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)

Nitric oxide (NO) is produced in excess in various pathological states, including sepsis and hepatic cirrhosis, and appears to be related to inflammatory status. In uremia, one would expect the levels of NO to increase. We aimed to determine whether hemodialysis (HD) would remove NO from the systemic circulation of uremic patients. Blood was collected before, after, and 1 day after HD from 12 uremic patients. Plasma nitrite and nitrate (NOx-) levels were measured by colorimetric Greiss reaction and cGMP was measured by an enzyme immunoassay kit. Our study demonstrated that uremic patients have high plasma NO levels, and HD led to a significant drop in plasma NOx- level (63 +/- 15% reduction). The level rose back to the pre-HD level on the following day. Plasma cGMP in the patients also decreased significantly after HD (27 +/- 14% reduction). In conclusion, we hypothesized that HD might be a possible approach for the removal of excess NO in pathological conditions such as sepsis and hepatic cirrhosis.
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PMID:Effect of hemodialysis on plasma nitric oxide levels. 1084 81

Protein C is a vitamin-K dependent zymogen of the anti-coagulant serine protease activated protein C (APC). In this paper, we report four lines of evidence that APC can activate protein C in pooled normal plasma, and purified protein C. First, the addition of APC to protein C-deficient plasma supplemented with protein C produces a prolongation of the clotting time of plasma that is proportional to the amount of protein C. This behavior was observed with APC from the Chromogenix APC resistance kit (Dia Pharm, Franklin, OH, USA) and from APC derived from the thrombin activation of human protein C (Enzyme Research Laboratories, South Bend, IN, USA). Secondly, using immunoblotting after gel electrophoresis, the disappearance of epitopes for monoclonal antibodies that recognize protein C but not APC indicates a time course for the activation by APC of protein C in pooled normal plasma and protein C purified from plasma. Thirdly, the same time course for the disappearance of protein C specific epitope can be followed using ELISA. Finally, protein C can be activated by APC as indicated by the increase in APC specific synthetic substrate Tryp-Arg-Arg-p nitroaniline hydrolysis. Kinetic data indicate a value of 4.7+/-0.4 mM(-1) s(-1) for the activation of protein C by APC under physiological conditions and in the presence of calcium. These observations document that APC must function not only in the inactivation of activated factors V and VIII, but also in the activation of protein C. This additional action of APC may be important to consider more broadly because of APC in the treatment of sepsis.
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PMID:Proteolysis of protein C in pooled normal plasma and purified protein C by activated protein C (APC). 1189 50

The aim of the present research was conducted to elucidate anti-septicaemic effect of a polysaccharide (PS) isolated from Panax ginseng C.A. Meyer (Araliaceae) by nitric oxide production from stimulated macrophage. In vitro assays for the activity measurement of PS, NO production test with Greiss reagent, phagocytic activity test using zymosan and cytokines production test using ELISA kit were also conducted. In vivo anti-septicaemic activity was assessed by using C57BL/6J mice. This was done with Staphylococcus aureus infection test. PS used at 0.025 mg/kg concentration showed a potent anti-septicaemic activity (80%, survival). However, it did not directly inhibit S. aureus in a minimum inhibitory concentration (MIC) test, conducted in vitro (data not shown). Nitric oxide production via macrophage activation showed the highest value of 5.5 nmol/ml at 1 microg/ml PS. In in vitro phagocytic activity test, PS at 10 microg/ml concentration showed a potent phagocytic activity for zymosan with 167% of the control. Production of TNF-alpha by macrophage activation at 10 microg/ml of PS was 96% lysis of L929. Also production of IL-1 and IL-6 by stimulation of macrophage with 100 microg/ml PS dose increased to 235 pg/ml and 0.47 ng/ml, respectively. The low mortality of PS treated (0.025 mg/kg) infected mice was concurrent with decreased bacterial content in the blood. Nitric oxide production in S. aureus infected mice whose macrophage was stimulated by PS (0.025 mg/kg) increased approximately 4 times than the untreated S. aureus infected group at 24 and 48 h incubation. In the PS treated (0.025 mg/kg) group, the intracellular concentration of S. aureus in macrophages decreased approximately by 50%, compared with the untreated group. Combine treatment with PS (0.025 mg/kg body weight) and vancomycin (10 mg/kg B.W.) resulted in 100% survival of the animals, whereas only 67% or 50% of the animals survived, respectively, when treated with PS or vancomycin alone. These results suggest that PS from Panax ginseng possess a potent anti-septicaemic activity by stimulating macrophage and a potentiality as an immunomodulator against sepsis occurred by Staphylococcus aureus.
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PMID:Anti-septicaemic effect of polysaccharide from Panax ginseng by macrophage activation. 1221 29

Nurses need to be aware of the signs and symptoms of sepsis. Staff education to encourage the early identification of this life-threatening condition will be aided by a new resource kit.
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PMID:Sepsis: early detection and care. 1238 78

Cytokines have been considered as important participants in the post-burn pathophysiological process. The aim of this study was to investigate the course of a proinflammatory cytokine interleukin-8 (IL-8) and an anti-inflammatory cytokine IL-10 in burned patients and whether there was a correlation between mortality and serum levels of these cytokines. Thirty-six acutely burned patients, admitted to Ankara Numune hospital burn unit, entered into the study. A series of serum samples were collected, and serum levels of IL-8 and IL-10 were determined using enzyme-linked immunosorbent assay kit. According to definition utilised, 21 patients developed septic shock and nine of them died. There was no mortality among the 17 non-septic patients. In all 36 patients, there was an increase in serum IL-8 levels, and a peak level was detected shortly after burn injury. The peak IL-8 value of the non-survivors was greater when compared with that of the others. On admission, a significant difference in serum IL-8 values was found between survivors and those who died. In all patients, a peak level of IL-10 was detected between 5 and 9 days of injury. In non-septic survivors, this peak level was less when compared with that of the others. After this peak level, in all patients, serum IL-10 levels showed a decrease, but in non-survivors, a second peak level was detected. A greater understanding of the pathology of the burn sepsis allows rationale use and assessment of current therapies. The results obtained in this study provide useful information on the formulation approaches to this task. Also, IL-8 and IL-10 are prognostic factors in burn sepsis.
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PMID:Investigation of the course of proinflammatory and anti-inflammatory cytokines after burn sepsis. 1505 59

Burn and septic injuries induce profound changes in coagulation status. This study examined the changes in plasma tissue factor pathway inhibitor (TFPI) and thrombin activatable fibrinolytic inhibitor (TAFI) levels in a rat model of burn and septic injuries. Rats underwent 30% TBSA cutaneous scald burn injury and septic insult was induced by caecal ligation and puncture (CLP). CLP was superimposed on burn injury to mimic the clinical model of sepsis complicating burn injury. Rats were pretreated with Cprofloxacin orally to colonize their gut with Enterococcus faecalis. TFPI and TAFI plasma levels were measured using functional activity assay kit with a chromogenic method at 24 and 72 hours following the injuries. TFPI levels decreased significantly at 24 hours in burn, CLP, and burn+CLP groups, followed by incomplete rebound recovery at 72 hours in all three groups. On the other hand, TAFI levels increased significantly at 24- and 72-hour time points in all three groups. These results suggest that burn, septic, and their combined injuries perturb coagulation cascade and thrombotic process toward the procoagulant pathway by impairing fibrinolysis.
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PMID:Tissue factor pathway inhibitor and thrombin activatable fibrinolytic inhibitor plasma levels following burn and septic injuries in rats. 1549 25

Quantification of biomarkers can provide important information about the safety and efficacy of candidate drugs. Unfortunately, limited sample volume and excess costs often limit analysis of multiple biomarkers. We developed, optimized, validated, and implemented a multiplex immunoassay for simultaneous measurement of multiple circulating cytokines: IL-1beta, TNFalpha, IL-6, IL-8, and IL-10. Multiplex immuoassays were performed using the Luminex LabMAP instrument. Capture antibodies for each cytokine were covalently bound to distinct microsphere subsets distinguished by differing dye ratios. The concentration of each individual cytokine determined by measuring orange fluorescence produced by a complex of a biotinylated cytokine-specific antibody and streptavidin-phycoerythrin. The lower limit of quantification for all assays was 20 pg/mL with the exception of IL-8 which was 100 pg/mL. The inter-assay precision was less than 25%CV for all analytes at all control levels both pre-study and in-study. The percent recovery ranged from 83 to 108% pre-study and 90 to 125% in-study. In a linearity assessment, a 15,000 pg/mL multi-analyte control could be diluted 1:50 and maintain expected accuracy. We measured the cytokine concentrations in more than 2000 serum samples from patients with sepsis. Multiplex results for IL-6 were compared to a conventional commercially available ELISA kit. The degree of agreement between the two methods as measured by the concordance correlation coefficient was 84.5%. Multiplex results were 2.36-fold higher than ELISA values on the average. After adjusting for this mean difference, the 95% empirical limits of agreement for the ratio of individual sample values were 0.33, 2.65. This multiplex immunoassay provided simultaneous measurement of circulating cytokines using 80% less patient specimen compared to traditional approaches and at a significantly decreased cost. Efficient use of this platform requires process improvements to fully maximize the positive impact of multiplex assays in clinical drug development.
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PMID:Development, validation, and implementation of a multiplex immunoassay for the simultaneous determination of five cytokines in human serum. 1562 May 30

Sepsis is one of the most complicated and common conditions clinicians encounter. The presence of causal bacteria has not been an essential element for sepsis, after the American College of Chest Physicians and the Society of Critical Care Medicine proposed SIRS as the new consensus and concept in 1991. The test kit "Hybrisep", detects pathogens in the blood directly. Effective use of it may be helpful in the further study of sepsis.
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PMID:[The new concept and diagnostic method of sepsis--not SARS, yes SIRS]. 1591 70

Lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) generation and the concomitant decline in the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) were demonstrated in human monocyte-derived dendritic cells (DC). Further, their relation to the maturation of DC, characterized by the production of cytokines, up-regulation of cell surface molecules and allo-stimulatory capacity, was examined. The LPS-induced ROS generation was demonstrated using electron paramagnetic resonance spectroscopy in intact cells, and was also confirmed using laser scanning confocal microscopy. The GSH/GSSG was assesed using a glutathione assay kit. When the DC were treated with alpha-phenyl-tert-butylnitrone, the ROS generation was attenuated, but the declined GSH/GSSG was not attenuated, and only cytokine production was suppressed among the above-mentioned maturation characteristics. When the DC were treated with glutathione monoethyl ester, both the ROS generation and the declined GSH/GSSG were attenuated, and the maturation characteristics were all suppressed. These findings suggest that the LPS-induced ROS generation and the concomitant decline in GSH/GSSG occur in human monocyte-derived DC and that the former is involved in cytokine production, while the latter is involved in the up-regulation of cell surface molecules and allo-stimulatory capacity. Since the cytokine production and the allo-stimulatory capacity of DC play an important role in inflammatory and immune responses, differential regulation of the ROS generation and the declined GSH/GSSG may be useful as therapeutic tools in diseases where both responses become entangled, such as sepsis and graft-versus-host disease.
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PMID:LPS-induced ROS generation and changes in glutathione level and their relation to the maturation of human monocyte-derived dendritic cells. 1628 Jan 35

Stapled hemorrhoidopexy is an alternative method to conventional surgical procedures for third-degree hemorrhoids. It has many advantages such as less pain, faster recovery and earlier return to work. Nevertheless, many reports mentioned the persistence of postoperative pain, hemorrhage, recurrence, sphincter injury, and pelvic sepsis. The complications mostly arose during the purse-string phase of the procedure. The internal hemorrhoids and loose rectal mucosa can fill the inside of the anoscope, obstruct the operation field and restrict the maneuverability of the needle holder. To overcome this difficulty, a specially designed anoscope may be used. The purse-string anoscope of the PPH 01 kit (Ethicon Endo-Surgery, Cincinnati, USA) was modified to overcome the obstruction of the staple line by internal hemorrhoids and rectal mucosal prolapse. Stapled mucosectomy with this modified anoscope was performed in 9 patients. The surgical procedure lasted approximately 25 min and the patients healed uneventfully, even though 4 of them had been operated on by surgeons in their first attempts with stapled hemorrhoidopexy. By using a modified anoscope, ideal purse-string suturing may become easier, intraoperative time may be shortened, and the learning curve may be reduced.
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PMID:A modified anoscope to facilitate the purse-string suture for stapled hemorrhoidopexy. 1632 20


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