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Biomedical subjects

S R Thom

Publications and source records attributed to S R Thom.

51 records · Page 3Linked to original sources
PubMed1993

Functional inhibition of leukocyte B2 integrins by hyperbaric oxygen in carbon monoxide-mediated brain injury in rats.

Exposure to hyperbaric oxygen [3 atmospheres absolute (ATA) for 45 min] inhibited carbon monoxide (CO)-mediated lipid peroxidation in the brains of rats by preventing the conversion of xanthine dehydrogenase to oxidase, a conversion process known to be due to the action of leukocytes. The effect was the same whether treatment was given 24 hr before or up to 45 min after poisoning. Hyperbaric oxygen did not inhibit the initial interaction of leukocytes with brain microvasculature, based on measurements of myeloperoxidase (MPO) in microvessel segments, but persistent adherence, which is due to B2 integrins, did not occur. Exposing rats to 3 ATA pressure (0.21 ATA O2) after CO poisoning had no significant effects. A progressive reduction in brain microvessel MPO titers occurred with exposure to O2 at 1, 2, or 3 ATA after CO poisoning, but 1 ATA O2 treatment did not significantly inhibit xanthine oxidase formation or lipid peroxidation. In vitro studies with polymorphonuclear leukocytes (PMN) from rats exposed to hyperbaric oxygen corroborated the absence of PMN B2 integrin function, but when these cells were stimulated they exhibited normal B2 integrin expression on their surface and also normal elastase release and superoxide radical production. Adherence functions of PMN that do not require B2 integrins appeared to remain intact after exposure to hyperbaric oxygen, as peritoneal neutrophilia in response to a glycogen challenge was not inhibited. B2 integrin function could be restored by incubating cells with 8 bromo cGMP, and incubation with phorbol ester stimulated the adherence function of both control and hyperbaric oxygen-exposed PMN. These results provide a clear mechanism for the inhibition of CO-mediated brain lipid peroxidation by hyperbaric oxygen and indicate that hyperoxia causes a discrete disturbance of PMN adherence function.

Animals↗
PubMed1992

Inert gas enhancement of superoxide radical production.

Two free radical generating systems, xanthine oxidase/hypoxanthine or phenazine methosulfate/NADH, were exposed to air plus He, N2, or Ar at partial pressures ranging from 0.2 to 6.0 MPa, and the rates of production of superoxide, hydroxyl, singlet O2, and H2O2 were measured. All three inert gases acted similarly to enhance the production of superoxide radicals by facilitating interactions between iron and H2O2, or O2 and organic radicals. These reactions occurred at quite low gas partial pressures, only 0.28 MPa, and hydrostatic pressures of up to 6.0 MPa had no effect on radical reactions. Enhanced radical production may be the basis for the inhibition of cellular growth mediated by inert gases, and inert gas enhancement of O2 toxicity.

Epinephrine↗
PubMed1992

Dehydrogenase conversion to oxidase and lipid peroxidation in brain after carbon monoxide poisoning.

The conversion of xanthine dehydrogenase to xanthine oxidase and lipid peroxidation were measured in brain from carbon monoxide- (CO) poisoned rats. Sulfhydryl-irreversible xanthine oxidase increased from a control level of 15% to a peak of 36% over the 90 min after CO poisoning, while the conjugated diene level doubled. Reversible xanthine oxidase was 3-6% of the total enzyme activity over this span of time but increased to 31% between 90 and 120 min after poisoning. Overall, reversible and irreversible xanthine oxidase represented 66% of total enzyme activity at 120 min after poisoning. Rats depleted of this enzyme by a tungsten diet and those treated with allopurinol before CO poisoning to inhibit enzyme activity exhibited no lipid peroxidation. Treatment immediately after poisoning with superoxide dismutase or deferoxamine inhibited lipid peroxidation but had no effect on irreversible oxidase formation. Biochemical changes only occurred after removal from CO, and changes could be delayed for hours by continuous exposure to 1,000 ppm CO. These results are consistent with the view that CO-mediated brain injury is a type of postischemic reperfusion phenomenon and indicate that xanthine oxidase-derived reactive oxygen species are responsible for lipid peroxidation.

Allopurinol↗
PubMed1991

Oxygen-dependent antagonism of lipid peroxidation.

Measurements of the rates for formation of conjugated dienes, malonylaldehyde, and lipid hydroperoxides show that increasing the concentration of O2 from 0.11 mM to 0.35 mM or 0.69 mM can slow the rate of linoleic acid peroxidation in a xanthine oxidase/hypoxanthine system. This effect is seen at pH 7.0 but not 7.4 and depends on the presence of monounsaturated fatty acids (oleic, cis, or trans vaccenic acid). Oxygen antagonism of ascorbic acid-iron-EDTA mediated lipid peroxidation is similarly dependent on fatty acid mixtures and occurs at pH 5.0 and 6.0 but not 7.0. The efficiency of initiation of peroxidation in the xanthine oxidase system is unaffected by monounsaturated fatty acids and O2 concentration. Increasing the O2 concentration increases the rate of superoxide radical production, but there is no change in salicylate hydroxylation (e.g., OH. production) or ferrous ion concentration. Oxygen-mediated slower rates of lipid peroxidation are associated with either increased H2O2 production or, based on an indirect assay, singlet O2 production. Increased O2 concentrations increase the rate of azobisisobutyronitrile-initiated lipid peroxidation as expected but addition of exogenous superoxide radicals slows the rate. Under similar conditions superoxide reacts with fatty acids to produce singlet O2. Overall, the data suggest that O2-mediated antagonism occurs because of termination reactions between hydroperoxyl (HO2.) and organic radicals, and singlet O2 or H2O2 are products of these reactions.

Ascorbic Acid↗
PubMed1990

Antagonism of carbon monoxide-mediated brain lipid peroxidation by hyperbaric oxygen.

The effects of oxygen at 1, 2, and 3, atmospheres absolute (ATA) were assessed on brain lipid peroxidation caused by carbon monoxide (CO) poisoning in a rat model. Oxygen at 3 ATA, but not 1 ATA, was found to prevent brain lipid peroxidation when administered to rats for 45 min, beginning 45 min subsequent to CO poisoning. Oxygen at 2 ATA had an intermediate effect. The action of hyperbaric oxygen could not be attributed to a more rapid diminution of carboxyhemoglobin, and appears to occur at the level of the brain tissue.

Animals↗
PubMed1990

Carbon monoxide-mediated brain lipid peroxidation in the rat.

Clinical and animal data suggest that the pathogenesis of CO poisoning extends beyond the inhibition of hemoglobin function, but no mechanism has been identified. Evidence of neurological compromise, particularly loss of consciousness, has been implicated as a marker for increased mortality and morbidity in clinical reports. Experiments were carried out with rats to assess whether CO exposure may cause brain lipid peroxidation. With the use of two methods, measurement of conjugated dienes and thiobarbituric acid reactivity, brain lipid peroxidation could be documented as a result of exposure to CO at a concentration sufficient to cause unconsciousness. Products of lipid peroxidation were increased by 75% over the base-line values 90 min after CO exposure. Unconsciousness was associated with a brief period of hypotension, so brief that in itself it caused no apparent insult. Lipid peroxidation occurred only after the animals were returned to CO-free air, and there was no direct correlation with the carboxyhemoglobin level. This work may provide an explanation for a number of currently poorly understood clinical observations regarding CO poisoning.

Animals↗
PubMed1989

Carbon monoxide poisoning: a review epidemiology, pathophysiology, clinical findings, and treatment options including hyperbaric oxygen therapy.

Carbon monoxide (CO) poisoning is the leading cause of poisoning deaths (accidental and intentional) in the United States. While confirmation of CO poisoning is easily obtained via assessment of carboxyhemoglobin (COHgb) levels, evaluation of the severity of intoxication is both difficult and inconsistent. Acute intoxication most commonly results in neurologic dysfunction and/or myocardial injury. Delayed neurologic sequelae are observed in approximately 10% of patients. New information from clinical observations and animal research has prompted a re-evaluation of the clinical assessment of the severity of CO intoxication and its resultant pathophysiology. Patients at the extremes of age (the very young and the elderly), those with pre-existing cardiovascular and/or pulmonary disease, as well as pregnancy are at increased risk. Once the diagnosis of CO poisoning has been established, treatment with 100% O2 is indicated. Based on the body of clinical, basic and scientific information currently available, patients who manifest signs of serious intoxication (i.e., unconsciousness or altered neurologic function, cardiac or hemodynamic instability) should be considered candidates for hyperbaric oxygen therapy (HBO) in addition to other appropriate supportive and intensive care. Any patient who has suffered an interval of unconsciousness, regardless of the patient's clinical exam on arrival, warrants HBO therapy. Treatment plans based on any specific COHgb level are not well founded.

Animals↗
PubMed1989

Smoke inhalation.

Appropriate intervention in patients with smoke inhalation requires an understanding of the dynamic aspects of this complex respiratory emergency. This article reviews the etiology, pathophysiology, and treatment of the smoke inhalation injury.

Carbon Monoxide Poisoning↗
PubMed1987

Preliminary report on the effect of hyperbaric oxygen on cystoid macular edema.

The treatment of established cystoid macular edema has been enigmatic. This is a preliminary study of five patients treated by intermittent hyperbaric oxygen with an intensive regimen of 1.5 hours two times per day for seven days and two hours per day for an additional 14 days. Visual acuity improved within 14 days in all five patients: One patient improved from 20/40 to 20/15, one from 20/50 to 20/25, one from 20/200 to 20/40, one from 20/70 to 20/25, and one diabetic patient improved from 20/70 to 20/25. Vision has tended to regress with time.

Aged↗
PubMed1987

Free radical reactions and the inhibitory and lethal actions of high-pressure gases.

This study was designed to test whether free radicals are involved in the deleterious effects of compressed gases on cells. The actions of xenon, nitrous oxide, argon, nitrogen, helium, and oxygen and their effects on the toxicity of paraquat (methyl viologen) were studied using Escherichia coli. Growth of E. coli in trypticase-soy broth in an atmosphere of 1.36 MPa (13.6 atm) N2O resulted in an induction of superoxide dismutase (SOD). In addition, when SOD was induced by oxygen, the resulting cells had increased resistance to the killing action of N2O. The toxicity of paraquat was increased in the presence of N2O but not He, N2, or Ar. However, addition of any of the latter three gases to N2O resulted in increased toxicity of paraquat beyond that due to N2O alone. Oxygen is known to increase the reaction of paraquat radicals within cells and to reduce leakage of the radicals out through the cell membrane. N2O and Xe seem to have this same action, and He, N2, or Ar could enhance the actions of N2O, Xe, or O2. The data indicate that the inhibitory and lethal actions of these gases may be due to enhanced reactivity of radicals with cell components and reduced leakage of the radicals to the environment.

Animals↗
PubMed1986

Intermittent hyperbaric oxygen therapy for reduction of mortality in experimental polymicrobial sepsis.

Hyperbaric oxygen therapy has a marked beneficial effect in experimental intraabdominal sepsis. Two rat models involving implantation of either rat fecal material or a mixture of pure cultures of Escherichia coli, Streptococcus faecalis, and Bacteroides fragilis were used in this study. A death rate of 100% was obtained in control animals implanted with fecal material; with intermittent hyperbaric oxygen treatment, a death rate of only 8% was observed (P less than .005). With a mixture of pure cultures of clinical pathogens, the death rate in control animals was 79%, and intermittent hyperbaric oxygen treatment reduced the rate to 23% (P less than .005). Data from cultures of blood indicated that the efficacy of hyperbaric oxygen was not related to antibacterial activity.

Animals↗
PubMed1984

Microbial growth modification by compressed gases and hydrostatic pressure.

Studies of the growth-modifying actions for Escherichia coli, Saccharomyces cerevisiae, and Tetrahymena thermophila of helium, nitrogen, argon, krypton, xenon, and nitrous oxide led to the conclusion that there are two definable classes of gases. Class 1 gases, including He, N(2), and Ar, are not growth inhibitors; in fact, they can reverse the growth inhibitory action of hydrostatic pressures. Class 2 gases, including Kr, Xe, and N(2)O, are potent growth inhibitors at low pressures. For example, at 24 degrees C, 50% growth-inhibitory pressures of N(2)O were found to be ca. 1.7 MPa for E. coli, 1.0 MPa for S. cerevisiae, and 0.5 MPa for T. thermophila. Class 1 gases could act as potentiators for growth inhibition by N(2)O, O(2), Kr, or Xe. Hydrostatic pressure alone is known to reverse N(2)O inhibition of growth, but we found that it did not greatly alter oxygen toxicity. Therefore, potentiation by class 1 gases appeared to be a gas effect rather than a pressure effect. The temperature profile for growth inhibition of S. cerevisiae by N(2)O revealed an optimal temperature for cell resistance of ca. 24 degrees C, with lower resistance at higher and lower temperatures. Overall, it appeared that microbial growth modification by hyperbaric gases could not be related to their narcotic actions but reflected definably different physiological actions.

Journal Article↗
PubMed1978

Interactions of helium, oxygen, and nitrous oxide affecting bacterial growth.

Helium at pressures of 20 to 70 atm in the presence of air found to stimulate growth of Streptococcus faecalis, Escherichia coli, and Staphylococcus aureus, mainly by increasing the rate of exponential growth. However, at these same pressures, helium potentiated the growth-inhibitory actions of oxygen and nitrous oxide (N2O). Oxygen was found to act essentially as an anesthetic gas in inhibiting growth of S. faecalis; its potency was approximately the same as that of N2O, and it acted additively in combination with N2O to inhibit the streptococcus. Oxygen proved to be more potent than N2O in inhibiting the growth of E. coli and S. aureus, and each gas potentiated the action of the other. Oxygen sensitivity was correlated with N2O sensitivity. Overall, our findings indicate that bacterial growth inhibition by anesthetic gases does not accurately reflect narcotic action.

Bacteria↗
PubMedDate not supplied

Platelet function in humans is not altered by hyperbaric oxygen therapy.

A pilot survey of platelet function was performed on 6 patients undergoing hyperbaric oxygen therapy (2.0 ATA O2 for 2 hours, 6 days/week) for prophylaxis against osteoradionecrosis. Blood was drawn immediately prior to and after the first, tenth and twentieth treatment for measurements of platelet aggregation, ATP release and expression of activated alphalIb3 integrin. No significant differences were observed due to hyperbaric oxygen exposures.

Adenosine Triphosphate↗