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Biomedical subjects

Robert D E Sewell

Publications and source records attributed to Robert D E Sewell.

10 recordsLinked to original sources

The bacterial profile of cotton lint from worldwide origins, and links with occupational lung disease.

BACKGROUND: Byssinosis, the cotton worker's lung disease persists today in many countries. Several agents have been investigated with respect to causality; among these are Gram-negative bacteria. These organisms are a source of lipopolysaccharide toxins, which are potentially hazardous to the respiratory tract. Despite byssinosis being most prevalent in countries where adequate preventive procedures are lacking, the majority of past studies have been conducted on cotton from the United States. METHODS: The current investigation, involved the identification of Gram-negative bacteria from cotton lint samples originating in 12 world regions. RESULTS: The current investigation, involved the identification of Gram-negative bacteria from cotton lint samples originating in 12 world regions. CONCLUSIONS: Building a bacterial profile of cotton samples with worldwide origins will be useful in isolating sources of these organisms, assessing the risk posed to industry, workers and ultimately assisting the prevention of byssinosis and related conditions.

Africa↗

The nootropic and neuroprotective proline-containing dipeptide noopept restores spatial memory and increases immunoreactivity to amyloid in an Alzheimer's disease model.

The effects of the novel proline-containing nootropic and neuroprotective dipeptide, noopept (GVS-111, N-phenylacetyl-L-prolylglycine ethyl ester) were investigated in NMRI mice following olfactory bulbectomy. We have shown previously that these animals developed Alzheimer's disease (AD)-like behaviour, morphology and biochemistry including impairment of spatial memory, regional neuronal degeneration and elevated Abeta peptide brain levels. In the current investigation, spatial memory was assessed using the Morris water maze and serum antibodies to in vitro morphologically characterized amyloid structures of both Abeta((25-35)) peptide and equine lysozyme, as well as to neurotrophic glial factor S100b, were analyzed by enzyme-linked immunosorbent assay (ELISA). Noopept (administered at a dose of 0.01 mg/kg for a period of 21 days and during a further 5 days training) restored spatial memory and increased serum antibody levels to oligomers of Abeta((25-35)) peptide but not to equine lysozyme amyloid or S100b protein in bulbectomized animals. The positive immunotropic effect of noopept to Abeta((25-35)) peptide prefibrillar aggregates was more marked in sham-operated compared to the bulbectomized subjects which were characterized by an overall suppression of immunoreactivity. Enhancement of the immune response to Abeta((25-35)) peptide prefibrils caused by noopept may attenuate the neurotoxic consequences of amyloid fibrillization and also be associated with an improvement in spatial memory in bulbectomized mice. These actions of noopept, combined with its previously reported neuroprotective and cholinomimetic properties, suggests that this dipeptide may well be useful for improving cognitive deficits induced by neurodegenerative diseases.

Alzheimer Disease↗

The fungal profile of cotton lint from diverse sources and implications for occupational health.

There is mounting evidence that inhalation of fungal spores and their fragments and toxins may cause respiratory illness, particularly in indoor environments and industrial settings. However, analysis of these organisms on cotton has not been carried out in detail and, hence, further examination may prove important in identifying sources of these organisms and assessing the risks posed to cotton workers. This study identified fungi from cotton lint samples originating in 12 world regions and revealed six different fungal genera, with the following rank order of sample isolation incidence: Aspergillus > Cladosporium > Fusarium > Rhizopus > Penicillium > Alternaria. Aspergillus was the most common genus and Aspergillus niger in particular was the pecies most frequently identified. Improved understanding of the variety of organisms that contaminate cotton may help to reduce prevalence of organic dust-related lung diseases.

Cotton Fiber↗

Co-administration of fluoxetine and WAY100635 improves short-term memory function.

The aim of this study was to determine whether the action of the antidepressant fluoxetine or the anxiolytic buspirone could be modified by specific 5-hydroxytriptamine (5-HT(1A)) receptor blockade in a short-term memory paradigm. Male Wistar rats were trained to perform the putative short-term memory task, delayed non-matching to position. WAY100635, a selective 5-HT(1A) receptor antagonist (0.15 mg/kg), was administered 15 min before either the selective serotonin reuptake inhibitor fluoxetine (3 mg/kg), or the partial 5-HT(1A) receptor agonist and dopamine D2 receptor antagonist, buspirone (0.3 mg/kg). 8-Hydroxy-di-n-propylamino tetralin (8-OH-DPAT), a full 5-HT(1A) receptor agonist (0.3 mg/kg), was also included in the study as a positive control. WAY100635 alone had no effect on any behavioural parameter measured (response accuracy, delay lever press activity and trial completion). 8-OH-DPAT impaired response accuracy in a delay-dependent manner, an effect reversed by WAY100635. Fluoxetine also impaired response accuracy delay-dependently. WAY100635 pretreatment not only reversed this deficit but improved response accuracy, in the presence of a significant deficit in trial completion. At the dose used, buspirone showed no significant differences compared to the control group. The data suggest that fluoxetine impairs short-term memory function by the indirect activation of 5-HT(1A) receptors, but that its co-administration with WAY100635 improves short-term memory function.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Effect of 2-(4-aminophenylmethyl)-6-hydroxy-3, 4-dihydronaphthalen-1(2H)-one on all-trans and 13-cis-retinoic acid levels in plasma quantified by high perfomance liquid chromatography coupled to tandem mass spectrometry.

The effect of the titled tetralone as a retinoic acid metabolism blocking agent (RAMBA) in vivo in comparison with ketoconazole, a well known cytochrome P450 inhibitor, was studied. Development of a HPLC/MS/MS method for the quantification of retinoic acid levels extracted from rat plasma was used to demonstrate that ketoconazole and the tetralone (100 mg/kg) enhanced the endogenous plasma concentration of retinoic acid. Levels of retinoid were raised from a control value of 0.11 to 0.15 and 0.17 ng/mL after treatment with tetralone and ketoconazole respectively showing that the tetralone and ketoconazole lead to comparable effects, indicating an inhibitory activity of the tetralone on retinoic acid metabolism.

Animals↗

Does the human leukaemia differentiation factor fragment HLDF6 improve memory via brain DNA and protein synthesis?

The novel human differentiating factor peptide fragment HLDF6 (Thr-Gly-Glu-Asn-His-Arg) was synthesized and purified. HLDF6 (0.1mg/kg i.p. but not 1mg/kg i.p.) improved not only long-term (24h) memory in adult rats in the water maze behavioural paradigm but also performance in the delayed matching-to-position (DMTP) task (0.3 and 1.0 but not 0.1mg/kg i.p). Hence, HLDF6 not only enhanced allocentric spatial learning and reference memory (water maze) but also improved temporal, spatial and working memory processes in the DMTP behavioural paradigm. Immunoreactivity blotting analysis of HLDF (the protein precursor of HLDF6) was performed and the following rank order of visual intensities from brain structures was noted: hippocampus cerebral cortex cerebellum hypothalamus striatum. Subsequently, we found that the highest absolute levels of HLDF were expressed in the hippocampus and cerebral cortex as detected by ELISA. We also demonstrated that HLDF6 enhanced [(3)H]-thymidine and [(14)C]-leucine incorporation into whole brain and hippocampal homogenates (maxima occurring within the range 10 (-12)-10 (-6) M) suggesting that this hexapeptide promoted de novo DNA and protein biosynthesis. We discuss this data in terms of their implications for links with other integrative metabolic pathways involving immediate early gene activation which may underpin a potential application for HLDF6 in limiting memory impairments associated with neurodegenerative diseases.

Animals↗

The measurement and health impact of endotoxin contamination in organic dusts from multiple sources: focus on the cotton industry.

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.

Air Pollutants, Occupational↗

Buspirone differentially modifies short-term memory function in a combined delayed matching/non-matching to position task.

This study investigated the action of 5-hydroxytryptamine (5-HT) mimetics on short-term memory function. The objective was to determine whether two closely related tasks could differentiate between partial 5-HT(1A) receptor activation, full 5-HT(1A) receptor activation and generalised enhanced serotonin (5-HT) activity. Male hooded Lister rats were trained to perform an operant-based combined delayed matching/non-matching to position task. Drugs used were: fluoxetine (3 mg/kg, i.p.), a selective 5-HT reuptake inhibitor; the full 5-HT(1A) receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.3 mg/kg, s.c.); and the partial 5-HT(1A) receptor agonist, buspirone (1 mg/kg, i.p.). Buspirone differentially disrupted response accuracy depending on the style of trial. There was no such difference in the case of 8-OH-DPAT, which impaired accuracy in both delayed matching/non-matching to position task, while fluoxetine affected neither. Thus, the findings suggest that partial 5-HT(1A) receptor activation compromises cognitive function to a greater extent than full 5-HT(1A) receptor activation, although a dopaminergic component cannot be excluded since buspirone possesses some dopamine D2 receptor antagonist activity. Furthermore, it suggests that there is a differential role for 5-HT in these two closely related behavioural tasks.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Morphine, cocaine and antidepressant induced motivational activity and midbrain dopaminergic neurotransmission.

Positive motivational properties of opioids, stimulants and serotonin selective reuptake inhibitors have been reported following place preference conditioning. The possibility that these effects are associated with changes in dopamine concentration in the nucleus accumbens or striatum was investigated. Male Wistar rats were place conditioned in a three compartment model to vehicle or drug (morphine 2.5 mg/kg, cocaine 5 mg/kg, sertraline 5 mg/kg or paroxetine 15 mg/kg) alternately for 8 days using a 30 min pre-treatment time. Control animals received saline only. Nucleus accumbens and striatal tissue were dissected 72 h after final drug dose, and the concentration of dopamine and its metabolites determined using high performance liquid chromatography (HPLC). Striatal dopamine D1-like receptor density was also determined through radioligand binding. Significant place preference (P<0.05) was observed with morphine, cocaine and sertraline. Morphine treated subjects showed a significant decrease (P<0.05) in striatal dopamine concentration, whilst cocaine and sertraline treatment resulted in a significant increase in striatal dopamine levels. Nucleus accumbens concentrations of dopamine, and striatal dopamine D1-like receptor density remained unchanged. The changes in striatal dopamine concentrations are consistent with withdrawal from opioid and stimulant compounds, and suggest that place preference conditioning may, in part, result from negative motivational or aversive effects.

3,4-Dihydroxyphenylacetic Acid↗

Correlative measurement of four biological contaminants on cotton lint, and their implications for occupational health.

Four biological contaminants of cotton fibers (gram-negative bacterial cells, endotoxin, fungal cells, and (1-3)-beta-D-glucan) were measured in 13 cotton lint samples from international origins, using traditional microbiological spread plating and adaptation of the Limulus amoebocyte lysate (LAL) assay. Correlations were evaluated using Spearman's rank correlation analyses. Contamination levels ranged from 713 +/- 212 to 216,830 +/- 30,413 CFU/g gram-negative bacteria; 281 +/- 29 to 9,250 +/- 820 CFU/g fungal cells; 8.30 +/- 0.89 to 137.89 +/- 21.55 ng/g endotoxin; and 15.96 +/- 5.18 to 2,964.42 +/- 313.90 LAL-reactive units/g glucan. Positive correlations existed between all contaminants; however, they were significant only between fungal cells and glucan (p < 0.05) and between endotoxin and glucan (p < 0.01). The highly significant positive correlation between endotoxin and glucan has implications for the health risk posed by the cotton-production environment, as simultaneous inhalation of these agents may cause or exacerbate lung inflammation.

Cotton Fiber↗