Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eleven premature neonates received gentamicin sulfate for treatment of suspected gram-negative sepsis with accompanying respiratory distress syndrome. Serum gentamicin concentrations were measured during and after treatment to monitor therapy and to determine the two-compartment distribution and elimination characteristics of the drug. The measured pharmacolinetic parameters were compared to those of 14 adult patients with similar glomerular filtration rates. Neonates, like adults and children, had a prolonged persistence of gentamicin in the serum after treatment was stopped. Although there were marked differences between neonates and adults in administered dose, clearance, and distribution volume when the data were expressed on the basis of body weight, these differences were no longer apparent when the data were expressed relative to body surface area. Differences in gentamicin disposition cannot explain the apparent lack of aminoglycoside nephrotoxicity among premature neonates.
 ...
PMID:Two-compartment gentamicin pharmacokinetics in premature neonates: a comparison to adults with decreased glomerular filtration rates. 735 7

Streptococcus suis causes meningitis, sepsis, and other serious infections in newborn and young pigs and in adult humans. The Gal alpha 1-4Gal-binding adhesin of S. suis was purified to homogeneity by ultrasonic treatment, fractional ammonium sulfate precipitation, and preparative polyacrylamide gel electrophoresis. Pigeon ovomucoid, a glycoprotein with Gal alpha 1-4Gal terminals, was used to detect the adhesin by blotting. The purified adhesin appeared as single band of an apparent size of 18 kDa and of a pI of 6.4; no disulfide bridges were present. The amount of adhesin as revealed by pigeon ovomucoid binding correlated with the hemagglutination activity of different S. suis strains. The purified adhesin bound to latex particles induced hemagglutination which was specifically inhibited with the same inhibitors as hemagglutination by the intact bacteria, thus demonstrating that the purified protein was the Gal alpha 1-4Gal-recognizing adhesin of S. suis. Two adhesin variants (PN and PO) with differing Gal alpha 1-4Gal binding specificity had the similar electrophoretic mobilities and the same N-terminal peptide sequences, indicating that they were closely related. This represents the first isolation of an adhesin with well-defined cell surface carbohydrate binding activity from Gram-positive bacteria associated with meningitis.
 ...
PMID:Purification of a galactosyl-alpha 1-4-galactose-binding adhesin from the gram-positive meningitis-associated bacterium Streptococcus suis. 749 14

Vascular endothelial injury observed in overwhelming sepsis may be caused by neutrophil-derived enzymes. Adherence to the endothelium, a prerequisite for this process, is mediated sequentially by the neutrophil adhesion molecules L-selectin and the beta 2 integrins including CD11b/CD18. The relationship between expression of these molecules, neutrophil adherence, endothelial activation, and consequent endothelial injury was assessed by changes in heparan sulfate and fibronectin matrices. Endothelial prestimulation with lipopolysaccharide caused both an increase in adherence and a generalized reduction in heparan sulfate; disruption of the fibronectin matrix occurred only on the further addition of FMLP. Although maximal disruption of these matrices was associated with elevation of neutrophil CD11b/CD18 and reduction in L-selectin expression, these changes did not determine either the nature or extent of endothelial damage. This model may provide further insights into the interrelationship between neutrophil activation and endothelial damage in gram-negative sepsis.
 ...
PMID:Degradation of glycosaminoglycans and fibronectin on endotoxin-stimulated endothelium by adherent neutrophils: relationship to CD11b/CD18 and L-selectin expression. 768 Jul

Sepsis induces a net catabolic state in gastrocnemius by increasing protein degradation and decreasing protein synthesis. To determine whether or not sepsis induces a preferential effect on the expression of individual proteins, proteins from gastrocnemius muscle of control and septic rats were separated by two-dimensional isoelectric focusing/sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Laser densitometry of proteins stained with silver provided evidence that the relative abundance of thirty-five proteins was significantly (p < .05) and reproducibly increased during sepsis compared to control. No individual protein underwent significant down-regulation in their relative abundance during sepsis. Twenty-three of the 35 proteins identified in two-dimensional gels of the gastrocnemius were also present in the plasma of septic rats. The remaining 12 proteins, therefore, were taken to represent skeletal muscle proteins. One of the 12 proteins was identified by immunoblot analysis to be carbonic anhydrase III. Another of the proteins was identified as triosephosphate isomerase based upon microsequencing of the N terminus.
 ...
PMID:Altered expression of skeletal muscle proteins during sepsis. 774 46

The effect of heparan sulfate (HS) on survival rate, bacterial translocation, and host defense was studied in a model of gut-derived sepsis that included transfusion-induced immunosuppression. Balb/c mice were treated pre- and postburn injury and bacterial challenge with HS, 5 mg/kg/day, or sterile phosphate-buffered saline. The HS pre- and postburn treated animals showed a significant improvement in survival compared to control animals (80 vs. 30%, p = .004, and 60 vs. 20%, p = .02, respectively). A lower amount of translocation was observed in the spleen (p < or = .001) of the HS group compared to control group. Quantitative colony counts and the calculated percentage of viable bacteria showed that the ability to kill translocated organisms was enhanced in all tissues of the animals receiving HS. These data suggest that treatment with HS positively affects the outcome in gut-derived sepsis. The beneficial effect was related both to an improved gut barrier function and to an enhanced host defense.
 ...
PMID:Heparan sulfate increases survival during gut-derived sepsis by decreasing bacterial translocation and enhancing host defense. 775 15

We investigated whether hypermagnesemia alleviates hypoxic or group B streptococcal (GBS) pulmonary hypertension (PH). Hypoxic PH was induced and maintained in 14 lambs by continuous ventilation with 12% oxygen. GBS PH was induced and maintained in 16 lambs by the continuous infusion of 5-10 x 10(8) colony-forming units.kg-1.h-1 of GBS. After the onset of PH, lambs were randomized to receive either magnesium sulfate (MgSO4, intermittent boluses of 0.38 mmol/kg, with a continuous infusion of 0.15 mmol.kg-1.h-1) or a similar volume of normal saline. Hypermagnesemia lowered pulmonary arterial pressure (PAP) and delayed the fall in systemic arterial pressure and stroke volume index seen in the control animals (each P < 0.05). At a serum magnesium concentration ([Mg]) of 2.75 +/- 0.25 mmol/l, PAP was 27 +/- 3 compared with 40 +/- 4 Torr in the control animals ([Mg] = 0.87 +/- 0.06 mmol/l; P < 0.05). In the GBS PH trial, hypermagnesemia prevented the continued increase in PAP seen in the control animals. At [Mg] = 2.15 +/- 0.07 mmol/l, PAP fell 2 +/- 1 Torr from prerandomization values, whereas it rose 4 +/- 2 Torr in the control animals ([Mg] = 0.59 +/- 0.07 mmol/l; P < 0.05). However, during the same time the systemic arterial pressure fell further in the magnesium-treated animals (-19 +/- 1 vs. -2 +/- 5 Torr). MgSO4 attenuates PH in both models but may cause systemic hypotension in sepsis.
 ...
PMID:Magnesium attenuates pulmonary hypertension due to hypoxia and group B streptococci. 800 24

Shigellemia is rare in developed countries and might result from the emergence of unusually virulent strains. We compared systemic invasiveness markers of isolates from the blood of 3 temporally clustered patients with Shigella sonnei bacteremia in Boston with those of 11 unrelated contemporaneous strains from stools of people in New England. We found no difference between the two groups in O-chain length by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, mouse 50% lethal dose, in vivo response to iron, and susceptibility to serum, which varied from moderately susceptible to ultrasusceptible. Mean intraperitoneal 50% lethal doses of smooth form I colonies for mice were equally low (10(5.8) CFU) in both groups, and the 50% lethal doses were lowered equally further in the two groups by predosing with iron to levels useful in mouse model sepsis studies. S. sonnei bacteremia may reflect compromised host defenses, not bacterial virulence.
 ...
PMID:Comparative virulence of blood and stool isolates of Shigella sonnei. 819 2

We evaluated the efficacy and safety of combination therapy with sulbactam/cefoperazone (SBT/CPZ) and amikacin sulfate (AMK) in severe infections associated with hematological disorders. The clinical efficacy rate in 82 evaluable patients was 70.7%. The efficacy rate in sepsis from which causative organisms were isolated was high, 75% (3/4). No significant difference was found between those cases for which no previous antibiotic therapies were made and those for which antibiotic therapies were done and changed to the combination during the course of the therapies. No side effects nor substantial abnormal laboratory test results attributable to the test drugs were observed. From these observations, we have concluded that the combination therapy with SBT/CPZ plus AMK is a very useful empiric therapy for severe infections associated with hematological disorders.
 ...
PMID:[Clinical evaluation of combination therapy with sulbactam/cefoperazone and amikacin sulfate for infections associated with hematological disorders]. 825 93

We analyzed differences in host regulation of tumor necrosis factor-alpha (TNF-alpha) production and pathophysiological responses in conscious rats after infection with two strains of pathogenic Candida albicans spp. (CA-1 and CA-2) compared with Escherichia coli serotype 055:B5 (EC). The hypothesis was tested that, in contrast to EC, hypotension, organ injury, and mortality after candidemia are not obligatorily dependent on TNF-alpha or TNF-alpha-induced cyclooxygenase pathway metabolites. Dose, viability, and strain-specific dependencies were established after intravenous 10(6) or 10(9) viable CA, as well as heat-killed (HK) or Formalin-inactivated (FI) CA blastospores, compared with live EC at the 24-h LD25 [10(9) colony-forming units (CFU)] and LD100 (10(10) CFU). Shock without endotoxemia developed 4-8 h after 10(9) live CA-1 or CA-2 (LD100 at 24 h) with disseminated yeast-mycelial transformation and increased microvascular permeability in multiple organs but not after HK or FI CA-1. Peak serum TNF-alpha after an LD100 of CA-1 or CA-2 was < 3% of LD25 EC values and was < 1% of peak values during lethal bacteremia. Similar pathogen-specific differences were found in liver- and lung-associated TNF. Production of functionally inactive TNF-alpha during candidemia was excluded by enzyme-linked immunosorbent assay and sodium dodecyl sulfate-polyacrylamide gel electrophoresis with Western blotting. Passive immunization against TNF-alpha 2 h before microbial challenge was not protective against CA but prevented otherwise lethal EC sepsis. Cyclooxygenase inhibition also failed to attenuate candidemic shock. We conclude that the magnitude and kinetics of TNF-alpha production and TNF-alpha-dependent immunophysiological responses are differentially regulated after lethal fungal vs. gram-negative bacterial infection. Thus TNF-alpha is not a pivotal mediator of the acute Candida septic shock syndrome with disseminated candidiasis.
 ...
PMID:TNF-alpha and cyclooxygenase metabolites do not modulate C. albicans septic shock with disseminated candidiasis. 833 78

Translocation of enteric microorganisms from the intestinal tract to extraintestinal sites has been proposed as an early step in the development of gram-negative sepsis. This study examined the role of altered bowel transit in influencing intestinal bacteriostasis and bacterial translocation using morphine as a pharmacologic inhibitor of such transit. In the first experiment, either normal saline (N = 8) or morphine sulfate (20 mg/kg; N = 8) was injected subcutaneously. Two hours later, morphine (7.5 mg/kg) was infused subcutaneously for an additional 22 hr; control animals received saline alone. After completion of this regimen, a volume of 0.2 ml of 2.5 mM FITC dextrans (10,000 daltons) were injected intraduodenally in each group. The bowel was removed 25 min later, divided into 5-cm segments, and the content of dextrans measured. Small bowel propulsion was expressed as the geometric center of the distribution of dextrans throughout the intestine (in percentage length of small bowel). Gut propulsion was significantly reduced after morphine treatment as compared to controls (32.8 +/- 8.2% vs. 55.8 +/- 4.0%; P < 0.01). In 16 additional rats, saline or morphine was again administered as described. After 24 hr, samples were obtained from the mesenteric lymph node (MLN) complex, blood, spleen, liver, duodenum, jejunum, ileum, and cecum for standard bacteriology. The bacterial counts increased significantly in each intestinal segment following morphine treatment. Microorganisms translocated to the MLN complex in 5, and to distant sites in four of eight morphine-treated animals, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Alterations in rat intestinal transit by morphine promote bacterial translocation. 834 12


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>