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Hydrogen peroxide from the oxidative burst is neither necessary nor sufficient for hypersensitive cell death induction, phenylalanine ammonia lyase stimulation, salicylic acid accumulation, or scopoletin consumption in cultured tobacco cells treated with elicitin.

H(2)O(2) from the oxidative burst, cell death, and defense responses such as the production of phenylalanine ammonia lyase (PAL), salicylic acid (SA), and scopoletin were analyzed in cultured tobacco (Nicotiana tabacum) cells treated with three proteinaceous elicitors: two elicitins (alpha-megaspermin and beta-megaspermin) and one glycoprotein. These three proteins have been isolated from Phytophthora megasperma H20 and have been previously shown to be equally efficient in inducing a hypersensitive response (HR) upon infiltration into tobacco leaves. However, in cultured tobacco cells these elicitors exhibited strikingly different biological activities. beta-Megaspermin was the only elicitor that caused cell death and induced a strong, biphasic H(2)O(2) burst. Both elicitins stimulated PAL activity similarly and strongly, while the glycoprotein caused only a slight increase. Only elicitins induced SA accumulation and scopoletin consumption, and beta-megaspermin was more efficient. To assess the role of H(2)O(2) in HR cell death and defense response expression in elicitin-treated cells, a gain and loss of function strategy was used. Our results indicated that H(2)O(2) was neither necessary nor sufficient for HR cell death, PAL activation, or SA accumulation, and that extracellular H(2)O(2) was not a direct cause of intracellular scopoletin consumption.

Algal Proteins↗

Immediate early transcription activation by salicylic acid via the cauliflower mosaic virus as-1 element.

Transgenic tobacco plants carrying a number of regulatory sequences derived from the cauliflower mosaic virus 35S promoter were tested for their response to treatment with salicylic acid (SA), an endogenous signal involved in plant defense responses. beta-Glucuronidase (GUS) gene fusions with the full-length (-343 to +8) 35S promoter or the -90 truncation were found to be induced by SA. Time course experiments revealed that, in the continuous presence of SA, the -90 promoter construct (-90 35S-GUS) displayed rapid and transient induction kinetics, with maximum RNA levels at 1 to 4 hr, which declined to low levels by 24 hr. Induction was still apparent in the presence of the protein synthesis inhibitor cycloheximide (CHX). Moreover, mRNA levels continued to accumulate over 24 hr rather than to decline. By contrast, mRNA from the endogenous pathogenesis-related protein-1a (PR-1a) gene began to accumulate at later times during SA treatment and steadily increased through 24 hr; transcription of this gene was almost completely blocked by the presence of CHX. Further dissection of the region from -90 and -46 of the 35S promoter revealed that the SA-responsive element corresponds to the previously characterized activation sequence-1 (as-1). These results represent a definitive analysis of immediate early responses to SA, relative to the late induction of PR genes, and potentially elucidate the early events of SA signal transduction during the plant defense response.

Base Sequence↗

Binding of clometacin to human serum albumin. Interactions with clofibrate, indomethacin, salicylic acid and warfarin.

The binding of clometacin to human serum albumin (HSA) was studied in vitro by equilibrium dialysis. Our results show that binding to HSA is 99% at therapeutic levels. Binding is characterized by several numbers of binding sites (n = 8) with a moderate association constant (K = 2.7 X 10(4) M-1) and by another non-saturable phenomenon (nK = 4200 M-1). Moreover, interactions were studied with many drugs. Clometacin binding was altered by indomethacin, warfarin, chlorophenoxyisobutyrate (CPIB) and salicylic acid (SA). Conversely, clometacin inhibited the binding of these drugs. Finally, all these results were compared with those previously obtained with indomethacin, a positional isomer of clometacin.

Analgesics↗

Comparison of salicylic acid and urea versus ammonium lactate for the treatment of foot xerosis. A randomized, double-blind, clinical study.

Xerosis is defined as dehydration of skin characterized by redness, dry scaling, and fine crackling that may resemble the crackling of porcelain. The present double-blind trial was a randomized paired comparison study evaluating the keratolytic effect of 5% salicylic acid and 10% urea ointment (Kerasal) on one foot and 12% ammonium lactate lotion (Lac-Hydrin) on the other foot in mild-to-moderate xerosis. Seventy patients were initially enrolled in the trial. Fifty-four patients were evaluated after 2 weeks of treatment; of those 54 patients, 39 were evaluated after 4 weeks of treatment. Although there was significant improvement in severity of xerosis after 2 and 4 weeks of treatment, there was no statistically significant difference between treatment groups. Irrespective of the mechanism of action, this study shows that both Kerasal and Lac-Hydrin 12% lotion result in reduction in the severity of xerosis after 4 weeks of therapy.

Administration, Topical↗

Salicylic acid influences Hsp70/Hsc70 expression in Lycopersicon esculentum: dose- and time-dependent induction or potentiation.

Overexpression of heat-shock (HS) proteins (HSP) is often sufficient to protect against lethal environmental stresses. Anti-inflammatory salicylates potentiate the induction of the 70 kDa HSP (Hsp70) in mammals in response to HS and enhance thermotolerance. In plants, salicylic acid (SA) is a natural signalling molecule, mediating resistance in response to avirulent pathogens. The influence of SA on the HS response in plants is, however, unknown. We investigated the effect of SA, alone or with HS, on Hsp70/Hsc70 expression in tomato cells using biometabolic labelling and Western blotting. A dose- and time-dependent influence on Hsp70/Hsc70 accumulation was observed: SA at 1.0 mM (3 h) potentiated heat-induced accumulation, while 1.0 mM (5 h) and 0.5 mM (8 h) induced expression, the latter preceded by increased membrane permeability. These results suggest that in plants, as in mammals, low SA concentrations do not induce Hsp70/Hsc70 expression but potentiate HS induction and confer membrane protection, while cytotoxic levels induce Hsp70/Hsc70.

Carrier Proteins↗

Chemical inactivation of the cinnamate 4-hydroxylase allows for the accumulation of salicylic acid in elicited cells.

The cinnamate (CA) 4-hydroxylase (C4H) is a cytochrome P450 that catalyzes the second step of the main phenylpropanoid pathway, leading to the synthesis of lignin, pigments, and many defense molecules. Salicylic acid (SA) is an essential trigger of plant disease resistance. Some plant species can synthesize SA from CA by a mechanism not yet understood. A set of specific inhibitors of the C4H, including competitive, tight-binding, mechanism-based irreversible, and quasi-irreversible inhibitors have been developed with the main objective to redirect cinnamic acid to the synthesis of SA. Competitive inhibitors such as 2-hydroxy-1-naphthoic acid and the heme-coordinating compound 3-(4-pyridyl)-acrylic acid allowed strong inhibition of C4H activity in a tobacco (Nicotiana tabacum cv Bright Yellow [BY]) cell suspension culture. This inhibition was however rapidly relieved either because of substrate accumulation or because of inhibitor metabolism. Substrate analogs bearing a methylenedioxo function such as piperonylic acid (PIP) or a terminal acetylene such as 4-propynyloxybenzoic acid (4PB), 3-propynyloxybenzoic acid, and 4-propynyloxymethylbenzoic acid are potent mechanism-based inactivators of the C4H. PIP and 4PB, the best inactivators in vitro, were also efficient inhibitors of the enzyme in BY cells. Inhibition was not reversed 46 h after cell treatment. Cotreatment of BY cells with the fungal elicitor beta-megaspermin and PIP or 4PB led to a dramatic increase in SA accumulation. PIP and 4PB do not trigger SA accumulation in nonelicited cells in which the SA biosynthetic pathway is not activated. Mechanism-based C4H inactivators, thus, are promising tools for the elucidation of the CA-derived SA biosynthetic pathway and for the potentiation of plant defense.

Benzoates↗

[Spectrophotometric determination of complex formation constants of naproxen with caffeine, nicotinamide and salicylic acid in aqueous solution].

The interaction between water insoluble drug naproxen with caffeine, nicotinamide and salicylic acid in aqueous solutions were determined by spectrophotometry. Naproxen was found to form 1:1 molecular complex with these substances. The complex formation constants were determined by spectrophotometry at room temperature. The thermodynamic functions associated with complexation of naproxen-drugs were also evaluated. It may be concluded that the complex formation may be attributed to hydrogen bonding since enthalpy changes were shown to be a few KJ.mol-1.

Caffeine↗

Pharmacokinetics of acetaminophen, antipyrine, and salicylic acid in the lactating and nursing rabbit, with model predictions of milk to serum concentration ratios and neonatal dose.

The rabbit was utilized for examining the pharmacokinetics of three compounds (acetaminophen, AC; antipyrine, AN; and salicylic acid, SA) in nursing adults and their suckling offspring and for assessing the ability of a diffusional model to predict milk to serum drug concentration ratios (M/S) from in vitro experiments. AC, AN, and SA serum concentration time profiles declined monoexponentially for both adults and their pups. The mean systemic clearance (Cls) for AC in the adults and pups was 16.1 and 13.7 ml/min/kg, respectively. The mean half-lives of AC (t1/2) were 25.5 and 33.3 min in the adult and pup groups, respectively. AN declined in parallel for adult rabbits and an older group of suckling pups (23-25 days old). In a younger group of pups (18-21 days old) it declined with a longer t1/2 (97.5, 95.1, and 347.6 min in the adults, older pups, and younger pups, respectively). The mean AN Cls in the adults, the older pups, and the younger pups was 5.34, 6.30, and 1.91 ml/min/kg, respectively. The time course of SA was prolonged in the suckling pups (t1/2 of 633 min in the pups vs 78.7 min in the adult). The mean Cls values in the adults and the pups were 1.05 and 0.27 ml/min/kg, respectively. The mean systemic clearance of unbound drug (Clu) for SA was 11.2 ml/min/kg in the adults and 0.92 ml/min/kg in the pups. The serum protein binding of AC and AN was limited, whereas the mean free fraction for SA was 9.7% in adult serum and 32.5% in pup serum. AC and AN in milk paralleled serum drug profiles; a time lag was noted for milk SA. M/S ratios were determined in vivo (M/Sobs; AN = 0.885, AC = 0.580, and SA = 0.125) using area under the milk and serum concentration time profiles. Predicted M/S values (M/Spred; AN = 0.779, AC = 0.578, and SA = 0.085) were calculated from in vitro measurements of the unbound fractions of drug in skim milk and serum, the skim to whole milk drug concentration ratio, milk and serum pH, and the pKa of the model compound. Mean values for M/Sobs were highly correlated with M/Spred values (r2 = 0.976) when the present data were combined with previous data for propranolol, phenobarbital, phenytoin, and diazepam (Fleishaker, J.C., and McNamara, P.J., J. Pharmacol. Exp. Ther. 244, 919, 1988). These results support the usefulness of the diffusional model for predicting M/S in vivo, provided that the distributional process is governed by passive diffusion.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetaminophen↗

Determination of hydroxyl radicals with salicylic acid in aqueous nitrate and nitrite solutions.

The qualitative and quantitative analyses of reactive oxygen species are essential to determine their steady-state concentration and related reaction mechanisms in environmental aquatic systems. In this study, salicylic acid was employed as an innovative molecular probe of hydroxyl radical(OH) generated in aqueous nitrate and nitrite solutions through photochemical reactions. Kinetic studies showed that the steady-state concentrations of OH in aqueous NO3- (10 mmol/L, pH = 5) and NO2- (10 mmol/L, pH = 5) solutions under ultraviolet irradiation were at a same magnitude, 10(-15) mol/L. Apparent quantum yields of OH at 313 nm were measured as 0.011 and 0.07 for NO3- and NO2- respectively, all comparable to the results of previous studies.

Anti-Infective Agents↗

Measurement of salicylic acid in human serum using stable isotope dilution and gas chromatography-mass spectrometry.

A simple, highly selective, and sensitive method using stable isotope dilution and gas chromatography-mass spectrometry has been developed to quantify salicylic acid (SA) at concentrations naturally occurring in biological fluids, such as in the serum of subjects not taking aspirin. After extraction of liquid-liquid with diethyl ether and ethyl acetate and preparation of the tert-butyldimethylsilyl derivative, SA content was detected using deuterated SA as internal standard. The mean recovery of SA from serum was 85 +/- 6%. Intra- and interday precision and % relative error were <15% in all cases. With a detection limit of 0.6 ng and a quantification limit of 2 ng, the method is therefore also adequate for population studies because of the small amount of blood necessary to perform the analyses.

Blood Chemical Analysis↗

Effect of several hydrophilic polymers on the permeation of morphine and salicylic acid through excised hairless rat skin.

Several hydrophilic polymers changed the cumulative amount of morphine (MOR) permeated through excised hairless rat skin from 1% MOR hydrochloride solution containing ethanol and l-menthol at concentrations of 40% and 5%, respectively, as permeation enhancers. Anionic polymers (carboxyvinylpolymer and methylvinylether-maleic anhydride copolymer) in the test solutions decreased the skin permeation of MOR, whereas cationic polymers (polyethyleneimine and chitosan) increased it, compared with that without polymers. Little change, however, was observed by the addition of nonionic polymers (hydroxypropylcellulose and polyethyleneoxide). On the other hand, the cationic and anionic polymers in the test solutions decreased and increased, respectively, the skin permeation of salicylic acid (SA) from the same enhancing system containing sodium salicylate. These opposite results were probably caused by the change in escaping tendency of the drugs from the vehicles, which was due to the drug-polymer interaction. (The escaping tendency has a great effect on the drug partition from the polymer solution to the skin barrier). The effect of hydrophilic polymers on the partition was then evaluated by Donnan membrane theory. The partition of MOR was increased and decreased by the presence of polymers having identical and opposite charge to MOR. The low partition of the drugs to skin may also be caused by low diffusion of the drugs in the polymer solutions. The drug release from the hydrophilic polymer solutions was then measured, and the release rate was found to have decreased in the presence of polymers having opposite charge to MOR and SA. It is suggested that these drug-polymer interactions changed the drug partition to skin thus changing the skin permeation of the drug.

Analgesics, Opioid↗

Transcriptional profiling of sorghum induced by methyl jasmonate, salicylic acid, and aminocyclopropane carboxylic acid reveals cooperative regulation and novel gene responses.

We have conducted a large-scale study of gene expression in the C4 monocot sorghum (Sorghum bicolor) L. Moench cv BTx623 in response to the signaling compounds salicylic acid (SA), methyl jasmonate (MeJA), and the ethylene precursor aminocyclopropane carboxylic acid. Expression profiles were generated from seedling root and shoot tissue at 3 and 27 h, using a microarray containing 12,982 nonredundant elements. Data from 102 slides and quantitative reverse transcription-PCR data on mRNA abundance from 171 genes were collected and analyzed and are here made publicly available. Numerous gene clusters were identified in which expression was correlated with particular signaling compound and tissue combinations. Many genes previously implicated in defense responded to the treatments, including numerous pathogenesis-related genes and most members of the phenylpropanoid pathway, and several other genes that may represent novel activities or pathways. Genes of the octadecanoic acid pathway of jasmonic acid (JA) synthesis were induced by SA as well as by MeJA. The resulting hypothesis that increased SA could lead to increased endogenous JA production was confirmed by measurement of JA content. Comparison of responses to SA, MeJA, and combined SA+MeJA revealed patterns of one-way and mutual antagonisms, as well as synergistic effects on regulation of some genes. These experiments thus help further define the transcriptional results of cross talk between the SA and JA pathways and suggest that a subset of genes coregulated by SA and JA may comprise a uniquely evolved sector of plant signaling responsive cascades.

Acetates↗

Elimination of salicylic acid in goats and cattle.

Sodium salicylate was administered to cattle and goats IV and PO according to a crossover design. Total urinary excretion of SA and its metabolites was measured for 3 days after dosing. Salicyluric acid (SUA) was the only metabolite detected in urine of either species. Recovery of sodium salicylate and SUA in goats amounted to 67.9 and 34.6% of the dose, respectively, after IV administration. After oral dosing, total recoveries were 30.2% (sodium salicylate) and 71.7% (SUA) of dose. By comparison, cattle excreted significantly (P less than 0.05) less sodium salicylate (54.0%) and more SUA (49.9%) after IV dosing. The same pattern was observed after oral administration, wherein cattle excreted less than 12% as sodium salicylate and more than 99% as SUA. In both species, almost 90% of the drug excreted as sodium salicylate was found in urine within the first 12 hours after an IV dose and within 24 hours after oral dosing. The excretion of SUA was somewhat slower in both species, especially after oral administration. The data suggested that there were only quantitative differences in the metabolism and elimination of sodium salicylate between the 2 species, with cattle excreting a higher proportion of the drug as the glycine conjugate SUA.

Administration, Oral↗

Salicylic acid induction-deficient mutants of Arabidopsis express PR-2 and PR-5 and accumulate high levels of camalexin after pathogen inoculation.

In Arabidopsis, systemic acquired resistance against pathogens has been associated with the accumulation of salicylic acid (SA) and the expression of the pathogenesis-related proteins PR-1, PR-2, and PR-5. We report here the isolation of two nonallelic mutants impaired in the pathway leading to SA biosynthesis. These SA induction-deficient (sid) mutants do not accumulate SA after pathogen inoculation and are more susceptible to both virulent and avirulent forms of Pseudomonas syringae and Peronospora parasitica. However, sid mutants are not as susceptible to these pathogens as are transgenic plants expressing the nahG gene encoding an SA hydroxylase that degrades SA to catechol. In contrast to NahG plants, only the expression of PR-1 is strongly reduced in sid mutants, whereas PR-2 and PR-5 are still expressed after pathogen attack. Furthermore, the accumulation of the phytoalexin camalexin is normal. These results indicate that SA-independent compensation pathways that do not operate in NahG plants are active in sid mutants. One of the mutants is allelic to eds5 (for enhanced disease susceptibility), whereas the other mutant has not been described previously.

Alleles↗

Lysine acetyl salicylic acid in acute renal pain.

The effect of repeated doses of 1.8 g lysine acetyl salicylic acid (LAS) i.v. on severe pain secondary to acute renal colic (ARC) was studied in 45 consecutive patients. Clinically acceptable analgesia was obtained in 65% of the cases. No additional pain relief was achieved with the combination of pethidine 100 mg i.v. + metoclopramide 10 mg, i.m. (narcotics). Pain relief occurred within five minutes in one third of the patients while in the rest within 30 minutes. Significant reduction of systolic blood pressure (mean +/- S.D.) 23.8 +/- 19.5, pulse rate (mean +/- S.D.) 19.5 +/- 10.1 and vomiting were noted in patients who had pain relief. The incidence of nausea has increased after LAS administration. No other side effects were observed. LAS might therefore be applied as a first-hand alternative to narcotics for the treatment of ARC.

Acute Disease↗

Aspirin and salicylic acid do not inhibit methyl jasmonate-inducible expression of a gene for ornithine decarboxylase in tobacco BY-2 cells.

Similar to the prostanoid-mediated inflammatory response in mammals, jasmonate-mediated wound response in plant leaves is inhibited by salicylic acid (SA) or acetylsalicylate (aspirin). In tobacco BY-2 cells, expression of the gene for ornithine decarboxylase (ODC) involved in putrescine synthesis is rapidly inducible by methyl jasmonate (MeJA). A nuclear gene for ODC isolated from tobacco, gNtODC-1, was an intron-less gene and MeJA induced the expression of a GUS fusion gene with the gNtODC-1 promoter in transformed tobacco cells. Although SA alone did not induce the expression, 0.2 to 20 microM SA increased the MeJA-induced expression of the fusion gene to about two-fold. A similar increase was observed with aspirin but not with 3- or 4-hydroxybenzoic acids. SA at concentrations up to 200 microM did not inhibit the MeJA-induction of mRNAs for the GUS fusion gene and the endogenous gene for ODC.

Acetates↗