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)

The integrin CD11b is an important adhesion molecule mediating the transendothelial migration of circulating polymorphonuclear granulocytes into an inflammatory region. The expression of CD11b is closely related to the ability to polymerize actin, a major component of the cytoskeleton within the phagocyte. In this study we compared the CD11b expression as well as the polymerization of actin of isolated neutrophils from patients endangered by sepsis with cells from healthy donors. The patient population was subdivided into a group of patients with severe thermal injuries and a group of patients who were admitted to an intensive care unit on suspicion of sepsis. The following results were obtained: (1) cells from burn patients, but not from non-burn patients, showed a reduced basal expression of CD11b during the first week after the burn trauma; (2) stimulation with the chemotactic peptide formyl-Met-Leu-Phe (FMLP) led to a strong overexpression of CD11b on the cells from the burn patients, this effect was not observed using cells of the second subgroup; (3) the content of polymerized actin was reduced within resting and stimulated cells from burn patients during the first 2 weeks postinjury, non-burn patient cells showed an enhanced F-actin content within the first week; (4) the ability of burn and non-burn patient cells to polymerize actin after stimulation with FMLP was slightly impaired during the first week post injury/admission. The results demonstrate that cells from patients endangered by sepsis show dysfunctions on the level of adhesion molecule expression and the strongly related actin polymerization.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of the adhesion molecule CD11b and polymerization of actin by polymorphonuclear granulocytes of patients endangered by sepsis. 855 83

The influence of pentoxifylline on human polymorphonuclear granulocyte (PMN) respiratory burst activity (RBA) was studied in 23 patients fulfilling the established criteria of sepsis and in 10 healthy donors. Pentoxifylline (PTX) was administered (5 mg/kg) by intravenous infusion in 13 septic patients over a period of 180 min. The control group consisted of 10 patients with septic syndrome who received an infusion of physiological saline. For determination of RBA, 10 mL of blood was drawn at respective time intervals before, during, and after treatment with PTX or a placebo. RBA measurements were performed using a chemiluminescence assay after stimulation of PMN with formyl-methionyl-leucyl-phenylalanine (FMLP), phorbol-myristate-acetate, and opsonized zymosan, respectively. RBA measurements of each patient were performed in replicate samples. CL was measured for 1 h at respective time intervals (1, 3, 5, 8, 10, 15 min etc). RBA of PMN of septic patients was compared with RBA of PMN of healthy donors and patients receiving PTX were compared with controls. Our results demonstrate that PMN of patients with sepsis had an increased oxidative response compared with healthy donors. We found that PTX administered intravenously was able to reduce this reactivity. RBA was significantly decreased during PTX infusion when PMN were stimulated with FMLP and phorbol-myristate-acetate, compared with the control group. No significant decrease was observed when PMN were stimulated with opsonized zymosan. These data suggest that PTX may be a valuable drug in septic state.
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PMID:In vivo modulation of human neutrophil function by pentoxifylline in patients with septic syndrome. 857 49

Abnormalities of polymorphonuclear leukocyte (PMN) function contribute to high rates of postoperative infection in the newborn and to the vulnerability of newborns to overwhelming bacterial and fungal sepsis. The authors investigated (1) the effects of major surgery and sepsis on PMN chemotaxis in the newborn and (2) the role of cytoskeletal rearrangements in regulating chemotaxis. The subjects studied included newborns with sepsis (n = 16), newborns who underwent major surgery (n = 7), healthy full-term newborns (n = 21), and healthy adult volunteers (n = 28). Peak actin polymerisation was diminished in all newborns (relative to the adults) after stimulation with formyl methionyl leucyl phenylalanine (FMLP) (10 nmol/L), and with zymosan activated serum (ZAS) (10%). Major surgery and sepsis in newborns caused no further reduction in actin polymerisation. Changes in PMN shape after stimulation with FMLP were reduced in the newborns. PMN chemotaxis was significantly lower in healthy newborns than in adults (17 +/- 4 microns v 24 +/- 5 microns; P < .0001) and was even lower in septic newborns (11 +/- 4 microns; P < .005). Surgery and anaesthesia did not alter chemotaxis.
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PMID:Defective neutrophil actin polymerisation and chemotaxis in stressed newborns. 880 Dec 96

We have examined the effect of propofol on the neutrophil respiratory burst. Chemiluminescence was used as a measure of the respiratory burst following stimulation with 10(-5) M N-formyl-L-methionyl-L-leucyl-L-phenylalanine. Propofol 1.25, 2.5 and 5.0 x 10(-5) M inhibited neutrophil chemiluminescence by 29.6, 43.0 and 57.6%, respectively, in neutrophils prepared from healthy adult volunteers, and by 25.5, 37.4 and 54.7% in cells from patients with severe sepsis. We conclude that propofol interferes with the ability of human neutrophils to generate reactive oxygen species.
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PMID:The effect of propofol on the neutrophil respiratory burst. 888 20

Previous studies provided evidence that sepsis-induced muscle proteolysis in experimental animals is caused by increased ubiquitin-proteasome-dependent protein breakdown. It is not known if a similar mechanism accounts for muscle proteolysis in patients with sepsis. We determined mRNA levels for ubiquitin and the 20 S proteasome subunit HC3 by Northern blot analysis in muscle tissue from septic (n = 7) and non-septic (n = 11) patients. Plasma and muscle amino acid concentrations and concentrations in urine of 3-methylhistidine (3-MH), creatinine, and cortisol were measured at the time of surgery to assess the catabolic state of the patients. A three- to fourfold increase in mRNA levels for ubiquitin and HC3 was noted in muscle tissue from the septic patients concomitant with increased muscle levels of phenylalanine and 3-MH and reduced levels of glutamine. Total plasma amino acids were decreased by approximately 30% in the septic patients. The 3-MH/creatinine ratio in urine was almost doubled in septic patients. The cortisol levels in urine were higher in septic than in control patients but this difference did not reach statistical significance. The results suggest that sepsis is associated with increased mRNAs of the ubiquitin-proteasome pathway in human skeletal muscle.
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PMID:Sepsis is associated with increased mRNAs of the ubiquitin-proteasome proteolytic pathway in human skeletal muscle. 900 83

The role of T-lymphocytes (T cells) and interferon-gamma (IFN-gamma) in the pathogenesis of sepsis-induced microvascular endothelial injury remains unclear. We sought to determine whether the syngeneic coculture of human T cells in the presence of LPS promoted subsequent neutrophil (PMN)-mediated endothelial cytotoxicity. Syngeneic T cells were cocultured with 51Cr-loaded human adipose microvascular endothelial cell (HAMVEC) monolayers in the absence and presence of LPS. Subsequent PMN-mediated HAMVEC cytotoxicity (measured as percent specific 51Cr release) was absent in cultures that contained T cells but no LPS and was significantly increased when T cells were cocultured in the presence of LPS. This was true both following addition of unstimulated PMNs (-0.8 +/- 3.0% vs 4.9 +/- 4.7% for T cells alone vs T cells plus LPS, respectively) and PMNs stimulated with f-Met-Leu-Phe (-0.4 +/- 3.1% vs 10.7 +/- 3.0% for T cells alone vs T cells plus LPS, respectively). Increased cytotoxicity was associated with increased expression of the endothelial adhesion molecules ICAM-1 and VCAM-1. Control experiments failed to demonstrate cytotoxicity when HAMVEC were cultured in the presence of IFN-gamma alone, LPS alone, or T cells without LPS. It appears that there is a necessary requirement of both LPS and (presumably activated) T cells or their products (other than IFN-gamma) for enhanced PMN-mediated endothelial cytotoxicity. This phenomenon may also be mediated by increased expression of endothelial adhesion molecules that promote subsequent PMN adhesion.
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PMID:Endotoxin-induced, neutrophil-mediated endothelial cytotoxicity is enhanced by T-lymphocytes. 920 40

Sepsis is associated with reduced protein synthesis and increased protein degradation in skeletal muscle. We examined the effects of insulin-like growth factor I (IGF-I) on protein synthesis and breakdown in muscles from nonseptic and septic rats. Sepsis was induced by cecal ligation and puncture; control rats were sham operated. Extensor digitorum longus muscles were incubated in the absence or presence of IGF-I at concentrations ranging from 100 ng/ml to 10 micrograms/ml. Total and myofibrillar protein breakdown rates were measured as net release of tyrosine and 3-methylhistidine, respectively. Protein synthesis was determined by measuring incorporation of [U-14C]phenylalanine into protein. IGF-I stimulated protein synthesis in a dose-dependent fashion in muscles from both sham-operated and septic rats, with a maximal effect seen at a hormone concentration between 500 and 1,000 ng/ml. IGF-I inhibited total and myofibrillar protein breakdown in muscles from sham-operated rats, whereas in muscles from septic rats, IGF-I had no effect on protein breakdown, even at high concentrations. The results suggest that protein breakdown in skeletal muscle becomes resistant to IGF-I during sepsis and that this resistance reflects a postreceptor defect.
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PMID:IGF-I stimulates protein synthesis but does not inhibit protein breakdown in muscle from septic rats. 948 20

Recent studies suggest lipopolysaccharide (LPS) mediated cell death as underlying mechanism of hyporesponsiveness and dysfunction of macrophages in the late phase of septic shock. In the present study LPS (0.001 - 30 microg/ml) caused a concentration-dependent toxicity in the macrophage cell line (J774.1A) within 24 h. The toxicity induced by LPS (1 microg/ml) was completely inhibited by the serine protease inhibitors, N-alpha-tosyl-L-phenylalanine chloromethyl ketone (TPCK) and N-alpha-tosyl-L-lysine chloromethyl ketone (TLCK) as measured by the mitochondrial-dependent oxidation of 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromid (MTT) to formazan. These inhibitors antagonize the activation of nuclear transcription factor-kappaB (NF-kappaB) indirectly by inhibiting I kappaB alpha-protease. SN50, a direct inhibitor of NF-kappaB translocation into the nucleus also protected macrophages from LPS-mediated toxicity. We conclude from these data that the early phase signal transduction pathway leading to LPS-mediated cytotoxicity in macrophages involves the activation of NF-kappaB. Thus, I kappaB alpha-protease inhibitors might serve as therapeutical agents to maintain macrophage viability during sepsis and to prevent sepsis-induced immune dysfunction.
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PMID:Protease inhibitors protect macrophages from lipopolysaccharide-induced cytotoxicity: possible role for NF-kappaB. 951 10

Hydrogen peroxide (H2O2) pretreatment of human neutrophils results in a suppression of the superoxide anion (O2) production in response to surface-acting stimulants such as lipopolysaccharide (LPS) and opsonized zymosan. This effect was not observed when phorbol myristate acetate (PMA), formyl-methionyl-leucyl-phenylalanine (fMLP) or tumor necrosis factor alpha (TNF alpha) were used as a stimuli. Since the response to PMA and other stimuli was unimpaired by preincubation with H2O2, we assume that the H2O2 modulated O2 production is probably due to alteration of the LPS receptor conformation rather than effecting directly NADPH-oxidase. The balance of reactive oxygen species (ROS) produced by neutrophils in the state of sepsis may thus be autoregulated by negative feedback phenomena of locally produced H202.
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PMID:Hydrogen peroxide modulation of the superoxide anion production by stimulated neutrophils. 954 2

Generation of reactive oxygen intermediates (ROI) has been implicated in tissue damage in a variety of disease states including sepsis and trauma. On the other hand, generation of ROI in polymorphonuclear granulocytes (PMN) presents a crucial element in the defence of the host against invading microorganisms. In the present study we investigated the generation of superoxide anions (O2-) and hydrogen peroxide (H2O2) by neutrophils (PMN)5 of 17 critically ill patients treated at a intensive care unit (ICU) after polytrauma (n = 6), heart operation (n = 6) or during septic shock (n = 5) using flow cytometry. O2- production of PMN from ICU patients was significantly lower (p < 0.01) than that in healthy volunteers (HV) during non-receptor mediated stimulation with phorbol-myristate-acetate (PMA) but higher (p < 0.001) during receptor mediated stimulation with formylmethionine-leucine-phenylalanine (FMLP). H2O2 generation of PMN from ICU patients was increased after stimulation with FMLP (p < 0.01) and remained unchanged after stimulation with PMA. Patients in septic shock had lower O2(-)-generation of PMN than did injured patients and patients after heart operations. We conclude that receptor mediated formation of O2- and H2O2 is stimulated in ICU patients. However, in patients in septic shock O2(-)-generation decreases, which potentially might contribute to the immunoparalysis present in septic shock.
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PMID:Receptor and non-receptor mediated formation of superoxide anion and hydrogen peroxide in neutrophils of intensive care patients. 988 46


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