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Comparison of the Ability of Salicylic Acid and Ferricyanide to Induce Flowering in the Long-day Plant, Lemna Gibba G3.

Both salicylic acid and ferricyanide induce flowering in the long-day plant Lemna gibba L., strain G3 under 8- and 9-hour short days. In both cases the effect is daylength-dependent. Salicylic acid is ineffective on daylengths less than 8 hours and ferricyanide is ineffective on daylengths less than 5 hours. When both substances are given together a striking synergistic interaction is observed, and some flowering is obtained on daylengths as short as 3 hours. However, even with the optimal combinations the flower-inducing effect remains daylength-dependent.Flowering of L. gibba G3 is inhibited under continuous light in both half-strength Hutner's medium (0.5 H), which contains 1.25 millimolar ammonium, and in ammonium-free half-strength Hutner's medium (NH(4) (+)-free 0.5 H). Salicylic acid is able to reverse the inhibition substantially in 0.5 H medium and to cause complete reversal in NH(4) (+)-free 0.5 H medium. By contrast, ferricyanide has no effect in 0.5 H medium and causes only a small reversal in NH(4) (+)-free 0.5 H medium. Flowering of L. gibba G3 is also inhibited under continuous light by copper. This inhibition is largely reversed by salicylic acid but ferricyanide has no effect.

Journal Article↗

A rapid high-performance liquid chromatographic method for the simultaneous quantitation of aspirin, salicylic acid, and caffeine in effervescent tablets.

A rapid reversed-phase high-performance liquid chromatographic procedure is developed and validated for the simultaneous quantitation of aspirin, salicylic acid, and caffeine extracted from an effervescent tablet. The method uses a Hypersil C18 column (5 micro m, 15 cm x 4.6 mm) for an isocratic elution in a water-methanol-acetic acid mobile phase at a wavelength of 275 nm. The tablets' buffering effects and acid neutralizing capacity require an extraction solvent of methanol-formic acid. The range of linearity for aspirin is 0.5-1.25 mg/mL, caffeine 0.065-0.195 mg/mL, and salicylic acid 0.4-6.0% of aspirin. The overall recovery is 100.2%, 100.7%, and 99.2% for aspirin, caffeine, and salicylic acid, respectively. Under the conditions of the method, aspirin, caffeine, and salicylic acid are adequately resolved with proper peak symmetry in less than 7 min.

Aspirin↗

Salicylamide reverses the aspirin-antagonistic effect of salicylic acid on rat platelet cyclooxygenase.

The antagonistic effect of salicylic acid (SA), the major metabolite of aspirin, on aspirin (ASA)-induced inhibition of cyclooxygenase has been recognized in vivo and in vitro. Salicylamide is available with aspirin in some analgesic preparations. Salicylamide shares important characteristics with salicylic acid including the lack of effect on cyclooxygenase and platelet aggregation as well as a close structural resemblance. This prompted us to study the interaction of salicylamide with aspirin and/or SA on rat platelet and cyclooxygenase. Our results showed that salicylamide has, unlike SA, no blocking effect on the anticyclooxygenase effect of aspirin in vitro. Moreover, salicylamide could dose-dependently prevent the aspirin-blocking effect of SA on platelet cyclooxygenase. These results suggest that salicylamide and SA compete for a receptor on cyclooxygenase different to that of aspirin. A functional model of cyclooxygenase enzyme is proposed.

Animals↗

Effect of the application of an anionic detergent combined with FABRY's tincture and its components on human skin resident flora. Part 2: Dermofug solution combined with either salicylic acid tincture or phenol acid tincture.

Using the forehead skin test, we investigated the combined application of 10 v/v% Dermofug solution and 3 w/v% salicylic acid tincture or 1 v/v% phenol acid tincture. The former combination showed better antibacterial efficacy against the coagulase-negative staphylococci and Propionibacterium spp. in the stratum corneum/acroinfundibulum as well as in the infrainfundibulum of the sebaceous glands. No antibacterial efficacy could be determined against Propionibacterium spp. in the infrainfundibulum of the sebaceous glands after the combined application of Dermofug solution and 1 v/v% phenol acid tincture. In contrast, the combined application of Dermofug solution and 3 w/v% salicylic acid tincture led to a long-term reduction of the cfu-counts of Propionibacterium spp. in the infrainfundibulum of the sebaceous glands. The following conclusions can be drawn from our study and applied to external therapy: a detergent like Dermofug should be used instead of an alcohol to enhance the penetration of a drug into the infrainfundibulum of the sebaceous glands, since the former can block the growth of Propionibacterium spp. in the infrainfundibulum. Secondly, it should be kept in mind that the addition of salicylic acid to a topical antibiotic ointment does not only enhance the penetration of the antibiotic into the infrainfundibulum of the sebacous glands, but that the antibacterial effect of the salicylic acid itself may be the reason for the better clinical antibacterial efficacy of such combinations.

Bacteria↗

Transcriptional and post-translational regulation of S-adenosyl-L-methionine: salicylic acid carboxyl methyltransferase (SAMT) during Stephanotis floribunda flower development.

Methyl salicylate (MeSA) and a number of other volatiles are primarily emitted in the evening/night by Stephanotis floribunda leading to attraction of night active pollinators. A second minor emission peak for MeSA occurs in the morning/day. To understand these emission patterns, we have studied in detail the temporal regulation of the last step of the biosynthetic pathway of MeSA, the convertion of salicylic acid (SA) to MeSA catalysed by S-adenosyl-L-methionine: salicylic acid carboxyl methyltransferase (SAMT). We observed that in young flowers a maximum in SAMT activity occurs in the night, and that in flowers which were open longer than 4 days, two SAMT activity maxima occurred per day. These maxima correlated well with dawn and dusk and the previously detected MeSA emission peaks. The SAMT mRNA levels, however, have a broad maximum during the dark phase, while the SAMT protein levels continuously increase during floral development without showing daily rhythms. Furthermore, under continuous illumination (LL) the SAMT mRNA levels and activity patterns oscillate, suggesting the involvement of a circadian clock in the regulation network. Taken together, this analysis clearly demonstrates that regulation of MeSA emission occurs both at the transcriptional and post-translational levels, indicating that control at more than one level is necessary to guarantee the precise timing of volatile emission in flowers of S. floribunda.

Apocynaceae↗

Plasma protein binding interaction between valproic and salicylic acids in rhesus monkeys.

The effects of three levels of salicylic acid on the steady-state plasma concentrations of free and total valproic acid were examined in catheterized rhesus monkeys. Valproate was infused intravenously for a total of 41 hr, and salicylate was added after the first 8 hr. The three salicylate infusions were randomly assigned to each monkey. Valproate free fraction was determined by equilibrium dialysis. Statistically significant increases in valproate free fraction and total body clearance were observed after addition of salicylic acid. The increase in valproate clearance was positively correlated with the molar ratio of salicylate to valproate steady-state plasma concentrations. There was no significant change in valproate free concentration after salicylate treatment. The proposed mechanism of this in vivo interaction includes plasma protein binding displacement with no change in valproate intrinsic clearance.

Animals↗

[Water content of the skin following salicylic acid and urea treatment].

Water content of the epidermis was measured before and after a 3-h , 4-day, and 10-day treatment using 10% salicylic acid or 10% carbamide ointment. The measurement was performed using the Corneometer CM 420 from the firm "Schwarzhaupt Medizintechnik GmbH". Salicylic acid ointment was applied on one and carbamide ointment on the other back of the hand. Neither salicylic acid nor carbamide seem to influence significantly the water content of the healthy epidermis. In two patients with more severe hyperkeratosis carbamide increased the water content more than salicylic acid did.

Administration, Topical↗

Simultaneous quantitation of etoricoxib, salicylic acid, valdecoxib, ketoprofen, nimesulide and celecoxib in plasma by high-performance liquid chromatography with UV detection.

A specific, accurate, precise and reproducible high performance liquid chromatography (HPLC) method was developed and validated for the simultaneous quantitation of etoricoxib, salicylic acid, valdecoxib, ketoprofen, nimesulide and celecoxib in human plasma. The method employed a simple liquid-liquid extraction of etoricoxib, salicylic acid, valdecoxib, ketoprofen, nimesulide and celecoxib and internal standard (IS, DRF-4367) from human plasma (500 microL) into acetonitirile. The organic layer was separated and evaporated under a gentle stream of nitrogen at 40 degrees C. The residue was reconstituted in the mobile phase and injected onto a Kromasil KR 100-5C18 column (4.6 x 250 mm, 5 microm). The chromatographic separation was achieved by gradient elution consisting of 0.05 M formic acid (pH 3)-acetonitrile-methanol-water at a flow rate of 1.0 mL/min. The eluate was monitored using an ultraviolet (UV) detector set at 235 nm. The ratio of peak area of each analyte to IS was used for quantification of plasma samples. Nominal retention times of etoricoxib, salicylic acid, valdecoxib, ketoprofen, nimesulide, IS and celecoxib were 15.63, 17.20, 21.66, 24.95, 26.27, 30.24 and 32.22 min, respectively. The standard curve for etoricoxib, salicylic acid, valdecoxib, ketoprofen and celecoxib was linear (r2 > 0.999) in the concentration range 0.1-50 microg/mL and for nimesulide (r2 > 0.999) in the concentration range 0.5-50 microg/mL. Absolute recovery was >83% from human plasma for all the analytes and IS. The lower limit of quantification (LLOQ) of nimesulide was 0.5 microg/mL and for etoricoxib, salicylic acid, valdecoxib, ketoprofen and celecoxib the LLOQ was 0.1 microg/mL. The inter- and intra-day precisions in the measurement of QC samples, 0.1, 0.3, 15.0 and 40.0 microg/mL (for all analytes except nimesulide), were in the range 2.29-9.37% relative standard deviation (RSD) and 0.69-10.28% RSD, respectively. For nimesulide the inter- and intra-day precisions in the measurement of quality control (QC) samples, 0.5, 1.5, 15.0 and 40.0 microg/mL, were in the range 3.21-7.37% RSD and 0.97-7.06% RSD, respectively. Accuracy in the measurement of QC samples for all analytes was in the range 91.03-106.38% of the nominal values. All analytes including IS were stable in the battery of stability studies, viz. bench top, autosampler and freeze-thaw cycles. Stability of all analytes was established for 21 days at -20 degrees C. The application of the assay in an oral pharmacokinetic study in rats co-administered with celecoxib and valdecoxib is described.

Animals↗

Teratogenicity of aspirin and its metabolite, salicylic acid, in cultured rat embryos.

Rat embryos were exposed to aspirin or its metabolite, salicylic acid in culture. In these embryos acute reduction of heart beat was observed during 4 hours of administration compared to that in non-treated one. Protein contents and crown-rump length of cultured embryos were significantly decreased in aspirin-treated group, but were not so decreased in salicylic acid-treated one. The predominant defects of the embryos exposed to aspirin were edematous facial malformations and abnormality of tail. On the other hand, facial anomalies such as cleft lip and curly tail were observed in the embryos cultured with salicylic acid. Anomalies induced by aspirin were systemic, while salicylic acid induced localized malformations. These results might be due to the differences between aspirin and its metabolite, salicylic acid in their teratogenicity.

Abnormalities, Drug-Induced↗

[Determination of aspirin and free salicylic acid in lysinipirine injection by high performance liquid chromatography].

The contents of aspirin and free salicylic acid in lysinipirine injection were determined by high performance liquid chromatography (HPLC). A Hypersil BDS C18 column was used with the mobile phase of methanol-water-acetic acid (35:65:3, volume ratio) and the detection wavelength of 280 nm. The average recoveries of aspirin and salicylic acid added were 99.27% (RSD = 0.8%) and 99.61%(RSD = 1.3%), respectively. The calibration curves had good linearity in the range of 0.028 g/L -0.141 mg/L and 0.77 mg/L -3.85 mg/L, and the correlation coefficients were 0.9999 and 0.9998 for aspirin and salicylic acid respectively.

Anti-Inflammatory Agents, Non-Steroidal↗

High-pressure liquid chromatographic determination of salicylic acid in aspirin powder and pharmaceutical dosage forms.

A sensitive, simple, and rapid method for the quantitation of salicylic acid in aspirin powders and its dosage forms was developed. The method is based on reversed-phase high-pressure liquid chromatography using a mobile phase containing 20% methanol in aqueous phosphate buffer of pH 2.3. Other common ingredients present with aspirin such as acetaminophen, caffeine, codeine phosphate, phenacetin, and salicylamide do not interfere. Salicylic acid quantities as low as 0.1 microgram can be assayed with a relative standard deviation of +/- 2.3%. Sensitivity can be increased by using lower sensitivity settings. The method was tried on numerous commercial products and an old aspirin powder. The results generally were excellent, except that all of the aspirin and salicylic acid could not be extracted from suppositories. The old aspirin powder failed the USP limit test for salicylic acid. The powder apparently absorbed moisture and contained salicylamide as an impurity.

Aspirin↗

Determination of aspirin and salicylic acid in transdermal perfusates.

A high-performance liquid chromatographic (HPLC) method has been developed for the simultaneous determination of aspirin and salicylic acid in transdermal perfusates. The compounds were separated on a C8 Nucleosil column (5 microm, 250x4.6 mm) using a mobile phase containing a mixture of water-acetonitrile-orthophosphoric acid (650:350:2, v/v/v) and a flow-rate of 1 ml/min. The transdermal samples were in phosphate-buffered saline (PBS) and could be injected directly onto the HPLC system. The method was reproducible with inter-day R.S.D. values of no greater than 3.46 and 2.60% for aspirin and salicylic acid, respectively. The method was linear over the concentration range 0.2-5.0 microg/ml and had a limit of detection of 0.05 microg/ml for both compounds. For certain samples, it was necessary to ensure that no transmembrane leakage of the aspirin prodrugs had occurred. In these cases, a gradient was introduced by increasing the acetonitrile content of the mobile phase after the salicylic acid had eluted. The method has been applied to the determination of aspirin and salicylic acid in PBS following in vitro application of the compounds to mouse skin samples.

Animals↗

Targeted delivery of salicylic acid from acne treatment products into and through skin: role of solution and ingredient properties and relationships to irritation.

Salicylic acid (SA) is a beta hydroxy acid and has multifunctional uses in the treatment of various diseases in skin such as acne, psoriasis, and photoaging. One problem often cited as associated with salicylic acid is that it can be quite irritating at pH 3-4, where it exhibits the highest activity in the treatment of skin diseases. We have identified strategies to control the irritation potential of salicylic acid formulations and have focused on hydroalcoholic solutions used in acne wipes. One strategy is to control the penetration of SA into the skin. Penetration of the drug into various layers of skin, i.e., epidermis, dermis, and receptor fluid, was measured using a modified Franz in vitro diffusion method after various exposure times up to 24 hours. A polyurethane polymer (polyolprepolymer-15) was found to be an effective agent in controlling delivery of SA. In a dose-dependent fashion it targeted delivery of more SA to the epidermis as compared to penetration through the skin into the receptor fluid. It also reduced the rapid rate of permeation of a large dose of SA through the skin in the first few hours of exposure. A second strategy that proved successful was incorporation of known mild nonionic surfactants like isoceteth-20. These surfactants cleanse the skin, yet due to their inherent mildness (because of their reduced critical micelle concentration and monomer concentration), keep the barrier intact. Also, they reduce the rate of salicylic acid penetration, presumably through micellar entrapment (either in solution or on the skin surface after the alcohol evaporates). Cumulative irritation studies showed that targeting delivery of SA to the epidermis and reducing the rapid early rate of penetration of large amounts of drug through the skin resulted in a reduced irritation potential. In vivo irritation studies also showed that the surfactant system is the most important factor controlling irritancy. SA delivery is secondary, as formulations with less SA content reduced the rate of delivery to the receptor and yet were some of the most irritating formulations tested, presumably due to the action of the specific anionic surfactant on the barrier. Alcohol content also did not appreciably affect irritation and SA delivery; formulations with considerably lower alcohol content but containing anionic versus nonionic surfactant systems exhibited considerably higher irritancy. Thus the surfactant type was again the predominant factor in those studies, although arguably alcohol plays some role (solubilization of SA). Results showed that both polymers and mild surfactants work in concert to provide the optimal formulation benefits of targeted delivery and reduced irritation. Synergistic relationships among hydroalcoholic formulation components will be discussed along with the mechanisms likely involved in controlling delivery of SA to skin.

Acne Vulgaris↗

[Influence of exogenous salicylic acid on the level of phytohormones in tissues of Phlox paniculata and Phlox setacea leaves with special reference to resistance against the powdery mildew causative agent Erysiphe cichoracearum D.C. f. phlogis Jacz].

We studied the effects of exogenous salicylic acid on the level of endogenous cytokinins and abscisic and salicylic acids in the tissues of leaves of phloxes contrasting in resistance against the powdery mildew causative agent: susceptible Phlox paniculata L. and resistant Ph. setacea L. Studies were carried out under the conditions of biotic stress. The initial level of salicylic and abscisic acids and cytokinins is the highest in the resistant phlox species. After treatment with salicylic species, the total level of cytokinins and endogenous salicylic acid increased in both species. When the treated phlox species were infected by the powdery mildew causative agent, the level of abscisic and salicylic acids increased in the susceptible Ph. paniculata, while that of cytokinins increased in the resistant Ph. setacea. The role of salicylic acid in the induction of plant defense reactions against phytopathogens is discussed.

Abscisic Acid↗

[Special qualification of a photometric procedure for determination of salicylic acid in therapeutic drug monitoring].

A procedure for the determination of salicylic acid from human serum is presented. It is based on an acidic extraction, a basic reextraction and the detection of salicylic acid as its iron-III-complex by photometry. The procedure is quantitative over a wide range of linearity, easy to carry out and is especially suitable for therapeutic drug monitoring in the treatment of juvenile rheumatoid arthritis.

Arthritis, Juvenile↗

Pharmacokinetics and metabolic rates of acetyl salicylic acid and its metabolites in an Otomi ethnic group of Mexico.

The objective of this study was to determine pharmacokinetic differences of acetyl salicylic acid (ASA) and its metabolites: gentisic acid (GA), salicylic acid (SA) and salicyluric acid (SUA) between Otomies and Mesticians healthy subjects. Design. Ten Otomies and 10 Mesticians were included. After a single dose of aspirin given orally (15 mg/kg), blood and urine samples were collected at different times. Results. Pharmacokinetic parameters of salicylates showed significant differences, except distribution volume of SA, and elimination half-life of SUA. Metabolic rates of ASA showed significant differences for all rates between both groups. On the other hand, percentages of dose excreted were more reduced for SA and SUA for the Otomies than for the Mesticians. Conclusion. Results reflect differences in the hydrolysis way i.e. from ASA to SA and aromatic hydroxylation i.e. from SA to GA, which were slower in Otomies subjects, showing a possible pharmacokinetic differences about the capabilities of ASA biotransformation as a consequence of ethnic differences.

Adolescent↗

Interaction of salicylic acid with adenosine and adenosine triphosphate. Potential mechanism of intensifying acetylsalicylic acid-induced GI blood loss.

Complex formation between salicylic acid and adenosine or adenosine triphosphate in 0.2m phosphate buffer at pH=7 was investigated as a potential factor contributing to the prolongation of acetylsalicylic acid-induced GI blood loss. Spectrophotemetric techniques were used to evalute the complexation. Concerntration dependency of the absorbance decrease was measured at 27 and 37 degrees C. The addition of salicylic acid to either adenosine or adenosine triphosplate solutions appeared also to cause a decrease in surface tension which may play a role in reducing platelet aggregation induced by adenosine diphosphate. The results obtained seem to support the opinion that the mechansim of acetylsalicylic acid-induced GI blood loss is due to a combination of both local and systemic effect.

Adenosine↗