Analysis of ether glycerophosphocholines at the level of C[double bond, length as m-dash]C locations from human plasma.

Plasmanyl and plasmenyl glycerophosphocholine are ether lipids featuring the 1-O-alkyl or 1-O-alk-1'-enyl ether linkage at the sn-1 position of the glycerol backbone, respectively. Aberrant levels of ether glycerophosphocholines (ether PCs) have been correlated with cellular dysfunctions and various human diseases. Profiling ether PCs with accurate structural information is challenging because of the common presence of isomeric and isobaric species in a lipidome. The Paternò-Büchi (PB) reaction, a double bond (C[double bond, length as m-dash]C) specific derivatization method, is capable of pinpointing C[double bond, length as m-dash]C locations in unsaturated lipids, when coupled with subsequent tandem mass spectrometry (MS/MS). In this study, we have tailored the acetone PB reaction for the analysis of ether PCs. PB-MS/MS via low energy collision-induced dissociation (CID) provides diagnostic ions specific to the alkenyl ether C[double bond, length as m-dash]C bond, which are different from those derived from the isolated C[double bond, length as m-dash]C bond in the alkyl or acyl chain, thereby facilitating the distinction of isomeric plasmenyl from plasmanyl PCs. PB-MS/MS coupled with high resolution MS and multi-stage MS/MS further enable confident identification of isomeric ether PCs and isobaric diacyl PCs from mixtures. A total of 45 ether PCs in human plasma have been identified for ether linkage type and chain composition, while 28 ether PCs have structures being fully characterized down to C[double bond, length as m-dash]C locations.

Dose- and time-dependent pharmacokinetics of apigenin trimethyl ether.

Apigenin trimethyl ether (5,7,4'-trimethoxyflavone, ATE), one of the key polymethoxyflavones present in black ginger (rhizome of Kaempferia parviflora) possesses various health-promoting activities. To optimize its medicinal application, the pharmacokinetics of ATE was assessed in Sprague-Dawley rats with emphases to identify the impacts from dose and repeated dosing on its major pharmacokinetic parameters. Plasma ATE levels were monitored by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Upon single intravenous administration (2 mg/kg), plasma levels of ATE declined through an apparent first-order process while dose-escalation to 4 and 8 mg/kg led to its non-linear disposition, which could be described by the Michaelis-Menten model. Similarly, dose-dependent oral pharmacokinetics was confirmed and when the dose was escalated from 5 to 15 and 45 mg/kg, much longer mean residence time (MRT0→last), higher dose-normalized maximal plasma concentration (Cmax/Dose) and exposure (AUC/Dose) were observed at 15 and/or 45 mg/kg. One-week daily oral administration of ATE at 15 mg/kg caused its accelerated elimination and the plasma exposure (AUC) after intravenous (2 mg/kg) and oral administration (15 mg/kg) dropped ~40 and 60%, respectively. As ATE displayed both dose- and time-dependent pharmacokinetics, caution is needed in the medicinal applications of ATE and/or black ginger.

Detection of unusual very-long-chain fatty acid and ether lipid derivatives in the fibroblasts and plasma of patients with peroxisomal diseases using liquid chromatography-mass spectrometry.

Metabolic changes occur in patients with peroxisomal diseases owing to impairments in the genes involved in peroxisome function. For diagnostic purposes, saturated very-long-chain fatty acids (VLCFAs) such as C24:0 and C26:0, phytanic acid, pristanic acid, and plasmalogens are often measured as metabolic hallmarks. As the direct pathology of peroxisomal disease is yet to be fully elucidated, we sought to explore the fatty acid species that accumulate in patients with peroxisomal diseases. We developed a method for detecting a range of fatty acids implicated in peroxisomal diseases such as Zellweger syndrome (ZS) and X-linked adrenoleukodystrophy (X-ALD). To this end, we employed an ultra-performance liquid chromatography-mass spectrometry (LC-MS) coupled with negatively charged electrospray ionization. Fatty acids from patients and control subjects were extracted from total lipids by acid-hydrolysis and compared. In accordance with previous results, the amounts of VLCFAs, phytanic acid, and pristanic acid differed between the two groups. We identified extremely long and highly polyunsaturated VLCFAs (ultra-VLC-PUFAs) such as C44:12 in ZS samples. Moreover, three unknown molecules were prominent in control samples but scarcely detectable in ZS samples. LC-MS/MS analysis identified these as 1-alkyl-sn-glycerol 3-phosphates derived from ether lipids containing fatty alcohols such as C16:0, C18:0, or C18:1. Our method provides an approach to observing a wide range of lipid-derived fatty acids and related molecules in order to understand the metabolic changes involved in peroxisomal diseases. This technique can therefore be used in identifying metabolic markers and potential clinical targets for future treatment.

Human Exposure and Elimination Kinetics of Chlorinated Polyfluoroalkyl Ether Sulfonic Acids (Cl-PFESAs).

The incomplete mass-balance of organic fluorine in human serum indicates the existence of unknown per- and polyfluoroalkyl substances (PFASs) with persistent and bioaccumulative properties. Here we characterized human exposure and elimination kinetics of chlorinated polyfluoroalkyl ether sulfonic acids (Cl-PFESAs) in metal plating workers (n = 19), high fish consumers (n = 45), and background controls (n = 8). Cl-PFESAs were detected in >98% of the sampled individuals with serum concentrations ranging <0.019-5040 ng/mL. Statistically higher median serum levels were observed in high fish consumers (93.7 ng/mL) and metal plating workers (51.5 ng/mL) compared to the background control group (4.78 ng/mL) (Kruskal-Wallis rank sum test, p < 0.01). Cl-PFESAs could account for 0.269 to 93.3% of ∑PFASs in human serum indicating that this compound class may explain a substantial fraction of previously unidentified organic fluorine in the Chinese population. Estimated half-lives for renal clearance (median 280 years; range 7.1-4230 years) and total elimination (median 15.3 years; range 10.1-56.4 years) for the eight carbon Cl-PFESA suggest that this is the most biopersistent PFAS in humans reported to date. The apparent ubiquitous distribution and slow elimination kinetics in humans underscore the need for more research and regulatory actions on Cl-PFESAs and PFAS alternatives with similar chemical structures.

Deriving Biomonitoring Equivalents for selected E- and P-series glycol ethers for public health risk assessment.

Glycol ethers are a widely used class of solvents that may lead to both workplace and general population exposures. Biomonitoring studies are available that have quantified glycol ethers or their metabolites in blood and/or urine amongst exposed populations. These biomonitoring levels indicate exposures to the glycol ethers, but do not by themselves indicate a health hazard risk. Biomonitoring Equivalents (BEs) have been created to provide the ability to interpret human biomonitoring data in a public health risk context. The BE is defined as the concentration of a chemical or metabolite in a biological fluid (blood or urine) that is consistent with exposures at a regulatory derived safe exposure limit, such as a tolerable daily intake (TDI). In this exercise, we derived BEs for general population exposures for selected E- and P-series glycol ethers based on their respective derived no effect levels (DNELs). Selected DNELs have been derived as part of respective Registration, Evaluation, Authorisation and Regulation of Chemicals (REACh) regulation dossiers in the EU. The BEs derived here are unique in the sense that they are the first BEs derived for urinary excretion of compounds following inhalation exposures. The urinary mass excretion fractions (Fue) of the acetic acid metabolites for the E-series GEs range from approximately 0.2 to 0.7. The Fues for the excretion of the parent P-series GEs range from approximately 0.1 to 0.2, with the exception of propylene glycol methyl ether and its acetate (Fue = 0.004). Despite the narrow range of Fues, the BEs exhibit a larger range, resulting from the larger range in DNELs across GEs. The BEs derived here can be used to interpret human biomonitoring data for inhalation exposures to GEs amongst the general population.

[The connection of polymorphism I/D of the gene angiotensin-converting ferment and D442G gene of protein-carrier of cholesterol ethers with atherosclerosis risk factors in patients of elderly and senile age with coronary heart disease in the Republic Sakha (Yakutia)].

The authors analyse allocation of genotypes frequencies of polymorphism I/D of the gene of angiotensin-converting ferment (ASYA) and D442G gene of protein-transmitting agent of cholesterol ethers (CETP) in patients of elderly, senile age and long-livers with coronary heart disease taking into account their nationality, age and sex. With the age, the frequency reduction of occurrence of genotype ACE*I/*I has been observed and there is a tendency to increase of genotype frequency ACE*D/*D. Sexual distinctions in frequency of revealing of homozygous genotype ACE*D/*D have been revealed at the relative analysis of genotypes ACE*D/*D and ACE*D/*I. The carriers of genotype ACE*D/*D significantly more are males than females. In the general group (especially in the group of Yakuts), the carriers of genotype ACE*I/*I have demonstrated significantly more often the hypertrophy of myocardium of the left ventricle, which is accurately reflected with the help of ECG sign of Sokolov-Lion. While studying the polymorphism D442G of the gene CETP, the carriers of genotype CETP:D*/*G are significantly more often met among Yakuts, than non-indigenous population. The comparison of genotypes frequencies I/D-polymorphism of the gene ACE have showed reliable distinctions of BBI, indexes of blood lipids. The comparison of genotypes CETP*D/*D, CETP*D/*G has not yielded authentic connection with risk factors of coronary heart disease.

Development and validation of a LC-MS/MS method for the quantification of the regioisomers of dihydroxybutylether in human plasma.

Dihydroxybutylether (DHBE), a strong choleretic drug, is a mixture of three regioisomers: 4-(3-hydroxybutoxy)-2-butanol (I), 3-(4-hydroxy-2-butoxy)-1-butanol (II) and 3-(3-hydroxylbutoxy)-1-butanol (III). A liquid chromatography-tandem mass spectrometry method was developed and validated for the quantification of dihydroxybutylether (DHBE) regioisomers in human plasma. After plasma samples were deproteinized with 10% perchloric acid, the post-treatment samples were analyzed on a Capcell Pak C(18) MGII column interfaced with a triple quadrupole tandem mass spectrometer in positive electrospray ionization mode. Methanol and water was used as the mobile phase with a gradient elution at a flow rate of 1mL/min. Acetaminophen was used as an internal standard (IS). Multiple selected reaction monitoring was performed using the transitions m/z 163→55 and m/z 152→110 to quantify DHBE regioisomers and IS, respectively. Five DHBE isomers (a, b, c, d and e) were separated under the present chromatographic condition. The assay was linear over the concentration range of 5.0-200ng/mL for DHBE isomers a, b and c, and 10.0-400ng/mL for DHBE isomers d and e. The intra- and inter-day precision was within 13.6% in terms of relative standard deviation (RSD%) and the accuracy within 7.3% in terms of relative error. This simple and sensitive and easily reproducible LC-MS/MS method was successfully applied to the pharmacokinetic study of DHBE regioisomers in healthy male Chinese volunteers after an oral dose of 1.0g DHBE.

[Analysis of sevoflurane stability during low flow anesthesia].

Using the mass spectrometric method we studied the interaction of volatile anesthetic sevoflurane with a CO2 absorber during low flow anesthesia (0.5 l/min fresh gas mixture). The results of measurements of sevoflurane and one of the most toxic breakdown products of sevoflurane CF = C(CF3)-O-CH2F (substance A) throughout the anesthesia in the mode of inhalation-exhalation. The highest recorded concentration of substance A was 65 ppm. Biochemical analysis of blood before and after anesthesia did not show connection with nephropathy and function of liver toxicity.

Serum levels of polybrominated diphenyl ethers (PBDEs) in foam recyclers and carpet installers working in the United States.

Increased exposure to the flame retardants known as polybrominated diphenyl ethers (PBDEs) may be expected to occur during the recycling of polyurethane foam containing these chemicals. To date, no studies in the United States have investigated occupational exposure to these flame retardants during recycling processes. The objective of the present study was to determine if individuals working in foam recycling facilities, and/or carpet installers who may install carpet padding manufactured from recycled foam, possess significantly higher PBDE serum levels relative to that of the general U.S. population. As a control group, serum was collected from four spouses and one clerical worker. In addition, levels in workers were also compared to the recently published national health and nutrition examination survey (NHANES) data set on PBDEs in the general U.S. population. Serum samples were collected in duplicate and analyzed by two different laboratories as quality control. Total PBDE levels were found to be significantly higher (p < 0.05) in the individuals recycling foam and installing carpet (n = 15) relative to the control group (n = 5). Median sigmaPBDE levels in the foam recyclers, carpet layers, and control group were 160, 178, and 19 ng/g lipid, respectively. In contrast, concentrations of a polybrominated biphenyl (BB-153) and a polychlorinated biphenyl (CB-153) were equivalent among all groups tested. The PBDE congeners BDE-47, 99, 100, and 153 contributed 90% of the sigmaPBDE concentration in serum and no differences in congener patterns were apparent among the different groups. Relative to concentrations measured in the NHANES, foam recyclers and carpet layers have body burdens that are an order of magnitude higher. These data suggest individuals recycling foam-containing products, and/ or using products manufactured from recycled foam (i.e., carpet padding), have higher body burdens of PBDEs, and thus may be at higher risk from adverse health effects associated with brominated flame retardant exposure.

Hemocompatibility of poly(ether imide) membranes functionalized with carboxylic groups.

Materials for blood-contacting applications have to meet high requirements in terms to prevent thrombotic complications after the medical treatment. Surface induced thrombosis, e.g., after application of cardiovascular devices, is linked clearly to the activation of coagulation system and platelet adhesion and activation. The flat sheet poly(ether imide) membrane (PEI) was modified by binding of iminodiacetic acid (IDA) for different periods of time to obtain surfaces with carboxylic (-COOH) groups, namely PEI-1 (modified for 1 min) and PEI-2 (modified for 30 min). The successful binding of the ligands was monitored by thionin acetate assay. The physico-chemical characteristics of the materials were analyzed by SEM, AFM, water contact angle, and Zeta potential measurements. Hemocompatibility of the polymer materials was studied by analyzing the activation of coagulation system (plasma kallikrein-like activity) and platelet adhesion/activation by using immunofluorescence technique. The blood response to PEI membranes was compared to that of a commercial poly(ethylene terephthalate) (PET) membrane. Our results showed that the increase of the negative charges on the modified PEI membrane surfaces (number of -COOH groups) caused a higher contact activation of the coagulation system and a higher rate of platelet adhesion and activation compared to non-modified PEI. However, overall the hemocompatibility of all PEI membranes was higher than that of PET.

Quantification of fuel oxygenate ethers in human blood using solid-phase microextraction coupled with gas chromatography-high-resolution mass spectrometry.

Widespread use of fuel oxygenates, coupled with their high water solubility and slow degradation rate, have led to an increase in the potential for human exposure. We developed an accurate, precise, sensitive, and high-throughput analytical method to simultaneously quantify trace levels (low parts-per-trillion) of four fuel oxygenates in human blood: methyl tert-butyl ether (MTBE), ethyl tert-butyl ether (ETBE), di-isopropyl ether (DIPE), and tert-amyl methyl ether (TAME). The analytes were extracted from the head space above human blood samples, using solid-phase microextraction, desorbed into the heated injector, and chromatographically resolved by capillary gas chromatography. Analytes were detected by high-resolution mass spectrometry with multiple ion monitoring, and quantified against known standard levels by use of stable isotope-labeled internal standards for recovery correction. The low limits of detection (0.6 ng/L) allowed for measurement of MTBE, ETBE, DIPE, and TAME in parts-per-trillion levels with excellent precision (coefficient of variation ranging from 1.7 to 5.4%) and accuracy (96-100%). This method provides a means to assess fuel oxygenate exposure and study the potential relationship between exposure and adverse health outcomes.

Inflammatory pain in the rabbit: a new, efficient method for measuring mechanical hyperalgesia in the hind paw.

The discovery of novel analgesic compounds that target some receptors can be challenging due to species differences in ligand pharmacology. If a putative analgesic compound has markedly lower affinity for rodent versus other mammalian orthologs of a receptor, the evaluation of antinociceptive efficacy in non-rodent species becomes necessary. Here, we describe a new, efficient method for measuring inflammation-associated nociception in conscious rabbits. An electronic von Frey device is used, consisting of a rigid plastic tip connected to a force transducer in a hand-held probe. The plastic tip is applied to the plantar surface of a hind paw with increasing force until a withdrawal response is observed. The maximum force (g) tolerated by the rabbit (i.e., withdrawal threshold) is recorded. In young, conscious rabbits (500-700 g), baseline hind paw withdrawal thresholds typically fell within the 60-80 g range. Three hours after injection of the inflammatory agent carrageenan (3%, 200 microL, intra-plantar), withdrawal thresholds dropped by approximately 30-40 g, indicating the presence of punctate mechanical hyperalgesia. The development of hyperalgesia was dose dependently prevented by the NSAID indomethacin (ED50=2.56 mg/kg, p.o.) or the bradykinin B2 receptor peptide antagonist HOE 140 (intra-paw administration). An established hyperalgesia was dose dependently reversed by morphine sulfate (ED50=0.096 mg/kg, s.c.) or the bradykinin B1 receptor peptide antagonist [des-Arg10, Leu9]-kallidin (ED50=0.45 mg/kg, s.c.). Rabbits treated with the novel B(1) receptor small molecule antagonist compound A also showed dose-dependent reversal of hyperalgesia (ED50=20.19 mg/kg, s.c.) and analysis of plasma samples taken from these rabbits showed that, unlike other rabbit pain models, the current method permits the evaluation of pharmacokinetic-pharmacodynamic (PK-PD) relationships (compound A plasma EC50=402.6 nM). We conclude that the Electrovonfrey method can be used in rabbits with inflammatory pain to generate reliable dose- and plasma concentration-effect curves for different classes of analgesics.

Bisaryloxime ethers as potent inhibitors of transthyretin amyloid fibril formation.

Amyloid fibril formation by the plasma protein transthyretin (TTR), requiring rate-limiting tetramer dissociation and monomer misfolding, is implicated in several human diseases. Amyloidogenesis can be inhibited through native state stabilization, mediated by small molecule binding to TTR's primarily unoccupied thyroid hormone binding sites. New native state stabilizers have been discovered herein by the facile condensation of arylaldehydes with aryloxyamines affording a bisarylaldoxime ether library. Of the library's 95 compounds, 31 were active inhibitors of TTR amyloid formation in vitro. The bisaryloxime ethers selectively stabilize the native tetrameric state of TTR over the dissociative transition state under amyloidogenic conditions, leading to an increase in the dissociation activation barrier. Several bisaryloxime ethers bind selectively to TTR in human blood plasma over the plethora of other plasma proteins, a necessary attribute for efficacy in vivo. While bisarylaldoxime ethers are susceptible to degradation by N-O bond cleavage, this process is slowed by their binding to TTR. Furthermore, the degradation rate of many of the bisarylaldoxime ethers is slow relative to the half-life of plasma TTR. The bisaryloxime ether library provides valuable structure-activity relationship insight for the development of structurally analogous inhibitors with superior stability profiles, should that prove necessary.

Comparison of the effects of perfusion in determining brain penetration (brain-to-plasma ratios) of small molecules in rats.

In the process of drug discovery, brain and plasma measurements of new chemical entities in rodents are of interest, particularly when the target receptors are in the brain. Brain-to-plasma ratios (B/P) obtained from a rodent pharmacokinetic assay are useful in helping determine which compounds are brain penetrant. The study reported here was performed to determine whether whole-body saline perfusion for complete blood removal was required to accurately measure brain tissue compound concentrations. Diazepam was used as a positive control since it is highly brain penetrant. Compound A was used as a negative control since it had known poor brain penetration. After intravenous dosing with either diazepam or compound A, rats were anesthetized and blood was collected, then the brain was removed following no perfusion or whole-body perfusion with saline. The analytes described (compound A, diazepam, and the internal standard) were recovered from plasma or brain homogenate by use of protein precipitation, and were subsequently analyzed by use of liquid chromatography/tandem mass spectrometry (LC/MS/MS). The B/P values determined by use of LC-MS were not significantly different in perfused vs. non-perfused rats (P > or = 0.05). This approach (whole brain collected from non-perfused male rats) is an attractive alternative over brain penetration studies of perfused rats, since it has markedly reduced the technical time and potential for pain and distress required for generating B/P data due to elimination of the requirement for anesthesia and surgical preparation of animals.

Optimization of the headspace solid-phase microextraction for determination of glycol ethers by orthogonal array designs.

A headspace solid-phase microextraction (HS-SPME), in conjunction with gas chromatography-flame ionization detection for use in the determination of six frequently used glycol ethers at the microg/l level is described. A 75 microm Carboxenpolydimethylsiloxane fiber was used to extract the analytes from an aqueous solution. Experimental HS-SPME parameters such as extraction temperature, extraction time, salt concentration and sample volume, were investigated and optimized by orthogonal array experimental designs. The relative standard deviations for the reproducibility of the optimized HS-SPME method varied from 1.48 to 7.59%. The correlation coefficients of the calibration curves exceeded 0.998 in the microg/l range of concentration with at least two orders of magnitude. The method detection limits for glycol ethers in deionized water were in the range of 0.26 to 3.42 microg/l. The optimized method was also applied to the analysis of glycol ethers in urine and blood samples with the method detection limits ranged from 1.74 to 23.2 microg/l.

Glutathione S-conjugation of the sevoflurane degradation product, fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (compound A) in human liver, kidney, and blood in vitro.

Fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (FDVE) is a fluorinated alkene formed by degradation of the volatile anesthetic sevoflurane in anesthesia machines. FDVE is nephrotoxic in rats and undergoes glutathione-dependent conjugation to form two alkane (G1, G2) and two alkene glutathione S-conjugates (G3, G4), cleavage to cysteine S-conjugates, and beta-lyase-catalyzed metabolism to reactive thionoacyl fluorides, which may react with cellular macromolecules to cause nephrotoxicity. Although similar metabolites have been identified in human urine in vivo, little is known about sites and mechanisms of GSH conjugation in humans. This investigation quantified FDVE-GSH conjugates formed by human hepatic and renal microsomal and cytosolic fractions and blood in vitro. LC-MS/MS analysis identified all four GSH conjugates (G1-G4) formed in all human subcellular fractions. Quantitative analysis indicated that the relative order of formation was G2 > G1 > G4 > G3 with human liver and kidney subfractions. In blood, the order was G1 > G4 > G2 > G3. These results demostrate that FDVE undergoes GSH-dependent conjugation in human liver and kidney microsomes and cytosol as well as blood, which may account for the detection of corresponding mercapturic acids in the urine of patients exposed to FDVE.

Fluorescence determination of sulphobutylether-beta-cyclodextrin in human plasma by size exclusion chromatography with inclusion complex formation.

A selective method for the determination of sulphobutylether-beta-cyclodextrin (SBECD) in human plasma has been developed and validated over the range 4-200 microg ml(-1). SBECD is extracted from plasma using end-capped cyclohexyl solid phase extraction cartridges. This is followed by high performance size exclusion chromatography with a mobile phase consisting of 1-naphthol (0.1 mM) in methanol-potassium nitrate (0.2 M) (1:9 v/v), 1 ml min(-1). The high aqueous content of the mobile phase quenches the fluorescence of 1-naphthol. However, the naphthol forms an inclusion complex with SBECD. The non-polar 'bucket' environment of the inclusion region restores the fluorescence, which is measured at excitation and emission wavelengths of 290 and 360 nm, respectively, when SBECD elutes from the column.

Haematological and spermatotoxic effects of ethylene glycol monomethyl ether in copper clad laminate factories.

OBJECTIVES: To investigate the effects of ethylene glycol monomethyl ether (EGME) on haematology and reproduction in exposed workers. METHODS: 53 Impregnation workers from two factories that make copper clad laminate with EGME as a solvent were recruited as the exposed group. Another group of 121 lamination workers with indirect exposure to EGME was recruited as the control group. Environmental monitoring of concentrations of EGME in air and biological monitoring of urinary methoxyacetic acid (MAA) concentrations were performed. Venous blood was collected for routine and biochemical analyses. Semen was collected from 14 workers exposed to EGME for sperm analysis and was compared with 13 control workers. RESULTS: Results of haematological examination showed that the haemoglobin, packed cell volume, and red blood cell count in the male workers exposed to EGME were significantly lower than in the controls. The frequency of anaemia in the exposed group (26.1%) was significantly higher than in the control group (3.2%). However, no differences were found between the female workers exposed and not exposed to EGME. After adjustment for sex, body mass index, and duration of employment, red blood cell count was significantly negatively associated with air concentrations of EGME, and haemoglobin, packed cell volume, and red blood cell count were significantly negatively associated with urinary concentrations of MAA. The pH of semen in the exposed workers was significantly lower than in the control workers, but there were no significant differences in the sperm count or sperm morphology between the exposed and control groups. CONCLUSION: It can be concluded that EGME is a haematological toxin, which leads to anaemia in the exposed workers. However, the data from this study did not support the theory of a spermatotoxic effect of EGME.

Absence of biochemical evidence for renal and hepatic dysfunction after 8 hours of 1.25 minimum alveolar concentration sevoflurane anesthesia in volunteers.

BACKGROUND: Sevoflurane is degraded by carbon dioxide absorbents to a difluorovinyl ether (compound A) that can cause renal and hepatic injury in rats. The present study applied sensitive markers of renal and hepatic function to determine the safety of prolonged (8 h), high concentration (3% end-tidal) sevoflurane anesthesia in human volunteers. METHODS: Thirteen healthy male volunteers provided informed consent to undergo 8 h of 1.25 minimum alveolar concentration sevoflurane anesthesia delivered with a fresh gas flow of 2 l/min. Glucose, protein, albumin, N-acetyl-beta-D-glucosaminidase (NAG), and alpha- and pi-glutathione-S-transferase (GST) levels were analyzed in urine collected at 24 h before and for 3 days after sevoflurane anesthesia. Daily blood samples were analyzed for creatinine, blood urea nitrogen (BUN), alanine aminotransferase, alkaline phosphatase, and bilirubin concentrations. Circuit compound A and plasma fluoride concentrations were measured. RESULTS: During anesthesia, average and maximum inspired compound A concentrations were 27 +/- 7 and 34 +/- 6 (mean +/- SD) and median mean blood pressure, esophageal temperature, and end-tidal carbon dioxide levels were 63 mmHg, 36.8 degrees C, and 32 mmHg, respectively. The average serum inorganic fluoride concentration 2 h after anesthesia was 66.2 +/- 14.7 microM. Results of tests of hepatic function and renal function (BUN, creatinine concentration) were unchanged after anesthesia. Glucose, protein, albumin, and NAG excretion were not significantly increased after anesthesia. Urine concentrations of alpha-GST and pi-GST were increased on day 1 after anesthesia and alpha-GST was increased on day 2 after anesthesia but returned to normal afterward. CONCLUSIONS: Prolonged (8 h), high concentration (3%) sevoflurane anesthesia administered to volunteers in a fresh gas flow of 2 l/min does not result in clinically significant changes in biochemical markers of renal or hepatic dysfunction.

Effect of temperature on the solubility of desflurane, sevoflurane, enflurane and halothane in blood.

We have investigated the effect of temperature on the blood-gas solubility of desflurane, sevoflurane, enflurane and halothane. Blood was equilibrated with gas mixtures of known composition in open cuvette or closed flask tonometers over a temperature range of 29-39 degrees C, and the concentration of each anaesthetic in blood was measured at 37 degrees C by repeated headspace analysis using a gas chromatograph. Solubility increased by 5.4% of the solubility at 37 degrees C for each degree that equilibration temperature was reduced. This result was true for all anaesthetics in all blood samples, and is in keeping with results for other volatile anaesthetics.