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Biomedical subjects

A Chesson

Publications and source records attributed to A Chesson.

At least 19 recordsLinked to original sources

Unintended effects and their detection in genetically modified crops.

The commercialisation of GM crops in Europe is practically non-existent at the present time. The European Commission has instigated changes to the regulatory process to address the concerns of consumers and member states and to pave the way for removing the current moratorium. With regard to the safety of GM crops and products, the current risk assessment process pays particular attention to potential adverse effects on human and animal health and the environment. This document deals with the concept of unintended effects in GM crops and products, i.e. effects that go beyond that of the original modification and that might impact primarily on health. The document first deals with the potential for unintended effects caused by the processes of transgene insertion (DNA rearrangements) and makes comparisons with genetic recombination events and DNA rearrangements in traditional breeding. The document then focuses on the potential value of evolving "profiling" or "omics" technologies as non-targeted, unbiased approaches, to detect unintended effects. These technologies include metabolomics (parallel analysis of a range of primary and secondary metabolites), proteomics (analysis of polypeptide complement) and transcriptomics (parallel analysis of gene expression). The technologies are described, together with their current limitations. Importantly, the significance of unintended effects on consumer health are discussed and conclusions and recommendations presented on the various approaches outlined.

Animals↗

Extent of incorporation of hydroxycinnamaldehydes into lignin in cinnamyl alcohol dehydrogenase-downregulated plants.

Down-regulation of cinnamyl alcohol dehydrogenase leads to an accumulation of cinnamaldehydes available for incorporation into the developing lignin polymer. Using electron spin resonance spectroscopy we have demonstrated that the parent radical of 4-hydroxy-3-methoxycinnamaldehyde is generated by peroxidase catalysed oxidation. The extent of radical generation is similar to that of 4-hydroxy-3-methoxycinnamyl alcohol and is increased by further aromatic methoxylation. From the distribution of the electron-spin density, it was predicted that the regiochemistry of 4-hydroxy-3-methoxycinnamaldehyde coupling would be similar to that of the corresponding alcohol, with the possibility of a higher degree of 8-O-4 linkages occurring. These predictions were confirmed by polymerisation studies, which also showed that after radical coupling the alpha,beta-enone structure was regenerated. This suggests that, although the cross-linking and physical properties of cinnamaldeyde rich lignins differ from that of normal lignins, cinnamaldehydes are incorporated into the lignin polymer under the same controlling factors as the cinnamyl alcohols.

Alcohol Oxidoreductases↗

Practice parameters for the evaluation of chronic insomnia. An American Academy of Sleep Medicine report. Standards of Practice Committee of the American Academy of Sleep Medicine.

Chronic insomnia is the most common sleep complaint which health care practitioners must confront. Most insomnia patients are not, however, seen by sleep physicians but rather by a variety of primary care physicians. There is little agreement concerning methods for effective assessment and subsequent differential diagnosis of this pervasive problem. The most common basis for diagnosis and subsequent treatment has been the practitioner's clinical impression from an unstructured interview. No systematic, evidence-based guidelines for diagnosis exist for chronic insomnia. This practice parameter paper presents recommendations for the evaluation of chronic insomnia based on the evidence in the accompanying review paper. We recommend use of these parameters by the sleep community, but even more importantly, hope the large number of primary care physicians providing this care can benefit from their use. Conclusions reached in these practice parameters include the following recommendations for the evaluation of chronic insomnia. Since the complaint of insomnia is so widespread and since patients may overlook the impact of poor sleep quality on daily functioning, the health care practitioner should screen for a history of sleep difficulty. This evaluation should include a sleep history focused on common sleep disorders to identify primary and secondary insomnias. Polysomnography, and the Multiple Sleep Latency Test (MSLT) should not be routinely used to screen or diagnose patients with insomnia complaints. However, the complaint of insomnia does not preclude the appropriate use of these tests for diagnosis of specific sleep disorders such as obstructive sleep apnea, periodic limb movement disorder, and narcolepsy that may be present in patients with insomnia. There is insufficient evidence to suggest whether portable sleep studies, actigraphy, or other alternative assessment measures including static charge beds are effective in the evaluation of insomnia complaints. Instruments such as sleep logs, self-administered questionnaires, symptom checklist, or psychological screening tests may be of benefit to discriminate insomnia patients from normals, but these instruments have not been shown to differentiate subtypes of insomnia complaints.

Chronic Disease↗

Effect of phenolic structures on the degradability of cell walls isolated from newly extended apical internode of tall fescue (Festuca arundinacea Schreb.).

Apical internodes of tall fescue (Festuca arundinacea Schreb. var. Clarine) harvested at flowering were sectioned into 5 or 10 equal parts to study in situ degradability and cell wall composition, respectively. The basal (youngest) section had the greatest primary wall content. Cell walls in the upper (older) sections had the highest xylose/arabinose ratio and lignin content and a lignin rich in syringyl units, all typical of extensive secondary wall development. Almost all of the p-coumaric (p-CA) and about half of the ferulic acid (FA) were released by 1 M NaOH and presumed to be ester-linked. The total FA content was approximately double that of p-CA in all sections other than the youngest with a distribution similar to that of total p-CA. However, the ratio of esterified to ether and ether plus ester linked (Et & Et+Es) FA differed with age. Whereas the esterified form remained essentially constant ( approximately 4.5 g/kg of cell wall), Et & Et+Es ferulate increased with increasing age of the tissue and was significantly related to lignin deposition (r = 0.79, P < 0.01). The extent of cell wall degradation after 48 h of incubation in the rumen was inversely related to maturity, falling from 835 g/kg of dry matter in the youngest section to 396 g/kg in the oldest. Both the rate and extent of cell wall degradation were significantly negatively related to the ratio of xylose to arabinose, lignin content, proportion of syringyl units present in lignin, and concentration of Et & Et+Es FA present. A positive relationship between Et & Et+Es FA was also found, with the rate (P < 0.01) being better correlated than the extent (P < 0.05) of cell wall degradation. Application of the newly extended internode model to fescue produced results consistent with the view that both the lignin content and the extent to which lignin was covalently bound to the other wall polymers crucially influenced the rate and extent of degradation.

Animal Feed↗

The Taskforce 2000 survey on medical education in sleep and sleep disorders.

Previous research has shown evidence of a widening gap between scientific research and clinical teaching in sleep and sleep disorders. To address the deficiencies in current medical education in sleep, the Taskforce 2000 was established by the American Sleep Disorders Association. The present study was undertaken to assess the teaching activities, needs and interests of the membership of the two largest professional sleep societies (American Sleep Disorders Association and Sleep Research Society). Survey instruments included a brief, 5-item postcard survey, which was mailed to all members, followed by an in-depth, 34-item questionnaire, which was completed by 158 respondents from the intitial postcard survey (N = 808). Results indicated that the majority of respondents (65.2%) are currently involved in teaching sleep to medical students or postgraduate trainees, although the average amount of teaching time was only 2.1 hours for undergraduate and 4.8 hours for graduate education in sleep. Teaching of sleep laboratory procedures and clinical evaluation of sleep-disordered patients is limited at either an undergraduate or postgraduate level. The major deficiencies noted were the lack of time in the medical curriculum and the need for better resources and teaching facilities. A large majority of respondents indicated their willingness to be involved in sleep education for physicians, and rated this a high priority for the professional organization.

Curriculum↗

Assessment of the role of diet in cancer prevention.

Population studies have demonstrated a clear relationship between the incidence of various cancers and consumption of different classes of foods, indicating that diet can have a protective effect. Diets, however, contain many hundreds of nutrient and non-nutrient compounds. Moving beyond the generalities provided by population studies requires short-term studies in which diets can be adjusted to test the effects of specific ingredients or compounds. The cost of this approach is the loss of direct outcome measures. Biomarkers related to early events in the cancer process which can show significant change within the duration of a trial, have to substitute. The choice of marker and the ability to validate its use are crucial both to the refining of dietary advice and to the search for the active principles of diet.

Animals↗

Oxidative coupling during lignin polymerization is determined by unpaired electron delocalization within parent phenylpropanoid radicals.

The high degree of selectivity observed in the incorporation of phenylpropanoids into lignin may be a consequence of the influence exerted by methoxyl substituents on the ambident radicals generated during biosynthesis. Since unpaired electron distribution may be regarded as an important factor in determining positional selectivity during oxidative coupling, electron spin resonance spectroscopy and Austin Model 1 molecular computation were used to study the effects of methoxyl substitution on unpaired electron distribution in lignin precursor radicals. The data obtained were used to predict the effect of substitution on coupling and were compared with the linkage types observed in complementary dehydrogenation polymerization studies employing each of the lignin precursors. We report that methoxyl substitution increases unpaired electron density on the phenolic oxygen of the precursor phenylpropanoid radicals and that this subsequently determines the nature of the bond formation during polymerization.

Computer Simulation↗

Low-level EMFs are transduced like other stimuli.

The aims of this study were to test the theory that transduction of low-level electromagnetic fields (EMFs) is mediated like other stimuli, and to determine the false-negative rate of the method used to assess the occurrence of transduction (intra-subject comparison of stimulus and non-stimulus states (ICOS)). A light stimulus was chosen as a basis of comparison because light could be applied and removed at precise time points, similar to the manner in which EMFs were controlled. Subjects exposed to a weak light stimulus during 2-second epochs exhibited alterations in brain electrical activity that were similar to those previously observed in subjects exposed to EMFs. The false-negative rate of the ICOS method was 61%, since it registered an effect in only 39% of the subjects (11/28) whereas all subjects were actually aware of the light. In a second group of subjects that were exposed to 0.8 G (1.5 or 10 Hz), 58% (11/19) exhibited similar alterations in brain activity, as determined using ICOS. Previous measurements in the same subjects using a different method showed that the EMFs actually affected brain electrical activity in all subjects; consequently, the false-negative rate was 42% when an EMF was used as the stimulus. The results suggested that the post-transduction brain electrical processes in human subjects were similar in the cases of EMF and light stimuli, as hypothesized, and that the high negative rate of the ICOS method (here and in previous studies) was composed partly or entirely of false-negative results.

Adolescent↗

The effect of Lactobacillus spp. on the attachment of enterotoxigenic Escherichia coli to isolated porcine enterocytes.

A total of 43 strains of lactobacilli were isolated from the gastrointestinal tract of piglets at the time of weaning. Isolates, grown on solid media, were allocated to strongly adherent or non/weakly adherent groups on the basis of numbers attaching to isolated porcine enterocytes. Strains of Lactobacillus fermentum were disproportionally represented amongst the strongly-adherent strains and Lact. acidophilus and Lact. salivarius amongst the non/weakly-adherent group. Lactobacilli showed significantly better attachment ability when grown on agar than when grown in broth culture. Strongly adherent strains were not found to effect the attachment of enterotoxigenic Escherichia coli to porcine enterocytes, tested under the conditions of exclusion (lactobacilli added to the enterocytes before E. coli), competition (lactobacilli and E. coli added simultaneously) and displacement (E. coli added before lactobacilli). Tests were made with [14C]-labelled E. coli. Suspensions of bacteria and enterocytes were passed through a filter selected to retain enterocytes but pass free bacterial cells. Counts (dpm) obtained from filters after solubilization were taken as a measure of E. coli attachment. Some strains of lactobacilli coaggregated with enterotoxigenic E. coli with K88 fimbriae, but not with a K88-negative mutants strain. These were excluded from the competitive exclusion experiments. In the apparent absence of a direct effect on the association of E. coli with host tissue, removal of potential gut pathogens by aggregation could contribute to the probiotic properties ascribed to lactic acid bacteria.

Animals↗

Electrical states in the rabbit brain can be altered by light and electromagnetic fields.

The effect of low-frequency magnetic fields on the rabbit electroencephalograph (EEG) was studied using a quantitative procedure that permitted statistical evaluation of the response of individual animals. The field conditions used were those predicted by various theories to result in field-animal interactions; light and sham exposure were employed as positive and negative controls, respectively. Sixty-seven percent of the rabbits exhibited changes in the EEG power spectra when light was presented in 2-s epochs; none of the animals responded to sham exposure. When 1 Gauss, 5 Hz, was presented in 2-s epochs, 100% of the animals tested responded to the presence of the field. The rabbits did not respond when the magnetic-field frequency was higher than the physiological range (1-20 Hz) or when it was tuned for resonance of K+. The results showed that an electrical state function may be operationally defined for the rabbit brain, and used to assess the occurrence of an interaction between an animal and external magnetic fields.

Animals↗

Fluoxetine prophylaxis of migraine.

Many patients with severe migraine remain refractory to the current treatment regimens or cannot tolerate the side effects. Since current research implicates serotonin dysregulation in migraine pathogenesis, we investigated in a double blind, placebo controlled study the prophylactic effect of the serotonergic drug fluoxetine. Sixteen subjects were randomly assigned to 8 week fluoxetine treatment and 16 to the placebo group; nine subjects in each group completed the study. Migraine headache scores were obtained for two weeks prior to commencement of treatment, and then for each successive two week period. Zung depression scores were obtained before and after completion of the study. Fluoxetine caused significant reduction in headache scores starting with weeks 3-4 of treatment; there was no significant change with placebo. Depression scores did not differ between groups before treatment, and did not significantly change with either treatment. Fluoxetine appears to be a safe and effective drug for migraine prophylaxis, and deserves further therapeutic trials with larger groups for longer periods of time.

Double-Blind Method↗

Estimation of the potential digestibility and rate of degradation of water-insoluble dietary fiber in the pig cecum with a modified nylon bag technique.

Potential digestibility and rate of degradation of water-insoluble material (WIM) prepared from rutabaga, wheat bran and digesta recovered from the terminal ileum of pigs fed bran- or rutabaga-based diets were measured in the cecum of surgically modified pigs. WIM samples recovered from the cecum after fixed incubation times were analyzed and the rate of total disappearance of organic matter, cellulose, uronic acid and noncellulosic neutral sugars was calculated. Maximum degradation of each WIM occurred within 48 h after incubation and was for rutabaga and its ileal digesta 90 and 70%, respectively, and for bran and bran ileal digesta 55 and 45%, respectively. Cellulose and uronic acid in bran samples did not appear to be degraded, material disappearance being attributable to the loss of noncellulosic neutral sugars. Estimation of potential organic matter digestibility showed rutabaga to be 93%, rutabaga digesta 79%, bran 56% and bran digesta 43% digestible. Fractional rates of digestion in rutabaga samples were significantly faster than in corresponding bran samples. When related to the role of fiber in nutrition the results obtained suggest that cereal fiber would be only slightly modified during gut transit, unlike vegetable fiber in which microbial digestion would probably result in the total destruction of the fiber cell wall matrix.

Animals↗

Glycosidic linkages of swede cell walls and their residues recovered from the terminal ileum of the pig.

The glycosidic linkage pattern of unfractionated swede cell walls was determined by methylation analysis. The main linkages in descending order of concentration were: (1----4)-linked glucose, (1----4)-linked xylose, terminal galactose, (1----4)-linked mannose, terminal arabinose and (1----2)-linked rhamnose. The major branch points were to the O-2 or O-3 atoms of xylose, O-4 of rhamnose and O-6 of glucose. The subsequent degradation of swede cell walls by passage through the small intestine of the pig was studied by quantitative methylation analysis of material recovered from animals cannulated 150 mm before the ileo-caecal junction. In addition to a substantial loss of uronic acid and phenolic material, the proportions of the different glycosidic linkages recovered from the digesta varied greatly from those of the parent material. Pectic polysaccharides had apparent digestibilities in the range of 0.60-0.75 while those of hemicellulosic components varied between 0.15 and 0.57. Glucose units linked 1----4 (with an apparent digestibility of 0.24) accounted for the greatest weight loss of neutral sugars from the cell wall, followed by terminal galactose, terminal arabinose and 2-linked arabinose.

Animals↗

Modifications to swede (Brassica napus L.) anterior to the terminal ileum of pigs: some implications for the analysis of dietary fibre.

The degradation of a swede (Brassica napus L., cv. Danestone) diet anterior to the terminal ileum was studied in two pigs fitted with T-shaped cannulas 150 mm before the ileo-caecal junction. Digestibility was calculated with reference to chromic oxide and polyethylene glycol. In addition to the total loss of free glucose and fructose, there were substantial modifications to cell-wall material recovered in digesta. These included the apparent loss of 46-50% of uronic acid residues, 72-78% of phenolic material and 10-24% of cellulose initially present in the feed, and a partial solubilization of some hemicellulose components. Since 'fibre' recovered at the terminal ileum differed in a number of important respects from ingested fibre, a number of methods for the analysis of dietary fibre were examined to establish (1) the extent to which analysis of feed represented material recovered at the terminal ileum and (2) whether such methods could be applied directly to digesta samples. Results were compared with a complete analysis of water-soluble (620 g/kg dry matter) and water-insoluble (380 g/kg dry matter) fractions of feed. Chemical fractionation techniques gave more reliable quantitative estimates of fibre than in vitro enzymic digestion methods which overestimated fibre. Acid- and neutral-detergent methods both gave too low an estimate of fibre. As none of the methods could allow for the loss of components (particularly pectic polysaccharides) found by sampling at the terminal ileum, none gave an accurate qualitative or quantitative representation of fibre at this point in the gut. It is suggested that, as vegetable fibre recovered at the terminal ileum has already undergone partial hydrolysis, a more dynamic model of dietary fibre, in which the action of gut micro-organisms is considered, may be required to establish possible physiological roles of fibre or fibre components in the digestive tract. Recovery of digesta from sites of interest may be the only way of reliably estimating fibre or specific fibre components at different levels of the gut. This approach to dietary fibre may be impractical when applied directly to humans but the digestive tract of the pig may be a suitable alternative model.

Animal Feed↗

Influence of plant phenolic acids on growth and cellulolytic activity of rumen bacteria.

Isolated rumen bacteria were examined for growth and, where appropriate, for their ability to degrade cellulose in the presence of the hydroxycinnamic acids trans-p-coumaric acid and trans-ferulic acid and the hydroxybenzoic acids vanillic acid and 4-hydroxybenzoic acid. Ferulic and p-coumaric acids proved to be the most toxic of the acids examined and suppressed the growth of the cellulolytic strains Ruminococcus albus, Ruminococcus flavefaciens, and Bacteroides succinogenes when included in a simple sugars medium at concentrations of >5 mM. The extent of cellulose digestion by R. flavefaciens and B. succinogenes but not R. albus was also substantially reduced. Examination of rumen fluid from sheep maintained on dried grass containing 0.51% phenolic acids showed the presence of phloretic acid (0.1 mM) and 3-methoxyphloretic acid (trace) produced by hydrogenation of the 2-propenoic side chain of p-coumaric and ferulic acids, respectively. The parent acids were found in trace amounts only, although they represented the major phenolic acids ingested. Phloretic and 3-methoxyphloretic acids proved to be considerably less toxic than their parent acids. All of the cellulolytic strains (and Streptococcus bovis) showed at least a limited ability to hydrogenate hydroxycinnamic acids, with Ruminococcus spp. proving the most effective. No further modification of hydroxycinnamic acids was produced by the single strains of bacteria examined. However, a considerable shortfall in the recovery of added phenolic acids was noted in media inoculated with rumen fluid. It is suggested that hydrogenation may serve to protect cellulolytic strains from hydroxycinnamic acids.

Journal Article↗

Plant cell wall fractionation and structural analysis.

The structure of the major plant polysaccharides contributing to dietary fiber, their organization within the plant cell wall, and the problems associated with their analysis are briefly reviewed. Alkaline, acidic, and detergent fractionation methods are described and considered in relation to their specificity. The analysis of pectin, often ignored as a component of dietary fiber, is examined in detail. The solubility of pectins from a number of common plant foods was determined, indicating that a considerable portion of pectin polyuronide is lost to many of the commonly used analytical procedures.

Cell Wall↗