Japanese guidelines for occupational allergic diseases 2020.

Occupational allergic diseases are likely to worsen or become intractable as a result of continuous exposure to high concentrations of causative allergens. These are socioeconomically important diseases that can lead to work interruptions for patients and potentially job loss. We published the first guideline for managing occupational allergic diseases in Japan. The original document was published in Japanese in 2013, and the following year (2014) it was published in English. This guideline consists of six chapters about occupational asthma, occupational allergic rhinitis, occupational skin diseases, hypersensitivity pneumonitis, occupational anaphylaxis shock, and the legal aspects of these diseases. Providing general doctors with the knowledge to make evidence-based diagnoses and to understand the occupational allergic disease treatment policies, was a breakthrough in allergic disease treatment. Due to the discovery of new occupational allergens and the accumulation of additional evidence, we published a revised version of our original article in 2016, and it was published in English in 2017. In addition to including new knowledge of allergens and evidence, the 2016 revision contains a "Flowchart to Diagnosis" for the convenience of general doctors. We report the essence of the revised guidelines in this paper.

[LONG-TERM RESULTS OF AIRBORNE POLLEN SURVEYS IN THE JAPANESE ARCHIPELAGO FROM THE PERSPECTIVE OF POLLEN ANTIGEN].

BACKGROUND: In 1986, the Ministry of Health and Welfare started an airborne pollen survey as part of measures against JC pollinosis. We reported the important tree pollen antigens in 2016. We have now estimated the longitudinal investigated results for successful prevention and treatment for allergic symptoms related to grass and weed pollen in Japan. METHOD: Since July 1986 we have monitored airborne pollen, year- round, using a gravitational pollen sampler (Durham's sampler), at more than 20 locations across Japan. Specimens were mailed to our facility, where they were stained with Calberla solution, counted under an optical microscope, and converted to the number of pollen per square centimeter. For convenience the number of collected pollen were compiled every six months, with the January to June samples classified as spring pollen and the July to December as autumn pollen even same family. RESULT: Total pollen counts at each location were extremely small compared to tree-pollen, averaging 73~650 pollen grains per year. The Sagamihara location had the greatest count. Unlike cedar and cypress there were no significant annual fluctuations, but grass and Ambrosia pollen counts are increasing in some regions. Spring grass pollen gave the largest count, at 30% of the total collected. CONCLUSION: This indicated we need to examine the rinoconjuctivitis and oral allergy syndrome related to herbaceous pollen carefully.The importance of airborne pollen surveys for the treatment of the patients with pollen allergies was suggested.

Heterologous expression of geraniol dehydrogenase for identifying the metabolic pathways involved in the biotransformation of citral by Acinetobacter sp. Tol 5.

The biotransformation of citral, an industrially important monoterpenoid, has been extensively studied using many microbial biocatalysts. However, the metabolic pathways involved in its biotransformation are still unclear, because citral is a mixture of the trans-isomer geranial and the cis-isomer neral. Here, we applied the heterologous expression of geoA, a gene encoding geraniol dehydrogenase that specifically converts geraniol to geranial and nerol to neral, to identify the metabolic pathways involved in the biotransformation of citral. Acinetobacter sp. Tol 5 was employed in order to demonstrate the utility of this methodology. Tol 5 transformed citral to (1R,3R,4R)-1-methyl-4-(1-methylethenyl)-1,3-cyclohexanediol and geranic acid. Biotransformation of citral precursors (geraniol and nerol) by Tol 5 transformant cells expressing geoA revealed that these compounds were transformed specifically from geranial. Our methodology is expected to facilitate a better understanding of the metabolic pathways involved in the biotransformation of substrates that are unstable and include geometric isomers.

LONGITUDINAL MONITORING OF TREE AIRBORNE POLLEN IN JAPAN.

RATIONAL: In Japan patients with Japanese Cedar (JC) pollinosis have increased nation widely since the latter of 1970's. The Ministry of Health and Welfare of Japanese Governments has begun to take preventive measures against JC pollinosis and airborne pollen monitoring has begun to investigate as a causative agent since 1986. We have estimated the longitudinal investigation result for successful prevention and treatment against pollinosis in Japan. METHOD: We have monitored airborne pollen all year around since July 1986 by gravitational pollen sampler, Durham's sampler, at more than 20 locations in the Japanese Islands. Pollen samples were sent to our hospital and counted pollen number per cm2 after stained by Calberla solution and then classified main pollen grains as a causative agent of pollinosis. RESULT AND DISCUSSION: JC pollen number was the most of all, more than 40%, next cypress family, about 20%. They were occupied of more than 60% of all and they increased with the remarkable annual fluctuation as the allergen of JC pollinosis. Beech family pollen counting were also increasing and occupied about 10% of all pollen counts. In Hokkaido the prevalence of birch family pollen count was larger than that in other districts. There is cross-reactivity between beech and birch family which related with oral allergic syndrome.Perspective and Conclusion: In future new occurrences of oral allergy syndrome due to increasing allergic tree pollen grains would be appeared. The contentious pollen research should be important for patients with pollinosis in Japan.

Japanese guidelines for occupational allergic diseases 2017.

In 2013, a guideline for occupational allergic diseases was published for the first time in Japan. Occupational allergic diseases are likely to worsen or become intractable as a result of continuous exposure to high concentrations of causative antigens, and are socioeconomically important diseases with which the patients might sometimes lose jobs due to work interruptions. Guidelines for occupational allergic diseases have been published in many countries. This guideline consists of six chapters about occupational asthma, occupational allergic rhinitis, occupational skin diseases, hypersensitivity pneumonitis and occupational anaphylaxis shock, and legal aspects of these diseases. The guideline is characterized with the following basic structure: Clinical Questions (CQs) are set with reference to Minds (Medical Information Network Distribution Service), statements by the committee are correspondingly listed, recommended grades and evidence levels are defined, and then descriptions and references are indicated.

Sexual Differences in Chemical Composition and Aroma-active Compounds of Essential Oil from Flower Buds of Eurya japonica.

This study was conducted to determine the composition of essential oil from buds of male and female Eurya japonica flowers and to determine the aroma-active compounds of this plant by gas chromatography-mass spectrometry (GC-MS), sensory evaluation, and odor activity values (OAV). The oils contained eighty-five compounds. We identified for the first time forty-four compounds in E. japonica. Through sensory evaluation, nineteen aroma-active compounds were identified by gas chromatography-olfactometry (GC-O). Because the chemical composition can affect the interaction between plants and herbivorous insects, our results suggest that essential oils from male and female flower buds of E. japonica differently affect herbivores. Sexual differences in essential oils deserve further investigations in this plant-insect system.

Chemical composition, aroma evaluation, and inhibitory activity towards acetylcholinesterase of essential oils from Gynura bicolor DC.

The compositions of the essential oils obtained from leaves and stems of Gynura bicolor DC. were analyzed by GC-MS. One hundred eight components of these oils were identified. (E)-ß-caryophyllene (31.42 %), α-pinene (17.11 %), and bicyclogermacrene (8.09 %) were found to be the main components of the leaf oil, while α-pinene (61.42 %), ß-pinene (14.39 %), and myrcene (5.10 %) were the major constituents of the stem oil. We found 73 previously unidentified components in these oils from G. bicolor. The oils were also subjected to odor evaluation. Eleven and 12 aroma-active compounds were detected in the leaf and stem oils, respectively. The abilities of these oils to inhibit acetylcholinesterase (AChE) activity were determined. The sesquiterpenoids in the oils were found to inhibit AChE activity more strongly than the monoterpenoids in the oils did. It was suggested that the three main components in each essential oil act synergistically against AChE activity. These results show that the essential oils obtained from G. bicolor are a good dietary source of AChE activity inhibition.

Chemical Composition and Characteristic Odor Compounds in Essential Oil from Alismatis Rhizoma (Tubers of Alisma orientale).

Chemical composition and potent odorants that contribute to the characteristic odor of essential oil from Alismatis Rhizoma (tubers of Alisma orientale) were investigated by gas chromatography-mass spectrometry (GC-MS), GC-olfactometry (GC-O), aroma extract dilution analysis (AEDA) and relative flavor activity (RFA) methods. Fifty components, representing 94.5% of the total oil, were identified. In this study, we newly identified thirty-nine compounds in the oil from tubers of A. orientale. The major constituents of the essential oil were khusinol (36.2%), δ-elemene (12.4%), germacron (4.1%), alismol (3.8%), ß-elemene (3.1%), and α-bisabolol (1.9%). Through sensory analysis, sixteen aroma-active compounds were detected and the key contributing aroma-active compounds were δ-elemene (woody, flavor dilution (FD)-factor = 4, RFA = 0.3) ß-elemene (spicy, FD = 5, RFA = 0.7), spathulenol (green, FD = 5, RFA = 1.0), γ-eudesmol (woody, FD = 6, RFA = 1.5), and γ-cadinol (woody, FD = 5, RFA = 1.0). These compounds are thought to contribute to the odor from tubers of A. orientale. These results imply that the essential oil from the tubers of A. orientale deserve further investigations in the phytochemical and medicinal fields.

Chemical Composition and Aroma Evaluation of Essential Oils from Skunk Cabbage (Symplocarpus foetidus).

Two sample preparation methods, namely hydrodistillation (HD) and solvent-assisted flavor evaporation (SAFE), have been used to investigate the essential oils of the aerial parts (leaves and stems) of Symplocarpus foetidus, a plant with a characteristic odor, by gas chromatography mass spectrometry (GC-MS). Characteristic aroma-active compounds in the oils were detected by GC-Olfactometry (GC-O) and aroma extract dilution analysis (AEDA). From the HD method, the main compounds in the oil were found to be p-vinyl-guaiacol (15.5%), 2-pentyl-furan (13.4%), and (Z)-ligustilide (9.5%). From the SAFE method, the main compounds were 2-butoxy-ethanol (49.6%), ethyl-pentanoate (4.5%), and mesitylene (4.0%). In HD oil, the most intense aroma-active compounds were 2-pentyl-furan (flavor dilution factor (FD) = 32, odor activity value (OAV) = 57), p-vinyl-guaiacol (FD = 16, OAV = 41), and dimethyl disulfide (FD = 16, OAV = 41). In SAFE oil, the main aroma-active compounds were 2-butoxy ethanol (FD = 32, OAV = 16), and 2-methoxy thiazole (FD = 32, OAV = 25).

Evaluation of the Key Odorants in Volatile Oils from Tubers of Apios americana Medikus.

This study was investigated the chemical composition of volatile oils and aroma evaluation from the tubers of Apios americana Medikus. Theses volatile oils were obtained by the hydrodistillation (HD) and the solvent-assisted flavor evaporation (SAFE) methods. These oils were analyzed by Gas chromatography (GC), GC-mass spectrometry (GC-MS), GC-olfactometry (GC-O), aroma extract dilution analysis (AEDA) and odor activity values (OAV) for the first time. The major compounds in the HD oil were palmitic acid (36.5%), linoleic acid (10.5%) and nonadecanol (5.7%). Meanwhile, in the SAFE oil, the major compounds were 4-hydroxy-4-methyl-2-pentanone (34.2%), hexanal (11.0%) and hexanol (7.9%). Through aroma evaluation, 20 (HD) and 14 (SAFE) aroma-active compounds were identified by GC-O. As a result, the most intense aroma-active compounds in both extraction methods were 1-octen-3-ol and hexanal, both of which showed high odor activity values (OAV).

Chemical Composition and Character Impact Odorants in Volatile Oils from Edible Mushrooms.

The aim of this study was to investigate the chemical composition and the odor-active components of volatile oils from three edible mushrooms, Pleurotus ostreatus, Pleurotus eryngii, and Pleurotus abalonus, which are well-known edible mushrooms. The volatile components in these oils were extracted by hydrodistillation and identified by GC/MS, GC-olfactometry (GC-O), and aroma extract dilution analysis (AEDA). The oils contained 40, 20, and 53 components, representing 83.4, 86.0, and 90.8% of the total oils in P. ostreatus, P. eryngii, and P. abalonus, respectively. Odor evaluation of the volatile oils from the three edible mushrooms was also carried out using GC-O, AEDA, and odor activity values, by which 13, eight, and ten aroma-active components were identified in P. ostreatus, P. eryngii, and P. abalonus, respectively. The most aroma-active compounds were C8 -aliphatic compounds (oct-1-en-3-ol, octan-3-one, and octanal) and/or C9 -aliphatic aldehydes (nonanal and (2E)-non-2-enal).

Chemical Compositions and Aroma Evaluation of Volatile Oil from the Industrial Cultivation Medium of Enterococcus faecalis.

Enterococcus faecalis is one of the major lactic acid bacterium (LAB) species colonizing the intestines of animals and humans. The characteristic odor of the volatile oils obtained from both the liquid medium after incubation (MAI) and liquid medium before incubation (MBI) in the cultivation process of E. faecalis was investigated to determine the utility of the liquid medium. In total, fifty-six and thirty-two compounds were detected in the volatile oils from the MAI (MAI oil) and MBI (MBI oil), respectively. The principle components of MAI oil were 2,5-dimethylpyrazine (19.3%), phenylacetaldehyde (19.3%), and phenylethyl alcohol (9.3%). The aroma extract dilution analysis (AEDA) method was performed using gas chromatography-olfactometry (GC-O). The total number of aroma-active compounds identified in the volatile oil from MBI and MAI was thirteen compounds; in particular, 5-methyl-2-furanmethanol, phenylacetaldehyde, and phenylethyl alcohol were the most primary aroma-active compounds in MAI oil. These results imply that the industrial cultivation medium after incubation of E. faecalis may be utilized as a source of volatile oils.

Volatile Compounds with Characteristic Odor of Essential Oil from Magnolia obovata Leaves by Hydrodistillation and Solvent-assisted Flavor Evaporation.

The present study focuses on the volatile compounds with characteristic odor of essential oil from the leaves of Magnolia obovata by hydrodistillation (HD) and solvent-assisted flavor evaporation (SAFE) method. Eighty-seven compounds, representing 98.0% of the total oil, were identified using HD. The major compounds of HD oil were (E)-ß-caryophyllene (23.7%), α-humulene (11.6%), geraniol (9.1%), and borneol (7.0%). In SAFE oil, fifty-eight compounds, representing 99.7% of the total oil, were identified. The main compounds of SAFE oil were (E)-ß-caryophyllene (48.9%), α-humulene (15.7%), and bicyclogermacrene (4.2%). In this study, we newly identified eighty-five compounds of the oils from M. obovata leaves. These oils were also subjected to aroma evaluation by gas chromatography-olfactometry (GC-O) and aroma extract dilution analysis (AEDA). As a result, twenty-four (HD) and twenty-five (SAFE) aroma-active compounds were detected. (E)-ß-Caryophyllene, α-humulene, linalool, geraniol, 1,8-cineole, and bicyclogermacrene were found to impart the characteristic odor of M. obovata leaves. These results imply that the oils of M. obovata leaves must be investigated further to clarify their potential application in the food and pharmaceutical industries.

Metabolism of (-)-cis- and (-)-trans-rose oxide by cytochrome P450 enzymes in human liver microsomes.

The in vitro metabolism of (-)-cis- and (-)-trans-rose oxide was investigated using human liver microsomes and recombinant cytochrome P450 (P450 or CYP) enzymes for the first time. Both isomers of rose oxide were incubated with human liver microsomes, and the formation of the respective 9-oxidized metabolite were determined using gas chromatography-mass spectrometry (GC-MS). Of 11 different recombinant human P450 enzymes used, CYP2B6 and CYP2C19 were the primary enzymes catalysing the metabolism of (-)-cis- and (-)-trans-rose oxide. CYP1A2 also efficiently oxidized (-)-cis-rose oxide at the 9-position but not (-)-trans-rose oxide. α-Naphthoflavone (a selective CYP1A2 inhibitor), thioTEPA (a CYP2B6 inhibitor) and anti-CYP2B6 antibody inhibited (-)-cis-rose oxide 9-hydroxylation catalysed by human liver microsomes. On the other hand, the metabolism of (-)-trans-rose oxide was suppressed by thioTEPA and anti-CYP2B6 at a significant level in human liver microsomes. However, omeprazole (a CYP2C19 inhibitor) had no significant effects on the metabolism of both isomers of rose oxide. Using microsomal preparations from nine different human liver samples, (-)-9-hydroxy-cis- and (-)-9-hydroxy-trans-rose oxide formations correlated with (S)-mephenytoin N-demethylase activity (CYP2B6 marker activity). These results suggest that CYP2B6 plays important roles in the metabolism of (-)-cis- and (-)-trans-rose oxide in human liver microsomes.

Identification of Aroma-active Compounds in Essential Oil from Uncaria Hook by Gas Chromatography- Mass Spectrometry and Gas Chromatography-Olfactometry.

The chemical composition of essential oil extracted from Uncaria Hook ("Chotoko" in Japanese), the branch with curved hook of the herbal medicine Uncaria rhynchophylla has been investigated by GC and GC-MS analyses. Eighty-four compounds, representing 90.8% of the total content was identified in oil obtained from Uncaria Hook. The main components i were (E)-cinnamaldehyde (13.4%), α-copaene (8.0%), methyl eugenol (6.8%), δ-cadinene (5.3%), and curcumene (3.6%). The important key aroma-active compounds in the oil were detected by gas chromatography-olfactometry (GC-O) and aroma extract dilution analysis (AEDA), using the flavor dilution (FD) factor to express the odor potency of each compounds. Furthermore, the odor activity value (OAV) has been used as a measure of the relative contribution of each compound to the aroma of the Uncaria Hook oil. The GC-O and AEDA results showed that α-copaene (FD = 4, OAV = 4376), (E)-linalool oxide (FD = 64, OAV = 9.1), and methyl eugenol (FD = 64, OAV = 29) contributed to the woody and spicy odor of Uncaria Hook oil, whereas furfural (FD = 8, OAV = 4808) contributed to its sweet odor. These results warrant further investigations of the application of essential oil from Uncaria Hook in the phytochemical and medicinal fields.

Characteristic odor components of essential oils from Eurya japonica.

The chemical compositions of essential oils from the flower and aerial parts (i.e., leaf and branch) of Eurya japonica were determined and quantified using gas chromatography-mass spectrometry (GC-MS). A total of 87 and 50 compounds were detected in the oils from the flower and aerial parts, respectively. The main compounds of the flower oil were linalool (14.0%), (9Z)-tricosene (12.0%), and nonanal (7.4%). In the oil from the aerial parts, linalool (37.7%), α-terpineol (13.5%), and geraniol (9.6%) were detected. In the oils from the flower and aerial parts, 13 and 8 aroma-active compounds were identified by GC-olfactometry (GC-O) analysis, respectively. The key aroma-active compounds of the flower oil were heptanal [fatty, green, flavor dilution (FD) = 128, odor activity value (OAV) = 346], nonanal (sweet, citrus, FD = 128, OAV = 491), and eugenol (sweet, spicy, FD = 64, OAV = 62): in the oil from the aerial parts, the key aroma-active compounds were linalool (sweet, citrus, FD = 64, OAV = 95), (E)-ß-damascenone (sweet, FD = 256, OAV = 4000), and (E)-ß-ionone (floral, violet, FD = 128, OAV = 120). This study revealed that nonanal and eugenol impart the sweet, citrus, and spicy odor of the flower oil, while (E)-ß-damascenone and (E)-ß-ionone contribute the floral and sweet odor of the oil from the aerial parts.

Agroecosystem development of industrial fermentation waste -- characterization of aroma-active compounds from the cultivation medium of Lactobacillus brevis.

Volatile oils obtained from both the liquid medium after incubation (MAI) and liquid medium before incubation (MBI) during the cultivation process of Lactobacillus brevis were isolated by hydrodistillation (HD) and analyzed to determine the utility of the liquid waste. The composition of the volatile oils was analyzed by capillary gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). In total, 55 and 36 compounds were detected in the volatile oils from MAI (MAI oil) and MBI (MBI oil), respectively. The principle components of MAI oil were N-containing compounds, including 2,3-dimethylpyrazine (16, 37.1 %), methylpyrazine (4, 17.1 %). The important aroma-active compounds in the oils were detected by GC-Olfactometry (GC-O), and their intensity of aroma were measured by aroma extract dilution analysis (AEDA). Expressly, pyrazine compounds were determined as key aroma components; in particular, 2,5-dimethylpyrazine and 2,3-dimethylpyrazine were the most primary aroma-active compound in MAI oil. These results imply that the waste medium after incubation of L. brevis may be utilized as a source of volatile oils.

Characteristic Chemical Components and Aroma-active Compounds of the Essential Oils from Ranunculus nipponicus var. submersus Used in Japanese Traditional Food.

Ranunculus nipponicus var. submersus is an aquatic macrophyte; it is known as a wild edible plant in Japan for a long time. In this study, the essential oils from the fresh and dried aerial parts of R. nipponicus var. submersus were extracted by hydrodistillation and analyzed by gas chromatography (GC) and GC-mass spectrometry (GC-MS). Moreover, important aroma-active compounds were also detected in the oil using GC-olfactometry (GC-O) and aroma extract dilution analysis (AEDA). Thus, 98 compounds (accounting for 93.86%) of the oil were identified. The major compounds in fresh plant oil were phytol (41.94%), heptadecane (5.92%), and geranyl propionate (5.76%), while those of. Dried plant oil were ß-ionone (23.54%), 2-hexenal (8.75%), and dihydrobovolide (4.81%). The fresh and dried oils had the green-floral and citrus-floral odor, respectively. The GC-O and AEDA results show that phenylacetaldehyde (green, floral odor, FD-factor = 8) and ß-ionone (violet-floral odor, FD-factor = 8) were the most characteristic odor compounds of the fresh oils. ß-Cyclocitral (citrus odor, FD-factor = 64) and ß-ionone (violet-floral odor, FD-factor = 64) were the most characteristic odor compounds of the dried oil. These compounds are thought to contribute to the flavor of R. nipponicus var. submersus.