Invited Review: From nose to gut - the role of the microbiome in neurological disease.

Inflammation and neurodegeneration are key features of many chronic neurological diseases, yet the causative mechanisms underlying these processes are poorly understood. There has been mounting interest in the role of the human microbiome in modulating the inflammatory milieu of the central nervous system (CNS) in health and disease. To date, most research has focussed on a gut-brain axis, with other mucosal surfaces being relatively neglected. We herein take the novel approach of comprehensively reviewing the roles of the microbiome across several key mucosal interfaces - the nose, mouth, lung and gut - in health and in Parkinson's disease (PD), Alzheimer's disease (AD) and multiple sclerosis (MS). This review systematically appraises the anatomical and microbiological landscape of each mucosal surface in health and disease before considering relevant mechanisms that may influence the initiation and progression of PD, AD and MS. The cumulative effects of dysbiosis from the nose to the gut may contribute significantly to neurological disease through a wide variety of mechanisms, including direct translocation of bacteria and their products, and modulation of systemic or CNS-specific immunity. This remains an understudied and exciting area for future research and may lead to the development of therapeutic targets for chronic neurological disease.

A rapid and selective method for determining potential nitrosating agents in cosmetic products by chemiluminescence detection of nitric oxide.

A method was developed for rapid and selective determination of potential nitrosating agents at the part-per-billion level in cosmetic products. These compounds are chemically reduced to nitric oxide, which is determined by its chemiluminescent reaction with ozone. Suspended materials and colors in cosmetic products do not interfere. Hence their removal before analysis is not required. A detection limit of 33 ppb, calculated as nitrite, was obtained. No false-positive interferences were observed from antifoaming agents, several N-nitroso compounds, and nitrate up to 20 ppm. Among cosmetic products surveyed, potential nitrosating agents were found at levels ranging from 113 to 5021 ppb. No consistent relationship was found between levels of potential nitrosating agents and N-nitrosamines in the same products. However, the highest levels of nitrosating agents were most often associated with the highest levels of N-nitrosamines known to be present in the products.

Determination of 2-ethylhexyl 4-(N-methyl-N-nitrosamino) benzoate in commercial sunscreens and cosmetic products.

An analytical method has been developed for determination of 2-ethylhexyl 4-(N-methyl-N-nitrosamino) benzoate (NMPABAO), a nitrosamine contaminant in sunscreen products containing 2-ethylhexyl 4-(N,N-dimethylamino) benzoate (Padimate O). The method involves extraction of NMPABAO by column chromatography followed by liquid chromatographic separation and analysis wit a nitric oxide detector. To confirm the presence of NMPABAO in sunscreen products, the N-nitrosamine was synthesized and its structure was determined by infrared spectrophotometry, nuclear magnetic resonance spectrometry, and mass spectrometry (MS). For method validation, recovery studies were performed on a commercial suntan lotion, cream, and gel. Recoveries of NMPABAO added to representative test samples averaged 83%. The method has an estimated detection limit of 30 ppb. The method was used to analyze 25 commercial cosmetic and sunscreen products containing Padimate O. Eleven products contained NMPABAO at levels ranging from 160 to 21000 ppb. NMPABAO presence in 4 products was confirmed by MS at levels > or = 4000 ppb. The highest levels of NMPABAO were associated with products that contained the nitrite-releasing preservative 2-bromo-2-nitro-1,3-propanediol.

Determination of musk ambrette in fragrance products by capillary gas chromatography with electron capture detection: interlaboratory study.

A gas chromatographic method that uses an internal standard additions techniques is described for the determination of musck ambrette (MA) in fragrance products. A solution containing the product and a known amount of an internal standard, musk tibetene (MT), is injected directly into a gas chromatograph equipped with an electron capture detector. The chromatographic separation of the components on a wide-bore fused silica capillary column is recorded and a response constant is calculated from MA and MT peak heights. A similar response constant is also calculated for a standard solution containing known concentrations of MA and MT. The MA content of the fragrance product is then calculated. Average recoveries of MA from fragrance products ranged from 97.6 to 102.3%. The method was also evaluated collaboratively by 6 laboratories. In this study, the reproducibility relative standard deviation for MA in 6 fragrance test samples ranged from 2.78 to 22.87%.

Fluorometric determination of benzylideneacetone in fragrance products by liquid chromatography with post-column derivatization.

A method is described for the liquid chromatographic (LC)-fluorometric determination of benzylideneacetone in fragrance products. Benzylideneacetone is first separated from other fragrance ingredients by LC and then reacted post-column with a methanolic solution of isonicotinic acid hydrazide and aluminum nitrate. The reactants are maintained at 65 degrees C for about 1.5 min to quantitatively form the fluorescent isonicotinoyl hydrazone derivative of benzylideneacetone. The aluminum ion forms a complex with the hydrazone to enhance the fluorescence of the derivative. The amount of benzylideneacetone is determined by measuring the intensity of the fluorescence emitted by the hydrazone derivative and comparing that value with those obtained for derivatized standards. Recovery studies were conducted by spiking commercial fragrances with benzylideneacetone at concentrations of 0.01, 0.05, and 0.1% (w/v). Recoveries ranged from 98 to 104% with a mean recovery of 100.2% and a standard deviation of 2.4%.

Liquid chromatographic-fluorometric determination of cinnamyl alcohol in perfumes, colognes, and toilet waters.

A liquid chromatographic (LC) method is described for the determination of cinnamyl alcohol (3-phenyl-2-propen-1-ol) in fragrance compositions. The fragrance product is partially cleaned up by diluting the fragrance with a 95% ethanol-water mixture and passing it through a short column containing RP-8 packing. An aliquot of the effluent is then analyzed by LC using an RP-18 column interfaced to a spectrophotofluorometer equipped with double monochromators. The fluorescence emission intensity of the eluted cinnamyl alcohol is measured and compared with that of a standard to calculate the amount of cinnamyl alcohol present. Recoveries from fragrance products fortified with cinnamyl alcohol at levels ranging from 0.0020 to 0.060 mg/mL ranged from 85 to 105% with a mean of 94%. The lowest level of determination was 0.0005 mg/mL.

Liquid chromatographic separation and fluorometric determination of cis- and trans-isoeugenol in perfumes, colognes, and toilet waters.

A liquid chromatographic (LC)-fluorometric method is described for the determination of cis- and trans-isoeugenol (2-methoxy-4-propenylphenol) in perfumes, colognes, and toilet waters. A test portion of the product is added to diethyl ether, and the isoeugenol isomers are extracted with sodium hydroxide solution. The basic extract is then acidified, and the isoeugenol isomers are extracted with isooctane. Aliquots of the isooctane extract are analyzed by using a silver ion cation exchange LC column interfaced to a spectrophotofluorometer. Each isomer in the product is determined by comparing its fluorescence emission intensity with that of an external standard consisting of a mixture of both isomers in which the relative concentration of each has been determined. Average recoveries from various commercial fragrances fortified with a mixture of cis- and trans-isoeugenol with total isoeugenol content of 0.1, 0.5, and 4.0 mg/mL ranged from 87 to 105% for the trans-isomer (SD = 4.6%) and from 83 to 113% for the cis-isomer (SD = 6.7%). The limit of determination is approximately 0.002 mg/mL.

Determination of cinnamyl anthranilate in perfume, cologne, and toilet water by liquid chromatography with fluorescence detection.

A liquid chromatographic method with fluorescence detection was developed for the determination of cinnamyl anthranilate in perfumes and other fragrance compositions. The method was evaluated by conducting recovery studies of 10 different commercial fragrance compositions to which cinnamyl anthranilate had been added at levels of 0.1, 0.5, and 1.0 mg/mL. Recoveries ranged from 91 to 103% with a mean of 97% and a standard deviation of +/- 3.3%.

Screening cosmetic products for N-nitroso compounds by chemiluminescent determination of nitric oxide.

Cosmetic products were screened for total N-nitroso compounds by chemiluminescent measurement of nitric oxide liberated by the reductive cleavage of the N-nitroso group. The cosmetic was first partitioned between methylene chloride and water to separate polar and nonpolar N-nitroso compounds. Each extract was then examined for the presence of N-nitroso compounds by adding the cleavage reagent and sweeping the nitric oxide formed into a chemiluminescent analyzer. Although the method is not intended to be quantitative, recovery studies were conducted to determine measurable levels. Recovery studies of polar N-nitroso compounds were conducted by adding N-nitrosodiethanolamine (NDELA) to a cream, a shampoo, and a lotion at 3 levels, i.e., 80, 320, and 960 ppb, and then determining NDELA by the method. Recoveries ranged from 48 to 83% (mean 68%; SD = 11.9). For recoveries of nonpolar N-nitroso compounds, 100, 200, and 500 ppb of N-nitrosomethyltetradecylamine were added to the 3 cosmetic products. Recoveries ranged from 58 to 70% (mean 63%; SD = 5.3).

High-performance liquid chromatographic-fluorometric determination of cinnamaldehyde in perfume, cologne and toilet water.

A high-performance liquid chromatographic (HPLC)-fluorometric method is described for the determination of trans-cinnamaldehyde in fragrances. The fragrance is added to isooctane and extracted with an aqueous solution of the sodium salt of 6-aminocaproic acid to isolate the aldehyde fraction. After dilution with water, an aliquot of the extract is added to a solution of 1,2-diaminonaphthalene monosulfate in dilute formic acid. The fluorescent derivative of cinnamaldehyde, 2-styrylnaphth[1,2-d]imidazole, is prepared by incubating and then cooling the solution and adding pyridine. Aliquots of the fluorophore solution are analyzed on a reversed-phase C18 HPLC column by using a buffered tetrahydrofuran-water eluent. Cinnamaldehyde is quantitated by comparing fluorescence emission intensity with that of a standard. Recoveries from samples of various commercial fragrances, spiked with cinnamaldehyde at the 0.01, 0.05 and 0.1% levels, ranged from 94 to 112% with a mean of 103% and a standard deviation of 5.3. The limit of detection is approximately 1 ng.

High pressure liquid chromatographic-thermal energy determination of N-nitrosodiethanolamine in cosmetics.

Methods for the determination and confirmation of N-nitrosodiethanolamine (NDELA) in cosmetic products were developed. The NDELA fraction was isolated from a cosmetic product by a series of solvent extractions which were designed to concentrate the NDELA and remove ingredients deleterious to the analytical system. The isolated fraction was then analyzed for NDELA using a high pressure liquid chromatograph (HPLC) interfaced with a thermal energy analyzer (TEA). The compound was measured by comparison of detector response with those of known standards. NDELA was verified by gas chromatography-mass spectrometry of the silyl derivative after preliminary cleanup of the sample by gradient elution HPLC on a Partisil 10 PAC column. The limit of detection of NDELA by TEA is 2-3 ng, which corresponds to 20-30 ppb in the cosmetic product. Analysis of an emulsion cream and a hair grooming gel spiked at 3 and 4 ng concentration levels, respectively, yielded recoveries ranging from 71 to 103% (average 88%).

Anthelmintic activity of diuredosan in dogs experimentally infected with Ancylostoma caninum and Trichuris vulpis.

The efficacy of diuredosan was determined in dogs experimentally infected with Ancylostoma caninum and Trichuris vulpis. Diuredosan at dosages of 25, 50, and 100 mg/kg was 99% effective against A caninum. Efficacies against T vulpis were 88, 85, and 94% at dosages of 25, 50, and 100 mg/kg, respectively.