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Second-derivative synchronous fluorescence spectroscopy for the simultaneous determination of naproxen and salicylic acid in human serum.

Second-derivative synchronous fluorescence spectrometry was used to develop a simple, rapid and sensitive spectrofluorimetric method for the simultaneous determination of naproxen and salicylic acid in human serum. The method is based on the intrinsic fluorescence of naproxen and salicylic acid in chloroform-1% acetic acid solution. A delta gamma of 130 nm was used for the direct measurement of salicylic acid in the binary mixture, whereas naproxen was determined from direct measurements at delta gamma = 60 nm and by means of a correction equation which incorporates the concentration of salicylic acid. The range of application is 0-14 mg l-1 for naproxen and 0-13 mg l-1 for salicylic acid. The detection limits for naproxen and salicylic acid are 0.003 and 0.01 mg l-1, respectively. Serum samples are extracted into chloroform-1% acetic acid solution prior to instrumental measurement. Analytical recoveries range from 97 to 105% (mean 102%) for naproxen and from 97 to 112% (mean 103%) for salicylic acid. The within-run precision (RSD) for the method for four naproxen-salicylic acid mixtures varied from 1.2 to 6.7% and the day-to-day precision for mixtures varied from 2.1 to 5.0%.

Humans↗

Ortho-anisic acid as internal standard for the simultaneous quantitation of salicylic acid and its putative biosynthetic precursors in cucumber leaves.

Salicylic acid (SA) acts as an endogenous signal for the induction of systemic acquired resistance (SAR) in plants infected by pathogens. In order to study SA biosynthesis in plants, a quantitative method using an internal standard was developed for the simultaneous measurement of SA and three of its putative bioprecursors, namely trans-cinnamic acid (CA), trans-ortho-hydroxycinnamic acid (oHCA), and benzoic acid (BA). ortho-Anisic acid (oANI) was found to be a suitable internal standard for all four compounds. It was not present as endogenous compound in cucumber leaves, no substance interfered with its detection, and it followed identical losses as SA, CA, oHCA, and BA during the extraction procedure. Baseline separation of these four compounds and of eight other plant phenolics was achieved in 35 min using deactivated reversed-phase HPLC. On-line detection was performed fluorimetrically for SA, oANI, and oHCA (with the excitation and emission wavelengths optimized for each compound) and with uv detection for CA and BA. Correlation equations for SA, CA, oHCA, and BA using oANI as internal standard were linear for a broad range of concentrations. The limits of detection (in ng/g fresh weight, FW) obtained during routine analyses were as follows: SA, 4; oHCA, 100; CA, 150; and BA, 500. The method was used to quantify levels of free and acid-hydrolyzed bound SA in cucumber plants either 5 days postinoculation with Pseudomonas lachrymans or after mock-inoculation with water on their first leaf.(ABSTRACT TRUNCATED AT 250 WORDS)

Benzoates↗

Factors affecting the serum protein binding of salicylic acid in newborn infants and their mothers.

The protein binding of salicylic acid in serum of 49 full-term newborn infants and their mothers immediately after delivery was determined, and potential variables affecting the results obtained were examined. The free fraction of salicylic acid added in vitro at an initial drug concentration of 20 mg/100 ml ranged from 0.104 to 0.242 in the infants and from 0.180 to 0.406 in the mothers. The ratio of free fraction values, infant:mother, was 0.67 +/- 0.13 (mean +/- SD). The more extensive serum protein binding of salicylic acid in the newborns' serum explains why serum salicylate concentrations at the time of delivery are usually higher in newborn infants than in their mothers. A cascade of patient characteristics (induction of labor by oxytocin, serum albumin concentration, duration of labor, mother's age, type of anesthesia, use of analgesics, and nonalbumin protein concentration) explained 61% and 37% of the variability of the salicylic acid free fraction values in the serum of infants and their mothers, respectively.

Adolescent↗

Influencing of resorption and side-effects of salicylic acid by complexing with beta-cyclodextrin.

After oral administration of 14C-labelled salicylic acid and its beta-cyclodextrin complex to rats, the blood radioactivity-level increases in the first 2 h than decreases. The blood level obtained with the inclusion complex is somewhat but not significantly lower than with free acid. Since the resorption of cyclodextrin is a considerably slower process, it is very likely that the resorption of salicylic acid take place in the form of free acid after dissociation of the complex. The urinary excretion cumulative curves show that the free salicylic acid is completely excreted, while about 10% of the salicylic acid administered in the form of complex is lost. The cyclodextrin complex formation increases the pK value of all hydroxy-benzoic acids. Direct observations reveals that complex formation decreases the stomach-irritating effect of salicylic acid. The ratio of radioactivity was nearly the same in the organs of animals treated by both free salicylic and cyclodextrin complex.

Animals↗

The influence of gel formulation on the diffusion of salicylic acid in polyHEMA hydrogels.

The influence of solute concentration, gel hydration, and crosslinking density on diffusion rates in polyHEMA hydrogels has been investigated using a radio-tracer technique. At hydrations above 31% water, diffusion is by pore flow, and increases in the crosslinking density of gels bring about a decrease in the diffusion coefficient, D. Below 31% hydration, diffusion is predominantly by solution diffusion and changes in crosslinking density have little effect on the diffusion coefficient. The diffusion coefficient is invariant with solute concentration within the range reported, although a very high solute concentration, for the gels of lower hydration, the diffusion coefficient is higher than expected. A high value for D may be due to saturation of the binding sites of the diffusant on the polymer chains, leaving a greater proportion of diffusant available for transport.

Diffusion↗

[Effects of peeling agents (resorcinol, crystalline sulfur, salicylic acid) on the epidermis of guinea pig (author's transl)].

The mode of action of "classical peeling agents" such as resorcinol, crystalline sulfur, and salicylic acid on the epidermis is almost unknown. There are only a few experimental data available. Therefore the effects of resorcinol, crystalline sulfur, and salicylic acid were studied. A 1% and 3% concentration of these chemicals in vaselinum flavum or Unguentum Cordes was applied to the ears and flanks of adult male guinea pigs up to 14 days. Prior to biopsies at various time intervals, 3H-thymidine was injected intradermally. Specimens were paraffin embedded and routinely processed for autoradiographical analysis. The following parameters were assessed: Labelling index (L.I. in %); number of labelled basal cells per unit length of basement membrane; papillomatosis-index; and acanthosis-factor (projection histoplanimetry). The data were statistically analysed. The peeling agents induced a concentration-dependent increase of the L.I., acanthosis, and papillomatosis. Crystalline sulfur caused the most pronounced effect, followed by resorcinol. In contrast salicylic acid caused only a minute acanthosis factor and a slight increase in labelling. The correlation coefficient r of epidermal thickness to the L.I. for all concentrations and peeling agents used reaches the high figure of 0.978 for the ear. The 1% and 3% salicylic acid has a lower acanthosis factor than vaselinum flavum by itself. Preliminary autoradiographical studies in humans with 1% and 10% salicylic acid confirm these data. Salicylic acid counteracts acanthosis. These experiments show that crystalline sulfur and resorcinol have a potent effect on cell proliferation and acanthosis. They peel via proliferation hyperkeratosis. The mode of peeling by salicylic acid must be different, as cell proliferation and acanthosis are barely enhanced. The clinically known "keratolytic" effect of salicylic acid may be due to a direct action on the intercellular cement substance of the horny cells.

Animals↗

Salicylic acid modulates oxidative stress and glutathione peroxidase activity in the rat colon.

Oxidative stress is a characteristic of cancerous colon tissue and inflammatory bowel diseases that increase colon cancer risk. Epidemiological evidence supports a protective effect of plant-derived compounds. Aspirin is also protective against colon cancer. The mechanism of action is unclear although salicylic acid, the main metabolite of aspirin, has been shown to decrease the synthesis of pro-inflammatory and potentially neo-plastic prostaglandins. Salicylic acid is found in significant quantities in a plant-based diet. However, in plants salicylic acid is also reported to modulate the expression of numerous enzymes with antioxidant activity. The aim of this study was to assess whether salicylic acid can modulate pro-cancerous biological pathways in the colon. Oxidative stress, prostaglandins and cytosolic glutathione peroxidase (cyGPX) were analysed in proximal, transverse and distal colon from a rat model of diet-induced oxidative stress. Elevated plasma pyruvate kinase activity (1293+/-206 U/ml) and increased indices of lipid peroxidation in colon (proximal 6.4+/-0.84 nM MDA/mg protein; transverse 6.9+/-0.97 nM MDA/mg protein; distal 5.2+/-0.62 nM MDA/mg protein) from rats fed a Vitamin E deficient diet were significantly decreased on supplementation with salicylic acid (plasma pyruvate 546+/-43 U/ml; salicylic acid proximal 3.6+/-0.39 nM MDA/mg protein; transverse 4.5+/-0.61 nM MDA/mg protein; distal 4.4+/-0.27 nM MDA/mg protein). Reductions in oxidative stress and prostaglandin production on supplementation with salicylic acid were associated with an elevation in glutathione peroxidase activity (Vitamin E deficient proximal 0.056+/-0.013 U/mg protein; transverse 0.073+/-0.008 U/mg protein; distal 0.088+/-0.010 U/mg protein; Vitamin E deficient with salicylic acid proximal 0.17+/-0.01 U/mg protein; transverse 0.23+/-0.016 U/mg protein; distal 0.16+/-0.020 U/mg protein). Gpx1 and Gpx2 gene transcripts were not elevated in association with increased activity of the soluble glutathione peroxidase activity. Glutathione peroxidases are key antioxidant enzymes, catalysing the decomposition of potentially toxic lipid peroxides. Gpx activity and regulation of Gpx gene transcription has been shown previously to be complex with activity not necessarily mirrored by a corresponding elevation in gene transcription. By supplementing the diet of Vitamin E deficient rats with salicylic acid (1 g/kg diet), this study assessed effects of salicylic acid on cytosolic glutathione peroxidase activity in the colon. The ability of salicylic acid to modulate antioxidant enzymes in colon tissue may be an important mechanism in inhibiting colon cancer development.

Animals↗

Rapid direct determination of trace amounts of salicylic acid in deproteinized serum by means of high-pressure liquid--liquid chromatography.

A simple method for the quantitative analysis of salicylic acid in blood serum is described. A liquid--liquid chromatographic system, consisting of a long-chain aliphatic amine as the stationary phase and dilute aqueous perchloric acid as the mobile phase, enables the direct injection of deproteinized serum into the system. No change in the chromatographic properties of the system was noticed after 2000 injections of deproteinized serum. Quantitative analysis is possible using peak area or peak height measurements. The method has a high precision: relative standard deviations of 0.4% and 5% are found for samples containing 10 micrograms and 10 ng injected salicylic acid respectively. The detection limit is found to be about 1 ng slicylic acid, corresponding to 40 ppb salicylic acid in serum. Simultaneously administered drugs such as indomethacin, acetylsalicylic acid, caffeine and phenacetin, and metabolites of salicylic acid do not interfere with the analysis. The time course of the concentration of salicylic acid in serum is demonstrated after oral administration of 1 g sodium-salicylate. The phase system was also found to be suitable for the analysis of salicylic acid in urine.

Blood Proteins↗

[Topical use of salicylic acid esters in pharmacotherapy--pharmacologic principles].

The local application of 2-hydroxyethyl salicylic acid esters and ether salicylic acid esters offers the possibility of therapy with salicylic acid that avoids a systemic burden of the body. This justifies the unavoidable uptake of ethylene glycol. Under therapeutic conditions and following guidelines for the recommended amount and frequency of application, the amount of ethylene glycol taken into the organism appears to be without risk for the user.

Administration, Topical↗