufficiency. α-Diversity was reduced in both ICR variants but not after SBR. All resections resulted in an increase in Proteobacteria. Pathobionts, such as Clostridia, Shigella, and Enterococcus, increased after SBR while Muribaculaceae, Lactobacillus, and Lachnospiraceae decreased. Limited ICR resulted in an increase of members of the Clostridium sensu stricto group, Terrisporobacter and Enterococcus and a decrease of Muribaculaceae. The increase of Enterococcus was even more pronounced after extended ICR while Muribaculaceae and Akkermansia were dramatically reduced. Both ICR variants caused a decrease in steroid biosynthesis and glycosaminoglycan degradation-associated pathways, suggesting altered bile acid transformation and mucus utilization.NEW & NOTEWORTHY Resection-induced dysbiosis affects disease progression in patients with short bowel syndrome. Severe dysbiosis occurs after removal of the ileocecal valve, even in the absence of short bowel conditions, and is associated with the loss of Muribaculaceae and Akkermansia and an increase of Clostridium and Enterococcus. The preservation of the cecum should be considered in surgical therapy, and dysbiosis should be targeted based on its specific anatomical signature to improve postoperative bacterial colonization.
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Insuficiência Intestinal , Síndrome do Intestino Curto , Camundongos , Masculino , Animais , Síndrome do Intestino Curto/metabolismo , Disbiose , RNA Ribossômico 16S/genética , Camundongos Endogâmicos ICR , EnterococcusRESUMO
Despite gradual progress over the past decades, the simulation of progressive damage in composite laminates remains a challenging task, in part due to inherent uncertainties of material properties. This paper combines three computational methods - finite element analysis (FEA), machine learning and Markov Chain Monte Carlo - to estimate the probability density of FEA input parameters while accounting for the variation of mechanical properties. First, 15,000 FEA simulations of open-hole tension tests are carried out with randomly varying input parameters by applying continuum damage mechanics material models. This synthetically-generated data is then used to train and validate a neural network consisting of five hidden layers and 32 nodes per layer to develop a highly efficient surrogate model. With this surrogate model and the incorporation of statistical test data from experiments, the application of Markov Chain Monte Carlo algorithms enables Bayesian parameter estimation to learn the probability density of input parameters for the simulation of progressive damage evolution in fibre reinforced composites. This methodology is validated against various open-hole tension test geometries enabling the determination of virtual design allowables.
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The interaction of bacteria and archaea with electrodes is a relatively new research field which spans from fundamental to applied research and influences interdisciplinary research in the fields of microbiology, biochemistry, biotechnology as well as process engineering. Although a substantial understanding of electron transfer processes between microbes and anodes and between microbes and cathodes has been achieved in mesophilic organisms, the mechanisms used by microbes under extremophilic conditions are still in the early stages of discovery. Here, we review our current knowledge on the biochemical solutions that evolved for the interaction of extremophilic organisms with electrodes. To this end, the available knowledge on pure cultures of extremophilic microorganisms has been compiled and the study has been extended with the help of bioinformatic analyses on the potential distribution of different electron transfer mechanisms in extremophilic microorganisms.
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Extremófilos , Archaea , Eletrodos , Transporte de Elétrons , ElétronsRESUMO
INTRODUCTION: Cholestatic liver disease (CLD) is associated with intestinal barrier dysfunction. The peptide hormone ghrelin may exert both hepatoprotective and barrier-strengthening effects. Here, we have evaluated these effects under the conditions of experimental cholestasis. METHODS: C57BL/6J mice with bile duct ligation (BDL) or sham surgery were treated with ghrelin or solvent for 9 days. Liver injury was assessed by histological and laboratory analyses. Paracellular macromolecule permeability and transmural electrical resistance (TMER) of colonic tissues were measured using a Ussing chamber. Expression of tight junction (TJ) genes was quantified by real-time PCR. Amplicon metagenomic sequencing was employed to analyze bacterial 16S rRNA from colonic stool samples. RESULTS: Mice with BDL exhibited weight loss and signs of severe liver injury. These changes were unaffected by ghrelin treatment. FITC-4-kDa-dextran flux was increased and TMER decreased after BDL. Treatment with ghrelin tended to reduce these effects. Furthermore, application of ghrelin was associated with higher mRNA levels of claudin-4, occludin, and ZO-1 in colonic tissues of mice with BDL. Reduced alpha-diversity of the microbiome was observed in solvent-treated mice with BDL but not in ghrelin-treated animals. CONCLUSION: Ghrelin treatment did not improve weight loss and liver damage but increased gene expression of colonic TJ proteins and restored the alpha-diversity of the microbiome. Since protective effects of ghrelin might be masked by the severity of the model, we suggest follow-up studies in models of milder CLD.
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Colestase , Microbiota , Camundongos , Animais , Grelina/farmacologia , Grelina/uso terapêutico , Camundongos Endogâmicos C57BL , RNA Ribossômico 16S/genética , Ductos Biliares/cirurgia , Colestase/microbiologia , Colestase/patologia , Fígado/patologia , Redução de Peso , Solventes , Modelos Animais de DoençasRESUMO
Muscle wasting represents a constant pathological feature of common chronic gastrointestinal diseases, including liver cirrhosis (LC), inflammatory bowel diseases (IBD), chronic pancreatitis (CP) and pancreatic cancer (PC), and is associated with increased morbidity and mortality. Recent clinical and experimental studies point to the existence of a gut-skeletal muscle axis that is constituted by specific gut-derived mediators which activate pro- and anti-sarcopenic signalling pathways in skeletal muscle cells. A pathophysiological link between both organs is also provided by low-grade systemic inflammation. Animal models of LC, IBD, CP and PC represent an important resource for mechanistic and preclinical studies on disease-associated muscle wasting. They are also required to test and validate specific anti-sarcopenic therapies prior to clinical application. In this article, we review frequently used rodent models of muscle wasting in the context of chronic gastrointestinal diseases, survey their specific advantages and limitations and discuss possibilities for further research activities in the field. We conclude that animal models of LC-, IBD- and PC-associated sarcopenia are an essential supplement to clinical studies because they may provide additional mechanistic insights and help to identify molecular targets for therapeutic interventions in humans.
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Gastroenteropatias/patologia , Músculo Esquelético/patologia , Atrofia Muscular/patologia , Animais , Doença Crônica , Humanos , Transdução de Sinais/fisiologiaRESUMO
DRA (downregulated in adenoma, SLC26A3) and NHE3 (Na+/H+ exchanger 3, SLC9A3) together mediate intestinal electroneutral NaCl absorption. Both transporters contain PDZ (postsynaptic density 95, disc large, zonula occludens 1) binding motifs and interact with PDZ adaptor proteins regulating their activity and recycling. SNX27 (sorting nexin 27) contains a PDZ domain and is involved in the recycling of cargo proteins including NHE3. The interaction of SNX27 with DRA and its potential role for the activity and recycling of DRA have been evaluated in this study. SNX27 specifically interacts with DRA via its PDZ domain. The knockdown (KD) of SNX27 reduced DRA activity by 50% but was not accompanied by a decrease of DRA surface expression. This indicates that DRA is trafficked to specific functional domains in the plasma membrane in which DRA is particularly active. Consistently, the disruption of lipid raft integrity by methyl-ß-cyclodextrin has an inhibitory effect on DRA activity that was strongly reduced after SNX27 KD. In differentiated intestinal Caco2 cells, superresolution microscopy and a novel quantitative axial approach revealed that DRA and SNX27 colocalize in rab5-positive early endosomes at the apical pole. SNX27 regulates the activity of DRA in the apical plasma membrane through binding with its PDZ domain. This interaction occurs in rab5-positive early endosomes at the apical pole of differentiated intestinal Caco2 cells. SNX27 is involved in the direct recycling of DRA to the plasma membrane where it is inserted into lipid rafts facilitating increased activity.NEW & NOTEWORTHY SNX27 has a PDZ domain and is involved in the regulation and recycling of transmembrane proteins. The role of SNX27 on the activity and recycling of the intestinal Cl-/HCO3- exchanger DRA has not yet been studied. This study shows that SNX27 directly interacts with DRA in early endosomes at the apical pole of intestinal Caco2 cells and mediates its direct recycling to facilitate high activity in lipid rafts in the apical plasma membrane.
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Polaridade Celular , Antiportadores de Cloreto-Bicarbonato/metabolismo , Endossomos/metabolismo , Células Epiteliais/metabolismo , Mucosa Intestinal/metabolismo , Nexinas de Classificação/metabolismo , Transportadores de Sulfato/metabolismo , Células CACO-2 , Antiportadores de Cloreto-Bicarbonato/genética , Humanos , Microdomínios da Membrana/metabolismo , Domínios PDZ , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Transporte Proteico , Nexinas de Classificação/genética , Transportadores de Sulfato/genética , Proteínas rab5 de Ligação ao GTP/metabolismoRESUMO
BACKGROUND: In short bowel syndrome, epithelial surface loss results in impaired nutrient absorption and may lead to intestinal insufficiency or intestinal failure. Nucleotide oligomerization domain 2 (Nod2) dysfunction predisposes to the development of intestinal failure after intestinal resection and is associated with intestinal barrier defects. Epithelial barrier function is crucial for intestinal absorption and for intestinal adaptation in the short bowel situation. AIMS: The aim of the study was to characterize the effects of the GLP-2 analogue Teduglutide in the small intestine in the presence and absence of Nod2 in a mouse model of short bowel syndrome. METHODS: Mice underwent 40% ICR and were thereafter treated with Teduglutide versus vehicle injections. Survival, body weight, stool water, and sodium content and plasma aldosterone concentrations were determined. Intestinal and kidney tissue was examined with light and fluorescence microscopy, Ussing chamber studies and quantitative PCR in wild type and transgenic mice. RESULTS: Teduglutide reduced intestinal failure incidence in Nod2 k.o. mice. In wt mice, Teduglutide attenuated intestinal insufficiency as indicated by reduced body weight loss and lower plasma aldosterone concentrations, lower stool water content, and lower stool sodium losses. Teduglutide treatment was associated with enhanced epithelial paracellular pore function and enhanced claudin-10 expression in tight junctions in the villus tips, where it colocalized with sodium-glucose cotransporter 1 (SGLT-1), which mediates Na-coupled glucose transport. CONCLUSIONS: In the SBS situation, Teduglutide not only maximizes small intestinal mucosal hypertrophy but also partially restores small intestinal epithelial function through an altered distribution of claudin-10, facilitating sodium recirculation for Na-coupled glucose transport and water absorption.
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Proteína Adaptadora de Sinalização NOD2/metabolismo , Peptídeos/farmacologia , Síndrome do Intestino Curto/metabolismo , Animais , Modelos Animais de Doenças , Fármacos Gastrointestinais/farmacologia , Peptídeo 2 Semelhante ao Glucagon/metabolismo , Absorção Intestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Junções Íntimas/metabolismoRESUMO
Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) gene mutations are a risk factor for Crohn's disease and also associated with worse outcome in short bowel syndrome (SBS) patients independent of the underlying disease. The aim of this study was to analyze the effect of Nod2 deficiency on barrier function and stool microbiome after extensive ileocecal resection in mice. Male C57BL6/J wild-type (WT) and Nod2-knockout (KO) mice underwent 40% ileocecal resection. Sham control mice received simple transection of the ileum. Clinical outcome was monitored daily. Barrier function was measured with Ussing chambers using FITC-4-kDa-Dextran flux, transmucosal electrical resistance, and dilution potentials. Immunofluorescence of claudin-2 was studied. Composition of the stool microbiome was assessed by 16S rRNA gene sequencing. Resected Nod2-KO mice had impaired clinical outcome compared with resected WT mice. This was accompanied by increased stool water contents and increased plasma aldosterone. Histomorphological adaptation was independent of Nod2. Barrier function studies revealed impaired sodium to chloride permeability and altered claudin-2 localization in the absence of Nod2. Resection induced decreases of bacterial diversity and a shift of bacteriodetes-to-firmicutes ratios. Ileum and cecum resection-induced increase in proteobacteria was absent in Nod2-deficient mice. Verrucomicrobia were temporarily increased in Nod2-KO mice. Nod2 deficiency functionally impairs adaptation to short bowel syndrome via a lesser increase of epithelial sodium pore permeability, altered epithelial barrier function, and the microbiome.NEW & NOTEWORTHYNOD2 gene mutations are associated with the development of severe short bowel syndrome and intestinal failure. The influence of Nod2 mutations on intestinal adaptation in experimental short bowel syndrome has not been studied yet. Here, we provide data that Nod2 deficiency worsens clinical outcome and functional adaptation under SBS conditions in mice, indicating that NOD2 is required for successful adaptation after ileocecal resection.
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Adaptação Fisiológica , Absorção Intestinal , Mucosa Intestinal/metabolismo , Proteína Adaptadora de Sinalização NOD2/genética , Síndrome do Intestino Curto/genética , Aldosterona/metabolismo , Animais , Cloretos/metabolismo , Condutividade Elétrica , Microbioma Gastrointestinal , Íleo/metabolismo , Íleo/microbiologia , Transporte de Íons , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína Adaptadora de Sinalização NOD2/deficiência , Síndrome do Intestino Curto/metabolismo , Síndrome do Intestino Curto/fisiopatologia , Sódio/metabolismoRESUMO
BACKGROUND: Short bowel syndrome results from extensive small bowel resection and induces adaptation of the remaining intestine. Ileocecal resection (ICR) is the most frequent situation in humans. Villus hypertrophy is one hallmark of mucosal adaptation, but the functional mechanisms of mucosal adaptation are incompletely understood. AIMS: The aim of the study was to characterize a clinically relevant model of short bowel syndrome but not intestinal failure in mice and to identify outcome predictors and mechanisms of adaptation. METHODS: Male C57BL6/J mice underwent 40% ICR and were followed for 7 or 14 days. Small bowel transection served as control. All mice underwent autopsy. Survival, body weight, wellness score, stool water content, plasma aldosterone concentrations, and paracellular permeability were recorded. RESULTS: Unlike controls, resected mice developed significant diarrhea with increased stool water. This was accompanied by sustained weight loss throughout follow-up. Villus length increased but did not correlate positively with adaptation. Plasma aldosterone concentrations correlated inversely with body weight at day 14. After ICR, intestinal epithelial (i.e., tight junctional) sodium permeability was increased. CONCLUSIONS: 40% ICR results in moderate to severe short bowel syndrome. Successful adaptation to the short bowel situation involves villus elongation but does not correlate with the degree of villus elongation alone. In addition, increased intestinal epithelial sodium permeability facilitates sodium-coupled solute transport. Hyperaldosteronism correlates with the severity of weight loss, indicates volume depletion, and counterregulates water loss.
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Modelos Animais de Doenças , Hiperaldosteronismo/metabolismo , Mucosa Intestinal/metabolismo , Síndrome do Intestino Curto/metabolismo , Sódio/metabolismo , Animais , Hiperaldosteronismo/patologia , Mucosa Intestinal/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Técnicas de Cultura de Órgãos , Distribuição Aleatória , Síndrome do Intestino Curto/patologiaRESUMO
Chromate is one of the major anthropogenic contaminants on Earth. Leucobacter chromiiresistens is a highly chromate-resistant strain, tolerating chromate concentrations in LB medium of up to 400 mM. In response to chromate stress, L. chromiiresistens forms biofilms, which are held together via extracellular DNA. Inhibition of biofilm formation leads to drastically decreased chromate tolerance. Moreover, chromate is reduced intracellularly to the less-toxic Cr(III). The oxidation status and localization of chromium in cell aggregates were analyzed by energy-dispersive X-ray spectroscopy coupled to scanning transmission electron microscopy and X-ray absorption spectroscopy measurements. Most of the heavy metal is localized as Cr(III) at the cytoplasmic membrane. As a new cellular response to chromate stress, we observed an increased production of the carotenoid lutein. Carotenoid production could increase membrane stability and reduce the concentration of reactive oxygen species. Bioinformatic analysis of the L. chromiiresistens genome revealed several gene clusters that could enable heavy-metal resistance. The extreme chromate tolerance and the unique set of resistance factors suggest the use of L. chromiiresistens as a new model organism to study microbial chromate resistance.IMPORTANCE Chromate is a highly toxic oxyanion. Extensive industrial use and inadequate waste management has caused the toxic pollution of several field sites. Understanding the chromate resistance mechanisms that enable organisms to thrive under these conditions is fundamental to develop (micro)biological strategies and applications aiming at bioremediation of contaminated soils or waters. Potential detoxifying microorganisms are often not sufficient in their resistance characteristics to effectively perform, e.g., chromate reduction or biosorption. In this study, we describe the manifold strategies of L. chromiiresistens to establish an extremely high level of chromate resistance. The multitude of mechanisms conferring it make this organism suitable for consideration as a new model organism to study chromate resistance.
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Actinomycetales/metabolismo , Cromatos/metabolismo , Actinomycetales/genética , Biodegradação Ambiental , Membrana Celular/genética , Membrana Celular/metabolismo , Cromo/metabolismo , Oxirredução , Espectroscopia por Absorção de Raios XRESUMO
A Gram-stain-positive, rod-shaped, non-motile, spore-forming bacterium, strain EA-1T, was isolated from hydrothermal sediment samples from the Azores (São Miguel, Portugal). 16S rRNA gene sequence analysis of the isolated bacterium revealed a phylogenetic affiliation with the genus Kyrpidia. The sequence similarity of the five 16S rRNA gene copies to its closest relative, Kyrpidia tusciae, ranged from 97.79 to 97.85â%. The in silico estimate of DNA-DNA hybridization was 56.0â%. The dominant fatty acids of the novel isolate were anteiso-C17â:â0 (49.9â%), iso-C17â:â0 (23.0â%) and iso-C16â:â0 (13.3â%), while the quinone detected was menaquinone MK-7. Analysis of polar lipids identified phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine and additional unidentified compounds comprising two glycolipids, two phospholipids and two lipids. The presence of meso-diaminopimelic acid in the peptidoglycan and mannose, arabinose and ribose in the cell wall of strain EA-1T were detected. The strain was able to grow heterotrophically as well as autotrophically with carbon dioxide as the sole carbon source and with hydrogen and oxygen as electron donor and acceptor, respectively. Based on its chemotaxonomic, physiological and genomic characteristics, the new strain is considered to represent a novel species within the genus Kyrpidia, for which the name Kyrpidiaspormannii sp. nov. is proposed. The type strain is strain EA-1T (=DSM 106492T=CCOS1194T).
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Bacillales/classificação , Sedimentos Geológicos/microbiologia , Fontes Hidrotermais/microbiologia , Filogenia , Açores , Bacillales/genética , Bacillales/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , Parede Celular/química , DNA Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Graxos/química , Glicolipídeos/química , Hibridização de Ácido Nucleico , Peptidoglicano/química , Fosfolipídeos/química , Portugal , RNA Ribossômico 16S/genética , Análise de Sequência de DNARESUMO
The first enantioselective total synthesis of natural dicerandrolâ C (1 c) as its enantiomer containing a dimeric tetrahydroxanthenone skeleton is described starting from the enantiopure chromane 6 which was obtained through a Wacker-type cyclization with >99 % ee. For the formation of the dimeric skeleton a palladium-catalyzed Suzuki reaction was used. The synthesis allowed the confirmation of the absolute configuration of the dicerandrols.
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Xantonas/química , Xantonas/síntese química , Catálise , Ciclização , Dimerização , Paládio/química , Estereoisomerismo , Xantenos/químicaRESUMO
The first enantioselective synthesis of a secalonic acid containing a dimeric tetrahydroxanthenone skeleton is described, using a Wacker-type cyclization of a methoxyphenolic compound to form a chiral chroman with a quaternary carbon stereogenic center with >99% ee. Further steps are a Sharpless dihydroxylation and a Dieckmann condensation to give a tetrahydroxanthenone. A late-stage one-pot palladium-catalyzed Suzuki-dimerization reaction leads to the 2,2'-biphenol linkage to complete the enantioselective total synthesis of secalonic acid E in 18â steps with 8% overall yield.
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Fibre-reinforced polymers (FRPs) are widely used in industry due to their impressive strength-to-weight ratio, corrosion resistance and high durability. One of the primary components of FRPs is synthetic resins, specifically epoxy, which has been identified as harmful to the environment. To address this concern, an eco-friendly alternative made from basalt fibres and bio resin has the potential to reduce the environmental impact. This study investigates Basalt Fibre-Reinforced Polymer (BFRP) laminates manufactured using two bio resins, AMPRO™ BIO and Change Climate, comparing them to one conventional epoxy resin, WEST SYSTEM®, in terms of tensile modulus, strength and fracture toughness, as well as shear properties. The results indicate that BFRP laminates made with bio resins exhibit comparable or better mechanical properties to their conventional counterparts with tensile strength being between 6 and 17% more in bio resins compared to the conventional resin, thereby paving the way for further exploration of sustainable FRP laminates in future engineering applications.
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OBJECTIVES: The gut-liver axis is discussed to play an important role in hepatic cirrhosis. Decompensated liver cirrhosis is associated with portal hypertension, which can lead to a variety of complications. Transjugular intrahepatic portosystemic shunt (TIPS) is an established treatment option for the complications of portal hypertension. In this study we focused on the effect of TIPS on intestinal microbial composition in cirrhotic patients. METHODS: Thirty patients with liver cirrhosis were compared to 18 healthy adults. Seventeen patients with cirrhosis and portal hypertension received a TIPS. Clinical characteristics, including age, sex, and liver function measured with a Child-Pugh score and model for end-stage liver disease score, were obtained. Intestinal microbial composition was assessed via 16S rRNA gene amplicon sequencing from stool probes before and after TIPS. RESULTS: TIPS led to a reduction of hepatic venous pressure gradient. However, TIPS did not cause a shift in the intestinal bacterial communities. Independent from the application of TIPS, antibiotic therapy was associated with a significant difference in the intestinal bacterial microbiota and also a reduced α-diversity. In addition, a significant difference was observed in the intestinal bacterial composition between patients with liver cirrhosis and healthy controls. CONCLUSION: The presence of liver cirrhosis and the use of antibiotic therapy, but not the application of TIPS, were associated with a significant shift of the intestinal bacterial communities, showing a high impact on the microbiota of patients with liver cirrhosis.
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Antibacterianos , Microbioma Gastrointestinal , Hipertensão Portal , Cirrose Hepática , Derivação Portossistêmica Transjugular Intra-Hepática , Humanos , Cirrose Hepática/microbiologia , Cirrose Hepática/complicações , Feminino , Masculino , Microbioma Gastrointestinal/fisiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Antibacterianos/uso terapêutico , Hipertensão Portal/etiologia , Idoso , Adulto , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/análise , Estudos de Casos e Controles , Fezes/microbiologiaRESUMO
Blennolideâ A can be synthesized through an enantioselective domino-Wacker/carbonylation/methoxylation reaction of 7a with 96 % ee and an enantioselective Wacker oxidation of 7b with 89 % ee. Further transformations led to the α,ß-unsaturated ester (E)-17, which was subjected to a highly selective Michael addition, introducing a methyl group to give 18a. After a threefold oxidation and an intramolecular acylation, the tetrahydroxanthenone 4 was obtained, which could be transformed into (-)-blennolideâ A (ent-1) in a few steps.
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Produtos Biológicos/síntese química , Xantonas/síntese química , Produtos Biológicos/química , Catálise , Fungos/química , Fungos/metabolismo , Oxirredução , Paládio/química , Estereoisomerismo , Xantonas/químicaRESUMO
For the synthesis of (-)-diversonol (ent-1), an enantioselective domino-Wacker/carbonylation/methoxylation reaction and an enantioselective Wacker oxidation were used to give the chroman in high yield and 96% and 93% ee, respectively. Dihydroxylation at the vinyl moiety using the Sharpless procedure and a Wittig-Horner reaction followed by hydrogenation, benzylic oxidation, and an intramolecular acylation provided the tetrahydroxanthenone, from which ent-1 is accessible in a few steps. Furthermore, the synthesis of the diastereomeric diversonol rac-1,9a-epi-diversonol (rac-41) is also described.
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Xantonas/síntese química , Hidrogenação , Estrutura Molecular , Oxirredução , Paládio/química , Resorcinóis/química , Estereoisomerismo , Xantonas/químicaRESUMO
Microbial water quality is routinely examined using the fecal indicator bacteria Escherichia coli, coliform bacteria and enterococci. Several practical cases in German drinking water distribution systems indicated invertebrates such as insects or gastropods as a source for the microbiological deterioration. Therefore, we examined three genera of Gastropoda (Arion, Helix and Cepaea) for the presence of fecal indictor bacteria in excreta using standard methods. Enterococci and coliform bacteria were detected in high concentrations (mean values of 1.5 × 106 and 6.3 × 106 per gram feces, respectively). E. coli was also detected, still specification revealed that what was assigned by standard ISO-methods to be E. coli was indeed a novel species of Buttiauxella, exhibiting ß-D-glucuronidase activity, thus, explaining the false-positive results. Microbiome analyses confirmed the cultural results. Enterobacteriaceae were dominant in the samples, yet only very few sequences could be assigned to Escherichia. Our study suggests, that enterococci and coliform bacteria are an integral component in the gastropod microbiome, whereas E. coli might be derived from other sources with gastropods being a vector. The results further indicate, that the current concept of fecal indicator bacteria needs to be extended, as not only humans and homeothermic animals could be a source for fecal indictor bacteria, but also gastropods need to be taken into consideration.
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Água Potável , Escherichia coli , Animais , Humanos , Microbiologia da Água , Bactérias , Enterobacteriaceae , Enterococcus , Fezes/microbiologia , Monitoramento AmbientalRESUMO
Ileocecal resection (ICR) is frequently performed in Crohn's disease (CD). NOD2 mutations are risk factors for CD. Nod2 knockout (ko) mice show impaired anastomotic healing after extended ICR. We further investigated the role of NOD2 after limited ICR. C57B16/J (wt) and Nod2 ko littermates underwent limited ICR including 1-2 cm terminal ileum and were randomly assigned to vehicle or MDP treatment. Bursting pressure was measured on POD 5, and the anastomosis was analyzed for matrix turn-over and granulation tissue. Wound fibroblasts from subcutaneously implanted sponges were used for comparison. The M1/M2 macrophage plasma cytokines were analyzed. Mortality was not different between groups. Bursting pressure was significantly decreased in ko mice. This was associated with less granulation tissue but was not affected by MDP. However, anastomotic leak (AL) rate tended to be lower in MDP-treated ko mice (29% vs. 11%, p = 0.07). mRNA expression of collagen-1α (col1 α), collagen-3α (col3 α), matrix metalloproteinase (mmp)2 and mmp9 was increased in ko mice, indicating increased matrix turn-over, specifically in the anastomosis. Systemic TNF-α expression was significantly lower in ko mice. Ileocolonic healing is impaired in Nod2 ko mice after limited ICR by local mechanisms maybe including local dysbiosis.
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We report the case of a 74-year-old female with abdominal pain, tarry stools, and tachycardia. Previous history included diabetes mellitus with micro- and macroangiopathy. Imaging revealed portal gas, left sided colitis, and emphysematous gastritis, besides severe atherosclerosis with subtotal celiac trunk occlusion and moderate stenosis of the inferior mesenteric artery. Upper endoscopy revealed findings consistent with focal necrotizing gastritis at the greater curvature and acute esophageal necrosis. Blood cultures immediately grew Clostridium perfringens. The patient was treated with broad spectrum antibiotics and was discharged after 21 days in the hospital. This case demonstrates the rare coincident occurrence of nontransmural ischemia of the left colon, the esophagus, and the stomach as a result of low-flow circulatory compromise, which then precipitated C. perfringens associated emphysematous gastritis and blood stream infection.