Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic alcohol abuse is of significant clinical and economic relevance. A major part of internal medical pathology is associated with chronic alcoholism. 50% of all accidents with subsequent traumatic injuries are related to alcohol intake. Patients who are chronic alcohol abusers have prolonged hospital stays and substantial increases in postoperative morbidity. A sophisticated diagnosis of alcoholism within standard clinical routine is often difficult, and in most cases the treatment of alcohol-related diseases and complications is protracted and requires increased energy expenditure by the treating physicians. In surgical patients, chronic alcohol abuse is associated with a 3- to 4-fold risk of infections, sepsis, cardiac and bleeding complications. Therefore, the patients themselves, along with the general practitioner and an in-hospital interdisciplinary team should cooperate in medical and operative treatment in order to attain better clinical outcome. Each patient history should include a detailed assessment of the quantity of daily alcohol intake. Alcoholic diagnostic regimens including questionnaires (i.e. CAGE, AUDIT) in combination with specific laboratory markers (CDT, GGT, MCV), if implemented, could prove valuable, especially in cases where major surgical procedures are considered. Strict abstinence by alcoholic patients with organ pathology in medical and elective surgical settings as well as the prophylactic treatment of pre-operative alcohol withdrawal appear to be useful strategies to reduce the risk of complications. Short-term interventions are associated with reduced alcohol intake and decreased incidence of re-trauma. Considering the clinical relevance of alcohol abuse, sufficient screening, interventions, and open approaches to address alcohol problems should be important components of the daily clinical routine in outpatient clinics, emergency rooms, in GPs' offices and in general hospitals.
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PMID:[The alcoholic patient in the daily routine]. 1460 33

The inflammatory process is associated with alterations in iron metabolism. Transferrin, an acute-phase N-glycosylated glycoprotein, plays an important role in iron transport. Human serum transferrin contains two biantennary glycans, each consisting of 0 to 4 molecules of sialic acid (SA); its SA content is heterogeneous with high concentration of tetrasialotransferrin (4SA) and low amounts of disialo-, trisialo-, penta-, and hexasialotransferrin. The hepatic uptake of iron is greater for desialylated transferrin isoforms (disialotransferrin) than for the other forms. We hypothesized that serum levels of carbohydrate-deficient transferrin (CDT, disialotransferrin) may increase rapidly in septic patients. Blood samples were obtained from critically ill patients with (n = 15) and without (n = 14) documented sepsis and compared with healthy volunteers. The different forms of transferrin were studied by capillary zone electrophoresis; SA concentrations were measured by enzymatic colorimetric assay. There was a significant increase in the proportion of CDT in septic compared with nonseptic patients and volunteers (18.3% [1.3-30.5] vs. 0.7% [0.5-0.9]; P < 0.01 and 0.9% [0.5-1.1]; P < 0.05). Conversely, tri- and tetrasialotransferrin levels were lower in septic patients. Total and free SA concentrations were significantly higher in septic patients than in healthy volunteers. In a sheep model of septic shock secondary to peritonitis, serum free SA was already increased after 15 h. Sepsis is associated with decreased SA content on circulating transferrin and with an increase in blood free SA concentrations. In view of these rapid modifications and the long half-life of transferrin, the most likely explanation is degradation of transferrin by neuraminidase. Further studies including measurement of blood neuraminidase concentration and activity are needed to understand the process and exact role of SA decrease in septic patients.
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PMID:Rapid alterations in transferrin sialylation during sepsis. 1598 20

We have developed new clinical (C) and laboratory (L) staging systems to improve the clinical management of chronic lymphedema. These systems were retrospectively assessed in 220 chronic lymphedema patients followed up for 4 years. Clinical evaluation of the treatment response/disease progression was performed at 6 month intervals and laboratory evaluation at a yearly interval except for recurrent sepsis cases. The reliability of C-stage and L-stage for the progression of disease were analyzed separately. The C-staging was based on the subjective and objective findings of local and systemic conditions, while L-staging was based on lymphoscintigraphicfindings. Clinical implementation of this new staging system facilitated interpretation of the progress/deterioration of the clinical response to CDT treatment, and it was found to be a useful guideline for the decision/selection of further surgical treatment. We propose that these two separate staging systems could now become a new guideline for improved management of lymphedema with a better prediction of treatment outcome and decision point for additional medical/surgical therapy. Further clinical implementation and evaluation is necessary to demonstrate clinical usefulness especially to guide surgical therapy and L-staging in followup.
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PMID:New clinical and laboratory staging systems to improve management of chronic lymphedema. 1635 89

Tachyplesin-1, a disulfide stabilized beta-hairpin antimicrobial peptide, can be found at the hemocytes of horse shoe crab Tachypleus tridentatus. A cysteine deleted linear analog of tachyplesin-1 or CDT (KWFRVYRGIYRRR-NH2) contains a broad spectrum of bactericidal activity with a reduced hemolytic property. The bactericidal activity of CDT stems from selective interactions with the negatively charged lipids including LPS. In this work, CDT-LPS interactions were investigated using NMR spectroscopy, optical spectroscopy and functional assays. We found that CDT neutralized LPS and disrupted permeability barrier of the outer membrane. Zeta potential and ITC studies demonstrated charge compensation and hydrophobic interactions of CDT with the LPS-outer membrane, respectively. Secondary structure of the peptide was probed by CD and FT-IR experiments indicating beta-strands and/or beta-turn conformations in the LPS micelle. An ensemble of structures, determined in LPS micelle by NMR, revealed a beta-hairpin like topology of the CDT peptide that was typified by an extended cationic surface and a relatively shorter segment of hydrophobic region. Interestingly, at the non-polar face, residue R11 was found to be in a close proximity to the indole ring of W2, suggesting a cation-n type interactions. Further, saturation transfer difference (STD) NMR studies established intimate contacts among the aromatic and cationic residues of CDT with the LPS micelle. Fluorescence and dynamic light scattering experiments demonstrated that CDT imparted structural destabilization to the aggregated states of LPS. Collectively, atomic resolution structure and interactions of CDT with the outer membrane-LPS could be exploited for developing potent broad spectrum antimicrobial and anti-sepsis agents.
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PMID:Structure, activity and interactions of the cysteine deleted analog of tachyplesin-1 with lipopolysaccharide micelle: Mechanistic insights into outer-membrane permeabilization and endotoxin neutralization. 2246 70

Clostridium difficile is a bacterial pathogen and is the most commonly reported source of nosocomial infection in industrialized nations. Symptoms of C. difficile infection (CDI) include antibiotic-associated diarrhea, pseudomembranous colitis, sepsis and death. Over the last decade, rates and severity of hospital infections in North America and Europe have increased dramatically and correlate with the emergence of a hypervirulent strain of C. difficile characterized by the presence of a binary toxin, CDT (C. difficile toxin). The binary toxin consists of an enzymatic component (CDTa) and a cellular binding component (CDTb) that together form the active binary toxin complex. CDTa harbors a pair of structurally similar but functionally distinct domains, an N-terminal domain (residues 1-215; (1-215)CDTa) that interacts with CDTb and a C-terminal domain (residues 216-420; (216-420)CDTa) that harbors the intact ADP-ribosyltransferase (ART) active site. Reported here are the (1)H, (13)C, and (15)N backbone resonance assignments of the 23 kDa, 205 amino acid C-terminal enzymatic domain of CDTa, termed (216-420)CDTa. These NMR resonance assignments for (216-420)CDTa represent the first for a family of ART binary toxins and provide the framework for detailed characterization of the solution-state protein structure determination, dynamic studies of this domain, as well as NMR-based drug discovery efforts.
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PMID:1H, 13C, and 15N resonance assignments of an enzymatically active domain from the catalytic component (CDTa, residues 216-420) of a binary toxin from Clostridium difficile. 2688 52