Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085437 (bacterial meningitis)
 4,038 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With the use of gas-liquid chromatographic techniques, the chemical characteristics of Streptococcus pneumoniae type 3, Escherichia coli, group B Neisseria meningitidis, Haemophilus influenzae type b, and Staphylococcus aureus, organisms that commonly cause bacterial meningitis, were identified. The combination of lipid, carbohydrate, and lipopolysaccharide components provided discriminating markers for chemotyping these bacteria. E. coli had a high content of 17- and 19-carbon cyclopropane fatty acids, whereas none of the other organisms tested revealed any cyclic acids, apart from a possible trace amount in S. pneumoniae. The content of isomethyl branching fatty acids clearly distinguished S. pneumoniae and S. aureus. N. meningitidis and H. influenzae were somewhat similar in their overall fatty acid compositions, but the presence of galactose without rhamnose in extracts of N. meningitidis readily distinguished N. meningitidis from H. influenzae. Only extracts from E. coli contained mannose; erythrose was an exclusive marker in extracts of S. pneumoniae. These data suggest that these differences in chemotype might be useful in developing a gas-liquid chromatographic assay of spinal fluid for the rapid laboratory diagnosis of bacterial meningitis.
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PMID:Diagnosis of bacterial meningitis by gas-liquid chromatography. I. Chemotyping studies of Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Staphylococcus aureus, and Escherichia coli. 39 61

Cytokines have been implicated in the pathogenesis of gram-negative bacterial meningitis. The effects of pentoxifylline and dexamethasone on the release of tumor necrosis factor (TNF), interleukin (IL)-1, and IL-6 from primary murine microglial cell cultures were explored using bioassays. When added concomitantly with lipopolysaccharide, pentoxifylline blocked the release of TNF and IL-1 but not IL-6, while dexamethasone inhibited the release of TNF and IL-6. After a 2-h exposure of microglia to lipopolysaccharide, pentoxifylline but not dexamethasone still inhibited the release of TNF. Release of TNF was enhanced 20-fold by priming of the microglia with interferon-gamma; only pentoxifylline blocked the priming effect of interferon-gamma on TNF release. These results demonstrate that pentoxifylline and dexamethasone differentially regulate the release of cytokines in microglial cell cultures and provide potential insight into their role in the treatment of gram-negative bacterial meningitis.
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PMID:Cytokine release from microglia: differential inhibition by pentoxifylline and dexamethasone. 152 22

The possible contribution of additional immunologic variables to the susceptibility of late complement component-deficient individuals to meningococcal disease has not been systematically examined in previous studies. Thus, we studied three groups of patients: (1) 24 healthy individuals, (2) 8 complement-sufficient individuals with a history of recurrent bacterial meningitis, and (3) 19 complement-deficient individuals with prior meningococcal infection. No statistical differences were noted among the three groups for the following parameters: the absolute number and the percentage of lymphocytes; CD3+, CD4+, CD8+, CD20+, and CD16+ cells; and the CD4+/CD8+ ratio. The concentration of C4 and circulating immune complexes was also similar among the groups. The concentrations of IgG, IgM, and IgA were slightly, but significantly, decreased in the complement-deficient individuals. Of interest, the coefficient of spontaneous and lipopolysaccharide-stimulated activation of neutrophils was significantly depressed in the deficient individuals. We hypothesize that the terminal complement components may participate in maximal neutrophil activation.
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PMID:Immunological evaluation of late complement component-deficient individuals. 164 49

Injury to the blood brain barrier (BBB) is a fundamental sequela of bacterial meningitis, yet the precise mechanism facilitating exudation of albumin across the endothelium of the cerebral microvasculature remains conjectural. After intracisternal inoculation of Escherichia coli (0111:B4) lipopolysaccharide in rats to elicit a reversible meningitis and BBB injury, we utilized in situ tracer perfusion and immunolabeling procedures to identify by transmission electron microscopy the precise topography and microvascular exit pathway(s) of bovine serum albumin (BSA). Results revealed that during meningitis there was: (a) an inducible increase in immunodetectable monomeric BSA binding to the luminal membrane of all microvascular segments in the pia-arachnoid and superficial brain cortex; (b) similar uptake of both colloidal Au-BSA (as well as monomeric BSA) by plasmalemmal vesicles but no detectable transcytosis to the abluminal side; and (c) predominant exit of both perfused Au-BSA and immunodetectable monomeric BSA through open intercellular junctions of venules in the pia-arachnoid. This was corroborated in separate experiments documenting focal pial venular leaks of in situ perfused 0.01% colloidal carbon black during experimental meningitis. These results provide precise localization of BBB injury in meningitis to meningeal venules, confirm a paracellular exit pathway of albumin via open intercellular junctions, and suggest an injury mechanism amenable to specific therapeutic intervention.
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PMID:Ultrastructural localization of albumin transport across the cerebral microvasculature during experimental meningitis in the rat. 187 66

To evaluate the role of endotoxin during Gram-negative bacterial meningitis, the nervous lesions of piglets, calves, rabbits and mice were compared by direct inoculation of Escherichia coli lipopolysaccharide into the central nervous system. Suppurative leptomeningitis was induced in piglets by small doses of lipopolysaccharide. Mice also had a mild suppurative inflammation in the leptomeninges. In contrast, calves showed suppurative pachymeningitis, but no lesions in the leptomeninges. Leptomeningeal inflammation was not induced in rabbits. Induction of the leptomeningitis by endotoxin was compared with sensitivity to intravenous or intraperitoneal endotoxin in these species.
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PMID:A comparison of central nervous lesions directly induced by Escherichia coli lipopolysaccharide in piglets, calves, rabbits and mice. 201 76

Interleukin-1 (IL-1) is the key initiator of host responses to infection. We describe here the lipopolysaccharide-(LPS) (20 micrograms/ml) stimulated IL-1 production of peripheral blood monocytes in 2 children with Haemophilus influenzae meningitis. We found a depressed IL-1 production at the acute stage of the infection when the meningitis was most active with return to normal coinciding with clinical recovery. These results show an inverse correlation with acute phase reactants and IL-1 production. Normalization of IL-1 production seems to be a good prognostic sign in bacterial meningitis.
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PMID:Interleukin-1 production in bacterial meningitis. 232 Sep 58

The factors responsible for blood-brain barrier (BBB) injury during bacterial meningitis are incompletely defined. We evaluated the role of Haemophilus influenzae type b (Hib) lipopolysaccharide (LPS) in the alteration of blood-brain barrier permeability (BBBP) in an adult, normal and leukopenic, rat model of meningitis. Intracisternal inoculation of Hib LPS resulted in (a) dose-dependent increases in BBBP from 2 pg to 20 ng, with significant attenuation in the peak response after challenge with 500 ng and 1 microgram; (b) time-dependent increases in BBBP, with a delayed onset of at least 2 h, maximum alteration at 4 h, and complete reversal at 18 h; (c) greater BBBP than after challenge with the live parent strain; (d) and a close correlation (r = 0.86) between CSF pleocytosis and BBBP at 4 h. The LPS effect was significantly inhibited by preincubation with Polymyxin B and neutrophil acyloxyacyl hydrolase, however two different oligosaccharide-specific monoclonal antibodies did not inhibit activity. No change in BBBP after inoculation with Hib LPS occurred in leukopenic rats. Hib LPS, in the setting of an intact leukocyte response, exerts profound effects on BBBP.
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PMID:Haemophilus influenzae lipopolysaccharide-induced blood brain barrier permeability during experimental meningitis in the rat. 326 27

We have investigated the possible role of nitric oxide (NO) in the pathophysiology of bacterial meningitis (BM) by using the rat model of experimental BM. The nitrite concentration in cerebrospinal fluid (CSF) was used as a measure of NO production in vivo since NO rapidly degrades to nitrite and nitrate. Rats were inoculated intracisternally with live bacteria (5 x 10(6) CFU of Haemophilus influenzae type b strain DL42 or Rd-/b+/O2), with bacterial endotoxin (20 ng of DL42 lipooligosaccharide [LOS] or 200 ng of Escherichia coli lipopolysaccharide), or with a saline control vehicle. CSF samples were collected preinoculation and at the time of maximal alteration in blood-brain barrier permeability (BBBP). CSF [nitrite] was quantified by measuring A550 after addition of the Greiss reagent and comparison to a standard curve of sodium nitrite. Rats inoculated with either DL42, Rd-/b+/O2, LOS, or lipopolysaccharide demonstrated a significantly elevated mean peak CSF [nitrite] (8.34, 15.62, 10.75, and 10.44 mM, respectively) versus the concentration prior to treatment and/or those in saline-treated animals (5.29 and 5.33 mM, respectively; P < 0.05 for each comparison). We then determined if there was a correlation between CSF [nitrite] and percent BBBP (%BBBP) at various time points postinoculation with Rd-/b+/O2. %BBBP was defined as the concentration of systemically administered 125I-labeled bovine serum albumin in the CSF divided by the level of 125I-labeled bovine serum albumin in serum multiplied by 100. The mean %BBBP increased in tandem with the mean CSF [nitrite] (R = 0.84, P = 0.018), which peaked at 18 h in the absence of a change in the serum [nitrite]. Systemic administration of the NO synthase inhibitor N-nitro-L-arginine methyl ester demonstrated a significant reduction of mean CSF nitrite production (0.95 versus 6.0 mM in controls; P = 0.02) when administered intravenously to animals which had been inoculated intracisternally with 20 ng of LOS. Suppression of mean leukocyte pleocytosis (3,117 versus 11,590 leukocytes per mm3 in control LOS-challenged rats; P = 0.03) and mean alterations of BBBP (2.11 versus 6.49% in control LOS-challenged rats; P = 0.009) was observed concomitantly with decreased CSF [nitrite]. These results support the hypothesis that NO contributes to increased %BBBP in experimental BM.
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PMID:Potential role of nitric oxide in the pathophysiology of experimental bacterial meningitis in rats. 755 88

Tumor necrosis factor-alpha (TNF-alpha) is a pathogenic factor in bacterial meningitis. The effect of thalidomide on TNF-alpha production by microglia, the resident macrophages of the brain, was evaluated. In primary human fetal microglial cell cultures stimulated with lipopolysaccharide or lipoarabinomannan, thalidomide inhibited TNF-alpha release in a dose-dependent manner. The inhibitory effect of thalidomide was similar to that of dexamethasone, although expression of TNF-alpha mRNA in microglial cells was reduced only by thalidomide. The results of this in vitro study suggest that thalidomide could have therapeutic potential in gram-negative bacterial and tuberculous meningitis.
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PMID:Thalidomide inhibits tumor necrosis factor-alpha production by lipopolysaccharide- and lipoarabinomannan-stimulated human microglial cells. 756 Nov 98

Alterations in the blood-brain and blood-cerebrospinal fluid barriers occur during bacterial meningitis. Preventing barrier alterations is important as the increases in barrier permeability are thought to contribute to adverse neurological outcomes. The objective of this study was to characterize pharmacokinetically cerebrovascular permeability alterations during meningeal inflammation. 14C-Sucrose was used as a quantitative marker of cerebrovascular integrity 8 hr after induction of experimental meningitis by intracisternal injection of 0, 25 or 200 micrograms lipopolysaccharides. Serum and brain tissues were obtained after tracer dosing. 14C-Sucrose influx transfer coefficients (Kin(app)) and cerebrovascular volumes (Vbr) were calculated for each brain region. Regional Vbr values were unaffected by lipopolysaccharide pretreatment. However, statistically significant increases in 14C-sucrose K(in)(app) values were observed in various brain regions (1.6- to 3.3-fold from control; P < .05). These permeability alterations cannot be attributed to changes in the systemic pharmacokinetics of 14C-sucrose as total clearance and the volume of distribution were unaffected by lipopolysaccharide treatment. This approach can be used in future studies to examine the contribution of various inflammatory mediators to altered cerebrovascular permeabilities during experimental meningitis.
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PMID:Cerebrovascular permeability changes during experimental meningitis in the rat. 756 88


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