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Biomedical subjects

Helen Scott

Publications and source records attributed to Helen Scott.

At least 19 recordsLinked to original sources
PubMed2006

TGFbeta1 regulates the inflammatory response during chronic neurodegeneration.

The ME7 model of murine prion disease shows an atypical inflammatory response characterized by morphologically activated microglia and an anti-inflammatory cytokine profile with a marked expression of TGFbeta1. The investigation of the role of TGFbeta1 during a time course disease shows that its expression is correlated with (i) the onset of behavioral abnormalities, (ii) increased activated microglia, (iii) thickening of the basement membrane, and (iv) is associated with increased PrP(sc) deposition. Increasing TGFbeta1 using an adenoviral vector has no significant impact on prion-associated behavioral impairments or on neuropathology. In contrast, inhibition of TGFbeta1 activity using an adenovirus expressing decorin induces severe cerebral inflammation, expression of inducible nitric oxide synthase and acute neuronal death in prion-diseased animals only. These data suggest that TGFbeta1 plays a critical role in the downregulation of microglial responses minimizing brain inflammation and thus avoiding exacerbation of brain damage.

Animals↗
PubMed2005

Developmental changes in AMPA and kainate receptor-mediated quantal transmission at thalamocortical synapses in the barrel cortex.

During the first week of life, there is a shift from kainate to AMPA receptor-mediated thalamocortical transmission in layer IV barrel cortex. However, the mechanisms underlying this change and the differential properties of AMPA and kainate receptor-mediated transmission remain essentially unexplored. To investigate this, we studied the quantal properties of AMPA and kainate receptor-mediated transmission using strontium-evoked miniature EPSCs. AMPA and kainate receptor-mediated transmission exhibited very different quantal properties but were never coactivated by a single quantum of transmitter, indicating complete segregation to different synapses within the thalamocortical input. Nonstationary fluctuation analysis showed that synaptic AMPA receptors exhibited a range of single-channel conductance (gamma) and a strong negative correlation between gamma and functional channel number, indicating that these two parameters are reciprocally regulated at thalamocortical synapses. We obtained the first estimate of gamma for synaptic kainate receptors (<2 pS), and this primarily accounted for the small quantal size of kainate receptor-mediated transmission. Developmentally, the quantal contribution to transmission of AMPA receptors increased and that of kainate receptors decreased. No changes in AMPA or kainate quantal amplitude or in AMPA receptor gamma were observed, demonstrating that the developmental change was attributable to a decrease in the number of kainate synapses and an increase in the number of AMPA synapses contributing to transmission. Therefore, we demonstrate fundamental differences in the quantal properties for these two types of synapse. Thus, the developmental switch in transmission will dramatically alter information transfer at thalamocortical inputs to layer IV.

Animals↗
PubMed2004

A comprehensive evaluation of food fortification with folic acid for the primary prevention of neural tube defects.

BACKGROUND: Periconceptional use of vitamin supplements containing folic acid reduces the risk of a neural tube defect (NTD). In November 1998, food fortification with folic acid was mandated in Canada, as a public health strategy to increase the folic acid intake of all women of childbearing age. We undertook a comprehensive population based study in Newfoundland to assess the benefits and possible adverse effects of this intervention. METHODS: This study was carried out in women aged 19-44 years and in seniors from November 1997 to March 1998, and from November 2000 to March 2001. The evaluation was comprised of four components: I) Determination of rates of NTDs; II) Dietary assessment; III) Blood analysis; IV) Assessment of knowledge and use of folic acid supplements. RESULTS: The annual rates of NTDs in Newfoundland varied greatly between 1976 and 1997, with a mean rate of 3.40 per 1,000 births. There was no significant change in the average rates between 1991-93 and 1994-97 (relative risk [RR] 1.01, 95% confidence interval [CI] 0.76-1.34). The rates of NTDs fell by 78% (95% CI 65%-86%) after the implementation of folic acid fortification, from an average of 4.36 per 1,000 births during 1991-1997 to 0.96 per 1,000 births during 1998-2001 (RR 0.22, 95% CI 0.14-0.35). The average dietary intake of folic acid due to fortification was 70 μg/day in women aged 19-44 years and 74 μg/day in seniors. There were significant increases in serum and RBC folate levels for women and seniors after mandatory fortification. Among seniors, there were no significant changes in indices typical of vitamin B12 deficiencies, and no evidence of improved folate status masking haematological manifestations of vitamin B12 deficiency. The proportion of women aged 19-44 years taking a vitamin supplement containing folic acid increased from 17% to 28%. CONCLUSIONS: Based on these findings, mandatory food fortification in Canada should continue at the current levels. Public education regarding folic acid supplement use by women of childbearing age should also continue.

Journal Article↗
PubMed2004

Economic cost of community-acquired pneumonia in New Zealand adults.

AIMS: The aim of this study was to evaluate the economic cost of community-acquired pneumonia (CAP) in New Zealand adults. Although this is an important illness, there is little published information on the national costs of treatment. Without such information, new treatment options cannot be evaluated in economic terms. METHODS: Costs were estimated from a societal perspective for the adult population (aged 15 years and over) using New Zealand age-specific hospital admission rates (average of 2000-2002), population data (2003), and unit costs (2003) in combination with international data on the proportion of pneumonia cases hospitalised. Univariate and multivariate sensitivity analyses were used to determine the major cost drivers and evaluate uncertainty in the estimates. RESULTS: It was estimated that in 2003 there were 26,826 episodes of pneumonia in adults; a rate of 859 per 100,000 people. The annual cost was estimated to be 63 million dollars, (direct medical costs of 29 million dollars; direct non-medical costs of 1 million dollars; lost productivity of 33 million dollars). CONCLUSIONS: The major generators of costs for community-acquired pneumonia are the number of hospitalisations (particularly for the group aged 65 years and over) and loss of productivity. Intensified prevention and effective community treatment programmes focussing on the 65 years and older age groups should be investigated (as they have the greatest potential to reduce healthcare costs).

Adolescent↗
PubMed2003

Dissociation of high-affinity cocaine analog binding and dopamine uptake inhibition at the dopamine transporter.

Cocaine initiates its euphoric effects by binding to the dopamine transporter (DAT), blocking uptake of synaptic dopamine. It has been hypothesized that the DAT transmembrane aspartic acid residue D79 forms an ionic interaction with charged nitrogen atoms in both dopamine and cocaine. We examined the consequences of novel and previously studied mutations of the D79 residue on DAT uptake of [3H]dopamine, DAT binding of the cocaine analog [3H]WIN 35,428, and drug inhibition of each process, all under identical conditions. The rat D79E DAT mutation decreased dopamine uptake Vmax by 7-fold and decreased dopamine turnover by 4-fold. Wild-type DAT displayed near-perfect agreement in the uptake and binding inhibition potencies for substrates, but cocaine and other nonsubstrate inhibitor drugs were approximately 3-fold less potent in uptake than in binding assays. Apparent affinities for substrates were unaffected by the D79E mutation unless the catechol moiety was modified. Strikingly, potencies for nonsubstrate inhibitors in uptake and binding assays matched for D79E DAT, because of a 3-fold lowering of binding affinities relative to WT DAT. The present findings reveal a complex role for D79 in determining substrate specificity and high-affinity binding of DAT inhibitors. We propose that at least two discrete inhibitor-binding DAT conformations or populations exist and that the DAT conformation/population responsible for inhibitor high-affinity binding is less responsible for dopamine uptake. The findings may be extensible to other psychostimulants and antidepressants that display discrepancies between binding affinity and monoamine uptake inhibition potency and may be relevant to development of a long-sought "cocaine antagonist".

Animals↗
PubMed2002

Preventing avoidable hospital admission of older people.

The National Service Framework for Older People (Department of Health, 2001) stresses the importance of preventing unnecessary hospital admissions for older people. Such admissions arise when there is inadequate health and social support available in the community to meet the needs of this age group. This article reports on a study designed to evaluate the effectiveness of a programme of enhanced primary care support intended to reduce the risk of hospital admission for people aged 75 years and above. Nineteen patients out of a possible 322 in one GP practice were judged by GPs and district nurses to be "at risk" of avoidable hospital admission. All at-risk patients were visited by a GP or district nurse to review their needs for enhanced support, six patients subsequently accepting a referral for additional support. No statistically significant difference in the number of hospital admissions in the intervention group was observed compared with a group of patients with similar demographic characteristics but deemed not to be at such high risk, suggesting that the intervention might have been effective in reducing the number of avoidable hospital admissions.

Aged↗