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1 Department of Biological Sciences and Department of Periodontics, 3Department of Community Dentistry, Case Western Reserve University School of Dental Medicine, 10900 Euclid Avenue, Cleveland, OH 44106-4905, USA; and 2Department of Dermatology, University Hospitals of Cleveland and Case Western Reserve University, Cleveland, OH, USA; * corresponding author, axw47 po.cwru.
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Chemicals. Roxithromycin was obtained from Hoechst-Marion Roussel Romainville, France ; . Erythromycin, prostaglandin PG ; E2, 6-keto-PGF1 , leukotriene LT ; B4 rabbit antisera, and anti actin mouse antibody were obtained from Sigma Milan, Italy ; . Clarithromycin and azithromycin were purified from the commercial products Klacid Abbott ; and Zitnromax Pfizer ; , respectively. LPS was derived from Salmonella typhosa 0901 ; purchased from Difco Detroit, MI ; . Dulbecco's modified Eagle's medium and fetal bovine serum were obtained from BioWhittaker Heidelberg, Germany ; . Carboxymethylcellulose and cadmium powder 325 mesh ; were obtained from Aldrich Milan, Italy ; . Nonfat dry milk and nitrocellulose membranes were obtained from Bio-Rad Milan, Italy ; . Anti-cyclooxygenase COX ; -2 and anti-inducible NO synthase iNOS ; mouse antibodies were purchased from Transduction Laboratories Lexington, KY ; . Anti-mouse immunoglobulins coupled to peroxidase were purchased from Amersham Milan, Italy ; . TNF- and IL-1 enzymelinked immunosorbent assay ELISA ; kits were obtained from Genzyme Milan, Italy ; . IL-6 ELISA kits were obtained from Endogen Woburn, MA ; . All other compounds were from Sigma. Animals. Male Wistar rats Harlan, Italy ; weighing 240 to 260 g were used for this study. Animals were housed in propylene cages with food and water ad libitum. The light cycle was automatically controlled on at 7: and off at 7: 00 ; , and the room temperature was thermostatically regulated to 22 1C. Before the experiments, animals were housed in these conditions for 3 to 4 days to become acclimatized. Some rats were adrenalectomized or shamoperated under ether anesthesia and used 3 to 4 days after the surgical procedure. Adrenalectomized animals received isotonic saline as drinking water until use. Animal care was in accordance with Italian and European regulations on the protection of animals used for experimental and other scientific purposes. Carrageenin-Induced Pleurisy. Rats were slightly anesthetized with ether, and 0.2 ml of 1% -carrageenin, suspended in sterile saline solution, was injected into the pleural cavity. Roxithromycin, clarithromycin, erythromycin, and azithromycin, suspended in olive oil, were administered p.o. via gastric gavage 0.5 ml rat ; at 10, 20, and 40 mg kg 1 h before carrageenin injection. In some experiments, the macrolides were administered to adrenalectomized rats. The control groups received an equal volume of the vehicle. Carrageenin pleurisy was also induced in some rats treated with indomethacin 5 mg kg ; dissolved in carboxymethylcellulose and administered p.o. 1 h before the phlogogenic agent. Four hours after the induction of pleurisy, animals were sacrificed in an atmosphere of CO2. Pleural exudate from each animal was harvested by washing the pleural cavity with 2 ml of sterile saline solution containing 5 U ml heparin and 10 g ml indomethacin. Exudates with blood contamination were rejected. The exudate volumes were measured, the samples were centrifuged at 800g for 10 min, and the cell pellet was resuspended in saline for total and differential cell count. Total cell count was estimated after trypan blue staining with the use of the Burker counting chamber. In some experiments, differential cell count was determined by May-Grunwald Giemsa staining. The supernatants were then aliquoted and stored at 80C until use. Cell Culture. The murine monocyte macrophage cell line J774 was from the European Collection of Animal Cell Cultures Salisbury, UK ; . J774 cells were grown in Dulbecco's modified Eagle's medium and cultured at 37C in humidified 5% CO2 95% air. Culture medium was supplemented with 10% fetal bovine serum, 2 mM L-glutamine, 25 mM HEPES, 100 U ml penicillin, 100 g ml streptomycin, and 5 mM sodium pyruvate at 37C. The cells were plated onto 24-well culture plates Falcon, Meylan, France ; at a density of 2.5 105 ml and allowed to adhere for 2 h. Thereafter, the medium was replaced with fresh medium, and cells were activated by 1 g LPS in the presence or absence of various concentrations 5 80 M ; the antibiotics. Indomethacin 1 M ; and NG-monomethyl-L-arginine L-NMMA; 30 M ; have been used as reference drugs. In some and acomplia and zithromax. Older adults: this medicine has been tested in a limited number of patients 60 years of age and older and has not been shown to cause different side effects or problems in older people than it does in younger adults. Common side effects are fatigue and anxiety but the drug appears to be well tolerated in most study patients and actonel.

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