Enhanced activity of mouse peritoneal cells after aclacinomycin administration

We have investigated the activation of mouse peritoneal macrophages by injection of aclacinomycin (ACM). Macrophages from ACM-treated mice have an increased phagocytic activity as measured by Candida ingestion. The microbicidal activity indirectly evaluated by chemiluminescence and superoxide determination in response to stimulation with zymosan and 4 beta-phorbol-12-myristate-13 alpha-acetate is also greater in the cells from treated mice. Direct measurement of the cytostatic function, and of in vitro and in vivo cytotoxicity shows comparable significant increases against L1210 or P815 target cells. The enhanced antitumoral activity could not be attributed to the residual presence of ACM in the peritoneal cells since no drug was detected by high-performance liquid chromatography and since their freeze-thaw lysates incubated with P815 cells did not modify the growth of tumor cells as measured by [3H]-thymidine incorporation. We also checked that the presence of ACM did not influence the intensity of the chemiluminescence. In all tests performed, only i.p. ACM administration could stimulate the peritoneal cells. Since the doses of ACM inducing an increase in macrophage activity are effective on the survival of tumor-bearing mice, the participation of this mechanism in tumor control might be suggested.     

Feasibility of near real-time image-guided sinus surgery using intraoperative fluoroscopic computed axial tomography.

OBJECTIVE: One of the main limitations of image-guided surgery is that navigation relies on the use of a CT scan obtained before surgery and is unable to be updated during the procedure. A software addition has been developed to allow reconstruction of CT-like images from a series of fluoroscopic scans and integrate these into an image-guided system (GE Healthcare Surgical Navigation, Lawrence, MA). We report our initial experience with a series of patients undergoing intraoperative fluoroscopic navigation in sinus surgery. STUDY DESIGN AND SETTINGS: After institutional review board clearance, we prospectively studied 14 consecutive patients undergoing image-guided sinus surgery with the use of intraoperative fluoroscopy. RESULTS: All patients had preoperative and postoperative fluoroscopic images reconstructed into CT-like images. By the conclusion of the study, images were adequate in quality and accurate navigation was achieved. CONCLUSION: Real-time image-guided sinus surgery using fluoroscopy is feasible. Future studies will need to focus on defining the procedures that could benefit, such as tumor resection, to enhance patient safety during these operations.     

Upper gastrointestinal tract dysfunction in bulimia

Bulimia nervosa is a health problem of increasing magnitude that is estimated to affect 2–5% of the American adolescent and young adult female population. Because of the magnitude of this clinical problem and because of the importance of the upper gastrointestinal tract in its expression, a intradepartmental program of health care for patients affected with the disease was initiated. Eleven consecutive symptomatic bulimic individuals have been evaluated jointly by the gastroenterology and the psychiatry departments of the University of Pittsburgh. Five of these 11 individuals were found to have clinically important upper gastrointestinal pathology including ulcerative esophagitis, erosive gastritis, duodenal ulcer, and delayed gastric emptying. These gastrointestinal conditions could have been either a result of or have contributed to the symptomatology of these five patients. These data suggest that bulimic subjects have clinically important gastroenterological disease processes that require specific diagnosis and treatment independent of the psychiatric treatment provided for the bulimic condition.This work was supported in part by grants from NIDDK AM 32556.     

Inhibition of 2-nitropropane-induced rat liver DNA and RNA damage by benzyl selenocyanate

We observed that pretreatment of male F344 rats with benzyl selenocyanate, a versatile organoselenium chemopreventive agent in several animal model systems, decreases the levels of DNA and RNA modifications produced in the liver by the hepatocarcinogen 2- nitropropane. To clarify the mechanisms involved, we pretreated male F344 rats with either benzyl selenocyanate, its sulfur analog benzyl thiocyanate, phenobarbital or cobalt protoporphyrin IX; the latter is a depletor of P450. We then determined (1) the ability of liver microsomes to denitrify 2-nitropropane, (2) effects on 2-nitropropane- induced liver DNA and RNA modifications and (3) amount of nitrate excreted in rat urine following administration of the carcinogen. Pretreatment with benzyl selenocyanate or phenobarbital increased the denitrification activity of liver microsomes by 217 and 765%, respectively, increased liver P4502B1 by 31- and 435-fold, respectively, decreased the levels of 2-nitropropane-induced modifications in liver DNA (29-70% and 17-30%, respectively) and RNA (67-85% and 30-50%, respectively), and increased the 24-h urinary excretion of nitrate by 157 and 209%, respectively. Pretreatment with benzyl thiocyanate had no significant effect on any of these parameters. Pretreatment with cobalt protoporphyrin IX decreased liver P4502B 1 by 87%, decreased the denitrification activity of liver microsomes by 76%, decreased the 24 h urinary excretion of nitrate by 88.5%, but increased the extent of 2-nitropropane-induced liver nucleic acid modifications by 17-67%. These results indicate that the metabolic sequence from 2-nitropropane to the reactive species causing DNA and RNA modifications does not involve the removal of the nitro group. Moreover, they suggest that benzyl selenocyanate inhibits 2-NP-induced liver nucleic acid modifications in part by increasing its detoxication through induction of denitrification, although it is evident that other mechanisms must also be involved.      

Early onset of autoimmunity in MRL/++ mice following immunization with beta 2 glycoprotein I.

Antiphospholipid antibodies (aPL) are associated with thrombosis, thrombocytopenia and recurrent fetal loss in humans and in some animal models. Immunization with beta 2 glycoprotein I (beta 2GPI) induced aPL production in normal rabbits and mice. However, the association of these antibodies with disease manifestations remains controversial. To determine whether induction of aPL by beta 2GPI immunization in an autoimmune strain of mice (MRL/++) would result in acceleration of clinical and serological autoimmune disease manifestations, three groups of 8-week-old female mice were studied. One group was immunized with beta 2GPI, and one with ovalbumin (OVA); the third was not immunized. After two booster injections, sera were analysed for the presence of anticardiolipin (aCL) and anti-DNA by ELISA and anti-nuclear antibody (ANA) by immunofluorescence. Mice were studied for thrombocytopenia, proteinuria, fecundity rates, litter sizes and the development of central nervous system dysfunction. Elevated levels of aCL, anti-DNA and ANA were detected in all beta 2GPI-immunized, in three OVA-immunized, and in none of the unimmunized mice. The anti-DNA antibodies were inhibited by CL micelles, suggesting cross-reactivity between aCL and anti-DNA. Platelet counts, fecundity rates and litter size were reduced in beta 2GPI-immunized but not in OVA-immunized or unimmunized mice. None of the mice developed neurological dysfunction or significant proteinuria over a 10-week period post-immunization. These findings suggest that beta 2GPI immunization induces aPL in MRL/++ mice associated with accelerated autoimmune manifestations resembling the antiphospholipid syndrome.