Abstract  We report an atopic dermatitis patient with recurrent hand dermatitis who developed a severe allergic contact dermatitis from the use of Elidel cream. Diagnostic patch tests showed an isolated contact allergy to the emulsifier oleyl alcohol present in the product. Pimecrolimus appeared to have had an aggravating effect on the dermatitis in spite of its immunosuppressive effects. The initial clinical appearance of the patient's widespread dermatitis was atypical with resemblance to subacute cutaneous lupus erythematosus. Even though emulsifiers are widely used in topical products, contact allergic reactions to these are relatively uncommon.

Abstract  Maleic anhydride was modified with long chain alcohols (1-hexadecanol, 1-octadecanol, 1-eicosanol and docosyl) to their corresponding amphiphilic mono-L cis-butene dicarboxylates (L = hexadecyl, octadecyl, eicosyl and docosyl). Subsequently, corresponding amphiphilic lanthanide (Y3+, Eu3+) complexes with these four mono-L cis-butene dicarboxylate ligands [Ln(L')3, Ln = Eu, Y; L' = MAH, MAO, MAE, MAD] were synthesized. Then, under heating at various temperatures (700, 800, 900, 1000, and 1,100 degrees C), twenty kinds of nanosized Y2O3:Eu3+ phosphors were prepared using these four as-derived amphiphilic lanthanide (Y3+, Eu3+) complexes as precursors. All four complexes can form nanosized micelle-like aggregates by special self-assembly. Results show that, under heating at 1,000 degrees C, the four Y2O3:Eu3+ phosphors present more regular dispersion particle-like morphology, and the particle size is in the range of 30-80 nm. They exhibit an especially strong emission at 609 nm, and the luminescence intensity of the sample derived from MAD at 1,000 degrees C is best.

Abstract  Surface layers of natural and technical amphiphiles, e.g., octadecanol, stearic acid and related compounds as well as perfluorinated fatty alcohols (PFA), have been investigated on the surface of acoustically levitated drops. In contrast to Langmuir troughs, traditionally used in the research of surface layers at the air-water interface, acoustic levitation offers the advantages of a minimized and contact-less technique. Although the film pressure cannot be directly adjusted on acoustically levitated drops, it runs through a wide pressure range due to the shrinking surface of an evaporating drop. During this process, different states of the generated surface layer have been identified, in particular the phase transition from the gaseous or liquid-expanded to the liquid-condensed state of surface layers of octadecanol and other related amphiphiles. Characteristic parameters, such as the relative permeation resistance and the area per molecule in a condensed surface layer, have been quantified and were found comparable to results obtained from surface layers generated on Langmuir troughs.

Abstract  The purpose of this study was to prepare wax-incorporated pectin-based emulsion gel beads using a modified emulsion-gelation method. The waxes in pectin-olive oil mixtures containing a model drug, metronidazole, were hot-melted, homogenized and then extruded into calcium chloride solution. The beads formed were separated, washed with distilled water and dried for 12 h. The influence of various types and amounts of wax on floating and drug release behavior of emulsion gel beads of calcium pectinate was investigated. The drug-loaded gel beads were found to float on simulated gastric fluid if the sufficient amount of oil was used. Incorporation of wax into the emulsion gel beads affected the drug release. Water-soluble wax (i.e. polyethylene glycol) increased the drug release while other water-insoluble waxes (i.e. glyceryl monostearate, stearyl alcohol, carnauba wax, spermaceti wax and white wax) significantly retarded the drug release. Different waxes had a slight effect on the drug release. However, the increased amount of incorporated wax in the formulations significantly sustained the drug release while the beads remained floating. The results suggest that wax-incorporated emulsion gel beads could be used as a carrier for intragastric floating drug delivery.

Abstract  The primary and secondary objectives of this study were to develop and evaluate the predictability of in vitro-in vivo correlation models for theophylline sustained release (SR) granules. Theophylline SR granules meeting the USP Drug Release Test criteria were prepared using ethyl cellulose (EC) and/or stearyl alcohol (SA) and the wet granulation method. In vitro dissolution studies of granule formulation were performed, and a commercial dosage form was prepared using USP XXIII apparatus II at pH 4.5. Differences and similarities between in vitro dissolution curves were compared using both model-dependent (t-test) and -independent (f1, f2 test) statistical techniques, and it was shown that the three dissolution profiles i.e model-dependent, model-independent, and methods based on ANOVA were very similar. The in vivo performance of the commercial dosage form was tested by oral route using male rabbits and in vitro-in vivo correlations were established. This study indicates that the dosage forms with similar in vitro dissolution profiles may have a similar in vivo performance, and that this performance could be estimated using appropriate correlation equations.

Abstract  Oleyl alcohol was complexed with new amphiphilic polyvinylalcohol derivatives with the aim of increasing its aqueous solubility, thus improving bioavailability and favoring its antitumor activity. Water-soluble amphiphilic polymers were prepared by polyvinyl alcohol (PVA) substitution with oleyl chains through a succinyl spacer at 2% and 3% substitution degree. The complexes were obtained by spray-drying hydroalcoholic solutions of the substituted polymers and free oleyl alcohol at different weight ratios (3:1; 5:1; 10:1 w/w). The main physicochemical characteristics of the complexes were analyzed and correlated to the cytotoxic activity of oleyl alcohol toward tumor cell lines. The complexes strongly increased the aqueous solubility of oleyl alcohol and provided oleyl alcohol release in the presence of extractive conditions (simulating in vivo absorption). The complexes obtained by 10:1 polymer:fatty alcohol weight ratio offered higher release rates than the 5:1 and 3:1 ratios, respectively. Complexation also increased oleyl alcohol cytotoxicity toward tumor cells due to increased availability of the active molecule in the aqueous phase. Pure polymers were found to be biocompatible and no toxic effect was detected up to the highest concentration used in the present study (500 mu g/ml). The complexation of oleyl alcohol with the polymers analyzed here efficiently increased the availability of the fatty alcohol in aqueous environment. The enhanced cytotoxicity toward tumor cells of the complexed oleyl alcohol and the polymer biocompatibility make these amphiphilic PVA derivatives interesting candidates for soluble pharmaceutical formulations containing hydrophobic drugs whose therapeutic potential is often underestimated due to unsuitable levels of their aqueous solubilization.

Abstract  The possibility of employing methylated crude palm oil (CPOE) as an extraction solvent to reduce end-product inhibition and to enhance solvent productivity in acetone-butanol-ethanol (ABE) fermentation was evaluated using oleyl alcohol as the standard butanol extractant. Fermentation was carried out at an initial glucose concentration of 90 g/l. CPOE did not inhibit the growth of the fermentative organism. Without solvent extraction, butanol production ceased after 30 h at a concentration of 15.4 g/l limiting cell growth to 3.98 g/l and glucose consumption to 62%. Applying CPOE as the extraction solvent, about 47% of the total butanol produced was extracted, glucose consumption was increased to 83% and relatively high glucose consumption rates and solvent productivities were obtained. Butanol production increased to 20.9 g/l; total ABE solvents and yield also increased from 21.2 g/l and 38% (in conventional fermentation) to 29.8 g/l and 40.4%, respectively.

Abstract  Fast-disintegrating (FD) tablets containing nicorandil-loaded dry emulsions were prepared and their controlled-release properties were examined and compared with the plain FD tablets (FD tablets without dry emulsions) and commercial tablets. The dry emulsions were prepared with myristyl alcohol and stearyl alcohol and their property was modified by mixing the ratio of the two alcohols. Disintegration time of the prepared FD tablets was sufficiently fast (i.e., 12 to 23 s). In vitro release of nicorandil from the FD tablets containing the dry emulsions was sustained over 6 h, while that from plain FD and commercial tablets was complete within 5 min. In vivo absorption of nicorandil from the tablets was evaluated by oral administration in beagle dogs. FD tablets containing dry emulsions showed a similar AUC, lower Cmax, and delayed Tmax compared to the plain FD and commercial tablets. These results suggest that the dry emulsion-loaded FD tablets can be utilized to improve the sustained-release property of active drugs.

Abstract  The cholesterol linoleate hydroperoxides formed in LDL after oxidant stress are measured by HPLC, with UV detection at 234 nm. Calibration is performed with a conjugated diene internal standard. This internal standard is synthesized by the transesterification of the methyl ester of conjugated diene linoleic acid with a long-chain alcohol, such as arachidyl alcohol (C20). Different long-chain alcohols can be used during the transesterification, to achieve internal standards with variable HPLC retention times. The method allows measurement of cholesterol linoleate hydroperoxide in LDL very early during attack with Cu2+ or other initiator, so that the kinetics of antioxidant loss and hydroperoxide formation can be concurrently monitored.

Abstract  BACKGROUND: There are 3 new topical treatments for herpes labialis that have either been approved by the US Food and Drug Administration (penciclovir cream [Denavir] and n-docosanol cream [Abreva]) or recently undergone extensive clinical evaluation (acyclovir cream). The relative efficacy of these products is unknown.

OBJECTIVE: To compare the efficacy of penciclovir cream, acyclovir cream, n-docosanol cream, and acyclovir ointment in an experimental animal model of cutaneous herpes simplex virus type 1 (HSV-1) disease.

DESIGN: The backs of guinea pigs were infected with HSV-1 using a vaccination instrument. Active treatments and corresponding vehicle controls were applied for 3 to 5 days beginning 24 hours after inoculation.

MAIN OUTCOME MEASURES: After completion of treatment, the animals were killed and the severity of the infection assessed from the number of lesions, the total lesion area, and the lesion virus titer.

RESULTS: Penciclovir cream effected modest reductions in lesion number (19%), area (38%), and virus titer (88%) compared with its vehicle control, and each of these differences was significantly greater (P<.05) than the reductions effected by acyclovir ointment (0%, 21%, and 75%, respectively). The acyclovir cream effect (reductions of 4%, 28%, and 77%, respectively) was less than that of penciclovir cream, and this difference was confirmed by 2 additional head-to-head experiments. Two experiments with n-docosanol cream failed to show statistically significant differences by any parameter between n-docasonol cream and vehicle control-treated sites or between n-docosanol and untreated infection sites.

CONCLUSIONS: In this model, the efficacy of penciclovir cream was greater than acyclovir cream, acyclovir cream was greater than or equal to acyclovir ointment, and acyclovir ointment was greater than n-docosanol cream. Since our model was designed to evaluate compounds that function primarily through antiviral activity, the negative findings with n-docosanol in these studies do not exclude that it might work clinically through other mechanisms.

Abstract  It was shown by the combination of thermogravimetric analysis and Karl Fisher titrations that temperatures in excess of 200 degrees C are required to remove tightly bound water from proteins. The heating of enzymes to this temperature caused no cleavage of the polypeptide chains and very little, if any, chemical degradation of particular amino acid residues as judged by electrophoretic and amino acid analysis respectively. It was hypothesised that those enzymes that require very little water for their catalytic activity, should remain active at such elevated temperatures provided that they can be stabilised against thermodenaturation. This conclusion has been verified by the observation that immobilised Candida antarctica lipase catalysed transesterification of octadecanol with palmityl stearate at 130 degrees C for a considerable period of time.

Abstract  A two-phase aqueous/organic partitioning bioreactor scheme was used to degrade mixtures of toluene and benzene, and toluene and p-xylene, using simultaneous and sequential feeding strategies. The aqueous phase of the partitioning bioreactor contained Pseudomonas sp. ATCC 55595, an organism able to degrade benzene, toluene and p-xylene simultaneously. An industrial grade of oleyl alcohol served as the organic phase. In each experiment, the organic phase of the bioreactor was loaded with 10.15 g toluene, and either 2.0 g benzene or 2.1 g p-xylene. The resulting aqueous phase concentrations were 50 mg/l, 25 mg/l and 8 mg/l toluene, benzene and p-xylene respectively. The simultaneous fermentation of benzene and toluene consumed these compounds at volumetric rates of 0.024 g l-1 h-1 and 0.067 g l-1 h-1, respectively. The simultaneous fermentation of toluene and p-xylene consumed these xenobiotics at volumetric rates of 0.066 g l-1 h-1 and 0.018 g l-1 h-1, respectively. A sequential feeding strategy was employed in which toluene was added initially, but the benzene or p-xylene aliquot was added only after the cells had consumed half of the initial toluene concentration. This strategy was shown to improve overall degradation rates, and to reduce the stress on the microorganisms. In the sequential fermentation of benzene and toluene, the volumetric degradation rates were 0.056 g l-1 h-1 and 0.079 g l-1 h-1, respectively. In the toluene/p-xylene sequential fermentation, the initial toluene load was consumed before the p-xylene aliquot was consumed. After 12 h in which no p-xylene degradation was observed, a 4.0-g toluene aliquot was added, and p-xylene degradation resumed. Excluding that 12-h period, the microbes consumed toluene and p-xylene at volumetric rates of 0.074 g l-1 h-1 and 0.025 g l-1 h-1, respectively. Oxygen limitation occurred in all fermentations during the rapid growth phase.

Abstract  Fatty acids, alcohols, and mycolic acid cleavage products were determined for 13 ATCC strains and 24 clinical isolates, which were initially identified by biochemical and growth characteristics as the Mycobacterium terrae complex. The clinical isolates were also analyzed by partial sequencing of the 16S rRNA gene, which divided them into five genetic entities, M. triviale (three strains), M. terrae (four strains), M. nonchromogenicum sensu stricto (seven strains), Mycobacterium sp. strain MCRO 6 (seven strains), and Mycobacterium sp. strain 31958 (one strain). After acidic methanolysis, secondary alcohols were a characteristic feature in all members of the M. terrae complex but M. triviale. In addition to the prominent secondary alcohols, 2-octadecanol and 2-eicosanol, two previously unidentified alcohols, 2-(8,15-dimethyl)docosenol and 2-(8,17-dimethyl)tetracosenol, were detected in M. nonchromogenicum, Mycobacterium sp. strain MCRO 6, and Mycobacterium sp. strain 31958. Only 2-(8,17-dimethyl)tetracosenol was detected in trace amounts in M. terrae. Genetic differences were associated with differences in phenotypic characteristics, including growth at 42 degrees C and pyrazinamidase production. Based on fatty acid and alcohol composition and biochemical and genetic characteristics, M. non-chromogenicum and Mycobacterium sp. strains MCRO 6 and 31958 were found to be a closely related group, named the M. nonchromogenicum complex. Detected genetic variations associated with phenotypic characteristics may indicate further species separation of this complex. In conclusion, the results of gas-liquid chromatography fatty acid analysis, combined with those of a Tween 80 test, enable identification of the species of the M. terrae complex and their separation from other nonpigmented slowly growing mycobacteria.

Abstract  n-Docosanol-treated cells resist infection by a variety of lipid-enveloped viruses including the herpesviruses. Previous studies of the mechanism of action demonstrated that n-docosanol inhibits an event prior to the expression of intermediate early gene products but subsequent to HSV attachment. The studies reported here indicate that n-docosanol inhibits fusion of the HSV envelope with the plasma membrane. Evidence suggests that antiviral activity requires a time-dependent metabolic conversion of the compound. Cellular resistance to infection declines after removal of the drug with a t1/2 of approximately 3 h. Reduced expression of viral genes in n-docosanol-treated cells was confirmed by a 70% reduction in expression of a reporter gene regulated by a constitutive promoter inserted into the viral genome. Inhibited release in treated cells of virion-associated regulatory proteins--an immediate post entry event--was indicated by a 75% reduction in the expression of beta-galactosidase in target cells carrying a stably transfected lacZ gene under control of an HSV immediate--early promoter. Finally, the fusion-dependent dequenching of a lipophilic fluorescent probe, octadecyl rhodamine B chloride, inserted into the HSV envelope was significantly inhibited in treated cells. Inhibition of fusion between the plasma membrane and the HSV envelope, and the subsequent lack of replicative events, may be the predominant mechanism for the anti-HSV activity of n-docosanol.

Abstract  BACKGROUND: The introduction of fat to the duodenum leads to an increase in mesenteric blood flow. The exact mechanism, however, is unknown. In this study we investigate the influence of the terminal carboxy group of the oleic acid molecule on superior mesenteric artery blood flow.

METHODS: In six healthy male volunteers duplex ultrasound was used to evaluate the effects of duodenal perfusion of 48 mmol oleic acid and 48 mmol oleyl alcohol on superior mesenteric artery blood flow variables and diameter.

RESULTS: The blood flow variables time-average velocity and maximal diastolic velocity increased significantly, and the resistance index decreased significantly during perfusion with oleic acid, but during oleyl alcohol perfusion no changes were found. No significant changes in vessel diameter were observed at any time.

CONCLUSION: The carboxy group of the oleic acid molecule has an important role in the duodenum in mediating the postprandial increase in superior mesenteric artery blood flow.

Abstract  Cells of the ciliate Tetrahymena thermophila failed to establish cultures in lipid-free standard synthetic nutrient medium if the initial population density was 250 cells per ml or less. These cells died within 10 h, but were saved and formed dense cultures if their medium was supplemented with 10 micrograms per ml of either certain phospholipids, 1,2-di-, 1-monoglycerides, fatty acids, long-chain alcohols, or sterols. Cell multiplication was followed in cultures in which the standard synthetic medium was supplemented with a selection of the compounds listed above. It was observed that the cells in the supplemented cultures in their exponential phases of growth had about the same average doubling times as control cells starting multiplication at 10-fold higher initial cell densities in lipid-free medium. These cells have been grown for decades in lipid-free synthetic nutrient media at short (ca. two-three h) doubling times. Therefore lipids have been considered nutritionally non-essential for growth and multiplication of these cells. We propose that those compounds that rescue the cells at low cell densities act as "proliferation signals," sensu lato. This effect of lipids and long-chain alcohols has so far remained unnoticed.

Abstract  A 29-year-old man being treated for itchy lesions on the amputation stump of the thigh became allergic to betamethasone valerate and gentamicin sulfate cream (Rinderon VG). Closed patch tests with all the ingredients of the cream revealed positive reactions to cetyl alcohol 30% to 5% pet. Gas chromatographic analysis of the cetyl alcohol in the cream base detected stearyl alcohol (C18), myristyl alcohol (C14) and lauryl alcohol (C12) in addition to the main component of cetyl alcohol (C16). Patch testing with 99% pure analytical reagent grade saturated alcohols (C10, C11, C12, C13, C14, C15, C16, C17, C18, C19, C20) showed negative reactions. Thus, it is concluded that some minor impurities in cetyl alcohol not detected by gas chromatography might be the cause of this dermatitis.

Abstract  Noncontact thermometry based on the fluorescence excitation spectrum of aqueous Eu(3+) (EDTA) near 579 nm allows us to measure the temperature of an evaporating drop of water. The results for drop diameters in the 500-microm-3-mm range confirm theoretical temperature predictions for steady state evaporation. Calibration of the excitation spectrum in a constant temperature cell indicates that +/-1.0 degrees C resolution is possible for temperatures below 20 degrees C. The spectrum depends only on the solution temperature when Eu(3+) (EDTA) concentrations are below 1 x 10(-3) M and when the solution pH is between 4.0 and 10.0. Excitation spectra from levitated waterdrops contain additional noise which degrades the temperature resolution to +/-1.2 degrees C. With this technique we are able to follow the temperature change in an evaporating drop of water as a monolayer of 1-octadecanol forms on the surface and retards the evaporation.

Abstract  Extractive fermentation has been proposed to enhance the productivity of fermentations that are end product inhibited. Unfortunately, good extractants for butanol, such as decanol, are toxic to Clostridium acetobutylicum. The use of mixed extractants, namely, mixtures of toxic and nontoxic coextractants, was proposed to circumvent this toxicity. Decanol appeared to inhibit butanol formation by C. acetobutylicum when present in a mixed extractant that also contained oleyl alcohol. However, maintenance of the pH at 4.5 alleviated the inhibition of butanol production and the consumption of butyrate during solventogenesis. A mixed extractant that contained 20% decanol in oleyl alcohol enhanced butanol formation by 72% under pH-controlled conditions. The production of acetone and acetoin was also increased, even though these two products were not extractable. The enhancement of butanol formation was not limited by the toxicity of decanol. Supplementation of glucose and butyrate in the extractive fermentation yielded a 47% increase in butanol. The enhancement of butanol formation appeared to be dependent on the presence of dissolved decanol in the broth but was not observed unless an organic phase was present to extract butanol. A mechanism for the effects of decanol on product formation is proposed.

Abstract  Mathematical formulation was made for the performance evaluation of extractive fermentation using multiple solvents. Two types of solvent-supplying strategies were considered. One is to add multiple solvents simultaneously and the product is removed at one time. Another is to add them one by one consecutively. Computer simulation was made for batch, fed-batch, and repeated fed-batch operation of acetone-butanol fermentation to show the power of the approach. The result shows that the significant performance improvement in terms of the productivity and the product concentration is expected when two extractants such as oleyl alcohol and benzyl benzoate are used as compared with the case of using only one solvent.

Abstract  Addition of oleate, oleyl alcohol, or palmitate to HeLa cell medium resulted in a rapid stimulation of PC synthesis and activation of CTP: phosphocholine cytidylyltransferase. Stimulation was optimal with 0.35 mM oleate, 0.3 mM oleyl alcohol and 5 mM palmitate, or 1 mM palmitate if EGTA were added to the medium. The cytidylyltransferase was activated by translocation of the inactive cytosolic form to membranes. In untreated cells approx. 30% of the total cytidylyltransferase was membrane bound, while in treated cells, 80-90% was membrane associated. Addition of bovine serum albumin (10 mg/ml) to cells previously treated with oleate (0.35 mM) rapidly removed cellular fatty acid, and the membrane-bound cytidylyltransferase activity returned to approx. 30%. Similar results were obtained by extraction of membranes with albumin in vitro. Although 95% of the free fatty acid was extracted, 30-40% of the membrane cytidylyltransferase remained bound. Translocation of cytidylyltransferase between isolated cytosol and microsomal fractions was promoted by addition of oleate, palmitate, oleyl alcohol, and monoolein. Addition of diacylglycerol, lysophosphatidylcholine, lysophosphatidylethanolamine, calcium palmitate, and detergents such as Triton X-100, cholate or Zwittergent did not stimulate translocation of the enzyme. Addition of oleoyl-CoA promoited translocation, however, 40% of it was hydrolyzed releasing free oleic acid. Cytosolic cytidylyltransferase bound to microsomes pre-treated with phospholipase C, which had 7-fold elevated diacylglycerol content. Fatty acid-promoted translocation was blocked by Triton X-100, but not by 1 M KCl. These results suggest that a variety of compounds with differing head group size and charge, and number of hydrocarbon chains can function as translocators, and that hydrophobic rather than ionic interactions mediate the binding of cytidylyltransferase to membranes.