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PubMed1982

Endogenous synthesis of volatile nitrosamines: model calculations and risk assessment.

A kinetic model for estimating the gastric synthesis of N-nitroso compounds and a method for estimating the risk from exposure to volatile nitrosamines are described. A tentative calculation of the possible risks for human gastric cancer, based on extrapolating from literature data on the induction of tumours in rats, suggests that the endogenous formation of non-volatile N-nitroso compounds is more important than that of volatile nitrosamines.

Food Analysis↗
PubMed1995

Relative potencies of volatile anesthetics in altering the kinetics of ion channels in BC3H1 cells.

Single channel recording techniques have been used to study effects of the volatile anesthetics enflurane, halothane, isoflurane and methoxyflurane, and the gaseous agent nitrous oxide, on the properties of nicotinic channels activated by acetylcholine. Single channel currents activated by 250 nM acetylcholine were recorded from cell-attached patches of BC3H1 mouse tumor cells grown in culture. All of the potent volatile agents shortened the duration of individual opening events and caused openings to appear grouped together in bursts. The slower time constant of channel open-time distributions was decreased 50% by approximately 0.22% enflurane (0.12 mM), 0.25% isoflurane (0.10 mM), 0.30% halothane (0.16 mM), 0.076% methoxyflurane (0.21 mM) or 80% nitrous oxide (20 mM) at room temperature. Even when values were corrected to 37 degrees C, the concentrations required to decrease channel open time are less than clinical dosages. Anesthetic potency in altering channel properties was directly related to both clinical potency and lipid solubility, although those agents with greater clinical potencies required relatively higher concentrations to reduce channel open time. Results are interpreted in terms of a simple sequential channel blocking model, a sequential blocking model in which anesthetics also enhance the rate at which open channels normally close, and a cyclic blocking model in which blocked channels may close directly without having to pass back through the open state. All of the agents appeared to act in a qualitatively similar fashion and no differences were found that could account for the differing clinical profiles of the volatile anesthetics.

Anesthetics, Inhalation↗
PubMed1995

[Is there a receptor for volatile anesthetics?].

Because of the presence of inequality of the effect of volatile anesthetics on various neurotransmission systems, a specific receptor is proposed. Nonetheless, the differences are only of the magnitude, and almost all synapses are equally affected. The outstanding features of the action of volatile anesthetics are this wide range of the target, and the steep dose-response curve. The steep dose-response curve indicates that various synapses respond to anesthetics with high cooperativity. When a string of amino acids folds into biologically meaningful structure by enclosing hydrophobic areas inside, some hydrophobic parts are left at the protein-water interface. These hydrophobic patches become the binding site for anesthetics. Because of the wide difference in the structures of anesthetics, it is difficult to assume a specific binding site of lock-and-key type for all anesthetics with all synaptic proteins. Presumably volatile anesthetics bind most hydrophobic patches nonselectively. The affinity to each patch may differ, and the relative specificity to each synapse may ensue. To define these areas as a receptor is a matter of opinion.

Anesthetics, Inhalation↗
PubMed1995

Different subunit requirements for volatile and nonvolatile anesthetics at gamma-aminobutyric acid type A receptors.

The ability of volatile (halothane and isoflurane) and nonvolatile (alphaxalone and pentobarbital) general anesthetics to modulate radioligand binding to gamma-aminobutyric acid (GABA)A receptors was examined in an immortalized cell line (WSS-1) expressing rat alpha 1 and gamma 2 subunits. Volatile anesthetics enhance [3H]flunitrazepam binding to WSS-1 cells in a concentration-dependent manner, with potencies and efficacies comparable to those found with native GABAA receptors. Transfection of these cells with cDNAs encoding rat beta 2 or beta 3 subunits had a significant influence on anesthetic efficacy but not potency in this assay. Thus, transfection with the beta 2 subunit reduced the efficacy of both isoflurane and halothane, whereas transfection with the beta 3 subunit increased the efficacy of isoflurane but not halothane, compared with values obtained in WSS-1 cells. In contrast, alpha-xalone (an anesthetic steroid) had no effect, whereas at high concentrations pentobarbital (an anesthetic barbiturate) produced a modest inhibition of [3H]flunitrazepam binding to GABAA receptors in WSS-1 cells. Transfection of WSS-1 cells with cDNAs encoding either beta 2 or beta 3 subunits resulted in a concentration-dependent enhancement of [3H]flunitrazepam binding by these nonvolatile anesthetics. Moreover, pentobarbital was significantly more potent in enhancing [3H]flunitrazepam binding to WSS-1 cells transfected with the beta 2 subunit, compared with the beta 3 subunit. The difference in subunit requirements between volatile and nonvolatile anesthetics for enhancement of [3H]flunitrazepam binding indicates that these classes of agents affect GABAA receptor function at distinct loci. These studies also provide evidence that the beta subunit is required for these nonvolatile anesthetics to positively modulate GABAA receptors.

Anesthetics↗
PubMed1994

Volatile anesthetic-induced efflux of calcium from IP3-gated stores in clonal (GH3) pituitary cells.

BACKGROUND: Many hormones and neurotransmitters produce their effects by stimulating the generation of inositol 1,4,5-trisphosphate (IP3), a chemical second messenger that releases Ca2+ from intracellular stores. Interruption of this pathway is a potential mechanism through which volatile anesthetics might inhibit chemically mediated communication between cells. This study used GH3 cells (a clonal cell line) as a model system in which to characterize the effects of volatile anesthetics on IP3-induced mobilization of Ca2+ from intracellular stores. METHODS: Intracellular Ca2+ concentration ([Ca2+]i) was continuously monitored in suspensions of GH3 cells at 37 degrees C using the fluorescent Ca2+ indicator Fura-2. Thyrotropin releasing hormone (TRH) was used to discharge IP3-sensitive intracellular Ca2+ stores. The effects of halothane, isoflurane, and octanol on TRH-induced Ca2+ mobilization were assessed as a function of time and anesthetic concentration. To distinguish between anesthetic effects on Ca2+ uptake and Ca2+ release, experiments were performed using thapsigargin (a Ca(2+)-ATPase inhibitor) to inhibit Ca2+ uptake into IP3-sensitive stores. RESULTS: Halothane increased resting [Ca2+]i and caused a time- and concentration-dependent inhibition of TRH-induced increases in [Ca2+]i (IC50 = 0.6 mM). Thapsigargin, in concentrations that completely inhibit Ca2+ uptake by IP3-sensitive stores, also caused a time-dependent reduction in the [Ca2+]i response to TRH; the time constant of this decay describes the rate of spontaneous leak of Ca2+ from IP3-sensitive stores (tau = 98 +/- 9 s). In the presence of thapsigargin, halothane produced concentration-dependent increases in the rate of leak from IP3-sensitive stores (tau = 74 +/- 12 and 46 +/- 6 s at 0.5 and 1.0 mM halothane, respectively). Isoflurane and octanol also produced concentration-dependent inhibition of the [Ca2+]i response to TRH. CONCLUSIONS: Halothane causes a concentration-dependent leak of Ca2+ from IP3-sensitive stores, leading to depletion of the stores and inhibition of IP3-induced increases in [Ca2+]i. This effect occurs at clinically relevant concentrations of halothane (as well as isoflurane and octanol) and may be an important mechanism underlying some of the physiologic effects of volatile anesthetics.

Anesthetics↗
PubMed1994

[Depressant effects of volatile anesthetics on second messenger system in mRNA-expressed Xenopus laevis oocytes].

In this study I attempted to elucidate the depressant effects of volatile anesthetics on inositol trisphosphate (IP3)-mediated signal transduction pathway and to identify the site of action. For this purpose, we used Xenopus laevis oocytes which translated and expressed 5-HT receptors after injection of mRNA isolated from the rat brain. In this system, binding of the agonist to G-protein coupled receptors activates phospholipase C that produces IP3. Mobilization of Ca2+ by IP3 from the storage finally opens Ca2+ dependent Cl- channels. Halothane, isoflurane and methoxyflurane depressed Cl- current elicited by 5-HT. For the further quantitative study, methoxyflurane was used because of its better solubility and less vapor pressure that avoided evaporation of the agent. The 5-HT elicited Cl- current was depressed in a non-competitive fashion. Response were 75, 60, 20% of control in the presence of 0.5, 1 and 3 mM methoxyflurane, respectively. Responses elicited by a pressure-injection of Ca2+ or IP3 remained unchanged in the presence of high concentrations of either halothane, isoflurane or methoxyflurane. These results suggest that the depressant mechanism by volatile anesthetics on the signal transduction pathway involves neither Ca2+ dependent Cl- channel dynamics nor intracellular Ca2+ mobilization by IP3. Changes of microdomain characteristics of the membrane in the presence of anesthetic molecules including membrane-bound proteins and enzyme system may be a main mechanism of action of volatile anesthetics.

Anesthetics↗
PubMed1994

Identification of volatile forms of methyl groups released by Halobacterium salinarium.

halobacterium salinarium (formerly H. halobium) is a chemotactic and phototactic archaeon from which volatile methyl groups are released continually, a phenomenon related to its sensory system. We found that released methyl groups comprised two different chemical species, methanol and methanethiol, the sulfur analog of methanol. Radiolabeling experiments showed that the methyl groups of both compounds, as well as the sulfur of methanethiol, were derived from methionine but were donated to cellular components and subsequently cleaved to produce the respective volatile compounds. Previous work had shown that chemostimuli and photostimuli result in transient increases in the rate of release of volatile methyl groups. We found that these increases reflected increased release of methanol but not of methanethiol. Thus, the methyl group chemistry of the H. salinarium sensory system is analogous to the well-studied chemotactic system of Escherichia coli. The reactions that result in methanethiol release are of unknown function and have unusual features. They may involve a methionine-gamma-lyase activity we detected in H. salinarium. Sulfur derived from methionine was found attached to specific proteins in reduction-sensitive disulfide linkages.

Carbon-Sulfur Lyases↗
PubMedDate not supplied

The influence of volatile anesthetics on portwine stain.

To examine the relationship between volatile inhalation anesthetics and the fading of portwine stain (PWS), the study retrospectively investigated the incidence of termination of pulsed dye laser treatment vis-à-vis PWS fade during use of a general inhalation anesthetic in 107 infants and children with facial PWS. The fading of PWS is disadvantageous to the pulsed dye laser treatment. All patients received pulsed dye laser treatment under general anesthesia using one of four kinds of volatile inhalation anesthetics (halothane, enflurane, isoflurane, and sevoflurane). Two hours before the induction of anesthesia, all patients were rectally irrigated. Treatment was discontinued in none of the 44 patients in the halothane group or the 7 patients in the enflurane group; in one of the 29 in the isoflurane group; and in 10 of the 27 patients in the sevoflurane group. The sevoflurane group showed a significantly (P < 0.01) higher incidence of PWS fading. Thus, when using a volatile inhalation anesthetic in combination with pulsed dye laser treatment for PWS, caution should be exercised if sevoflurane is selected, as PWS fading is harmful to the pulsed dye laser.

Anesthesia, General↗
PubMedDate not supplied

Modeling the effects of water usage and co-behavior on inhalation exposures to contaminants volatilized from household water.

The volatilization of volatile organic chemicals during domestic water usage can result in significant indoor air concentrations, and the subsequent inhalation of these contaminants is an important route of exposure. The magnitude of these exposures is highly dependent on the activities undertaken by the exposed individual, as well as the activities of other occupants of the home. The indoor air quality-exposure Model for the Analysis of Volatiles and Residential Indoor Air Quality (MARVIQ) was used to ascertain the impact of water-use activities on the potential contaminant dose to household members. Human time-activity patterns of various population groups were sampled from the California Air Resources Board database, applying distributions of water-use occurrence and water-use duration to each activity based on survey results. Indoor air concentrations in a sample house and the resulting potential inhalation dose to the occupants were computed for different individuals and pairs of individuals to test for exposure and coexposure effects. The simulated daily exposure is well described by a simplified equation that is a function of the amount of time the individual spends in the shower, the bath, and the bathroom; the total water usage in the home; and the fraction of time the individual is at home. These results can be used to identify high-risk populations, individuals, and households. The study also demonstrates the importance of further research on joint time-activity patterns in multiperson households for assessment of exposure and coexposure effects.

Adult↗
PubMed1997

[Involvement of enhanced glutamate release in halogenated volatile anesthetic-induced excitation in mouse brain].

The present experiments aimed to elucidate the mechanisms of excitatory effects of volatile anesthetics. In ddN mice, enflurane (2% in air), sevoflurane (2%) or isoflurane (1.2%) induced opisthotonus. In ddY mice, a halogenated ethane, tetrachlorodifluoroethane (CCl2FCCl2F:DF-112, 2%) induced tonic-clonic convulsion. These CNS excitatory effects were suppressed by pretreatment with an N-methyl-D-aspartate antagonist, MK-801 (0.5mg.kg-1). Halogenated volatile anesthetics (enflurane, sevoflurane, isoflurane and halothane) increased glutamate release from synaptosomes of the mouse cerebral cortex at concentrations corresponding to those used clinically. The convulsive gas, DF-112, released glutamate more potently than the anesthetics. These data suggest the involvement of enhanced glutamate release in the mechanisms of excitatory effects of halogenated volatile anesthetics.

Anesthetics, Inhalation↗
PubMed1998

Inhalation of volatile substances: an emerging threat to readiness?

Volatile substance abuse is the deliberate inhalation of volatile substances to achieve intoxication. We discuss the history and pathophysiological effects of commonly abused volatile substances. We explore three deaths and one serious accident in active duty military settings. The causes for abuse in the military environment are numerous and include remote duty, peer influence, low cost, rapid onset, limitation of ethanol use, difficult detection/screening for use, and lack of knowledge among users and authorities. The lethality of these substances and their casual use can constitute a threat to military readiness. Our experience suggests an increase in the use of these substances in the military paralleling their increasing use in the general population. Education and awareness training could limit fatalities and decrease the threat in military and civilian populations.

Adult↗
PubMed1998

Effects of volatile anesthetics on respiratory activity and chemosensitivity in the isolated brainstem-spinal cord of the newborn rat.

To elucidate the various actions of volatile anesthetics on respiratory activity and chemosensitivity, we have studied the activities of the respiration-related structures in the medulla of the in vitro brainstem-spinal cord preparation of the newborn rat. Halothane decreased respiratory burst frequency (fR), inspiratory duration (Ti), integrated ventral C4 root activity (integral of C4) and respiratory minute activity (RMA) in a concentration-dependent fashion. Bicuculline counteracted the depressive effect of halothane on fR, integral of C4, and RMA. Inspiratory neuronal activity recorded at the rostral ventrolateral medulla (RVL) corresponded to these changes. Activities of Pre-Inspiratory (Pre-I) neurons and expiratory neurons in the RVL were also inhibited by halothane. The C4 activity did not always correspond to Pre-I neurons' discharge. In this comparative study of three volatile anesthetics, the inhibitory effect on fR appeared to be greater with enflurane than with halothane or isoflurane. The reversal effects of bicuculline on decreases in fR, integral of C4, and RMA also seemed to be greater with enflurane than with halothane or isoflurane. Hypercapnia (pH 7.0) induced a significant increase in fR and RMA, and a significant decrease in Ti. Although halothane inhibited overall activities, chemo-responsiveness to hypercapnia changed similarly even during halothane application. Hypocapnia (pH 7.8) significantly decreased fR, and increased integral of C4 and Ti. Hypocapnia during halothane application also induced a significant decrease in fR and RMA. These results suggest that the modification of GABAA receptor-mediated neurotransmission is in part responsible for the respiratory depression by volatile anesthetics, affecting especially fR, integral of C4, and RMA. Low respiratory rate by enflurane is associated with GABAergic modification. Prolongation of Ti by enflurane, seen clinically, does not seem to be either central or GABAergic. These findings demonstrate the responsiveness to CO2 and the respiratory compensation mechanism via respiratory frequency in the isolated preparation. It is, furthermore, indicated that halothane preserves the central chemosensitivity while its concentration is high enough to reduce the respiratory activities.

Anesthetics, Inhalation↗
PubMed2003

Volatiles released from cotton plants in response to Helicoverpa zea feeding damage on cotton flower buds.

Feeding of Helicoverpa zea larvae on cotton ( Gossypium hirsutum L.) flower buds (squares) for 24 or 48 h induced the release of a number of terpenes [( E)-beta-ocimene, linalool, ( E)-beta-farnesene, ( E, E)-alpha-farnesene, ( E)-4,8-dimethyl-1,3,7-nonatriene, ( E, E)-4,8,12-trimethyl-1,3,7,11-tridecatetraene], isomeric hexenyl butyrates, 2-methylbutyrates, indole and ( Z)-3-hexenyl acetate. These compounds are not released in significant amounts from undamaged squares and freshly damaged squares. The release of inducible compounds was not limited to the damaged squares themselves. The compounds were also released systemically from the upper undamaged leaves of the same plant after 72 h. However, the composition of the blend of systemically released volatiles differed from the blend released by damaged squares. The compounds that were systemically released from undamaged leaves in response to feeding on the squares were ( Z)-3-hexenyl acetate, ( E)-beta-ocimene, linalool, ( E)-4,8-dimethyl-1,3,7-nonatriene, ( E)-beta-farnesene, ( E, E)-alpha-farnesene, and indole. This study shows that insect damage inflicted to the reproductive parts of a plant causes a systemic emission of volatiles from its vegetative parts.

Animals↗
PubMed2004

Application of comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry in the analysis of volatile oil of traditional Chinese medicines.

This paper reports comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC x GC-TOF MS) analysis of Pogostemon cablin Benth (Cablin Parchouli) volatile oil. The suitable column system and operation conditions were chosen on the basis of the properties of composition of the volatile oil. One-dimensional gas chromatography (ID-GC) and GC x GC, GC-MS and GC x GC-TOF MS were compared under appropriate conditions, and the enhanced sensitivity and superior resolution of GC x GC were demonstrated. 394 components were tentatively identified by GC x GC-TOF MS.

Gas Chromatography-Mass Spectrometry↗
PubMed2005

Impact of phase ratio, polydimethylsiloxane volume and size, and sampling temperature and time on headspace sorptive extraction recovery of some volatile compounds in the essential oil field.

This study evaluates concentration capability of headspace sorptive extraction (HSSE) and the influence of sampling conditions on HSSE recovery of an analyte. A standard mixture in water of six high-to-medium volatility analytes (isobutyl methyl ketone, 3-hexanol, isoamyl acetate, 1,8-cineole, linalool and carvone) was used to sample the headspace by HSSE with stir bars coated with different polydimethylsiloxane (PDMS) volumes (20, 40, 55 and 110 microL, respectively), headspace vial volumes (8, 21.2, 40, 250 and 1000 mL), sampling temperatures (25, 50 and 75 degrees C) and sampling times (30, 60 and 120 min, and 4, 8 and 16 h). The concentration factors (CFs) of HSSE versus static headspace (S-HS) were also determined. Analytes sampled by the PDMS stir bars were recovered by thermal desorption (TDS) and analysed by capillary GC-MS. This study demonstrates how analyte recovery depends on its physico-chemical characteristics and affinity for PDMS (octanol-water partition coefficients), sampling temperatures (50 degrees C) and times (60 min), the volumes of headspace (40 mL) and of PDMS (in particular, for high volatility analytes). HSSE is also shown to be very effective for trace analysis. The HSSE CFs calculated versus S-HS with a 1000 mL headspace volumes at 25 degrees C during 4 h sampling ranged between 10(3) and 10(4) times for all analytes investigated while the limits of quantitation determined under the same conditions were in the nmol/L range.

Dimethylpolysiloxanes↗
PubMed2005

Volatile and polar compounds in Rosadamascena Mill 1803 cell suspension.

Studies were conducted on low molecular metabolites (volatiles and polar compounds) produced by Rosa damascena Mill 1803 cell suspension culture, cultivated under different regimes: as a free suspension (in flasks and in bioreactor) and in a two-phase system (in the presence of Amberlite XAD-4 as a second phase). It was established that the main groups of volatiles were hydrocarbons and free acids and their esters and only traces of terpenoids were found. The main components of polar fraction were free acids, especially amino acids and oxidized acids. Depending on the culture conditions, significant differences were established in the amounts of all compounds under study in biomasses, culture media and adsorbed on the second phase (Amberlite XAD-4).

Cell Culture Techniques↗
PubMed2006

Development of gas chromatography-mass spectrometry with microwave distillation and simultaneous solid-phase microextraction for rapid determination of volatile constituents in ginger.

In this study, gas chromatography-mass spectrometry (GC-MS) following microwave distillation and solid-phase microextraction (MD-SPME) was developed for the analysis of essential oil compounds in fresh ginger. In the proposed method, the isolation, extraction and concentration of volatile components in ginger were carried out in one single step, using the MD-SPME technique, and the analytes on the SPME fiber were analyzed by GC-MS. Some parameters, including SPME fiber coating, microwave power and irradiation time, were optimized. The optimal experiment parameters obtained were: 65 microm PDMS/DVB SPME fiber, a microwave power of 400 W and an irradiation time of 2 min. To demonstrate its feasibility, MD-SPME was compared with conventional SPME for the extraction of essential oil compounds in fresh ginger. Using MD-SPME followed by GC-MS, 54 compounds were separated and identified in ginger, which mainly included geranial (5.25%), zingiberene (15.48%), beta-sesquiphellandrene (5.54%) and beta-phellandrene (22.84%), whereas only 39 compounds were separated and identified by conventional SPME followed by GC-MS. The relative standard deviation (R.S.D.) values of less than 10% show that the proposed method has good repeatability. The result show that MD-SPME, followed by GC-MS, is a simple, rapid, solvent-free method for the determination of volatile compounds in ginger.

Gas Chromatography-Mass Spectrometry↗
PubMed2006

Analysis of volatile components of Curcuma sichuanensis X. X. Chen by gas chromatography-mass spectrometry.

Volatile components of Curcuma sichuanensis X. X. Chen growing in Sichuan, China, were extracted by steam distillation and analyzed by using gas chromatography and gas chromatography-mass spectrometry. A total of 44 volatile essential oil components were identified in the extract of C. sichuanensis X. X. Chen, representing 87.1% of the total integrated chromatographic peaks. The major compounds were found to be epi-curzerenone (26.9%), germacrone (12.4%), isocurcumenol (9.7%), beta-elemene (6.4%) and curzerene (6.2%). The results of semi-quantitative analysis indicated that levels of total sesquiterpene fraction (85.4%) were more than 55 times higher than those of monoterpene components (1.5%).

China↗