Abstract  π-A isotherms, atomic force microscopy (AFM), and sum frequency generation (SFG) vibrational spectroscopy are employed to investigate the molecular structure and lateral interactions in mixed monolayers of dioctadecyldimethylammonium chloride (DOAC) and stearyl alcohol (SA) at air/water and air/solid interfaces. To avoid possible interference between the two molecules in the SFG spectroscopic measurements, perprotonated DOAC and perdeuterated SA (dSA) were used. The thermodynamic analyses for the π-A isotherms show that DOAC is miscible with dSA. SFG observations reveal that DOAC molecules become conformationally ordered as dSA molecules are introduced into the monolayer. AFM observations demonstrate coexistence of DOAC-rich and dSA-rich domains in the mixed monolayer with ratios different from their initial composition in the subphase. The present study suggests that DOAC molecules in the mixed monolayer are condensed by mixing with dSA in which the repulsive interactions between positively charged head groups of the DOAC molecules are largely reduced along with an increase of van der Waals interactions with dSA.

Abstract  49 substances permitted for use in food in the United States was tested for mutagenicity in the Ames Salmonella typhimurium assay and in Escherichia coli strain WP2. Four of these substances caused increases in revertant counts in S. typhimurium. Two of these four (papain and pepsin) were found to contain histidine, and therefore the results of the tests on these two substances could not be taken as demonstrating mutagenicity. The other two substances causing increases in revertant counts (hydrogen peroxide and potassium nitrite) were mutagenic. The results on one chemical, beta-carotene, were evaluated as inconclusive or questionable. The remaining 44 substances were nonmutagenic in the test systems used. It is concluded that, for those generally physiologically innocuous chemicals tested, there are very few 'false positives' in the bacterial test systems used.

Abstract  In order to obtain a novel prescription to treat scald, a new ointment was assessed. The ointment was made of pepsin soluble collagen (PSC), Bletilla striata polysaccharide (CBSP), lentinan, 1-octadecanol, dodecyl sodium sulfate, white vaseline, methyl hydroxybenzoate, propyl hydroxybenzoate, propylene glycol and distilled water. Experiment involving mice with their biochemical assays was used to evaluate the suitability of the ointment. The ointment which include by 1.5 g PSC, 1.5 g CBSP, 1.5 g lentinan, 20 g 1-octadecanol, 1.46 g dodecyl sodium sulfate, 23 g white vaseline, 0.025 g methyl hydroxybenzoate, 0.015 g propyl hydroxybenzoate, 11 g propylene glycol, and 40 g distilled water is optimal ointment. The scar outcomes rate all reach 100.00% in ointment group and model group. However, the ointment group of scar outcomes rate is higher than model group in the tenth day. The ointment 1, 2 and 3 group can significantly improve the activity of superoxide dismutase, increase the content of monoamine oxidase and reduce the content of malondialdehyde. The ointment had no influence on the body mass, the relative organ mass, blood hematology and serum biochemical indices of the mice. The results of the study indicated that the ointment can be used to treat scalds on mouse, increase the rate of the scar outcome and promote scald heal.

Abstract  Purpose: To ascertain the influence of paraffin, white soft paraffin and pre-hydrated white soft paraffin on the viscosity of a cream formulated with a corticosteroid. Methods: The formulations were prepared via homogenization with variable velocity in the range 3300 4000 rpm. Individual series of preparations contained the same proportion of macrogol cetostearyl alcohol, cetyl alcohol, stearyl alcohol, sorbitan stearate, propylene glycol, metyl parahydroxybenzoate, propyl parahydroxybenzoate and water. The semi-solid preparations were assessed by viscometric and microscopic methods. Results: The viscosity of the samples measured ranged from 13050 to 15660 mPas. The particles in dispersed phase sized from 15 to 90 mu m. Within the multiple emulsion, the continuous phase included fine particles with diameter < 5 mu m. Change of the liquid paraffin used from Ondina 934 to Vara 600P significantly decreased the viscosity of the formulation. Several phases within the formulations were distinguished microscopically. Increased viscosity was observed in formulations with increasing proportion of white soft paraffin. Conclusion: Both the ratio of liquid paraffin to white soft paraffin, as well as the initial hydration of white soft paraffin influenced the viscosity of the cream as well as the diameter of particles in the dispersed phase.

Abstract  BIOSIS COPYRIGHT: BIOL ABS. The application of Salmonella/microsomal mammalian tests to column chromatography fractions isolated from river and marine sediments collected in the vicinity of Barcelona City, Spain, demonstrated a positive response (TA98+S9 mix) among the polar fractions. Chemical analysis by high resolution gas chromatography coupled to negative ion chemical ionization mass spectrometry (HRGC-NICI MS) provided sensitivity and selectivity to detect several mutagenic chemical classes. Among them, nitrated PAHs, azaarenes, aromatic amines, anhydrides, and ketones were identified. A total of 116 compounds were tentatively identified, 22 for the first time, of which 16 possessed mutagenic activity. However, a lack of correlation between chemical composition and fraction mutagenicity in the medium polarity fractions, especially in the river sediment, was evidenced. The occurrence of multiple interactions between components in spiked organic extracts is demonstrated.

Abstract  Structure-activity relationships between acute toxicities of 95 alcohols to rat and mouse (oral LD50) and four special substructure factors, hydroxyl number, carbon atom number were examined by means of expert system method. The results showed that the expert system based QSAR model was excellent for classification for miscellaneous alcohols (only 9 of them were wrong classified). It was also used to predict the toxicity of other 25 alcohols, and the false prediction rate was only 12%.

Abstract  Breflate is a water soluble prodrug developed to facilitate parenteral administration of the investigational antineoplastic agent brefeldin A (BFA). Previously, using analytical methods based upon reversed-phase high performance liquid chromatography (HPLC) with low wavelength UV detection or gas chromatography (GC) with electron capture detection following derivatization with heptafluorobutyrylimidazole, it was demonstrated that breflate undergoes rapid and efficient conversion to BFA following bolus i.v. injection in mice and dogs. However, plasma concentrations of the drug and prodrug achieved during the administration of nontoxic doses of breflate to beagle dogs as a 72 h continuous i.v. infusion were undetectable (< 0.1 microgram ml-1) by these methods. The sensitivity and specificity required for therapeutic drug level monitoring were achieved by GC with selected-ion mass spectrometry (MS) detection. Breflate, BFA and 1-eicosanol, the latter added to the sample as an internal standard (IS), were extracted from plasma into tert-butyl methyl ether (TBME) and esterified with trifluoroacetic anhydride. Methanol was added to the reaction mixture to effect the convenient removal of excess reagent as the volatile methyl ester during evaporation of the solvent. The residual material was analyzed directly upon reconstitution by capillary GC with automated splitless injection. Electron-ionization (70 eV) MS detection was performed by sequentially scanning ions at m/z 58, 202 and 325. The lowest concentration of either analyte quantified with acceptable reproducibility, as defined by an inter-day R.S.D. of about 20%, was near 10 ng ml-1 in plasma using a sample volume of 100 microliters. The assay has proven to be sufficiently sensitive, specific and reproducible for the routine analysis of pharmacokinetic specimens acquired during IND (investigational new drug)-directed toxicology studies in dogs.

Abstract  Continuous butanol/isopropanol fermentation with immobilized Clostridium isopropylicum was performed in a downflow column reactor using molasses as the substrate. In order to prevent product inhibition and at the same time obtain high concentration of the products, the column reactor was coupled with a pervaporation module using a supported liquid membrane. The liquid membrane was prepared with oleyl alcohol nontoxic to the microorganism. In comparison with the continuous fermentation without product removal, the specific butanol production rate was 2 times higher. The butanol concentration in the permeate was 230 kg/m(3), which was about 50 times higher than that in the culture broth. A numerical investigation suggested a further increase in the productivity by improving the module construction.

Abstract  The rabbit external ear canal was used to define which chemicals caused comedone formation on topical application. Some of the tested ingredients are currently used in topically applied formulations. Certain raw materials have been shown to produce follicular hyperkeratosis in the rabbit ear assay. This study quantifies comedogenic potential of cosmetic materials, including: isopropyl palmitate, isopropyl myristate, butyl stearate, isopropyl isostearate, decyl oleate, isostearyl neopentanoate, isocetyl stearate, myristle myristate, cocoa butter, cetyl alcohol, paraffin, stearyl alcohol sodium lauryl sulfate (SLS), and petrolatum. The first nine were deemed positive. Factors aiding clinical relevance are listed.

Abstract  We developed an oil/water-type tacrolimus (FK506) cream formulation as an alternative to Protopic ointment for atopic dermatitis treatment. We determined the effects of solvents used in topical preparations on FK506 solubility and stability, and evaluated FK506 transdermal absorption into rat skin from solutions, emulsions, and creams. Screening indicated that diethyl sebacate (DES), isopropyl myristate (IPM), propylene glycol (PG), and oleyl alcohol (OA) were adequate FK506 solvents. When FK506 solutions prepared using these solvents were transdermally administered, AUC(0-24) values for DES and IPM were higher than or similar to that for 0.1% Protopic ointment. The AUC(0-24) values for PG and OA were low, so these solvents did not enhance absorption. The residual ratios of FK506 in DES and IPM solutions after incubation at 70 degrees C for 9 d were 95.6% and 88.6%, respectively, so DES and IPM were chosen for emulsion preparation. When the emulsions were transdermally administered, the IPM emulsion AUC(0-24) values increased 4.6-fold; DES emulsions did not show high transdermal absorption, but showed sustained characteristics. A cream formulation prepared by mixture of IPM and DES also showed high absorption and transdermal absorption increased with increasing IPM ratio. We developed an FK506 cream formulation with a controllable transdermal absorption rate by manipulating the IPM: DES ratio. (C) 2014 Elsevier B.V. All rights reserved.

Abstract  The effects of various vehicles on percutaneous absorption of ketoprofen in a solution formulation and in a pressure-sensitive adhesive (PSA) matrix were evaluated. The permeation rate of ketoprofen across hairless mouse skin was evaluated using a flow-through diffusion cell system at 37 degrees C. The solubility of ketoprofen was determined using the equilibrium solubility method. Among tested vehicles, octanol, ethanol, and propylene glycol (PG)/oleyl alcohol (OA) mixture showed the highest flux of 30 mu g/cm(2) per h from 5 mg/ml solution. However, it was not possible to demonstrate any correlation between the solubility of ketoprofen and its permeation rate, indicating change in the barrier property of the skin and/or carrier mechanism by vehicles used. When the effects of various vehicles on the percutaneous absorption of ketoprofen from acrylic PSA matrix were evaluated, oleic acid showed a slightly higher flux of 2 mu g/cm(2) per h than all other solvents tested. As the concentration of ketoprofen in acrylic PSA matrix increased from 6.3 to 16.7%, the permeation rate also increased almost linearly. The permeation rate of ketoprofen from polyisobutylene (PIB)-type PSA matrix was more than three times higher than that from acrylic PSA matrix. (C) 1998 Elsevier Science B.V. All rights reserved.

Abstract  In this study, the integrated in situ extraction-gas stripping process was coupled with continuous ABE fermentation using immobilized Clostridium acetobutylicum. At the same time, oleyl alcohol was cocurrently flowed into the packed bed reactor with the fresh medium and then recycled back to the packed bed reactor after removing butanol in the stripper. A high glucose consumption of 52 g/L and a high butanol productivity of 11 g/L/h were achieved, resulting in a high butanol yield of 0.21 g-butanol/g-glucose. This can be attributed to both the high bacterial activity for solvent production as well as a threefold increase in the bacterial density inside the packed bed reactor. Also reported is that 64 % of the butanol produced can be recovered by the integrated in situ extraction-gas stripping process. A high butanol productivity and a high glucose consumption were simultaneously achieved.

Abstract  PURPOSE: Microemulsion (ME) systems allow for the microscopic co-incorporation of aqueous and organic phase liquids. In this study, the phase diagrams of four novel ME systems were characterized.

METHODS: Water and IPM composed the aqueous and organic phases respectively, whereas Tween 80 served as a nonionic surfactant. Transdermal enhancers such as n-methyl pyrrolidone (NMP) and oleyl alcohol were incorporated into all systems without disruption of the stable emulsion.

RESULTS: A comparison of a W/O ME with an O/W ME of the same system for lidocaine delivery indicated that the O/W ME provides significantly greater flux (p < 0.025). The water phase was found to be a crucial component for flux of hydrophobic drugs (lidocaine free base, estradiol) as well as hydrophilic drugs (lidocaine HCl, diltiazem HCl). Furthermore, the simultaneous delivery of both a hydrophilic drug and a hydrophobic drug from the ME system is indistinguishable from either drug alone. Enhancement of drug permeability from the O/W ME system was 17-fold for lidocaine free base, 30-fold for lidocaine HCl, 58-fold for estradiol, and 520-fold for diltiazem HCl.

CONCLUSIONS: The novel microemulsion systems in this study potentially offers many beneficial characteristics for transdermal drug delivery.

Abstract  Sodium hyaluronate (HYA) warrants attention as a material for inhalation due to its (i) therapeutic potential, (ii) utility as a formulation excipient or drug carrier, and (iii) ability to target lung inflammation and cancer. This study aimed to overcome formulation and manufacturing impediments to engineer biocompatible spray-dried HYA powders for inhalation. Novel methodology was developed to produce HYA microparticles by spray drying. Different types of surfactant were included in the formulation to improve powder respirability, which was evaluated in vitro using cascade impactors. The individual formulation components and formulated products were evaluated for their biocompatibility with A549 respiratory epithelial cells. The inclusion of stearyl surfactants, 5% w/v, produced the most respirable HYA-powders; FPF 59.0-66.3%. A trend to marginally higher respirability was observed for powders containing stearylamine>stearyl alcohol>cetostearyl alcohol. Pure HYA was biocompatible with A549 cells at all concentrations measured, but the biocompatibility of the stearyl surfactants (based on lethal concentration 50%; LC50) in the MTT assay ranked stearyl alcohol>cetostearyl alcohol>stearylamine with LC50 of 24.7, 13.2 and 1.8μg/mL, respectively. We report the first respirable HYA powders produced by spray-drying. A lead formulation containing 5% stearyl alcohol was identified for further studies aimed at translating the proposed benefits of inhaled HYA into safe and clinically effective HYA products.

Abstract  Sphingosine has been shown to activate protein kinases in Jurkat T cell cytosol [Pushkareva, Khan, Alessenko, Sahyoun and Hannun (1992) J. Biol. Chem. 267, 15246-15251]. In this study, two sphingosine-activated protein kinases were distinguished by their substrate specificity, their dose-response to sphingosine and the specificity of their activation by sphingosine and dihydrosphingosine stereoisomers. A p32-sphingosine-activated protein kinase responded to low concentrations of D-erythrosphingosine with an initial activation observed at 2.5 microM and a peak activity at 10-20 microM. This kinase showed a modest specificity for D-erythro-sphingosine over other sphingosine stereoisomers, and a preference for sphingosines over dihydrosphingosines. Phosphorylation of a p18 substrate required higher concentrations of sphingosine (20-100 microM) and showed a significant preference for the erythro isomers of sphingosine and dihydrosphingosine over the threo isomers. The ability of other lipids to modulate sphingosine activation of these kinases was also examined. Oleic acid, but not oleic alcohol or the methyl ester, induced the phosphorylation of a distinct set of substrates (probably through the activation of protein kinase C), and inhibited sphingosine-induced phosphorylation with an IC50 of approximately 20 microM. Oleic anhydride failed to induce changes in basal protein phosphorylation but inhibited sphingosine-activated protein kinases, thus distinguishing the effects of fatty acids on protein kinase C from the inhibition of sphingosine-induced phosphorylation. These studies define two distinct sphingosine-activated protein kinases and reveal an important interaction between two classes of putative lipid second messengers.

Abstract  The adsorption behavior of 1,1,2,2,-tetrahydroheptadecafluorodecanol (FC10OH), 1-eicosanol (C20OH), and their mixtures at the hexane solution/water interface is summarized briefly and examined from the viewpoints of interfacial tensions in the presence of domains, domain formation, and the correlation between the phase transition and the miscibility of film forming substances in the adsorbed films. The two-dimensional analogue of the Laplace equation showed that the interfacial tension is always higher in the presence of domains than that in the absence of them. The higher tendency of domain formation of FC10OH compared to C20OH is mainly ascribed to the excess Gibbs energy of mixing of fluorocarbon chains and hydrocarbon solvent being positive and to the interaction energy between domains being more stable against cohesion for FC10OH than for C20OH. The thermodynamic equations derived here suggested the heteroazeotropy in the phase diagram of adsorption and the temperature dependence of interfacial tension at the phase transition points, which are in accord with the experimental findings qualitatively.

Abstract  Addition of stearyl alcohol to the culture medium of Ralstonia sp. NT80 induced expression of a significant amount of secretory lipase. Comparative proteomic analysis of extracellular proteins from NT80 cells grown in the presence or absence of stearyl alcohol revealed that stearyl alcohol induced expression of several secretory proteins including lipase, haemolysin-coregulated protein and nucleoside diphosphate kinase. Expression of these secreted proteins was upregulated at the transcriptional level. Stearyl alcohol also induced the synthesis of polyhydroxyalkanoate. Secretory protein EliA was required for all these responses of NT80 cells to stearyl alcohol. Accordingly, the effects of stearyl alcohol were significantly reduced in the eliA deletion mutant cells of NT80 (ΔeliA). The remaining concentration of stearyl alcohol in the culture supernatant of the wild-type cells, but not that in the culture supernatant of the ΔeliA cells, clearly decreased during the course of growth. These observed phenotypes of the ΔeliA mutant were rescued by gene complementation. The results suggested that EliA is essential for these cells to respond to stearyl alcohol, and that it plays an important role in the recognition and assimilation of stearyl alcohol by NT80 cells.

Abstract  A total of 96 sputum specimens from patients with suspected or known mycobacterial and nonmycobacterial pulmonary infections were analyzed by gas chromatography-mass spectrometry for the presence of 2-eicosanol. This secondary alcohol was detected in all of the 25 sputum specimens culture positive for Mycobacterium tuberculosis, in 7 of the 9 sputum specimens culture positive for M. avium complex, and in all 3 of the studied sputum specimens associated with M. malmoense. The alcohol was not detected in any of the 45 culture-negative sputum specimens or in 14 sputum specimens culture positive for Staphylococcus aureus, Pseudomonas aeruginosa, Haemophilus influenzae, and Streptococcus pneumoniae. The ratio of tuberculostearic acid to 2-eicosanol was much lower in sputum samples culture positive for mycobacteria than in the corresponding in vitro-grown cultures. The present findings indicate that 2-eicosanol may be useful as a chemical marker for rapid diagnosis of pulmonary infections caused by the M. avium complex, M. malmoense, and M. tuberculosis.

Abstract  Electrolytic respirometry was used to determine the biodegradation kinetic parameters of five volatile aromatic organic compounds: benzene, 1,2-dichlorobenzene, 1,3-dichlorobenzene, 1,4-dichlorobenzene, and 1,2,3-trichlorobenzene. A protocol developed earlier was modified to accommodate the volatile characteristic of the test compounds. Specifically, the model used in data analysis was modified using Henry's law constant to incorporate the effect of partitioning of a volatile substrate between the gas and liquid phases in a batch reactor. Similar kinetic parameters were obtained for benzene and its four chlorinated analogs. Substrate inhibition was observed in the case of 1,3- and 1,4-dichlorobenzene, and intermediate product inhibition was observed in the case of 1,2-dichlorobenzene. In addition, all chlorinated benzenes exhibited complete inhibition above certain threshold concentrations.

Abstract  This article presents the inaugural intercalation study of a layered metal sulfonate network. Silver triflate forms intercalation complexes with straight chain primary alcohols from ethanol (C(2)H(5)OH) to eicosanol (C(20)H(41)OH). Single-crystal data for the EtOH adduct, 1, are presented which show that the intercalation is coordinative to Ag. In contrast to many other layered hosts, no preheating of Ag triflate is required to liberate a coordination site for intercalation to take place, owing to the ability of the triflate ion to reorient. Crystal structure parameters for 1: C(4)H(6)F(6)S(2)O(7)Ag(2), a = 5.345(7) A, b = 11.310(2) A, c = 12.004(2) A, alpha = 116.87(1) degrees, beta = 90.46(1) degrees, gamma = 99.59(1) degrees, triclinic, space group P, Z = 2. Intercalate 1 presents the triflate ion in an unprecedented mu(5)-coordination mode. PXRD data on the family of complexes show that the intercalation is topotactic, as verified by the linear increase in d-spacing and calculated c-axis lengths for the intercalates, with increasing chain length. The data also show that the alcohol intercalates adopt an interdigitated rather than bilayer arrangement.

Abstract  The purpose of this work was to develop a novel polyurethane hydrogel system for sustained drug release, which could be used as a vaginal drug-delivery vehicle. The blank polyurethane hydrogels were synthesized by a polyol oligomeric, a diisocyanate and a triol (used as cross-linking agent). In order to improve the swelling ability of a polyurethane hydrogel, a small amount of 1-octadecanol was added. Additionally, the structure, mechanical properties and thermal properties of polymers were assessed by FT-IR, WAXD, DSC and mechanical tests. The results show that no more than 2.5 wt% of 1-octadecanol additives is sufficient to affect the release profile without changing the structure and mechanical properties of the polyurethane hydrogels obviously. Tinidazole was chosen as a model drug, the release data of drug from polyurethane hydrogels were fitted using the Ritger-Peppas equation and the result showed that it was non-Fickian diffusion, which means that the drug release was controlled by both swollen control and diffusion control. In conclusion, our work proves that the synthesized polyurethane hydrogel modified by 1-octadecanol may be a promising sustained release drug carrier.

Abstract  Petroleum middle distillates (PMDs), a class of hydrocarbons which boil between 350-700 degrees F, are tumor promoters in mouse skin. The promotional activity is produced under conditions that also result in local changes, including chronic irritation and epidermal hyperplasia. The present study was conducted by comparing equal weekly doses of irritating and minimally or nonirritating test materials, to assess whether tumor promotion was a secondary response to these effects. Four PMDs, C10-C14 normal paraffins (NP), lightly refined paraffinic oil (LRPO), Jet Fuel A (JF), and steam-cracked gas oil (SCGO), were evaluated. Test materials were applied undiluted (2x/week) or as 28.6% (7x/week) or 50% (4x/week) concentrations in mineral oil for 52 weeks following initiation with dimethylbenzanthracene (DMBA). When applied undiluted, all materials produced moderate irritation and significant increase in tumor incidence. When NP, LRPO, or JF were applied in mineral oil diluent, skin irritation was generally ameliorated and few, if any, tumors were produced. SCGO was irritating and produced a significant increase in tumor frequency when administered in mineral-oil diluent. These data indicate that the promotional activity of straight-run PMDs is likely related to chronic irritation at the application site and not to dose. Thus, when used appropriately in the absence of prolonged irritation, these materials should not present a tumorigenic hazard to humans.