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Systemic and topical drugs for aging skin.

The rejuvenation of aging skin is a common desire for our patients, and several options are available. Although there are some systemic methods, the most commonly used treatments for rejuvenation of the skin are applied topically. The most frequently used topical drugs include retinoids, alpha hydroxy acids (AHAs), vitamin C, beta hydroxy acids, anti-oxidants, and tocopherol. Combination therapy is frequently used; particularly common is the combination of retinoids and AHAs. Systemic therapies available include oral retinoids and vitamin C. Other available therapies such as chemical peels, face-lifts, collagen, and botulinum toxin injections are not discussed in this article.

Administration, Oral↗

Identification of novel hydroxy fatty acids in the barnacle Balanus balanoides.

The ability of the barnacle Balanus balanoides tissues to produce eicosanoid hatching factors from endogenous polyunsaturated fatty acids has been investigated. GC-MS analysis of an active HPLC fraction from the trihydroxy fatty acid band on TLC revealed the presence of a number of trihydroxy fatty acids and two compounds which were tentatively identified as chlorinated dihydroxy fatty acids. The identified trihydroxy fatty acids are 10,11,12-trihydroxy-5,8,14-eicosatrienoic acid, 10,11,12-trihydroxy-5,8,14,17-eicosatetraenoic acid, 13,14,15-trihydroxy-5,8,11,17-eicosatetraenoic acid and 12,13,14-trihydroxy-4,7,10,16,19-docosapentaenoic acid. The tentatively identified chlorinated dihydroxy fatty acids are 9-chloro- and/or 11-chloro-8,12-dihydroxyeicosatetraenoic acid. The formation of these compounds is evidence of lipoxygenase activities in Balanus balanoides and their identification will facilitate the understanding of the roles eicosanoids play in barnacle physiology, especially with regard to the larval hatching process.

Animals↗

Effects of beta-hydroxy butyric acid on insulin binding to its receptor and on autophosphorylation of the receptor.

We examined the effects of beta-hydroxy butyric acid (B-OH-butyrate) on insulin binding to its receptor and on autophosphorylation of the receptor in vitro. The affinity of isolated rat adipocyte insulin receptors was significantly increased by B-OH-butyrate at neutral pH. Similar results were obtained with soluble insulin receptors prepared from hepatocytes. Autophosphorylation of insulin receptor, however, was not affected by OH-butyrate at neutral pH. These results suggested insulin resistance in ketoacidosis is not caused by an interaction between B-OH-butyrate and the insulin receptor.

3-Hydroxybutyric Acid↗

Transfer of "Pseudomonas riboflavina" (Foster 1944), a gram-negative, motile rod with long-chain 3-hydroxy fatty acids, to Devosia riboflavina gen. nov., sp. nov., nom. rev.

The taxonomic position of "Pseudomonas riboflavina" was studied by 16S rRNA gene sequencing and chemotaxonomic methods. This organism is a gram-negative, strictly aerobic rod and has a DNA guanine-plus-cytosine content of 61.4 mol%; the major isoprenoid quinone is ubiquinone 10, and the unusual cellular fatty acids 3-hydroxytetracosenoic acid (3-OH 24:1) and 3-hydroxyhexacosenoic acid (3-OH 26:1) are the major 3-hydroxy cellular fatty acids. A phylogenetic analysis based on 16S rRNA sequences revealed that "P. riboflavina" IFO 13584T (T = type strain) occupies an independent position in the alpha subclass of the Proteobacteria. On the basis of our data, we propose that "P. riboflavina" IFO 13584T should be transferred to the genus Devosia gen. nov. as Devosia riboflavina sp. nov., nom. rev.

Base Sequence↗

Separation of prostaglandins, thromboxane, hydroxy fatty acids and arachidonic acid by high pressure liquid chromatography.

Separation of the major metabolites of arachidonic acid (AA) produced by the cyclo-oxygenase and the lipoxygenases was achieved by using reverse phase high-pressure liquid chromatography. Prostaglandins (PGs), thromboxane B2 (TXB2), and AA were separated on a C-18 radial compression column. An initial isocratic elution resolved the PGs and TXB2 which was followed by a linear gradient in order to elute AA. Variations of the gradient elution shape were required to permit the separation of 12-L-hydroxy-5,8,10-heptadecatrienoic acid, 5-12 and 15-hydroxy-5,8,11,14-eicosatetraenoic acid. The recovery of the labeled AA and its metabolites was investigated. Use of these separation methods and radiolabeled substrates should permit investigators to obtain reproducibly in one chromatographic run adequate separation and quantitation of both PGs and hydroxy fatty acid systems.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Preparation of 18O-labelled standards of hydroxy-eicosatetraenoic acids and thromboxanes for quantitative measurement by gas chromatography/mass spectrometry.

A study on the extent of 18O incorporation into various hydroxy-eicosatetraenoic acids, thromboxane B2 and 2,3-dinor-thromboxane B2 by base-catalysed hydrolysis of their methyl ester derivatives is presented. The amount as well as the position of the inbuilt 18O atoms were determined by gas chromatography/mass spectrometry, utilizing electron impact and positive and negative ion chemical ionization.

Gas Chromatography-Mass Spectrometry↗

Quantification of bacterial lipopolysaccharides (endotoxin) by GC-MS determination of 3-hydroxy fatty acids.

A GC-MS method for the quantification of bacterial lipopolysaccharides (LPS, endotoxin) is presented. After hydrolytic cleavage of 3-hydroxy fatty acids (3-OH FAs) from the lipid A region of LPS, derivatisation of both the hydroxyl and the carboxyl group was performed in one step with a mixture of methyl-bis(trifluoracetamide)(MBTFA) and N-methyl-N-(tert-butyldimethylsilyl)trifluoracetamide (MTBSTFA). Using GC-MS in the EI mode with selected ion monitoring (SIM) for analysis, baseline separation of 3-OH FAs (and of possibly interfering 2-OH FAs) was achieved. The sensitivity of the method (LOD 7-50 pg/injection for the different 3-OH FAs investigated) allows for the efficient quantification of LPS in occupational and environmental samples. Degradation of 3-OH FAs as well as of their derivatives during sample preparation and GC-MS separation as a possible source of errors in analytical methods based on 3-OH FA determination is reported for the first time. Thermal elimination of water from the underivatised 3-OH FAs and of trifluoroacetic acid from the derivatives was identified as the cause of degradation. The resulting alpha,beta-unsaturated compounds showing the same mass spectra as the 3-OH FA derivatives were detected as more or less prominent satellite peaks. By using alkaline instead of acidic hydrolysis and cool on-column instead of split/splitless injection, elimination was reduced to an acceptable level.

Environmental Monitoring↗

Presence of 5-hydroxy-indolacetic acid in Diloboderus abderus larvae without monoamine-oxidase-like activity.

The authors confirmed the presence of monoamines and 5-hydroxy-indolacetic acid (5-HIAA) in the cephalic region of Diloboderus abderus larvae employing a high pressure liquid chromatography (HPLC) with electrochemical detector. An anticholinesterase insecticide produced an increase in the serotonin and 5-HIAA endogenous levels, and did not modify the catecholamines. Monoamine-oxidase activity was undetectable with a radioactive method using 3H-tyramine as substrate.

Animals↗

Synthesis of 3-hydroxy-3-cyclohexylbutyric acid derivatives. 1. Cyclic homologues of 3-hydroxy-3-methylglutaric acid.

Z and E isomers of 3-methyl-3-(carboxymethyl)hexahydro-1 (3H)-isobenzofuranones (I), lactones of 3-hydroxy-3-(2-carboxycyclohexyl) butyric acids (II), were prepared and tested on cholesterol biosynthesis in vitro. Compound I of the Z series was prepared through its ethyl ester by hydrogenation, over Rh/Al2O3 catalyst, of the phenyl ring of 3-methyl-3-[(ethoxycarbonyl)methyl]-1(3H)-isobenzofuranone. Compound I of the E series was prepared, through its ethyl ester, by Reformatsky reaction from ethyl (E)-2-acetylcyclohexanecarboxylate. 3-Methyl-3-(carboxymethyl)-5,6,7,8-tetrahydro-1(3H)-isobenzofuranone, 3-methyl-3-ethyl-5,6,7,8-tetrahydro-1(3H)-isobenzofuranone, and 3-methyl-3-(carboxymethyl)-1(3H)-isobenzofuranone were also prepared and tested. The above compounds inhibited acetate incorporation in cholesterol and fatty acids in rat liver slices at 5 X 10(-3) M but lack specific inhibitory activity on HMG-CoA reductase.

Acetates↗

A reliable and sensitive method for the simultaneous determination of dopamine, noradrenaline, 5-hydroxytryptamine and 5-hydroxy-indolacetic acid in small brain samples.

A sensitive and reliable fluorometric method for the simultaneous determination of dopamine, noradrenaline, 5-hydroxytryptamine and 5-hydroxy-indol acetic acid in small samples of brain tissues is described. The procedure is based on solvent extraction; catecholamines are oxidized by the Chang's method and 5-hydroxytryptamine and 5-hydroxy-indol acetic acid determined by reaction with o-phthalaldehyde, alpha-methyl-p-tyrosine causes a negligible interference with the procedure. Results of determination of these amines in different brain areas are reported.

Animals↗

Mono (S) hydroxy fatty acids: novel ligands for cytosolic actin.

The ubiquitous hydroxylated fatty acids derived from arachidonic acid (HETEs) or linoleic acid (HODEs) exhibit diverse biological effects including chemotaxis, cell proliferation, and modulation of several enzymatic pathways, including the 5-lipoxygenase leading to the inflammatory leukotrienes. It was observed that 12(S)- and 15(S)-HETE and 13(S)-HODE (12- and 15-lipoxygenase-derived metabolites, respectively) inhibited the 5-lipoxygenase present in rat basophilic leukemia (RBL-1) cell homogenates whereas the 15(R) chiral enantiomer and the nonhydroxylated linoleic, oleic, and stearic acids were either less potent or ineffective. In examining the mechanism of this inhibition, the relative effectiveness of several fatty acids in displacing [3H]15-HETE bound to cytosol preparations were compared and the results indicated that these (S) hydroxy fatty acids and 5(S)-HETE were significantly more potent than either the 15(R) enantiomer, 15(S)-HETE methyl ester, arachidonic acid, or prostaglandin F2alpha. In order to identify the protein(s) that specifically binds HETEs, 15(S)-HETE biotin hydrazide was used as a probe to detect any HETE-protein complexes as this compound both inhibited the 5-lipoxygenase and interfered with the binding of [3H]15-HETE to cytosol preparations. SDS-PAGE analysis and chemiluminescent detection revealed that the major cytosolic proteins that bound this biotinylated probe had molecular masses of 43 and 51 kD. Fatty acid competition experiments indicated that the order of effectiveness in displacing this probe from these proteins was 13(S)-HODE > 5(S)-HETE approximately equal to 15(S)-HETE > > stearic acid approximately equal to arachidonic acid approximately equal to 15(R)-HETE. Amino acid sequence analysis showed that the 43 kD protein was actin. These findings suggest the possibility that actin may play a major role in the biological effects of monohydroxylated metabolites derived from cellular 5-, 12-, and 15-lipoxygenases.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Detection of 3-hydroxy fatty acids at picogram levels in biologic specimens. A chemical method for the detection of Neisseria gonorrhoeae?

A method for the detection of 3-hydroxy dodecanoic acid at low picogram levels is described. The procedure involves preparation of a heptafluorobutryl derivative of the butyl ester of the fatty acid and its detection by gas-liquid chromatography using an electron capture detector. The method was adapted for use with biological specimens. Potential of the method for screening for gonococcal infection is discussed. Limitations of the method are that about 105 Neisseria gonorrhoeae cells are required for detection and that interfering substances are a major problem working at maximum sensitivity of the electron capture detector necessitating complex purification procedures. The method eliminates the need to maintain the viability of cells in specimens, thus facilitating collection and transport of specimens.

Bacteriological Techniques↗