Effects of some non-steroidal anti-inflammatory drug copper complexes on polymorphonuclear leukocyte oxidative metabolism

Interaction between anti-inflammatory drugs and reactive oxygen metabolites must be considered in the course of pharmacological studies intended to develop new compounds. Effects of indomethacin, aspirin, and 3,5-diisopropylsalicylic acid (3,5-DIPS) and their copper complexes on PMNL oxidative metabolism and the evolution of an acute inflammatory reaction were studied in the rat. Experiments were performed in vitro by assessment of superoxide generation and reduction of chemiluminescence by PMNLs incubated or not (control) in medium containing various concentrations of these compounds. A dose-related decrease of these parameters was observed, however, copper complexes were found to be more effective than their parent drugs or Cu gluconate. Copper complexes were also more effective anti-inflammatory agents than their parent ligands or Cu gluconate when the volume of exudate and number of exudate PMNLs were assessed after induction of pleurisy in rats by injection of isologous serum. It is concluded that modulation of the PMNL oxidative burst by copper complexes offers an accounting for the anti-inflammatory activity of these compounds.     

Chlamydial infection of subcutaneous conjunctival transplants in guinea pigs

The development and testing of candidate vaccines for trachoma are constrained because only humans and nonhuman primates are susceptible to conjunctival infection with Chlamydia trachomatis. Guinea pig inclusion conjunctivitis (GPIC), an analogous disease of guinea pigs, provides a useful, less expensive model to study ocular chlamydial infections. GPIC is caused by a Chlamydia psittaci strain whose external constituents are very similar to those of C. trachomatis. To develop a better model for studying GPIC immunity, conjunctival pockets were established under the abdominal skin of guinea pigs by subcutaneous implantation. Up to six implants could be produced in each animal. The success rate of implantation was 79.0% (n = 148). These pockets were then infected with GPIC. The organism was recovered from the autografts indicating local replication, and tests for serum antibody by microimmunofluorescence showed production of GPIC-specific antibody of IgG and IgM classes after infection. There was minimal antibody response after moderate inoculating doses to the implants, and the titers increased more slowly than after eye infection with GPIC; with higher concentration of the inoculum, however, the antibody response increased to the same levels as with the ocular challenge but more slowly. Inoculation of pockets with GPIC also produced acute inflammatory changes in infected autografts (n = 101). Histologic examination of infected grafts showed chlamydial inclusions in epithelial cells and significant infiltration with lymphocytes and polymorphonuclear cells. Subcutaneous autografts may provide a useful model for chronologic studies of chlamydial infection. The delayed immunologic response, however, suggests that these pockets of implanted epithelium do not have full access to the immune system.     

Analgesic profile of the sodium salt of pemedolac

Pemedolac Na, 1-ethyl-1,3,4,9-tetrahydro-4-(phenylmethyl)-pyrano [3,4-b] indole-1-acetic acid sodium salt, exhibited equipotent analgesic effects after oral, iv, and im administration, suggesting that it is well absorbed. In mouse writhing models, the ED₅₀ values ranged from 0.3 mg (0.81 μmol)/kg (vs. acetylcholine) to 4.3 mg (11.6 μmol)/kg (vs. paraphenylbenzoquinone [PBQ]). In the rat Randall-Selitto model, the ED₅₀ o the compound was approximately 0.001 mg (2.7 nmol)/kg, with a flat dose response curve. The peak effects lasted for 7–9 h, 10–18 h, and 5 h following oral, im, and iv injections, respectively. Intracerebroventricular (i.c.v.) injections of pemedolac Na inhibited the PBQ-induced writing in mice with an ED₅₀ of 43.5 μg (0.12 μmol)/mouse, and this effect was not antagonized by naloxone. It was inactive in the hot plate and tail flick tests, demonstrating that pemedolac Na does not act via an opiate mechanism. These results indicate that pemedolac Na is a viable parenteral and oral analgesic, typified by high analgesic potency, a rapid onset and long duration of action, and an extremely wide safety index. © Wiley-Liss, Inc.     

Useful predictors of bile duct stones in patients undergoing laparoscopic cholecystectomy. McGill Gallstone Treatment Group.

OBJECTIVE: The authors determined the most useful predictors of common bile duct (CBD) stones as diagnosed by endoscopic retrograde cholangiopancreatography (ERCP) in patients who underwent laparoscopic cholecystectomy (LC). METHODS: Prospective and retrospective collection of historical, biochemical and ultrasonographic data was used. Receiver operating characteristics curve analysis was used to determine optimal biochemical cut-off values. Multivariate analysis using logistic regression with generation of the best model identifying independent predictors of CBD stones also was employed. Prospective validation of the model was performed on an independent group of patients. RESULTS: Endoscopic retrograde cholangiopancreatographies were performed before LC in 106 patients, and after LC in 33. Only four of ten clinical variables evaluated independently predicted the presence of CBD stones. The optimal model predicted a 94% probability of CBD stones in a patient older than 55 years of age who presented with an elevated bilirubin (over 30 mumol/L) and positive ultrasound findings (a dilated CBD, and a CBD stone seen on ultrasound). This model was validated prospectively in a subsequent series of 49 patients in which the probability of CBD stone was only 8% when all four predictors were absent. CONCLUSIONS: The identified independent clinical predictors of a CBD stone helps select a population of symptomatic gallstone bearers who benefit most from cholangiographic assessment.     

Interleukin-6, a marker of preservation injury in clinical lung transplantation.

Interleukin-6 (IL-6) is one of the cytokines produced by human alveolar macrophages, lung parenchyma, and other cells in response to injury and infection. We hypothesized that IL-6 is released from poorly preserved lung grafts and may serve as a marker of preservation injury. Sixteen patients who received lung allografts were enrolled in this study. The average ischemic time was 284 +/- 78 minutes. Serum IL-6 level was measured before and at 4 and 24 hours after reperfusion of the grafts by an enzyme-linked immunosorbent assay. Preservation injury was assessed by (1) the need for prolonged intubation (> 7 days), (2) the arterial/alveolar oxygen tension ratio (PaO2/PAO2 ratio) at 4 hours after graft reperfusion (only in heart-lung or double lung recipients), (3) the presence of diffuse alveolar damage on first lung biopsy, and (4) the 30-day graft survival rate. IL-6 level peaked at 4 hours after reperfusion and returned to baseline at 24 hours. The patients were divided into group I (n = 6) and group II (n = 10), depending on whether the 4-hour IL-6 level was more than 1000 pg/ml or less than 500 pg/ml, respectively. Group I patients required longer intubation (p < 0.01) and had a lower PaO2/PAO2 ratio (p < 0.001), more diffuse alveolar damage (p < 0.01), and a lower graft survival rate (p < 0.01) than those of group II. No bacterial, fungal, or viral infection was found during postoperative week 1 in either group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Rubber band as external assist device to provide simple grip for quadriplegic patients

The rubber band as an external assist device provides an effective grip for the hand of high spinal cord injury quadriplegic patients. This technique can also be useful for preoperative patients who are undergoing physical and occupational therapy or to assess patients' needs for surgery. The rubber band as an adaptive device is preferred because of its availability, low visibility, and ease of application. We attempt to provide a more standardized method of the rubber band technique and to popularize it.     

A comparison of the effects of scopolamine and diazepam on acquisition and retention of inhibitory avoidance in mice

Administration of either the muscarinic antagonist scopolamine or the benzodiazepine diazepam prior to training produced a dose-dependent impairment in the retention of one-trial inhibitory avoidance training in mice. To investigate the nature of this drug effect, the effects of scopolamine and diazepam were subsequently assessed on both acquisition and retention of inhibitory avoidance using a multiple-trial, training-to-criterion procedure. The training was conducted using either continuous trials in which the mouse was free to shuttle back and forth between shock and safe compartments or discrete trials in which the mouse was moved from the shock compartment of the safe compartment at the start of each trial. In either case, training continued until the mouse refrained from crossing into the shock compartment for a specified length of time on a single trial. Scopolamine (1.0 mg/kg) administered before training significantly increased the number of trials required to attain criterion, but did not affect retention when these mice were tested 2, 16, or 28 days later. In contrast, diazepam (1.0 mg/kg) did not significantly alter the number of trials necessary to reach criterion, but impaired retention of the inhibitory response in mice trained using discrete trials. The differences in the amnestic effects of scopolamine and diazepam revealed by this detailed analysis suggest that diazepam does not impair inhibitory avoidance performance through an effect on cholinergic function.