ABSTRACT
Hearing impairment is a common and frequently permanent sequel of Streptococcus suis meningitis in humans. Nevertheless, mechanisms underlying the development of cochlear damage have not been addressed so far. In the present work, we characterized a mouse model of suppurative labyrinthitis and meningitis induced by a systemic infection with S. suis and studied the impact of the injected bacterial dosage on the progression of such inflammatory events. We observed that high infection doses of bacteria lead to sustained bacteremia, with an increase in the permeability of the blood-labyrinth and blood-brain barriers, causing suppurative labyrinthitis and meningitis, respectively. However, in mice infected with a low dose of S. suis, bacteria disappeared quickly from blood, hence, cochlear inflammation and meningitis were not consistent features. This model of S. suis infection seems ideal to evaluate novel drugs that may help alleviate the negative consequences of such important sequelae of S. suis-induced meningitis and labyrinthitis.
Subject(s)
Labyrinthitis/pathology , Meningitis, Bacterial/pathology , Streptococcal Infections/pathology , Streptococcus suis/pathogenicity , Vestibular Diseases/pathology , Animals , Bacteremia/microbiology , Bacteremia/pathology , Blood/microbiology , Disease Models, Animal , Female , Labyrinthitis/complications , Labyrinthitis/microbiology , Meningitis, Bacterial/complications , Meningitis, Bacterial/microbiology , Mice , Streptococcal Infections/complications , Streptococcal Infections/microbiology , Time Factors , Vestibular Diseases/complications , Vestibular Diseases/microbiologyABSTRACT
Polymorphonuclear leucocytes (PMNL) are an essential component of the defence system against invading bacteria. There is evidence that some anaesthetics are able to suppress PMNL functions, promoting, perhaps, perioperative infection. We studied the effects of thiopentone, etomidate, ketamine, and midazolam on the generation of bactericidal agents (superoxide anion, hydrogen peroxide, and myeloperoxidase) by PMNL in vitro. Thiopentone inhibited superoxide anion (P < or = 0.01) as well as hydrogen peroxide production (P < or = 0.001). However, there was no statistically significant effect on myeloperoxidase release. Neither etomidate nor ketamine influenced the PMNL functions tested to any extent. Midazolam suppressed superoxide anion generation (P < or = 0.01) but only if a concentration far beyond clinical relevance was used.
Subject(s)
Bacterial Physiological Phenomena , Etomidate/pharmacology , Ketamine/pharmacology , Midazolam/pharmacology , Neutrophils/metabolism , Thiopental/pharmacology , Adult , Humans , Hydrogen Peroxide/metabolism , In Vitro Techniques , Male , Neutrophils/drug effects , Neutrophils/physiology , Peroxidase/metabolism , Superoxides/metabolismABSTRACT
Polymorphonuclear leukocytes (PMNL) play a vital role in the defence against invading bacteria. It is known that some anaesthetics inhibit PMNL function and, thus, possibly enhance perioperative infection. We investigated the effect of methohexitone, flunitrazepam, and droperidol on three bactericidal PMNL functions, i.e., superoxide anion production, hydrogen peroxide generation, and activity of released myeloperoxidase, in vitro. Approved photometrical assays were used. Superoxide anion was measured by the reduction of cytochrome C, hydrogen peroxide by the horse radish peroxidase catalysed oxidation of phenol red, and myeloperoxidase by the turnover of 2,2'-azino-di(3-ethylbenzthiazoline) sulfonic acid. Methohexitone (P < or = 0.001) and flunitrazepam (P < or = 0.01) inhibited superoxide anion production, and methohexitone (P < or = 0.01) reduced hydrogen peroxide generation but only at concentrations beyond clinical relevance. Droperidol did not cause any alteration of the PMNL functions tested. Consequently, it seems unlikely that the usual doses of methohexitone, flunitrazepam, or droperidol promote bacterial infections in vivo by impairing the activity of myeloperoxidase or by inhibiting the generation of superoxide anion or hydrogen peroxide.
Subject(s)
Anesthesia, Intravenous , Droperidol/pharmacology , Flunitrazepam/pharmacology , Methohexital/pharmacology , Neutrophils/drug effects , Adult , Humans , Hydrogen Peroxide/antagonists & inhibitors , Hydrogen Peroxide/metabolism , Male , Neutrophils/enzymology , Neutrophils/metabolism , Peroxidase/metabolism , Superoxides/antagonists & inhibitors , Superoxides/metabolismABSTRACT
Polymorphonuclear leukocytes (PMNL) play an important part in protecting against invading bacteria. It is known that some anaesthetics may impair PMNL functions, thus possibly promoting infection. We investigated the effect of fentanyl and alfentanil on superoxide anion production, hydrogen peroxide generation, and activity of released myeloperoxidase in vitro. However, the two opioids did not have any significant influence on the tested PMNL functions.
