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

In a retrospective study covering the period January 1972 to June 1974, recovery rates of bacteria and of fungi were generally equivalent with tryptic soy broth, Thiol, thioglycolate, and Columbia broth media (all under vacuum with carbon dioxide and sodium polyanetholesulfonate). An additional biphasic medium consisting of brain heart infusion broth and a brain heart infusion agar slant, which was inoculated only where fungal sepsis was suspected clinically, yielded significantly higher recovery rates of fungi. There were 29 instances of cultures with fungi in both the biphasic and broth media, 80 instances of cultures with fungi only in the biphasic medium, and no instances of fungi only in the broth media. The isolates were as follows: Candida albicans, 74; C. parapsilosis, 20; C. tropicalis, 16; Torulopsis glabrata, 18; Torulopsis sp., 1; Cryptococcus neoformans, 12; C. laurentii, 2; and Histoplasma capsulatum, 16. Despite routine subcultures of the broth media to chocolate blood agar within 24 h of inoculation and after 5 days of incubation, detection of fungemia was significantly improved by the use of a biphasic medium.
 ...
PMID:Detection of fungi in blood cultures. 117 6

Seventy-four New Zealand white rabbit pups were divided into four groups: group I, 2 days of age (n = 9); group II, 3 to 5 days of age (n = 24); group III, 6 to 8 days of age (n = 27); and group IV, 10 to 13 days of age (n = 14). Mouth swabs (MS), rectal swabs (RS), small bowel specimens (SB), and large bowel specimens (LB) were obtained from each rabbit, incubated for 24 hours in thioglycolate broth, and plated on blood agar in aerobic and anaerobic environments. After 24 hours, growth on blood agar plates were observed. All MS specimens and all but one RS specimen showed positive growth. Growth of both LB and SB specimens increased significantly with age (P < .04). In addition, SB growth was significantly less than RS or MS growth in groups I, II, and III (P < .05). LB growth was significantly less than RS or MS growth in group I (P < .01) and tended to be less in groups II and III (62.5% v 100% and 93% v 100%, respectively). These data show that nearly half of normal rabbits under 6 days of age have sterile small and large intestines despite almost 100% growth from rectal and mouth swabs. These findings partially explain the absence of spontaneous bacterial translocation in young rabbit pups (under 4 days of age) and have important implications for the prophylaxis and treatment of neonatal sepsis.
 ...
PMID:Colonization of intestinal bacteria in the normal neonate: comparison between mouth and rectal swabs and small and large bowel specimens. 780 23

Macrophage hyperactivity has been suggested to play an important role in septic complications and the development of multiple organ failure. Intraperitoneal administration of macrophage stimulants, e.g., zymosan, induce a systemic inflammatory response, with concomitant gut origin sepsis, and organ dysfunction. However, little is known about alterations in endothelial permeability during macrophage hyperactivation. In the present study, the effect of macrophage hyperactivation on endothelial permeability, assessed by 125I-labeled HSA and 51Cr-labeled EDTA, and the difference between cytolytic and noncytolytic inflammatory macrophages induced by i.p. injection of .25 or .50 mg/g of zymosan, concanavalin A (Con A) or thioglycollate medium (TM) diluted in 4 mL of paraffin, as well as the potential relationship with the doses used, were evaluated in the rat. Overactivation of cytolytic inflammatory macrophages induced a pronounced alteration in endothelial barrier permeability, characterized by a decrease in whole body plasma volume and an increase in whole body interstitial fluid volume, while overactivation of noncytolytic inflammatory macrophages only induced leakage of proteins and plasma to several of the organs studied. Macrophage activators, like zymosan, Con A and TM, exhibited varying effects on endothelial permeability related to the dose used. The results in the present study imply that overactivation of cytolytic inflammatory macrophages may play an important role in endothelial barrier injury and that zymosan possesses a more potent effect as compared to Con A when administered at the same dose.
 ...
PMID:Alterations in endothelial barrier permeability in multiple organs during overactivation of macrophages in rats. 885 47

Group B streptococci (GBS) are an important cause of neonatal sepsis, pneumonia and meningitis. In the early phase of infection, macrophages and polymorphonuclear cells (PMN) are the first immune cells that interact with GBS. In this in vitro study, to gain insight into GBS-macrophage interaction in the absence of type-specific antibodies, we examined the features of GBS survival in thioglycollate-elicited murine peritoneal macrophages and the effect of GBS on the protein kinase C (PKC)-dependent transduction pathway. Our results demonstrate that type Ia GBS, strain 090 (GBS-Ia) and type III GBS strain COH 31r/s (GBS-III), after in vitro phagocytosis survive and persist intracellularly in macrophages for up to 24 and 48 hr, respectively. However, macrophage activation by interferon-gamma (IFN-gamma) and lipopolysaccharide from Escherichia coli (LPS) caused a significant reduction in the time of intracellular persistence. Macrophage activation by IFN-gamma and LPS seems to be a multifactorial event involving multiple intracellular signal pathways also including PKC. Since PKC is one of the components in the signal network leading to macrophage activation and an important target for several intracellular micro-organisms, we wondered whether PKC could have a role in intracellular GBS survival. Both PKC depletion by treatment with phorbol 12-myristate 13-acetate (PMA) for 18 hr and PKC inhibition by Calphostin C rendered macrophages more permissive for the intracellular GBS survival. Furthermore, GBS-infected macrophages were unable to respond to PMA and LPS, activators of PKC, by inducing antimicrobial activity. The ability of GBS to impair PKC-dependent cell signalling was also demonstrated by the reduced c-fos gene expression in GBS-infected macrophages with respect to control macrophages, after LPS stimulation. In conclusion, our results indicate that GBS survive in macrophages and impairment of PKC signal transduction contributes to their intracellular survival.
 ...
PMID:Group B streptococci persist inside macrophages. 953 23

It is thought that lipopolysaccharide (LPS) from gram-negative bacteria contributes significantly to the pathogenesis of septic shock. In vitro studies to address the mechanisms involved in this process have often investigated human monocytes or mouse macrophages, since these cells produce many of the mediators found in septic patients. Targeting of these mediators, especially tumor necrosis factor alpha (TNF-alpha), has been pursued as a means of reducing mortality in sepsis. Two experimental approaches were designed to test the assumption that in vitro studies with macrophages accurately predict in vivo mechanisms of LPS pathogenesis. In the first approach, advantage was taken of the fact that on consecutive days after injection of thioglycolate into mice, increased numbers of macrophages could be harvested from the peritoneum. These cells manifested markedly enhanced levels of in vitro TNF-alpha, interleukin 6 (IL-6), and nitric oxide production in response to LPS. In D-galactosamine-sensitized mice, however, thioglycolate treatment significantly decreased mortality due to LPS, as well as levels of circulating TNF-alpha and IL-6. Anti-TNF-alpha treatment confirmed this cytokine's role in the observed lethality. In a second experimental approach, we compared the mouse macrophage-stimulating potencies of different LPS preparations with their lethalities to mice. In these studies, the in vitro macrophage-stimulating profiles presented by rough-LPS and smooth-LPS preparations were the reverse of their relative lethal potencies in vivo. In conclusion, peritoneal macrophages appear not to be the major cells responsible for the overall host response during endotoxic shock. These findings underscore the importance of verifying the correlation of in vivo systems with in vitro systems when attributing specific functions to a cell type.
 ...
PMID:Mechanisms involved in the pathogenesis of sepsis are not necessarily reflected by in vitro cell activation studies. 978 46

Previous publications demonstrated that elevated systemic levels of interleukin (IL)-8 decrease local neutrophil recruitment. We tested whether sustained, high plasma levels of IL-8 would prevent local inflammation after inflammatory insults. Mice carrying the transgene for human IL-8 were separated on the basis of their plasma levels of IL-8 into IL-8-positive (plasma levels >90 ng/ml) and IL-8-negative (IL-8 below detection). Presence of the IL-8 transgene did not improve survival or morbidity nor did it alter peritoneal neutrophil recruitment induced by the cecal ligation and puncture model of sepsis. In an acute lung injury model created by intratracheal injection of acid, IL-8-positive mice showed no reduction in alveolar neutrophil recruitment. There was no difference in the local recruitment of neutrophils when either thioglycollate or glycogen was injected intraperitoneally. We examined the chemotactic response to murine chemokines to test how neutrophil recruitment occurs in the setting of elevated plasma IL-8 and found that neutrophils from both IL-8-positive and -negative mice respond equally well to recombinant KC or macrophage inflammatory protein (MIP)-2. We measured KC and MIP-2 in the peritoneum after thioglycollate injection and demonstrated that IL-8-positive mice have significantly higher levels of the chemokines compared to the IL-8-negative mice. Antibody inhibition of KC and MIP-2 in the IL-8-positive mice significantly decreased peritoneal neutrophil recruitment in response to thioglycollate, clarifying their important role in the local neutrophil recruitment. Our data demonstrate that despite the presence of high plasma levels of IL-8, neutrophils may still be recruited to sites of local inflammation because of chemokine redundancy.
 ...
PMID:CXC chemokine redundancy ensures local neutrophil recruitment during acute inflammation. 1154 8

During bacterial infections, the balance between resolution of infection and development of sepsis is dependent upon the macrophage response to bacterial products. We show that priming of murine bone marrow-derived macrophages (BMMs) with CSF-1 differentially regulates the response to two such stimuli, LPS and immunostimulatory (CpG) DNA. CSF-1 pretreatment enhanced IL-6, IL-12, and TNF-alpha production in response to LPS but suppressed the same response to CpG DNA. CSF-1 also regulated cytokine gene expression in response to CpG DNA and LPS; CpG DNA-induced IL-12 p40, IL-12 p35, and TNF-alpha mRNAs were all suppressed by CSF-1 pretreatment. CSF-1 pretreatment enhanced LPS-induced IL-12 p40 mRNA but not TNF-alpha and IL-12 p35 mRNAs, suggesting that part of the priming effect is posttranscriptional. CSF-1 pretreatment also suppressed CpG DNA-induced nuclear translocation of NF-kappaB and phosphorylation of the mitogen-activated protein kinases p38 and extracellular signal-related kinases-1/2 in BMMs, indicating that early events in CpG DNA signaling were regulated by CSF-1. Expression of Toll-like receptor (TLR)9, which is necessary for responses to CpG DNA, was markedly suppressed by CSF-1 in both BMMs and thioglycolate-elicited peritoneal macrophages. CSF-1 also down-regulated expression of TLR1, TLR2, and TLR6, but not the LPS receptor, TLR4, or TLR5. Hence, CSF-1 may regulate host responses to pathogens through modulation of TLR expression. Furthermore, these results suggest that CSF-1 and CSF-1R antagonists may enhance the efficacy of CpG DNA in vivo.
 ...
PMID:Colony-stimulating factor-1 suppresses responses to CpG DNA and expression of toll-like receptor 9 but enhances responses to lipopolysaccharide in murine macrophages. 1175 85

Sepsis is associated with enhanced production of tissue-type plasminogen activator (tPA). We investigated the function of endogenous tPA in the immune responses to Escherichia coli-induced abdominal sepsis using tPA gene-deficient (tPA(-/-)) and normal wild-type (WT) mice. tPA(-/-) mice demonstrated an impaired defense against E. coli peritonitis as indicated by higher bacterial loads at the primary site of the infection, enhanced dissemination, and reduced survival. The protective function of tPA was independent of plasmin since plasminogen gene-deficient (Plg(-/-)) mice were indistinguishable from WT mice. Relative to WT mice, tPA(-/-) mice demonstrated similar neutrophil counts in the peritoneal cavity despite much higher bacterial loads and higher local concentrations of neutrophil attracting chemokines, suggesting a reduced migratory response. In line, tPA(-/-) mice demonstrated a reduced thioglycolate-induced neutrophil influx into the peritoneal cavity and i.p. injection of WT mice with a replication-defective adenoviral vector expressing tPA caused an enhanced cell migration to the peritoneal cavity during E. coli peritonitis. These findings identify a novel protective function of tPA in abdominal sepsis caused by E. coli that seems independent of its role in the generation of plasmin.
 ...
PMID:Endogenous tissue-type plasminogen activator is protective during Escherichia coli-induced abdominal sepsis in mice. 1681 77

Sepsis is a multifactorial, and often fatal, disorder typically characterized by widespread inflammation and immune activation with resultant endothelial activation. In the present study, we postulated that the adipokine adiponectin serves as a critical modulator of survival and endothelial activation in sepsis. To this aim, we evaluated both loss-of-function (adiponectin gene-deficient mice) and subsequent gain-of-function (recombinant adiponectin reconstitution) strategies in two well-established inflammatory models, cecal ligation perforation (CLP) and thioglyocollate-induced peritonitis. Adipoq(-/-) mice, subjected to CLP, exhibited a profound ( approximately 8-fold) reduction in survival compared with their wild-type Adipoq(+/+) littermates after 48 h. Furthermore, compared with wild-type controls, thioglycollate challenge resulted in a markedly greater influx of peritoneal neutrophils in Adipoq(-/-) mice accompanied by an excess production of key chemoattractant cytokines (IL-12p70, TNFalpha, MCP-1, and IL-6) and upregulation of aortic endothelial adhesion molecule VCAM-1 and ICAM-1 expressions. Importantly, all of these effects were blunted by recombinant total adiponectin administration given 3 days prior to thioglycollate challenge. The protective effects of adiponectin were ascribed largely to higher-order adiponectin oligomers, since administration of recombinant C39A trimeric adiponectin did not attenuate endothelial adhesion molecule expression in thioglycollate-challenged Adipoq(-/-) mice. These data suggest a critical role of adiponectin as a modulator of survival and endothelial inflammation in experimental sepsis and a potential mechanistic link between adiposity and increased sepsis.
 ...
PMID:Adiponectin deficiency promotes endothelial activation and profoundly exacerbates sepsis-related mortality. 1917 45

In sepsis, phagocytosis and the killing of bacteria by phagocytes are important. Similarly, the clearance of accumulating apoptotic cells is critical in maintaining normal immunity. Upon maturation, peritoneal macrophages (PM) become a major source of proinflammatory cytokines, while losing their efficacy of phagocytosis. However, the underlying mechanism remains unknown. Here we investigated the differential effects of apoptotic thymocytes (AoTC) on TNF-alpha release in immature thioglycolate-elicited PM (TGPM) and mature resident PM (RPM) in vitro by culturing them with or without AoTC and/or LPS. MFG-E8 expression was assessed using Western blotting and the ability to engulf AoTC was determined histologically. Cytokine secretion was measured by ELISA. MAP kinase phosphorylation was assessed using Western blotting. Mature RPM express <50% of TGPM MFG-E8 levels and have a 30% lower capacity to clear AoTC. The proinflammatory response (TNF-alpha release) to LPS is 5 times higher, and the capability to phagocytose is decreased along with further down-regulation of MFG-E8 after LPS-stimulation. RPMs also lack phagocytosis-induced inhibition of TNF-alpha release after LPS stimulation. LPS-induced phosphorylation of ERK1/2, p38 and JNK is more enhanced in RPM compared to TGPM. MFG-E8-mediated apoptotic cell phagocytosis results in an inhibition of MAPK and NFkappaB signaling pathways. Differential MAPK activation may play a role in the enhanced LPS responsiveness of RPM and the lack of MFG-E8 impedes post-phagocytic suppression of LPS-response through the inhibition of those signaling pathways. These results provide a potential mechanistic insight into the benefit of promoting apoptotic cell clearance via MFG-E8 under inflammatory conditions.
 ...
PMID:Maturation-induced down-regulation of MFG-E8 impairs apoptotic cell clearance and enhances endotoxin response. 1902 Jul 71


1 2 3 Next >>