Anesthetic Properties of 4-Iodopropofol

2001 ◽  
Vol 94 (6) ◽  
pp. 1050-1057 ◽  
Author(s):  
Ratnakumari Lingamaneni ◽  
Matthew D. Krasowski ◽  
Andrew Jenkins ◽  
Tuyen Truong ◽  
Austin L. Giunta ◽  
...  
Keyword(s):  
Gabaa Receptor ◽  
Intravenous Injection ◽  
Gabaa Receptors ◽  
Intraperitoneal Injection ◽  
Glutamate Release ◽  
Hippocampal Slices ◽  
In Vitro Assays ◽  
Gamma Aminobutyric Acid ◽  
General Anesthetics

Background Positive modulation of gamma-aminobutyric acid type A (GABAA) receptor function is recognized as an important component of the central nervous system depressant effects of many general anesthetics, including propofol. The role for GABAA receptors as an essential site in the anesthetic actions of propofol was recently challenged by a report that the propofol analog 4-iodopropofol (4-iodo-2,6-diisopropylphenol) potentiated and directly activated GABAA receptors, yet was devoid of sedative-anesthetic effects in rats after intraperitoneal injection. Given the important implications of these findings for theories of anesthesia, the authors compared the effects of 4-iodopropofol with those of propofol using established in vivo and in vitro assays of both GABAA receptor-dependent and -independent anesthetic actions. Methods The effects of propofol and 4-iodopropofol were analyzed on heterologously expressed recombinant human GABAA alpha1beta2gamma2 receptors, evoked population spike amplitudes in rat hippocampal slices, and glutamate release from rat cerebrocortical synaptosomes in vitro. Anesthetic potency was determined by loss of righting reflex in Xenopus laevis tadpoles, in mice after intraperitoneal injection, and in rats after intravenous injection. Results Like propofol, 4-iodopropofol enhanced GABA-induced currents in recombinant GABAA receptors, inhibited synaptic transmission in rat hippocampal slices, and inhibited sodium channel-mediated glutamate release from synaptosomes, but with reduced potency. After intraperitoneal injection, 4-iodopropofol did not produce anesthesia in mice, but it was not detected in serum or brain. However, 4-iodopropofol did produce anesthesia in tadpoles (EC50 = 2.5 +/- 0.5 microM) and in rats after intravenous injection (ED50 = 49 +/- 6.2 mg/kg). Conclusions Propofol and 4-iodopropofol produced similar actions on several previously identified cellular and molecular targets of general anesthetic action, and both compounds induced anesthesia in tadpoles and rats. The failure of 4-iodopropofol to induce anesthesia in rodents after intraperitoneal injection is attributed to a pharmacokinetic difference from propofol rather than to major pharmacodynamic differences.

Analysis of voltage-gated and synaptic conductances contributing to network excitability defects in the mutant mouse tottering

1994 ◽  
Vol 71 (1) ◽  
pp. 1-10 ◽  
Author(s):  
S. A. Helekar ◽  
J. L. Noebels
Keyword(s):  
Gabaa Receptor ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Channel Blockers ◽  
Gamma Aminobutyric Acid ◽  
Voltage Gated ◽  
Voltage Dependent ◽  
Prolonged Duration ◽  
Ca3 Pyramidal Neurons ◽  
The Difference

1. Intracellular current- and voltage-clamp recordings were carried out in CA3 pyramidal neurons from hippocampal slices of adult tg/tg mice and their coisogenic C57BL/6J (+/+) controls with the use of the single-electrode switch-clamp technique. The principal aim of this study was to investigate the mechanisms responsible for the tg gene-linked prolongation (mean 60%) of a giant synaptic response, the potassium-induced paroxysmal depolarizing shift (PDS) at depolarized membrane potentials (Vm -47 to -54 mV) during synchronous network bursting induced by 10 mM potassium ([K+]o). 2. To examine the role of intrinsic voltage-dependent conductances underlying the mutant PDS prolongation, neurons were voltage clamped by the use of microelectrodes filled with 100 mM QX-314 or QX-222 chloride (voltage-gated sodium channel blockers) and 2 M cesium sulphate (potassium channel blocker). The whole-cell currents active during the PDS showed a significantly prolonged duration (mean 34%) at depolarized Vms in tg/tg compared with +/+ cells, indicating that a defect in voltage-dependent conductances is unlikely to completely account for the mutant phenotype. 3. Bath application of 40 microM (DL)-2-aminophosphonovalerate (DL-APV) produced a 30% reduction in PDS duration in both genotypes but failed to significantly alter the tg gene-linked prolongation compared with the wild type. These data indicate that the mutant PDS abnormality does not result from a selective increase of the N-methyl-D-aspartate (NMDA) receptor-mediated excitatory synaptic component. 4. Blockade of gamma-aminobutyric acid-A (GABAA) transmission with picrotoxin (50 microM) or bicuculline (1–5 microM) completely eliminated the difference in PDS duration between the genotypes. Furthermore, although both GABAA receptor antagonists increased the mean PDS duration in +/+ neurons, they did not significantly alter it in tg/tg neurons. These findings are consistent with a reduction in GABAA receptor-mediated synaptic inhibition during bursting in the tg CA3 hippocampal network. 5. To test this hypothesis, bursting CA3 pyramidal neurons were loaded intracellularly with chloride by the use of KCl-filled microelectrodes to examine the effect of reversing the hyperpolarizing chloride-dependent GABAA receptor-mediated inhibitory postsynaptic component of the PDS. Chloride loading prolonged PDS duration in both genotypes, but the increase was greater in +/+ than in tg/tg neurons, indicating that a smaller GABAA inhibitory postsynaptic potential (IPSP) component was reversed in the mutant.(ABSTRACT TRUNCATED AT 400 WORDS)

In vitro and in vivo GABAA Receptor Interaction of the Propanidid Metabolite 4-(2-[Diethylamino]-2-Oxoethoxy)-3-Methoxy-Benzeneacetic Acid

Pharmacology ◽  
2018 ◽  
Vol 103 (1-2) ◽  
pp. 10-16 ◽  
Author(s):  
Alessia Cenani ◽  
Robert J. Brosnan ◽  
Heather K. Knych
Keyword(s):  
Gabaa Receptor ◽  
Gabaa Receptors ◽  
Water Solubility ◽  
Plasma Concentrations ◽  
Receptor Activation ◽  
Receptor Interaction ◽  
Dependent Manner ◽  
Benzeneacetic Acid

Background: Propanidid is a γ-aminobutyric acid type A (GABAA) receptor agonist general anesthetic and its primary metabolite is 4-(2-[diethylamino]-2-oxoethoxy)-3-methoxy-benzeneacetic acid (DOMBA). Despite having a high water solubility at physiologic pH that might predict low-affinity GABAA receptor interactions, DOMBA is reported to have no effect on GABAA receptor currents, possibly because the DOMBA concentrations studied were simply insufficient to modulate GABAA receptors. Our objectives were to measure the propanidid and DOMBA concentration responses on ­GABAA receptors and to measure the behavioral responses of DOMBA in mice at concentrations that affect GABAA receptor currents in vitro. Methods: GABAA receptors were expressed in oocytes using clones for the human GABAA α1, β2 and γ2s subunits. The effects of DOMBA (0.2–10 mmol/L) and propanidid (0.001–1 mmol/L) on oocyte GABAA currents were studied using standard 2-electrode voltage clamp techniques. Based on in vitro results, 6 mice received ­DOMBA 32 mg intraperitoneal and were observed for occurrence of neurologic effects and DOMBA plasma concentration was measured by liquid chromatography tandem mass spectrometry. Results: DOMBA both directly activates GABAA receptors and antagonizes its GABA-mediated opening in a concentration-dependent manner at concentrations between 5–10 and 0.5–10 mmol/L respectively. In vivo, DOMBA produced rapid onset sedation at plasma concentrations that correlate with direct GABAA receptor activation. Conclusion: DOMBA modulation of GABAA receptors is associated with sedation in mice. Metabolites of propanidid analogues currently in development may similarly modulate GABAA, and impaired elimination of these metabolites could produce clinically relevant neurophysiologic effects.

scholarly journals An association study in the Taiwan Biobank elicits the GABAA receptor genes GABRB3, GABRA5, and GABRG3 as candidate loci for sleep duration in the Taiwanese population

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Sheue-Jane Hou ◽  
Shih-Jen Tsai ◽  
Po-Hsiu Kuo ◽  
Wan-Yu Lin ◽  
Yu-Li Liu ◽  
...  
Keyword(s):  
Sleep Quality ◽  
Association Study ◽  
Gabaa Receptor ◽  
Sleep Duration ◽  
Gabaa Receptors ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Bonferroni Correction ◽  
Taiwanese Population ◽  
Sleep Timing

Abstract Background Gamma-aminobutyric acid type A (GABAA) receptors mainly mediate the effects of gamma-aminobutyric acid, which is the primary inhibitory neurotransmitter in the central nervous system. Abundant evidence suggests that GABAA receptors play a key role in sleep-regulating processes. No genetic association study has explored the relationships between GABAA receptor genes and sleep duration, sleep quality, and sleep timing in humans. Methods We determined the association between single-nucleotide polymorphisms (SNPs) in the GABAA receptor genes GABRA1, GABRA2, GABRB3, GABRA5, and GABRG3 and sleep duration, sleep quality, and sleep timing in the Taiwan Biobank with a sample of 10,127 Taiwanese subjects. There were 10,142 subjects in the original study cohort. We excluded 15 subjects with a medication history of sedative-hypnotics. Results Our data revealed an association of the GABRB3-GABRA5-GABRG3 gene cluster with sleep duration, which has not been previously identified: rs79333046 (beta = − 0.07; P = 1.21 × 10–3) in GABRB3, rs189790076 (beta = 0.92; P = 1.04 × 10–3) in GABRA5, and rs147619342 (beta = − 0.72; P = 3.97 × 10–3) in GABRG3. The association between rs189790076 in GABRA5 and sleep duration remained significant after Bonferroni correction. A variant (rs12438141) in GABRB3 was also found to act as a potential expression quantitative trait locus. Additionally, we discovered interactions between variants in the GABRB3-GABRA5-GABRG3 gene cluster and lifestyle factors, such as tea and coffee consumption, smoking, and physical activity, that influenced sleep duration, although some interactions became nonsignificant after Bonferroni correction. We also found interactions among GABRB3, GABRA5, and GABRG3 that affected sleep duration. Furthermore, we identified an association of rs7165524 (beta = − 0.06; P = 2.20 × 10–3) in GABRA5 with sleep quality and an association of rs79465949 (beta = − 0.12; P = 3.95 × 10–3) in GABRB3 with sleep timing, although these associations became nonsignificant after Bonferroni correction. However, we detected no evidence of an association of individual SNPs in GABRA1 and GABRA2. Conclusions Our results indicate that rs189790076 in GABRA5 and gene–gene interactions among GABRB3, GABRA5, and GABRG3 may contribute to sleep duration in the Taiwanese population.

scholarly journals Ginkgo Extract EGb761 Confers Neuroprotection by Reduction of Glutamate Release in Ischemic Brain

2012 ◽  
Vol 15 (1) ◽  
pp. 94 ◽  
Author(s):  
Alexander Mdzinarishvili ◽  
Rachita K. Sambria ◽  
Dorothee Lang ◽  
Jochen Klein
Keyword(s):  
Glutamate Release ◽  
Hippocampal Slices ◽  
Brain Slices ◽  
Cell Swelling ◽  
Experimental Stroke ◽  
Cell Degeneration ◽  
Edema Formation ◽  
Ginkgo Extract

Purpose - Ginkgo extract EGb761 has shown anti-edema and anti-ischemic effects in various experimental models. In the present study, we demonstrate neuroprotective effects of EGb761 in experimental stroke while monitoring brain metabolism by microdialysis. Methods - We have used oxygen-glucose deprivation in brain slices in vitro and middle cerebral artery occlusion (MCAO) in vivo to induce ischemia in mouse brain. We used microdialysis in mouse striatum to monitor extracellular concentrations of glucose and glutamate. Results - In vitro, EGb761 reduced ischemia-induced cell swelling in hippocampal slices by 60%. In vivo, administration of EGb761 (300 mg/kg) reduced cell degeneration and edema formation after MCAO by 35-50%. Immediately following MCAO, striatal glucose levels dropped to 25% of controls, and this reduction was not significantly affected by EGb761. Striatal glutamate levels, in contrast, increased 15-fold after MCAO; after pretreatment with EGb761, glutamate levels only increased by 4-5fold. Conclusions - We show that pretreatment with EGb761 strongly reduces cellular edema formation and neurodegeneration under conditions of ischemia. The mechanism of action seems to be related to a reduction of excitotoxicity, because ischemia-induced release of glutamate was strongly suppressed. Ginkgo extracts such as EGb761 may be valuable to prevent ischemia-induced damage in stroke-prone patients. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

On the synchronous activity induced by 4-aminopyridine in the CA3 subfield of juvenile rat hippocampus

1993 ◽  
Vol 70 (3) ◽  
pp. 1018-1029 ◽  
Author(s):  
M. Avoli ◽  
C. Psarropoulou ◽  
V. Tancredi ◽  
Y. Fueta
Keyword(s):  
Nmda Receptor ◽  
Gabaa Receptor ◽  
Action Potentials ◽  
Hippocampal Slices ◽  
Field Potential ◽  
Pyramidal Cells ◽  
Occurrence Rate ◽  
Gamma Aminobutyric Acid ◽  
Synchronous Activity ◽  
Ca3 Pyramidal Cells

1. Extracellular field potential and intracellular recordings were made in the CA3 subfield of hippocampal slices obtained from 10- to 24-day-old rats during perfusion with artificial cerebrospinal fluid (ACSF) containing the convulsant 4-aminopyridine (4-AP, 50 microM). 2. Three types of spontaneous, synchronous activity were recorded in the presence of 4-AP by employing extracellular microelectrodes positioned in the CA3 stratum (s.) radiatum: first, inter-ictal-like discharges that lasted 0.2-1.2 s and had an occurrence rate of 0.3-1.3 Hz; second, ictal-like events (duration: 3-40 s) that occurred at 4-38 x 10(-3) Hz; and third, large-amplitude (up to 8 mV) negative-going potentials that preceded the onset of the ictal-like events and thus appeared to initiate them. 3. None of these synchronous activities was consistently modified by addition of antagonists of the N-methyl-D-aspartate (NMDA) receptor to the ACSF. In contrast, the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 2-10 microM) reversibly blocked interictal- and ictallike discharges. The only synchronous, spontaneous activity recorded in this type of medium consisted of the negative-going potentials that were abolished by the GABAA receptor antagonists bicuculline methiodide (5-20 microM) or picrotoxin (50 microM). Hence they were mediated through the activation of the GABAA receptor. 4. Profile analysis of the 4-AP-induced synchronous activity revealed that the gamma-aminobutyric acid (GABA)-mediated field potential had maximal negative amplitude in s. lacunosum-moleculare, attained equipotentiality at the border between s. radiatum and s. pyramidale, and became positive-going in s. oriens. These findings indicated that the GABA-mediated field potential presumably represented a depolarization occurring in the dendrites of CA3 pyramidal cells. 5. This conclusion was supported by intracellular analysis of the 4-AP-induced activity. The GABA-mediated potential was reflected by a depolarization of the membrane of CA3 pyramidal cells that triggered a few variable-amplitude, fractionated spikes or fast action potentials. By contrast, the ictal-like discharge was associated with a prolonged depolarization during which repetitive bursts of action potentials occurred. Short-lasting depolarizations with bursts of action potentials occurred during each interictal-like discharge. 6. The GABA-mediated potential recorded intracellularly in the presence of CNQX consisted of a prolonged depolarization (up to 12 s) that was still capable of triggering a few fast action potentials and/or fractionated spikes.(ABSTRACT TRUNCATED AT 400 WORDS)

Synaptic transmission between ventrolateral funiculus axons and lumbar motoneurons in the isolated spinal cord of the neonatal rat

1994 ◽  
Vol 72 (5) ◽  
pp. 2406-2419 ◽  
Author(s):  
M. Pinco ◽  
A. Lev-Tov
Keyword(s):  
Spinal Cord ◽  
Nmda Receptor ◽  
Gabaa Receptor ◽  
Gabab Receptor ◽  
Short Latency ◽  
Neonatal Rat ◽  
Gamma Aminobutyric Acid ◽  
Long Latency ◽  
Ventrolateral Funiculus

1. We studied the projections of ventrolateral funiculus (VLF) axons to lumbar motoneurons in the in vitro spinal cord preparation of 1- to 6-day-old rats using extracellular and sharp-electrode intracellular recordings. 2. Ipsilateral and contralateral VLF projections to lumbar motoneurons (L4-L5) could be activated in the neonatal rat by stimulation of the surgically peeled VLF at the rostral (L1-L2) and caudal lumbar (L6) cord. Motoneurons were activated ipsilaterally through short- and long-latency projections in all cases and contralaterally through long-latency projections in most cases. 3. Suppression of the excitatory components of VLF postsynaptic potentials (PSPs) by application of the specific antagonists of N-methyl D-aspartate (NMDA) and non-NMDA receptors, 2-amino-5-phosphonovaleric acid (APV) and 6-cyano-7-nitroquin-oxaline-2,3-dione (CNQX), revealed depolarizing PSPs that could be reversed at -55 to -60 mV by injection of depolarizing current steps to the motoneurons. These depolarizing PSPs were blocked by addition of strychnine and bicuculline and are therefore suggested to be glycine and gamma-aminobutyric acid-A (GABAA) receptor-mediated inhibitory PSPs. The identity of a small (< or = 0.2 mV) residual depolarizing component that persisted in the presence of APV, CNQX, strychnine, and bicuculline remains to be determined. 4. Short-latency excitatory PSPs (EPSPs) could be resolved from the ipsilaterally elicited VLF PSPs after the reduction of the polysynaptic activity in the preparation by administration of mephenesin, which was followed by suppression of the glycine and GABAA receptor-mediated components of the PSPs by bath application of strychnine and bicuculline. The latencies of these EPSPs were similar to those of the monosynaptic dorsal root afferent EPSPs recorded from the same motoneurons. These short-latency VLF EPSPs were shortened by the NMDA antagonist APV and revealed an NMDA receptor-mediated component after administration of the non-NMDA receptor antagonist CNQX. Addition of the GABAB receptor agonist L-(-) baclofen or the glutamate analogue L-2-amino-4-phosphonobutyric acid (L-AP4) attenuated the pharmacologically resolved short-latency EPSPs.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of Gaseous Anesthetics Nitrous Oxide and Xenon on Ligand-gated Ion Channels

2000 ◽  
Vol 93 (4) ◽  
pp. 1095-1101 ◽  
Author(s):  
Tomohiro Yamakura ◽  
R. Adron Harris
Keyword(s):  
Nitrous Oxide ◽  
Ion Channels ◽  
Nmda Receptors ◽  
Glutamate Receptors ◽  
Gabaa Receptors ◽  
Receptor Type ◽  
Gamma Aminobutyric Acid ◽  
General Anesthetics ◽  
Gated Ion Channels ◽  
Ligand Gated Ion Channels

Background Ligand-gated ion channels are considered to be potential general anesthetic targets. Although most general anesthetics potentiate the function of gamma-aminobutyric acid receptor type A (GABAA), the gaseous anesthetics nitrous oxide and xenon are reported to have little effect on GABAA receptors but inhibit N-methyl-d-aspartate (NMDA) receptors. To define the spectrum of effects of nitrous oxide and xenon on receptors thought to be important in anesthesia, the authors tested these anesthetics on a variety of recombinant brain receptors. Methods The glycine, GABAA, GABA receptor type C (GABAC), NMDA, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), kainate, 5-hydroxytryptamine3 (5-HT3), and nicotinic acetylcholine (nACh) receptors were expressed in Xenopus oocytes and effects of nitrous oxide and xenon, and as equipotent concentrations of isoflurane and ethanol, were studied using the two-electrode voltage clamp. Results Nitrous oxide (0.58 atmosphere [atm]) and xenon (0.46 atm) exhibited similar effects on various receptors. Glycine and GABAA receptors were potentiated by gaseous anesthetics much less than by isoflurane, whereas nitrous oxide inhibited GABAC receptors. Glutamate receptors were inhibited by gaseous anesthetics more markedly than by isoflurane, but less than by ethanol. NMDA receptors were the most sensitive among glutamate receptors and were inhibited by nitrous oxide by 31%. 5-HT3 receptors were slightly inhibited by nitrous oxide. The nACh receptors were inhibited by gaseous and volatile anesthetics, but ethanol potentiated them. The sensitivity was different between alpha4beta2 and alpha4beta4 nACh receptors; alpha4beta2 receptors were inhibited by nitrous oxide by 39%, whereas alpha4beta4 receptors were inhibited by 7%. The inhibition of NMDA and nACh receptors by nitrous oxide was noncompetitive and was slightly different depending on membrane potentials for NMDA receptors, but not for nACh receptors. Conclusions Nitrous oxide and xenon displayed a similar spectrum of receptor actions, but this spectrum is distinct from that of isoflurane or ethanol. These results suggest that NMDA receptors and nACh receptors composed of beta2 subunits are likely targets for nitrous oxide and xenon.

Inflammation Increases Neuronal Sensitivity to General Anesthetics

2016 ◽  
Vol 124 (2) ◽  
pp. 417-427 ◽  
Author(s):  
Sinziana Avramescu ◽  
Dian-Shi Wang ◽  
Irene Lecker ◽  
William T. H. To ◽  
Antonello Penna ◽  
...  
Keyword(s):  
Gabaa Receptor ◽  
Cortical Neurons ◽  
Receptor Activity ◽  
Aminobutyric Acid ◽  
General Anesthetics ◽  
Enhanced Sensitivity ◽  
Behavioral Sensitivity ◽  
Underlying Mechanisms

Abstract Background Critically ill patients with severe inflammation often exhibit heightened sensitivity to general anesthetics; however, the underlying mechanisms remain poorly understood. Inflammation increases the number of γ-aminobutyric acid type A (GABAA) receptors expressed on the surface of neurons, which supports the hypothesis that inflammation increases up-regulation of GABAA receptor activity by anesthetics, thereby enhancing the behavioral sensitivity to these drugs. Methods To mimic inflammation in vitro, cultured hippocampal and cortical neurons were pretreated with interleukin (IL)-1β. Whole cell patch clamp methods were used to record currents evoked by γ-aminobutyric acid (GABA) (0.5 μM) in the absence and presence of etomidate or isoflurane. To mimic inflammation in vivo, mice were treated with lipopolysaccharide, and several anesthetic-related behavioral endpoints were examined. Results IL-1β increased the amplitude of current evoked by GABA in combination with clinically relevant concentrations of either etomidate (3 μM) or isoflurane (250 μM) (n = 5 to 17, P &lt; 0.05). Concentration–response plots for etomidate and isoflurane showed that IL-1β increased the maximal current 3.3-fold (n = 5 to 9) and 1.5-fold (n = 8 to 11), respectively (P &lt; 0.05 for both), whereas the half-maximal effective concentrations were unchanged. Lipopolysaccharide enhanced the hypnotic properties of both etomidate and isoflurane. The immobilizing properties of etomidate, but not isoflurane, were also increased by lipopolysaccharide. Both lipopolysaccharide and etomidate impaired contextual fear memory. Conclusions These results provide proof-of-concept evidence that inflammation increases the sensitivity of neurons to general anesthetics. This increase in anesthetic up-regulation of GABAA receptor activity in vitro correlates with enhanced sensitivity for GABAA receptor–dependent behavioral endpoints in vivo.

Enterobacter sakazakii: Infectivity and Enterotoxin Production In Vitro and In Vivo

2003 ◽  
Vol 66 (3) ◽  
pp. 370-375 ◽  
Author(s):  
FRANCO J. PAGOTTO ◽  
MARIA NAZAROWEC-WHITE ◽  
SABAH BIDAWID ◽  
JEFFREY M. FARBER
Keyword(s):  
Intraperitoneal Injection ◽  
Severe Form ◽  
In Vitro Assays ◽  
Neonatal Meningitis ◽  
Enterobacter Sakazakii ◽  
Causal Organism ◽  
Suckling Mice ◽  
Enterotoxin Production

Enterobacter sakazakii has been implicated as the causal organism in a severe form of neonatal meningitis, with reported mortality rates of 40 to 80%. Dried infant formula has been identified as a potential source of the organism in both outbreaks and sporadic cases. In this study, clinical and foodborne isolates of E. sakazakii were evaluated for enterotoxin production by the suckling mouse assay. In addition, suckling mice were challenged both orally and by intraperitoneal injection. Of 18 E. sakazakii strains evaluated, four were found to test positive for enterotoxin production. All strains of E. sakazakii were lethal to suckling mice at 108 CFU per mouse by intraperitoneal injection, while two strains caused death by the peroral route. In in vitro assays, CHO, Vero, and Y-1 cells demonstrated both cell lysis and rounding when exposed to E. sakazakii strain LA filtrates. This is the first report describing any putative virulence factors of E. sakazakii.

Effect of exposure in vitro to ethanol and hypoxia on gamma-aminobutyric acid efflux in the hippocampus of the fetal and adult guinea-pig

1995 ◽  
Vol 7 (5) ◽  
pp. 1339 ◽  
Author(s):  
MC Catlin ◽  
DH Penning ◽  
JF Brien
Keyword(s):  
Guinea Pig ◽  
Hippocampal Slices ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Gaba System ◽  
Direct Exposure ◽  
Interface System ◽  
Near Term ◽  
Co2 Environment

The objective of this study was to determine the effects of acute direct exposure to ethanol, hypoxia or ethanol plus hypoxia on K+-stimulated gamma-aminobutyric acid (GABA) efflux (neuronal release minus uptake) in the hippocampus of the near-term fetal and adult guinea-pig. Transverse hippocampal slices were studied in a static-interface system. Exposure in vitro to ethanol or hypoxia involved 10-min incubation with 50 mM ethanol or 10-min incubation in a 95% N2/5% CO2 environment. GABA was quantitated by HPLC. Ethanol did not alter K+-stimulated GABA efflux; hypoxia augmented K+-stimulated GABA efflux three-fold in the near-term fetus and seven-fold in the adult; concurrent exposure to ethanol did not alter the effect of hypoxia. The data demonstrate that, for acute direct exposure to hypoxia and/or ethanol, only hypoxia increases K+-stimulated GABA efflux, the magnitude of which is dependent on the extent of development of the GABA system.

Sign in / Sign up

Export Citation Format

Share Document