kaolinite and Edema

Topics: Animals; Anti-Inflammatory Agents; Bradykinin; Carrageenan; Cell Migration Inhibition; Dextrans; Disease Models, Animal; Drug Evaluation, Preclinical; Edema; Foot; Formaldehyde; Guinea Pigs; Histamine; Inflammation; Kaolin; Ovalbumin; p-Methoxy-N-methylphenethylamine; Povidone; Rabbits; Rats; Saccharomyces cerevisiae; Serotonin; Species Specificity

The goal of this study was to investigate the topical anti-inflammatory effects of the megamolecular polysaccharide sacran extracted from cyanobacterium Aphanothece sacrum using various inflammatory animal models. Sacran showed potent anti-inflammatory effects with optimum effective concentrations at 0.01 and 0.05% (w/v). Sacran markedly inhibited paw swelling and neutrophil infiltration in carrageenan-induced rat paw edema. Additionally, 6,7-dimethoxy-1-methyl-2(1H)-quinoxalinone-3-propionyl-carboxylic acid (DMEQ)-labeled sacran had the ability to penetrate carrageenan-induced rat paw skin rather than normal skin. Also, sacran significantly suppressed kaolin-induced and dextran-induced rat paw edema throughout the duration of the study. Furthermore, sacran significantly suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema and mRNA expression levels of cyclooxygenase (COX)-2 as well as pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. Safety of sacran solution was verified by negligible cytotoxicity in HaCaT cells. These results suggest that sacran may be useful as a therapeutic agent against inflammatory skin diseases with no life-threatening adverse effects.

Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Cell Line; Cyanobacteria; Cyclooxygenase 2; Cytokines; Dextrans; Disease Models, Animal; Edema; Female; Humans; Kaolin; Male; Mice, Inbred BALB C; Polysaccharides; Quinoxalines; Rats; Rats, Wistar; Tetradecanoylphorbol Acetate

intra-articular co-injection of kaolin with carrageenan (CGN) in rodents is widely used as an experimental model of arthritis. However, the ability of kaolin to cause arthritis and related immune responses when administered alone is unclear. We evaluated the contribution of prostanoids and sensory C-fibres (and their neuropeptide substance P) to kaolin-induced inflammation in the rat knee.. Wistar rats, 8-10 weeks old, received an intra-articular injection of kaolin (1-10 μg/joint) or saline into the knee joint. Knee inflammation, proinflammatory cytokines, pain behaviour and secondary tactile allodynia were assessed over 5 h, when synovial leukocyte counts, histopathological changes and proinflammatory cytokine levels were evaluated.. The intra-articular injection of kaolin caused a dose- and time-dependent knee swelling and impairment of motion that were associated with secondary tactile allodynia, elevated concentrations of IL-1β, IL-6 and TNFα, leukocyte infiltration, and histopathological changes in the ipsilateral hindpaw. The neurokinin-1 (NK1) receptor antagonist SR140333 or neonatal treatment with capsaicin markedly reduced the inflammatory parameters, cytokines and allodynia but failed to significantly inhibit the impaired motion. The cyclo-oxygenase inhibitor indomethacin partially inhibited knee oedema and allodynia but did not affect the leukocyte influx, myeloperoxidase activity or impaired motion in the kaolin-injected rat.. We show the first evidence that intra-articular injection of kaolin without CGN produced severe acute monoarthritis. This was highly dependent on substance P (released from C-fibres) and NK1 receptor activation, which stimulated local production of proinflammatory cytokines. This model may be of critical importance for mechanistic studies and screening new anti-inflammatory/analgesic drugs.

Topics: Animals; Animals, Newborn; Antidiarrheals; Arthritis; Capsaicin; Cytokines; Disease Models, Animal; Edema; Enzyme Inhibitors; Hyperalgesia; Indomethacin; Kaolin; Knee Joint; Male; Pain Measurement; Peroxidase; Piperidines; Quinuclidines; Rats; Rats, Wistar; Receptors, Neurokinin-1; Synovial Fluid

In the present work, the antiarthritic activity of hautriwaic acid is reported. This ent-clerodane diterpene isolated from Dodonaea viscosa was evaluated in mice using a kaolin/carrageenan-induced monoarthritis model. The inflammation observed in the joint (knee) on days 1-8 ranged from 50-70 %. After 10 days of treatment with different doses of hautriwaic acid (5, 10, 20 mg/kg), a decrease in knee inflammation was detected. This recovery was observed with both reference drugs, methotrexate (1 mg/kg) and diclofenac (0.75 mg/kg). In these groups of mice, the concentration of proinflammatory cytokines interleukin-1 beta, interleukin-6, and tumor necrosis factor alpha in the joint was significantly lower than that of the negative control group (animals with damage without any treatment). The negative control group presented a decrease in the concentration of interleukin-10, while the groups that received hautriwaic acid at different dose exhibited an increase in this interleukin. This anti-inflammatory cytokine was not modified in the joint of mice with diclofenac, but in mice that received methotrexate, a significant decrease was observed. Hautriwaic acid isolated from D. viscosa diminished the joint edema induced by this mixture of polysaccharides (carrageenan), possibly by acting as immunomodulator of the inflammatory response.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Carrageenan; Diclofenac; Diterpenes; Dose-Response Relationship, Drug; Edema; Female; Interleukin-10; Kaolin; Methotrexate; Mice, Inbred Strains; Sapindaceae; Tumor Necrosis Factor-alpha

Olive leaf extract (OLE) has antioxidant and antiinflammatory actions. However, the role of OLE in mechanical inflammatory arthritis (osteoarthritis, OA) is unclear. This study investigated the effect of OLE on the development of kaolin and carrageenan-induced arthritis, a murine model of OA. Administration of OLE significantly ameliorated paw swelling, the paw Evans blue content and the histopathological scores. In the human monocyte cell line, THP-1, the OLE reduced the LPS-induced TNF-α production and was dose dependent. Croton oil-induced ear edema in mice also revealed that treatment with OLE suppressed ear edema, myeloperoxidase (MPO) production and was dose dependent. These results indicated that OLE is an effective antiarthritis agent through an antiinflammation mechanism. Also OLE may be beneficial for the treatment of OA in humans.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Carrageenan; Cell Line, Tumor; Croton Oil; Dose-Response Relationship, Drug; Edema; Evans Blue; Humans; Inflammation; Kaolin; Lipopolysaccharides; Male; Mice; Mice, Inbred BALB C; Olea; Peroxidase; Phytotherapy; Plant Extracts; Plant Leaves; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

Semi-synthetic cephalosporin antibiotics have structures similar to that of penicillins, and both groups of compounds are characterized by similar properties and determined by the same methods. Most antibiotics, including cephalosporins and their decomposition products, contain electron donor groups that can bind naturally occurring metal ions in vivo. Cephalosporin antibiotics exhibit a change in their toxicological properties and biological performance when they were tested as metal complexes. The proposed reason for such a behavior is the capability of chelate binding of the cephalosporins to the metals. In an attempt to understand the coordination mode of metals with cephalosporins, different spectroscopic techniques such as IR, UV-visible, NMR spectroscopy and voltammetric measurements were carried out to elucidate the structure of the metal-cephalosporin complexes. Synthesis, characterization and biological screening of the cephalosporins and of the cephalosporin-metal complexes are discussed in this review. However, little information is available on the influence of the metal ions on the pharmacokinetics of the cephalosporin derivatives.

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Biopharmaceutics; Cephalosporins; Copper; Edema; Kaolin; Magnetic Resonance Spectroscopy; Male; Metals; Microbial Sensitivity Tests; Rats; Rats, Wistar; Solubility; Spectrophotometry, Infrared; Spectrophotometry, Ultraviolet; Thermogravimetry; Zinc

Since pain is an important symptom in arthritis, useful behavioral indices for pain in experimental arthritis animal models are important tools for investigative work on arthritis. The purpose of this study was to develop simple and quantifiable behavioral tests, which would represent the level of arthritic pain that develops after induction of inflammation in the knee. Two models of knee joint arthritis were produced: (1) KC model-injection of kaolin and carrageenan into the synovial cavity of the knee, and (2) CFA model-injection of complete Freund's adjuvant into the synovial cavity of the knee. The following three variables were measured before and at various times after the induction of arthritis. As an estimate of the degree of edema, the circumference of the knee was measured. As pain indices, (1) the vocalization threshold of compression force applied to the knee joint was measured to represent tenderness of the joint, and (2) the struggle threshold of the knee extension angle was measured to represent a reduction in range of motion in the arthritic joint. A time course study showed that behavioral changes last for at least 1 week for the KC model and at least 2 weeks for the CFA model. Correlation studies showed that all three variables significantly correlated with each other in both the KC and CFA arthritic models. Systemically injected morphine produced a partial reversal of these indices with the expected time course and dose response of a morphine-induced analgesic. It is concluded that two variables, the struggle threshold for knee extension and the vocalization threshold for knee compression, could be used as simple and useful pain indices in experimental models of arthritis.

Topics: Analgesics, Opioid; Animals; Arthritis; Biomechanical Phenomena; Carrageenan; Disease Models, Animal; Edema; Freund's Adjuvant; Kaolin; Knee Joint; Male; Morphine; Motor Activity; Pain; Pain Measurement; Pain Threshold; Range of Motion, Articular; Rats; Rats, Sprague-Dawley; Stress, Psychological; Vocalization, Animal

The possible anti-inflammatory activity of the 90% ethanolic extract of Dalbergia sissoo leaves (DSELE) was studied in different models of inflammation in rats after oral administration at doses of 100, 300 and 1000 mg/kg. DSELE significantly inhibited carrageenin, kaolin and nystatin-induced paw oedema, as well as the weight of granuloma induced by a cotton pellet. It also inhibited dye leakage in acetic acid-induced vascular permeability test in mice. DSELE was devoid of ulcerogenic effect on the gastric mucosa of rats in acute and chronic tests. In acute toxicity studies, it was found to be safe up to 10.125 g/kg, p.o. in the rat. It was concluded that the D. sissoo leaf extract possessed significant anti-inflammatory activity (in acute, sub-acute and chronic models of inflammation) without any side effect on gastric mucosa.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Capillary Permeability; Carrageenan; Dose-Response Relationship, Drug; Edema; Female; Gastric Mucosa; Kaolin; Male; Mice; Nystatin; Plant Extracts; Plant Leaves; Plants, Medicinal; Rats; Rats, Wistar; Rosales

The ethanolic extract of the bark of Syzygium cumini was investigated for its anti-inflammatory activity in animal models. The extract did not show any sign of toxicity up to a dose of 10.125 g/kg, p.o. in mice. Significant anti-inflammatory activity was observed in carrageenin (acute), kaolin-carrageenin (subacute), formaldehyde (subacute)-induced paw oedema and cotton pellet granuloma (chronic) tests in rats. The extract did not induce any gastric lesion in both acute and chronic ulcerogenic tests in rats. Thus, the present study demonstrated that S. cumini bark extract has a potent anti-inflammatory action against different phases of inflammation without any side effect on gastric mucosa.

Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Dose-Response Relationship, Drug; Edema; Female; Formaldehyde; Gastric Mucosa; Granuloma, Foreign-Body; Kaolin; Male; Mice; Plant Extracts; Plants, Medicinal; Rats; Rats, Wistar; Rosales

Fepradinol is an effective non-steroidal anti-inflammatory agent. The effect on rat paw oedema induced by various phlogistic agents was investigated. The inhibitory effect of fepradinol (25 mg kg-1, p.o.) on dextran-induced oedema was nearly equal to that of cyproheptadine (10 mg kg-1, p.o.). On oedema induced by platelet-activating factor only fepradinol (25 mg kg-1, p.o.) and phenidone (100 mg kg-1, p.o.) clearly inhibited the inflammatory process. Both the above induced oedemas are thought to be unrelated to prostaglandins in the rat system and therefore, the anti-inflammatory activity against them is not shared by selective cyclo-oxygenase inhibitors. Fepradinol (25 mg kg-1, p.o.) displayed an inhibitory effect on the early and late stage of kaolin- and nystatin-induced oedemas in contrast with indomethacin (10 mg kg-1, p.o.) and piroxicam (10 mg kg-1, p.o.) which only inhibited the late stage. The results obtained in this study confirm that fepradinol is a potent anti-inflammatory agent and indicate that its mechanism of action is different from that of other anti-inflammatory compounds.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Dextrans; Edema; Ethanolamines; Foot; Kaolin; Male; Nystatin; Platelet Activating Factor; Rats; Rats, Wistar

A new synthesis is proposed for cordiachromene A (CCA), a bioactive component of the ascidian Aplidium antillense Gravier, using a method producing a racemic mixture. The anti-inflammatory activities of a natural extract and a chemically synthetic form of CCA were assessed in vivo by carrageenan-induced rat-paw edema. The activity of synthetic CCA was confirmed by a test on kaolin-induced granuloma in the rat. Strong activities were measured for both CCA, but comparison of results of the first test suggests that only the natural optically active isomer has an anti-inflammatory effect. CCA is similar to indomethacin in its effect on carrageenan-induced rat-paw edema and ten times as active as phenylbutazone.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Chromones; Edema; Foot Diseases; Granuloma; Isomerism; Kaolin; Male; Mice; Rats

1. An extract prepared from the tentacle of the jellyfish (CE), Catostylus mosaicus exhibited haemolytic, oedema and haemorrhage-inducing activities. 2. Acetone treatment of the tentacle extract produced an acetone soluble extract (AE) which showed an increase in specific haemolytic and haemorrhagic activities by 25- and 120-fold respectively; the minimum oedema dose was reduced by 30-fold. 3. The AE caused a rapid onset of oedema in the mouse foot pad. The effect was long-lasting, reaching a maximum in about 30 min after injection and sustained up to 4 hr. 4. Fractionation of the AE on Q-Sepharose gave 4 bound fractions which induced oedema and haemorrhage; however only 3 of the fractions exhibited haemolytic activity.

Topics: Acetone; Animals; Chromatography, Ion Exchange; Cnidarian Venoms; Edema; Hemolysis; Hemorrhage; Kaolin; Kinetics; Mice; Povidone; Rabbits; Solubility

Meloxicam (Mel) is a new non-steroidal anti-inflammatory drug (NSAID) which was selected with regard to its remarkable efficacy in adjuvant arthritis of the rat. Similar to the situation in man, three main metabolites were identified in rat urine which are rapidly excreted since they are not detectable in blood, where only the parent compound was found. The latter is practically not eliminated in urine. Since it has been proposed that the nephrotoxicity of NSAIDs is due to inhibition of prostaglandin E2 (PG) biosynthesis, the aim of the study was to determine whether the metabolites can contribute to the known effects of the parent compound in this pathway. For this purpose, PG-biosynthesis was measured in vitro using a radiochemical technique with an enzyme preparation from bull seminal vesicles. In an in vivo assay the effect of the compounds against kaolin-induced oedema in the rat hind paw was determined. In the test systems described, the efficacy of Mel has been demonstrated. In contrast to this finding, the metabolites in relevant doses showed neither in vitro nor in vivo effects. From the results it can be concluded that the metabolites do not change renal blood flow and therefore have no capability for nephrotoxicity. These findings are in accordance with the observations in the rat kidney during subacute and chronic toxicity studies, where no nephrotoxic effects could be detected after therapeutic doses.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Dose-Response Relationship, Drug; Edema; Exudates and Transudates; Kaolin; Male; Meloxicam; Prostaglandins; Rats; Thiazines; Thiazoles

1. The hypothesis of a pro-inflammatory activity in lymphocytes related to the development of nonimmune acute inflammation was tested in leucopenic rats injected subcutaneously with various stimuli representing different pharmacological classes of paw edema-inducing agents into the subplantar area of one of the hind paws. 2. Amethopterin-induced leucopenia rendered animals hyporeactive to carrageenin and trypsin, but not to kaolin or dextran. 3. Administration of splenic lymphocytes to leucopenic rats to correct lymphopenia partially restored the inhibited responses to carrageenin and the early phase of responses to trypsin. 4. These results suggest that lymphocytes may play a pro-inflammatory role in nonimmune acute inflammation, which is more demonstrable in some pharmacological classes of paw edema than in others.

Topics: Animals; Carrageenan; Dextrans; Edema; Hindlimb; Inflammation; Kaolin; Leukocyte Count; Leukopenia; Lymphocyte Depletion; Lymphocytes; Male; Methotrexate; Rats; Rats, Inbred Strains

Plasma levels of some arachidonic acid metabolites were investigated in acute and chronic models of inflammation in rats. As a model of chronic inflammation, adjuvant arthritis in rats induced by the injection of Freund's complete adjuvant, and as an acute model for inflammation, kaolin-induced paw oedama were used. Plasma leukotriene(LT) C4-like and prostaglandin(PG) E2-like activities were quantitated by bioassay in guinea-pig ileum and rat stomach fundus respectively. In the course of adjuvant arthritis, plasma levels of LTC4- and PGEi2-like activities were increased. Plasma LTC4-like activity reached a maximum within 3 weeks, while PGE2-like activity reached a maximum 10 days after adjuvant injection. In the early phase of adjuvant arthritis, levels of both LTC4- and PGE2-like activities were found to be low but both activities were increased in the late phase of inflammation.

Topics: Animals; Arthritis; Arthritis, Experimental; Biological Assay; Dinoprostone; Edema; Gastric Fundus; Guinea Pigs; Ileum; Kaolin; Rats; SRS-A

The author compared the efficiency of 3-amino-4-mercapto-6-methylpyridazine (1; pyridazine S1) and some standard pharmaca by means of acute and subacute inflammation models. As evidence by the acute assay, the kaolin and carragheenin-induced oedemata of the rat paw as well as the Evans's blue excretion the potency of 1 compared with that of acetylsalicylic acid. Phenylbutazone and indomethacin exhibited a higher degree of activity. In the cotton-induced granuloma test, 1 was ineffective, whereas indomethacin applications had a powerful effect against inflammatory reactions. The results obtained during this investigation suggest that the activity spectrum of 1 is similar to that of acetylsalicylic acid.

Topics: Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Carrageenan; Disease Models, Animal; Edema; Evans Blue; Exudates and Transudates; Granuloma; Indomethacin; Inflammation; Kaolin; Male; Phenylbutazone; Pyridazines; Rats; Rats, Inbred Strains

The bentonite and kaolin oedemas were simultaneously induced in the rat hind paws and their courses and morphological patterns were observed under the conditions of the same biological background. Gross examination has confirmed the former experience that the kaolin oedema has a more pronounced acute phase (maximum after five to seven hours) followed by subsequent spontaneous regression of the oedema, while the bentonite oedema has its acute phase less pronounced, attains its peak only on the second day, maintaining this same size over several weeks without substantial changes. The courses of the two oedemas were in correlation with the results of histological evaluation (oedematous exudation, polymorphonuclear and mononuclear infiltration and the phagocytic activity of the latter). Resorption of kaolin in the newly-developed non-specific granulation tissue was much faster than that of bentonite (after about three weeks, while bentonite was not resorbed even after six weeks). Further, pharmacological and histological examination was performed of the effects on the bentonite oedema of sodium salicylate and Prednisone during the first 24 hours. Both substances suppressed the oedema, sodium salicylate delayed both polymorphonuclear and mononuclear infiltration, Prednisone delayed only mononuclear infiltration. The presence of mononuclear population was confirmed also by means of the positive activity of non-specific esterase and the negative activity of alkaline phosphatase. The bentonite rat-paw oedema has thus been proved to be a suitable model of inflammatory reaction for testing anti-inflammatory drugs not only in short-term (acute) tests, but also in long-term ones, where it yields a uniform picture of non-specific foreign-body low-turnover granuloma.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents; Bentonite; Edema; Female; Follow-Up Studies; Foot Diseases; Hindlimb; Inflammation; Kaolin; Male; Neutrophils; Phagocytes; Rats; Rats, Inbred Strains

Local anti-inflammatory activity of etofenamate gel (5% etofenamate) was investigated in rats. Etofenamate gel (5--50 mg/paw) produced a dose related inhibition in the hind paw edema caused by carrageenin with a topical application to the inflamed paw, and its ED50-value was 33.0 mg/paw. A weak but significant inhibiton was seen with an application of 50 mg/paw to the non-inflamed paw, but not with 10 mg/paw. Anti-edema activity of oral etofenamate (ED50 = 8.49 mg/kg) was comparable to flufenamic acid. Against the hind paw edema caused by a mixture of kaolin and carrageenin, etofenamate gel showed a significant therapeutic activity with repeated application of 10--50 mg/paw to the inflamed paw, but not with 10 mg/paw to the non-inflamed paw. Etofenamate gel (50 mg/paw/day), applied topically to the inflamed hind paw of adjuvant rats, showed a significant therapeutic activity. The potency of oral etofenamate (4--8 mg/kg/day) in adjuvant rats was comparable to flufenamic acid. No gastrointestinal ulcer was produced by a topical application of etofenamate gel (up to 1,000 mg/rat) to the clipped skin, though oral etofenamate (40 mg/kg) produced the ulcer. From these results, it was suggested that etofenamate gel, applied to the skin of rats, showed local anti-edema activity approximately comparable to oral etofenamate, and the ratio of ulcerogenic effective to anti-edema dose of etofenamate gel was larger than that of oral etofenamate.

Topics: Administration, Oral; Administration, Topical; Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Carrageenan; Edema; Female; Flufenamic Acid; Gels; Kaolin; Male; Ointments; Peptic Ulcer; Rats; Rats, Inbred Strains

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Copper; Disease Models, Animal; Edema; Guinea Pigs; Inflammation; Kaolin; Male; Rats

Several gold salts were compared in kaolin-induced rat paw oedema, u.v. erythema in guinea pigs, delayed type hypersensitivity and humoral immunity in mice, and adjuvant-induced arthritis in the rat. In the latter the additional parameters of serum gold and copper levels and lysosomal enzyme activity were determined. In addition, the in vitro inhibition of several lysosomal enzymes derived from mouse macrophages was studied. The gold compounds examined were aurothiomalate, aurothioglucose, triethylphosphine gold chloride (SK & F 36914) and its glucopyranoside derivative (SK & F D-39162), triphenylphosphine gold chloride and sodium gold chloride dihydrate. SK & F 36914 and SK & F D-39162 has significant activity after oral dosage upon paw kaolin and u.v. erythema in rats and guinea pigs, respectively. Gastric swelling also occurred. In Wistar rats, adjuvant arthritis was little affected by the gold salts but in the Lewis rats there was suppression. In both strains there was less elevation in serum copper levels with treatment by SK & F 36914 and SK & F D-39162, but not by aurothiomalate. None of the compounds had any measurable effect on delayed hypersensitivity or humoral antibody levels in mice. The in vitro activities of cathepsin B1 and cathepsin D were inhibited by all the gold compounds. Reactivity of gold compounds with glutathione and cysteine in vitro was dependent on compound solubility and the nature of the gold ligand. Considerable differences exist between the profiles of activity for the different gold salts evaluated. These observations indicate that some gold salts do possess anti-inflammatory activity with a potency similar to that of indomethacin.

Topics: Animals; Antibody Formation; Arthritis, Experimental; Cysteine; Edema; Erythema; Glutathione; Gold; Guinea Pigs; Hypersensitivity, Delayed; Immunity; Inflammation; Kaolin; Lysosomes; Male; Mice; Rats; Ultraviolet Rays

Copper complexes of a range of ligands have been prepared and evaluated for antiinflammatory activity and irritancy after oral, subcutaneous, and local administration in rats and guinea pigs. The antiinflammatory activities were found to depend on the species used and the route of administration. When nonantiinflammatory ligands were used, the response was generally dose dependent. With D-penicillamine and when the ligands were themselves antiinflammatory in animal models of inflammation--as was the case with flufenamic acid, levamisole, aspirin, L-histidine, and 2-amino-2-thiazoline--differences in antiinflammatory activity were observed between the copper complexes and the free ligands. In some cases, the copper complexes were the more effective. There was a weak correlation between local (subplantar) irritation and the dose of copper but, for four compounds studied in more detail, the response in the local subplantar test and degree of antiinflammatory activity were not related, suggesting that the action of copper is not solely by a counterirritant mechanism. No obvious differences between the activities of copper(I) and copper(II) compounds were observed, suggesting that a common metabolite may be involved in the antiinflammatory action of copper.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Copper; Edema; Female; Guinea Pigs; Injections, Subcutaneous; Irritants; Kaolin; Ligands; Male; Rats; Stomach Ulcer

Topics: Animals; Edema; Erythrocyte Membrane; Female; Humans; Kaolin; Phenylacetates; Rats; Structure-Activity Relationship

The development of novel anti-inflammatory drugs (AID) has been claimed to be dependent on the discovery of models of inflammation that differ from those currently used for drug screening, e.g. carrageenen paw oedema and u.v. erythema. We have thus evaluated the effect of a variety of drugs in a number of novel models of inflammation in the rat produced in the hind paw. We have utilized kaolin, zymosan, anti-rat IgG (anti-IgG) and the Reversed Passive Arthus (RPA) reaction to produce these oedema models. We found that the non-steroidal AID's, e.g. aspirin, flufenamic acid, indomethacin, naproxen, and phenylbutazone, were active in all four tests. Of the nine novel AID examined, levamisole and tetramisole demonstrated considerable activity in all four tests and dapsone was especially active in the anti-IgG and RPA tests. In contrast, the anti-rheumatic d-penicillamine was inactive in all four models. Each of the ten compounds tested which has been claimed to influence complement function, was active in the RPA but not in the kaolin model. These results are discussed in the context of the aetiology of each oedema and the suspected mode of action of the various drugs.

Topics: Animals; Anti-Inflammatory Agents; Antibodies, Anti-Idiotypic; Arthus Reaction; Disease Models, Animal; Drug Evaluation, Preclinical; Edema; Immunoglobulin G; Kaolin; Male; Ovalbumin; Rats; Stomach Ulcer; Zymosan

1,6-Dimethyl-4-oxo-1,6,7,8,9,9a-hexahydro-4H-pyrido[1,2-a]pyrimidine-3-carbamide (Chinoin 127), a non-narcotic analgesic with potent antiinflammatory activity is described. Chinoin-127 is more potent as an analgesic in the hot plate, Randall-Selitto and writhing tests than is acetylsalicylic acid (ASA) and an effective antiphlogistic agent in a battery of tests (carrageenin, kaolin and dextran induced rat paw edema, Northover test, carrageenin induced abscess, implanted cotton pellet method, adjuvant arthritis) used for measuring antiinflammatory activity. The PG-synthesis inhibitors (indometacin, suprofen) were found to be devoid of analgesic activity, and great test-dependent variations in their antiinflammatory effect were observed. They proved to be inactive in the Northover test. Unusual grade of inhibition in the carrageenin-induced rat paw edema test was obtainable by the simultaneous administration of Chinoin 127 and indometacin.

Topics: Abscess; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Capillary Permeability; Carrageenan; Dextrans; Edema; Female; Granuloma; Kaolin; Male; Mice; Prostaglandins; Pyrimidinones; Rats; Stomach Ulcer

Levamisole potentiated paw oedema induced by carrageenan in the rat whereas penicillamine was without effect. On the other hand, levamisole inhibited paw oedema induced by kaolin, penicillamine again having no effect. The copper complex of penicillamine was inhibitory in the carrageenan test but failed to show inhibition in the kaolin model of inflammation. These results show that levamisole and penicillamine are capable of exerting anti-inflammatory activity in the rat but only under certain conditions.

Topics: Animals; Carrageenan; Edema; Female; Inflammation; Kaolin; Levamisole; Male; Penicillamine; Rats

Effect of tolmetin sodium(Tol) on acute and subacute exudative inflammation was tested in experimental animals. Tol had a potent inhibitory activity (ED50 = 0.75 mg/kg, p.o.) on the increased vascular permeability induced by acetic acid in mice, and the potency was about 0.4 times that of indomethacin (Ind), and 6-93 times that of ibuprofen (Ibu), phenylbutazone(Phe) and aspirin(Asp). The inhibitory activity of Tol(ED50 = 18.2 mg/kg, p.o.) on UV-induced erythema in guinea pigs was about 0.3 times that of Ind. A recovery of the hind paw edema of rats, produced by a mixture of kaolin and carrageenin, was promoted by oral administration of Tol(2.5 approximately 20 mg/kg x 5/2 days). Tol(80 mg/kg/day, p.o.) showed a significant activity in inhibiting the exudation caused by croton oil in rats, and the activity was about 0.025 times that of Ind and greater than that of Ibu, Phe and Asp. Tol(100-800 microgram/ml) inhibited in a dose-dependent manner the phytohemagglutinin-induced blast transformation of cultured lymphocytes from rat thymus, as did salicylic acid. In vitro, Tol showed a potent activity similar to that of Ibu and Phe in preventing the denaturation of bovine serum albumin and the lysis of rat erythrocytes. From these results, it is suggested that Tol has a particularly potent inhibitory activity on acute exudative inflammation, and the mode of action may be attributed to a mechanism similar to that seen with other acidic non-steroidal anti-inflammatory drugs.

Topics: Animals; Anti-Inflammatory Agents; Capillary Permeability; Carrageenan; Cell Differentiation; Edema; Erythrocyte Membrane; Exudates and Transudates; Guinea Pigs; Hemolysis; Hot Temperature; In Vitro Techniques; Inflammation; Kaolin; Lymphocytes; Male; Mice; Protein Denaturation; Pyrroles; Rats; Sunburn; Tolmetin

Topics: Animals; Arthritis; Arthritis, Experimental; Edema; Gold; Kaolin; Male; Rats

The Freund's adjuvant technic, using killed Mycobacterium butyricum suspended in mineral oil, is a refined tool for anti-inflammatory drug evaluation. Its use has long been reserved for testing and not for screening due to technical problems in the preparation of valid animal models. After reviewing the methodology, the authors demonstrated that the availability of arthritic rats from a modern breeding center (Charles River France, SA, Elbeuf, France) make the procedure applicable to drug screening. This has both practical and economic advantages. The animals can be used as test organisms for drug evaluation 14 da after treatment. Three criteria for measuring the effectiveness of anti-arthritic drugs have been established: an arithritic index determined by examination of the 4 paws; changes in the erythrocyte sedimentation rate; and changes in levels of plasma fibrinogen. The curative activity of test substances can be evaluated by a single series of measurements of these 3 criteria after 14 da of treatment. This test was compared with 2 others; edema of the paw induced by the subcutaneous injection of kaolin or carrageenan, and was found to be superior.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Blood Sedimentation; Breeding; Carrageenan; Drug Evaluation, Preclinical; Edema; Fibrinogen; Freund's Adjuvant; Inflammation; Kaolin; Male; Rats; Specific Pathogen-Free Organisms

Subplantar administration of either Phytohaemagglutinin-P (PHA), Concanavalin-A (Con A) or kaolin into the rat hind paw produced a dose related oedema which was still present at 48 h. Both of the lectins were more inflammagenic than kaolin on a weight per weight basis. As a result of studies using mediator inhibitors and depletors it appears that 5HT, but not histamine, may play a role in the early phases (0.5-1.5 h) of both PHA and Con A responses. Neither mediator appears to be involved in the kaolin oedema. Kinins are also likely mediators of the inflammatory response to all three irritants and could be detected in irritant injected air blebs in the rat. Prostaglandins are unlikely to play a significant role in PHA or Con A oedema since indomethacin-induced inhibition of their synthesis has only a slight inhibitory effect on the lectin induced paw oedemas and only small amounts of prostaglandin-like material could be detected in PHA or Con A blebs. However, kaolin oedema appears to have a significant prostaglandin component since large amounts of prostaglandin-like materials were detected in kaolin blebs and also indomethacin reduced the kaolin induced paw oedema. Other mediators of the inflammatory process such as complement are likely to be involved in all three irritant induced oedemas.

Topics: Animals; Anti-Inflammatory Agents; Concanavalin A; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Edema; Histamine; Inflammation; Kaolin; Kinins; Lectins; Male; Prostaglandins; Rats; Serotonin

Topics: Animals; Anti-Inflammatory Agents; Cyclooxygenase Inhibitors; Edema; Female; Kaolin; Models, Biological; Pregnancy; Rats; Uterine Contraction; Uterus

Topics: Age Factors; Albumins; Animals; Bradykinin; Carrageenan; Consciousness; Dextrans; Disease Models, Animal; Edema; Foot; Guinea Pigs; Histamine; Inflammation; Kaolin; Methods; Mice; Povidone; Rats; Saccharomyces cerevisiae; Serotonin; Sex Factors; Species Specificity; Temperature; Time Factors

Twelve Indian patients with pre-eclampsia, 15 with eclampsia and 15 with normal pregnancy in the third trimester were investigated. A systemic bleeding diathesis was encountered in two patients with eclampsia and in none with pre-eclampsia; two patients with pre-eclampsia, however, had excessive uterine haemorrhage. Coagulation studies showed statistically significant prolongation of thrombin time, elevation of serum fibrinogen degradation products (FDP) and hypofibrinogenaemia in patients with pre-eclampsia as well as eclampsia. In patients with eclampsia, significant thrombocytopenia also occurred. Euglobulin lysis time showed no significant change in patients with pre-eclampsia and eclampsia. There was no significant difference in the coagulation profile between patients with eclampsia and pre-eclampsia, except for more hypofibrinogenaemia in the former. The laboratory findings suggest the occurrence of intravascular coagulation in patients with pre-eclampsia and eclampsia.

Topics: Adult; Albuminuria; Blood Coagulation; Blood Coagulation Disorders; Blood Platelets; Eclampsia; Edema; Female; Fibrinogen; Hemorrhagic Disorders; Humans; Hypertension; India; Kaolin; Middle Aged; Phosphatidylethanolamines; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third; Prothrombin Time; Serum Globulins; Thrombocytopenia; Uterine Hemorrhage

Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Drug Synergism; Edema; Hindlimb; Histamine; Histamine H1 Antagonists; Inflammation; Kaolin; Male; Rats; Serotonin; Serotonin Antagonists; Time Factors

Topics: Aerosols; Animals; Anti-Inflammatory Agents; Bradykinin; Carrageenan; Chemical Phenomena; Chemistry; Edema; Erythema; Guinea Pigs; Hindlimb; In Vitro Techniques; Kaolin; Malonates; Methods; Methylamines; Rats; Sunburn; Triazines; Ultraviolet Rays

Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Deficiency Diseases; Depression, Chemical; Diet; Edema; Fatty Acids, Essential; Hindlimb; Indomethacin; Kaolin; Male; Ovalbumin; Rats

Topics: Animals; Arachidonic Acids; Bradykinin; Carrageenan; Drug Synergism; Edema; Histamine; Kaolin; Male; Prostaglandins; Rats; Serotonin

Topics: Acetates; Animals; Anti-Inflammatory Agents; Benzoates; Carrageenan; Edema; Kaolin; Methylation; Pyrroles; Structure-Activity Relationship

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Carrageenan; Dextrans; Edema; Formaldehyde; Hyaluronoglucosaminidase; Injections, Intraperitoneal; Injections, Subcutaneous; Kaolin; Polysaccharides; Rats; Sulfates; Time Factors; Trypsin Inhibitors

Topics: Animals; Anti-Inflammatory Agents; Dimethylamines; Edema; Foot; Granuloma; Indomethacin; Kaolin; Lethal Dose 50; Mice; Rats; Structure-Activity Relationship; Triazines

Topics: Administration, Oral; Analgesics; Animals; Anti-Inflammatory Agents; Carrageenan; Edema; Erythema; Female; Fever; Granuloma; Guinea Pigs; Hyperesthesia; Injections, Intravenous; Kaolin; Male; Mice; Peritonitis; Phenylbutazone; Pyrazoles; Rats; Terpenes; Ultraviolet Rays

Topics: Animals; Edema; Esterases; Hindlimb; Inflammation; Kaolin; Kidney; Liver; Peptide Hydrolases; Phenylbutazone; Rats

Topics: Animals; Anthelmintics; Anti-Inflammatory Agents; Arthritis; Disease Models, Animal; Dracunculiasis; Edema; Imidazoles; Kaolin; Niridazole; Pleurisy; Rats; Thiazoles; Turpentine

Topics: Adrenocorticotropic Hormone; Aminopyrine; Animals; Anti-Inflammatory Agents; Aspirin; Carrageenan; Dextrans; Dimethyl Sulfoxide; Disease Models, Animal; Edema; Flufenamic Acid; Formaldehyde; Granuloma; Indomethacin; Inflammation; Kaolin; Male; Mefenamic Acid; Ovalbumin; Oxyphenbutazone; Phenylbutazone; Prednisolone; Rats; Sodium Salicylate; Trypsin

Topics: Acetophenones; Analgesics; Animals; Anti-Inflammatory Agents; Benzene Derivatives; Carrageenan; Chelating Agents; Chemical Phenomena; Chemistry; Edema; Granuloma; Inflammation; Kaolin; Rats

Topics: Animals; Anti-Inflammatory Agents; Arthritis; Edema; Hindlimb; Hyaluronoglucosaminidase; Kaolin; Male; Plethysmography; Polysaccharides; Rats; Time Factors

Topics: Acetates; Animals; Anti-Inflammatory Agents; Antifungal Agents; Arthritis; Carrageenan; Chymotrypsin; Dextrans; Edema; Fatty Acids; Formaldehyde; Hindlimb; Irritants; Kaolin; Lactones; Male; Mustard Plant; Plants, Medicinal; Rats; Yeasts

Topics: Animals; Anti-Inflammatory Agents; Blood Coagulation Tests; Carbon Isotopes; Carrageenan; Edema; Kaolin; Rats; Temperature

Topics: Aniline Compounds; Animals; Anti-Inflammatory Agents; Asbestos; Dextrans; Disease Models, Animal; Drug Combinations; Edema; Evaluation Studies as Topic; Female; Formaldehyde; Granuloma; Indomethacin; Inflammation; Kaolin; Phenylbutazone; Prednisolone; Rats; Rats, Inbred Strains; Salicylates; Serotonin; Sodium Salicylate

Topics: Acetates; Animals; Anti-Inflammatory Agents; Benzoates; Carrageenan; Edema; Granuloma; Indomethacin; Kaolin; Male; Phenylbutazone; Pyrroles; Structure-Activity Relationship

Topics: Animals; Anthracenes; Arthritis; Carrageenan; Chlorpromazine; Diazepam; Edema; Foot; Hindlimb; Inflammation; Kaolin; Male; Pleurisy; Rats; Rats, Inbred Strains; Tranquilizing Agents; Turpentine

Topics: Animals; Anti-Inflammatory Agents; Burns; Dextrans; Edema; Female; Formaldehyde; Kallikreins; Kaolin; Male; Protease Inhibitors; Rats

Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Dextrans; Edema; Hyaluronoglucosaminidase; Injections, Intraperitoneal; Injections, Subcutaneous; Kaolin; Male; Polysaccharides; Rats; Trypsin

Topics: Animals; Arthritis; Arthus Reaction; Bradykinin; Capillary Permeability; Carrageenan; Depression, Chemical; Dextrans; Disease Models, Animal; Dogs; Edema; Exudates and Transudates; Female; Formaldehyde; Granuloma; Guinea Pigs; Histamine; Hyaluronoglucosaminidase; Kaolin; Lymph; Male; Mice; Mycobacterium Infections; Ovalbumin; p-Methoxy-N-methylphenethylamine; Phytotherapy; Plants, Medicinal; Rabbits; Rats; Serotonin; Species Specificity; Swine

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Carrageenan; Edema; Granuloma; Kaolin; Phenylacetates; Quinones; Rats

Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Edema; Exudates and Transudates; Hindlimb; Inflammation; Kaolin; Male; Phenylbutazone; Quinones; Rats

Topics: Animals; Carrageenan; Dextrans; Edema; Ethanol; Female; Formaldehyde; Hindlimb; Irritants; Kaolin; Male; Methysergide; Monoamine Oxidase Inhibitors; Nialamide; Propylamines; Rats; Reserpine; Saccharomyces; Tranylcypromine

Topics: Adrenalectomy; Animals; Anti-Inflammatory Agents; Aspirin; Bromelains; Carrageenan; Chymotrypsin; Edema; Enzyme Activation; Female; Flufenamic Acid; Granuloma; Guinea Pigs; Histamine Release; Hot Temperature; Hydrocortisone; Immune Sera; Indomethacin; Injections, Intramuscular; Kaolin; Male; Peptide Hydrolases; Phenylbutazone; Rats; Serotonin; Serratia; Time Factors

Topics: Allopurinol; Animals; Anti-Inflammatory Agents; Arthritis; Edema; Kaolin; Male; Models, Biological; Pleurisy; Rats; Turpentine; Xanthine Oxidase

Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Edema; Hexosamines; Inflammation; Injections; Kaolin; Neuraminic Acids; Phenylbutazone; Rats

Topics: Aminopyrine; Analgesics; Animals; Anti-Inflammatory Agents; Aspirin; Bradykinin; Carrageenan; Chloroform; Cycloparaffins; Dextrans; Edema; Erythema; Female; Flufenamic Acid; Fluorine; Guinea Pigs; Histamine H1 Antagonists; Hyaluronoglucosaminidase; Kaolin; Male; Mice; ortho-Aminobenzoates; Permeability; Phenylbutazone; Prednisolone; Radiation-Protective Agents; Rats; Serotonin Antagonists; Skin; Ultraviolet Rays

Topics: Animals; Anti-Inflammatory Agents; Aspirin; Biological Assay; Edema; Hydrocortisone; Kaolin; Male; Phenylbutazone; Rats

Topics: Acetylcholine; Aerosols; Albumins; Anaphylaxis; Animals; Anti-Inflammatory Agents; Bradykinin; Bronchial Spasm; Edema; Erythema; Exudates and Transudates; Female; Gossypium; Granuloma; Guinea Pigs; Histamine; History of Medicine; In Vitro Techniques; Inflammation; Irritants; Kaolin; Lung; Male; Prednisolone; Rats; Serotonin; Ultraviolet Rays; Vitamin K; Vitamin K 1

Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Croton Oil; Dexamethasone; Edema; Formaldehyde; Hydrocortisone; Indomethacin; Irritants; Kaolin; Male; Mefenamic Acid; Phenylbutazone; Rats; Saccharomyces

Topics: Animals; Anti-Inflammatory Agents; Antivenins; Bees; Capillary Permeability; Capillary Resistance; Carrageenan; Dextrans; Edema; Exudates and Transudates; Female; Formaldehyde; Guinea Pigs; Kaolin; Male; Ovalbumin; p-Methoxy-N-methylphenethylamine; Polyurethanes; Povidone; Rats; Saponins; Seeds; Serotonin Antagonists; Tea

Topics: Abscess; Animals; Anti-Inflammatory Agents; Carrageenan; Croton Oil; Edema; Female; Formaldehyde; Gossypium; Granuloma; Inflammation; Irritants; Kaolin; Male; Models, Theoretical; Mononuclear Phagocyte System; Parabiosis; Rats; Saccharomyces; Thorium Dioxide; Zymosan

Topics: Animals; Anti-Infective Agents; Cyproheptadine; Edema; Exudates and Transudates; Kaolin; Kinins; Male; Phenylbutazone; Povidone; Rats; Serotonin

Topics: Adenine Nucleotides; Adenosine Triphosphate; Animals; Dextrans; Edema; Fluorescence; Hindlimb; Kaolin; Male; Rats; Venoms

Topics: Aminopyrine; Animals; Anti-Inflammatory Agents; Edema; Hindlimb; Indomethacin; Inflammation; Kaolin; Male; Phenylbutazone; Rats; Sodium Salicylate

Topics: Animals; Edema; Female; Gels; Kaolin; Male; Rats; Saponins; Vasodilator Agents

Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Edema; Kaolin; Models, Biological; Phenylbutazone; Rats; Silicon Dioxide

Topics: Agar; Animals; Anti-Inflammatory Agents; Capillary Permeability; Carrageenan; Dextrans; Edema; Formaldehyde; Granuloma; Histamine; Kaolin; Mice; Phenylbutazone; Rats; Serotonin

Topics: Analgesics; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antipyretics; Edema; Inflammation; Kaolin; ortho-Aminobenzoates; Pharmacology; Rats; Research; Toxicology

Topics: Analgesics; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antipyretics; Edema; Kaolin; Pharmacology; Rats; Research; Salicylates; Toxicology

Topics: Analgesics; Analgesics, Non-Narcotic; Animals; Antipyretics; Aspirin; Edema; Kaolin; Phenylbutazone; Quinoxalines; Rats; Silicon Dioxide

Topics: Aspirin; Drug Hypersensitivity; Edema; Kaolin; Neoplasms; Neoplasms, Experimental; Pharmacology; Rats; Research; Toxicology

Topics: Aminopyrine; Analgesics; Analgesics, Non-Narcotic; Animals; Antipyretics; Antipyrine; Azoles; Edema; Inflammation; Kaolin; Magnesium; Phenacetin; Phenylbutazone; Prednisolone; Rats; Salicylamides

Topics: Analgesics; Analgesics, Non-Narcotic; Animals; Antipyretics; Benzoxazines; Chickens; Edema; Kaolin; Oxotremorine; Rats; Serotonin