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Hydroxyl radical generation by rheumatoid blood and knee joint synovial fluid.

OBJECTIVE: To demonstrate directly that highly reactive hydroxyl radicals (OH.) can be generated in patients with rheumatoid arthritis and contribute to joint damage, and to examine the ability of blood to cause OH. generation. METHODS: The sensitive and specific technique of hydroxylation of aromatic compounds (salicylate and phenylalanine) was used to measure OH.. Synovial fluid and blood from patients with active rheumatoid arthritis were aspirated and immediately added to tubes containing salicylate and phenylalanine as detectors of OH., or to tubes containing saline as a control. Levels of specific products of attack of OH. upon salicylate (2,3- and 2,5-dihydroxybenzoates) and phenylalanine (ortho- and meta-tyrosines) were measured by high performance liquid chromatography. RESULTS: Synovial fluid samples aspirated into saline never contained ortho- or meta-tyrosines or 2,3-dihydroxybenzoate. Of 53 patients examined, synovial fluid and blood from 36 caused formation of ortho- and meta-tyrosines when aspirated into solutions containing phenylalanine. Repeated sampling from three "positive" patients showed consistent evidence of these hydroxylation products. Similarly, of 22 patients examined, synovial fluid and blood from 18 caused formation of 2,3- and 2,5-dihydroxybenzoates when aspirated into salicylate solutions. Further evidence for the role of OH. was provided by inhibition of the hydroxylation by the specific OH. scavengers mannitol and sodium formate. CONCLUSIONS: Aspirated knee joint fluids and blood from rheumatoid arthritis patients can generate OH., consistent with current views on the importance of this radical as a cytotoxic agent in rheumatoid disease. The ability of body fluids to cause OH. formation is not correlated with simple laboratory indices of disease activity, but is reproducible on sequential sampling from the same patients. The mechanism and significance of the phenomenon in rheumatoid arthritis pathology remain to be established.

Arthritis, Rheumatoid↗

Significance of inducible defense-related proteins in infected plants.

Inducible defense-related proteins have been described in many plant species upon infection with oomycetes, fungi, bacteria, or viruses, or insect attack. Several types of proteins are common and have been classified into 17 families of pathogenesis-related proteins (PRs). Others have so far been found to occur more specifically in some plant species. Most PRs and related proteins are induced through the action of the signaling compounds salicylic acid, jasmonic acid, or ethylene, and possess antimicrobial activities in vitro through hydrolytic activities on cell walls, contact toxicity, and perhaps an involvement in defense signaling. However, when expressed in transgenic plants, they reduce only a limited number of diseases, depending on the nature of the protein, plant species, and pathogen involved. As exemplified by the PR-1 proteins in Arabidopsis and rice, many homologous proteins belonging to the same family are regulated developmentally and may serve different functions in specific organs or tissues. Several defense-related proteins are induced during senescence, wounding or cold stress, and some possess antifreeze activity. Many defense-related proteins are present constitutively in floral tissues and a substantial number of PR-like proteins in pollen, fruits, and vegetables can provoke allergy in humans. The evolutionary conservation of similar defense-related proteins in monocots and dicots, but also their divergent occurrence in other conditions, suggest that these proteins serve essential functions in plant life, whether in defense or not.

Gene Expression Regulation, Plant↗

Novel shift of Jak/Stat signalling characterizes the protective effect of aurintricarboxylic acid (ATA) from tumor necrosis factor-alpha toxicity in human B lymphocytes.

Previous results demonstrated that the occurrence of death in human peripheral B lymphocytes by TNF-alpha was paralleled by the activation of the cytoplasmic Jak1 and Tyk2 protein kinases, along with the recruitment of transcription factors Stat3 and Stat5b. In this study we demonstrate that the balance of survival signals in the presence of TNF-alpha was altered by the addition of a salicylate compound, the endonuclease inhibitor aurintricarboxylic acid (ATA). Apoptosis effected by TNF-alpha alone was suppressed by ATA and this event was paralleled by phosphorylation and nuclear translocation of Jak2, Stat2, Stat4 and NF-kB, along with inhibition of caspase activation. These results confirm that among the different cellular responses evoked by TNF-alpha in human B cells, recruitment of Jak/Stat proteins and possible related gene modulation represent contributing factors and address the issue of the development of potential therapeutic strategies aimed at the control of systemic or local effects produced by TNF-alpha.

Aurintricarboxylic Acid↗

Antioxidant activity of the microalga Chlorella vulgaris cultered on special conditions.

The chemical composition of Chlorella vulgaris indicates that it has a high nutritional value to a wide range of essential nutrients, such as vitamins, minerals and proteins. Moreover, it contains other compounds such as n-3 and n-6 polynsaturated fatty acids, provitamins and phenolic compounds. In addition, this alga can be produced in large-scale systems. The objective of the present study was to evaluate the antioxidant capacity of a Chlorella cultured on three differents temperatures (15 degrees C, 20 degrees C and 30 degrees C) in 3 Klux. Chlorella cultured samples were submitted to sequential extration using as solvents: ether, methanol and water. The antioxidant activity in the extracts was measured by b-carotene/linoleic acid system, at 50 degrees C and absorbances reading at 470 nm. One control with BHT, 100 ppm was used in this determination. The total phenolic compounds was determined with Folin-Ciocalteu reagent using the spectrophotometric measured at 780 nm with catechin as standard. The phenolic acid analysis were carried out using gas chromatograph equipped with a capillary column and flame ionization detector. Non conjugated and total phenolic acids were identified on the basis of the relative retention time of their derivatives compared with the standard phenolic acids. The methanolic extract from Chlorella cultured at 30 degrees C showed higher antioxidant activity (85%) quite similar of BHT (86%). By the Rancimat test (lipidic medium) two fractions from methanolic extracts showed too higher antioxidant activity with induction times > 37.50 h at 60 degrees C and 11.5 h at 100 degrees C. The total phenolic compounds were 24.95 mg in 1 g of dry alga matter from methanolic extract and five phenolic acids were identified. The phenolic compounds salicylic, trans cinnamic, synaptic, chlorogenic, chimic and caffeic acids found in the methanolic Chlorella extract may be responsible for its higher antioxidant activity.

Antioxidants↗

Application of automated flow injection analysis to drug liberations studies with the Franz diffusion cell.

The flow-injection method with sensitive fluorimetric detection is used to monitor the liberation profiles of a topical dermatological formulation containing the model compound salicylic acid. The connection of a standard Franz diffusion cell with the automated flow-injection system enables an acquisition of multi-point liberation data in a form of series of fluorescence peaks in a short time. Examples of liberation profiles for a topical dermatological formulation containing salicylic acid are shown.

Autoanalysis↗

Kawasaki-like syndrome after treatment with mesalazine.

We report a patient who developed a severe hypersensitivity reaction, including rash, lymph node enlargement, fever, hepatitis, and eosinophilia, after sulphasalazine therapy. Five years later, he developed a similar reaction after exposure to mesalazine, the salicylic compound of sulphasalazine. We conclude that patients with known severe systemic reaction to sulphasalazine therapy are also at risk for such a reaction when treated with a 5-ASA preparation.

Adult↗

The economic potential and the role of aspirin and alcohol ingestion in relation to haematemesis and meleana.

The economic potential and the role of aspirin and alcohol ingestion have been explored in relation to acute upper gastrointestinal haemorrhage complicating duodenal ulcer disease or portal hypertension. Of special interest in the study was the clear indication of the relevance of socioeconomic impact in the haemorrhage patients, the majority of whom were found to belong to the class of unskilled wage earners. Though a history of regular ingestion of salicylate compounds and alcohol was commonly obtained on specific questioning, only in six of the thirty-one patients could the onset of the overt haemorrhage be attributed to adverse synergism between these two groups of drugs.

Adult↗

Influence of acetylsalicylic acid on glucose turnover in normal man.

This study was designed to evaluate the influence of intravenous infusion (72 mg min-1) of lysine acetylsalicylate (LAS), an inhibitor of endogenous prostaglandin synthesis, on glucose homeostasis in normal man. LAS infusion produced a transient decrease of both hepatic glucose production (Ra, p less than 0.01) and peripheral glucose uptake (Rd, p less than 0.01). Since Ra fell more than Rd, a slight but significant decrease of plasma glucose concentration occurred. Glucose metabolic clearance rate also showed a rapid, although transient, decrease after the start of LAS infusion. Plasma insulin rose twofold in response to LAS, while plasma glucagon remained unchanged. The failure of the glucose clearance to increase as a consequence of the augmented insulin levels suggests that salicylate compounds may cause a state of insulin resistance.

Adult↗

[Clarification of mechanism of acetylsalicylic acid].

Acetylsalicylic acid is probably the most widely used of all drugs. Recent data has provided new insights into its mechanism of action and documented its usefulness in cardiovascular prevention. At the same time we now understand better why plants benefit from new production of the mother compound-salicylic acid. Thus very old drugs can be quite newsworthy.

Aspirin↗

Theophylline magnesium salicylate, a new xanthine compound.

Interaction of 1 mole of magnesium salicylate and 2 moles of theophylline in water precipitated a crystalline compound, identified as theophylline magnesium salicylate pentahydrate from analytical and supportive physicochemical data. Similarly, barium salicylate and theophylline produced theophylline barium salicylate. No precipitates were formed with calcium salicylate or strontium salicylate under the same conditions. Theophylline magnesium salicylate is not a mixture of components and differs in composition from the known theophylline calcium salicylate dihydrate. Unlike the latter compound, it is not alkaline.

Animals↗

In vivo volatile emissions from peanut plants induced by simultaneous fungal infection and insect damage.

Peanut plants, Arachis hypogaea, infected with white mold. Sclerotium rolfsii, emit a blend of organic compounds that differs both quantitatively and qualitatively from the blend emitted from plants damaged by beet armyworm (BAW; Spodoptera exigua) larvae or from uninfected, undamaged plants. Attackby BAW induced release of lipoxygenase products (hexenols, hexenals, and hexenyl esters), terpenoids, and indole. The plant-derived compound methyl salicylate and the fungal-derived compound 3-octanone were found only in headspace samples from white mold infected plants. White mold-infected plants exposed to BAW damage released all the volatiles emitted by healthy plants fed on by BAW in addition to those emitted in response to white mold infection alone. When BAW larvae were given a choice of feeding on leaves from healthy or white mold-infected plants, they consumed larger quantities of the leaves from infected plants. Exposure to commercially available (Z)-3 hexenyl acetate, linalool, and methyl salicylate, compounds emitted by white mold-infected plants, significantly reduced the growth of the white mold in solid-media cultures. Thus, emission of these compounds by infected plants may constitute a direct defense against this pathogen.

Animals↗

Inhibition of lyso-PAF: acetyl-CoA acetyltransferase by salicylates and other compounds.

Diflunisal and benoxaprofen (20-100 microM) produced dose-dependent inhibitions of lyso-platelet activating factor: acetyl-CoA acetyltransferase in a lysate of rat pleural neutrophils. Salicylate and aspirin were inhibitory at concentrations of 1 mM and above. Nordihydroguaiaretic acid was a relatively potent inhibitor (I50 = 6 microM). Other compounds, including anti-inflammatory steroids, cyclooxygenase and 5-lipoxygenase inhibitors, appeared ineffective at relevant concentrations. Inhibitions by diflunisal and salicylate occurred at concentrations similar to expected plasma levels in humans at therapeutic doses. An inhibition of platelet-activating factor synthesis may contribute to the antiinflammatory, analgesic, or antipyretic actions of these compounds.

Acetyl-CoA C-Acetyltransferase↗