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Antibodies against lysophosphatidylcholine and oxidized LDL in patients with SLE.

Lysophosphatidylcholine (LPC) is present in oxidized low density lipoprotein (oxLDL), which is implicated in atherosclerosis. Antibodies to cardiolipin (aCL) and oxLDL (aoxLDL) have been shown to crossreact. LPC is formed by hydrolysis of phosphatidylcholine (PC) in LDL and cell membranes, induced by phospholipase A2 or by oxidation. We here demonstrate the presence of enhanced antibody levels to LPC in 184 patients with SLE as compared to 85 healthy, age-matched controls. The antibody reactivity to LPC was not specifically related to oxidation of the fatty acid moiety in LPC, since LPC containing only the saturated fatty acid palmitic acid showed equivalent antibody levels as LPC containing unsaturated fatty acids. aPC were significantly lower as compared to aLPC, indicating that hydrolysis of PC at the sn-2 position increases the antigenic potential of the molecule. Beta-glycoprotein 1 was a cofactor for aCL, but not for aoxLDL or aLPC, and the antigenicity of these compounds is therefore not directly related to beta2GP1. There was a close correlation between aoxLDL, aCL and aLPC and both LPC and oxLDL competitively inhibited aCL-binding to CL. LPC, oxLDL and CL thus display a common antigenic site, which could be formed by removal of a fatty acid at the sn-2 position, possibly due to the activity to phospholipase A2 and/or oxidation. This study indicates the potential role of LDL-oxidation and phospholipase A2 in SLE.

Adult↗

Apoptosis inducing activity of viscin, a lipophilic extract from Viscum album L.

Detection of antiproliferative activity and bioactivity-guided fractionation of viscin, a lipophilic extract from Viscum album L., led to the isolation of betulinic acid, oleanolic acid and ursolic acid as active components. Viscin, betulinic acid, oleanolic acid and ursolic acid inhibited growth and induced apoptotic cell death in Molt4, K562 and U937 leukaemia cells. The growth inhibitory effect of viscin was more pronounced in Molt4 and U937 cells (IC50 (concentration that inhibited cell proliferation by 50%): 118 +/- 24 and 138 +/- 24 microg mL(-1)) than in K562 cells (IC50: 252 +/- 37 microg mL(-1)). Oleanolic acid was the least effective in all cell lines (7.5-45.5% inhibition at 10 microg mL(-1)) and ursolic acid the most active in Molt4 and U937 cells (81.8 and 97.8% inhibition, respectively, at 5 microg mL(-1)). A dose-dependent loss of membrane phospholipid asymmetry associated with apoptosis was induced in all cell lines as shown in flow cytometry by the externalization of phosphatidylserine and morphological changes in cell size and granularity. There were differences in individual cell lines' response towards the apoptosis-inducing effect of viscin, betulinic acid, oleanolic acid and ursolic acid. The triterpenoids beta-amyrin, beta-amyrinacetate, lupeol, lupeolacetate, beta-sitosterol and stigmasterol, and the fatty acids oleic acid, linoleic acid, palmitic acid and stearic acid were also present in the lipophilic extract.

Antineoplastic Agents, Phytogenic↗

Production of gamma-lactones by the brown-rot basidiomycete Piptoporus soloniensis.

A wild strain of brown-rot basidiomycete Piptoporus soloniensis produced a sweet flavor similar to tropical fruits in liquid cultures. The major and minor compounds were identified to be gamma-decalactone and gamma-octanolactone by gas chromatography-mass spectrometry analysis, respectively. The growth and production of gamma-decalactone by P. soloniensis in broth to which fatty acids had been added were investigated. The addition of 12-hydroxystearic acid and ricinoleic acid to the culture markedly enhanced the production of gamma-decalactone. On the other hand, addition of myristic acid, palmitic acid, stearic acid and oleic acid to the culture resulted in a higher production of gamma-octanolactone. The addition of hexanoic acid, octanoic acid, decanoic acid, lauric acid, linoleic acid and linolenic acid to the culture reduced the growth of P. soloniensis and production of gamma-decalactone and gamma-octanolactone. This strain accumulated oxalic acid in liquid culture and grew sufficiently under strongly acidic conditions.

Journal Article↗

Effects of fatty acids on growth and poly-3-hydroxybutyrate production in bacteria.

The effects of saturated and unsaturated fatty acids (lauric acid, palmitic acid, steric acid, oleic acid, linoleic acid, soybean oil) on Sphaerotilus natans, 0B17 (Pseudomonas sp.), and recombinant Escherichia coli DH5(/pUC19/CAB were studied. Oleic acid enhances Poly-3-hydroxybutyrate (PHB) production in these three bacterial strains, suggesting that the single double bond of the acid activates the polyhydroxylkanoate accumulation enzymatic reaction. Under the effect of lauric acid and linoleic acid, the growth of S. natans and 0B17 were totally inhibited. However, the enhanced PHB accumulation in recombinant E. coli was observed.

Bioreactors↗

Lipid analysis of immature pig oocytes.

The detailed analysis of the lipid composition of immature pig oocytes represents the first such study carried out on mammalian eggs. In order to undertake a large scale lipid analysis using conventional extraction and chromatographic techniques a procedure for mass harvesting relatively large numbers of pig oocytes (200-300 oocytes/ovary) was developed. The study revealed that triacylglycerol was the major lipid component (100.71 nmol/mg protein) followed by cholesterol (32.71 nmol/mg protein). Phosphatidylcholine constituted the major phospholipid component (27.83 nmol/mg protein). Pig oocytes contained relatively low proportions of phosphatidylethanolamine (16.41% total phospholipid) and relatively high proportions of lysophosphatidylcholine (4.68% total phospholipid). The free fatty acid pattern was strikingly similar to the fatty acid composition of phosphatidylcholine. This observation, in conjunction with the observed high levels of lysophosphatidylcholine and the low ratio of phosphatidylethanolamine to phosphatidylcholine, suggests a fast rate of phospholipid turnover in the immature pig oocyte. Analysis of fatty acids esterified to the individual phospholipids and neutral lipids has shown that in all the classes examined, particularly in the neutral lipid fractions, there are high levels of the saturated fatty acid palmitic acid (16:0) and the monounsaturated fatty acid oleic acid (18:1). Triacylglycerol, free fatty acids and most of the phospholipids, particularly phosphatidylethanolamine, are considerably enriched in n-6 polyunsaturated fatty acids, specifically linoleic (18:2), arachidonic (20:4) and adrenic (22:4) acids. This may indicate an ability of oocytes to synthesize prostaglandins and leukotrienes. The results show that the lipid environment of the immature pig oocyte may be adapted to the highly specialized requirements of the cell, promoting growth and development with a potential role in the regulation of maturation.

Animals↗

Deterioration of goat spermatozoa in skimmed milk-based extenders as a result of oleic acid released by the bulbourethral lipase BUSgp60.

The aim of the present study was to elucidate the mode of action of goat bulbourethral lipase (BUSgp60 lipase) previously identified as responsible for the deterioration of goat sperm viability in skimmed milk-based extenders. Milk fractions were purified by micro- and ultrafiltration and characterized by SDS-PAGE, thin layer chromatography, triglyceride quantitative analysis and by their ability to potentiate the lipase and the sperm-deteriorating activity of the bulbourethral lipase. Components in both the phosphocaseinate and soluble whey protein fractions enhanced the lipase activity of BUSgp60 but only the phosphocaseinate fraction, which contains triglycerides, promoted deterioration of spermatozoa in the presence of bulbourethral gland secretion. These data suggest that the sperm-deteriorating effect of bulbourethral gland secretion is due to the catalysis of triglyceride hydrolysis, and that proteins increase this activity. BUSgp60 hydrolysed milk triglycerides and triolein very effectively, and its lipase activity was enhanced by several highly purified milk proteins. The major cis-unsaturated fatty acid from milk (oleic acid) but not the major saturated fatty acid (palmitic acid) exhibited dose-dependent detrimental effects on goat spermatozoa. Therefore, the catalysis of oleic acid formation from residual milk triglycerides by BUSgp60 appears responsible for the deterioration of goat spermatozoa when unwashed semen is diluted in skimmed milk-based extenders. The precise mechanism of action of oleic acid remains to be elucidated but the drawbacks of washing buck semen might be avoided by inhibiting BUSgp60 or by depriving it of substrate.

Analysis of Variance↗

Thermogenesis and fatty acid composition of brown adipose tissue in rats rendered hyperthyroid and hypothyroid-with special reference to docosahexaenoic acid.

The effects of hyperthyroidism and hypothyroidism on brown adipose tissue (BAT) thermogenesis and phospholipid fatty acid composition were investigated in rats. Chronic triiodothyronine (T3) treatment (hyperthyroidism) increased the interscapular BAT pad weight, its triacylglycerol content, and its DNA content. It did not affect basal and noradrenaline-stimulated in vitro oxygen consumption of BAT expressed per microg DNA, although it significantly increased the oxygen consumption of the whole BAT pad. T3 treatment had little effect on phospholipid content and phospholipid fatty acid composition. In contrast, chronic methimazole treatment (hypothyroidism) decreased the BAT pad weight and the triacylglycerol content, but did not significantly change the DNA content in comparison with the control. It significantly decreased the noradrenaline-stimulated BAT oxygen consumption expressed per microg DNA and per BAT pad, but did not change the basal oxygen consumption. Methimazole treatment significantly affected phospholipid content and phospholipid fatty acid composition. Among the major fatty acids of BAT, it decreased docosahexaenoic acid (DHA), arachidonic acid, palmitic acid, palmitoleic acid, and oleic acid, and it increased linoleic acid, stearic acid, and eicosapentaenoic acid. A regression analysis revealed a positive relationship between in vitro respiration and DHA levels in phospholipids (r = 0.404, p<0.05). These results suggest that thyroid hormones have trophic action on BAT and are necessary for BAT thermogenic activity. This study also suggests that DHA is involved in the regulation of BAT thermogenic activity, as we previously indicated.

Adipose Tissue, Brown↗

The influence of temperature, phylogeny, and lung structure on the lipid composition of reptilian pulmonary surfactant.

The lungs of all air-breathing vertebrates contain a form of pulmonary surfactant that lines the alveolar air-water interface where it modifies the interfacial surface tension. These pulmonary surfactants all consist of varying amounts of phospholipids (saturated and unsaturated) and cholesterol. The extent of variation between vertebrate groups and between species within a vertebrate group has been attributed to differences in factors such as phylogeny, body temperature, habitat, and lung structure. The influence of these factors on amphibian surfactant composition and function has been studied, but the reptiles, which comprise a polyphyletic group of vertebrates, have never been critically examined. The surfactant lipid composition from species belonging to the three groups of reptiles, the Archosauria (crocodiles), Lepidosauria (snakes and lizards), and Anapsida (turtles), has been determined. New data is presented in conjunction with already published data to create an evolutionary framework that concentrates particularly on the influence of phylogeny, body temperature, and lung structure on the composition of the surfactant lipids. Large amounts of pulmonary surfactant were found in all species of reptiles. All species lavaged at 23 degrees C (except C. atrox) demonstrated DSP/PL ratios of 23-33%. Animals with multicameral lungs exhibited an elevated CHOL/DSP ratio compared with species with unicameral lungs. In all groups, phosphatidylcholine (PC) was the dominant (60-80%) phospholipid. Phosphatidylserine and phosphatidylinositol (PS/PI) and sphingomyelin (S) represented the other phospholipids, while phosphatidylglycerol (PG), lysophosphatidylcholine (LPC), and phosphatidylethanolamine (PE) were occasionally observed. In two species of lizards (C. nuchalis and P. vitticeps), the saturated fatty acid, palmitic acid (16:0), was the dominant tail group on the phospholipids. Oleic acid (18:1) was the dominant monounsaturated fatty acid, whereas polyunsaturates comprised about a fifth of the total fatty acid profile. Short-term (4 h) changes in temperature did not affect the relative proportions of the fatty acids in either species. Comparison of the current data with previously published literature suggests that phylogeny and habitat do not significantly influence surfactant lipid composition, but body temperature and to a lesser extent lung structure are important determinants of reptilian surfactant lipid composition.

Alligators and Crocodiles↗

Effect of cod-liver oil extract on the buccal permeation of ergotamine tartrate.

Ergotamine tartrate (ET) is used clinically in the treatment of migraines. However, the bioavailability of ET is rather poor following oral administration. Therefore, we tried to improve ET delivery using buccal administration. The purpose of this study was to investigate the characteristics of the permeation of ET through the hamster cheek pouch in vitro using a two-chamber diffusion cell, and to evaluate the effect of permeation enhancers on the transbuccal delivery of ET. Cod-liver oil extract (CLOE), polyoxyethylene hydrogenated castor oil (HCO 60), sodium glycocholate (GC), and sodium caprate (CA) were selected as premeation enhancers considering their low irritancy of the mucosa. When the enhancers were added to the donor cell at a 5% concentration each, the ET permeation rate markedly increased compared with that in a control not containing enhancer. Among these enhancers, CLOE exhibited the greatest effect. Because CLOE is composed of 16 kinds of fatty acids, the enhancement action of each of the major components was separately determined. As major fatty acids, palmitic acid, oleic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) were selected and their enhancing effects were studied. The enhancing effect of each fatty acid was significantly lower than that of CLOE.

Animals↗

The relationship between lipid composition of red blood cells and their susceptibility to lipid peroxidation.

Red blood cells from 31 healthy donors were examined for the cholesterol content, the fatty acid composition, and the susceptibility to lipid peroxidation induced by either hydrogen peroxide or phenylhydrazine. Lipid peroxidation was monitored by the release of pentane and ethane. In addition, plasma fatty acids were measured in order to find out, whether plasma and red cell fatty acids were correlated. In experiments with hydrogen peroxide, a significant positive correlation was found between the proportion of arachidonic acid (C 20:4n - 6; r = 0.57, p less than 0.01) and docosahexaenoic acid (C 22:6n - 3; r = +0.71, p less than 0.01), and the release of pentane and ethane, respectively. A significant negative correlation was found between the membrane cholesterol content and the pentane release (r -0.44, p less than 0.05). In experiments performed with phenylhydrazine, red cell membrane lipid composition did not influence the susceptibility of red cells to lipid peroxidation. A close correlation was found between plasma and red cell fatty acids (palmitic acid, r = +0.46, p less than 0.01; linoleic acid, r = +0.41, p less than 0.05; arachidonic acid, r = +0.59, p less than 0.01; docosahexaenoic acid, r = +0.67, p less than 0.01). The results demonstrated that the degree of peroxide-induced oxidation of erythrocyte lipids depends on the content of polyunsaturated fatty acids in the membrane, which on the other hand, is determined by plasma fatty acids. It is suggested that dietary variations may influence the susceptibility of red cells to lipid peroxidation.

Adult↗

Studies on the fatty acid composition of intramuscular lipids of cattle, pigs and birds.

The fatty acid composition of the intramuscular lipids of cattle, pigs and birds were determined relative to breed and feeding regime. The cattle included Yellow Cattle, Hereford and Japanese Black; pigs included Wild-boar, Touyuens and Yorkshires; the birds were Wild-birds, Jungle-fowl and broilers. The pen fed animals such as Japanese Black cattle and Yorkshire pigs had a higher amounts of oleic acid, palmitic acid and palmitoleic acid. On the other hand, wild or pasture fed animals such as the Herefords, Wild-boars and Touyuens had higher amounts of omega-3 fatty acids such as alpha-linolenic acid, icosapentaenoic acid and omega-6 fatty acids such as linoleic acid and arachidonic acid. Among Wild-fowl, open-yard fed birds or broilers, there was no difference in fatty acid composition. It is suggested the meat of pasture fed or wild fed animals such as Herefords, Yellow Cattle and Wild-boar is better for health than meat from pen fed animals.

Animals↗

Identification and molecular characterization of acyl-CoA synthetase in human erythrocytes and erythroid precursors.

Full-length cDNA species encoding two forms of acyl-CoA synthetase from a K-562 human erythroleukaemic cell line were cloned, sequenced and expressed. The first form, named long-chain acyl-CoA synthetase 5 (LACS5), was found to be a novel, unreported, human acyl-CoA synthetase with high similarity to rat brain ACS2 (91% identical). The second form (66% identical with LACS5) was 97% identical with human liver LACS1. The LACS5 gene encodes a highly expressed 2.9 kb mRNA transcript in human haemopoietic stem cells from cord blood, bone marrow, reticulocytes and fetal blood cells derived from fetal liver. An additional 6.3 kb transcript is also found in these erythrocyte precursors; 2.9 and 9.6 kb transcripts of LACS5 are found in human brain, but transcripts are virtually absent from human heart, kidney, liver, lung, pancreas, spleen and skeletal muscle. The 78 kDa expressed LACS5 protein used the long-chain fatty acids palmitic acid, oleic acid and arachidonic acid as substrates. Antibodies directed against LACS5 cross-reacted with erythrocyte membranes. We conclude that early erythrocyte precursors express at least two different forms of acyl-CoA synthetase and that LACS5 is present in mature erythrocyte plasma membranes.

Adult↗

[Studies on chemical constituents in dried buds of Lonicera similis Hemsl].

OBJECTIVE: To study the chemical constituents in the dried buds of Lonicera similis. METHOD: Chromatography and spectral analysis were used to isolate and elucidate the constituents. RESULT: Nine compounds were isolated from the dried buds of L. similis, and identified as caffeic acid; 3,5-O-dicaffeoylquinic acid; chlorogenic acid; palmitic acid; luteolin; quercetin; beta-sitosterol; nonacosanol; nonacosane. CONCLUSION: All the compounds were isolated from the plant for the first time.

Caffeic Acids↗

Lipid membrane peroxidation in beta-thalassemia major.

The composition of membrane lipids was studied in 17 splenectomized and eight unsplenectomized patients with beta-thalassemia major and compared to normal controls. The results showed a nearly twofold increase in total cell lipids; a reduction in the percentage, but not the absolute amount of phosphatidylethanolamine, and a corresponding increase in phosphatidylcholine in the lipids; a considerable increase in the percentage of the saturated fatty acid, palmitic acid, and a reciprocal decrease in the polyunsaturated fatty acid, arachidonic acid; a twofold increase in the amount of malonyldialdehyde (MDA) generated after peroxide threat to the RBC when calculated either per gram hemoglobin or per cell; no change in the amount of MDA generated when calculated per microgram of membrane phosphorus at risk per cell; and a considerable decrease in serum alpha-tocopherol (vitamin E) levels. Thalassemic erythrocytes contain more lipid per cell which is susceptible to peroxidation. In addition, the distribution of fatty acids in these cells suggests that autooxidation of that lipid may have occurred. Autooxidation may be initiated by free radicals, which are constantly formed in the normal red cell, and may be especially prevalent when unstable hemoglobins are present. The low MCHC or some other intracellular defect of thalassemic cells may allow such potent oxidants to find their way to the cell membrane. Vitamin E, a biologic antioxidant is decreased in these patients, and clinical supplementation may be indicated to prevent some of the membrane damage in thalassemia.

Adolescent↗

Effects of free fatty acid on polymerization of islet amyloid polypeptide (IAPP) in vitro and on amyloid fibril formation in cultivated isolated islets of transgenic mice overexpressing human IAPP.

BACKGROUND: Islet amyloid polypeptide (IAPP) is deposited as amyloid in the islets of Langerhans in type 2 diabetes. The mechanism behind the formation of the cytotoxic fibrils is unknown. Islet amyloid develops in a mouse IAPP null mouse strain that expresses human IAPP (+hIAPP/-mIAPP) after 9 months on a high-fat diet. Herein we investigate the effect that individual free fatty acids (FFAs) exert on formation of amyloid-like fibrils from synthetic IAPP and the effects of FFAs on IAPP polymerization in +hIAPP/-mIAPP islets cultivated in vitro. MATERIALS AND METHODS: In the study myristic acid, palmitic acid, stearic acid, oleic acid, and linoleic acid were used together with albumin. Thioflavin T (Th T) assay was used for quantification of amyloid-like fibrils. Islets were isolated from the +hIAPP/-mIAPP transgenic strain and cultured in the presence of the FFAs for 2 days. Immuno-electron microscopy was used for evaluation. RESULTS: The Th T assay showed that all studied FFAs potentiated fibril formation but that myristic acid revealed the highest capacity. In some cells from cultured islets, intragranular aggregates were present. These aggregates had a filamentous appearance and labeled with antibodies against IAPP. In some cells cultured in the presence of linoleic acid, large amounts of intracellular amyloid were present. Earlier, this has not been observed after such a short incubation period. CONCLUSIONS: Our studies suggest that FFAs can potentiate amyloid formation in vitro, probably without being integrated in the fibril. Cultivation of +hIAPP/-mIAPP transgenic mouse islets with FFAs results in altered morphology of the secretory granules with appearance of IAPP- immunoreactive fibrillar material. We suggest that such fibrillar material may seed extracellular amyloid formation after exocytosis.

Amyloid↗

Myocardial extraction of lactates, non-esterified fatty acids and their fractions in patients with dilated cardiomyopathy at rest and after the cold pressor test.

UNLABELLED: A decrease in the myocardial extraction or excretion of lactates indicates its hypoxia. The authors analyzed changes in the extraction of lactates, non-esterified fatty acids (NEFA) and their fractions: C 14:0, C 16:0, C 16:1, C 18:1, C 18:2 in a group of 15 patients with dilated cardiomyopathy (DC) and in 10 controls at rest and after the cold pressor test (CPT). At rest, 5 patients with DC produced lactates or extracted less than 10%. During CPT, production of lactates was observed in another four patients (mean values: 17.9 +/- 32.6% vs 24.5 +/- 5.2%, ns). NEFA extraction was found in the DC group: 18.4 +/- 20.6% vs. 13.9 +/- 33.3% /p < 0.05/). The acids involved were C 14:0, C 16:0, C 16:1 and C 18:0. In the controls, NEFA extraction did not change significantly: 12.1 +/- 8.6% vs 29.7 +/- 33.2%. CONCLUSIONS: 1. In part of patients with DC, production of lactates was found. The degree of lactate excretion increased due to CPT; 2. In DC, adrenergic stimulus (CPT) impairs the myocardial utilization of NEFA. This applied mainly to myristic acids, palmitic acid, palmitooleic acid and stearic acid; 3. This phenomenon probably is a result of profound functional and morphological damage to the mitochondrial system in DC.

Adult↗

[Chemical constituents of the roots of Ostericum grosseserratum (Maxim.) Kitag].

This paper reports the isolation of eleven compounds from the roots of Ostericum grosseserratum, of which nine compounds were elucidated as myristic acid, palmitic acid, stearic acid, octacosanoic acid, succinic acid, beta-sitosterol, sitosterol-beta-D-glucoside, isoscopletin and sucrose. The results are helpful in the study of plant taxonomy.

Drugs, Chinese Herbal↗

[Topical administration of an hyperoxygenated fatty acid compound. Preventive and curative effects on pressure ulcer].

INTRODUCTION: Hyper-oxygenized acidic fats are a very useful topical use product for preventing pressure ulcers and to treat stage I pressure ulcers. Mepentol is a hyper-oxygenized acidic fats product (linoleic acid, gamma linolenic acid, oleic acid, palmitic acid, stearic acid, palmitoleic acid, arachidonic acid and eicosenoic acid) with extracts of Equisetum Avrense and Hypericum Perforatum. It works in three main facets: improve as is possible the epidermis's resistance, repair the damage to the epidermis produced by a prolonged pressure, and restore capillary circulation and counter arrest the effect of oxygen radicals produced during reactive hyperemia which are caused by periods of prolonged pressure. The exclusive formula, based on hyperoxygenized acidic fats and the above referred plant extracts, gives to Mepentol a demonstrated effectiveness, and also special features, like speed of action, great speed of topical absorption and a peculiar fragrance. PATIENTS, MATERIAL AND METHOD: In order to evaluate the tissue level effect of Mepentol, we carried out an experimental research project based on two different objectives: determine the effect at capillary circulation level in heels of healthy volunteers and in patients under risk of developing pressure ulcers, a well as in the treatment of stage I pressure ulcers in patients under high risk of developing pressure ulcers. To do so, the authors determined the capillary blood flow by means of a Doppler laser flow meter. RESULTS: After the application of a hyper-oxygenized acidic fats product, the authors noted an increase of 122.29 +/- 68.74% in flow units related to base values. The authors also observed an increase in microcirculation in heels of patients under high risk of developing pressure ulcers, as well as those who suffer from stage I lesions. These increases remain constant over long periods of time. COMMENTARY: Based on the tests carried out, Mepentol shows an undoubtable effect which improves local circulation in zones under risk of developing pressure ulcers as well as for stage I lesions; this supports the use of this product as a preventive measure against pressure ulcers and as treatment for stage I lesions.

Administration, Topical↗