Effects Of Anti-inflammatory Agents Research Articles

The effect of anti-inflammatory agents on the clinical expression of bovine ephemeral fever

The effect of two anti-inflammatory drugs on the development and persistence of clinical signs in cattle experimentally infected with bovine ephemeral fever (BEF) virus was investigated by their administration, either before or after the commencement of fever. A total of 16 cattle was given phenylbutazone sodium (PBZ). The drug prevented fever and other clinical signs in six cattle when given daily during the incubation period, and at 8-h intervals for 5 days when clinical disease might be expected. When treatment with PBZ was deferred until 2–4 h after the commencement o of fever, the rectal temperature returned to normal within 4 h in four of six cattle and the development of other clinical signs was suppressed. Clinical signs of ephemeral fever occurred in four untreated cattle infected at the same time. Viraemia, the development of neutralizing antibodies (at 8–11 days), resistance to subsequent challenge with BEF virus, neutrophilia, lymphopenia and a rise in plasma fibrinogen occurred in all BEF-infected animals whether treated or untreated, despite different clinical appearances. The mean peak of plasma fibrinogen in the untreated cattle was 6.9 g l −1; 3.2 g l −1 when treated 2–4 h after fever developed and 3.8 g l −1 when treated from 18-h post-infection. BEF virus was isolated from leucocytes of each of the cattle, but the frequency of isolation was lower in the treated group. The results indicate that treatment with PBZ blocked the host response which produces the clinical signs and did not have an anti-viral effect. In a similar experiment, a long-acting anti-inflammatory drug, flunixin meglumine, failed to prevent BEF or to modify the clinical signs once they had developed, except for the rectal temperature which returned to normal within 2–4 h of the administration of the drug. The efficacy of this drug was not improved by increasing the dosage to two or three times the recommended level.

P-271 - Effect of antiinflammatory agents on arachidonic acid-induced mouse ear edema

P-271 - Effect of antiinflammatory agents on arachidonic acid-induced mouse ear edema

Leukocyte Stimulation of Intimal Lesion Formation Is Inhibited by Treatment with Diclofenac Sodium and Dexamethasone

This investigation tested the effect of anti-inflammatory agents acting at different levels of the arachidonic acid cascade on leukocyte migration into the vessel wall. An animal model of vasculitis was used in which leukocytes stimulate migration of smooth muscle cells from the media into the intima resulting in formation of intimal lesions. In this model, an endotoxin-soaked thread is implanted in the adventitia along the ventral side of the rat femoral artery. At 2 days, subendothelial and medial leukocyte accumulation occurs exclusively in the ventral half of the vessel. At 14 days, intimal lesions composed primarily of smooth muscle cells are localized to the ventral half of the vessel. Treatment with neither the lipoxygenase inhibitor L-651,392 nor the dual cyclooxygenase and lipoxygenase inhibitor BW755C affected leukocyte migration into the vessel wall or subsequent lesion formation. Treatment with the cyclooxygenase inhibitor diclofenac sodium greatly reduced both leukocyte accumulation and lesion formation, whereas leukocyte migration and lesion formation were nearly totally inhibited by treatment with dexamethasone. Thus, it has been demonstrated that although leukocyte accumulation in the vessel wall stimulates intimal lesion formation, pharmacologic inhibition of leukocyte accumulation prevents lesion formation.

Effects of anti-inflammatory agents on hamster tongue mucosa treated with a phorbol ester : Ronald Mosley, DMD, (Singh, B.B.) Medical College of Georgia, Dept. of Oral Pathology, Augusta, GA 30912-1270

Effects of anti-inflammatory agents on hamster tongue mucosa treated with a phorbol ester : Ronald Mosley, DMD, (Singh, B.B.) Medical College of Georgia, Dept. of Oral Pathology, Augusta, GA 30912-1270

Radiation proctitis in the rat. Sequential changes and effects of anti-inflammatory agents.

Female Wistar rats were treated with single exposure irradiation to 2 cm of distal colon to cause radiation proctitis. All animals were evaluated by examination, colonoscopy and histologic evaluation for changes post-irradiation. Exposures of 10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5 and 30 Gy caused dose-related clinical and histologic changes peaking at 7 to 15 days post-exposure. Rats treated with 20 Gy were colonoscoped and biopsied daily and showed sequential post-irradiation endoscopic changes ranging from mucosal edema and mild inflammatory changes to erosion and ulcers. Histologically, crypt abscess and mural wall necrosis similar to changes found in the human rectum after radiotherapy were noted. Treatment with nonsteroidal anti-inflammatory agents, (aspirin, indomethacin, piroxicam), misoprostol (a prostaglandin E1 analogue), or sucralfate (an anti-ulcer agent) did not ameliorate nor exacerbate radiation proctitis in rats exposed to 22.5 Gy. We conclude from these data that the female Wistar rat is a good model for studying radiation proctitis because endoscopic, histologic, and clinical changes seen post-exposure closely resemble those found in man.

Effects of antiinflammatory agents on edema and DNA synthesis induced by 12-O-tetradecanoylphorbol-13-acetate in the guinea pig.

Inflammation and hyperplasia are frequently associated in skin diseases. In order to verify this relationship, we studied the antagonistic effect of different classes of antiinflammatory agents on the inflammatory and hyperplasiogenic responses elicited by one topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA) to the ear of the guinea-pig. Edema and DNA synthesis were chosen as relevant parameters. All antiinflammatory agents tested significantly inhibited DNA synthesis induced by TPA. Moreover, all compounds except quinacrine and phenylbutazone also inhibited edema formation. In conclusion, our results demonstrate that while edema and hyperplasia are frequently associated, this is not always the case.

Effects of anti-inflammatory Agent No.6 for injection on the oxidative burst of rat peritoneal macrophages.

Anti-inflammatory Agent No.6 for injection (AI-6) is an effective anti-infective agent composed of four traditional Chinese medicinal herbs. It was demonstrated in our experiment that the agent was able to enhance oxidative burst of rat peritoneal macrophages as shown by the increased production of H2O2 and increased reduction of nitroblue tetrazolium (NBT). It seems likely that by these means AI-6 could promote the bactericidal function of macrophages. NBT reduction of macrophages was observed by both spectrophotometric quantification and electron microscopy.

Effect of Anti-inflammatory Agent No.6 for injection on the cAMP content of rat peritoneal macrophages

The effect of Anti-inflammatory Agent No.6 for injection (AI-6) on the cAMP content of rat peritoneal macrophages (Mϕ) was studied in the present work. It was demonstrated in in vitro studies that AI-6, while showing no effect on the basal cAMP level in resident peritoneal Mϕ, significantly facilitated the formyl Methionyl-Leucyl-Phenylalanine-induced increase in the intracellular cAMP concentration (control: 34.01 ±3.48 pmol/107 cells, test; 41.68±2.76 pmol/107 cells;P< 0.05). In vivo, AI-6 was found to increase the intracellular cAMP concentration of fetal calf serum(FCS)-elicited rat peritoneal Mϕ (control: 28.5±3.17 pmol/mg protein, test: 41.01±4.13 pmol/mg protein;P< 0.01). The possible effect of the drug-induced changes in cAMP level on Mϕ function is discussed.

The effects of anti-inflammatory agents on the serology and arthritis of the MRL lpr/lpr mouse.

Mice of the MRL/MpJ lpr/lpr (MRL/I) strain spontaneously develop an autoimmune connective tissue disease that shares immunological and histopathological features with Systemic Lupus Erythematosus and rheumatoid arthritis [1]. To evaluate the usability of the MRL/1 mouse strain for detecting anti-arthritic drugs we have studied the effect of various classes of compounds upon six disease parameters, namely: survival, lymphoproliferation (spleen weight), arthritis (histology), serum levels of the acute-phase reactant Serum Amyloid P component (SAP), the anti dsDNA antibodies (Ab) and the IgG + IgM rheumatoid factors (RF).

Effect of anti-inflammatory agents on the haemorrhagic response of mouse skin to Bordetella pertussis heat-labile toxin.

Bordetella pertussis heat-labile toxin (HLT) was assayed by the haemorrhagic response produced by subcutaneous injection into weaned mice. Young mice, 3-5 weeks old of either sex, were highly responsive but they became resistant to HLT as they matured. Two anti-inflammatory agents, prednisolone and meclofenamate, inhibited the skin reactions in young mice. When given intraperitoneally, prednisolone was most inhibitory if it was injected just before, or at the same time as, HLT challenge. Prednisolone given 3 h after challenge, when the skin reactions had started to develop, did not significantly attenuate the final response. Both drugs were even more effective when mixed with the HLT challenge and injected subcutaneously. These findings are discussed in relation to the possible mechanism of action of HLT and to the reported beneficial effects of corticosteroids in the treatment of whooping cough.

The Effect of Anti-Inflammatory Agents on Release of Elastase from Human Neutrophils in Vitro

The Effect of Anti-Inflammatory Agents on Release of Elastase from Human Neutrophils in Vitro

An assay of mononuclear cell dynamics in various subcutaneous cranial sites

Although polymorphonuclear leukocyte kinetics at sites of tissue injury have been well documented, analogous mononuclear cell data have yet to be reported because of the lack of suitable assay techniques. In this study, counts of mononuclear cells adherent to nitrocellulose filter discs implanted in four subcutaneous sites for nine consecutive days showed a greater degree of cellular accumulation in the temporalis than in the frontalis region, the data for the masseter and submandibular regions being similar and intermediate. This type of assay may prove useful in elucidating the role of mononuclear cells in wound healing and the effect of antiinflammatory agents on mononuclear cell kinetics.

Effect of anti-inflammatory agents on the glycosaminoglycan metabolism in cultured human synovial cells.

The interaction of various anti-inflammatory agents with the metabolism of proteoglycans (glycosaminoglycans) was studied by determination of the distribution of radiolabelled glycosaminoglycans into the intracellular, pericellular and extracellular compartments of cultured synovial cells. The agents interfere dose dependently with different metabolic processes: Benzarone and flufenamic acid (10−4 mol/l) show an inhibition of the synthesis of glycosaminoglycans probably operative at an early phase of the metabolism (transcription or translation process). Colchicine causes an inhibition of both the biosynthesis and secretion of glycosaminoglycans at concentrations ≧10−7 mol/l. An inhibition of the degradation is assumed at a lower concentration (10−8 mol/l). Exposure of the cells to glycosaminoglycan polysulfate leads to an inhibition of the synthesis and degradation as well, the latter being the dominant effect at lower concentrations (0.3–30 mg/l). The secretion of hyaluronate and chondroitin sulfate and the proteolytic degradation of proteochondroitin sulfate seems to be inhibited by the proteinase inhibitor gabexate mesilate at concentrations ≧10−3 mol/l.

Effect of anti-inflammatory agents and lipoxygenase inhibitors on phospholipid metabolism

Effect of anti-inflammatory agents and lipoxygenase inhibitors on phospholipid metabolism

Effects of anti-inflammatory agents on exaggeration of carrageenin edema by phospholipase A2 and polyunsaturated fatty acids

Phospholipase A2 (125 ng), arachidonic acid (50 ug), 8, 11, 14-eicosatrienoic acid (50 ug) and prostaglandin E2 (500 ng) exaggerated carrageenin-induced edema when administered subcutaneously with carrageenin to the rat paw. On the other hand, 11, 14, 17-eicosatrienoic acid, 6, 9, 12-octadecatrienoic acid, 9, 12-octadecadienoic acid and 4, 7, 10, 13, 16, 18-docosahexaenoic acid (each 50ug) did not potentiate the edemainducing activity of carrageenin.Prednisolone, clidanac, indomethacin, phenylbutazone, aspirin, aminopyrine, tiaramide, quinacrine and theophylline administered orally to rats inhibited the carrageenin edema, but the profile of inhibitory effects on potentiating actions by phospholipase A2, arachidonic acid and prostaglandin E2 varied from compound to compound.

Effects of antiinflammatory agents and prostaglandins on acid and bicarbonate secretions in the amphibian-isolated gastric mucosa

Effects of antiinflammatory agents and prostaglandins on H+ and HCO−3 secretions and electrical properties were investigated in the amphibian-isolated gastric mucosa. Gastric HCO−3 transport was studied in Rana temporaria fundus, in which H+ secretion had been inhibited with the histamine H2-receptor antagonists metiamide or cimetidine (10−3M), and in Necturus antrum, which secreted HCO−3 spontaneously. Hydrocortisone (100–500 μg/ml) had no effect on H+ or HCO−3 secretion in the fundus. Indomethacin (10−4 M) was a considerably more potent inhibitor of HCO−3 secretion than of H+ secretion in the fundus and also inhibited HCO−3 transport in the antrum. Fenclofenac (3 × 10−3 M) almost abolished fundic HCO−3 transport and also depressed H+ secretion. There was a marked fall in transmucosal potential difference and a decrease in electrical resistance in fenclofenac-treated mucosae whereas indomethacin had less effect on electrical properties at the concentrations used here. The prostaglandins, E2, 16,16-dimethyl E2 and I2 all inhibited H+ secretion but only 16,16-dimethyl E2 stimulated HCO−3 secretion. The inhibitory action of indomethacin on HCO−3 secretion was prevented by co-administration of 16,16-dimethyl PGE2 (10−6M). It is proposed that the inhibitory action of nonsteroidal antiinflammatory drugs and the stimulatory action of some prostaglandins on HCO−3 secretion contributes to their ulcerogenic and anti-ulcer actions on the gastric mucosa.

The neutrophil adherence assay as a method for detecting unique anti-inflammatory agents.

Neutrophil adhesiveness is an important component of the pathophysiology of the inflammatory process. Modulation of this function could result in a reduction in the degree of inflammation and connective tissue damage. A simple technique using filtration of whole blood through nylon fiber columns has been developed to study the effect of anti-inflammatory agents on the adherence of rat peripheral blood neutrophils. Gold and chloroquine, in addition to many standard anti-inflammatory drugs, have been shown to cause inhibition of neutrophil adherence. Measurement of this parameter of cell behavior has the potential of detecting anti-inflammatory agents not normally effective in the standard animal models.

Effects of antiinflammatory agents on the acute response of immune synovitis in rabbits.

Immune synovitis in rabbits was investigated as a potential in vivo model for evaluating new antiinflammatory agents. Antigen-induced increases in knee width as well as beta-glucuronidase and acid phosphatase activities in exudates were observed. Histologically, polymorphonuclear leukocytes appeared within hours in synovial tissues and reached maximum infiltration at about 24 hours. Subsequently, mononuclear cells, including plasma cells, appeared. The 6-hour Arthus-like phase of synovitis can be depressed by some antiinflammatory agents, colchicine and steroids being particularly effective. It is suggested that this model can be utilized to define potentially more effective antiinflammatory drugs.

An overview of nonsteroidal antiinflammatory agents (NSAIA).

Since the rediscovery of willow bark extract (salicin) in 1763, there has been a continuing effort to improve efficacy and reduce the side effects of antiinflammatory agents through chemical modification and innovation. The second-generation NSAIA's, phenylbutazone and indomethacin, provided clear support for the idea that these objectives were obtainable. The success of steroid programs in enhancing potency and modifying side effects, coupled with the development of effective screening techniques for identifying antiinflammatory activity, stimulated an enormous effort to develop new NSAIA's. The products of this effort are now coming to the clinic. Although less successful than the steroid program in enhancing potency, the effort has succeeded in changing and reducing side effects. As a result, the clinician has a greater choice of agents for dealing with individual patient variability and achieving greater patient acceptance.

Effects of anti-inflammatory agents on release of lysosomal enzymes from rabbit polymorphonuclear leucocytes induced by phospholipase C (author's transl)

Effects of anti-inflammatory agents on release of lysosomal enzymes from rabbit polymorphonuclear leucocytes induced by phospholipase C (author's transl)