deoxycholic-acid and Bacterial-Infections

We demonstrated binding interactions of polymyxin B (PMB), PMB formulations in the mole ratios of 1:2 and 1:3 of PMB:sodium deoxycholate sulfate (SDCS) and a commercial PMB formulation (CPMB) with lipopolysaccharides (LPS). The 1:2 PMB formulation (78.5-135.2 nM) exhibited a lower number of binding sites to the tested LPS compared to CPMB (112.6-140.9 nM) whereas 1:3 PMB formulation exhibited a higher number of binding sites (143.9-340.2 nM). Similarly, in the presence of LPS, the 1:2 PMB formulation (163.8-221.4 nm) exhibited smaller particle sizes compared to PMB, CPMB and 1:3 PMB formulation (248.8-603.5 nm). Molecular docking simulation suggested that the fatty acyl tails of LPS wrap together to produce a pseudo-globular structure of PMB-LPS complex, and among those 1:2 PMB formulation formed a more stable structure. The primary forces behind this complex are hydrogen bonds and salt bridges among the LPS, PMB, and SDCS. This study revealed that the PMB, CPMB, and PMB formulations inserted into the LPS micelles to disrupt the LPS membrane, whereas the SDCS may induce aggregation. The 1:2 PMB formulation also had higher bacterial uptake than other PMB formulations. The 1:2 PMB formulation neutralized the LPS micelles and was effective against Escherichia coli and Pseudomonas aeruginosa.

Topics: Anti-Bacterial Agents; Bacterial Infections; Bacterial Outer Membrane; Cell Membrane Permeability; Deoxycholic Acid; Drug Compounding; Escherichia coli; Lipopolysaccharides; Micelles; Microbial Sensitivity Tests; Molecular Docking Simulation; Molecular Structure; Polymyxin B; Pseudomonas aeruginosa; Structure-Activity Relationship

Bacterial translocation leading to subsequent infectious complications is a significant determinant of outcome in acute hemorrhagic pancreatitis (AHP). The colonic ileus and impaired intestinal barrier function that often accompany AHP may predispose to translocation. Sennoside is a naturally occurring cathartic and choleretic agent that stimulates intestinal mucous secretion and has potent promotility effects. The impact of sennoside-induced intestinal motility and secretory function on bacterial translocation and survival was studied in a rat model of AHP. Severe acute pancreatitis was induced in rats by the intraductal infusion of 2% sodium deoxycholate (DCA, 0.4 ml/kg). A group of sham-operated rats (group A) received intraductal saline, whereas experimental animals were subsequently administered distilled water (group B) or sennoside solution (group C) by gavage every 8 h. After 48 h, intestinal transit of fluorescein isothiocyanate-labeled dextran, serum endotoxin, and amylase levels, and bacterial translocation to mesenteric lymph nodes (MLNs) and pancreatic tissue were determined. The pancreas and intestine were sampled for histologic study. All group A animals survived and did not develop pancreatitis or endotoxemia, whereas groups B and C all demonstrated severe hemorrhagic pancreatitis with evidence of necrosis. Mortality at 48 h was 55% in group B versus 12.5% in group C. Inhibition of intestinal motility was noted in 40% versus 20%, and endotoxin levels were 61.36+/-28.26 pg/L versus 5.41+/-3.58 pg/L in group B versus group C rats, respectively (p<0.001). Pancreatic tissue and MLN cultures were positive in 100% of group B survivors versus 14% of group C survivors (p<0.05). Histologic examination of the intestine in group C animals showed increased mucous secretion, proliferation of goblet cells, and evidence of rapid turnover/renewal of enterocytes. Treatment with the cathartic agent, sennoside, reduced translocation of endotoxin and bacteria, restored intestinal motility, increased mucous secretion, and reduced mortality in a model of acute hemorrhagic pancreatitis in the rat. Other cathartics may have similar properties and may be useful in preventing infectious complications in acute pancreatitis.

Topics: Acute Disease; Amylases; Animals; Anthraquinones; Bacterial Infections; Cathartics; Deoxycholic Acid; Disease Models, Animal; Endotoxemia; Endotoxins; Gastrointestinal Motility; Hemorrhage; Intestinal Mucosa; Jejunum; Lymph Nodes; Male; Necrosis; Pancreatic Diseases; Pancreatitis; Rats; Rats, Wistar; Senna Extract; Sennosides

Salt dependent gram-negative bacilli responsible for gastroenteritis and tissue infections are often not recovered because proper media for isolation are not used. A salt-starch XLD agar with 1.5% NaC1 and 0.5% starch medium has been found to permit the isolation of pathogenic Enterobacteriaceae, non-Enterobacteriaceae gram-negative bacilli, and salt-dependent gram-negative bacilli, among which is Vibrio parahemolyticus. As far as the Enterobacteriaceae are concerned, the selectivity and sensitivity of the medium are the same as with standard media with the added advantage of isolating salt-dependent organisms, thereby saving time and money. It can be used for routine blood cultures, investigation of sea water, seafood and tissue infections related to marine activities.

Topics: Agar; Bacteria; Bacterial Infections; Deoxycholic Acid; Diagnosis, Differential; Enterobacteriaceae; Feces; Humans; Lysine; Skin; Sodium Chloride; Species Specificity; Starch; Vibrio parahaemolyticus; Xylose

Topics: Africa; Americas; Asia; Bacterial Infections; Bile Acids and Salts; Carcinogens; Colon; Colonic Neoplasms; Deoxycholic Acid; Diet; Dietary Fats; Europe; Feces; Gastrointestinal Motility; Humans; Intestinal Absorption; Methylcholanthrene