deoxycholic-acid and Sepsis

Chitosan (CH) coated ciprofloxacin-sodium deoxycholate surfplex (CFn-SDC) loaded nanoemulsion (LE-CH-CFn-SDC) developed in order to improve tissue penetration of the CFn as well as to mop up the endotoxin (Lipopolysaccharides or LPS) released from bacteria during antibiotic treatment.. Size and zeta potential was evaluated for nanoemulsions prepared by high-speed homogenization and sonication. Drug analysis in samples was done by HPLC equipped with fluorescence detector. All formulations were evaluated for any change in LPS induced NO and TNF-α release and ROS generation in J774 macrophages. The formulations were also evaluated for in-vitro killing efficiency on E-Coli. The efficacy of formulations in terms of survival and pharmacokinetics and inhibition of induction of cytokines was carried out in E-coli induced peritonitis model in rats. LE-CH-CFn-SDC interacted with LPS both by electrostatic and hydrophobic interactions.. LE-CH-CFn-SDC resulted in reduction of endotoxin release and MIC values for E. coli. LE-CH-CFn-SDC also reduced NO and TNF-α as well as ROS generation by reducing the uptake of LPS in J774 macrophages. LE-CH-CFn-SDC improved CFn pharmacokinetics and tissue distribution, by reducing the bacterial burden, LPS and cytokines (TNF-α and IL-6) thereby improving survival in a rat model of E. coli induced peritonitis.. In conclusion, this work highlights the effectiveness of the chitosan-coated nanoemulsion as intracorporeal approach for therapeutic intervention of E. coli induced peritonitis as well as in sepsis.

Topics: Animals; Anti-Bacterial Agents; Cations; Chitosan; Ciprofloxacin; Deoxycholic Acid; Drug Carriers; Emulsions; Escherichia coli; Escherichia coli Infections; Lipopolysaccharides; Microbial Sensitivity Tests; Nanostructures; Particle Size; Peritonitis; Rats, Wistar; Sepsis; Technology, Pharmaceutical

A ciprofloxacin (CFn)-loaded lipid emulsion was developed for treatment of intra-abdominal infections, especially sepsis. Loading efficiency depended on the proportion of chitosan (CH) and sodium deoxycholate (SDC). The average globule size was 225 to 325 nm. Animal survival improved when the prototype formulation was administered to LPS-induced septic mice. At 4 microg/ml, reduction in TNF-alpha and NO production were observed (P < 0.05) but at lower concentration these changes were not significant (P > 0.05) as compared to positive control (LPS-1 microg/ml). This indicates that chitosan can modify LPS interaction with macrophages, and that formulations have potential to control inflammation associated with sepsis.

Topics: Animals; Anti-Infective Agents; Chitosan; Ciprofloxacin; Deoxycholic Acid; Drug Compounding; Lipopolysaccharides; Mice; Mice, Inbred BALB C; Nanocapsules; Sepsis; Treatment Outcome

Polymyxin B (PMB), an antibiotic, and sodium deoxycholate (NaD), a bile salt, are surface-active agents. Each protected mice against an otherwise lethal challenge with purified endotoxin (P less than .001). To determine if either of these agents was effective in treating established, overwhelming gram-negative septicemia, we infected rabbits by intraperitoneal injection of Escherichia coli K1. Animals were treated with moxalactam 1 hr after infection, then randomly assigned to groups receiving either saline, PMB, or NaD. Serial samples of blood were assayed for bacterial concentration, levels of plasma endotoxin, arterial blood gases, and complete blood cell counts. Physiologic functions were monitored continuously. Although levels of bacteremia and endotoxemia were similar in all three groups, rabbits receiving PMB had significantly higher mean arterial blood pressure, blood pH, and bicarbonate concentrations than did control rabbits (P less than .05). Rabbits receiving NaD fared no better than controls. In this model, PMB moderates some of the deleterious effects of established, overwhelming gram-negative bacterial sepsis.

Topics: Acidosis; Animals; Carbon Dioxide; Deoxycholic Acid; Endotoxins; Escherichia coli; Escherichia coli Infections; Hydrogen-Ion Concentration; Hypotension; Leukocyte Count; Mice; Oxygen; Platelet Count; Polymyxin B; Polymyxins; Rabbits; Sepsis

Simultaneous application of the lysostaphin sensitivity test for identification of Staphylococcus aureus and the deoxycholate test for the identification of Streptococcus pneumoniae was evaluated for reliability in rapid identification (1 h) of these organisms from blood cultures by using BACTEC 6B and 7C bottles. The procedure was applied to 127 cultures, 74 lysostaphin tests and 53 deoxycholate tests. Lysostaphin-tested organisms included 23 S. aureus, 40 Staphylococcus epidermidis, 1 Listeria sp., 1 Peptococcus sp., 2 Micrococcus sp., 2 diphtheroids, and 5 mixed cultures. Deoxycholate-tested organisms included 14 S. pneumoniae, 32 Streptococcus spp. (not S. pneumoniae), 1 Listeria sp., 1 Peptococcus sp., 2 diphtheroids, and 3 mixed cultures. Analysis of the data revealed positive and negative predictive values of 95.8 and 94%, respectively, for the lysostaphin test and 100 and 97.4%, respectively, for the deoxycholate test. The combined tests provide rapid reliable identification or elimination of S. aureus and S. pneumoniae in blood cultures.

Topics: Blood; Deoxycholic Acid; Humans; Lysostaphin; Sepsis; Staphylococcus aureus; Streptococcus pneumoniae

Plasma lysozyme was measured in turkeys with experimental fowl cholera produced by either of two serotypes of Pasteurella multocida. Lysozyme was not detected in preexposure plasma, whereas plasma sampled when turkeys were terminally bacteremic contained 7.0-7.5 microgram of lysozyme/ml. Plasma lysozyme was measured in turkeys inoculated intravenously with P. multocida lipopolysaccharide (LPS). Turkeys inoculated with 10 microgram of LPS produced plasma lysozyme detectable for 2 hr after inoculation; those inoculated with 500 microgram of LPS produced plasma lysozyme detectable for at least 6 hr after inoculation. Egg-white lysozyme, equivalent in concentration to the plasma lysozyme detected in bacteremic turkeys, was active upon young cultures of P. multocida and increased the degree of lysis of P. multocida cells treated with deoxycholate. Lysozyme, ethylenediaminetetraacetate, and deoxycholate in combination produced the highest degree of lysis of P. multocida cells.

Topics: Animals; Deoxycholic Acid; Edetic Acid; Lipopolysaccharides; Microbial Sensitivity Tests; Muramidase; Pasteurella; Sepsis; Turkeys

Topics: Animals; Bile; Bilirubin; Cholesterol; Cholic Acids; Deoxycholic Acid; Liver; Male; Rats; Sepsis; Staphylococcal Infections