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A Dunne

Publications and source records attributed to A Dunne.

At least 19 recordsLinked to original sources
PubMed2002

Dose-response effects of a novel fat emulsion (Olibra) on energy and macronutrient intakes up to 36 h post-consumption.

OBJECTIVE: To investigate the dose-response effects of a novel fat emulsion (Olibra) on energy and macronutrient intakes up to 36 h post-consumption in non-overweight subjects. DESIGN: A single-blind, placebo-controlled, within-subject cross-over design was used. SETTING: Metabolic suite of the University of Ulster, Coleraine. SUBJECTS: Fifty subjects (30 female, 20 male) from the student and staff population of the University of Ulster, Coleraine. INTERVENTIONS: Subjects were given in random order, 7 days apart, a 200 g portion of yoghurt containing a total of 15 g of fat, which varied in quantity of Olibra fat (0, 2, 4, 6 g) at 09:00 h. At 13:00 h subjects were given ad libitum access to a range of foods. Amounts of food consumed were measured by covert pre- and post-consumption weighing of individual serving dishes. For the remainder of the day and the following 24 h, subjects weighed and recorded all food intakes. RESULTS: Relative to the control yoghurt, mean energy (7.42 vs 5.83, 5.60, 5.24 MJ), fat (97.4 vs 74.4, 74.2, 67.5 g; 48.8 vs 46.8, 48.9, 47.6% energy), protein (59.1 vs 50.0, 44.0, 40.8 g; 13.2 vs 13.9, 12.9, 12.8% energy), and carbohydrate (171.5 vs 140.9, 130.2, 126.0 g; 38.0 vs 39.3, 38.2, 39.6% energy), intakes were progressively reduced with increasing doses of Olibra fat in the total group (P<0.001). A similar response was observed in the female group up to 4 g (P<0.001) and in the male group after 2 and 6 g (P<0.05). Energy and macronutrient intakes for the remainder of each study day and over the following 24 h were significantly lower after all dose levels compared to the control (P<0.001). CONCLUSION: The results suggest that Olibra fat reduced the effect of overeating during an ad libitum lunch meal and subsequent food intake up to 36 h post-consumption.

Adult↗
PubMed2001

Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction.

The recognition of microbial pathogens by the innate immune system involves Toll-like receptors (TLRs), which recognize pathogen-associated molecular patterns. Different TLRs recognize different pathogen-associated molecular patterns, with TLR-4 mediating the response to lipopolysaccharide from Gram-negative bacteria. All TLRs have a Toll/IL-1 receptor (TIR) domain, which is responsible for signal transduction. MyD88 is one such protein that contains a TIR domain. It acts as an adapter, being involved in TLR-2, TLR-4 and TLR-9 signalling; however, our understanding of how TLR-4 signals is incomplete. Here we describe a protein, Mal (MyD88-adapter-like), which joins MyD88 as a cytoplasmic TIR-domain-containing protein in the human genome. Mal activates NF-kappaB, Jun amino-terminal kinase and extracellular signal-regulated kinase-1 and -2. Mal can form homodimers and can also form heterodimers with MyD88. Activation of NF-kappaB by Mal requires IRAK-2, but not IRAK, whereas MyD88 requires both IRAKs. Mal associates with IRAK-2 by means of its TIR domain. A dominant negative form of Mal inhibits NF-kappaB, which is activated by TLR-4 or lipopolysaccharide, but it does not inhibit NF-kappaB activation by IL-1RI or IL-18R. Mal associates with TLR-4. Mal is therefore an adapter in TLR-4 signal transduction.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Monocytes harbour replication-competent, non-latent HIV-1 in patients on highly active antiretroviral therapy.

OBJECTIVE: To determine whether HIV-1 can be recovered from blood monocytes as well as resting, memory CD4 T lymphocytes of patients on highly active antiretroviral therapy (HAART) with undetectable plasma viraemia and whether infection is active or latent. DESIGN: Five patients with plasma HIV-1-RNA levels of less than 500 copies/ml for at least 3 months and less than 50 copies/ml at the time of sampling were initially selected, followed by an additional five patients with viral loads of less than 50 copies/ml for 3 months or more. METHODS: Monocytes were isolated from blood by plastic adherence, then further purified by a second adherence step or CD3 depletion before co-culture with CD8-depleted donor peripheral blood mononuclear cells. Virus isolates were examined for mutations conferring resistance to reverse transcriptase or protease inhibitors and for genotype. The highly purified monocytes were also analysed for the presence of proviral and unintegrated viral DNA and multiply spliced (MS) viral mRNA by polymerase chain reaction. RESULTS: Virus was recovered from monocytes of five patients. Sequencing of the recovered viruses did not reveal multiple drug resistance, and was consistent with a non-syncytium-inducing/CCR5 phenotype. Proviral DNA was detectable in monocytes from all subjects, and unintegrated HIV-1 DNA and MS RNA was found in four out of five populations examined. CONCLUSION: Recovery of replication-competent virus from some HAART patients indicates that monocytes can also harbour HIV-1. Detection of circular, viral DNA and spliced RNA, albeit at very low levels, in these cells suggests that their infection is recent and transcriptionally active rather than latent.

Antiretroviral Therapy, Highly Active↗
PubMed2001

Does plasma HIV RNA predict outcome in a cohort of treated HIV-infected individuals followed over 3 years?

BACKGROUND: Despite reductions in AIDS illness and mortality, it is increasingly apparent that a significant proportion of individuals treated with combination antiretroviral (cARV) therapy have continuing or recrudescent HIV RNA in plasma. The predictive value of plasma HIV RNA in treated individual remains uncertain and rates of and risk factors for adverse outcomes such as hospitalisation, opportunistic infections and deaths are needed. OBJECTIVES: The objectives of this study were to establish a retrospective cohort of individuals treated with cARVs, to assess factors associated with detectable HIV RNA and to determine rates of and risk factors for hospitalisation, opportunistic infection and mortality over 3 years of follow-up. STUDY DESIGN: All individuals treated at The Alfred Hospital, Melbourne, Victoria between January and June 1997 who had had plasma HIV RNA measured were included in the retrospective cohort. Clinical, virological and hospitalisation data were recorded and validated by cross-reference with electronically stored laboratory, hospital activity and state notification databases. Outcome was assessed at October 2000. RESULTS: Amongst the 555 individuals tested, 438 (60.7%) had detectable (>500 copies/ml) HIV RNA (bDNA assay, version 2) at baseline. The overall mortality rate was 5.5 per 100 person years; the AIDS rate 1.99 per 100 person years and hospitalisation rate 16.4 per 100 person years. Risk factors for death in this population identified by univariate analysis were HIV RNA concentration at baseline and at follow-up October 2000, nadir and most recent CD4 lymphocyte number, not receiving cARV as initial treatment, total number of ARV agents and number of changes in ARV per year, developing AIDS and being hospitalised during follow-up. In a multivariate model, the most recent CD4 lymphocyte number, the number of different ARVs per year and having more than one hospitalisation remained predictive of death. CONCLUSIONS: HIV RNA remained detectable in the majority (60.7%) of this treatment-experienced population over 3 years, yet mortality rate remained relatively low at 5.5 per 100 person years. Factors associated with death were immunological (CD4 lymphocyte number) and treatment related (numbers of changes of ARV and hospitalisation) rather than virological (HIV RNA) in this cohort. We believe hospitalisation rates may be a useful marker of HIV disease in cARV treated populations and may identify groups at risk of poorer outcome and in need of intervention.

Adult↗
PubMed2001

In vivo-in vitro correlation (IVIVC) modeling incorporating a convolution step.

The purpose of in vivo-in vitro correlation (IVIVC) modeling is described. These models are usually fitted to deconvoluted data rather than the raw plasma drug concentration/time data. Such a two-stage analysis is undesirable because the deconvolution step is unstable and because the fitted model predicts the fraction of a dosage unit dissolved/absorbed in vivo which generally is not the primary focus of our attention. Interest usually centers on the plasma drug concentration or some function of it (e.g., AUC, Cmax). Incorporation of a convolution step into the model overcomes these difficulties. Odds, hazards, and reversed hazards models which include a convolution step are described. The identity model (which states that average in vivo and in vitro dissolution/time curves are coincident or directly superimposable) is a special case of these models. The odds model and the identity model were fitted to data sets for two different products using nonlinear mixed effects model fitting software. Results show that the odds model describes both data sets reasonably well and is a significantly better fit than the identity model in each case.

Cross-Over Studies↗
PubMed2001

The effects of yoghurt containing a novel fat emulsion on energy and macronutrient intakes in non-overweight, overweight and obese subjects.

OBJECTIVE: To investigate the effects of a yoghurt containing a novel fat emulsion on energy and macronutrient intakes up to 8 h post-consumption in non-overweight, overweight and obese subjects, and to assess energy compensation over the following 24 h. DESIGN: A double-blind, placebo-controlled, within-subject crossover design was used. Twenty (10 female, 10 male) non-overweight (body mass index (BMI) 20-24.9 kg/m(2)), 20 (10 female, 10 male) overweight (BMI 25-29.9 kg/m(2)) and 20 (13 female, 7 male) obese (BMI>30 kg/m(2)) subjects participated in the study. Subjects were given in random order, 7 days apart, either a 200 g portion of a test (5 g of a novel fat emulsion+1 g milk fat) or control (6 g milk fat) yoghurt at 09:00 h. At 4 and 8 h post-consumption subjects were given ad libitum access to a range of foods. Amounts of food consumed were determined by pre and post-covert weighing of individual serving dishes. Over the following 24 h subjects weighed and recorded all food intakes. RESULTS: Mean energy intakes were significantly lower after the test yoghurt compared with the control yoghurt in non-overweight (3.79 vs 5.43 MJ; P<0.01) and overweight (4.43 vs 6.12 MJ; P<0.001) subjects 4 h post-consumption and in non-overweight (3.82 vs 5.38 MJ; P<0.001), overweight (3.94 vs 5.80 MJ; P<0.001) and obese (4.91 vs 6.26 MJ; P<0.01) subjects 8 h post-consumption. The corresponding macronutrient intakes were also significantly reduced in non-overweight and overweight subjects (P<0.01) at 4 h post-consumption and in all subjects 8 h post-consumption (P<0.01). In the total group, energy intakes over the following 24 h were also significantly reduced (6.35 vs 7.70 MJ; P<0.01) after the test yoghurt relative to the control yoghurt. CONCLUSIONS: These results suggest that the effects of this novel fat emulsion are maintained at least up to 8 h and are evident in non-overweight, overweight and obese subjects.

Adult↗
PubMed2000

Studies on the specificity of the tetrapyrrole substrate for human biliverdin-IXalpha reductase and biliverdin-IXbeta reductase. Structure-activity relationships define models for both active sites.

A comparison of the initial rate kinetics for human biliverdin-IXalpha reductase and biliverdin-IXbeta reductase with a series of synthetic biliverdins with propionate side chains "moving" from a bridging position across the central methene bridge (alpha isomers) to a "gamma-configuration" reveals characteristic behavior that allows us to propose distinct models for the two active sites. For human biliverdin-IXalpha reductase, as previously discussed for the rat and ox enzymes, it appears that at least one "bridging propionate" is necessary for optimal binding and catalytic activity, whereas two are preferred. All other configurations studied were substrates for human biliverdin-IXalpha reductase, albeit poor ones. In the case of mesobiliverdin-XIIIalpha, extending the propionate side chains to hexanoate resulted in a significant loss of activity, whereas the butyrate derivative retained high activity. For human biliverdin-IXalpha reductase, we suggest that a pair of positively charged side chains play a key role in optimally binding the IXalpha isomers. In the case of human biliverdin-IXbeta reductase, the enzyme cannot tolerate even one propionate in the bridging position, suggesting that two negatively charged residues on the enzyme surface may preclude productive binding in this case. The flavin reductase activity of biliverdin-IXbeta reductase is potently inhibited by mesobiliverdin-XIIIalpha and protohemin, which is consistent with the hypothesis that the tetrapyrrole and flavin substrate bind at a common site.

Animals↗
PubMed2000

Adolescent males' experience of the counselling process.

This study examines 11 adolescent males' self-reports of their experiences of 23 counselling sessions to identify what they found helpful and unhelpful during key moments in the therapeutic process. The findings suggest that the experiences of the adolescent males in this study are similar in many ways to the to the reported experiences of adults in counselling. In particular, the experience of emotional support and relief appears to be highly significant for adolescent males, who give significantly lesser importance to cognitive task factors.

Adolescent↗
PubMed2000

Sociodemographic determinants of perceived influences on food choice in a nationally representative sample of Irish adults.

OBJECTIVE: To identify the most important motivations for food choice from the point of view of the consumer in the Irish population, and to characterize those subjects who do and do not regard nutrition as a significant consideration in food choice. DESIGN: As part of a pan-European Union (EU) survey on consumer attitudes to food, nutrition and health, a quota-controlled, nationally representative sample of Irish adults (n = 1009) aged 15 years upwards, completed an interview-assisted, close-ended questionnaire. Subjects selected three factors, from a list of 15, which they believed had the greatest influence on their food choice. SETTING: The interviews for the survey were conducted in subjects' homes. RESULTS: 'Quality/freshness of food' was the most frequently selected food choice factor (51%) followed by 'taste' (43%) and 'trying to eat a healthy diet' (36%). Female gender, increasing age and higher levels of education were found to be independent sociodemographic factors affecting the selection of 'trying to eat a healthy diet' as an important factor in food choice. CONCLUSIONS: Although included in the top five most frequently selected factors affecting food choice, nutrition/healthy eating does not appear to have top priority for the majority of Irish adults. There are differences between the various sociodemographic groups within the population; males and younger subjects appear to require specific nutrition promotion messages.

Adolescent↗
PubMed2000

The influence of survey duration on estimates of food intakes and its relevance for public health nutrition and food safety issues.

OBJECTIVE: To examine the influence of food consumption survey duration on estimates of percentage consumers, mean total population intakes and intakes among consumers only and to consider its relevance for public health nutrition and food safety issues. DESIGN: Prospective food consumption survey. SETTING: A multicentre study in five centres in the European Union-Dublin, Ghent, Helsinki, Potsdam and Rome. SUBJECTS: Teenage subjects were recruited through schools; 948 (80%) out of 1180 subjects completed the survey. INTERVENTIONS: 14-day food diaries were used to collect the food consumption data. RESULTS: For mean total population intakes, 53% of the foods had slopes significantly different to 0 (P<0.05). In practical terms (g/day), these differences were small, with 41% of foods having differences of </=1 g/day and a further 35% having differences of 1-5 g/day. Estimates of percentage consumers based on 3 days and 14 days were 1.9 and 3.6 times the 1-day estimate, respectively. For 72% of foods, at least 50% of non-consumers on day 1 became consumers over the subsequent 13 days. Estimates of mean consumer only intakes based on 3 days and 14 days were 53% and 32% of the 1 day value. CONCLUSION: In practical terms, survey duration influences estimates of percentage consumers and intakes among consumers only but not mean total population intakes. Awareness of this influence is important for improved interpretation of dietary data for epidemiological studies, development of food-based dietary guidelines and food chemical intakes. SPONSORSHIP: The Institute of European Food Studies, a non-profit research organization based in Trinity College Dublin. European Journal of Clinical Nutrition (2000) 54, 166-173

Adolescent↗
PubMed2000

Short-term effects of yoghurt containing a novel fat emulsion on energy and macronutrient intakes in non-obese subjects.

BACKGROUND: The satiating properties of fat remain poorly understood, particularly with reference to its physicochemical characteristics. OBJECTIVE: To investigate the short-term effects of consumption of yoghurt containing either a novel fat emulsion or normal milk fat, on the energy and macronutrient intakes of non-obese subjects. DESIGN: Two double-blind, placebo-controlled, within-subject crossover studies were conducted three months apart. Twenty-nine (15 F, 14 M) and thirty (16 F, 14 M) subjects participated in Study 1 and Study 2 respectively. In each study, subjects were given in random order, 7 days apart, either a 200g portion of a test (5g of a novel fat emulsion + 1 g milk fat) or control (6g milk fat) yoghurt at 1300 h. At 4h post-consumption subjects were given ad libitum access to a range of foods. Amounts of food consumed by individuals were determined by pre- and post-covert weighing of individual serving dishes. RESULTS: Mean energy intakes were significantly lower after the test yoghurt compared with the control yoghurt in Study 1 (6.4 vs 7.6 MJ; P< 0.001), Study 2 (6.9 vs 7.9 MJ; P<0.001), and for both studies combined (6.7 vs 7.7 MJ; P<0.001). The corresponding fat intakes in Study 1, Study 2 and in the combined studies were all significantly reduced (P< 0.001). Protein and carbohydrate intakes were also significantly reduced in Study 1 (P< 0.05), Study 2 (P< 0.01), and for the combined studies (P< 0.001). CONCLUSIONS: These results suggest that the physicochemical characteristics of small amounts of dietary fat affect short-term satiety.

Adult↗
PubMed2000

Enhancing the capacity of food consumption surveys of short duration to estimate long-term consumer-only intakes by combination with a qualitative food frequency questionnaire.

In principle, a proper risk assessment for a food chemical requires that the time-frame for food chemical intake estimates matches the time-frame for the toxicological assessments upon which the safety statements (ADI, PTWI, etc.) are based. For food additives, the toxicological assessments are based on exposure over a lifetime. While food consumption data cannot be collected over the lifetimes of individuals, the information should reflect habitual intakes as closely as possible. This study investigated the possibility of combining a 3-day food diary with a food frequency questionnaire to estimate mean consumer-only food intakes comparable to estimates based on a 14-day diary. The study population consisted of 948 teenagers and analysis was based on 32 clearly defined foods. For 47% of the foods, the difference was < or = 1 g/day. When expressed as portion sizes, 56% of the foods showed differences representing < 5% of an average portion and no food showed a difference > 14% of an average portion. When between-method differences (portions/day) were plotted against the mean of the methods, the mean between-method difference was 0.02(+/- 0.06) portions/day with limits of agreement of -0.10 to 0.14. This preliminary investigation suggests that the combined 3-day diary and FFQ method provides comparable estimates of mean consumer only intakes to a 14-day diary. Therefore, a qualitative FFQ may be a useful adjunct to a food consumption survey of short duration if estimates of longer term food intakes are required.

Adolescent↗
PubMed1999

A new approach to modelling the relationship between in vitro and in vivo drug dissolution/absorption.

A major goal of the pharmaceutical scientist is finding a relationship between an in vitro characteristic of an oral dosage form and its in vivo performance. One such relationship between drug dissolution (or absorption) in vivo and that in vitro is known as an 'in vitro-in vivo correlation' (IVIVC) whose importance stems from the fact that it may be used to minimize the number of human studies required during product development, assist in setting meaningful in vitro dissolution specifications and justify biowaivers for scale-up and post approval changes. A number of ways of describing an IVIVC have been reported with 'level A' being the most informative and therefore most desirable. In the majority of cases reported to date, both the model and the statistical methods employed for level A IVIVC are very simplistic. The model assumes that the rate and extent of dissolution in vivo are the same as those in vitro. The statistical methods ignore the repeated measures nature of the data and use a response variable as an independent variable without accounting for measurement error. This paper describes some new models which include the simple model as a special case. The modelling approach is based on considering the time at which a drug molecule enters solution (in vitro or in vivo) to be a random variable. The in vitro and in vivo distributions are then related to one another using a proportional odds, proportional hazards or proportional reversed hazards model. The models can be extended by adding a linear time component which describes a time varying relationship. Following the addition of random effects to these structural models in order to account for the repeated measures nature of the data collected, the models may be described as generalized linear mixed effects models. The models were fitted to some data sets using a maximum likelihood based method and the results indicate that these models have potential for describing an in vitro-in vivo relationship which cannot be described using the currently available models.

Absorption↗
PubMed1999

Discussion

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Journal Article↗
PubMed1999

Functional domains of Tat required for efficient human immunodeficiency virus type 1 reverse transcription.

Tat expression is required for efficient human immunodeficiency virus type 1 (HIV-1) reverse transcription. In the present study, we generated a series of 293 cell lines that contained a provirus with a tat gene deletion (Deltatat). Cell lines that contained Deltatat and stably transfected vectors containing either wild-type tat or a number of tat mutants were obtained so that the abilities of these tat genes to stimulate HIV-1 gene expression and reverse transcription could be compared. tat genes with mutations in the amino terminus did not stimulate either viral gene expression or HIV-1 reverse transcription. In contrast, tat mutants in the activation, core, and basic domains of Tat did not stimulate HIV-1 gene expression but markedly stimulated HIV-1 reverse transcription. No differences in the levels of virion genomic RNA or tRNA3Lys were seen in the HIV-1 Deltatat viruses complemented with either mutant or wild-type tat. Finally, overexpression of the Tat-associated kinases CDK7 and CDK9, which are involved in Tat activation of HIV-1 transcription, was not able to complement the reverse transcription defects associated with the lack of a functional tat gene. These results indicate that the mechanism by which tat modulates HIV-1 reverse transcription is distinct from its ability to activate HIV-1 gene expression.

Amino Acid Sequence↗
PubMed1999

Dietary antioxidant supplementation and DNA damage in smokers and nonsmokers.

Deficiencies of antioxidant nutrients have been implicated in the etiology of lung and other cancers. However, most intervention trials with antioxidant nutrients have not shown beneficial effects, and some have indicated that beta-carotene may be deleterious. This randomized, double-blind, placebo-controlled study evaluated the effects of five short-term (4-wk) antioxidant nutrient supplement regimens [ascorbic acid (350 mg), RRR-alpha-tocopherol (250 mg), beta-carotene (60 mg), selenium (80 micrograms as sodium selenite), ascorbic acid (350 mg) + RRR-alpha-tocopherol (250 mg)] on plasma antioxidants and mononuclear leukocyte DNA damage in male smokers (n = 9) and nonsmokers (n = 12). Plasma concentrations of ascorbic acid and tocopherol were significantly increased by supplementation, but there was no significant change in plasma beta-carotene or blood glutathione peroxidase activity after supplementation with beta-carotene or selenium. DNA damage in mononuclear leukocytes, as assessed by comet assay, was not affected by any supplementation regimen. DNA damage, as assessed by 8-hydroxydeoxyguanosine in mononuclear leukocytes, was not influenced by ascorbic acid, alpha-tocopherol, or selenium supplementation in smokers or nonsmokers, but beta-carotene supplementation resulted in significant differences between smokers and nonsmokers in the level of oxidative DNA damage, with decreases in smokers and increases in smokers. This is a further indication of the differential effects of supplemental beta-carotene in smokers and nonsmokers.

Adult↗
PubMed1998

Predicting percentage of individuals consuming foods from percentage of households purchasing foods to improve the use of household budget surveys in estimating food chemical intakes.

OBJECTIVE: To examine the hypothesis that there is sufficient agreement between percentage of households purchasing selected foods using household budget surveys and percentage of individuals consuming these foods as determined in individual-based surveys to allow the former to act as a surrogate for the latter when estimating food chemical intakes using household budget data. DESIGN: Database study. SETTING: Databases from Sweden, The Netherlands. Ireland and the UK. SUBJECTS: 319 foods (Sweden n = 60, The Netherlands n = 80, Ireland n = 90, UK n = 89). RESULTS: Pearson correlations demonstrated a high degree of linear association between % households purchasing and % consumers (r = 0.86). Regression analysis defined a close positive relationship between the two datasets (slope 0.95, intercept +2.74). Across countries, using the regression equation, the % households predicted % consumers to within 5% of the true value for between 33 and 48% of foods and to within 10% for between 53 and 78% of foods. CONCLUSIONS: Values for % households can be used as a crude surrogate for % consumers and can thus play a role in improving estimates of food additive intake.

Adult↗