Stroke units.
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Cerebrovascular Disorders↗
Biomedical subjects
D Jamieson
Publications and source records attributed to D Jamieson.
Potential artifacts in TBARS measurement in tissues from animals treated with antioxidants.
When measuring endogenous TBARS levels from tissues of animals (in vitro) the presence of exogenous antioxidants in the tissue is likely to interfere with the TBARS assay to give artificially low values. Such low values do not then reflect protection against peroxidation in vivo. The type and extent of the reduction in TBARS values depend on the TBARS assay conditions. Firstly there appears to be an initial (probably iron induced) burst of peroxidation during homogenisation, which is antioxidant susceptible. In addition added TBARS products are formed during the final heating stage in methods which retain membrane bound reactants throughout the assay, and this step is also susceptible to antioxidant presence.
Animals↗
Are leukotrienes or PAF involved in hyperbaric oxygen toxicity?
Several very selective leukotriene inhibitors, and a PAF inhibitor, suitable for in vivo use, have been tested for their effects on hyperbaric oxygen toxicity. The leukotriene D4 inhibitor, L660771, and the 5-lipoxygenase pathway inhibitor L663536, failed to affect convulsions or lung damage induced by hyperbaric oxygen (pressure range 515-615 kPa) in either rats or mice. The specific PAF antagonist L659989 showed marginal protection against hyperoxic convulsions and did not alter pulmonary damage. The specific LTB4 antagonist SC-41930 was very effective in inhibiting hyperbaric oxygen-induced convulsions in both rats and mice. SC-41930 also very significantly protected rats against pulmonary oxygen toxicity, but had only marginally significant effects on pulmonary protection in mice.
Animals↗
Effects of a fish oil rich diet on hyperoxic lung damage in mice.
Mice were fed a chow diet plus 10% cellulose, 10% fish oil or 10% sunflower oil for 3 weeks, then exposed to 100% oxygen for 75 h. Large changes in lung fatty acid composition occurred, but this did not affect hyperoxic lung damage nor levels of thiobarbituric acid reactive substances or myeloperoxidase in lungs of mice following exposure to hyperoxia. Thus there is no evidence that the ingestion of large quantities of fish oil increased the susceptibility to the oxidative stress induced by hyperoxia.
Animals↗
Effect of humidity on hyperoxic toxicity.
Time to onset of hyperbaric oxygen-induced convulsions was measured in mice and rats exposed to hyperbaric oxygen (515-585 kPa) under conditions of low humidity (dry gas, < 10% relative humidity) or in a humidified environment (60% relative humidity). At all pressures tested, the duration of convulsive activity was markedly increased (P < 0.001), because of the earlier onset of severe generalized convulsions, in the groups of rodents exposed to the higher humidity. Pulmonary oxygen poisoning was determined by increases in lung wet and dry weights. Such pulmonary damage was also significantly (P < 0.001) increased in the humidified groups. Hyperoxic toxicity was also measured in rats and mice exposed to approximately 100% oxygen (normobaric hyperoxia) under conditions of 30 or 62% relative humidity. In contrast to the results obtained with hyperbaric oxygen exposure, there was slightly less toxicity in the rodents maintained at 62% compared with 30% humidity in normobaric hyperoxia.
Animals↗
Effects of antioxidants on oxygen toxicity in vivo and lipid peroxidation in vitro.
Convulsions and pulmonary damage result when animals are exposed to hyperbaric oxygen at pressures above about 300 kPa. Several hydroxyl radical scavengers (namely dimethylsulphoxide, dimethylthiourea and mannitol), the iron chelator desferrioxamine and the lipid antioxidant butylated hydroxytoluene were tested for possible protection against such hyperbaric oxygen toxicity. Dimethylthiourea and dimethylsulphoxide prolonged the latency to the first convulsion, but, surprisingly, dimethylthiourea very significantly increased pulmonary damage at both pressures used (515 and 585 kPa). Desferrioxamine also slightly increased lung damage at 585 kPa. Other antioxidants did not alter neurotoxicity or pulmonary toxicity induced by hyperbaric oxygen at 515 or 585 kPa. The antioxidants were also tested for their ability to inhibit lipid peroxidation (TBARS formation) in vitro. Desferrioxamine (5 and 50 microM), and butylated hydroxytoluene (0.1 mM and 1 mM) greatly inhibited TBARS formation in brain and lung homogenates incubated at 37 degrees. None of the hydroxyl radical scavengers affected TBARS levels in homogenates. There was no correlation between in vitro inhibition of lipid peroxidation and in vivo protection against oxygen toxicity.
Animals↗
The effect of a fish oil enriched diet on oxygen toxicity and lipid peroxidation in mice.
Mice were fed a chow diet or diets enriched in fish oil, sunflower oil or beef tallow for 3 weeks. Fatty acid analysis was carried out in samples of plasma, brain and lungs from these animals and large changes were found in plasma and lungs with relatively small dietary-induced changes in brain tissue. Bleeding times were increased very significantly in the fish oil group, and slightly increased in the sunflower oil group. Endogenous lipid peroxidation (measured as thiobarbituric acid reactive substances) was unchanged in lung and brain, but lung tissue from fish oil fed mice produced more lipid peroxides in vitro during incubation at 37 degrees than those of other dietary groups. Mice fed the four different diets were exposed to hyperbaric oxygen at 618, 585 and 515 kPa and convulsive activity and lung damage was recorded. No dietary-induced alterations in susceptibility to oxygen toxicity were found.
Animals↗
Development of tolerance to kava in mice.
1. The development of tolerance to the aqueous extract of kava, and to the lipid soluble extract (kava resin) was tested in mice. 2. Tolerance to the unknown pharmacologically active ingredient(s) developed very rapidly, given parenterally, in the aqueous extract. A minimally effective daily dose (50 mg/kg) of the aqueous extract for 3 days was sufficient to produce tolerance to a test dose of 150 mg/kg, which is close to the ED50. As tolerance was evident at the first test period it can be assumed to be physiological tolerance. 3. Kava resin decreased spontaneous motility and caused a loss of muscle control. A minimally effective daily dose of kava resin (100 mg/kg) did not produce tolerance to the above effects of a weekly test dose of kava resin (166 mg/kg) within 7 weeks. In a further experiment the dose was raised to 150 mg/kg twice daily and this schedule caused partial tolerance to occur within 3 weeks, but very little further tolerance developed over the ensuing 2-week period. 4. To try to induce learned (behaviourally acquired) tolerance a dose of 166 mg/kg kava resin was injected daily and animals were tested each day while under the influence of the drug. However, even under these conditions, there was no tolerance evident within 3 weeks, when the experiment was terminated. 5. It appears difficult to induce the development of physiological or learned tolerance to kava resin in mice.
Animals↗
Relation of hyperglycemia early in ischemic brain infarction to cerebral anatomy, metabolism, and clinical outcome.
We studied the relation of serum glucose level measured in the first 12 hours of symptoms to the clinical findings, results of computed tomography (CT), and patterns of cerebral metabolism in 39 patients who had acute ischemic cerebral infarction. Structural damage was assessed by CT. Metabolic disruption was assessed using 18F-fluorodeoxyglucose and positron emission tomography (PET). Median initial serum glucose concentration was 155 mg/dl (6.7 mM). Clinical recovery was significantly poorer in patients with initial serum glucose levels higher than the median (p less than 0.05, chi square). PET tended to show normal results or minor abnormalities in patients with initial glucose levels less than the median, as opposed to lobar or multilobe abnormalities in patients with levels that were higher than the median (p less than 0.05, Kendall's Tau b). The severity of hypometabolism in the ischemic region, expressed as the percent asymmetry of local cerebral glucose metabolism between homologous brain regions, was greater in patients with initial glycemia concentrations higher than the median (p less than 0.001, t test). Relationships of serum glucose level with metabolic derangement and structural damage, but not outcome, held true in patients without a history of diabetes mellitus.
Aged↗
Middle cerebral artery strokes causing homonymous hemianopia: positron emission tomography.
Eight patients were evaluated with 18F-fluorodeoxyglucose positron emission tomography between 3 and 30 days after isolated stroke involving the middle cerebral artery territory that caused homonymous hemianopia. Diffuse hypometabolism was present throughout the damaged cerebral hemisphere, even in cortical areas not obviously ischemic by clinical examination or neuro-imaging. Glucose metabolism in primary and association visual cortex of the damaged hemisphere was decreased by more than 47% (p less than 0.01). Metabolism in the undamaged hemisphere was less profoundly affected, but significant decrements were found in calcarine (40%; p less than 0.01) and lateral occipital cortex (35%; p less than 0.05).
Brain Ischemia↗
Cerebral blood flow variations in CNS lupus.
We studied the patterns of cerebral blood flow (CBF), over time, in patients with systemic lupus erythematosus and varying neurologic manifestations including headache, stroke, psychosis, and encephalopathy. For 20 paired xenon-133 CBF measurements, CBF was normal during CNS remissions, regardless of the symptoms. CBF was significantly depressed during CNS exacerbations. The magnitude of change in CBF varied with the neurologic syndrome. CBF was least affected in patients with nonspecific symptoms such as headache or malaise, whereas patients with encephalopathy or psychosis exhibited the greatest reductions in CBF. In 1 patient with affective psychosis, without clinical or CT evidence of cerebral ischemia, serial SPECT studies showed resolution of multifocal cerebral perfusion defects which paralleled clinical recovery.
Adult↗
Positron emission tomography to study the effect of eye closure and optic nerve damage on human cerebral glucose metabolism.
We used 18F-2-fluoro-2-deoxyglucose and positron emission tomography to evaluate the effect of visual deprivation on brain glucose metabolism. In experiment 1, we compared local cerebral metabolic rates for glucose in seven normal volunteers studied with eyes closed to 11 age- and sex-matched normal volunteers studied with eyes open. Whole brain metabolism was similar in the two groups, and region/whole brain analysis of metabolic data showed that metabolism in the calcarine posterior cortex was decreased by 14% (P less than .05) with eye closure. Glucose metabolism in other regions was not different between the two groups. In experiment 2, we compared glucose metabolism in six patients with severe bilateral optic neuropathies to 12 age- and sex-matched normal controls. Whole brain glucose metabolism was unchanged in the optic neuropathy group compared to controls. However, statistically significant reductions in glucose metabolism in the optic neuropathy group were found in anterior calcarine cortex (17%), posterior calcarine cortex (27%), peristriate cortex (27%), and lateral occipital cortex (15%). The metabolic effects of damage to the pregeniculate visual system went well beyond those of simple eye closure.
Adolescent↗
Oxygen toxicity and reactive oxygen metabolites in mammals.
The current hypothesis for the damage caused to mammalian tissues by hyperoxia is that oxygen radicals and related reactive oxygen metabolites are formed at rates which exceed the ability of the cells' natural antioxidant defense mechanisms to detoxify these deleterious products. In this review a very brief description of oxygen pathology is given together with data on the relevance of in vivo tissue pO2 levels. After a short historical account of the biochemistry of oxygen toxicity in the pre-radical days. the evidence for the current status of the radical theory is reviewed. This covers the probable sources of excess reactive oxygen metabolite generation under conditions of increased oxygen tension, and the measurement of the reactive species thought to be important in causing this damage. The large volume of circumstantial evidence, including the production of tolerance, raising or lowering antioxidant defenses and the administration of exogenously produced radicals is considered.
Animals↗
Alzheimer's disease with prominent visual symptoms. Clinical and metabolic evaluation.
The authors examined eight patients with dementia of the Alzheimer's type (DAT), five with prominent visual symptoms early in the illness (VS) and three with no visual symptoms (NVS). Results of neuro-ophthalmologic examinations on VS patients showed relatively consistent abnormalities in figure copying, color vision tested by isochromatic plates, and stereopsis. Cerebral glucose metabolism determined by 18F-fluoro-2-deoxyglucose positron emission tomography (PET) was unchanged in primary visual cortex of VS and NVS patients compared with 12 normal volunteers of similar age and sex. Glucose metabolism in VS patients was decreased by 45 and 34% in left and right visual association cortex (P less than 0.01 and P less than 0.05, respectively) and 34 and 37% in left and right inferior parietal cortex (P less than 0.05) compared with controls; NVS patients had no significant metabolic alteration in these areas. Symptoms, physical examination, and metabolic imaging imply that these patients are a heterogenous but distinct clinical subgroup of DAT often with mild dementia who have visual symptoms due primarily to visual agnosia.
Aged↗
Temporal resolution in children.
The auditory temporal resolving power of young children was measured using an adaptive forced-choice psychophysical paradigm that was disguised as a video game. 20 children between 3 and 7 years of age and 5 adults were asked to detect the presence of a temporal gap in a burst of half-octave-band noise at band center frequencies of 400 and 2,000 Hz. The minimum detectable gap (gap threshold) was estimated adaptively in 20-trial runs. The mean gap thresholds in the 400-Hz condition were higher for the younger children than for the adults, with the 3-year-old children producing the highest thresholds. Gap thresholds in the 2,000-Hz condition were generally lower than in the 400-Hz condition and showed a similar age effect. All the individual adaptive runs were "adult-like," suggesting that the children were generally attentive to the task during each run. However, the variability of threshold estimates from run to run was substantial, especially in the 3-5-year-old children. Computer simulations suggested that this large within-subjects variability could have resulted from frequent, momentary lapses of attention, which would lead to "guessing" on a substantial portion of the trials.
Attention↗
Low temperature worsens mammalian oxygen toxicity.
Oxygen toxicity was assessed in mice exposed to 5 ATA of oxygen. Central nervous system toxicity was measured as the latent period before convulsions, and lung damage estimated by wet and dry weight measurements. Our results confirmed previous findings that hyperbaric oxygen induces hypothermia in animals, and this effect is profound in mice exposed to 5 ATA of oxygen at ambient temperatures of 15 degrees C and 5 degrees C. However, even marked hypothermia had very little effect on the latent times to convulsions in mice. Unexpectedly, the combination of hypothermia and hyperbaric oxygen produced much more severe lung damage than either treatment alone, with a 2.7-fold increase in weight in the 5 degrees C group (average rectal temperature of 16.1 degrees C). These results indicate that hyperoxic-induced hypothermia cannot be considered a protective mechanism against oxygen toxicity and indeed hypothermia can markedly potentiate hyperbaric oxygen toxicity.
Animals↗
Reactive oxygen metabolites and hyperoxic toxicity.
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Animals↗
Positron emission tomography in the investigation of central nervous system disorders.
Positron emission tomography is a noninvasive tomographic technique for measuring regional tissue concentrations of labeled radionuclides in man. Detection of two photons emitted from the annihilation of a positron and an electron is used to reconstruct the distribution of a positron-emitting isotope within an organ. PET provides the capacity to measure quantitatively the local tissue distribution of a variety of radionuclides that are attached to compounds that distribute according to function. Commonly measured functions include local cerebral metabolism using 18F-fluorodeoxyglucose or 11C-deoxyglucose, cerebral blood flow, cerebral oxygen utilization, and cerebral blood volume. Clinical applications of PET are multiple, involving normal and disease states. By demonstrating the metabolic alterations, PET adds another dimension to our understanding of the brain, which up until recently has been based on the structural changes seen on CT and MRI.
Aging↗