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Biomedical subjects

D G MacGregor

Publications and source records attributed to D G MacGregor.

At least 19 recordsLinked to original sources
PubMed2001

HEPES prevents edema in rat brain slices.

Brain slices gain water when maintained in bicarbonate-buffered artificial cerebro-spinal fluid (ACSF) at 35 degrees C. We previously showed that this edema is linked to glutamate receptor activation and oxidative stress. An additional factor that may contribute to swelling is acidosis, which arises from high CO2 tension in brain slices. To examine the role of acidosis in slice edema, we added N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) to osmotically balanced ACSF (HEPES-ACSF), thereby increasing buffering capacity beyond that provided by bicarbonate/CO2. Water gain was markedly inhibited in HEPES-ACSF. After 3 h incubation in HEPES-ACSF at 35 degrees C, water gain was limited to that of fresh slices after 1 h recovery in ACSF at room temperature. The effect of HEPES in decreasing slice water gain was concentration dependent from 0.3 to 20 mM. The inhibition of water gain by HEPES suggests that tissue acidosis is a contributing factor in brain slice edema.

Acidosis↗
PubMed2000

Integrating public perspectives in sample return planning.

Planning for extraterrestrial sample returns--whether from Mars or other solar system bodies--must be done in a way that integrates planetary protection concerns with the usual mission technical and scientific considerations. Understanding and addressing legitimate societal concerns about the possible risks of sample return will be a critical part of the public decision making process ahead. This paper presents the results of two studies, one with lay audiences, the other with expert microbiologists designed to gather information on attitudes and concerns about sample return risks and planetary protection. Focus group interviews with lay subjects, using generic information about Mars sample return and a preliminary environmental impact assessment, were designed to obtain an indication of how the factual content is perceived and understood by the public. A research survey of microbiologists gathered information on experts' views and attitudes about sample return, risk management approaches and space exploration risks. These findings, combined with earlier research results on risk perception, will be useful in identifying levels of concern and potential conflicts in understanding between experts and the public about sample return risks. The information will be helpful in guiding development of the environmental impact statement and also has applicability to proposals for sample return from other solar system bodies where scientific uncertainty about extraterrestrial life may persist at the time of mission planning.

Containment of Biohazards↗
PubMed2000

Violence risk assessment and risk communication: the effects of using actual cases, providing instruction, and employing probability versus frequency formats.

This article describes studies designed to inform policy makers and practitioners about factors influencing the validity of violence risk assessment and risk communication. Forensic psychologists and psychiatrists were shown case summaries of patients hospitalized with mental disorder and were asked to judge the likelihood that the patient would harm someone within six months after discharge from the hospital. They also judged whether the patient posed a high risk, medium risk, or low risk of harming someone after discharge. Studies 1 and 2 replicated, with real case summaries as stimuli, the response-scale effects found by Slovic and Monahan (1995). Providing clinicians with response scales allowing more discriminability among smaller probabilities led patients to be judged as posing lower probabilities of committing harmful acts. This format effect was not eliminated by having clinicians judge relative frequencies rather than probabilities or by providing them with instruction in how to make these types of judgments. In addition, frequency scales led to lower mean likelihood judgments than did probability scales, but, at any given level of likelihood, a patient was judged as posing higher risk if that likelihood was derived from a frequency scale (e.g., 10 out of 100) than if it was derived from a probability scale (e.g., 10%). Similarly, communicating a patient's dangerousness as a relative frequency (e.g., 2 out of 10) led to much higher perceived risk than did communicating a comparable probability (e.g., 20%). The different reactions to probability and frequency formats appear to be attributable to the more frightening images evoked by frequencies. Implications for risk assessment and risk communication are discussed.

Adult↗
PubMed2000

Impaired cerebral autoregulation 24 h after induction of transient unilateral focal ischaemia in the rat.

Cerebral blood flow (CBF) and cerebral autoregulation have been investigated 24 h after transient focal ischaemia in the rat. Cerebral blood flow was measured autoradiographically before and during a moderate hypotensive challenge, to test autoregulatory responses, using two CBF tracers, (99m)Tc-d,l-hexamethylproyleneamine oxide and 14C-iodoantipyrine. Prior to induced hypotension, CBF was significantly reduced within areas of infarction; cortex (28 +/- 20 compared with 109 +/- 23 mL/100 g/min contralateral to ischaemic focus, P = 0.001) and caudate (57 +/- 31 compared with 141 +/- 32 mL/100 g/min contralaterally, P = 0.005). The hypotensive challenge (mean arterial pressure reduced to 60 mmHg by increasing halothane concentration) did not compromise grey matter autoregulation in the contralateral hemisphere; CBF data were not significantly different at normotension and during hypotension. However, in the ipsilateral hemisphere, a significant volume of cortex adjacent to the infarct, which exhibited normal flow at normotension, became oligaemic during the hypotensive challenge (e.g. frontal parietal cortex 109 +/- 15% to 65 +/- 15% of cerebellar flow, P < 0.01). This resulted in a 2.5-fold increase in the volume of cortex which fell below 50% cerebellar flow (39 +/- 34 to 97 +/- 46 mm3, P = 0.003). Moderate hypotension induced a significant reduction in CBF in both ipsilateral and contralateral subcortical white matter (P < 0.01). In peri-infarct caudate tissue, CBF was not significantly affected by hypotension. In conclusion, a significant volume of histologically normal cortex within the middle cerebral artery territory was found to have essentially normal levels of CBF but impaired autoregulatory function at 24 h post-ischaemia.

Animals↗
PubMed1999

"How exposed is exposed enough?" Lay inferences about chemical exposure.

The concept of exposure is central to chemical risk assessment and plays an important role in communicating to the public about the potential health risks of chemicals. Research on chemical risk perception has found some indication that the model lay people use to judge chemical exposure differs from that of toxicologists, thereby leading to different conclusions about chemical safety. This paper presents the results of a series of studies directed toward developing a model for understanding how lay people interpret the concept of chemical exposure. The results indicate that people's beliefs about chemical exposure (and its risks) are based on two broad categories of inferences. One category of inferences relates to the nature in which contact with a chemical has taken place, including the amount of a chemical involved and its potential health consequences. A second category of inferences about chemical exposure relates to the pragmatics of language interpretation, leading to beliefs about the motives and purposes behind chemical risk communication. Risk communicators are encouraged to consider how alternative models of exposure and language interpretation can lead to conflicting conclusions on the part of the public about chemical safety.

Carcinogens, Environmental↗
PubMed1998

Protection by an adenosine analogue against kainate-induced extrahippocampal neuropathology.

1. The glutamate analogue kainic acid produces neuronal damage in the central nervous system. We have reported that analogues of adenosine, such as R-N6-phenylisopropyladenosine (R-PIA) can, at doses as low as 10 microg/kg IP, prevent the hippocampal damage that follows the systemic administration of kainate. The present work was designed to examine purine protection against kainate in extrahippocampal regions by using histological methods. 2. The results show that R-PIA, at a dose of 25 microg/kg IP in rats, can protect against the neuronal damage caused by kainate in the basolateral amygdaloid nuclei, the pyriform cortex and around the rhinal fissure. This protection could be prevented by the simultaneous administration of the A1 adenosine receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine, confirming that the protection involved adenosine A1 receptors. No protection was observed in the posterior amygdaloid nuclei or the entorhinal cortex, suggesting the absence of relevant adenosine receptors or a different mechanism of excitotoxicity.

Adenosine↗
PubMed1997

The attenuation of kainate-induced neurotoxicity by chlormethiazole and its enhancement by dizocilpine, muscimol, and adenosine receptor agonists.

Systemically administered kainate (10 mg.kg-1) caused neuronal loss in both the hippocampus and the entorhinal regions of the rat brain. This resulted in a loss of 68.3 +/- 13.8 and 53.3 +/- 12.8% of pyramidal neurones in the hippocampal CA1 and CA3a regions, respectively. Chlormethiazole attenuated the loss of neurones in the hippocampal cell layers CA1 (cell loss 10 +/- 3.2%) and CA3a (cell loss 10 +/- 7.7%). The neuroprotective activity of chlormethiazole was apparent in the presence or absence of a low dose of clonazepam (200 micrograms.kg-1 i.p.). The kainate-induced damage could also be measured by the increase in binding of the peripheral benzodiazepine ligand ([3H]PK11195) in the hippocampus. In kainate-treated rats there was a 350-500% increase in binding indicative of reactive gliosis. Chlormethiazole prevented this elevation in a dose- and time-dependent manner, with an ED50 of 10.64 mg.kg-1 and an effective therapeutic window from 1 to 4 h posttreatment. Dizocilpine also attenuated damage significantly. The GABAA agonist muscimol was also able to attenuate the increase in [3H]PK11195 binding in a dose-dependent manner, with an ED50 of approximately 0.1 mg.kg-1. If muscimol, dizocilpine, or the adenosine A1 receptor agonist R-N6-phenylisopropyl-adenosine were administered together with chlormethiazole at their respective ED25 doses, a potentiation was apparent in the degree of neuroprotection. It is concluded that the combination of neuroprotective agents with different mechanisms of action can lead to a synergistic protection against excitotoxicity.

Adenosine↗
PubMed1996

Ascorbate attenuates the systemic kainate-induced neurotoxicity in the rat hippocampus.

The neuronal damage induced by systemic administration of kainic acid reproduces the cellular and regional pattern of damage produced by repeated seizures. The ability of kainic acid to induce lipid peroxidation, and the ability of free radical inhibitors to prevent ischaemically-induced cell death, has led us to examine the possible role of free radicals in kainate-induced injury. Ascorbic acid was able to reduce kainate-induced damage of the rat hippocampus, measured by means of the gliotic marker ligand [3H]PK11195. Ascorbate was significantly effective at doses of 30 mg kg-1 and above, with total protection against kainate at 50 mg kg-1. Histologically, ascorbate at 50 mg kg-1 was able to prevent kainate-induced neuronal loss in the hippocampal CA1 and CA3a cell layers. The antioxidant was also effective when administered simultaneously with, or 1 h before the kainate. Protection was also obtained by allopurinol, 175 mg kg-1 and by oxypurinol, 40 mg kg-1. Ascorbate did not modify synaptically evoked potentials or long-term potentiation in hippocampal slices, ruling out any blocking activity at glutamate receptors. It is concluded that the neuronal damage produced by systemically administered kainate involves the formation of free radicals.

Analysis of Variance↗
PubMed1996

Prevention by a purine analogue of kainate-induced neuropathology in rat hippocampus.

Systemic injection of kainic acid produces a characteristic regional and cellular pattern of neuronal loss in the central nervous system by mechanisms which may be relevant to an understanding of neurodegenerative disorders. It has previously been found, by measuring the binding of a glial marker ligand, that analogues of adenosine, such as R-N6-phenylisopropyladenosine (R-PIA), can prevent kainate-induced damage of the hippocampus at doses as low as 10 micrograms/kg, i.p. The use of gliotic markers, however, is open to misinterpretation, and the present work was designed to re-examine purine protection against kainate using histological methods. The results show that R-PIA, at a dose of 25 micrograms/kg i.p. in rats, can protect against the neuronal damage caused by kainate and that this protection could be completely prevented by the simultaneous administration of 1,3-dipropyl-8-cyclopentylxanthine, indicating the involvement of adenosine A1 receptors in the protection.

Animals↗
PubMed1996

Risk perception and symptom reporting.

Public reaction to chemical technologies has included a perception that chemical exposure is a contributor to human health problems. Though these perceptions sometimes correspond with technical assessments of chemical risks, at other times they do not. This paper presents a descriptive model of the relationship between perception of one's health status and a set of factors that are used by individuals as part of causal reasoning about the meaning of somatic change. The model incorporates both personal events and experiences associated with somatic change (e.g., stress, sensory cues), as well as aspects of an individual's social context in which perceptions of chemical risks serve as a powerful framework for attributing meaning to chemical exposure. Within this model, the causal inferences that people make about the effects of chemical exposure on symptomatology are viewed as part of a natural, psychological adaptation in which the individual seeks to decrease their uncertainty about the factors or conditions that cause them to feel as they do.

Adaptation, Psychological↗
PubMed1994

Release and actions of adenosine in the central nervous system.

Adenosine is released from active neurons into the extracellular fluid at a concentration of about 1 mumol/l. Neither the precise cellular origin nor the biochemical form of release has been firmly established, though the nucleotide is probably released partly directly, as a result of raised intracellular levels, and partly as nucleotides, which are subsequently hydrolysed. Once in the extracellular medium, adenosine markedly inhibits the release of excitatory neurotransmitters and modulatory peptides and has direct inhibitory effects on postsynaptic excitability via A1 receptors. A population of A2 receptors may mediate depolarization and enhanced transmitter release. Adenosine also modulates neuronal sensitivity to acetylcholine and catecholamines, all these effects probably contributing to the behavioural changes observed in conscious animals. As a result of their many actions, adenosine analogues are being intensively investigated for use as anticonvulsant, anxiolytic, and neuroprotective agents.

Acetylcholine↗
PubMed1994

Time course of purine protection against kainate-induced increase in hippocampal [3H]-PK11195 binding.

Binding of a peripheral benzodiazepine receptor ligand was used to quantify the reactive gliosis resulting from neuronal damage induced by systemic injections of kainic acid 7 days previously. The enhancement of binding in rat hippocampus could be prevented by injections of the purine analogue (R)-N6-phenylisopropyladenosine at 25 microgram/kg up to 2 h before or after the toxin. These results indicate that the purine is able to prevent neurotoxicity by interrupting events occurring some time after kainate administration.

Animals↗
PubMed1994

Perception of risks from electromagnetic fields: a psychometric evaluation of a risk-communication approach.

Potential health risks from exposure to power-frequency electromagnetic fields (EMF) have become an issue of significant public concern. This study evaluates a brochure designed to communicate EMF health risks from a scientific perspective. The study utilized a pretest-posttest design in which respondents judged various sources of EMF (and other) health and safety risks, both before reading the brochure and after. Respondents assessed risks on dimensions similar to those utilized in previous studies of risk perception. In addition, detailed ratings were made that probed respondents' beliefs about the possible causal effects of EMF exposure. The findings suggest that naive beliefs about the potential of EMF exposure to cause harm were highly influenced by specific content elements of the brochure. The implications for using risk-communication approaches based on communicating scientific uncertainty are discussed.

Attitude to Health↗
PubMed1993

Inhibition by the adenosine analogue, (R-)-N6-phenylisopropyladenosine, of kainic acid neurotoxicity in rat hippocampus after systemic administration.

1. Binding of the peripheral benzodiazepine receptor ligand, [3H]-PK 11195, to rat hippocampal membranes has been used to quantify the reactive gliosis resulting from neuronal death induced by intraperitoneally administered kainic acid. 2. Intraperitoneal administration of kainic acid (10 mg kg-1) caused a 350-500% increase in [3H]-PK 11195 binding measured in rat hippocampal P2 membranes 7 days later. Co-treatment with the adenosine derivative R-phenylisopropyladenosine (R-PIA) (100, 25 or 10 micrograms kg-1, i.p.) abolished this elevation. The protective action of R-PIA could itself be abolished by co-treatment with 8-phenyltheophylline (1 mg kg-1). 3. Body temperatures were recorded in the antagonist experiments and no significant changes were recorded, suggesting that the protective action of R-PIA was not mediated by hypothermia. 4. Since systemic kainic acid-induced neurotoxicity has been claimed as a good model of neuronal death in temporal lobe epilepsy, the results suggest that the systemic administration of purines in low doses may provide protection against certain neurodegenerative insults.

Animals↗
PubMed1993

Mediation of the neuroprotective action of R-phenylisopropyl-adenosine through a centrally located adenosine A1 receptor.

1. Systemic injections of kainic acid, 10 mg kg-1, into adult rats resulted in lesions in the hippocampus, as assessed by peripheral benzodiazepine ligand binding. Co-administration of clonazepam at 1 mg kg-1 or 0.2 mg kg-1 prevented major seizures associated with kainate injections, but did not alter significantly the production of hippocampal damage. 2. The co-administration of the adenosine A1 agonist R-phenylisopropyladenosine (R-PIA, 25 micrograms kg-1, i.p.) abolished the lesions induced by kainic acid. 3. The presence of the selective A1 antagonist, 8-cyclopentyl-1,3-dipropylxanthine (250 or 50 micrograms kg-1, i.p.) abolished the R-PIA neuroprotective action. 4. The A1/A2 antagonist, 8-(p-sulphophenyl)theophylline (20 mg kg-1, i.p.) which cannot cross the blood brain barrier, did not alter significantly the neuroprotective action of R-PIA, indicating that the neuroprotective action of the purine may be predominantly central. 5. The time course of the neuroprotection was also examined. R-PIA was effective when administered 2 h before or after kainate administration. 6. The results emphasise the potential utility of systemically active adenosine A1 receptor ligands in reducing CNS gliosis induced by the activation of excitatory amino acid receptors.

Animals↗