thromboxane-b2 and Granuloma

To further study the mechanisms of damages and resorption of bone in chronic periapical periodontitis.. The quantities and distribution of PGE2 and TXB2 in apical granuloma of chronic periapical periodontitis were analyzed using radio immunization analysis.. The quantities of PGE2 and TXB2 in apical granuloma of chronic periapical periodontitis were significantly (P < 0.05) higher than those in controls.. The PGE2 has the close relation with the bone resorption of chronic periapical periodontitis during the whole process. Meanwhile, TXB2 also has certain relation with the bond absorption. The quantities of PGE2 and TXB2 are imbalanced.

Topics: Adolescent; Adult; Bone Resorption; Chronic Disease; Dinoprostone; Female; Granuloma; Humans; Male; Middle Aged; Periapical Periodontitis; Radioimmunoassay; Thromboxane B2

Each step of an inflammatory reaction is triggered by one or several chemical or biological mediators such as arachidonic acid derivatives (prostaglandins [PG], leukotrienes [LT], or thromboxanes [TX]), vasoactive amines (histamine or serotonin), and oxygen free radicals (superoxide ion, O2-, or hydrogen peroxide, H2O2). In perivenous inflammation, these mediators play a prominent role in favoring vasodilatation (histamine), increasing membrane permeability (PGE2, histamine, free radicals) and providing a chemotactic signal for specialized cells, ie, neutrophil polynuclears, macrophages, lymphocytes (LTB4, free radicals). The antiinflammatory effects of Daflon 500 mg,* a micronized purified flavonoid fraction (90% diosmin, 10% hesperidin), were studied in different in vivo and in vitro models. In a model of inflammatory granuloma in the rat, Daflon 500 mg (100 mg/kg, orally) reduced edema formation and inhibited the synthesis for PGE2 (78.5%), PGF2 alpha (45.2%) and TXB2 (59.5%) (Damon et al, Arzneim-Forsch/Drug Res 37:1149-1153, 1987). Intravenous injection of Daflon 500 mg (25 and 50 mg/kg) reduced the hyperglycemia induced by injection of alloxan in rat. This effect of Daflon 500 mg was linked to its ability to scavenge active oxygen radicals, demonstrated in vitro using human neutrophils (Lonchampt et al, Arzneim-forsch/Drug Res 39:882-885, 1989) or mouse peritoneal macrophages (Bodinier et al, manuscript in preparation) stimulated by zymosan. The free radical scavenger effect of Daflon 500 mg is observed at concentrations ranging from 10(-7) M to 10(-4) M, with half-maximal effect between 10(-6) M and 10(-5) M. Thus, Daflon 500 mg behaves as a potent protective agent against inflammatory disorders. These properties may explain, at least in part, the clinical activity of Daflon 500 mg and justify its therapeutic use.

Topics: Alloxan; Animals; Anti-Inflammatory Agents; Blood Glucose; Diabetes Mellitus, Experimental; Diosmin; Drug Combinations; Flavonoids; Free Radicals; Granuloma; Hesperidin; Humans; Inflammation; Kidney Glomerulus; Macrophages; Mice; Neutrophils; Permeability; Prostaglandins; Rats; Thromboxane B2

Release of arachidonic acid metabolites (eicosanoids) by alveolar macrophages may be important in regulating pulmonary inflammatory reactions. The purpose of this study was to characterize eicosanoids released by rat alveolar macrophages during the evolution of experimentally induced pulmonary inflammation. Immunization with subcutaneous bacillus Calmette-Guerin (BCG) followed 2 wk later by intravenous BCG challenge resulted in mild granulomatous pulmonary inflammation for up to 30 days. At serial intervals, alveolar macrophages were lavaged from the BCG-treated rats as well as from control normal rats. Lavaged macrophages were cultured in vitro, and culture supernatants were assayed by radioimmunoassay for release of prostaglandin E2 (PGE2), Leukotriene B4 (LTB4), and thromboxane B2 (TXB2). Cells were cultured alone, or with added LPS or calcium ionophore A23187 to stimulate eicosanoid release. During BCG-induced inflammation, spontaneous release of PGE2 and LTB4 was unchanged, while spontaneous release of TXB2 was depressed acutely and then returned to control levels. The capacity of alveolar macrophages to release specific eicosanoids in response to an in vitro stimulus was dramatically altered during the course of BCG-induced inflammation. Stimulated release of PGE2 was transiently increased during acute lung injury, but stimulated release of LTB4 was significantly decreased at all stages of inflammation. Stimulated release of TXB2 was unchanged. These results indicate that during the course of granulomatous pulmonary inflammation there are dynamic changes in the profile of eicosanoids released by alveolar macrophages, both spontaneously and in response to in vitro stimulation. This alteration in the release of eicosanoids by alveolar macrophages may be an important factor in the resolution of pulmonary inflammation.

Topics: Animals; Bronchoalveolar Lavage Fluid; Cells, Cultured; Culture Media; Dinoprostone; Eicosanoids; Granuloma; Inflammation; Leukotriene B4; Lung Diseases; Macrophages; Male; Mycobacterium bovis; Pulmonary Alveoli; Radioimmunoassay; Rats; Rats, Inbred F344; Thromboxane B2

S-5682 (Daflon-500 mg), a purified flavonoid fraction, consisting of 90% diosmin (a flavone derivative) and 10% hesperidin (a flavanone derivative), was administered to rats by intubation in the daily dose of 100 mg/d. 15 days after the start of treatment, polyurethane sponges were implanted in the subcutaneous connective tissue in the dorsolumbar region under rapid ether anaesthesia. Similar fragments of sponge were implanted in a group of control animals who received the vehicle (saccharose syrup) only, also by the oral route. The rats were sacrificed in fractions of 7 animals drawn from each of the two groups (control and treated) after 4, 8, 16 and 30 days (only 5 animals from each group on day 30) after implantation of the polyurethane sponges. The granulomas formed were removed, weighed and their prostaglandin (PG)E2, PGF2 alpha and thromboxane (Tx)B2 contents were determined. In addition a full cell count (polymorphs, lymphocytes, macrophages, plasmocytes and giant cells) was performed and the animals were histologically examined. The results show that treatment of the animals with S-5682 had the following effects: 1. A significant fall in the mean weight of the granulomas formed after 4 and 8 days was observed, reflecting inhibition of oedema formation during the early phase of the inflammatory reaction. 2. The synthesis of PGE2 (78.5% inhibition on day 4) and PGF2 alpha (45.2% on day 16) was inhibited. 3. There was very early inhibition of TxB2 synthesis (59.5% inhibition on day 4). 4. A later reduction in cell migration towards the inflammatory focus occurred which was statistically significant on day 16 (49.6% reduction in the total number of migrant cells). 5. Multiple histological aspects of the acute inflammatory reaction (diapedesis of polymorphs, lymphocytes, histiocytes and macrophages) and features of the chronic inflammatory reaction (newly formed microvascularisation of the granuloma tissue, perivascular oedema, presence of collagen fibres) were improved.

Topics: Animals; Dinoprost; Dinoprostone; Flavonoids; Granuloma; Inflammation; Male; Prostaglandins E; Prostaglandins F; Radioimmunoassay; Rats; Rats, Inbred Strains; Thromboxane B2

Arachidonic acid (AA) injected locally into carrageenin/sponge granulomas, but not if given orally, inhibited granuloma growth. Granuloma macrophage (M0) infiltration was inhibited, and prostaglandin E2 (PGE2) synthesis (ng/100 mg granuloma dry weight) stimulated, by AA treatment. M0 adenosine 3',5'-cyclic monophosphate (cAMP) levels and granuloma exudate volume were not affected. Granuloma M0s incubated in vitro with arachidonic acid synthesised thromboxane B2 (Txb2), 6-ketoprostaglandin F1 alpha (6-ketoPGF1 alpha), and preferentially, PGE2. The AA inhibition of granuloma growth was possibly mediated via the synthesis of PGE2.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anti-Inflammatory Agents; Arachidonic Acid; Arachidonic Acids; Carrageenan; Cyclic AMP; Dinoprostone; Eicosanoic Acids; Exudates and Transudates; Granuloma; Macrophages; Male; Prostaglandins E; Rats; Rats, Inbred Strains; Thromboxane B2

Seven-day-old carrageenin granuloma tissue of rats, when incubated in organ culture, produced 6-keto-prostaglandin F1 alpha, prostaglandin E2, prostaglandin F2 alpha, and thromboxane B2 in ratios of 16/7/1/1, respectively. Indomethacin (1 microgram/ml) inhibited this cyclooxygenase-mediated arachidonic acid metabolism. Dexamethasone (1 microgram/ml) also inhibited this metabolic cascade. Its inhibitory effect was not immediate; preincubation of the tissue with dexamethasone potentiated its inhibitory effectiveness. Cycloheximide (0.1 to 10 microgram/ml) also inhibited prostaglandin production. The inhibitory mechanism by cycloheximide of prostaglandin production was discussed in relation to that by dexamethasone.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Carrageenan; Culture Techniques; Cycloheximide; Dexamethasone; Granuloma; Indomethacin; Male; Prostaglandins; Prostaglandins E; Prostaglandins F; Rats; Thromboxane B2

Levels of PGE2, PGF2 alpha, PGI2 (measured as 6-keto-PGF1 alpha), and thromboxane B2 were determined in rat inflammatory excuates induced 1, 3, and 7 days after carrageenin injection into air-pouch granuloma. The PGE2 and 6-keto-PGF1 alpha levels found in the exudate could not account for the differences in PGE2-like activity as measured by biologic and serologic methods.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Carrageenan; Exudates and Transudates; Granuloma; Inflammation; Male; Prostaglandins E; Prostaglandins F; Rats; Thromboxane B2; Thromboxanes; Time Factors

Topics: Animals; Arachidonic Acids; Aspirin; Carrageenan; Depression, Chemical; Granuloma; Hydrocortisone; In Vitro Techniques; Indomethacin; Male; Prostaglandins F; Rats; Thromboxane B2; Thromboxanes

The effects of prostaglandin I2, 6-ketoprostaglandin F1alpha, prostaglandin E1 and thromboxane B2 on the vascular permeability response in rat carrageenin granuloma were studied with the aid of 131I- and 125I-human serum albumin as indicators for the measurement of local vascular permeability. A single injection of 5 microgram of prostaglandin I2 methyl ester or I2 sodium salt into the locus of the granulomatous inflammation elevated local vascular permeability 2.0-2.5 times over the control within 30 min. The potency was equal to that of the positive control prostaglandin E1 which has been known to be the most potent mediator in this index among several candidate prostaglandins for chemical mediator of inflammation. The other prostaglandin and thromboxane B2 tested were essentially inactive.

Topics: Animals; Capillary Permeability; Carrageenan; Granuloma; Male; Prostaglandins; Rats; Thromboxane B2