Effects of passive immunization with rabbit anti-phenobarbital IgG on cyclobarbital-induced sleeping time and hepatic enzyme activities of C3H mice.
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Effects of normal rabbit IgG (N-IgG) and phenobarbital specific IgG (Ab-IgG) on cyclobarbital-induced sleeping time were studied. Ab-IgG was specifically purified by Immunoadsorbent from rabbit antisera obtained by immunization with p-azophenobarbital bovine gamma globulin. N-IgG was purified from normal rabbit sera by DEAE-cellulose chromatography. The aggregate-free IgG were passively immunized to C3H mice 1 hr before intraperitoneal injection of cyclobarbital which has a high binding affinity to the antibodies. The pretreatment with N-IgG prolonged significantly cyclobarbital-induced sleeping time as compared with that of saline treated group, however, in the Ab-IgG treated group the duration of the sleeping was much the same as that seen in the saline group. To determine whether Ab-IgG has any influence on barbiturate tolerance, effects of N-IgG and Ab-IgG on the activities of hepatic enzymes in 9,000 X g supernatant (alkaline RNase and aminopyrine demethylase) of the mice were examined at 40 hours after cyclobarbital administration. The activities of both enzymes which could be induced by cyclobarbital were decreased significantly in Ab-IgG treated group as compared with those on N-IgG group. These results are discussed with relation to barbiturate tolerance. (+info)
Barbiturates induce mitochondrial depolarization and potentiate excitotoxic neuronal death.
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Barbiturates are widely used as anesthetics, anticonvulsants, and neuroprotective agents. However, barbiturates may also inhibit mitochondrial respiration, and mitochondrial inhibitors are known to potentiate NMDA receptor-mediated neurotoxicity. Here we used rat cortical cultures to examine the effect of barbiturates on neuronal mitochondria and responses to NMDA receptor stimulation. The barbiturates tested, secobarbital, amobarbital, and thiamylal, each potentiated NMDA-induced neuron death at barbiturate concentrations relevant to clinical and experimental use (100-300 microm). By using rhodamine-123 under quenching conditions, barbiturates in this concentration range were shown to depolarize neuronal mitochondria and greatly amplify NMDA-induced mitochondrial depolarization. Barbiturate-induced mitochondrial depolarization was increased by the ATP synthase inhibitor oligomycin, indicating that barbiturates act by inhibiting electron transport sufficiently to cause ATP synthase reversal. Barbiturates similarly amplified the effects of NMDA on cytoplasmic free calcium concentrations. The cell-impermeant barbiturate N-glucoside amobarbital did not influence mitochondrial potential or potentiate NMDA neurotoxicity or calcium responses. However, all of the barbiturates attenuated NMDA-induced calcium elevations and cell death when present at millimolar concentrations. Whole-cell patch-clamp studies showed that these effects may be attributable to actions at the cell membrane, resulting in a block of NMDA-induced current flux at millimolar barbiturate concentrations. Together, these findings reconcile previous reports of opposing effects on barbiturates on NMDA neurotoxicity and show that barbiturate effects on neuronal mitochondria can be functionally significant. Effects of barbiturates on neuronal mitochondria should be considered in experimental and clinical application of these drugs. (+info)
Relative activity of alpha-tocopherol and gamma-tocopherol in preventing oxidative red cell hemolysis.
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The purpose of this study was to compare the antioxidant activities of alpha-tocopherol and gamma-tocopherol in protecting the red cell membrane against lipid peroxidation. Tocopherols were incorporated into the red cell membrane by incubating cells with solutions of the tocopherols in bovine albumin. The cells were then washed and subjected to the dialuric acid hemolysis test. Analysis of variance of the response curves revealed that gamma-tocopherol had 38% of the activity of alpha-tocopherol. No evidence was found for an interaction between the two tocopherols when present in the red cell membranes simultaneously. (+info)
The epidemiology of drug use among New York State high school students: Distribution, trends, and change in rates of use.
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A two-wave panel survey was carried out on a representative sample of New York State public secondary school students in fall 1971 and spring 1972. The majority of adolsecents have drunk beer or wine (82 per cent) smoked cigarettes (72 per cent) or used hard liquor (65 per cent). Better than one third (35 per cent) report the use of one or more illegal drugs. The illicit drugs most frequently used are marijuana (29 per cent) and hashish (21 per cent). About one in eight adolescents have used pills such as amphetamines and barbiturates, and about one in 12 have tried LSD or other psychedelics. Four per cent have used cocaine and 3 per cent heroin. Use of illicit drugs tends to be experimental and sporadic rather than regular. By contrast, about one in four regularly use beer or wine or smoke cigarettes. Self-reported rates of use increase over the course of a school year, and there is considerable turnover with respect to which adolescents are users. The increased number of hard liquor and marijuana users through the high school years results predominantly from more stability among users, rather than increased conversion of nonusers to users over the teen years. (+info)
Online monitoring of Escherichia coli ghost production.
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Controlled expression of cloned phi X174 gene E in gram-negative bacteria results in lysis of the bacteria by the formation of a transmembrane tunnel structure built through the cell envelope complex. Production of bacterial ghosts is routinely monitored by classical microbiological procedures. These include determination of the turbidity of the culture and the total number of cells and the number of reproductive cells present during the time course of growth and lysis. Although conceptually simple, these methods are labor intensive and time consuming, providing a complete set of results after the determination of viable cell counts. To avoid culturing methods for bacterial growth, an alternative flow cytometric procedure is presented for the quantification of ghosts and polarized, as well as depolarized, nonlysed cells within a culture. For this method, which is based on the discriminatory power of the membrane potential-sensitive dye bis-(1,3-dibutylbarbituric acid) trimethine oxonol, a staining protocol was developed and optimized for the maximum discrepancy in fluorescence between bacterial ghosts and viable cells. The total quantitative analysis procedure takes less than 2 min. The results derived from classical or cytometric analyses correlate with respect to the total cell numbers and the viability of the culture. (+info)
Barbiturate intoxication. Morbidity and mortality.
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The complications encountered in caring for 185 patients intoxicated with barbiturates were reviewed. The population consisted of 142 patients with long-acting barbiturate concentrations of 8 mg per 100 ml or greater, 20 patients with short-acting barbiturate concentrations of 3 mg per 100 ml or greater and 23 consecutive patients with short-acting barbiturate intoxication referred for monitoring. Pneumonia was the major cause of morbidity and mortality and correlated best with the initial depth of coma and the use of an endotracheal tube in treatment. Cardiovascular instability manifested by pulmonary edema was the next leading cause of morbidity and mortality and correlated best with the initial depth of coma and the quantity of intravenous fluid administered. In retrospect, use of eliminative measures such as dialysis would probably not have altered the outcome in most of the patients who died and attempts at forced diuresis may have contributed to several deaths. Particular emphasis should be placed on the problems of sepsis and fluid therapy in the management of these patients. (+info)
Pressure antagonism of barbiturate anesthesia.
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The losses of righting reflex produced by various doses of phenobarbital in mice at 1 atm O2 versus 1 atm O2 plus 102 atm He were determined. The resulting dose-response curve at pressure gave an ED50 that was 64 per cent larger than the ED50 at 1 atm. This increment is essentially the same as that found for gaseous anesthetics under similar test conditions. The quantitative similarity of the results of pressure reversals of barbiturate and inhalational anesthetics suggests that the mechanisms or sites of action of these agents are similar. However, the dose-response curve at 103 atm was steeper than that at 1 atm. This raises an alternative possibility that anesthetics and pressure bear no mechanistic relationship to each other, but rather that pressure produces a generalized central nervous system stimulation that would antagonize any depressant effect. (+info)
Distribution of butalbital in postmortem tissues and fluids from non-overdose cases.
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During the investigation of fatal aviation accidents, postmortem samples from the pilots/co-pilots are submitted to the Federal Aviation Administration's (FAA) Civil Aerospace Medical Institute (CAMI) for toxicological analysis. Although therapeutic levels for most drugs are typically reported in the scientific literature for blood and plasma, blood specimens are received in only approximately 70% of our cases. Therefore, it is imperative for an accident investigator and forensic toxicologist to be able to estimate drug concentrations in an aviation accident victim's blood from available tissue drug concentrations. This is exemplified by a recent aviation fatality in which butalbital was identified in the muscle tissue of a pilot. In this case, no blood was available for analysis, but investigators needed to know the approximate butalbital concentration expected in the victim's blood. Certain side effects of butalbital, such as drowsiness, sedation, dizziness, and a feeling of intoxication, could affect pilot performance and become a significant factor in an aviation accident. Thus, our laboratory determined the distribution of butalbital in various postmortem tissues and fluids. The distribution coefficients for butalbital, expressed as specimen/blood ratios, were found to be as follows: 0.66 +/- 0.09 (muscle, n = 4), 0.98 +/- 0.09 (kidney, n = 4), 0.87 +/- 0.06 (lung, n = 4), 0.75 +/- 0.03 (spleen, n = 4), 0.96 +/- 0.07 (brain, n = 3), 2.22 +/- 0.04 (liver, n = 4), and 0.91 +/- 0.17 (heart, n = 2). The results obtained from our limited number of cases suggest that muscle, kidney, lung, spleen, brain, liver, and heart could be used, in a cautious and conservative fashion, to estimate butalbital blood concentrations. (+info)