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排序方式: 共有1189条查询结果,搜索用时 31 毫秒
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Marcus May Sandor Batkai Alexander A. Zoerner Dimitrios Tsikas Jens Jordan Stefan Engeli 《PloS one》2013,8(4)
Microdialysis sampling of lipophilic molecules in human tissues is challenging because protein binding and adhesion to the membrane limit recovery. Hydroxypropyl-ß-cyclodextrin (HP-ß-CD) forms complexes with hydrophobic molecules thereby improving microdialysis recovery of lipophilic molecules in vitro and in rodents. We tested the approach in human subjects. First, we determined HP-ß-CD influences on metabolite stability, delivery, and recovery in vitro. Then, we evaluated HP-ß-CD as microdialysis perfusion fluid supplement in 20 healthy volunteers. We placed 20 kDa microdialysis catheters in subcutaneous abdominal adipose tissue and in the vastus lateralis muscle. We perfused catheters with lactate free Ringer solution with or without 10% HP-ß-CD at flow rates of 0.3–2.0 µl/min. We assessed tissue metabolites, ultrafiltration effects, and blood flow. In both tissues, metabolite concentrations with Ringer+HP-ß-CD perfusate were equal or higher compared to Ringer alone. Addition of HP-ß-CD increased dialysate volume by 10%. Adverse local or systemic reactions to HP-ß-CD did not occur and analytical methods were not disturbed. HP-ß-CD addition allowed to measure interstitial anandamide concentrations, a highly lipophilic endogenous molecule. Our findings suggest that HP-ß-CD is a suitable supplement in clinical microdialysis to enhance recovery of lipophilic molecules from human interstitial fluid. 相似文献
23.
Alexandra V. Stavropoulou Florentia Fostira Maroulio Pertesi Marianthi Tsitlaidou Gerassimos E. Voutsinas Olga Triantafyllidou Aristotelis Bamias Meletios A. Dimopoulos Eleni Timotheadou Dimitrios Pectasides Christos Christodoulou George Klouvas Christos Papadimitriou Thomas Makatsoris George Pentheroudakis Gerasimos Aravantinos Vassilis Karydakis Drakoulis Yannoukakos George Fountzilas Irene Konstantopoulou 《PloS one》2013,8(3)
Germline mutations in the BRCA1 and BRCA2 genes contribute to approximately 18% of hereditary ovarian cancers conferring an estimated lifetime risk from 15% to 50%. A variable incidence of mutations has been reported for these genes in ovarian cancer cases from different populations. In Greece, six mutations in BRCA1 account for 63% of all mutations detected in both BRCA1 and BRCA2 genes. This study aimed to determine the prevalence of BRCA1 mutations in a Greek cohort of 106 familial ovarian cancer patients that had strong family history or metachronous breast cancer and 592 sporadic ovarian cancer cases. All 698 patients were screened for the six recurrent Greek mutations (including founder mutations c.5266dupC, p.G1738R and the three large deletions of exon 20, exons 23–24 and exon 24). In familial cases, the BRCA1 gene was consequently screened for exons 5, 11, 12, 20, 21, 22, 23, 24. A deleterious BRCA1 mutation was found in 43/106 (40.6%) of familial cancer cases and in 27/592 (4.6%) of sporadic cases. The variant of unknown clinical significance p.V1833M was identified in 9/698 patients (1.3%). The majority of BRCA1 carriers (71.2%) presented a high-grade serous phenotype. Identifying a mutation in the BRCA1 gene among breast and/or ovarian cancer families is important, as it enables carriers to take preventive measures. All ovarian cancer patients with a serous phenotype should be considered for genetic testing. Further studies are warranted to determine the prevalence of mutations in the rest of the BRCA1 gene, in the BRCA2 gene, and other novel predisposing genes for breast and ovarian cancer. 相似文献
24.
Melpomeni Peppa Chrysi Koliaki Athanasios Papaefstathiou Efstathios Garoflos Nicholas Katsilambros Sotirios A. Raptis Dimitrios I. Hadjidakis George D. Dimitriadis 《Obesity (Silver Spring, Md.)》2013,21(9):1807-1814
Objective : Although obesity is typically associated with increased cardiovascular risk, a subset of obese individuals display a normal metabolic profile (“metabolically healthy obese,” MHO) and conversely, a subset of nonobese subjects present with obesity‐associated cardiometabolic abnormalities (“metabolically obese nonobese,” MONO). The aim of this cross‐sectional study was to identify the most important body composition determinants of metabolic phenotypes of obesity in nonobese and obese healthy postmenopausal women. Design and Methods : We studied a total of 150 postmenopausal women (age 54 ± 7 years, mean ± 1 SD). Based on a cardiometabolic risk score, nonobese (body mass index [BMI] ≤ 27) and obese women (BMI > 27) were classified into “metabolically healthy” and “unhealthy” phenotypes. Total and regional body composition was assessed with dual‐energy X‐ray absorptiometry (DXA). Results : In both obese and nonobese groups, the “unhealthy” phenotypes were characterized by frequent bodyweight fluctuations, higher biochemical markers of insulin resistance, hepatic steatosis and inflammation, and higher anthropometric and DXA‐derived indices of central adiposity, compared with “healthy” phenotypes. Indices of total adiposity, peripheral fat distribution and lean body mass were not significantly different between “healthy” and “unhealthy” phenotypes. Despite having increased fat mass, MHO women exhibited comparable cardiometabolic parameters with healthy nonobese, and better glucose and lipid levels than MONO. Two DXA‐derived indices, trunk‐to‐legs and abdominal‐to‐gluteofemoral fat ratio were the major independent determinants of the “unhealthy” phenotypes in our cohort. Conclusions : The “metabolically obese phenotype” is associated with bodyweight variability, multiple cardiometabolic abnormalities and an excess of central relative to peripheral fat in postmenopausal women. DXA‐derived centrality ratios can discriminate effectively between metabolic subtypes of obesity in menopause. 相似文献
25.
Helmut D. Hummler Katharina Banke Marla R. Wolfson Giuseppe Buonocore Michael Ebsen Wolfgang Bernhard Dimitrios Tsikas Hans Fuchs 《PloS one》2016,11(2)
Background
Permissive hypercapnia has been shown to reduce lung injury in subjects with surfactant deficiency. Experimental studies suggest that hypercapnic acidosis by itself rather than decreased tidal volume may be a key protective factor.Objectives
To study the differential effects of a lung protective ventilatory strategy or hypercapnic acidosis on gas exchange, hemodynamics and lung injury in an animal model of surfactant deficiency.Methods
30 anesthetized, surfactant-depleted rabbits were mechanically ventilated (FiO2 = 0.8, PEEP = 7cmH2O) and randomized into three groups: Normoventilation-Normocapnia (NN)-group: tidal volume (Vt) = 7.5 ml/kg, target PaCO2 = 40 mmHg; Normoventilation-Hypercapnia (NH)-group: Vt = 7.5 ml/kg, target PaCO2 = 80 mmHg by increasing FiCO2; and a Hypoventilation-Hypercapnia (HH)-group: Vt = 4.5 ml/kg, target PaCO2 = 80 mmHg. Plasma lactate and interleukin (IL)-8 were measured every 2 h. Animals were sacrificed after 6 h to perform bronchoalveolar lavage (BAL), to measure lung wet-to-dry weight, lung tissue IL-8, and to obtain lung histology.Results
PaO2 was significantly higher in the HH-group compared to the NN-group (p<0.05), with values of the NH-group between the HH- and NN-groups. Other markers of lung injury (wet-dry-weight, BAL-Protein, histology-score, plasma-IL-8 and lung tissue IL-8) resulted in significantly lower values for the HH-group compared to the NN-group and trends for the NH-group towards lower values compared to the NN-group. Lactate was significantly lower in both hypercapnia groups compared to the NN-group.Conclusion
Whereas hypercapnic acidosis may have some beneficial effects, a significant effect on lung injury and systemic inflammatory response is dependent upon a lower tidal volume rather than resultant arterial CO2 tensions and pH alone. 相似文献26.
27.
Samantha L. van der Beek Azul Zorzoli Ebru anak Robert N. Chapman Kieron Lucas Benjamin H. Meyer Dimitrios Evangelopoulos Luiz Pedro S. de Carvalho Geert‐Jan Boons Helge C. Dorfmueller Nina M. van Sorge 《Molecular microbiology》2019,111(4):951-964
Biosynthesis of the nucleotide sugar precursor dTDP‐L‐rhamnose is critical for the viability and virulence of many human pathogenic bacteria, including Streptococcus pyogenes (Group A Streptococcus; GAS), Streptococcus mutans and Mycobacterium tuberculosis. Streptococcal pathogens require dTDP‐L‐rhamnose for the production of structurally similar rhamnose polysaccharides in their cell wall. Via heterologous expression in S. mutans, we confirmed that GAS RmlB and RmlC are critical for dTDP‐L‐rhamnose biosynthesis through their action as dTDP‐glucose‐4,6‐dehydratase and dTDP‐4‐keto‐6‐deoxyglucose‐3,5‐epimerase enzymes respectively. Complementation with GAS RmlB and RmlC containing specific point mutations corroborated the conservation of previous identified catalytic residues. Bio‐layer interferometry was used to identify and confirm inhibitory lead compounds that bind to GAS dTDP‐rhamnose biosynthesis enzymes RmlB, RmlC and GacA. One of the identified compounds, Ri03, inhibited growth of GAS, other rhamnose‐dependent streptococcal pathogens as well as M. tuberculosis with an IC50 of 120–410 µM. Importantly, we confirmed that Ri03 inhibited dTDP‐L‐rhamnose formation in a concentration‐dependent manner through a biochemical assay with recombinant rhamnose biosynthesis enzymes. We therefore conclude that inhibitors of dTDP‐L‐rhamnose biosynthesis, such as Ri03, affect streptococcal and mycobacterial viability and can serve as lead compounds for the development of a new class of antibiotics that targets dTDP‐rhamnose biosynthesis in pathogenic bacteria. 相似文献
28.
Silvia Ravera Sara Ferrando Dimitrios Agas Nicola De Angelis Mirco Raffetto Maria G. Sabbieti Antonio Signore Stefano Benedicenti Andrea Amaroli 《Journal of biophotonics》2019,12(9)
Photobiomodulation (PBM) is a non‐plant‐cell manipulation through a transfer of energy by means of light sources at the non‐ablative or thermal intensity. Authors showed that cytochrome‐c‐oxidase (complex IV) is the specific chromophore's target of PBM at the red (600‐700 nm) and NIR (760‐900 nm) wavelength regions. Recently, it was suggested that the infrared region of the spectrum could influence other chromospheres, despite the interaction by wavelengths higher than 900 nm with mitochondrial chromophores was not clearly demonstrated. We characterized the interaction between mitochondria respiratory chain, malate dehydrogenase, a key enzyme of Krebs cycle, and 3‐hydroxyacyl‐CoA dehydrogenase, an enzyme involved in the β‐oxidation (two mitochondrial matrix enzymes) with the 1064 nm Nd:YAG (100mps and 10 Hz frequency mode) irradiated at the average power density of 0.50, 0.75, 1.00, 1.25 and 1.50 W/cm2 to generate the respective fluences of 30, 45, 60, 75 and 90 J/cm2. Our results show the effect of laser light on the transmembrane mitochondrial complexes I, III, IV and V (adenosine triphosphate synthase) (window effects), but not on the extrinsic mitochondrial membrane complex II and mitochondria matrix enzymes. The effect is not due to macroscopical thermal change. An interaction of this wavelength with the Fe‐S proteins and Cu‐centers of respiratory complexes and with the water molecules could be supposed. 相似文献
29.
Weitz D Harder D Casagrande F Fotiadis D Obrdlik P Kelety B Daniel H 《The Journal of biological chemistry》2007,282(5):2832-2839
The ydgR gene of Escherichia coli encodes a protein of the proton-dependent oligopeptide transporter (POT) family. We cloned YdgR and overexpressed the His-tagged fusion protein in E. coli BL21 cells. Bacterial growth inhibition in the presence of the toxic phosphonopeptide alafosfalin established YgdR functionality. Transport was abolished in the presence of the proton ionophore carbonyl cyanide p-chlorophenylhydrazone, suggesting a proton-coupled transport mechanism. YdgR transports selectively only di- and tripeptides and structurally related peptidomimetics (such as aminocephalosporins) with a substrate recognition pattern almost identical to the mammalian peptide transporter PEPT1. The YdgR protein was purified to homogeneity from E. coli membranes. Blue native-polyacrylamide gel electrophoresis and transmission electron microscopy of detergent-solubilized YdgR suggest that it exists in monomeric form. Transmission electron microscopy revealed a crown-like structure with a diameter of approximately 8 nm and a central density. These are the first structural data obtained from a proton-dependent peptide transporter, and the YgdR protein seems an excellent model for studies on substrate and inhibitor interactions as well as on the molecular architecture of cell membrane peptide transporters. 相似文献
30.