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The over-expression of NF- κ B signalling in both muscle and immune cells contribute to the pathology in dystrophic muscle. The anti-inflammatory properties of glucocorticoids, mediated predominantly through monomeric glucocorticoid receptor inhibition of transcription factors such as NF- κ B (transrepression), are postulated to be an important mechanism for their beneficial effects in Duchenne muscular dystrophy. Chronic glucocorticoid therapy is associated with adverse effects on metabolism, growth, bone mineral density and the maintenance of muscle mass. These detrimental effects result from direct glucocorticoid receptor homodimer interactions with glucocorticoid response elements of the relevant genes. Compound A, a non-steroidal selective glucocorticoid receptor modulator, is capable of transrepression without transactivation. We confirm the in vitro NF- κ B inhibitory activity of compound A in H- 2Kb- tsA58 mdx myoblasts and myotubes, and demonstrate improvements in disease phenotype of dystrophin deficient mdx mice. Compound A treatment in mdx mice from 18 days of post-natal age to 8 weeks of age increased the absolute and normalized forelimb and hindlimb grip strength, attenuated cathepsin-B enzyme activity (a surrogate marker for inflammation) in forelimb and hindlimb muscles, decreased serum creatine kinase levels and reduced IL-6, CCL2, IFN γ, TNF and IL-12p70 cytokine levels in gastrocnemius ( GA) muscles. Compared with compound A, treatment with prednisolone, a classical glucocorticoid, in both wild-type and mdx mice was associated with reduced body weight, reduced GA, tibialis anterior and extensor digitorum longus muscle mass and shorter tibial lengths. Prednisolone increased osteopontin (S pp1) gene expression and osteopontin protein levels in the GA muscles of mdx mice and had less favourable effects on the expression of Foxo1, Foxo3, Fbxo32, Trim63, Mstn and Igf1 in GA muscles, as well as hepatic Igf1 in wild-type mice. In conclusion, selective glucocorticoid receptor modulation by compound A represents a potential therapeutic strategy to improve dystrophic pathology. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Highlights: [•] For the first time the therapeutic potential of CpdA in dengue virus infection. [•] Cytokine gene expression profile in dengue virus-infected cells. [•] Inhibition of dengue virus-induced cytokine production by CpdA. [•] Inhibition of dengue virus-induced leukocyte migration by CpdA. [•] Inhibition of dengue virus production by CpdA. [ABSTRACT FROM AUTHOR]

Glucocorticoids (GCs) are potent anti-inflammatory drugs, but their use is limited by their adverse effects on the skeleton. Compound A (CpdA) is a novel GC receptor modulator with the potential for an improved risk/benefit profile. We tested the effects of CpdA on bone in a mouse model of GC-induced bone loss. Bone loss was induced in FVB/N mice by implanting slow-release pellets containing either vehicle, prednisolone (PRED) (3.5 mg), or CpdA (3.5 mg). After 4 weeks, mice were killed to examine the effects on the skeleton using quantitative computed tomography, bone histomorphometry, serum markers of bone turnover, and gene expression analysis. To assess the underlying mechanisms, in vitro studies were performed with human bone marrow stromal cells (BMSCs) and murine osteocyte-like cells (MLO-Y4 cells). PRED reduced the total and trabecular bone density in the femur by 9% and 24% and in the spine by 11% and 20%, respectively, whereas CpdA did not influence these parameters. Histomorphometry confirmed these results and further showed that the mineral apposition rate was decreased by PRED whereas the number of osteoclasts was increased. Decreased bone formation was paralleled by a decline in serum procollagen type 1 N-terminal peptide (P1NP), reduced skeletal expression of osteoblast markers, and increased serum levels of the osteoblast inhibitor dickkopf-1 (DKK-1). In addition, serum CTX-1 and the skeletal receptor activator of NF-κB ligand (RANKL)/osteoprotegerin (OPG) ratio were increased by PRED. None of these effects were observed with CpdA. Consistent with the in vivo data, CpdA did not increase the RANKL/OPG ratio in MLO-Y4 cells or the expression of DKK-1 in bone tissue, BMSCs, and osteocytes. Finally, CpdA also failed to transactivate DKK-1 expression in bone tissue, BMSCs, and osteocytes. This study underlines the bone-sparing potential of CpdA and suggests that by preventing increases in the RANKL/OPG ratio or DKK-1 in osteoblast lineage cells, GC-induced bone loss may be ameliorated. © 2012 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Abstract: Nicotinic agonists have been shown to enhance performance in cognitive tasks based on attention and memory. The aim of this study was to use a test of olfactory working memory; the odour span task (OST) in rodents, to investigate the effects of subtype-specific nicotinic agonists on working memory in normal rats. Rats were trained in a non-matching to sample (NMTS) rule and then the full OST, which involved identifying a novel odour from an increasing number of presented odours. Male hooded Lister rats were treated with nicotine, selective nicotinic agonists or vehicle (saline). In order to validate the task, muscarinic and nicotinic receptor antagonists were also examined. Nicotine at both 0.05 and 0.1mg/kg significantly increased mean span length in the OST. The selective α4β2 nicotinic receptor agonist metanicotine (0.1mg/kgs.c.) and the selective α7 nicotinic receptor agonist (R)-N-(1-azabicyclo[2.2.2]oct-3-yl)(5-(2-pyridyl)thiophene-2-carboxamide) (compound A, 10mg/kg i.p.) also improved performance. In contrast, mecamylamine and scopolamine significantly decreased mean span length. These findings suggest a role for the activation of both α4β2 and α7 subtypes of neuronal nicotinic receptor in mediating enhancements of olfactory working memory capacity in normal, non-compromised rats. These nicotinic receptor subtypes may therefore prove to be useful targets for the development of novel treatments for neuropsychiatric disorders that involve cognitive dysfunction. [Copyright &y& Elsevier]

Nicotine enhances attentional and working memory aspects of executive function in the prefrontal cortex (PFC) where dopamine plays a major role. Here, we have determined the nicotinic acetylcholine receptor (nAChR) subtypes that can modulate dopamine release in rat PFC using subtype-selective drugs. Nicotine and 5-Iodo-A-85380 (β2* selective) elicited [3H]dopamine release from both PFC and striatal prisms in vitro and dopamine overflow from medial PFC in vivo. Blockade by dihydro-β-erythroidine supports the participation of β2* nAChRs. However, insensitivity of nicotine-evoked [3H]dopamine release to α-conotoxin-MII in PFC prisms suggests no involvement of α6β2* nAChRs, in contrast to the striatum, and this distinction is supported by immunoprecipitation of nAChR subunits from these tissues. The α7 nAChR-selective agonists choline and Compound A also promoted dopamine release from PFC in vitro and in vivo, and their effects were enhanced by the α7 nAChR-selective allosteric potentiator PNU-120596 and blocked by specific antagonists. DNQX and MK801 inhibited [3H]dopamine release evoked by choline and PNU-120596, suggesting crosstalk between α7 nAChRs, glutamate and dopamine in the PFC. In vivo, systemic (but not local) administration of PNU-120596, in the absence of agonist, facilitated dopamine overflow in the medial PFC, consistent with the activation of extracortical α7 nAChRs by endogenous acetylcholine or choline. These data establish that both β2* and α7 nAChRs can modulate dopamine release in the PFC in vitro and in vivo. Through their distinct actions on dopamine release, these nAChR subtypes could contribute to executive function, making them specific therapeutic targets for conditions such as schizophrenia and attention deficit hyperactivity disorder. [ABSTRACT FROM AUTHOR]

Background and purpose:Recently, we reported that 12(S)-HPETE (12(S)-hydroperoxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid) induces scratching in ICR mice. We hypothesized that 12(S)-HPETE might act as an agonist of the low-affinity leukotriene B4 receptor BLT2. To confirm the involvement of the BLT2 receptor in 12(S)-HPETE-induced scratching, we studied the scratch response using the BLT2 receptor agonists compound A (4′-{[pentanoyl (phenyl) amino]methyl}-1,1′-biphenyl-2-carboxylic acid) and 12(S)-HETE (12(S)-hydroxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid).Experimental approach:A video recording was used to determine whether the BLT2 receptor agonists caused itch-associated scratching in ICR mice. Selective antagonists and several chemicals were used.Key results:Both 12(S)-HETE and compound A dose dependently induced scratching in the ICR mice. The dose–response curve for compound A showed peaks at around 0.005–0.015 nmol per site. Compound A- and 12(S)-HETE-induced scratching was suppressed by capsaicin and naltrexon. We examined the suppressive effects of U75302 (6-[6-(3-hydroxy-1E,5Z-undecadienyl)-2-pyridinyl]-1,5-hexanediol, the BLT1 receptor antagonist) and LY255283 (1-[5-ethyl-2-hydroxy-4-[[6-methyl-6-(1H-tetrazol-5-yl)heptyl]oxy]phenyl]-ethanone, the BLT2 receptor antagonist) on the BLT2 agonist-induced scratching. LY255283 suppressed compound A- and 12(S)-HETE-induced scratching, but U75302 did not. LY255283 required a higher dose to suppress the compound A-induced scratching than it did to suppress the 12(S)-HETE-induced scratching. One of the BLT2 receptor agonists, 12(R)-HETE (12(R)-hydroxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid), also induced scratching in the ICR mice.Conclusions and implications:Our present results corroborate the hypothesis that the BLT2 receptor is involved in 12(S)-lipoxygenase-product-induced scratching in ICR mice. We also confirmed that this animal model could be a valuable means of evaluating the effects of BLT2 receptor antagonists.British Journal of Pharmacology (2008) 154, 1073–1078; doi:10.1038/bjp.2008.220; published online 9 June 2008 [ABSTRACT FROM AUTHOR]

Aim: To determine compound A, formaldehyde and methanol concentrations in low-flow anaesthesia using different carbon dioxide absorbers. Methods: Fifteen patients scheduled for general or urological surgery were exposed to low-flow (500 ml/min) anaesthesia with sevoflurane. The patients were randomly allocated to three groups: soda lime, DrägerSorb Free® or Amsorb Plus®. The concentrations of compound A, formaldehyde and methanol were sampled and analysed from the limbs of the anaesthesia circuit at T30 (30 min after the start of low-flow sevoflurane anaesthesia), T90 (90 min) and T150 (150 min). The temperatures of the absorbers were measured at the same time. Results: Statistically significant differences ( P < 0.05) were found in the production of compound A from soda lime (with the highest values), DrägerSorb Free® and Amsorb Plus® at each measurement time. Only traces of methanol (ranging from < 0.131 to 3.799 mg/m3) were measured, higher with Amsorb Plus® (statistically significant differences were found only at T90). The formaldehyde values (ranging from < 0.1227 to 17.79 mcg/m3 p.p.b.) were higher with soda lime, and the difference was statistically significant at T150 and, in the inspiratory limb only, at T90. The temperatures of the absorbers were higher for soda lime and lower for Amsorb Plus®; the difference was statistically significant at T0 in the upper canister and at T30 in both canisters. Conclusion: The concentrations of harmful products in the circuit were negligible and were lower using the new-generation absorbers. Using Amsorb Plus®, the temperatures in the canisters were lower than with the other two absorbers. [ABSTRACT FROM AUTHOR]

Background: The degradation of sevoflurane can lead to the production of compound A (CA) and carbon monoxide (CO) and an increase in temperature of the absorbent. CA is known to be nephrotoxic in rats. These reactions depend on the strong base and water contents of the carbon dioxide absorbent used. The purpose of this study was to measure the maximum amounts of CA and CO produced, and the temperature increase, for seven different carbon dioxide absorbents for sevoflurane containing different contents of strong bases. Methods: Seven absorbents [some free of strong bases (f)] were employed in hydrated (h) and completely desiccated (d) conditions in a patient model, using a circle anesthesia system connected to an artificial lung. Low-flow anesthesia with an oxygen–nitrous oxide mixture was maintained using 0.8% sevoflurane. For the quantification of CA and CO, a portable gas chromatograph was used. The temperature was measured inside the absorbent. Results: In consecutive order of CA-producing potency, Amsorb®(f)(d), Drägersorb(h), Medisorb®(h), lithium hydroxide(f)(d), Drägersorb(d), Medisorb®(d), Spherasorb®(h) and Spherasorb®(d) produced small amounts of CA. Loflosorb® and Superia®, which are free of strong bases, did not produce any CA or CO in hydrated or desiccated conditions. Only desiccated Drägersorb®, Medisorb® and Spherasorb® demonstrated small amounts of CO accompanied by a significant temperature increase. Conclusion: In this patient model, we demonstrated that different types of absorbent produced small amounts of CA and CO or none at all. No relationship could be established between temperature and CA concentration. [ABSTRACT FROM AUTHOR]

The major degradation product of the volatile anesthetic sevoflurane, the haloalkene fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (FDVE or “compound A”), is nephrotoxic in rats. FDVE undergoes complex metabolism and bioactivation, which mediates the nephrotoxicity. Nevertheless, the molecular and cellular mechanisms of FDVE toxification are unknown. This investigation evaluated the gene expression profile of kidneys in rats administered a nephrotoxic dose of FDVE. Male Fischer 344 rats (five per group) received 0.25 mmol/kg intraperitoneal FDVE or corn oil (controls) and were sacrificed after 24 or 72 h. Urine output and kidney histological changes were quantified. Kidney RNA was extracted for microarray analysis using Affymetrix GeneChip® Rat Expression Array 230A arrays. Quantitative real-time PCR confirmed the modulation of several genes. FDVE caused significant diuresis and necrosis at 24 h, with normal urine output and evidence of tubular regeneration at 72 h. There were 517 informative genes that were differentially expressed >1.5-fold (p < 0.05) versus control at 24 h, of which 283 and 234 were upregulated and downregulated, respectively. Major classes of upregulated genes included those involved in apoptosis, oxidative stress, and inflammatory response (mostly at 24 h), and regeneration and repair; downregulated genes were generally associated with transporters and intermediary metabolism. Among the quantitatively most upregulated genes were kidney injury molecule, osteopontin, clusterin, tissue inhibitor of metalloproteinase 1, and TNF receptor 12, which have been associated with other forms of nephrotoxicity, and angiopoietin-like protein 4, glycoprotein nmb, ubiquitin hydrolase, and HSP70. Microarray results were confirmed by quantitative real-time PCR. FDVE causes rapid and brisk changes in gene expression, providing potential insights into the mechanism of FDVE toxification, and potential biomarkers for FDVE nephrotoxicity which are more sensitive than conventional measures of renal function. [ABSTRACT FROM AUTHOR]

The volatile anaesthetics sevoflurane and desflurane feature new and promising properties. Their low blood and tissue solubility enables rapid onset of and emergence from anaesthesia, thus enhancing patient safety and comfort. This article is designed as an up-to-date review of the pharmacokinetic and pharmacodynamic properties of modern volatile anaesthetics. The first part focuses on pharmacokinetic issues such as substance properties, uptake and elimination. The second part covers the effects of inhaled anaesthetics on organ systems, with emphasis on the central nervous system, the cardiovascular system, the respiratory tract, liver and kidneys. [Copyright &y& Elsevier]

Abstract: The compound, 5-{4-[3-(4-cyclohexyl-2-propylphenoxy)propoxy]phenyl}-1,3-oxazolidine-2,4-dione (compound A) is a peroxisome proliferator-activated receptor-γ (PPARγ) agonist. PPARγ agonists have proven useful in the treatment of type 2 diabetes, which is characterized by hyperglycemia, insulin resistance and/or abnormal insulin secretion. The metabolism of this oxazolidinedione (OZD) was investigated in male rat, dog, monkey and human liver microsomes, and recombinant human cytochrome P450 enzymes (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4) in the presence of NADPH. Routes of metabolism included monohydroxylation of the cyclohexane ring at multiple positions, monohydroxylation of the n-propyl side chain or the tether linkage, and OZD ring opening, giving rise to the keto amide and alcohol amide entities. Liver microsomes showed subtle qualitative and quantitative metabolic differences among rat, dog, monkey and human preparations. Further, CYP2C8 and CYP2C19 did not display different regioselectivity for hydroxylation on the cyclohexane ring with both of them giving rise to C-3 and C-4 hydroxy metabolites, but they did display different stereoselectivity with CYP2C8 preferring cyclohexane hydroxylation in equatorial positions and CYP2C19 in axial positions. [Copyright &y& Elsevier]

Toxic degradation products are formed from a range of old and modern anesthetic agents. The common element in the formation of degradation products is the reaction of the anesthetic agent with the bases in the carbon dioxide absorbents in the anesthesia circuit. This reaction results in the conversion of trichloroethylene to dichloroacetylene, halothane to 2-bromo-2-chloro-1,1-difluoroethylene, sevoflurane to 2-(fluoromethoxy)-1,1,3,3,3-pentafluoro-1-propene (Compound A), and desflurane, isoflurane, and enflurane to carbon monoxide. Dichloroacetylene, 2-bromo-2-chloro-1,1- difluoroethylene, and Compound A form glutathione S-conjugates that undergo hydrolysis to cysteine S-conjugates and bioactivation of the cysteine S-conjugates by renal cysteine conjugate α -lyase to give nephrotoxic metabolites. The elucidation of the mechanisms of formation and bioactivation of degradation products has allowed for the safe use of anesthetics that may undergo degradation in the anesthesia circuit. [ABSTRACT FROM AUTHOR]

Compares the properties of two new-generation of carbon dioxide absorbents Amsorb Plus and Drägersorb with those of Amsorb and Sodasorb II. Methodology; Results; Conclusion.

Two new generation carbon dioxide absorbents, DrägerSorb® Free and Amsorb® Plus, were studied in vitro for formation of compound A or carbon monoxide, during minimal gas flow (500 ml.min−1) with sevoflurane or desflurane. Compound A was assessed by gas chromatography/mass spectrometry and carbon monoxide with continuous infrared spectrometry. Fresh and dehydrated absorbents were studied. Mean (SD) time till exhaustion (inspiratory carbon dioxide concentration ≥ 1 kPa) with fresh absorbents was longer with DrägerSorb® Free (1233 (55) min) than with Amsorb® Plus (1025 (55) min; p < 0.01). For both absorbents, values of compound A were < 1 ppm and therefore below clinically significant levels, but were up to 0.25 ppm higher with DrägerSorb® Free than with Amsorb® Plus. Using dehydrated absorbents, values of compound A were about 50% lower than with fresh absorbents and were identical for DrägerSorb® Free and Amsorb® Plus. With dehydrated absorbents, no detectable carbon monoxide was found with desflurane. [ABSTRACT FROM AUTHOR]

γ-Glutamyltransferase (γ-GT) catalyzes the hydrolysis of glutathione, glutathione S-conjugates, and γ-substituted l-glutamate derivatives. Acivicin is an irreversible inhibitor of γ-GT that has been used to study the role of γ-GT in glutathione homeostasis and glutathione-dependent bioactivation reactions. The present studies were undertaken because of reported conflicting effects of acivicin on the nephrotoxicity of some haloalkenes that undergo glutathione-dependent bioactivation. The objective of this study was to test the hypothesis that acivicin may alter renal glutathione concentrations; acivicin-induced changes in renal glutathione concentrations may alter the susceptibility of the kidney to the nephrotoxic effects of haloalkenes. Hence, diurnal and acivicin-induced changes in renal and hepatic glutathione concentrations along with renal and hepatic γ-GT activities were investigated. The previously observed diurnal variations in hepatic glutathione concentrations in fed rats were confirmed, but no diurnal variations were observed in renal glutathione concentrations or in renal or hepatic γ-GT activities. Renal and hepatic glutathione concentrations and γ-GT activities were measured in tissue homogenates from rats given 0, 0.1, or 0.2 mmol acivicin/kg (i.p.) and killed 0, 2, 4, 8, 12, or 24 hr later. Renal glutathione concentrations were increased above control values in acivicin-treated rats, whereas acivicin had no effect on hepatic glutathione concentrations. Renal γ-GT activities decreased within 2 hr after giving acivicin and remained decreased for 24 hr. Acivicin had no effect on hepatic γ-GT activities, except at 24 hr after treatment when values in acivicin-treated rats were elevated compared with controls. Although the present studies do not afford an explanation of the mechanism whereby acivicin increases the nephrotoxicity of some haloalkenes, they do indicate that acivicin is not a reliable probe to investigate the role of γ-GT in haloalkene-induced nephrotoxicity. [Copyright &y& Elsevier]

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 but not humans. Rat FDVE nephrotoxicity is attributed to FDVE glutathione conjugation and bioactivation of subsequent FDVE-cysteine S-conjugates, in part by renal β-lyase. Although FDVE conjugation and metabolism occur in both rats and humans, the mechanism for selective toxicity in rats and lack of effect in humans is incompletely elucidated. This investigation measured FDVE S-conjugate cytotoxicity in cultured human proximal tubular HK-2 cells, and compared this with known cytotoxic S-conjugates. HK-2 cells were incubated with FDVE and its GSH, cysteine S-mercapturic acid, cysteine S-sulfoxide, and mercapturic acid sulfoxide conjugates (0.1–2.7 mM) for 24 h. Cytotoxicity was determined by lactate dehydrogenase (LDH) release, total LDH, and the ability of viable cells to reduce a tetrazolium-based compound (MTT). FDVE was cytotoxic only at concentrations ≥0.9 mM. No increase in LDH release was observed with either FDVE-GSH conjugate. The FDVE-cysteine conjugates S-(1,1-difluoro-2-fluoromethoxy-2-(trifluoromethyl) ethyl)-l-cysteine (DFEC) and (Z)-S-(1-fluoro-2-fluoromethoxy-2-(trifluoromethyl) vinyl)-l-cysteine ((Z)-FFVC) caused significant differences in LDH release and MTT reduction only at 2.7 mM; (Z)-FFVC was slightly more cytotoxic. Both S-(1,1-difluoro-2-fluoromethoxy-2-(trifluoromethyl) ethyl)-l-cysteine sulfoxide (DFEC-SO) and (Z)-N-acetyl-S-(1-fluoro-2-fluoromethoxy-2-(trifluoromethyl) vinyl)-l-cysteine sulfoxide ((Z)-N-Ac-FFVC-SO) caused slightly greater changes in LDH release or total LDH than the corresponding equimolar DFEC and (Z)-N-acetyl-S-(1-fluoro-2-fluoromethoxy-2-(trifluoromethyl) vinyl)-l-cysteine ((Z)-N-Ac-FFVC) conjugates. In contrast to FDVE S-conjugates, S-(1,2-dichlorovinyl)-l-cysteine was markedly cytotoxic, at concentrations as low as 0.1 mM. These results show that human proximal tubular cells are relatively resistant to FDVE and FDVE S-conjugate cytotoxicity. This may partially explain the lack of FDVE nephrotoxicity in humans. [Copyright &y& Elsevier]

: Study objectiveTo determine compound A concentrations in a low-flow circuit containing Dra¨gersorb Free® (Dra¨ger, Lu¨beck, Germany), Amsorb® (Armstrong, Coleraine, Northern Ireland), and Sodasorb II® (W. R. Grace, Lexington, MA).: DesignRandomized study.: SettingHamamatsu University Hospital.: Patients24 ASA physical status I and II patients scheduled for general anesthesia greater than 3 hours’ duration.: InterventionsPatients were allocated to three groups of eight patients each to receive either using either Dra¨gersorb Free®, Amsorb®, or Sodasorb II®. Immediately before anesthesia induction, 1 kg of fresh absorbent was placed in the anesthesia canister. Anesthesia was maintained with sevoflurane (end-tidal concentration 1% to 3%) in oxygen and nitrous oxide (FIO2 > 0.3) at a total flow of 1 L/min.: MeasurementsInspiratory compound A concentration in the circuit was measured once every hour.: Main resultsMaximum compound A concentrations for Dra¨gersorb Free®, Amsorb®, and Sodasorb II® were 2.4 ± 0.8 (mean ± SD) ppm, 3.1 ± 0.5 ppm, and 28.0 ± 10.0 ppm (p < 0.01 vs. Dra¨gersorb Free® and Amsorb®). Concentrations with Dra¨gersorb Free® and Amsorb® remained at less than 4 ppm throughout the study.: ConclusionsBecause compound A concentrations in the circuit with Dra¨gersorb Free® and Amsorb® were negligible, sevoflurane can be used at a fresh gas flow of 1 L/min with these two absorbents. [Copyright &y& Elsevier]

Background: To define the best strategy to reduce Compound A production in Sevoflurane low-flow anaesthesia by experiments in vitro and in vivo of different absorbers and different anaesthesia machines.Methods: In vitro Compound A has been measured at 45 degrees C in vitro following Sevoflurane interactions with potassium hydroxide, sodium hydroxide, soda lime, Dragersorb 800 Plus and Amsorb, a new absorber that does not contain sodium or potassium hydroxide. In vivo Compound A concentration in the anaesthesia circuit (inspiratory branch) has been measured using an indirect sampling method through absorber vials (SKC) with active coal granules, during low flows (500 ml/min) general anaesthesia using soda lime, Dragersorb 800 Plus or Amsorb as absorber. Compound A was also measured during low flows (500 ml/min) general anaesthesia using as carbon dioxide absorber soda lime with different anaesthesia machines.Results: In vitro at 45 degrees C Compound A concentration with soda lime and Dragersorb 800 Plus was about 10 times higher than with Amsorb. In vivo the Compound A concentrations in the inspiratory branch of the circuit were lower in the group with Amsorb.Conclusion: The Compound A production is minimal with Amsorb as carbon dioxide absorber. [ABSTRACT FROM AUTHOR]

Studies the apparent and actual nephrotoxicity of halogenated inhalational anesthetics. Concern about reports of renal failure following methoxyflurane anesthetics; Observation of elevated serum fluoride concentrations being responsible for post-operative renal damage; Investigations through human and animal studies of the potential of sevoflurane, a new inhalational anesthetic, for producing nephrotoxicity.

Copyright of Anaesthesist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Anaesthesist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Anaesthesist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Sevoflurane, a new inhalational anesthetic, is metabolically broken down into several decomposition products in the presence of CO absorbents. One of the products, CF=C (CF) OCHF (compound A), which appears to be the most toxic, was quantitated in 20 surgical patients subjected to more than 3 h of anesthesia using a low-flow anesthesia circuit. To minimize the variables in the reaction velocity between sevoflurane and the CO absorbents, we maintained the sevoflurane concentration at 2%. Wakolime-A, one type of soda lime, resulted in the highest increase in compound A concentration. The peak concentration was 27.1±3.1 ppm, less than one-tenth of the LC (50% lethal concentration) of compound A, which was previously reported as 420 or 400 ppm in rats. We also measured the temperature in CO absorbents, which had been reported to influence compound A production. The elevation in the temperature was 27.9±1.3°C in Wakolime-A, 29.4±8.4°C in Baralyme, and 31.0±5.0°C in Sodasorb II. Further studies are needed to assess the safety and efficacy of sevoflurane. [ABSTRACT FROM AUTHOR]