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Influence of antemortem medication on the determination of brain death.
Saito T, Takeichi S, Nakajima Y, Yukawa N, Osawa M.
Department of Forensic Medicine, Tokai University School of Medicine, Isehara, Japan.
Post-mortem concentration of pentobarbital in the blood and brain of two deceased neurosurgical patients was determined by gas chromatography/mass spectrometry. Patients treated with barbiturate for elevated intracranial pressure after head injury may incur brain death. In the present two cases of brain death a large amount of barbiturate remained in the brain, even when the blood concentration was not detectable, possibly because the blood flow was stagnant in the brain. It is suggested that a patient under barbiturate coma should be given serious consideration as to the determination of brain death, even if barbiturate is negative in the blood.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8583693&dopt=Abstract barbiturate Butalbital Fioricet
Mutation of the GABAA receptor M1 transmembrane proline increases GABA affinity and reduces barbiturate enhancement.
Greenfield LJ Jr, Zaman SH, Sutherland ML, Lummis SC, Niemeyer MI, Barnard EA, Macdonald RL.
Departments of Neurology and Pharmacology, Medical College of Ohio, Toledo, OH, USA. jgreenfield mco.edu
All GABA(A) receptor (GABAR) subunits include an invariant proline in a consensus motif in the first transmembrane segment (M1). In receptors containing bovine alpha1, beta1 and gamma2 subunits, we analyzed the effect of mutating this M1 proline to alanine in the alpha1 or beta1 subunit using 3 different expression systems. The beta1 subunit mutant, beta1(P228A), reduced the EC(50) for GABA about 10-fold in whole cell recordings in HEK293 cells and L929 fibroblasts. The corresponding alpha1 subunit mutant (alpha1(P233A)) also reduced the GABA EC(50) when expressed in Xenopus oocytes; alpha1(P233A)beta1gamma2S receptors failed to assemble in HEK293 cells. Binding of [(3)H]flumazenil and [(3)H]muscimol to transfected HEK293 cell membranes showed similar levels of receptor expression with GABARs containing beta1 or beta1(P228A) subunits and no change in the affinity for [(3)H]flumazenil; however, the affinity for [(3)H]muscimol was increased 6-fold in GABARs containing beta1(P228A) subunits. In L929 cells, presence of the beta1(P228A) subunit reduced enhancement by barbiturates without affecting enhancement by diazepam or alfaxalone. Single channel recordings from alpha1beta1gamma2S and alpha1beta1(P228A)gamma2L GABARs showed similar channel kinetics, but beta-mutant containing receptors opened at lower GABA concentrations. We conclude that the beta1 subunit M1 segment proline affects the linkage between GABA binding and channel gating and is critical for barbiturate enhancement. Mutation of the M1 proline in the alpha1 subunit also inhibited receptor assembly.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11955521&dopt=Abstract barbiturate Butalbital Fioricet
Intracellularly labeled fusiform cells in dorsal cochlear nucleus of the gerbil. I. Physiological response properties.
Hancock KE, Voigt HF.
Department of Biomedical Engineering and Hearing Research Center, Boston University, Boston, Massachusetts 02215-2407, USA.
Fusiform cells in the dorsal cochlear nucleus (DCN) of barbiturate-anesthetized Mongolian gerbils were characterized physiologically and labeled with neurobiotin. This report is based on 17 fusiform cells for which there was reasonable confidence in the association between physiological data and recovered anatomy. The qualitative morphology of these cells was no different from that reported in previous studies. The acoustic response properties were generally consistent with those described in the barbiturate-anesthetized cat. Most responses were of the pauser or buildup type, but a dependence on stimulus frequency and intensity was observed. Stimulus-evoked sustained depolarizations and large, long-lasting afterhyperpolarizations were common membrane potential features. The cells in this study showed a greater tendency to discharge regularly than did those of the cat, likely as a result of the longer interstimulus interval used. Barbiturate anesthesia appears to mask an interspecies difference in DCN physiology that is apparent in unanesthetized, decerebrate preparations. The response of these fusiform cells to a depolarizing current pulse could be altered by the presence of a hyperpolarizing prepulse. Buildup, pauser, and chopper patterns could each be created using appropriate combinations of hyperpolarizing and depolarizing pulse amplitudes. Thus the adult gerbil appears to express the inactivating potassium conductance previously shown to affect fusiform cell firing patterns in vitro. The results further demonstrate that the effects of these potassium currents are readily observed in vivo. Finally, the fusiform cells in this study were quite variable with respect to a number of response properties, including the resting potential, input resistance, spontaneous activity, relative noise index, normalized tone slope, and regularity histogram shape. This diversity likely results from cell-to-cell variations in the balance of activity within the relatively complex network to which the fusiform cells belong, although effects of impalement may contribute to the extent of the diversity.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11976387&dopt=Abstract barbiturate Butalbital Fioricet
Steady-state concentration distribution of artificial receptor and target analyte in plasticized PVC membrane between solutions differing in target analyte concentration.
Zhang X, Zhao H, Weber SG.
Department of Chemistry, University of Pittsburgh, Pennsylvania 15260, USA.
A barbiturate receptor has proven effective in improving selectivity in solid-phase microextraction of barbiturates when doped into plasticized poly(vinyl chloride) (PVC). It would be beneficial to have selective extractions for any given organic species; however, the receptors do not exist. They will be found by screening of libraries of potential receptors; thus, a screening method is needed. It is important to screen the receptors in the medium in which they will work: plasticized PVC. We hypothesize that we can make receptors move in solution in response to the presence of a solute to which they bind. This work examines whether we can establish a sufficient free energy gradient for a good receptor to move to a predetermined place in space. A difference in the barbiturate solute (substrate or guest) concentration in solutions bathing the two sides of a plasticized PVC membrane containing the barbiturate receptor (or host) creates a spatial concentration gradient of the substrate in the membrane. This causes the receptor's chemical potential to vary across the membrane. Upon binding to the analyte, the receptor undergoes a local activity drop, which decreases its free energy. This process produces a flux of receptor to accumulate at place where there is a high substrate concentration. A concentration gradient of substrate can be maintained across the membrane at steady state. In membranes for which the formation of the complex is favored, the receptor responds to the gradient of substrate. In membranes for which binding is not favored, a gradient of substrate is completely ignored by the receptor. Thus, the receptor does respond to the gradient but only if the concentration gradient of guest corresponds to a chemical potential gradient.
Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12033325&dopt=Abstract barbiturate Butalbital Fioricet
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