salicylates and Edema

The emergency physician treats many patients with mild to moderate pain due to musculoskeletal injury. The physician must consider the extent of injury, the patient's medication history, and the potential for abuse when prescribing an oral analgesic. A study was designed to compare the efficacy of two oral analgesics, one containing a narcotic and one nonnarcotic, in relieving mild to moderate pain associated with grade 2 ankle sprain. Forty patients were enrolled--all with moderate pain--and were randomly allocated to treatment with either diflunisal or acetaminophen with codeine. Both analgesic agents were equally effective in relieving the pain. Side effects were experienced by six patients, all of whom were receiving acetaminophen with codeine; none of the patients given diflunisal noted side effects. Global assessments of the efficacy and tolerability of the study drugs showed that 89% of 19 patients given diflunisal and 43% of 21 patients given acetaminophen with codeine considered their respective analgesics excellent or very good.

Topics: Acetaminophen; Adult; Ankle Injuries; Codeine; Diflunisal; Drug Combinations; Edema; Female; Humans; Male; Middle Aged; Pain; Prospective Studies; Random Allocation; Salicylates; Sprains and Strains

Thirty patients with osteoarthritis of knees or hips took part in a double-blind randomized 12-week inter-group clinical trial of diflunisal 250 mg to 375 mg twice daily against aspirin 500 mg to 750 mg four times daily using the double-placebo technique. Changes were assessed in weight-bearing pain and night pain, stiffness after rest, a specified activity, and overall judgements by patient and physician, all graded on a five-point scale. Intermalleolar distance or knee flexion were measured. Side-effects and safety tests were monitored. Diflunisal produced statistically significant responses for all the criteria, when numbers of patients better or worse after 12 weeks were compared using the sign test. Neither the figures for aspirin alone, nor a comparison between the two treatment groups, reached statistical significance. Side-effects and especially dropouts were less on diflunisal. Nine patients on diflunisal but only two on aspirin wanted to continue treatment beyond 12 weeks, though still 'blind' when deciding this. Diflunisal may be a useful, less toxic and longer acting alternative to aspirin in the management of osteoarthritis.

Topics: Abdomen; Aspirin; Clinical Trials as Topic; Dizziness; Double-Blind Method; Drug Administration Schedule; Edema; Humans; Osteoarthritis; Pain; Salicylates; Time Factors

Medicinal properties of Gaultheria have been used in traditional medicine to treat pain and inflammation.. Hence, the purpose of this study was to evaluate the analgesic, antipyretic, and anti-inflammatory properties of Gaultheria trichophylla Royle extract and salicylate-rich fraction in vivo, in vitro, and in silico.. In vivo analgesic, antipyretic, and anti-inflammatory of extract and a salicylate-rich fraction (at doses of 100, 200, 300, and 150 mg/kg) were assessed using healthy albino mice employing acetic acid-induced writhing, tail immersion test, carrageenan-induced inflammation, and croton oil-induced edema. For in vitro testing of extracts COX and LOX enzyme inhibition assays were used. Molecular docking studies were conducted for in silico testing of the inhibitory activity of the dominant compound Gaultherin against COX and LOX.. G-EXT 200 and 300 and G-SAL 150 mg/kg reduced pyrexia significantly (P < 0.05 and P < 0.01). G-EXT-200, 300, and G-SAL 150 reduce the writing to a significant level (p > 0.05, p < 0.01). G-EXT 200 and 300 and G-SAL 150 mg/kg doses the analgesic effect was significant (p > 0.05, p > 0.01) and was comparable to tramadol. G-EXT 100 200, 300 mg/kg showed 43.8%, 47.94% and 56% respectively. G-SAL 150 mg, rich in salicylates, showed maximum inhibition of 65.75% next to standard drug diclofenac with 76.7% inhibition. G-EXT 100 and 200 mg/kg dose showed significant (p < 0.05) reduction in ear edema. With 300 mg/kg dose the effect was more (61.89%, p < 0.01). The salicylate-rich fraction G-SAL and Celecoxib showed an almost similar effect (p < 0.01). Significance inhibition was shown in the COX-2 test (G-EXT 39.70 and G-SAL 77.20 IC50 μg/ml) and in the 5-LOX test (G-EXT 28.3 and G-SAL 39.70 IC50 μg/ml). The preliminary in silico results suggest that the investigated compound showed excellent inhibitory activity against COX and LOX enzymes as evident from the free binding energy. Molecular docking revealed that Gaultherin binds well in the COX and LOX enzyme catalytic region.. The extract and salicylate-rich fraction obtained from G. trichophylla showed significant analgesic, anti-inflammatory, and antipyretic effects in vivo, in vitro, and in silico assays that support its use in traditional medicine.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Antipyretics; Carrageenan; Edema; Ericaceae; Fever; Gaultheria; Inflammation; Mice; Molecular Docking Simulation; Plant Extracts; Salicylates

Over the course of time several drugs have been synthesized and are available in market for the treatment of inflammation. However, they were unable to cure effectively and associated with side effects. To effectively deal with such diseases, heterocycles and their derivatives have gained their special position. For this reason 1,3,4-oxadiazole (15-16), 1,2,4-triazole (17-18), Schiff base (19-24) and 3,5-disubstituted pyrazole (25) derivatives were synthesized starting from salicylic acid and acyl acid hydrazides (12-14) as COX-1 and COX-2 inhibitors. In vivo anti-inflammatory activities were also tested by carrageenan-induced mice paw edema against albino mice of any sex. Structures of all the synthesized compounds were confirmed by FT-IR and

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Dose-Response Relationship, Drug; Edema; Female; Hydrazines; Male; Mice; Mice, Inbred BALB C; Molecular Docking Simulation; Molecular Structure; Salicylates; Structure-Activity Relationship

Salicytamide is a new drug developed through molecular modelling and rational drug design by the molecular association of paracetamol and salicylic acid. This study was conducted to assess the acute oral toxicity, antinociceptive, and antioedematogenic properties of salicytamide. Acute toxicity was based on the OECD 423 guidelines. Antinociceptive properties were investigated using the writhing, hot plate and formalin tests in Swiss mice. Antioedematogenic properties were evaluated using the carrageenan-induced paw oedema model and croton oil-induced dermatitis in Wistar rats. Salicytamide did not promote behavioural changes or animal deaths during acute oral toxicity evaluation. Furthermore, salicytamide exhibited peripheral antinociceptive activity as evidenced by the reduction in writhing behaviour (ED50 = 4.95 mg/kg) and licking time in the formalin test's inflammatory phase. Also, salicytamide elicited central antinociceptive activity on both hot plate test and formalin test's neurogenic phase. Additionally, salicytamide was effective in reducing carrageenan or croton oil-induced oedema formation. Overall, we have shown that salicytamide, proposed here as a new NSAID candidate, did not induce oral acute toxicity and elicited both peripheral antinociceptive effects (about 10-25 times more potent than its precursors in the writhing test) and antioedematogenic properties. Salicytamide also presented central antinociceptive activity, which seems to be mediated through opioid-independent mechanisms. These findings reveal salicytamide as a promising antinociceptive/antioedematogenic drug candidate.

Topics: Acetaminophen; Animals; Anti-Inflammatory Agents, Non-Steroidal; Drug Design; Edema; Mice; Nociception; Pain; Rats, Wistar; Salicylates

Topics: Chronic Disease; Cosmetics; Dermatitis, Allergic Contact; Edema; Erythema; Eyelid Diseases; Facial Dermatoses; Female; Humans; Middle Aged; Pruritus; Salicylates

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used medications in inflammatory illnesses. However, the gastrointestinal bleeding and toxicity associated with NSAIDs long term use prompted the quest towards investigations for new anti-inflammatory agents. Natural and natural-derived molecules proved its anti-inflammatory efficacy in vitro as well as in vivo. Given this background, the scope of this research involves structural changes of the natural polyphenol (tyrosol) generating two new salicylate derivatives and testing their biological properties, focusing on anti-inflammatory effects assessed in vitro and in vivo assays. The first molecular modification was the introduction of a carboxylic acid group adjacent to the phenol group present in this compound, which creates a new salicylate-like tyrosol. In addition, the acetylation of phenol group in this molecule produced an acetylsalicylate derivative, which may be regarded as aspirin-like natural polyphenol. Interestingly, tyrosol and its novel derivatives attenuated the edema in acute inflammatory response on carrageenan- induced local inflammation in mice. In addition, our results demonstrated that tyrosol and its novel derivatives were able to reduce the chemotaxis of neutrophil assessed in vitro model by chemo attractant (fMLP). Furthermore, only derivative 2 was able to reduce this effect in the acute inflammatory model. In (DPPH)- scavenging activity, tyrosol derivatives demonstrated a minor antioxidant activity, which may suggest that radical scavenging is not a major pathway involved in the anti-inflammatory effects of these derivatives. Salicylate-like tyrosol derivatives are of particular interest for future studies.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Cell Line; Cell Survival; Dose-Response Relationship, Drug; Edema; Inflammation; Male; Mice; Mice, Inbred BALB C; Molecular Structure; Phenylethyl Alcohol; Salicylates; Structure-Activity Relationship

We have developed the convenient methods for synthesis of polyfluorosalicylic acids and their derivatives. For the first time the biological properties of polyfluorosalicylates were investigated in vitro (permeability through the biological membranes, COX-1 inhibitory action) and in vivo (anti-inflammatory, analgesic activities, acute toxicity). Molecular docking of polyfluorinated salicylates confirmed in vitro and in vivo experiments.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase 1; Cyclooxygenase Inhibitors; Edema; Female; Halogenation; Male; Molecular Docking Simulation; Rats, Sprague-Dawley; Rats, Wistar; Salicylates; Sheep

The main objective of this study was to develop reversed hexagonal (H

Topics: Administration, Cutaneous; Analgesics; Animals; Anti-Inflammatory Agents; Biological Availability; Drug Delivery Systems; Edema; Fatty Alcohols; Female; Liquid Crystals; Male; Mice; Pain; Rats, Wistar; Salicylates; Skin; Skin Absorption; Skin Irritancy Tests

Resveratrol is a natural compound with a plethora of activities as well as limitations. We recently reported a series of resveratrol-salicylate analogs with potential chemopreventive activity. Herein, we report the anti-inflammatory and antioxidant properties of these resveratrol derivatives. Using an in vitro COX inhibition assay, and two in vivo protocols (carrageenan-induced peritonitis and paw edema), we identified a novel compound (C10) as a potent anti-inflammatory agent. The enhanced potency of C10 was associated with the ability of C10 to decrease the activity of myeloperoxidase (MPO) enzyme at 10mg/kg, whereas resveratrol and it's natural analog (TMS) did not exert the same effect. Additionally, C10 significantly reduced the concentration of intracellular reactive oxygen species. Because of the proven association between cancer, inflammation, and oxidative stress, we believe that C10 is a promising chemopreventive molecule.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Carrageenan; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Edema; Hep G2 Cells; Humans; Hydrogen Peroxide; Mice; Molecular Structure; Oxidative Stress; Peritonitis; Prostaglandin-Endoperoxide Synthases; Reactive Oxygen Species; Resveratrol; Salicylates; Stilbenes; Structure-Activity Relationship

In this study, a new series of 16 methyl salicylate derivatives bearing a piperazine moiety were synthesized and characterized. The in vivo anti-inflammatory activities of target compounds were investigated against xylol-induced ear edema and carrageenan-induced paw edema in mice. The results showed that all synthesized compounds exhibited potent anti-inflammatory activities. Especially, the anti-inflammatory activities of compounds

Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Cyclooxygenase 2; Cytokines; Disease Models, Animal; Edema; Gene Expression Regulation; Lipopolysaccharides; Mice; Molecular Structure; Piperazine; Piperazines; RAW 264.7 Cells; Salicylates; Xylenes

In this study, we evaluated the edema and hyperalgesic response induced by BpirMP, a P-I class metalloproteinase isolated from Bothrops pirajai snake venom. The animals were injected with the metalloproteinase or sterile PBS (control group) and evaluated for 1, 2, 3, 4, 5, 6 and 24h. The intraplantar injection of BpirMP (5-50μg/paw) induced a dose- and time-dependent response. BpirMP (50μg) induced paw edema in rats rapidly, with peak response two hours after injection of the toxin. Also, BpirMP injection caused a significant reduction in the nociceptive threshold of the animals tested, with peak response three hours after injection of the toxin. The inflammatory mediators involved in these responses were assayed by pretreatment of animals with synthesis inhibitors or receptor antagonists. Peak responses were significantly reduced by pretreatment of animals with pyrilamine, a histamine receptor antagonist, sodium cromoglycate, a mast cell degranulation inhibitor and valeryl salicylate and meloxicam, cyclooxygenase inhibitors. The analysis of the peritoneal cavity exudate revealed an acute inflammatory response with recruitment of leukocytes, increased levels of total proteins, nitric oxide and the cytokines IL-6, TNF-α and IL-10. In conclusion, our results demonstrated that BpirMP induces inflammation mediated by mast cell degranulation, histamine, prostaglandins and cytokine production.

Topics: Animals; Bothrops; Cell Degranulation; Cromolyn Sodium; Crotalid Venoms; Cyclooxygenase Inhibitors; Edema; Female; Histamine H1 Antagonists; Hyperalgesia; Inflammation; Interleukin-10; Interleukin-6; Leukocytes; Male; Mast Cells; Meloxicam; Metalloproteases; Mice; Mice, Inbred BALB C; Nitric Oxide; Nociception; Pyrilamine; Rats; Rats, Wistar; Salicylates; Thiazines; Thiazoles; Tumor Necrosis Factor-alpha; Viper Venoms

Laser speckle imaging with long exposure time has been applied noninvasively to visualize the immediate reaction of cutaneous vessels in mice in response to a known primary irritant and potential allergen—methyl salicylate. The compound has been used topically on the surface of the pinna and the reaction of the vascular network was examined. We demonstrate that irritant-induced acute vascular reaction can be effectively and accurately detected by laser speckle imaging technique. The current approach holds a great promise for application in routine screening of the cutaneous vascular response induced by contact agents, screenings of mouse ear swelling test, and testing the allergenic potential of new synthetic materials and healthcare pharmaceutical products.

Topics: Allergens; Animals; Diagnostic Imaging; Ear, External; Edema; Lasers; Mice; Salicylates

Topics: Adalimumab; Adrenal Cortex Hormones; Antibodies, Monoclonal, Humanized; Anus Diseases; Colonoscopy; Crohn Disease; Diagnosis, Differential; Drug Resistance; Edema; Female; Fissure in Ano; Follow-Up Studies; Giant Cells; Granuloma; Humans; Immunosuppressive Agents; Middle Aged; Recurrence; Salicylates; Skin Ulcer; Vulvar Diseases

Cystinuria is an autosomal recessive disorder characterized with abnormal tubular reabsorption of cystine and dibasic amino acids leading to cystine urolithiasis. The classical form is caused by mutations in the SLC3A1 gene (OMIM 220100). The cornerstone of the treatment is high hydration and alkalization of the urine to achieve urine pH between 7.0 and 7.5, at which point, cystine solubility in the urine is optimal. These measures very often fail, and thus addition of sulfhydryl agents like penicillamine and tiopronin (mercaptopropionyl glycine) is recommended. Herein, we report a 3-year-old boy with cystinuria resulting in recurrent nephrolithiasis requiring surgery and extracorporeal shock wave lithotripsy. Nine months after introduction of tiopronin, the boy manifested generalized edema, oliguria, and biochemical indices of nephrotic syndrome. Tiopronin was withdrawn, and the boy was given only supportive treatment. Within 10 days, he entered into clinical and biochemical remission. Pediatricians should be aware of this adverse effect of tiopronin, and therefore, testing of the urine with strips or sulfosalicylic acid at least once weekly at home may be very helpful for early detection of proteinuria.

Topics: Amino Acids, Sulfur; Benzenesulfonates; Child, Preschool; Cystinuria; Edema; Humans; Lithotripsy; Male; Nephrolithiasis; Nephrotic Syndrome; Proteinuria; Salicylates; Tiopronin

To evaluate the kinetics of the inflammatory tissue response to three root canal sealers using a physicochemical method for quantification of the enhanced vascular permeability and histopathological analysis.. Twenty-eight male Wistar rats randomly assigned to four groups according to the evaluation periods (1, 3, 7 and 14 days) were used to assess the vascular permeability and histopathological reaction to RoekoSeal, AH Plus and Sealapex (new formulation) sealers, using saline and Chloropercha as negative and positive controls, respectively. Seven rats were sacrificed per period. The biocompatibility of the sealers was evaluated spectrophotometrically and histopathologically.. At day 14, Sealapex produced significantly more inflammatory exudate than AH Plus and RoekoSeal (P < 0.05); however, there was no significant difference between AH Plus and RoekoSeal (P > 0.05). Sealapex (new formulation) was the most irritating sealer, producing severe inflammation with the presence of multinucleated giant cells. RoekoSeal was the most biocompatible sealer, producing the least amount of inflammatory exudate.. RoekoSeal root canal sealer was biocompatible when implanted in connective tissue.

Topics: Animals; Balsams; Calcium Hydroxide; Capillary Permeability; Dental Cements; Drug Combinations; Edema; Epoxy Resins; Foreign-Body Reaction; Gutta-Percha; Implants, Experimental; Inflammation; Injections, Subcutaneous; Male; Pilot Projects; Rats; Rats, Wistar; Root Canal Filling Materials; Salicylates; Statistics, Nonparametric; Time Factors; Zinc Oxide

The synthesis of gaultherin (1) and its analogs was carried out to provide 11 glycosides under phase-transfer catalytic conditions. The activities of all synthesized compounds were evaluated by nitric oxide production inhibitory assay in vitro. Methyl 2-O-(4-O-β-d-galactopyranosyl)-β-d-glucopyranosylbenzoate (5f) showed significantly anti-nociceptive and anti-inflammatory effects by the evaluation in vivo. Structure-activity relationships within these compounds were discussed.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Croton Oil; Disaccharides; Edema; Macrophages; Mice; Nitric Oxide; Salicylates; Stereoisomerism; Structure-Activity Relationship

Leukocyte recruitment of sites of inflammation and tissue injury involves leukocyte rolling along the endothelial wall, followed by firm adherence of the leukocyte, and finally transmigration of the leukocyte across cell junctions into the underlying tissue. The initial rolling step is mediated by the interaction of leukocyte glycoproteins containing active moieties such as sialyl Lewisx (sLex) with P-selectin expressed on endothelial cells. Consequently, inhibition of this interaction by means of a small molecule P-selectin antagonist is an attractive strategy for the treatment of inflammatory diseases such as arthritis. High-throughput screening of the Wyeth chemical library identified the quinoline salicylic acid class of compounds (1) as antagonists of P-selectin, with potency in in vitro and cell-based assays far superior to that of sLex. Through iterative medicinal chemistry, we identified analogues with improved P-selectin activity, decreased inhibition of dihydrooratate dehydrogenase, and acceptable CYP profiles. Lead compound 36 was efficacious in the rat AIA model of rheumatoid arthritis.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Arthritis, Rheumatoid; Biological Availability; Cytochrome P-450 Enzyme Inhibitors; Databases, Factual; Edema; Humans; Hydroxyquinolines; In Vitro Techniques; Leukocyte Rolling; Male; P-Selectin; Quinolines; Rats; Rats, Sprague-Dawley; Salicylates; Structure-Activity Relationship

The analgesic and anti-inflammatory activities of a salicylate derivatives fraction (SDF) isolated from Gaultheria yunnanensis (FRANCH.) REHDER and the mechanisms of actions were investigated in the present study. The major constituent of SDF, which represented around 50% of this fraction, was a methyl salicylate diglycoside named gaultherin. SDF showed a significant inhibition on the hind paw edema in rats (200, 400 mg/kg body wt., p.o.) and ear swelling in mice (200, 400, 800 mg/kg body wt., p.o.) caused by carrageenin and croton oil, respectively. In addition, SDF (400, 800 mg/kg body wt., p.o.) inhibited only the second phase (inflammatory) in the formalin test, and showed no effect in the hot-plate test in mice. The antinociceptive activity of SDF was predominantly peripheral and independent of the opioid system. These findings demonstrate that SDF from Gaultheria yunnanensis (FRANCH.) REHDER possesses analgesic and anti-inflammatory activities, which may be mediated, at least partly, through the suppression of inflammatory mediators or their release suggested by the animal experiment. The observed effects of SDF are probably due to the presence of high content of salicylate derivatives (80%), including gaultherin, MSTG-A and MSTG-B.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Carrageenan; Croton Oil; Disaccharides; Dose-Response Relationship, Drug; Ear; Edema; Female; Formaldehyde; Gaultheria; Glycosides; Hindlimb; Indomethacin; Male; Mice; Mice, Inbred Strains; Molecular Structure; Pain; Rats; Rats, Wistar; Salicylates

To prepare the derivatives of salicylic acid-g-chitosan and study their synergistic and complementary actions, the synergism of anti-inflammatory action of the derivatives was investigated with the experiments of xylene-induces mice ear edema, the analgesic activities by the tartaric emetic-induced mice twist test and the hot-plate test, and the complementary effects between salicylic acid and chitosan through morphological changes of stomach mucous membrane of rat, separately. The anti-inflammatory activities of salicylic acid-g-chitosan derivatives for anti-inflammatory activities were more potent than that of salicylic acid and chitosan and dexamethasone cream in external use, and more potent than that of aspirin orally. However, immediate analgesic activity of the derivatives was lower than that of aspirin and persistent activity was similar as that of aspirin. And the stomach mucous membrane morphology change of the derivatives was much milder than that of aspirin. The salicylic acid grafted chitosan derivatives showed synergistic and complementary effect on the anti-inflammatory and analgesic activities and so on.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Chitosan; Drug Synergism; Edema; Female; Gastric Mucosa; Male; Mice; Pain Measurement; Pain Threshold; Random Allocation; Rats; Rats, Sprague-Dawley; Salicylates

This work includes the synthesis of 15 final compounds (6a-h and 7b-h) as prodrugs of 5-ASA in the form of the acid itself, esters and amides linked by an amide linkage through a spacer to the endocyclic ring N of nicotinamide. Also, 15 new intermediate compounds were prepared. The target compounds (6b, 6f, 7b, and 7e-h) revealed potent analgesic and anti-inflammatory activities in comparison to sulfasalazine and 5-ASA. In addition, ulcerogenicity, LD50, in vivo and in vitro metabolism of compound 7f were determined.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Drug Stability; Edema; Feces; Gastrointestinal Contents; Hydrogen-Ion Concentration; Lethal Dose 50; Magnetic Resonance Spectroscopy; Male; Mesalamine; Mice; Pain; Prodrugs; Rats; Salicylamides; Salicylates; Stomach Ulcer; Streptococcus pyogenes; Structure-Activity Relationship

The effect of valeryl salicylate (VS), an inhibitor of cyclooxygenase-1 (COX-1), was evaluated in arachidonic acid or croton oil-induced ear oedema and carrageenan-induced paw oedema in mice. Ear oedema was induced by topical administration of arachidonic acid (2mg per ear; 20 microliters) or croton oil (1mg per ear; 20 microliters) to the inner surface of the left ear and the change in the ear's thickness was measured with a precision micrometer (Fisher, USA). VS significantly inhibited the arachidonic acid ear oedema after lh at doses of 1.5-45 micrograms per ear; however, only at the dose of 45 micrograms per ear was it able to significantly reduce the croton oil-induced oedema at 6h. Paw oedema was induced by the injection of 25 microliters of 1% carrageenan into the plantar aponeurosis of the right hind paw. The oedema was evaluated at 0.5, 1, 2, 4, 24, 48 and 72h. Previously in our experiments, we observed two peaks in paw oedema formation: one at 2h, in the early phase (0-4h), and the other, occurring at 48h after carrageenan injection, in the late phase (24-72h). The pre-treatment with VS significantly reduced the paw oedema at 2h, the same effect observed with celecoxib and indomethacin treatments. At 24h, VS did not inhibit oedema but significantly increased it mainly at 48h after carrageenan injection. These results showed that VS was pharmacologically active in these models and suggest that COX-1 may participate in the early and late phases of inflammation in the models studied.

Topics: Acute Disease; Animals; Arachidonic Acid; Carrageenan; Celecoxib; Croton Oil; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Ear, External; Edema; Foot; Indomethacin; Inflammation; Irritants; Isoenzymes; Male; Membrane Proteins; Mice; Prostaglandin-Endoperoxide Synthases; Pyrazoles; Salicylates; Sulfonamides

The basic phospholipase A(2) (VRV-PL-VIIIa) from Vipera russelli venom induces multiple toxic effects including neurotoxicity, myotoxicity, edema and hemorrhage. This phospholipase A(2) has been extensively characterized for its pharmacological properties except for hemorrhagic activity. In the present investigation, the lung hemorrhagic activity was assayed using lung dye diffusion method. The investigations to understand the mechanism of lung hemorrhage induction by VRV-PL-VIIIa was followed by chemical modification studies and also by interaction with an antihemorrhagic factor p-anisic acid (4-methoxy benzoic acid). In presence of 1:2 mol:mol PLA(2): anisic acid, the lung hemorrhagic and edema inducing activities were completely neutralized in experimental animals; however, catalytic and anticoagulant activities were not neutralized. Carbamylation of VRV-PL-VIIIa resulted in the loss of lung hemorrhage and edema inducing activities. In contrast, carbamylation of VRV-PL-VIIIa in the presence of anisic acid could not neutralize the lung hemorrhage and edema inducing activities. The anticoagulant and enzyme activities were only partially neutralized when carbamylated both in the presence and absence of anisic acid.

Topics: Animals; Anticoagulants; Betaine; Carbamyl Phosphate; Daboia; Edema; Group II Phospholipases A2; Hemolysis; Hemorrhage; Hydroxybenzoate Ethers; Lung Diseases; Male; Mice; Phospholipases A; Proteins; Prothrombin Time; Rats; Salicylates; Spectrometry, Fluorescence; Viper Venoms

Using rat paw carrageenan edema, the anti-inflammatory activity of nine selected arylcarboxylatocopper(II) aquacomplexes of the general composition Cu(RCOO)2.nH2O, where R represents 2-hydroxy-Y-methylphenyl, Y = 3 (n = 1.5), 4 (4) or 5 (2); 2-hydroxy-3,6-dimethylphenyl (n = 4); 2,5-diacetoxyphenyl (1); 2-methoxy-(1) and 4-methoxyphenyl (3); 2-furyl (3) and 2-thienyl (1), was assayed and compared to that of the free acids. Copper(II) salicylate tetrahydrate and salicylic acid were used as standards for comparison. All compounds were applied i.p. in a single dose of 50 mumol/kg body weight, calculated for the RCOO-fragment. m-Cresotato- (mean edema reduction 70%) and p-cresotatocopper(II) (80%) aquacomplexes were clearly more effective than copper(II) salicylate tetrahydrate (55%). The nonsubstituted hydroxyl of the salicylate skeleton of acidoligands is required for the activity of the complexes and of free acids tested. Isomeric cresotic acids (82-47-62%) and 2-furoic acid (48%) exhibited a higher effect than salicylic acid (42%). The relationship between the coordination-chemical properties and the biological effects of the complexes studied is discussed.

Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Copper; Edema; Organometallic Compounds; Rats; Salicylates; Salicylic Acid

"Milwaukee shoulder" is often associated with large effusions that cannot be managed with conventional therapy. We describe a 75-year-old man whose massive hydrops of both shoulders was resistant to treatment with nonsteroidal antiinflammatory drugs (NSAID), multiple aspirations, and injections of corticosteroid. The effusions resolved completely after treatment with oral colchicine and an NSAID containing magnesium.

Topics: Aged; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Choline; Colchicine; Cysts; Edema; Gout Suppressants; Humans; Male; Salicylates; Shoulder Joint; Tomography, X-Ray Computed; Triamcinolone Acetonide

Using rat paw dextran edema, the antiexudative activity of the complexes of the composition Cu(RCOO)2.nH2O--R represents 2-hydroxy-Y-phenyl: Y = 3 (n = 1,5), Y = 4 (4), Y = 5 (2) or 2-hydroxy-3,6-dimethylphenyl (n = 4)--and of the corresponding uncomplexed acids was assayed. Salicylic and acetylsalicylic acids and their Cu(II) salts were used as standards of comparison. The compounds were administered i.p. in a single dose of 10 mg/kg body weight. In general, the acids were more effective than their copper(II) salts except for the pair m-cresotic acid--Cu(II) complex. Only p-cresotic acid (mean edema reduction 56%) and copper(II) m-cresotate tetrahydrate (43%) exhibited a biological activity comparable to those of salicylic acid (62%) and copper(II) salicylate tetrahydrate (70%). The observed activities of complexes are discussed in relation to their proposed structures.

Topics: Animals; Copper; Edema; Rats; Salicylates

The effect of nutritional copper (Cu) deficiency on the antiinflammatory activity and pharmacokinetics of aspirin (ASA) was investigated in rats. Male, weanling Sprague-Dawley rats were fed either a Cu-deficient (CuD) or Cu-sufficient (CuS) diet for 49-50 d. The antiinflammatory activity of ASA was studied using the carrageenan-induced paw edema (CPE) test. ANOVA analyses of edema volumes at 2, 3, 4, 5, and 21 h postcarrageenan indicated significant differences between groups. The percent inhibition of edema due to ASA treatment in CuS was lower than that in CuD rats at 5 h, AUC5h, and AUC21h. ASA was found to be significantly more effective in inhibiting the CPE in CuD rats when compared to the CuS rats. Thus, we hypothesized that the increase in ASA's antiinflammatory activity in CuD rats was a result of a decrement in its elimination during nutritional Cu deficiency. The elimination of ASA in CuD and CuS rats was studied using an iv dose of 200 mg/kg. Concentrations of ASA and salicylic acid (SA) were determined in blood; whereas the concentrations of SA, salicylic phenol-glucuronide (SPG), and salicyluric acid (SUA) were determined in urine by HPLC. The results of the pharmacokinetic analyses from blood and urinary data indicated no significant differences in the disposition of ASA between CuD and CuS rats. For instance, the total body clearance for ASA (mean +/- SD, mL/min/kg) was 37.9 +/- 9.4 and 38.5 +/- 13.9 (p > 0.05); and the volume of distribution (Vd) for ASA (mean +/- SD, mL/kg) was 385.5 +/- 110.3 and 397.1.1 +/- 137.9 (p > 0.05) for CuD and CuS groups, respectively. Thus, contrary to our hypothesis, the enhanced antiinflammatory activity of ASA in CuD rats does not appear to be mediated via a decrement in the elimination of the drug. In addition, plasma ASA-esterase activity was found to be independent of Cu nutritional status.

Topics: Analysis of Variance; Animals; Aspirin; Carboxylic Ester Hydrolases; Chromatography, High Pressure Liquid; Copper; Diet; Edema; Male; Rats; Rats, Sprague-Dawley; Salicylates; Salicylic Acid

In the passive upright position, arterial and venous pressure in human feet increases capillary pressure, which leads to the filtration of fluid from the circulating plasma into the tissues of the feet. Loss of fluid concentrates both red cells and plasma so that the hematocrit and plasma protein concentration of venous blood leaving the feet greatly exceed their mean values in the circulation. To study this phenomenon in animals, the authors used beagle dogs maintained in an upright position and compared the results to those maintained in a prone position. In the passive upright position, red cell count, hematocrit, and total plasma protein concentrations were significantly increased. Therefore, we have determined the level of hydroxyl free radical formed as assessed by salicylate hydroxylation in the saphenous vein of dogs in an upright and normal position. Hydroxyl free radical formation was significantly higher in the veins of dogs in an upright position than in those in a prone position. The upright position model, which causes increases in hematocrit red cell count and total plasma protein in the saphenous vein, seems suitable for the study of drugs interfering in the pathophysiology of venous stasis. Indeed, the hematocrit increase of red cell count and total plasma protein in the saphenous vein of the beagle is similar to modifications observed in venous blood leaving the human foot after sitting. Moreover, the increase of .OH, concomitant with these modifications, may explain certain pathological observations, for instance, edema. The data clearly suggest that macromolecular extravasculation may be due to tissue injury caused by oxygen free radical formation in the blood vessels.

Topics: Animals; Blood Proteins; Body Fluids; Dogs; Edema; Erythrocyte Count; Free Radicals; Gentisates; Hematocrit; Hydroxybenzoates; Hydroxyl Radical; Hydroxylation; Male; Models, Biological; Posture; Salicylates; Salicylic Acid; Saphenous Vein

The synthesis of esters of 2-hydroxy benzoic acid-2-carboxyphenyl ester (salsalate) with guaiacol for the treatment of inflammatory bronchopneumopathies is reported. The antiinflammatory, analgesic and antipyretic activities of these derivatives were evaluated, together with their antioxidant, mucolytic and broncho-bacteriostatic properties in comparison to acetylsalicylic acid.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Antitussive Agents; Aspirin; Chromatography, Thin Layer; Edema; Expectorants; Guaiacol; Lethal Dose 50; Magnetic Resonance Spectroscopy; Male; Mice; Rats; Rats, Sprague-Dawley; Rats, Wistar; Salicylates; Spectrophotometry, Ultraviolet

Topically applied copper phenylbutazone, phenylbutazone, copper salicylate, salicylate and dimethylsulfoxide glycerol (80:20) were investigated as anti-inflammatory agents in rats and horses. Dimethylsulfoxide and glycerol (80:20) or dimethylsulfoxide, ethanol and glycerol (60:20:20) were used as the drug solvents. Subcutaneously administered carrageenin was used to induce inflammatory oedema, either in the paws of rats or the alar fold of the horse. The severity of the oedema and the anti-inflammatory effect of the drugs were assessed by measuring changes in the paw or alar-fold diameters. Copper salicylate and copper phenylbutazone were effective inhibitors of the inflammatory oedema in both species, but dimethylsulfoxide:glycerol (80:20) was not. In the rat, copper salicylate and copper phenylbutazone were superior anti-inflammatory agents compared to either salicylate or phenylbutazone, respectively. Following the topical application of four times the recommended daily dose of copper phenylbutazone to the horse for 5 days, minor skin irritation occurred and trace concentrations of phenylbutazone (maximum 0.6 microgram/ml) and negligible concentrations of oxyphenbutazone and gamma-hydroxyphenylbutazone were detected in the plasma.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Dimethyl Sulfoxide; Edema; Female; Glycerol; Horse Diseases; Horses; Male; Organometallic Compounds; Phenylbutazone; Rats; Rats, Inbred Strains; Salicylates

Cu(II) complexes with salicylates or aminopyrine were administered to rats with local inflammation (acute paw oedema elicited with carrageenan) to determine their anti-inflammatory activity and ulcerogenic effects following oral administration. The complexes were more effective than the parent ligands or appropriate mixtures of these ligands with Cu(II) as anti-inflammatory agents. All complexes indicated low ulcerogenity. The differences in pharmacologic activity between the complexes and mixtures in question are discussed.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Copper; Edema; Inflammation; Male; Organometallic Compounds; Rats; Rats, Inbred Strains; Salicylates; Stomach Ulcer

The cyclooxygenase inhibitors indomethacin, piroxicam, ibuprofen, naproxen and flurbiprofen failed to block rat paw oedema induced by PAF-acether, whereas aspirin and sodium salicylate were effective. Two mixed cyclooxygenase and lipoxygenase inhibitors NDGA, BW 755C and dexamethasone reduced oedema in a dose - dependently. The selective PAF-acether antagonist, BN 52021, was effective against PAF-acether at 5 - 20 mg/kg. The lipoxygenase derivates may be involved in paw oedema induced by PAF-acether in the rat and the inhibition produced by aspirin and by sodium salicylate should involve mechanisms other than the cyclooxygenase pathway.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arachidonate Lipoxygenases; Aspirin; Cyclooxygenase Inhibitors; Dexamethasone; Edema; Male; Platelet Activating Factor; Rats; Rats, Inbred Strains; Salicylates; Sodium Salicylate

A 23-year-old white female with a history of psychological instability presented with burning, adhesive, white plaques of the buccal mucosa. She had been unsuccessfully treated for 1.5 years with topical retinoids as well as topical and systemic corticosteroids. The differential diagnoses included leukoplakia, cheek biting and lichen planus. Clinical and histopathological examinations suggested the diagnosis of severe oral leukoedema. Careful history and clandestine surveillance of the patient finally revealed the lesions to be due to a caustic (over-the-counter product for the treatment of corns), which the patient regularly applied to her buccal mucosa.

Topics: Adult; Diagnosis, Differential; Drug Combinations; Edema; Factitious Disorders; Female; Humans; Lactates; Lactic Acid; Leukoplakia, Oral; Mouth Mucosa; Mouth Neoplasms; Salicylates

On the ground of conflicting evidence concerning the interaction of salicylate and aspirin, we investigated the results of such interaction on carrageenin edema of the rat hind paw. Aspirin and sodium salicylate were administered by stomach tube either singly or in combination, at a dose of 50 mg/kg each. The antiinflammatory effect was significantly greater when aspirin was administered prior to salicylate than when aspirin followed salicylate. It is therefore suggested that salicylate may antagonize the action of aspirin in vivo, and that the temporal order in which the two drugs interact with cyclooxygenase may be an important determinant of the outcome.

Topics: Animals; Aspirin; Carrageenan; Drug Antagonism; Edema; Kinetics; Male; Rats; Salicylates; Salicylic Acid

New 1-phenyl-2-R2-3-methyl-5-salicyloylimmino-3-pyrazolines were synthesized according to a previously described route. The obtained pyrazoline derivatives, together with some others reported in previous papers, were tested for analgesic and antiinflammatory activities. Some derivatives showed analgesic and/or antiinflammatory activity similar to that of acetylsalicylic acid.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Chemical Phenomena; Chemistry; Edema; Lethal Dose 50; Mice; Rats; Rats, Inbred Strains; Reaction Time; Salicylates

64Cu was administered in two anti-inflammatory formulations to normal rats and to rats with 2 forms of local inflammation, namely (a) an acute paw oedema (elicited with carrageenan) or (b) a chronic granulomatous response to an implanted irritant (Mycobacterium tuberculosis in a polyurethane sponge). The copper formulations used were (i) a slow release one consisting of Cu(II) salicylate applied dermally with ethanol/DMSO and (ii) short acting hydrophilic complex (Cu(I)Cu(II)-penicillamine)5- given subcutaneously. Three types of changes in copper biodistribution with these forms of inflammation were discerned based on determination of 64Cu and copper content in the following organs: inflammatory locus (foot or sponge implant), kidney, liver, spleen, adrenals, brain, blood, thymus, heart, and skin (site of application). The most evident changes were in the kidneys, liver, spleen, adrenals, thymus and serum from animals with chronic granulomatous inflammation. In contrast, a short term acute inflammatory stress (carrageenan paw oedema) had little effect. While copper D-penicillamine (applied subcutaneously) appeared to move as a bolus through the animals, the results with the percutaneous copper salicylate formulation are consistent with it providing a slow release source of copper(II). Exogenous 64Cu from both formulations was sequestered at inflammatory sites (relative to serum). This may partly explain how applied copper complexes can be anti-inflammatory.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents; Carrageenan; Copper; Edema; Granuloma; Inflammation; Injections, Subcutaneous; Male; Organometallic Compounds; Penicillamine; Radioisotopes; Rats; Rats, Inbred Lew; Salicylates; Tissue Distribution

We studied gallbladder involvement in 19 patients with Kawasaki syndrome who presented over a 4-year period from 1979 to 1982. Diagnosis and follow-up of gallbladder disease were defined by real-time ultrasound. Complete spontaneous resolution of abdominal symptomatology related to the hydropic gallbladder occurred without complication and did not require surgical intervention. We suggest that the incidence of hydrops of the gallbladder in mucocutaneous lymph node syndrome is higher than commonly appreciated, since diagnosis may be missed unless ultrasound is performed.

Topics: Acute Disease; Child; Child, Preschool; Edema; Female; Fluid Therapy; Gallbladder Diseases; Humans; Male; Mucocutaneous Lymph Node Syndrome; Salicylates; Ultrasonography

Proteinuria may be the initial manifestation of serious renal disease or merely a laboratory finding of little clinical importance. Excretion of urinary protein in excess of 150 mg per 24 hours in an adult is abnormal. It may be of glomerular, tubular or overflow origin. A comparison of the dipstick and sulfosalicylic acid techniques helps distinguish the source of protein, and electrophoresis is confirmatory. Transient and intermittent proteinuria are not clinically important. Persistent proteinuria requires further investigation.

Topics: Benzenesulfonates; Child; Edema; Electrophoresis; Humans; Hypertension; Kidney Diseases; Methods; Proteinuria; Salicylates; Urinary Tract Infections; Urine

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Copper; Dimethyl Sulfoxide; Edema; Female; Glycerol; Organometallic Compounds; Rats; Salicylates; Skin

A triglyceride of aspirin, A-45474: [2-(1,3-didecanoyloxy)-propyl]2-acetyloxybenzoate, was developed to reduce the direct gastric irritant properties of aspirin. Studies in the rat show that oral administration of A-45474 produces anti-inflammatory activity comparable to aspirin with negligible gastric irritation. Compared with aspirin, plasma salicylate levels of A-45474 appeared less rapidly and were more sustained. It is concluded that incorporation of aspirin in the 2-position of a triglyceride bearing n-decanoyl groups in the 1- and 3-positions markedly reduces the gastric irritating properties of aspirin while maintaining its pharmacological effects.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Biological Availability; Carrageenan; Delayed-Action Preparations; Edema; Injections, Intravenous; Intestinal Absorption; Male; Rats; Salicylates; Stomach; Time Factors; Triglycerides

A series of 1,3-dialkanoyl-2-(2-methyl-4-oxo-1,3-benzodioxan-2-yl)glycerides ("cyclic aspirin triglycerides") was synthesized. They demonstrated essentially all the systemic antiinflammatory activity associated with aspirin in the carrageenin-induced rat paw edema test. Examination of the rat stomachs showed that the 1,3-didecanoyl derivative did not cause gastric lesions.

Topics: Animals; Anti-Inflammatory Agents; Aspirin; Carrageenan; Edema; Male; Rats; Salicylates; Stomach Ulcer; Triglycerides

Three novel marine substances, 6-n-tridecylsalicylic acid, flexibilide and dendalone 3-hydroxybutyrate, isolated from a brown alga, a soft coral and a dictyoceratid sponge respectively, were active after oral administration in both acute and chronic animal models of inflammation. 6-n-Tridecylsalicylic acid has similar anti-inflammatory activity but less ulcerogenic activity on a molar basis than salicylic acid. The structure and activity of flexibilide did not resemble any known anti-inflammatory substance. Dendalone 3-hydroxybutyrate was a potent inhibitor of prostaglandin synthetase activity and platelet aggregation in vitro.

Topics: Animals; Anti-Inflammatory Agents; Drug Evaluation, Preclinical; Edema; Homosteroids; Indomethacin; Lactones; Male; Marine Biology; Phenylbutazone; Platelet Aggregation; Prostaglandins; Rats; Salicylates

A series of 1,3-bis(alkanoyl)-2-(O-acetylsalicyloyl)glycerides (aspirin triglycerides) having aspirin at the 2 position of glycerol and fatty acids at the 1 and 3 positions was prepared. The compounds were administered orally and tested for efficacy in the rat paw edema test, and the stomachs were examined for the presence of lesions. The results showed that the members of this series in which the fatty acids are of intermediate chain length (C4-C12) do not cause gastric lesions and have essentially all the systemic activity associated with aspirin.

Topics: Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Carrageenan; Dose-Response Relationship, Drug; Edema; Male; Rats; Salicylates; Stomach Ulcer; Structure-Activity Relationship; Time Factors; Triglycerides

While some salicylates (salicyclic acid and salicylaldehyde, especially) are as potent as aspirin as acute, orally-active anti-flammatory drugs in the rat, they are either inactive or far less potent as PG synthesis inhibitors when added directly to isolated platelets or when given orally. Although PGE1 and PGE2 produce anti-ulcerogenic effects when given to rats in the presence of selected non-steroidal anti-flammatory drugs, they fail to inhibit the acute anti-flammatory and anti-nociceptive effects of these drugs. They are anti-flammatory and anti-nociceptive under certain experimental conditions. PGE1 and PGE2 can also behave as hypothermic agents when given subcutaneously. Related studies, using PG synthesis stimulators in vivo and in vitro (substituted phenylureas), also cause anti-nociception and hypothermia. All of these indirect studies, when taken together, infer that PG synthesis inhibition per se fails to explain, entirely, the pharmacologic effects of non-steroidal anti-inflammatory drugs. They also suggest that the precise role of certain PGs in toxicopharmacology is far from simple and straightforward.

Topics: Analgesics; Animals; Blood Platelets; Body Temperature; Carrageenan; Edema; In Vitro Techniques; Inflammation; Male; Prostaglandins; Prostaglandins E; Rats; Salicylates; Stomach Ulcer

The effects of aspirin, salicylic acid and gentisic acid on the paw swellings in the arachidonic acid-potentiated and in the conventional carrageenan-induced oedema tests as well as on the content of prostaglandin-like activity and leucocyte migration in the exudate of inert implanted sponges in the rat have been studied. It is concluded that aspirin exerts two separate inhibitory effects on prostaglandin formation in vivo, a rapid action of the intact molecule on easily accessible tissues and a later action due to its metabolic conversion to salicylic acid. Salicylic acid inhibits prostaglandin biosynthesis in vivo as the salicylate ion itself and there is no formation of a subsequent 'active' metabolite.

Topics: Animals; Arachidonic Acids; Aspirin; Carrageenan; Edema; Exudates and Transudates; Female; Gentisates; Leukocytes; Prostaglandins; Rats; Salicylates

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents; Carrageenan; Edema; Gastrointestinal Motility; Guinea Pigs; Hydrocortisone; Intestines; Male; Prednisolone; Rats; Salicylates

Topics: Animals; Carrageenan; Edema; Male; Rats; Salicylates; Skin Absorption; Terpenes

Fendosal (HP 129) is one of a series of potent non-steroidal anti-inflammatory agents. Fendosal was compared with aspirin in several anti-inflammatory and analgesic bioassay procedures. Results indicate that fendosal has an anti-inflammatory activity 1.4 times greater than does aspirin in carrageenan-induced rat paw edema. Fendosal is 6.9 to 9.5 times more active than aspirin in the prophylactic and therapeutic adjuvant-induced polyarthritis models of chronic inflammation. The analgesic activity of fendosal is considered to be superior to that of aspirin, with the advantage of a prolonged duration of action. The gastric-irritating properties of fendosal are very low in comparison with those of aspirin. Fendosal has a much wider separation of effective and gastric-irritating doses than does aspirin.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Edema; Female; Granuloma; Hydroxybenzoates; Indoles; Rats; Salicylates

We have made a series of 4- and 5-aryl- and 4- and 5-heteroarylsalicylic acid derivatives with the objective of reducing gastric irritation and increasing potency. Here we describe a series of 4- and 5-heterocyclic salicylic acids and their antiinflammatory-analgesic potencies measured in comparison to aspirin. An improvement of the therapeutic index over aspirin of 100 was achieved; however, the heterocyclic salicylic acids lacked antipyretic activity. Some physicochemical parameters which may bear on the antiinflammatory activity of these compounds are discussed.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Chemical Phenomena; Chemistry, Physical; Dogs; Edema; Gastrointestinal Hemorrhage; Rats; Salicylates

The antiphlogistic activity of meseclazone and its major metabolite, 5-chlorosalicylic acid, have been directly compared to acetylsalicylic acid, phenylbutazone, indomethacin and hydrocortisone in rat paw edema induced by eleven different phlogistic agents. Based on the profile of activity and milligram/kilogram potency displayed by meseclazone, it most closely resembles acetylsalicylic acid and phenylbutazone in its mode of action.

Topics: Animals; Anti-Inflammatory Agents; Aspirin; Benzoxazines; Drug Evaluation, Preclinical; Edema; Hydrocortisone; Indomethacin; Isoxazoles; Male; Oxazines; Phenylbutazone; Rats; Salicylates

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Dogs; Edema; Female; Fluorobenzenes; Gastrointestinal Hemorrhage; Humans; In Vitro Techniques; Lethal Dose 50; Male; Mice; Peptic Ulcer; Platelet Aggregation; Rabbits; Rats; Salicylates; Time Factors

The ultimate cause of the clinical abnormalities associated with changes in oxygen supply and oxygen utilization is the development of abnormal tissue oxygen metabolism. Until now, there has been no satisfactory term to describe abnormal tissue oxygen metabolism. We propose the term "dysoxia" to fill this gap. There are a number of causes of dysoxia. One of the most interesting is that form of dysoxia related to abnormal mitochondrial structure and function. In this group of disorders, there is abnormal tissue oxygen metabolism, although oxygen supply is normal. Another interesting cause of dysoxia is exposure to high oxygen concentrations. High oxygen concentrations are involved in producing abnormal tissue oxygen metabolism under a number of different circumstances. The concept underlying dysoxia provides a unified approach to a large and important group of disorders involving most branches of clinical medicine.

Topics: Child; Child, Preschool; Cyanides; Dinitrophenols; Edema; Electron Transport; Humans; Hyperthyroidism; Hypothyroidism; Hypoxia; Infant, Newborn; Iron; Menkes Kinky Hair Syndrome; Mitochondria; Muscles; Oxygen; Oxygen Consumption; Reye Syndrome; Salicylates

Topics: Acacia; Adjuvants, Pharmaceutic; Animals; Aspartic Acid; Aspirin; Carrageenan; Diclofenac; Drug Evaluation, Preclinical; Edema; Female; Glucose; Glycyrrhiza; Male; Phenylacetates; Plants, Medicinal; Pyrroles; Rats; Salicylates; Stomach Ulcer; Tolmetin

Topics: Acetates; Animals; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Chelating Agents; Copper; Disease Models, Animal; Edema; Granuloma; Hydrocortisone; Lethal Dose 50; Mice; ortho-Aminobenzoates; Rats; Salicylates; Tryptophan; Ulcer

Evidence is presented which indicates that 7-chloro-3,3a-dihydro-2-methyl-2H,9H-isoxazolo-(3,2-b) (1,3)-benzoxazin-9-one (I) and 5-chlorosalicylic acid, its major metabolic end-product, are equally effective as anti-inflammatory and antipyretic agents, while the former is a somewhat more effective analgesic than its metabolite in the rat. However, at the equimolar doses used in this study, I is not ulcerogenic, while 5-chlorosalicylic acid does possess this untoward effect in the fasted rat. Moreover, the LD50 for 5-chlorosalicylic acid (261.0 mg/kg) is approximately 6.5 times less than that of I (1710.0 mg/kg) in the nonfasted rat. These results support the postulation that 5-chlorosalicylic acid is most likely responsible for the pharmacological activity displayed by I; i.e., the latter acts as a carrier or delivery system, allowing attenuation of the toxic properties of its active metabolite.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Arthritis; Body Temperature; Edema; Isoxazoles; Male; Oxazines; Oxazoles; Rats; Salicylates; Stomach Ulcer

Two and three Dow Cordis Hollow Fiber and Gambro Lundia artificial kidneys were used for high efficiency dialysis in large patients, intoxications, and for rapid ultrafiltration. BUN clearances of up to 240 ml/min were achieved. One episode of severe neuropathy occurred during high efficiency dialysis, and hypotensive episodes were more common. High efficiency dialysis has certain indications particularly in intoxication cases. However, because of possible side effects more experience is needed before its ultimate place in the treatment of uremia can be ascertained.

Topics: Barbiturates; Blood Urea Nitrogen; Body Weight; Calcium; Creatinine; Edema; Headache; Humans; Hypotension; Kidneys, Artificial; Nausea; Phenobarbital; Phenytoin; Poisoning; Primidone; Renal Dialysis; Salicylates; Substance-Related Disorders; Ultrafiltration; Uremia; Uric Acid

Subcutaneous implantation of small pieces of plastic foam leads to an exudation, the amount of which can be influenced by experimental conditions. The reproducibility of the amount of the exudation is very satisfactory. For 3 examples the possibility could be demonstrated that after cutaneous application of specific substances these can be analysed in the exudate. This could be done in the case of escin and salicylic acid (which is formed from the applied ester by enzymatic break-down during penetration of the epidermis) using thin-layer chromatography while heparin could be demonstrated disc-electrophoretically. All these substances lead to a statistically significant effect on the exudation process. Combining the 3 substances the therapeutic effect is very long lasting.

Topics: Animals; Chromatography, Thin Layer; Drug Interactions; Edema; Electrophoresis, Disc; Escin; Ethylene Glycols; Exudates and Transudates; Female; Heparin; Male; Povidone; Rats; Salicylates; Saponins; Skin Absorption; Time Factors

Topics: Administration, Topical; Drug Combinations; Edema; Escin; Ethylene Glycols; General Surgery; Hematoma; Heparin; Humans; Professional Practice; Salicylates; Saponins; Wounds and Injuries

Topics: Abnormalities, Drug-Induced; Acid Phosphatase; Animals; Cell Membrane; Drug Interactions; Drug Synergism; Edema; Embryo Implantation; Esters; Female; Fetal Death; Glucuronidase; Hindlimb; Inflammation; Lysosomes; Male; Methanol; Mice; Nicotinic Acids; Pregnancy; Rats; Salicylates; Stimulation, Chemical

Topics: Anhydrides; Animals; Anti-Inflammatory Agents; Carrageenan; Edema; Glucose; Male; Polymers; Rats; Salicylates; Starch; Structure-Activity Relationship

Topics: Acetanilides; Analgesics; Arthritis, Rheumatoid; Blood Sedimentation; Chronic Disease; Edema; Female; Finger Joint; Fingers; Humans; Male; Middle Aged; Muscle Contraction; Nausea; Pain; Physical Exertion; Salicylates; Suspensions

Topics: Adrenal Glands; Adult; Ankle Joint; Edema; Female; Glycosaminoglycans; Hematoma; Humans; Joint Diseases; Male; Salicylates; Sprains and Strains; Tissue Extracts

Topics: Accidents; Adrenal Cortex Hormones; Drug Combinations; Edema; Female; Gels; Glycosaminoglycans; Hematoma; Humans; Male; Salicylates; Wounds and Injuries

Topics: Analgesics; Anti-Inflammatory Agents; Antimalarials; Aspirin; Color Vision Defects; Corneal Opacity; Dimethyl Sulfoxide; Diplopia; Edema; Electrooculography; Electroretinography; Eye Diseases; Humans; Indoles; Nicotinic Acids; Optic Atrophy; Peptide Hydrolases; Pyrazoles; Retinal Hemorrhage; Salicylates; Vision Disorders

Topics: Animals; Anti-Inflammatory Agents; Benzyl Compounds; Edema; Female; Fever; Flufenamic Acid; Indomethacin; Lethal Dose 50; Male; Mefenamic Acid; Methylamines; Mice; Naphthalenes; Pain; Peptic Ulcer; Phenylbutazone; Pyrazoles; Rats; Salicylates; Terpenes; Uricosuric Agents

Topics: Adrenocorticotropic Hormone; Aminobenzoates; Anti-Inflammatory Agents; Dental Pulp Capping; Edema; Enzyme Therapy; Female; Glucocorticoids; Humans; Indomethacin; Inflammation; Male; Mouth Diseases; Muramidase; Nicotinic Acids; Oxyphenbutazone; Postoperative Complications; Pyrazoles; Salicylates; Stomatitis

Topics: Animals; Anti-Inflammatory Agents; Cortisone; Disease Models, Animal; Edema; Erythema; Inflammation; Phenylbutazone; Rabbits; Rats; Salicylates

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: Acetanilides; Adenosine Triphosphatases; Aminocaproates; Aminopyrine; Aminosalicylic Acids; Animals; Anti-Inflammatory Agents; Aspirin; Benzoates; Diphenhydramine; Edema; Flufenamic Acid; In Vitro Techniques; Male; Maleates; Mefenamic Acid; Mice; ortho-Aminobenzoates; Phenacetin; Quinine; Rabbits; Salicylates; Sarcolemma

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Aspirin; Azaguanine; Azathioprine; Bacteria; Benzimidazoles; Depression, Chemical; Edema; Enterococcus faecalis; Flufenamic Acid; Fungi; Indomethacin; Lactobacillus; Mefenamic Acid; Mercaptopurine; Oxyphenbutazone; Phenylbutazone; Purines; Pyrimethamine; Rats; Riboflavin; Salicylates; Staphylococcus; Tetracycline; Thioguanine

Topics: Adrenal Glands; Adrenalectomy; Aminopyrine; Animals; Anti-Inflammatory Agents; Bromelains; Edema; Furans; Glycosides; Hindlimb; Hydrocortisone; Male; Phenylbutazone; Propranolol; Rats; Rutin; Salicylates; Sodium; Time Factors

Topics: Adrenalectomy; Aminopyrine; Animals; Anti-Inflammatory Agents; Capillary Permeability; Edema; Fever; Granuloma; Guinea Pigs; Hydrocortisone; Male; Mice; Morphine; Peritonitis; Phenylbutazone; Pyridines; Rabbits; Rats; Salicylates; Wound Healing

Topics: Administration, Oral; Aminopyrine; Animals; Anti-Inflammatory Agents; Carrageenan; Edema; Male; Mice; Pain; Phenylbutazone; Pyridines; Rats; Salicylates; Sulfhydryl Compounds; Thiophenes

Topics: Aminopyrine; Amphetamine; Analgesics; Animals; Anti-Inflammatory Agents; Edema; Imipramine; Male; Mice; Morphine; Pain; Papaverine; Phenylbutazone; Pyridines; Rats; Salicylates; Thiophenes

Topics: Animals; Aspirin; Edema; Female; Gastric Mucosa; Guinea Pigs; Rats; Salicylates; Sulfates; Sulfur Isotopes

Topics: Adenosine Triphosphate; Analgesics; Animals; Anti-Inflammatory Agents; Central Nervous System; Chemical Phenomena; Chemistry; Connective Tissue; Edema; Flufenamic Acid; Glycosaminoglycans; Humans; Indomethacin; Mefenamic Acid; Oxyphenbutazone; Phenylbutazone; Pituitary-Adrenal System; Rats; Rheumatic Diseases; Salicylates

Topics: Animals; Calcinosis; Calciphylaxis; Connective Tissue; Edema; Female; Mast Cells; Potassium Permanganate; Purpura; Rats; Salicylates; Skin Diseases

Topics: Adrenocorticotropic Hormone; Animals; Anti-Inflammatory Agents; Edema; Hydrocortisone; Male; Rats; Salicylates; Staphylococcal Infections

Topics: Barbiturates; Bilirubin; Binding Sites; Blood Pressure; Blood Volume; Edema; Exchange Transfusion, Whole Blood; Humans; Infant, Newborn; Kernicterus; Liver Cirrhosis; Nephrosis; Salicylates; Serum Albumin

Topics: Adrenal Cortex Hormones; Contusions; Edema; Glycosaminoglycans; Humans; Knee Injuries; Salicylates

Topics: Adrenal Cortex Hormones; Animals; Anti-Inflammatory Agents; Drug Synergism; Edema; Glycosaminoglycans; Granuloma; Male; Neoplasms, Experimental; Rats; Salicylates; Sulfuric Acids

Topics: Adrenal Cortex Hormones; Arthritis; Arthritis, Rheumatoid; Blindness; Cataract; Conjunctivitis; Diplopia; Drug Therapy; Edema; Eye Diseases; Eye Manifestations; Glaucoma; Gold; Humans; Iatrogenic Disease; Intraocular Pressure; Iridocyclitis; Iritis; Keratitis; Lupus Erythematosus, Systemic; Myopia; Rheumatic Diseases; Salicylates; Spondylitis; Spondylitis, Ankylosing; Toxicology; Uveitis

Topics: Adrenal Cortex Hormones; Arthritis; Arthritis, Rheumatoid; Body Fluids; Drug Therapy; Edema; Electrophoresis; Phenylbutazone; Proteins; Salicylates

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Edema; Formaldehyde; Granuloma; Indoles; Inflammation; Pharmacology; Phenylbutazone; Rats; Research; Salicylates; Serotonin

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

Topics: Adrenal Cortex Hormones; Animals; Edema; Inflammation; Kallidin; Phenylbutazone; Rats; Salicylates

Topics: Adrenocorticotropic Hormone; Aldosterone; Analgesics; Analgesics, Non-Narcotic; Antipyretics; Ascorbic Acid; Bradykinin; Corticosterone; Cortisone; Desoxycorticosterone; Edema; Pharmacology; Phenylbutazone; Rats; Research; Salicylates; Salicylic Acid; Sulfinpyrazone; Uricosuric Agents

Topics: Edema; Inflammation; Salicylates; Salicylic Acid

Topics: Edema; Pulmonary Edema; Salicylates

Topics: Edema; Energy Metabolism; Inflammation; Permeability; Salicylates

Topics: Edema; Lung Diseases; Pulmonary Edema; Rheumatic Fever; Salicylates

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Animals; Cortisone; Edema; Egg White; Hypersensitivity; Pituitary Diseases; Pituitary Gland; Rats; Salicylates

Topics: Alkaloids; Edema; Epinephrine; Pulmonary Edema; Salicylates; Thiourea

Topics: Acidosis; Benzoates; Edema; Gentisates; Rheumatic Fever; Rheumatic Heart Disease; Salicylates