Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plesiomonas shigelloides is a Gram-negative rod associated with episodes of intestinal infections and outbreaks of diarrhea in humans. The extraintestinal infections caused by this bacterium, for example, endopthalmitis, meningitidis, bacteremia, and septicemia, usually have gastrointestinal origin and serious course. The lipopolysaccharide (LPS, endotoxin) as virulence factor is important in enteropathogenicity of this bacterium. LPSs of P. shigelloides and especially their lipid A part, that is, the immunomodulatory center of LPS, have not been extensively investigated. The structure of P. shigelloides O54 lipid A was determined by chemical analysis combined with MALDI-TOF mass spectrometry, and the intact Kdo-containing core region was investigated by NMR spectroscopy on deacylated LPS. Products from alkaline deacylation of LPS, containing 4-substituted uronic acids, are usually very complex and difficult to separate. Since Kdo residues, like sialic acids, form complexes with serotonin, we used immobilized serotonin for one-step isolation of oligosaccharide containing the intact Kdo region from the reaction mixture by affinity chromatography. The major form of lipid A was built of beta-d-GlcpN4PPEtn-(1-->6)-alpha-d-GlcpN1P disaccharide substituted with 14:0(3-OH), 12:0(3-OH), 14:0(3-O-14:0), and 12:0(3-O-12:0) acyl groups at N-2, O-3, N-2', and O-3', respectively. This is a novel structure among known lipid A molecules. Analysis of intact Kdo-lipid A region, lipid A and its linkage with the core oligosaccharide completes the structural investigation of P. shigelloides O54 LPS, resolving the entire molecule. Biological activities and observed discrepancy between in vitro and in vivo activity of P. shigelloides and Escherichia coli LPS are discussed.
 ...
PMID:Structure of the lipid A-inner core region and biological activity of Plesiomonas shigelloides O54 (strain CNCTC 113/92) lipopolysaccharide. 1649 Jul 65

Burn trauma is a clinical condition accompanied by muscle wasting that severely impedes rehabilitation in burn survivors. Mitochondrial uncoupling protein 3 (UCP3) is uniformly expressed in myoskeletal mitochondria and its expression has been found to increase in other clinical syndromes that, like burn trauma, are associated with muscle wasting (e.g., starvation, fasting, cancer, sepsis). The aim of this study was to explore the effects of burn trauma on UCP3 expression, intramyocellular lipids, and plasma-free fatty acids. Mice were studied at 6 h, 1 d and 3 d after nonlethal hindlimb burn trauma. Intramyocellular lipids in hindlimb skeletal muscle samples collected from burned and normal mice were measured using 1H NMR spectroscopy on a Bruker 14.1 Tesla spectrometer at 4 degrees C. UCP3 mRNA and protein levels were also measured in these samples. Plasma-free fatty acids were measured in burned and normal mice. Local burn trauma was found to result in: 1) upregulation of UCP3 mRNA and protein expression in hindlimb myoskeletal mitochondria by 6 h postburn; 2) increased intramyocellular lipids; and 3) increased plasma-free fatty acids. Our findings show that the increase in UCP3 after burn trauma may be linked to burn-induced alterations in lipid metabolism. Such a link could reveal novel insights into how processes related to energy metabolism are controlled in burn and suggest that induction of UCP3 by burn in skeletal muscle is protective by either activating cellular redox signaling and/or mitochondrial uncoupling.
 ...
PMID:Uncoupling protein 3 expression and intramyocellular lipid accumulation by NMR following local burn trauma. 1708 30

High-mobility group box 1 protein (HMGB1) is a nuclear component, but extracellularly it serves as a signaling molecule involved in acute and chronic inflammation, for example in sepsis and arthritis. The identification of HMGB1 inhibitors is therefore of significant experimental and clinical interest. We show that glycyrrhizin, a natural anti-inflammatory and antiviral triterpene in clinical use, inhibits HMGB1 chemoattractant and mitogenic activities, and has a weak inhibitory effect on its intranuclear DNA-binding function. NMR and fluorescence studies indicate that glycyrrhizin binds directly to HMGB1 (K(d) approximately 150 microM), interacting with two shallow concave surfaces formed by the two arms of both HMG boxes. Our results explain in part the anti-inflammatory properties of glycyrrhizin, and might direct the design of new derivatives with improved HMGB1-binding properties.
 ...
PMID:Glycyrrhizin binds to high-mobility group box 1 protein and inhibits its cytokine activities. 1746 68

The inducible form of nitric oxide synthase (NOS2) plays an important role in sepsis incurred as a result of infection with Gram-negative bacteria that elaborate endotoxin. The HMGA1 (high-mobility group A1) architectural transcription factor facilitates NOS2 induction by binding a specific AT-rich Oct (octamer) sequence in the core NOS2 promoter via AT-hook motifs. The small-molecule MGB (minor-groove binder) netropsin selectively targets AT-rich DNA sequences and can interfere with transcription factor binding. We therefore hypothesized that netropsin would improve survival from murine endotoxaemia by attenuating NOS2 induction through interference with HMGA1 DNA binding to the core NOS2 promoter. Netropsin improved survival from endotoxaemia in wild-type mice, yet not in NOS2-deficient mice, supporting an important role for NOS2 in the beneficial effects of MGB administration. Netropsin significantly attenuated NOS2 promoter activity in macrophage transient transfection studies and the AT-rich HMGA1 DNA-binding site was critical for this effect. EMSAs (electrophoretic mobility-shift assays) demonstrated that netropsin interferes with HMGA1 NOS2 promoter binding and NMR spectroscopy was undertaken to characterize this disruption. Chemical shift perturbation analysis identified that netropsin effectively competes both HMGA1 DNA-binding AT-hooks from the AT-rich NOS2 promoter sequence. Furthermore, NOESY data identified direct molecular interactions between netropsin and A/T base pairs within the NOS2 promoter HMGA1-binding site. Finally, we determined a structure of the netropsin/NOS2 promoter Oct site complex from molecular modelling and dynamics calculations. These findings represent important steps toward refined structure-based ligand design of novel compounds for therapeutic benefit that can selectively target key regulatory regions within genes that are important for the development of critical illness.
 ...
PMID:Netropsin improves survival from endotoxaemia by disrupting HMGA1 binding to the NOS2 promoter. 1893 43

Agonistic and antagonistic peptides for formyl peptide receptor like 1 (FPRL1) receptor have been investigated as novel drug candidates for inflammatory diseases such as sepsis, asthma, and rheumatoid arthritis. In this work, a novel protocol for the synthesis of hyaluronic acid (HA)-peptide (CWRYMVm) conjugate for FPRL1 receptor was successfully developed for further clinical applications of peptide drugs. Aminoethyl methacrylated HA (HAAEMA) was synthesized by the coupling reaction of tetrabutyl ammonium salt of HA (HA-TBA) and AEMA using benzotriazol-1-yloxy-tris(dimethylamino) phosphonium hexafluorophosphate (BOP) in dimethyl sulfoxide (DMSO). Then, HA-AEMA was conjugated with CWRYMVm in water via Michael addition reaction between methacrylate group of HA-AEMA and thiol group in cysteine. The formation of HA-peptide conjugate was confirmed by 1H NMR and gel permeation chromatography (GPC). The average number of conjugated peptide molecules could be controlled from 5 to 23 per single HA chain. The HA-peptide conjugate showed serum stability longer than four days. In Vitro signal transduction activity of the HA-peptide conjugate for FPRL1 receptor was confirmed from the elevated levels of phospho-extracellular signal-regulated kinase (pERK) and calcium ion in FPRL1 overexpressing RBL-2H3 cells. The partially decreased biological activity of HA-peptide conjugates by the steric hindrance of HA was recovered after its degradation by hyaluronidase treatment.
 ...
PMID:Signal transduction of hyaluronic acid-peptide conjugate for formyl peptide receptor like 1 receptor. 1900 92

This study proposes an NMR-based metabonomic approach to early prognostic evaluation of sepsis. Forty septic rats receiving cecal ligation and puncture (CLP) were divided into the surviving group and nonsurviving group on day 6, while 20 sham-operated rats served as the control group. Serum samples were collected from septic and sham-operated rats at 12 h after surgery and analyzed using (1)H NMR spectroscopy. Orthogonal partial least squares (OPLS) were applied and showed clustering according to predefined groups, indicating that NMR-based metabolic profiling could reveal pathologic characteristics in the serum of sham-operated, surviving, and nonsurviving septic rats. In addition, six characteristic metabolites including lactate, alanine, acetate, acetoacetate, hydroxybutyrate, and formate, which are mainly involved in energy metabolism, changed markedly in septic rats, especially in the nonsurvivors. Using these metabolites, a predictive model for prognostic evaluation of sepsis was constructed using a radial basis function neural network (RBFNN) with a prediction accuracy of about 87% by test samples. The results indicated that the NMR-based metabonomic approach is a potential technique for the early prognostic evaluation of sepsis.
NMR Biomed 2009 Jul
PMID:A metabonomic approach to early prognostic evaluation of experimental sepsis by (1)H NMR and pattern recognition. 1932 15

The Cronobacter spp., previously known as Enterobacter sakazakii, are Gram-negative enterobacterial pathogens that can cause necrotizing enterocolitis, meningitis, and septicemia with a high mortality rate in neonates. The O-specific polysaccharide (O-PS) was isolated from Cronobacter sakazakii strain 767 and structurally characterized using (1)H and (13)C NMR spectroscopy, including two-dimensional DQF-COSY, TOCSY, ROESY, HSQC, and HMBC experiments. Further compositional determination was undertaken using classical chemical methods followed by GLC, and GLC-MS analysis. The repeating unit of O-PS isolated from C. sakazakii 767 was a branched heptasaccharide composed of l-Rha, d-Glc, d-GlcNAc, and d-GalA, and had the structure shown below. One of the Rha residues was partially O-acetylated at C-4. C. sakazakii 767 was originally isolated from a fatal neonatal meningitic case, and the structure of its O-PS significantly differs from the O-PS structures previously described for Cronobacter spp.
 ...
PMID:Structure of the O-polysaccharide isolated from Cronobacter sakazakii 767. 2020 18

Strains of Cronobactersakazakii (previously known as Enterobactersakazakii) are medically recognized important Gram-negative bacterial pathogens that cause enterocolitis, septicemia, and meningitis, with a high mortality rate in neonates. The structure of their O-antigens, that form part of their somatic lipopolysaccharide (LPS) components, is of interest for their chemical and serological identification and their relationship to virulence. The O-polysaccharide (O-PS) of C.sakazakii HPB 2855 (SK 81), a strain isolated from an infant at the Hospital for Sick Children in Toronto in 1981, was shown to be a polymer of a partially O-acetylated-repeating hexasaccharide unit composed of d-glucose, d-galacturonic acid, 2-acetamido-2-deoxy-d-galactose, and l-rhamnose (1:1:1:3). From composition and methylation analysis, and the application of 1D and 2D (1)H and (13)C NMR spectroscopy, the O-PS was determined to be a polymer of a repeating oligosaccharide unit having the structure:
 ...
PMID:The structure of the O-antigen of Cronobacter sakazakii HPB 2855 isolate involved in a neonatal infection. 2068 49

The in vivo assessment of renal damage after ischemia-reperfusion injury, such as in sepsis, hypovolemic shock or after transplantation, is a major challenge. This injury often results in temporary or permanent nonfunction. In order to improve the clinical outcome of the kidneys, novel therapies are currently being developed that limit renal ischemia-reperfusion injury. However, to fully address their therapeutic potential, noninvasive imaging methods are required which allow the in vivo visualization of different renal compartments and the evaluation of kidney function. In this study, MRI was applied to study kidney oxygenation and function in a murine model of renal ischemia-reperfusion injury at 7 T. During ischemia, there was a strongly decreased oxygenation, as measured using blood oxygen level-dependent MRI, compared with the contralateral control, which persisted after reperfusion. Moreover, it was possible to visualize differences in oxygenation between the different functional regions of the injured kidney. Dynamic contrast-enhanced MRI revealed a significantly reduced renal function, comprising perfusion and filtration, at 24 h after reperfusion. In conclusion, MRI is suitable for the noninvasive evaluation of renal oxygenation and function. Blood oxygen level-dependent or dynamic contrast-enhanced MRI may allow the early detection of renal pathology in patients with ischemia-reperfusion injury, such as in sepsis, hypovolemic shock or after transplantation, and consequently may lead to an earlier intervention or change of therapy to minimize kidney damage.
NMR Biomed 2011 Feb
PMID:MRI of renal oxygenation and function after normothermic ischemia-reperfusion injury. 2095 64

We demonstrate the effective use of NMR spectroscopic profiles of urine and plasma from the first successful use of hepatocyte transplantation as a bridge to auxiliary partial orthotopic liver transplantation in a child antenatally diagnosed with severe ornithine transcarbamylase deficiency. In this single-patient study, NMR profiles indicated that the disrupted urea cycle could be normalized by hepatocyte cell infusion and this was confirmed using orthogonal partial least-squares-based chemometrics. However, despite dietary manipulations and adminstration of ammonia scavengers, the desired reduction in plasma ammonia was not consistently achieved between sessions of hepatocyte transplantation due to episodes of sepsis. A subsequent liver transplant corrected the metabolic abnormalities. The use of metabolic profiling has been shown to be a promising method for evaluating the efficacy of cell infusions and has demonstrated the capability for the early detection of response to therapy in real time, an approach that may be of use in wider clinical settings.
 ...
PMID:First example of hepatocyte transplantation to alleviate ornithine transcarbamylase deficiency, monitored by NMR-based metabonomics. 2108 1


<< Previous 1 2 3 4 5 6 7 8 Next >>