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Tolerance and safety of superficial chemical peeling with salicylic acid in various facial dermatoses.

BACKGROUND: Chemical peeling is a skin-wounding procedure that may have some potentially undesirable side-effects. AIMS: The present study is directed towards safety concerns associated with superficial chemical peeling with salicylic acid in various facial dermatoses. METHODS: The study was a non-comparative and a prospective one. Two hundred and sixty-eight patients of either sex, aged between 10 to 60 years, undergoing superficial chemical peeling for various facial dermatoses (melasma, acne vulgaris, freckles, post-inflammatory scars/pigmentation, actinic keratoses, plane facial warts, etc.) were included in the study. Eight weekly peeling sessions were carried out in each patient. Tolerance to the procedure and any undesirable effects noted during these sessions were recorded. RESULTS: Almost all the patients tolerated the procedure well. Mild discomfort, burning, irritation and erythema were quite common but the incidence of major side-effects was very low and these too, were easily manageable. There was no significant difference in the incidence of side-effects between facial dermatoses (melasma, acne and other pigmentary disorders). CONCLUSION: Chemical peeling with salicylic acid is a well tolerated and safe treatment modality in many superficial facial dermatoses.

Adolescent↗

Expression of a WIPK-activated transcription factor results in increase of endogenous salicylic acid and pathogen resistance in tobacco plants.

NtWIF is a transcription factor activated upon phosphorylation by wound-induced protein kinase (WIPK) in tobacco plants. Transgenic tobacco plants overexpressing NtWIF exhibited constitutive accumulation of transcripts for pathogenesis-related genes, PR-1a and PR-2. Salicylic acid levels were 50-fold higher than those in wild-type plants. The levels of jasmonic acid and IAA did not significantly differ, while an increase of ABA upon wounding was delayed by 3 h in the transgenics. When challenged with tobacco mosaic virus, lesions developed faster and were smaller in the transgenic plants. The results suggest that NtWIF is likely to influence salicylic acid biosynthesis, being located downstream of WIPK.

Activating Transcription Factors↗

Nuclear magnetic resonance and thermal studies on the interaction between salicylic acid and model membranes.

DSC and (1H and 31P) NMR measurements are used to investigate the perturbation caused by the keratolytic drug, salicylic acid (SA) on the physicochemical properties of the model membranes. Model membranes (in unilamellar vesicular (ULV) form) in the present studies are prepared with the phospholipids, dipalmitoyl phosphatidylcholine (DPPC), dipalmitoyl phosphatidylethanolamine (DPPE), dipalmitoyl phosphatidic acid (DPPA) and mixed lipid DPPC-DPPE (with weight ratio, 2.5:2.2). These lipids have the same acyl (dipalmitoyl) chains but differed in the headgroup. The molar ratio of the drug to lipid (lipid mixture), is in the range 0 to 0.4. The DSC and NMR results suggest that the lipid head groups have a pivotal role in controlling (i) the behavior of the membranes and (ii) their interactions with SA. In the presence of SA, the main phase transition temperature of (a) DPPE membrane decreases, (b) DPPA membrane increases and (c) DPPC and DPPC-DPPE membranes are not significantly changed. The drug increases the transition enthalpy (i.e., acyl chain order) in DPPC, DPPA and DPPC-DPPE membranes. However, the presence of the drug in DPPC membrane formed using water (instead of buffer), shows a decrease in the transition temperature and enthalpy. In all the systems studied, the drug molecules seem to be located in the interfacial region neighboring the glycerol backbone or polar headgroup. However, in DPPC-water system, the drug seems to penetrate the acyl chain region also.

1,2-Dipalmitoylphosphatidylcholine↗

Treatment of verruca plantaris with a combination of topical fluorouracil and salicylic acid.

A medical record review was conducted to determine the clinical outcome and average time to resolution of verruca plantaris in 20 patients treated with twice-daily applications of either 0.5% or 5.0% topical fluorouracil combined with topical 17% and 40% salicylic acid. Seven patients used 0.5% fluorouracil, and 13 used 5.0% fluorouracil. All of the lesions were sharply debrided at regular 1- or 2-week intervals. All 20 patients achieved full clinical resolution in a mean +/- SD of 82.5 +/- 56.6 days. Three patients (15%) had recurrent lesions, which subsequently resolved with repeated treatment. Two patients (10%) developed local dermatitis, which resolved with temporary discontinuation of the medication and the addition of a topical corticosteroid. It was observed that the twice-daily application of topical fluorouracil and salicylic acid is a safe and effective treatment for verruca plantaris.

Administration, Cutaneous↗

[Trypsin inhibitors of wheat seedlings infected and treated with salicylic acid].

Using the method of affinity chromatography for trypsin-sepharose, followed by PAGE electrophoresis the component composition of trypsin inhibitors was studied. The inhibitors were extracted from the winter wheat seedlings which were infected with Fusarium fungus and also from the seedlings treated with salicylic acid. Under the action of pathogen not only a quantitative increase in the protein components of trypsin inhibitor but also the appearance of a new component with a molecular weight of 29 kDa are observed. The influence of Fusarium graminearum and salicylic acid on the amino acid composition of trypsin inhibitors has been studied. After the inhibitors purification their antienzyme spectrum was studied along with their influence on the pathogen proteases. It was established that the inhibitors influence only the activity of trypsin and chymotrypsin and do not influence the activity of pepsin, elastases, papain, proteinases from the wheat seedlings. The existence of arginine and absence of lysine was demonstrated in the active centre of the inhibitors.

Chromatography, Affinity↗

Synthesis and characterization of acrylic type hydrogels containing azo derivatives of 5-amino salicylic acid for colon-specific drug delivery.

pH-sensitive hydrogels are suitable candidates for oral delivery of therapeutic peptides, proteins and drugs, due to their ability to respond to environmental pH changes. Terephthalic acid was covalently linked with 2-hydroxyethyl methacrylate (HEMA), abbreviated as cross-linking agent (CA). Acryloyl ester of 5-[4-(hydroxy phenyl) azo] salicylic acid (HPAS) as an azo derivative of 5-amino salicylic acid (5-ASA) was prepared under mild conditions. The HPAS was covalently linked with acryloyl chloride, abbreviated as APAS. Free radical cross-linking copolymerization of polymerizable azo derivative of 5-ASA (APAS) and methacrylic acid (MAA) in two different molar ratios, with the various ratios CA as cross-linking agent were carried out with using 2, 2'-azobisisobutyronitrile (AIBN) as initiator at the temperature range 60-70 degrees C. The composition of the cross-linked three-dimensional polymers was determined by FTIR spectroscopy. Glass transition temperature (Tg) of the network polymers was determined calorimetrically. The hydrolysis of drug-polymer conjugates was carried out in cellophane membrane dialysis bags containing aqueous buffer solutions (pH 7.4 and pH 1) at 37 degrees C. The effect of copolymer composition on the hydrolytic degradation was studied in simulated gastric fluid (SGF, pH 1) and simulated intestinal fluid (SIF, pH 7.4) at 37 degrees C. Monitoring of the hydrolysis process by HPLC and UV spectroscopy shows that the azo prodrug (HPAS) was released by hydrolysis of the ester bond located between the HPAS and the polymer chain. The drug-release profiles indicate that amount drug release dependent on the content of MAA groups and crosslinking.

Azo Compounds↗

A randomised, single-blind, single-centre clinical trial to evaluate comparative clinical efficacy of shampoos containing ciclopirox olamine (1.5%) and salicylic acid (3%), or ketoconazole (2%, Nizoral) for the treatment of dandruff/seborrhoeic dermatitis.

BACKGROUND: The association between seborrhoeic dermatitis and dandruff and the yeast Malassezia furfur is well recognized. Symptoms include scalp itchiness and scaling. Due to its antimycotic activity, ciclopirox olamine is established as an effective treatment for these scalp conditions. Salicylic acid has keratolytic properties and aids in the removal of scales. OBJECTIVE: To compare the therapeutic efficacy of a shampoo containing 1.5% ciclopirox olamine and 3% salicylic acid (CPO/SA) with Nizoral (2.0% ketoconazole shampoo) in a study involving 154 subjects with dandruff - 70 of whom also had seborrhoeic dermatitis of the scalp. Nizoral is currently a registered treatment for dandruff and seborrhoeic dermatitis. METHODS: The shampoos were used three times week for 4 weeks, with 2-week washout and follow-up periods. Clinical and self-assessments were made throughout treatment and after follow-up (day 43). Within and between-treatment assessments of signs and symptoms were analysed. RESULTS: In the two groups, seborrhoeic dermatitis and dandruff improved significantly throughout treatment, with lower clinical and self-assessment scores at both the end of treatment (day 29) and follow-up (day 43). Only the subjects treated with CPO/SA shampoo showed a significant reduction in the itching of seborrhoeic dermatitis at these times. CONCLUSION: The study demonstrated that both CPO/SA and Nizoral were safe and effective in the treatment of dandruff and seborrhoeic dermatitis.

Administration, Cutaneous↗

Salicylic Acid in Rice (Biosynthesis, Conjugation, and Possible Role).

Salicylic acid (SA) is a natural inducer of disease resistance in some dicotyledonous plants. Rice seedlings (Oryza sativa L.) had the highest levels of SA among all plants tested for SA content (between 0.01 and 37.19 [mu]g/g fresh weight). The second leaf of rice seedlings had slightly lower SA levels than any younger leaves. To investigate the role of SA in rice disease resistance, we examined the levels of SA in rice (cv M-201) after inoculation with bacterial and fungal pathogens. SA levels did not increase after inoculation with either the avirulent pathogen Pseudomonas syringae D20 or with the rice pathogens Magnaporthe grisea, the causal agent of rice blast, and Rhizoctonia solani, the causal agent of sheath blight. However, leaf SA levels in 28 rice varieties showed a correlation with generalized blast resistance, indicating that SA may play a role as a constitutive defense compound. Biosynthesis and metabolism of SA in rice was studied and compared to that of tobacco. Rice shoots converted [14C]cinnamic acid to SA and the lignin precursors p-coumaric and ferulic acids, whereas [14C]benzoic acid was readily converted to SA. The data suggest that in rice, as in tobacco, SA is synthesized from cinnamic acid via benzoic acid. In rice shoots, SA is largely present as a free acid; however, exogenously supplied SA was converted to [beta]-O-D-glucosylSA by an SA-inducible glucosyltransferase (SA-GTase). A 7-fold induction of SA-GTase activity was observed after 6 h of feeding 1 mM SA. Both rice roots and shoots showed similar patterns of SA-GTase induction by SA, with maximal induction after feeding with 1 mM SA.

Journal Article↗

[Salicylic acid poisoning].

The study analyses the role of salicylic acid (SA) in fatal intoxications with special reference to potentially avoidable, accidental poisonings. The study indicates a relation between SA intoxication and the presence of an infection of the respiratory tract. All deaths in Denmark in the period 1980 through 1989 registered as caused by SA were analysed as were all deaths submitted to forensic toxicological examination in a defined region of Denmark in the years 1985 through 1989. During the decade 1980 through 1989 the number of fatal intoxications due to SA increased from approx. five per year to approx. 23 per year. During the same period the sales of SA decreased. Many deaths in the material were registered as accidental, and an increasing frequency of accidental deaths was seen with a lower social level. Frequently, an infection of the respiratory tract was either indicated in a hospital case record or a police report, or found at autopsy.

Adult↗

Carbohydrate-deficient glycoprotein syndrome-associated pericardial effusion treated with corticosteroids and salicylic acid.

We describe an infant with a persistent pericardial effusion who was diagnosed with carbohydrate-deficient glycoprotein syndrome (CDGS)-Ia. She was born with mild dysmorphic features and common cardiac abnormalities. However, she re-presented at 2.5 months of age with a pericardial effusion. We decided to embark on a therapeutic trial of corticosteroids and salicylic acid therapy in an attempt to avoid pericardectomy. After 3 weeks of medical treatment the effusion resolved. This experience allows us to propose that medical management with corticosteroids and salicylic acid can be considered as an alternative to surgical therapy for CDGS-I patients with persistent pericardial effusions.

Adrenal Cortex Hormones↗

Adverse reactions to sulphasalazine and 5-amino salicylic acid in the same patient.

We report a patient who developed sulphasalazine-related hepatitis with a subsequent adverse reaction to rectal 5-amino salicylic acid, in the form of pain and fever without associated liver dysfunction, suggesting reactions to both components of sulphasalazine. Included is a review of the literature. Caution should be observed when prescribing 5-amino salicylic acid to sulphasalazine-intolerant patients.

Adult↗

Determination of free radical reaction products and metabolites of salicylic acid using capillary electrophoresis and micellar electrokinetic chromatography.

Hydroxylated radical products of salicylic acid are often used as a relative measurement in free radical research. Several analytical methods exist to determine the amount of 2,3-dihydroxybenzoic acid and 2,5-dihydroxybenzoic acid. In this study we use capillary zone electrophoresis (CZE) and micellar electrokinetic capillary chromatography (MECC) in order to determine these free radical products. The CZE experiment was optimized with a CZE simulation program HPCESIM in order to achieve an optimal pH. Calibration curves were recorded in the range 10(-6)-10(-4) M and the detection limit was determined. For both CZE and MECC it was 2x10(-7) M. Both methods resulted in a reproducible analysis of salicylate and its hydroxylated free radical products in 6 min.

Chromatography, Micellar Electrokinetic Capillary↗

Toxicity of acetaminophen, salicylic acid, and caffeine for first-passage rat renal inner medullary collecting duct cells.

Chronic excess ingestion of nonsteroid anti-inflammatory drugs causes renal medullary necrosis. Previously, using an immortalized line of mouse inner medullary collecting ducts cells (mIMCD3), we found that acetaminophen, salicylic acid, and caffeine are toxic, and the effects of acetaminophen and caffeine are strongly additive. Furthermore, toxicity was greater in proliferating than in nonproliferating cells. Important limitations were that mIMCD3 cells do not readily tolerate the high concentrations of salt and urea normally present in renal inner medullas and proliferate much more rapidly than inner medullary cells in vivo. Thus, these cells may not serve as an appropriate model for the in vivo IMCD. The present studies address these limitations by using passage-1 rat inner medullary collecting duct (p1rIMCD) cells, which tolerate high salt and urea and become contact inhibited when confluent. At 640 mOsmol/kg (the lowest normal inner medullary osmolality), the drugs, singly and in combination, reduce the number of proliferating (i.e., subconfluent) p1rIMCD cells more than they do confluent cells. Effects of acetaminophen and caffeine are strongly additive. Addition of as little as 0.1 mM caffeine significantly enhances the toxicity of acetaminophen plus salicylic acid. With confluent cells at 640 mOsmol/kg and very slowly growing cells at 1370 mOsmol/kg, combinations of drugs that include acetaminophen increase proliferation, accompanied by DNA damage and apoptosis. We conclude that these drugs are toxic to renal inner medullary collecting duct cells under the conditions of high osmolality normally present in the inner medulla, that combinations of the drugs are more toxic than are the drugs individually, and that the toxicity includes induction of proliferation of these cells that are otherwise quiescent in the presence of high osmolality.

Acetaminophen↗

Hydrogen peroxide does not function downstream of salicylic acid in the induction of PR protein expression.

The roles of salicylic acid (SA) and H2O2 in the induction of PR proteins in tobacco have been examined. Studies were conducted on wild-type tobacco and plants engineered to express a bacterial salicylate hydroxylase capable of metabolizing SA to catechol (SH-L plants). Wild-type and PR-1a-GUS-transformed plants express PR-1a following challenge with Pseudomonas syringae pathovar syringae, SA or 2,6-dichloro-isonicotinic acid (INA). In contrast, SH-L plants failed to respond to SA but did express PR-1a following INA treatment. H2O2 and the irreversible catalase inhibitor 3-amino-1,2,4-triazole (3-AT) were found to be weak inducers of PR-1a expression (relative to SA) in wild-type tobacco but were unable to induce PR-1a in SH-L plants, suggesting that the action of these compounds depends upon the accumulation of SA. A model has been proposed suggesting that SA binds to and inhibits a catalase inducing an increase in H2O2 leading to PR protein expression. Catalase activity has been measured in tobacco and no significant changes in activity following infection with P. syringae pv. syringae were detected. Furthermore, inhibition of catalase activity in vitro in plant extracts requires pre-incubation and only occurs at SA concentrations above 250 microM. Leaf disks preincubated with 1 mM SA do accumulate SA to these levels and PR-1a is efficiently induced but there is no apparent inhibition of catalase activity. It is also shown that a SA-responsive gene, PR-1a, and a H2O2-sensitive gene, AoPR-1, are both relatively insensitive to 3-AT suggesting that induction of these genes is unlikely to be due entirely to inhibition of an endogenous catalase.

Amitrole↗

Pretreatment with salicylic acid primes parsley cells for enhanced ion transport following elicitation.

Pretreatment with salicylic acid (SA), an inducer of plant disease resistance, enhanced the capacity of parsley cells for the induction of a rapid K(+)/pH response and the subsequent coumarin (phytoalexin) secretion. In SA-primed cells, a low elicitor dose induced these two responses to a similar extent as did a high elicitor dose in non-primed cells. These observations suggest that the SA-mediated augmentation of the early K(+)/pH response may contribute to the enhancement of subsequent coumarin secretion. As the amphotericin B-induced K(+)/pH response was not enhanced in SA-primed cells, it is concluded that signaling components that are improved by priming are located between elicitor signal perception and the plasma membrane transporters mediating the K(+)/pH response.

Amphotericin B↗

Use of a molecular form technique for the penetration of supersaturated solutions of salicylic acid across silicone membranes and human skin in vitro.

Permeation enhancement of salicylic acid (SA) from supersaturated solutions formed using a 'molecular form' technique was investigated. In a conventional cosolvent technique, two solvents are used, one in which the drug is considerably more soluble than the other. Propylene glycol and water have been predominantly used as cosolvents to create supersaturation in skin permeation enhancement. In this paper, we report the use of buffer solutions with different pHs as media for producing different molecular forms. Supersaturated solutions were prepared using pH 8:pH 2 (80:20 v/v), which gave a nominal pH when mixed of around 5. Model silicone membranes and human skin were used. Hydroxypropyl methyl cellulose (HPMC) was employed to stabilise the supersaturated states. Stability data showed that while the SA supersaturated solutions without HPMC crystallised between 15 min and 46 h depending on the degree of supersaturation, the solutions with HPMC were stable for more than 2 months. The flux of SA increased with the degree of saturation for solutions prepared in a 80:20 buffer pH 8/buffer pH 2 mixture. Although the fluxes of SA with and without HPMC were similar both through silicone membrane and human skin, HPMC was found to be effective in increasing the stability of supersaturated solutions of SA.

Algorithms↗

Harpin modulates the accumulation of salicylic acid by Arabidopsis cells via apoplastic alkalization.

It is reported here that salicylic acid (SA) is rapidly taken up by Arabidopsis cells, and its uptake is accompanied by media alkalization and cytosolic acidification, and it is inhibited by the ionophore nigericin, suggesting that its import is linked with that of H+ and driven by a proton gradient. Such import and accumulation declined sharply within a narrow physiological pH range (pH 5.7-6.1), corresponding to a reduction in the [H+] of the media from 1.99 micromol l(-1) to 0.79 micromol l(-1). Following the initial uptake, SA was exported back into the media as free SA against a continued [H+]-dependent import. Since the uptake and accumulation of SA declines sharply within a narrow pH range and cell wall alkalization is an early response during incompatible plant/pathogen interactions, the bacterial elicitor harpin(Pss) was used to investigate how SA transport may be modulated during defence responses. Harpin induced a rapid and sustained alkalization of the cell suspension media, reaching the critical pH (pH 5.9-6.1) at which SA import is inhibited at c. 60 min. Such media alkalization corresponded with a reduction in the SA associated with cells co-treated with harpin, and an inhibition of SA uptake in cells pretreated with harpin. Scavengers of ROS, or compounds which generate H2O2 or NO had little effect on the import or net export of SA, suggesting that media alkalization induced by harpin is sufficient to modulate the kinetics of SA transport.

Alkalies↗

Salicylic acid activates sigma factor B by rsbU-dependent and -independent mechanisms.

Salicylic acid (SAL) may impact Staphylococcus aureus virulence by activating the sigB operon (rsbU-V-W-sigB), thus leading to reductions in alpha-toxin production and decreased fibronectin binding (L. I. Kupferwasser et al., J. Clin. Investig. 112:222-233, 2003). As these prior studies were performed in strain RN6390 (an rsbU mutant) and its rsbU-repaired variant, SH1000, the current investigation was designed to determine if the SAL effect occurs via rsbU- and/or rsbV-dependent pathways in an rsbU-intact S. aureus strain (FDA486). We thus quantified the transcription from two sigB-dependent promoters (asp23 and sarA P3) in FDA486 in response to SAL exposure in vitro, using isogenic single-knockout constructs of rsbU, rsbV, or rsbW and a green fluorescent protein reporter system. SAL induced sarA P3 and asp23 promoter activities in a dose-dependent manner in the parental strain. In contrast, sigB activation by SAL was progressively more mitigated in the rsbU and rsbV mutants. As predicted, SAL caused significant reductions in both alpha-toxin production and fibrinogen and fibronectin binding in the parental strain. The extent of these reductions, compared with the parent, was reduced in the rsb mutants (rsbV > rsbU), especially at low SAL concentrations. Since generation of the free SigB protein usually requires a sequential rsbU-V-W-sigB activation cascade, the present phenotypic and genotypic data suggest key roles for both rsbU and rsbV in SAL-mediated activation of sigB in strains with a fully intact sigB operon.

Bacterial Proteins↗