Robert Sewell - Academia.edu (original) (raw)
Papers by Robert Sewell
British Journal of Pharmacology, Jun 1, 1998
Current Pharmaceutical Design, Jul 5, 2020
Biomolecules, Jul 25, 2019
Current Pharmaceutical Design, Jan 8, 2020
Bulletin of Experimental Biology and Medicine, May 1, 2020
Intranasal administration of antibodies to glutamate at dose of 250 μg/kg for two weeks facilitat... more Intranasal administration of antibodies to glutamate at dose of 250 μg/kg for two weeks facilitated spatial learning and memory formation in the Morris water maze in aging C57Bl/6 mice. Concurrently, in the animals treated with glutamate antibodies, there was a decrease in serotonin level, no change in dopamine but a reduction in 3-MT and HVA metabolite concentrations in the hippocampus. In the prefrontal cortex, a decrease in dopamine level occurred along with a simultaneous increase in the content of its metabolite, DOPAC, as well as an increase in excitatory and inhibitory amino acid neurotransmitters: aspartic acid, glutamate, glycine, taurine and GABA. It was concluded that Abs-Glu facilitated spatial learning and memory formation through a remodeling of the hippocampal and prefrontal cortical neurochemical system in aging C57Bl/6 mice.
The European Journal of Contraception & Reproductive Health Care, Apr 10, 2015
American Journal of Pharmaceutical Education, 2007
Objectives. To examine the effectiveness of providing formative feedback for summative computerai... more Objectives. To examine the effectiveness of providing formative feedback for summative computeraided assessment. Design. Two groups of first-year undergraduate life science students in pharmacy and neuroscience who were studying an e-learning package in a common pharmacology module were presented with a computer-based summative assessment. A sheet with individualized feedback derived from each of the 5 results sections of the assessment was provided to each student. Students were asked via a questionnaire to evaluate the form and method of feedback. Assessment. The students were able to reflect on their performance and use the feedback provided to guide their future study or revision. There was no significant difference between the responses from pharmacy and neuroscience students. Students' responses on the questionnaire indicated a generally positive reaction to this form of feedback. Conclusions. Findings suggest that additional formative assessment conveyed by this style and method would be appreciated and valued by students.
Frontiers in Pharmacology
Background: Neuropathy is a prevalent and debilitating complication of poorly managed diabetes, c... more Background: Neuropathy is a prevalent and debilitating complication of poorly managed diabetes, contributing towards poor quality of life, amputation risk, and increased mortality. The available therapies for diabetic neuropathic pain (DPN) have limitations in terms of efficacy, tolerability and patient compliance. Dysfunction in the peripheral and central monoaminergic system has been evidenced in various types of neuropathic and acute pain. The objective of the present study was to investigate 1-methyl 1, 2, 3, 4-tetrahydroisoquinoline (1MeTIQ), an endogenous amine found in human brain with a known neuroprotective profile, in a model of streptozotocin (STZ) induced neuropathic pain.Methods: Diabetic neuropathy in male BALB/c mice was induced by intraperitoneal injection of a single dose of STZ (200 mg/kg). Upon development of DPN after 4 weeks, mice were investigated for mechanical allodynia (von Frey filament pressure test) and thermal hyperalgesia (tail immersion test). Ondanset...
Inhalation Toxicology, 2004
Endotoxin is derived from Gram-negative bacterial membranes, and its inflammatory effects followi... more Endotoxin is derived from Gram-negative bacterial membranes, and its inflammatory effects following inhalation are well characterized. The significance of this fact becomes apparent when the wide-ranging environments containing high levels of this microbial product are considered. Endotoxin is present in numerous industrial environments, especially where organic fibers are processed. Microbial contamination of these fibers mainly occurs at the agricultural stage. Materials such as flax and hemp are affected in this way, but the most important product in this context is cotton, from which chronic dust inhalation causes the disease byssinosis. Despite the fact that endotoxin constitutes a significant threat to public health, there are currently no occupational exposure limits for this toxicant. This communication describes the toxicology of endotoxin, and its role in inhalation-induced disease, focusing on measurement of airborne endotoxin in the occupational and domestic environments using the Limulus amebocyte lysate (LAL) enzyme assay. Following the success of the LAL assay for measuring endotoxin in dusts, our laboratory has examined its application to aqueous washes from cotton fibers. Reproducibility of the results was high, and data are presented displaying levels of endotoxin contamination in fibers from different cotton producing countries. Hence, worldwide comparison of industrial endotoxin concentrations can be readily made using this test. It would be highly desirable if the performance of the LAL assay facilitated introduction of industrial endotoxin safety limits, and in spite of minor surmountable shortcomings, the test is accurate, reliable, and well field-tested, so its continued widespread use may achieve this goal.
European Journal of Pharmacology, 2021
Highlights-A synthesised anti-inflammatory cyclohexanone (CHD) was tested in vivo and in vitro-CH... more Highlights-A synthesised anti-inflammatory cyclohexanone (CHD) was tested in vivo and in vitro-CHD inhibited COX-2 and 5-LOX enzymes plus COX-2, TNF-α and IL-1β mRNA expression-CHD also produced GABAA and opioid mediated inhibitory activity in nociceptive tests-In silico CHD had preferential affinity for GABAA, opioid and COX-2 target sites-CHD may possess therapeutic effectiveness in the management of inflammation and pain
Neuropharmacology, Nov 1, 1981
ABSTRACT
Bulletin of Experimental Biology and Medicine, Feb 1, 2017
Chronic intranasal administration of fibrillar structures of proinflammatory S100A9 protein impai... more Chronic intranasal administration of fibrillar structures of proinflammatory S100A9 protein impaired passive avoidance learning in old C57Bl/6 mice. Combined treatment with S100A9 fibrils and antibodies to glutamate was followed by an increase in horizontal locomotor activity of animals in the open-field test and did not disturb spatial memory.
Frontiers in Molecular Neuroscience, Dec 16, 2021
Thiadiazine-Thione Derivatives Attenuate Neuropathic Neuroinflammation bonding and van der Waals ... more Thiadiazine-Thione Derivatives Attenuate Neuropathic Neuroinflammation bonding and van der Waals interactions. Overall, these results suggest that TDT1 and TDT2 exert their neuroprotective and analgesic potentials by ameliorating CCIinduced allodynia, hyperalgesia, neuroinflammation and neuronal degeneration in a dose-dependent manner.
Pharmacology Reviews and Communications, Dec 1, 2000
Alcohol and Alcoholism, Nov 1, 1983
The effects of selective dopaminergic and cholinergic agonists and antagonists on morphine abstin... more The effects of selective dopaminergic and cholinergic agonists and antagonists on morphine abstinence were assessed. Morphine dependence in rats was induced by the subcutaneous implantation of morphine pellets, and abstinence was precipitated using the benzomorphan antagonist Mr-1452. Withdrawal was assessed by scoring and counting behavioural signs; body weight and temperature changes were also measured. Atropine, sulpiride and clozapine attenuated certain withdrawal signs, whereas oxotremonne and the D-1 receptor agonist compound SKF-38393 intensified the overall abstinence syndrome. In addition, treatment with the D-2 receptor agonist compound LY-141865, although blocking the majority of signs, uncovered other dose-dependent behaviours, e.g. copulatory mounting, stereotyped circling and aggression. Compound LY-141865 also attenuated the cholinergic withdrawal signs in a similar way to atropine. These results support the concept of an acetylcholine-dopamine link during opiate abstinence.
Alcohol and Alcoholism, Nov 1, 1983
The effects of both acute and chronic administration of the antidepressants mianserin, nomifensin... more The effects of both acute and chronic administration of the antidepressants mianserin, nomifensine, and (+) and (−)-oxaprotiline were assessed on naloxone-precipitated abstinence in chronically morphinized rats. Chronic coadministration of the antidepressants with morphine during the induction of dependence produced no significant alleviation of withdrawal. Acute administration of nomifensine prior to precipitation of abstinence with naloxone produced an exacerbation of the withdrawal syndrome through stimulation of supersensitive dopamine receptor sites. By contrast, mianserin and (+)-oxaprotiline produced an overall significant alleviation of withdrawal, whereas (−)-oxaprotiline was without effect. The results are discussed in relation to the possible value of antidepressant treatment during opiate withdrawal.
Alcohol and Alcoholism, Nov 1, 1984
The effects of meptazinol and some opioid agonists and antagonists were studied on opioid-naive g... more The effects of meptazinol and some opioid agonists and antagonists were studied on opioid-naive guinea-pig ileum (GPIN) and ileum taken from morphine-dependent guinea-pigs (GPID). Meptazinol produced a biphasic effect in GPIN and GPID with a depression of the electrically induced twitch response at lower concentrations and contractural potentiation at higher concentrations. The effects of meptazinol in both GPIN and GPID were similar, thus distinguishing it from the other opioid agonists and antagonists which produced differential effects on these tissues. In morphine-pelletted rats, meptazinol (5 mg/kg i.p.) did not produce notable withdrawal as measured by behavioural observation. However, meptazinol (30 mg/kg i.p.) enhanced the signs associated with cholinergic activation. It is suggested that meptazinol possesses a cholinergic component and that the morphine-withdrawal signs observed to the higher meptazinol dose were more probably attributable to cholinergic stimulation rather than any underlying opioid-precipitated withdrawal.
Journal of Pharmacy and Pharmacology, Jul 1, 1988
Following subchronic (5-day) dosing with B-HT 920 (2-amino-6-allyl-5,6,7,8-tetrahydro-4H-thiazolo... more Following subchronic (5-day) dosing with B-HT 920 (2-amino-6-allyl-5,6,7,8-tetrahydro-4H-thiazolo(4,5-d)azepine (1 mg kg-1 day-1 i.p.) in rats there was a significant increase in both apomorphine-induced motor activity and stereotypy. On continued B-HT 920 treatment, however, the enhancement of apomorphine motor activity faded into insignificance but the increase in stereotypy persisted beyond 15 days. The results are discussed in terms of dopamine autoreceptor tolerance, postsynaptic D2 supersensitivity and possible differential effects in different brain loci on the above two receptor sub-classes.
Alcohol and Alcoholism, Nov 1, 1984
The acute and subchronic actions of the benzodiazepines triazolam, oxazepam and diazepam have bee... more The acute and subchronic actions of the benzodiazepines triazolam, oxazepam and diazepam have been examined using three behavioural tests. In the accelerating rotarod motor coordination test both diazepam and oxazepam on acute administration produced dose-related discoordination or motor impairment in mice. After chronic administration (50 mg/kg per day i.p. for 14 days) the corresponding dose-response lines were shifted to the right suggesting tolerance development. In a test for conflict behaviour in rats (conditioned suppression of drinking) oxazepam (20 mg/kg i.p.), triazolam (1 mg/kg i.p.) and diazepam (10 mg/kg i.p.) all augmented punished responding rates with no effect on unpunished responses and this has been speculated to reflect anxiolytic activity. These initial elevations in punished responding displayed a gradual decline during repeated daily administration over 20 days, there being little alteration in the unpunished response levels. In separate studies, chronic treatment of mice with triazolam in the drinking water over 30 days showed diminished pentylenetetrazol-induced seizure latencies compared to the level of protection afforded by triazolam at the beginning of the schedule. In additional experiments, mice injected daily with triazolam (1 mg/kg i.p. for 14 days) exhibited a higher seizure susceptibility than their corresponding controls. The results are discussed in relation to tolerance to the anxiolytic, anticonvulsant and neurological impairment properties of benzodiazepines.
British Journal of Pharmacology, Jun 1, 1998
Current Pharmaceutical Design, Jul 5, 2020
Biomolecules, Jul 25, 2019
Current Pharmaceutical Design, Jan 8, 2020
Bulletin of Experimental Biology and Medicine, May 1, 2020
Intranasal administration of antibodies to glutamate at dose of 250 μg/kg for two weeks facilitat... more Intranasal administration of antibodies to glutamate at dose of 250 μg/kg for two weeks facilitated spatial learning and memory formation in the Morris water maze in aging C57Bl/6 mice. Concurrently, in the animals treated with glutamate antibodies, there was a decrease in serotonin level, no change in dopamine but a reduction in 3-MT and HVA metabolite concentrations in the hippocampus. In the prefrontal cortex, a decrease in dopamine level occurred along with a simultaneous increase in the content of its metabolite, DOPAC, as well as an increase in excitatory and inhibitory amino acid neurotransmitters: aspartic acid, glutamate, glycine, taurine and GABA. It was concluded that Abs-Glu facilitated spatial learning and memory formation through a remodeling of the hippocampal and prefrontal cortical neurochemical system in aging C57Bl/6 mice.
The European Journal of Contraception & Reproductive Health Care, Apr 10, 2015
American Journal of Pharmaceutical Education, 2007
Objectives. To examine the effectiveness of providing formative feedback for summative computerai... more Objectives. To examine the effectiveness of providing formative feedback for summative computeraided assessment. Design. Two groups of first-year undergraduate life science students in pharmacy and neuroscience who were studying an e-learning package in a common pharmacology module were presented with a computer-based summative assessment. A sheet with individualized feedback derived from each of the 5 results sections of the assessment was provided to each student. Students were asked via a questionnaire to evaluate the form and method of feedback. Assessment. The students were able to reflect on their performance and use the feedback provided to guide their future study or revision. There was no significant difference between the responses from pharmacy and neuroscience students. Students' responses on the questionnaire indicated a generally positive reaction to this form of feedback. Conclusions. Findings suggest that additional formative assessment conveyed by this style and method would be appreciated and valued by students.
Frontiers in Pharmacology
Background: Neuropathy is a prevalent and debilitating complication of poorly managed diabetes, c... more Background: Neuropathy is a prevalent and debilitating complication of poorly managed diabetes, contributing towards poor quality of life, amputation risk, and increased mortality. The available therapies for diabetic neuropathic pain (DPN) have limitations in terms of efficacy, tolerability and patient compliance. Dysfunction in the peripheral and central monoaminergic system has been evidenced in various types of neuropathic and acute pain. The objective of the present study was to investigate 1-methyl 1, 2, 3, 4-tetrahydroisoquinoline (1MeTIQ), an endogenous amine found in human brain with a known neuroprotective profile, in a model of streptozotocin (STZ) induced neuropathic pain.Methods: Diabetic neuropathy in male BALB/c mice was induced by intraperitoneal injection of a single dose of STZ (200 mg/kg). Upon development of DPN after 4 weeks, mice were investigated for mechanical allodynia (von Frey filament pressure test) and thermal hyperalgesia (tail immersion test). Ondanset...
Inhalation Toxicology, 2004
Endotoxin is derived from Gram-negative bacterial membranes, and its inflammatory effects followi... more Endotoxin is derived from Gram-negative bacterial membranes, and its inflammatory effects following inhalation are well characterized. The significance of this fact becomes apparent when the wide-ranging environments containing high levels of this microbial product are considered. Endotoxin is present in numerous industrial environments, especially where organic fibers are processed. Microbial contamination of these fibers mainly occurs at the agricultural stage. Materials such as flax and hemp are affected in this way, but the most important product in this context is cotton, from which chronic dust inhalation causes the disease byssinosis. Despite the fact that endotoxin constitutes a significant threat to public health, there are currently no occupational exposure limits for this toxicant. This communication describes the toxicology of endotoxin, and its role in inhalation-induced disease, focusing on measurement of airborne endotoxin in the occupational and domestic environments using the Limulus amebocyte lysate (LAL) enzyme assay. Following the success of the LAL assay for measuring endotoxin in dusts, our laboratory has examined its application to aqueous washes from cotton fibers. Reproducibility of the results was high, and data are presented displaying levels of endotoxin contamination in fibers from different cotton producing countries. Hence, worldwide comparison of industrial endotoxin concentrations can be readily made using this test. It would be highly desirable if the performance of the LAL assay facilitated introduction of industrial endotoxin safety limits, and in spite of minor surmountable shortcomings, the test is accurate, reliable, and well field-tested, so its continued widespread use may achieve this goal.
European Journal of Pharmacology, 2021
Highlights-A synthesised anti-inflammatory cyclohexanone (CHD) was tested in vivo and in vitro-CH... more Highlights-A synthesised anti-inflammatory cyclohexanone (CHD) was tested in vivo and in vitro-CHD inhibited COX-2 and 5-LOX enzymes plus COX-2, TNF-α and IL-1β mRNA expression-CHD also produced GABAA and opioid mediated inhibitory activity in nociceptive tests-In silico CHD had preferential affinity for GABAA, opioid and COX-2 target sites-CHD may possess therapeutic effectiveness in the management of inflammation and pain
Neuropharmacology, Nov 1, 1981
ABSTRACT
Bulletin of Experimental Biology and Medicine, Feb 1, 2017
Chronic intranasal administration of fibrillar structures of proinflammatory S100A9 protein impai... more Chronic intranasal administration of fibrillar structures of proinflammatory S100A9 protein impaired passive avoidance learning in old C57Bl/6 mice. Combined treatment with S100A9 fibrils and antibodies to glutamate was followed by an increase in horizontal locomotor activity of animals in the open-field test and did not disturb spatial memory.
Frontiers in Molecular Neuroscience, Dec 16, 2021
Thiadiazine-Thione Derivatives Attenuate Neuropathic Neuroinflammation bonding and van der Waals ... more Thiadiazine-Thione Derivatives Attenuate Neuropathic Neuroinflammation bonding and van der Waals interactions. Overall, these results suggest that TDT1 and TDT2 exert their neuroprotective and analgesic potentials by ameliorating CCIinduced allodynia, hyperalgesia, neuroinflammation and neuronal degeneration in a dose-dependent manner.
Pharmacology Reviews and Communications, Dec 1, 2000
Alcohol and Alcoholism, Nov 1, 1983
The effects of selective dopaminergic and cholinergic agonists and antagonists on morphine abstin... more The effects of selective dopaminergic and cholinergic agonists and antagonists on morphine abstinence were assessed. Morphine dependence in rats was induced by the subcutaneous implantation of morphine pellets, and abstinence was precipitated using the benzomorphan antagonist Mr-1452. Withdrawal was assessed by scoring and counting behavioural signs; body weight and temperature changes were also measured. Atropine, sulpiride and clozapine attenuated certain withdrawal signs, whereas oxotremonne and the D-1 receptor agonist compound SKF-38393 intensified the overall abstinence syndrome. In addition, treatment with the D-2 receptor agonist compound LY-141865, although blocking the majority of signs, uncovered other dose-dependent behaviours, e.g. copulatory mounting, stereotyped circling and aggression. Compound LY-141865 also attenuated the cholinergic withdrawal signs in a similar way to atropine. These results support the concept of an acetylcholine-dopamine link during opiate abstinence.
Alcohol and Alcoholism, Nov 1, 1983
The effects of both acute and chronic administration of the antidepressants mianserin, nomifensin... more The effects of both acute and chronic administration of the antidepressants mianserin, nomifensine, and (+) and (−)-oxaprotiline were assessed on naloxone-precipitated abstinence in chronically morphinized rats. Chronic coadministration of the antidepressants with morphine during the induction of dependence produced no significant alleviation of withdrawal. Acute administration of nomifensine prior to precipitation of abstinence with naloxone produced an exacerbation of the withdrawal syndrome through stimulation of supersensitive dopamine receptor sites. By contrast, mianserin and (+)-oxaprotiline produced an overall significant alleviation of withdrawal, whereas (−)-oxaprotiline was without effect. The results are discussed in relation to the possible value of antidepressant treatment during opiate withdrawal.
Alcohol and Alcoholism, Nov 1, 1984
The effects of meptazinol and some opioid agonists and antagonists were studied on opioid-naive g... more The effects of meptazinol and some opioid agonists and antagonists were studied on opioid-naive guinea-pig ileum (GPIN) and ileum taken from morphine-dependent guinea-pigs (GPID). Meptazinol produced a biphasic effect in GPIN and GPID with a depression of the electrically induced twitch response at lower concentrations and contractural potentiation at higher concentrations. The effects of meptazinol in both GPIN and GPID were similar, thus distinguishing it from the other opioid agonists and antagonists which produced differential effects on these tissues. In morphine-pelletted rats, meptazinol (5 mg/kg i.p.) did not produce notable withdrawal as measured by behavioural observation. However, meptazinol (30 mg/kg i.p.) enhanced the signs associated with cholinergic activation. It is suggested that meptazinol possesses a cholinergic component and that the morphine-withdrawal signs observed to the higher meptazinol dose were more probably attributable to cholinergic stimulation rather than any underlying opioid-precipitated withdrawal.
Journal of Pharmacy and Pharmacology, Jul 1, 1988
Following subchronic (5-day) dosing with B-HT 920 (2-amino-6-allyl-5,6,7,8-tetrahydro-4H-thiazolo... more Following subchronic (5-day) dosing with B-HT 920 (2-amino-6-allyl-5,6,7,8-tetrahydro-4H-thiazolo(4,5-d)azepine (1 mg kg-1 day-1 i.p.) in rats there was a significant increase in both apomorphine-induced motor activity and stereotypy. On continued B-HT 920 treatment, however, the enhancement of apomorphine motor activity faded into insignificance but the increase in stereotypy persisted beyond 15 days. The results are discussed in terms of dopamine autoreceptor tolerance, postsynaptic D2 supersensitivity and possible differential effects in different brain loci on the above two receptor sub-classes.
Alcohol and Alcoholism, Nov 1, 1984
The acute and subchronic actions of the benzodiazepines triazolam, oxazepam and diazepam have bee... more The acute and subchronic actions of the benzodiazepines triazolam, oxazepam and diazepam have been examined using three behavioural tests. In the accelerating rotarod motor coordination test both diazepam and oxazepam on acute administration produced dose-related discoordination or motor impairment in mice. After chronic administration (50 mg/kg per day i.p. for 14 days) the corresponding dose-response lines were shifted to the right suggesting tolerance development. In a test for conflict behaviour in rats (conditioned suppression of drinking) oxazepam (20 mg/kg i.p.), triazolam (1 mg/kg i.p.) and diazepam (10 mg/kg i.p.) all augmented punished responding rates with no effect on unpunished responses and this has been speculated to reflect anxiolytic activity. These initial elevations in punished responding displayed a gradual decline during repeated daily administration over 20 days, there being little alteration in the unpunished response levels. In separate studies, chronic treatment of mice with triazolam in the drinking water over 30 days showed diminished pentylenetetrazol-induced seizure latencies compared to the level of protection afforded by triazolam at the beginning of the schedule. In additional experiments, mice injected daily with triazolam (1 mg/kg i.p. for 14 days) exhibited a higher seizure susceptibility than their corresponding controls. The results are discussed in relation to tolerance to the anxiolytic, anticonvulsant and neurological impairment properties of benzodiazepines.