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)

An azaindolidine derivative, SJC13, selectively inhibits expression and mRNA synthesis of E-selectin and vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVEC) stimulated with lipopolysaccharide (LPS). The present experiments were performed to determine the in vivo effects of SJC13 against the lethality of LPS. In a mouse model of septic shock, intravenous administration of SJC13 5 min prior to LPS injection prevented significantly the lethality at doses of 3 mg/kg and 10 mg/kg. The prophylactic effect was dose-dependent. When injected up to 1 h after LPS injection, SJC13 inhibited significantly the lethality. Neutrophil emigration into lung tissues during sepsis induced with LPS, as assessed by lung myeloperoxidase (MPO) content and histological examination, was significantly prevented by SJC13 administration. These data demonstrate that SJC13 has therapeutic anti-inflammation potential in vivo.
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PMID:Protection against septic shock in mice with SJC13, an azaindolidine derivative that is a cell adhesion molecule inhibitor. 889 55

We report here a case of Cogan's syndrome associated with systemic vasculitis as well as myeloperoxidase-specific antineutrophil cytoplasmic antibody (MPO-ANCA)-related glomerulonephritis. A 71-year-old woman with the diagnosis of aortitis syndrome and pulmonary fibrosis for 7 years, complained of vertigo and hearing impairment. A diagnosis of serous otitis media was made. Although steroid therapy was effective, the symptoms relapsed several times. Seven months after the first manifestation of aural symptoms, she developed painful red eyes bilaterally and proteinuria. On admission, perinuclear ANCA without cytoplasmic ANCA was detected by indirect immunofluorescence assay and MOP-ANCA was detected by enzyme linked immunosorbent assay using the 363 ELISA Unit. Renal biopsy showed necrotizing crescentic glomerulonephritis without immune deposits. A diagnosis of atypical Cogan's syndrome with systemic vasculitis and pulmonary fibrosis was made from the clinical and histological findings. As nephrotic syndrome progressed after admission, she was started on high-dose corticosteroid administration. Urinary protein and other symptoms, except for hearing acuity, improved in parallel with a decrease in the MPO-ANCA titer to normal values. While tapering the dose of corticosteroid, the MPO-ANCA titer increased again and dyspnea occurred. Although pulse methylpredonisolone therapy was performed, the patient died of respiratory failure complicated with sepsis. Postmortem lung biopsy showed pulmonary fibrosis and massive alveolar hemorrhage. The findings of this case study suggest that MPO-ANCA may be closely related to the pathogenesis of Cogan's syndrome.
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PMID:[A case of myeloperoxidase-specific antineutrophil cytoplasmic antibody (MPO-ANCA)-related glomerulonephritis associated with Cogan's syndrome]. 891 96

Endotoxin-induced lung injury is characterized by neutrophil infiltration of the lungs. The various mechanisms which mediate movement of neutrophils from vascular space to lung interstitium and alveoli remain unclear. Macrophage-inflammatory protein 2 (MIP-2) is a potent chemoattractant for neutrophils and may play a significant role in recruiting neutrophils in acute lung injury in rats. Experiments were performed in male Sprague Dawley rats to: (1) evaluate the kinetics of neutrophil influx in the lung following intraperitoneal administration of Salmonella enteritidis lipopolysaccharide (LPS); (2) determine the expression of transcripts for chemokines and adhesion molecules in the lung following intraperitoneal LPS; and (3) elucidate the effects of intra-alveolar instillation of recombinant rat MIP-2 on neutrophil influx into the lung. Intraperitoneal LPS resulted in an increase in neutrophil sequestration in the lung capillaries of rats as early as 45 min following administration, and there was a parallel increase in lung myeloperoxidase activity. There were also major increases in mRNA in whole-lung homogenates of LPS-treated rats for chemokines MIP-2 and KC (cytokine-induced neutrophil chemoattractant) and adhesion molecules P- and E-selectin at 1 and 2 h following LPS. When recombinant rat MIP-2 was instilled into the alveolar space of rats through a catheter wedged into a bronchus, there was profound neutrophil localization both in the vascular and alveolar space which significantly differed (P < 0.05) from the contralateral lungs of the same animals, and lungs of control animals instilled with control buffer. These observations reveal that MIP-2 is a potent chemoattractant in rat lungs, and suggest that chemoattractants locally released in alveoli can recruit neutrophils to those alveoli. This suggests that alveolar macrophages may play an important role in neutrophil sequestration in sepsis and other inflammatory lung diseases which produce a neutrophilic alveolitis.
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PMID:Intra-alveolar macrophage-inflammatory peptide 2 induces rapid neutrophil localization in the lung. 891 72

Urethan is a commonly used animal anesthetic for nonrecovery laboratory surgery. However, urethan has diverse biological effects that may complicate the interpretation of experimental findings. This study examined the effect of urethan on the response to an intravenous bolus of lipopolysaccharide (LPS; 30 mg/kg) in rats. In instrumented rats, urethan (1.2 gm/kg i.p.) completely prevented the fall in arterial pressure immediately after LPS administration but did not prevent late cardiovascular collapse. In uninstrumented rats, urethan also attenuated indexes of organ injury measured 4 h after LPS administration, including mural bowel hemorrhage, hemoconcentration, hypoglycemia, metabolic acidosis, and lung myeloperoxidase activity, a measure of neutrophil sequestration. The peak increase in tumor necrosis factor-alpha (TNF-alpha) 90 min after LPS administration was reduced 88% by urethan (2,060 +/- 316 vs. 16,934 +/- 847 pg/ml; P < 0.001). In uninstrumented animals, urethan at 1.2 gm/kg reduced the 90% mortality rate of a lethal dose of LPS to 0-10% when given up to 24 h before LPS administration but did not reduce mortality when given 2 h after LPS. Urethan neither directly bound LPS by Limulus assay nor inhibited LPS-stimulated TNF-alpha mRNA expression in cultured mouse peritoneal macrophages, but TNF-alpha mRNA expression was suppressed by serum from a urethan-treated rat. Moreover, rauwolscine, which shares alpha 2-adrenoceptor-blocking activity with urethan, also prevented death from a subsequent 90% lethal dose LPS bolus. We conclude that urethan or its metabolites protect against LPS, in part, by reducing TNF-alpha release and speculate that this may be mediated by alpha 2-adrenoceptors. These actions of urethan make it an undesirable anesthetic agent for in vivo studies of sepsis or LPS.
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PMID:Urethan anesthesia protects rats against lethal endotoxemia and reduces TNF-alpha release. 894 58

Inflammatory bowel disease is associated with mucosal neutrophil recruitment and activatation, mediated in part by arachidonic acid metabolites. G-CSF attenuates the immune response to sepsis and ameliorates glycogen storage disease Ib-related colitis. These actions may be effected through the shedding of neutrophil adhesion molecules, or inhibition of proinflammatory mediator synthesis. Immune complex colitis was used to evaluate the effect of rhG-CSF on colonic mucosal inflammation, neutrophil recruitment and the generation of eicosanoids. Immune complex colitis was induced in White New Zealand rabbits. Animals were pretreated with rhG-CSF either 24 h before induction, or at induction, with dosages of 50 and 200 micrograms/kg. rhG-CSF caused a time- and dose-dependent neutrophilia in all animals. Pretreatment with rhG-CSF resulted in increased tissue myeloperoxidase levels, despite a histologically similar mucosal polymorphonuclear cell infiltrate between treated and control colitis groups. Leukotriene B4 (LTB4) and thromboxane B2 (TXB2) dialysis fluid levels were lower in treated animals, in particular in the groups receiving two doses (LTB4: both P < 0.01; TXB2: both P < 0.01. Prostaglandin E2 (PGE2) levels in dialysis fluid of the rhG-CSF-treated animals showed no difference from controls. In this model of experimental colitis, high-dose therapy with G-CSF resulted in a marked decrease of proinflammatory mediators, but mucosal generation of the protective PGE2 was preserved. These results suggest that prolonged high-dose therapy with G-CSF may have anti-inflammatory effects in colitis.
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PMID:Efficacy of recombinant granulocyte colony-stimulating factor (rhG-CSF) in experimental colitis. 897 23

The role of bronchoalveolar macrophages (BAMs) in the aggravation of cerulein-induced pancreatitis was studied by measuring expression of cytokine-induced neutrophil chemoattractant (CINC) in vitro. Pancreatitis was induced by four intramuscular injections of cerulein (50 microg/kg at 1-hr intervals). Pancreatitis rats were injected intraperitoneally with 30 mg/kg lipopolysaccharide (LPS) 6 hr following the first cerulein injection as a septic challenge. Rats were divided into four groups: group I, nonpancreatitis without LPS; group II, pancreatitis without LPS; group III, nonpancreatitis with LPS; and group IV, pancreatitis with LPS. Hyperactivity of BAMs in response to LPS was assessed as a function of in vitro CINC production. CINC concentrations of the serum and bronchoalveolar lavage fluid in group IV were significantly higher than those in groups I, II, and III. BAMs in group II harvested 6 hr following the first cerulein injection had significantly greater CINC production than those in group I. Northern blot analysis revealed abundant CINC mRNA transcripts in BAMs from groups III and IV. Additionally, myeloperoxidase activity in the lung of group IV rats 8 and 12 hr following the first cerulein injection was significantly higher than that in group I, II, and III rats. Significant differences in static lung compliance in group IV were found compared with groups I, II, and III. These results indicate that BAMs from rats with cerulein-induced pancreatitis were primed and had enhanced release of CINC following LPS exposure. Enhanced expression of CINC may modulate the pathogenesis of pancreatitis-associated lung injury complicated with sepsis.
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PMID:Enhanced expression of cytokine-induced neutrophil chemoattractant (CINC) by bronchoalveolar macrophages in cerulein-induced pancreatitis rats. 900 32

Proper engagement of leukocyte and endothelial cell selectins with their counterreceptors is an initial step in neutrophil trafficking to sites of inflammation. Certain fucosylated carbohydrate determinants such as sialyl Lewis-x are proposed to act as these counterreceptors. We studied the effects of a synthetic sialyl Lewis-x analog, CY-1503, on the course of hemodynamic derangements and acute lung injury during experimental gram-negative sepsis. Anesthetized ventilated swine were made septic with an infusion of live Pseudomonas aeruginosa. A treatment group received an initial bolus of CY-1503 (60 mg/kg) before sepsis, followed by continuous infusion of CY-1503 (15 mg.kg-1.h-1). Treatment with CY-1503 did not prevent the development of pulmonary hypertension, systemic hypotension, decline in cardiac output, or severe neutropenia. However, CY-1503 significantly attenuated lung injury, demonstrated by decreased bronchoalveolar lavage protein content and neutrophil influx, lowered lung myeloperoxidase activity, and improved arterial oxygenation. Neutrophils from septic and CY-1503 animals showed significant activation, reflected by upregulated CD18 expression and priming for oxidant burst compared with control animals. This study suggests blockade of selectin interactions as a potential therapeutic intervention in sepsis-induced lung injury.
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PMID:Protective role of synthetic sialylated oligosaccharide in sepsis-induced acute lung injury. 904 48

The effects of lisofylline [(R)-1-(5-hydroxyhexyl)-3,7-dimethylxanthine] (LSF), an inhibitor of de novo phosphatidic acid (PA) generation, on sepsis-induced acute lung injury was studied using Hanford minipigs weighing 18 to 25 kg. Sepsis was induced by an intravenous infusion of Pseudomonas aeruginosa (1 x 10(6)/colony-forming units/kg/min over 2 h). Saline was used as the control vehicle. Six groups were studied: saline control group (SALINE: n = 5); sepsis control group (SEPSIS: n = 5); LSF control group (LSF: n = 5), which received a 25-mg/kgbolus of LSF 30 min before time zero followed by continuous infusion of 10 mg/kg/h throughout the study; LSF-treated septic groups, which were treated with LSF 30 min prior to sepsis (Pre: n = 5), 1 h postonset (Post-1 h: n = 8) or h postonset (Post-2 h: n = 8) of the bacterial infusion. Hemodynamics PaO2, neutrophil counts, and plasma porcine tumor necrosis factor-alpha concentrations were monitored for 6 h. After the minipigs were killed, lung tissue was sampled to measured wet-to-dry weight ratio (W/D), tissue albumin index (TAI), thiobarbituric acid-reactive material content (TBARM), and myeloperoxidase (MPO) activity. Compared with the SALINE group, the SEPSIS group showed significant systemic hypotension, pulmonary hypertension, arterial hypoxemia, neutropenia, and increase in TNF-alpha, MPO activity, W/D, TBARM, and TAI. LSF treatment attenuated sepsis-induced pulmonary hypertension, neutropenia, and hypoxemia, and increased MPO activity and lung injury measurements in the Pre and Post-1 h groups, but its efficacy was blunted in the Post-2 h group. Plasma TNF-alpha was decreased only in the Pre group. Thus, inhibition of intracellular PA generation through de novo pathways attenuates sepsis-induced acute lung injury.
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PMID:The effects of post-treatment with lisofylline, a phosphatidic acid generation inhibitor, on sepsis-induced acute lung injury in pigs. 911 28

Eleven patients, 13 to 76 (mean, 40) years of age, had granulocytic sarcoma of the female genital tract (FGT) (ovary, seven cases; vagina, three cases; cervix, one case). In nine cases, the FGT involvement was the initial clinical presentation of the disease, and in the other two cases, the FGT involvement was discovered during a relapse of acute myeloid leukemia. The tumors ranged from 0.5 to 14 (mean, 7.5) cm in greatest dimension. Two ovarian tumors were bilateral, and three were green. Microscopic examination revealed a predominantly diffuse pattern of growth, but cords and pseudoacinar spaces were also present focally in several cases. Sclerosis was seen in five tumors and was prominent in one. Prominent myeloid differentiation was readily recognizable on routinely stained sections in three cases, whereas the neoplastic cells in the other cases were primitive with only rare eosinophilic myelocytes. All 11 tumors were positive for chloroacetate esterase, nine of nine were strongly and diffusely positive for lysozyme, eight of eight for myeloperoxidase, seven of seven for CD68, and six of six for CD43. Examination of bone marrow or peripheral blood performed after the diagnosis of FGT involvement revealed acute myeloid leukemia in three of five cases. Two of these patients died of disease, 1 and 16 months after the initial diagnosis, and the third, who received chemotherapy, is alive and free of disease 8 months after the initial diagnosis. One of the two patients with negative bone marrow had recurrent granulocytic sarcoma 30 months after diagnosis and died of sepsis 1 month later; no residual disease was noted at autopsy. The other patient is alive and free of disease 18 months after the diagnosis. One of the four remaining patients with primary FGT involvement who did not have a bone marrow biopsy died of leukemia 24 months later; no follow-up information is available for the other three patients. One of the two patients with a prior diagnosis of acute myeloid leukemia was alive with disease 26 months later; follow-up is not available for the second patient. The diagnosis was often difficult in these cases, the most common problem being distinction from malignant lymphoma, but carcinoma, granulosa cell tumor, and, rarely, other tumors were considered. Immunohistochemical and enzyme histochemical staining were useful in establishing the diagnosis, although suspicion of the diagnosis on examination of routinely stained sections was of paramount importance.
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PMID:Granulocytic sarcoma of the female genital tract: a clinicopathologic study of 11 cases. 933 Dec 87

A large body of evidence has demonstrated that inhibition of the neutrophil's oxidant burst attenuates sepsis-induced acute lung injury. The present study sought to evaluate the ability of OPC-6535, a superoxide anion production inhibitor, to attenuate sepsis-induced acute lung injury. Four groups of swine were anesthetized, ventilated, and studied for 5 hr. Following surgical preparation, control (n = 10) and OPC-control (n = 2) animals received a 1-hr infusion of sterile saline. Sepsis was induced with a 1-hr intravenous infusion of live Pseudomonas aeruginosa. Untreated septic animals (n = 10) received no treatment. Animals treated with OPC-6535 (n = 6) received a 1 mg/kg bolus of OPC-6535 15 min prior to initiation of the bacterial infusion. Changes in systemic and pulmonary hemodynamics, arterial oxygen tension, bronchoalveolar lavage protein and neutrophil content, neutrophil integrin expression, neutrophil oxidant burst, and lung myeloperoxidase content were used as outcome measures. Treatment with OPC-6535 significantly reduced acute lung injury, as indicated by improved bronchoalveolar lavage protein and neutrophil content, resulting in a significant improvement in arterial oxygenation. Treatment with OPC-6535 failed to prevent the development of pulmonary hypertension and systemic hypotension. Neutrophils from animals with both treated and untreated sepsis exhibited significant up-regulation of CD18 and production of increased levels of oxidants, indicating significant activation when compared to neutrophils from control animals. Although animals treated with OPC-6535 produced 25% less superoxide anion than untreated septic animals, this decrease was not statistically significant. Treatment of animals with OPC-6535 prior to the onset of sepsis produced significant protection against acute lung injury but failed to attenuate hemodynamic derangements associated with sepsis.
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PMID:OPC-6535, a superoxide anion production inhibitor, attenuates acute lung injury. 934 16


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