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Advances in biologically based models for respiratory tract uptake of inhaled volatiles.

Physiologically based pharmacokinetic models for volatile organic chemicals typically describe the respiratory tract as a single compartment in which chemicals in the alveolar air space and the arterial blood are in instantaneous equilibrium. These models also assume that the distribution of chemical in the air-stream is uniform throughout the respiratory tract and that uptake is significant only in the alveolar region. A functional role for the upper respiratory tract in the uptake of volatile chemicals has been largely ignored. While these models have worked well for chemicals with low aqueous solubility in biological fluids, systemic uptake of highly soluble volatiles is overestimated. Thus, there is a significant effort to describe the critical determinants for uptake of soluble chemicals and to formulate models with more biologically relevant descriptions of respiratory tract structure and function. Investigators have addressed this problem from several viewpoints. Airflow patterns in the respiratory tract, regional metabolism, diffusion-dependent uptake, and the cyclic nature of respiration are now being incorporated into current models. Use of dosimetric models that incorporate relevant biology for inhaled chemicals will ultimately result in more meaningful human risk assessments.

Administration, Inhalation↗

Sex difference in attraction thresholds for volatile odors from male and estrous female mouse urine.

Volatile urinary odors from opposite sex conspecifics contribute to mate recognition in numerous mammalian species, including mice. We used a simple habituation/dishabituation testing procedure to ask whether the capacity to detect and investigate decreasing concentrations of volatile urinary odors is sexually differentiated in mice. Beginning 2 months after gonadectomy and in the absence of any sex steroid treatment, adult, sexually naive male and female CBA x C57Bl/6 F1 hybrid mice received two series of daily tests that involved the presentation of different dilutions of urine from C57Bl/6 males followed by urine from estrous females. Each test session began with three consecutive presentations of deionized water (10 microl on filter paper for 2 min, behind a mesh barrier which prevented direct physical access, in the home cage at 1-min intervals) followed by three presentations of one of five different dilutions of urine (a different dilution on each test day). Males and females showed equivalent, significant habituation/dishabituation responses (low investigation times for successive water presentations; increased investigation of the first urine stimulus, followed by a decline in successive urine investigation times) to both male and female urine/water dilutions of 1:1, 1:10, and 1:20. However, only female mice responded reliably to 1:40 and 1:80 dilutions of both types of urine, pointing to a sex dimorphism in the detection and/or processing of biologically relevant, volatile urinary odors by the main olfactory system.

Animals↗

Inhibition of protein synthesis and secretion by volatile anesthetics in guinea pig liver slices.

The decrease in protein synthesis and secretion caused by volatile anesthetics was investigated using Hartley male guinea pig liver slices. Precision-cut liver slices (250-300 mM thick) were incubated in sealed roller vials (3 slices/vial) containing Krebs-Hensleit buffer at 37 degrees C under 95% O2 atmosphere. Volatile anesthetics were injected through a teflon septa cap on a filter paper wick and vaporized to produce constant concentration in the medium. A concentration (1-2.1 mM) and time related (0-24) decrease in protein synthesis (3H-leucine incorporation) and secretion by halothane and d-halothane was observed. d-Halothane was less inhibiting than halothane. Inhibition was not on the uptake of the 3H-leucine but with its incorporation in the nascent peptide. The effects of enflurane (2.2 mM), isoflurane (2.2 mM), and sevoflurane (1.3 mM) on protein synthesis and secretion were also studied. The rank order of decrease in protein synthesis caused by the volatile anesthetics studied was halothane greater than isoflurane greater than enflurane greater than sevofluane greater than d-halothane. Enflurane, isoflurane, and sevoflurane increased the protein secretion while halothane and d-halothane caused a pronounced decrease. Alterations in protein synthesis and secretion appears to be an early and sensitive indicator of cytotoxin injury.

Anesthetics↗

Automatic evaluation of antifungal volatile compounds on the basis of the dynamic growth process of a single hypha.

An automatic analysing system was developed and employed for the evaluation of antifungal activity of volatile compounds in the gas phase. Aspergillus niger was inoculated on agar medium in the reaction vessel. The reaction vessel was incubated at 28 degrees C for 24 h and then a volatile compound was introduced into the vessel either in a batch or flow manner. The antifungal activity of the respective compounds estimated in situ was expressed by the dynamic response parameters of a single hypha. All volatiles tested in the present system inhibited hyphal growth, except linalyl acetate: Limone and geraniol were the most inhibitory. In contrast, linalyl acetate promoted hyphal growth. By definition of the parameters, the fungicidal and fungistatic effects could be distinguished.

Antifungal Agents↗

The volatiles of desert truffle: Tirmania nivea.

The volatile constituents of Tirmania nivea (white desert truffle) have been analysed, using gas chromatography/mass spectrometric technique. 11 compounds have been identified in the ascocarp volatiles. The major components were found to be unsaturated fatty acids; whereas hexadecanoic [correction of haxadecanoic] acid represented 49% of the volatiles isolate.

Ascomycota↗

[Breakdown of linoeic acid hydroperoxydes. Formation of volatile carbonyl compounds (author's transl)].

Linoleic acid hydroperoxydes (LOOH) containing 13-hydroperoxyoctadeca-9,11-(75%) and 9-hydroperoxyoctadeca-10,12-dienoic acid (25%) were emulsified at pH 6.5. After addition of hemoglobin, ferrous ions, ferric ions, cysteine or ascorbic acid the emulsions were stored 19 hours at 22 degrees C. The decrease in the diene and peroxyde concentrations and the formation of volatile carbonyl compounds were analysed. Ferrous ions and ascorbic acid were the strongest producers of volatile carbonyl compounds. In the presence of 10(-3) Mol ascorbic acid 6 mumol volatile aldehydes arise from 75 mumol LOOH. Hexanal (70 mol-%) was the main component of the aldehyde fraction. For plant foodstuffs the significance of the reaction of fatty acids hydroperoxydes with ascorbic acid for the formation of flavour substances is discussed.

Aldehydes↗

Identification of volatile compounds in hybrids between raspberry (Rubus idaeus, L.) and arctic bramble (Rubus arciticus, L.).

The present work is concerned with the aroma of hybrids between raspberry (Rubus idaeus, L.) and arctic bramble (Rubus arcticus, L.). Analyses of the volatiles were performed in three stages. The carbonyl compounds were determined as 2,4-dinitrophenylhydrazones, the volatile acids and the neutral components separately in a combined gas chromatography-mass spectrometer components separately in a combined gas chromatograph-mass spectrometer using glass capillary columns. Over 70 compounds were identified in the aroma concentrates of the hybrids. The major components included acetic and hexanoic acids, trans 3-penten-1-ol, 2-heptanol, 3-methyl-2-buten-1-ol, benzyl alcohol and linalool. 2,5-Dimethyl-4-methoxy-2,3-dihydro-3-furanone together with alpha and beta-ionones, characteristic compounds of arctic bramble and raspberry, respectively, were found in the hybrids in much lower concentrations than in the parent berries. Percentage concentrations of the main components in the volatile oils, together with their approximate concentrations in the press juices, were determined. The contents of the corresponding compounds in arctic bramble and in raspberry are also given.

Acids↗

Toxicological analysis of drugs and poisons in formalin-fixed organ tissues. 2. Volatile substances.

Diethylether, chloroform and toluene were administered by inhalation and ethanol intravenously to rabbits. As soon as possible after death, tissue specimens were collected from the brain, lung, liver, kidney and skeletal muscle and fixed in non-buffered 10% formalin at room temperature (10-20 degrees C) for 4 different periods (1, 2, 5 and 14 days). The volatile substances were analyzed and identified by gas chromatography/mass spectrometry (GC-MS). The measured concentrations of ethanol, diethylether, chloroform and toluene in the brain tissue 1 day after fixation decreased to 8, 23, 73 and 84% respectively compared with those in the non-fixed brain tissue (100%). The rank order of the rate of decrease in the fixed state was: ethanol > diethylether >> chloroform > toluene. These volatile substances could be detected clearly in all the tissue specimens, even after a 14-day fixation period. These results provide useful toxicological information that will help to differentiate whether volatile substances have been administered antemortem or postmortem.

Administration, Inhalation↗

[Quantitative determination of volatile nitrosamines in cigarette smoke (author's transl)].

Volatile nitrosamines from the smoke of different cigarettes were enriched by manifold clean-up procedures. Amines obtained after acid catalyzed denitrosation were transformed to fluorescent derivates of 7-chloro-4-nitrobenzofuranzane (NBD-Cl). These NBD-amines separated on polyamid sheets were fluorimetrically determined with a chromatogram-spectrophotometer. Recovery rates of 60--80% were found for the different nitrosamines in cigarette smoke condensate. The following nitrosamines were quantitatively determined: N-nitrosodimethylamine, N-nitrosodiethylamine, N-nitrosopiperidine, N-nitrosopyrrolidine, N-nitrosoethylmethylamine, N-nitroso-ethyln-propylamine and N-nitroso-methyl-n-propylamine, N-nitroso-ethyl-n-propylamine and N-nitroso-methyl-n-propylamine. The last mentioned nitrosamine was proved for the first time in cigarette smoke. At the same time correlations between the nitrosamine content of the corresponding tobacco or condensate and the content of nitrate, total nitrogen, nicotine, volatile bases and ammonia were investigated. The nitrate content as well as the content of volatile bases showed an influence on the nitrosamine yield. The content of the different nitrosamines varied cosiderably depending on tobacco origin, so that a NNO-determination is recommended as index.

Methods↗

Alternative method for rapidly screening microbial isolates for their potential to degrade volatile contaminants.

A method is described for rapidly screening the metabolic potential of bacteria to oxidize semivolatile and volatile compounds as a sole carbon source. The method is based on an automated system that utilizes Microplates manufactured by Biolog, Inc. (Hayward, CA, USA). This system detects bacterial respiratory activity from the oxidation of a carbon source introduced in volatile form. This is in contrast to the original design, which is based on inoculating a carbon source directly into each well. The 96-well (MT) microtiter plates contain nutrients and a tetrazolium dye. When a bacterial species is capable of oxidizing a volatile carbon substrate, the dye turns purple, and a spectrophotometric plate reader quantifies the response. As a test of this method 150 isolates, including isolates known to degrade some of the test compounds and negative controls were evaluated for their potential to oxidize carbon tetrachloride, toluene, and o-xylene. Thirty-seven isolates (25%) were qualitatively identified as contaminant oxidizers, and thirteen of these (35%) showed significant degradation capabilities for both toluene and o-xylene.

Bacteria↗

Refractive indices for volatile anesthetic gases: equipment and method for calibrating vaporizers and monitors.

OBJECTIVE: The objective of our study was to establish the refractive indices and the virial coefficients of the volatile anesthetic vapors. These indices and coefficients will allow refractometry to be used by manufacturers to produce accurate calibration, without requiring expensive high-precision calibration gases. METHODS: We used a precision refractometer to measure the refractive indices for five volatile anesthetic vapors. We prepared our calibration gases by mixing a gravimetrically calibrated amount of liquid agent with a constant gas flow. RESULTS: The refractive indices for the volatile anesthetic vapors are 1,603.2 for halothane, 1,540.4 for enflurane, 1,563.3 for isoflurane, 1,538.3 for sevoflurane, and 1,211.7 for desflurane. The maximum theoretical error in our measurements, due to all sensors and all uncertainty in our measurement of apparatus and physical constants, is +/- 0.56% of the reading (+/- 0.70% for desflurane). CONCLUSIONS: If refractometry replaced calibration gases in cylinders, as a calibration standard, manufacturers might avoid errors that now occur because calibration gases manufactured by numerous companies seem to differ. We propose that our values serve as an interim database.

Anesthesia, Inhalation↗

The effect of volatile and gaseous metabolites of swelling seeds on germination of fungal spores.

Effects of volatile and gaseous metabolites of swelling seeds of pea, bean, wheat, corn cucumber, tomato, lentil, carrot, red papper and lettuce on germination of spores of five genera of fungi were found to depend rather on the fungal than on the plant genus. Germination of spores of Botrytis cinerea, Mucor racemosus and Trichoderma viride was most severely inhibited. Spores of Verticillium dahliae were less sensitive and germination of spores of Fusarium oxysporum was inhibited only in two cases. On the other hand, exudates of pea and bean stimulated germination of spores of Fusarium oxysporum. Also spores of Trichoderma viride germinated better in an atmosphere enriched with exuded metabolites of swelling lettuce seeds. When carbon dioxide produced by the swelling seeds was absorbed in potassium hydroxide, spores of Trichoderma viride and Verticillium dahliae did not germinate at all, the inhibitory effects of volatile and gaseous exudates on germination of spores of Mucor racemosus were accentuated, and also the percentage of germinated spores of Fusarium oxysporum decreased. Germination of spores of Botrytis cinerea was not influenced. Absorption of volatile and gaseous metabolites in a solution of potassium permanganate decreased in most cases their inhibitory effects, particularly in Botrytis cinerea.

Carbon Dioxide↗

Does chronic occupational exposure to volatile anesthetic agents influence the rate of neutrophil apoptosis?

PURPOSE: The purpose of this preliminary investigation was to determine whether the rate of neutrophil apoptosis in health care workers is influenced by exposure to volatile anesthetic agents. METHODS: Percentage neutrophil apoptosis (Annexin-V FITC assay) was measured in health care workers (n = 20) and unexposed volunteers (n = 10). For the health care workers, time weighted personal exposure monitoring to N2O, sevoflurane and isoflurane was carried out. RESULTS: The sevoflurane and isoflurane concentrations to which health care workers were exposed were less than recommended levels in all 20 cases. Percent apoptosis was less at 24 (but not at one and 12) hr culture in health care workers [50.5 (9.7)%; P = 0.008] than in unexposed volunteers [57.3 (5.1)%]. CONCLUSION: Inhibition of neutrophil apoptosis at 24 hr culture was demonstrated in health care workers chronically exposed to volatile anesthetic agents. Exposure was well below recommended levels in the both scavenged and unscavenged work areas in which the study was carried out. Further study is required to assess the effect of greater degrees of chronic exposure to volatile anesthetic agents on neutrophil apoptosis.

Adult↗

Sampling airway surface liquid: non-volatiles in the exhaled breath condensate.

Exhaled breath condensate (EBC) samples contain molecules that have no appreciable vapor pressure; such molecules likely derive from droplets of airway fluid. We analyzed EBC gathered from a total of 62 healthy volunteers in order to quantify the volume of airway liquid that was the source of the non-volatiles; saliva was analyzed as a reference secretion. EBC urea averaged 0.52 +/- 0.12 micromol/L (n = 18), an 8,600-fold dilution from predicted blood urea nitrogen levels. Protein averaged 2.3 +/- 0.3 microg/ml (n = 31), three orders of magnitude less than in saliva (1.4 +/- 0.1 mg/ml, n = 15). EBC ammonia was 6.6 +/- 0.6 mmol/L (1/15 that of saliva) and EBC ammonium ion was 0.90 +/- 0.19 micromol/L, concentrations that are incompatible with an 8,600-fold dilution from a biological source. Thus, urea-derived dilution factors may be used to interpret EBC non-volatile molecules, but not EBC volatiles.

Albumins↗

The volatile anesthetics halothane and isoflurane differentially modulate proinflammatory cytokine-induced p38 mitogen-activated protein kinase activation.

PURPOSE: Volatile anesthetics affect the cardiovascular and immune systems. Toward a better understanding of the molecular mechanisms behind the modulation exerted by these agents, we focused on the effects of halothane and isoflurane on the activation of p38 mitogen-activated protein kinase (MAPK), which plays a critical role in the cellular responses to extracellular stimuli such as lipopolysaccharide (LPS) and proinflammatory cytokines, including tumor necrosis factor (TNF) and interleukin 1 (IL-1). METHODS: Human umbilical vein endothelial cells and HeLa cells, an established cell line, were examined by molecular biological methods. Cells were treated with proinflammatory compounds with or without the volatile anesthetics. p38 MAPK activation was investigated by Western blotting analysis with phosphospecific anti-p38 MAPK antibodies. RESULTS: Isoflurane activated p38 MAPK by itself, but halothane did not. Halothane or isoflurane augmented the LPS- and TNF-induced activation of p38 MAPK. In contrast, neither halothane nor isoflurane enhanced the p38 MAPK activation induced by IL-1. Neither of the anesthetics affected H(2)O(2) or MAPK kinase 3 (MKK3)-induced p38 MAPK activation. CONCLUSION: Our in vitro results indicate that the volatile anesthetics used in the clinical field and in animal experiments modify the p38 MAPK signaling cascade and suggest that the target molecules of the anesthetics are not unique and the anesthetics regulate them differentially at clinically relevant doses.

Anesthetics, Inhalation↗

Influence of different transition metals in phthalocyanines on their interaction energies with volatile organic compounds: an experimental and computational study.

Experimental partition coefficients were determined for a series of volatile organic compounds (VOCs) (acetonitrile, n-butylamine, n-octane tetrachloroethene, and toluene) for the interaction with 2,3,9,10,16,17,23,24-octakis(octyloxy)-phthalocyaninato complexes, PcM(OR)(8), with varying central metal atoms [M=H(2) (metal-free), Ni, Pd, Cu, Zn]. Large partition coefficients for toluene were observed in the case of the nickel and palladium phthalocyanines, whereas for the corresponding zinc-containing compound, interaction with n-butylamine resulted in a high value for the partition coefficient. Interaction energies for model coordination complexes were obtained at the ab initio LMP2/ LACVP* level of theory. The interaction of various small volatiles with the various PcM(OR)(8) compounds was studied using the PM3 semiempirical Hamiltonian. Large values for interaction energies correspond to particularly strong partition coefficients, suggesting that coordination of the volatiles to the central metal dominates over the often discussed pi-system stacking at the PcM(OR)(8)'s.

Acetonitriles↗

Controlled formation of volatile components in cider making using a combination of Saccharomyces cerevisiae and Hanseniaspora valbyensis yeast species.

The effect of pure and mixed fermentation by Saccharomyces cerevisiae and Hanseniaspora valbyensis on the formation of major volatile components in cider was investigated. When the interaction between yeast strains of S. cerevisiae and H. valbyensis was studied, it was found that the two strains each affected the cell growth of the other upon inoculation of S. cerevisiae during growth of H. valbyensis. The effects of pure and mixed cultures of S. cerevisiae and H. valbyensis on alcohol fermentation and major volatile compound formation in cider were assessed. S. cerevisiae showed a conversion of sugar to alcohol of 11.5%, while H. valbyensis produced alcohol with a conversion not exceeding 6%. Higher concentrations of ethyl acetate and phenethyl acetate were obtained with H. valbyensis, and higher concentrations of isoamyl alcohol and isobutyl were formed by S. cerevisiae. Consequently, a combination of these two yeast species in sequential fermentation was used to increase the concentration of ethyl esters by 7.41-20.96%, and to decrease the alcohol concentration by 25.06-51.38%. Efficient control of the formation of volatile compounds was achieved by adjusting the inoculation time of the two yeasts.

Acetates↗

Impact of botanical pesticides derived from Melia azedarach and Azadirachta indica plants on the emission of volatiles that attract Parasitoids of the diamondback moth to cabbage plants.

Herbivorous and carnivorous arthropods use chemical information from plants during foraging. Aqueous leaf extracts from the syringa tree Melia azedarach and commercial formulations from the neem tree Azadirachta indica, Neemix 4.5, were investigated for their impact on the flight response of two parasitoids, Cotesia plutellae and Diadromus collaris. Cotesia plutellae was attracted only to Plutella xylostella-infested cabbage plants in a wind tunnel after an oviposition experience. Female C. plutellae did not distinguish between P. xylostella-infested cabbage plants treated with neem and control P. xylostella-infested plants. However, females preferred infested cabbage plants that had been treated with syringa extract to control infested plants. Syringa extract on filter paper did not attract C. plutellae. This suggests that an interaction between the plant and the syringa extract enhances parasitoid attraction. Diadromus collaris was not attracted to cabbage plants in a wind tunnel and did not distinguish between caterpillar-damaged and undamaged cabbage plants. Headspace analysis revealed 49 compounds in both control cabbage plants and cabbage plants that had been treated with the syringa extract. Among these are alcohols, aldehydes, ketones, esters, terpenoids, sulfides, and an isothiocyanate. Cabbage plants that had been treated with the syringa extract emitted larger quantities of volatiles, and these increased quantities were not derived from the syringa extract. Therefore, the syringa extract seemed to induce the emission of cabbage volatiles. To our knowledge, this is the first example of a plant extract inducing the emission of plant volatiles in another plant. This interesting phenomenon likely explains the preference of C. plutellae parasitoids for cabbage plants that have been treated with syringa extracts.

Animals↗