The purpose with this study was to investigate the effect of a carbohydrate (CHO) mouth rinse protocol on simulated cross country (XC) sprint. The primaryaim was to investigate ifa 10 secCHO solutionmouth rinsingprotocolimprovedthe finish timein a simulated cross country (XC) sprint(800 meters for female and 1000 meters for male) compared with control (CON).The second aim was to examif post-finish blood lactateconcentrationwouldbe lowercompared with CONwith mouth rinsing. Seven participants(four males and three females)completed four simulated sprints, two CON and two experimentalrinse protocols, CHO solution and placebo (PLA).Time to completion was not different with CHO compared with CON or PLA (203.0 ±16.5 sec, 202.3 ± 15.7 sec, 203.3 ± 14.6respectively.p >.05).Mean power output was CON 264 ± 73, PLA 258 ± 65, CHO 261± 70.Blood lactateat 15 minweresimilar between CHO, CON and and PLA(9.9 ± 3.9 mmol 7.6 ± 4.0 mmol, 10.1 ± 3.7 mmol respectively.p >.05).We concludethat mouth rinsing a CHO solutionfor 10 sechave no effect on high intensity exercise with duration lasting between 3 and 4 minutes.

The goal of this project is to synthesize and purify a library of novel 4-alkyl-3,5-diamino-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazoles. These molecules are similar to other fiproles, which have been shown by Sammelson et al. to have pesticidal activities at the GABA receptor.' Fiproles are analogues of Fipronil, a very important pesticide. Replacing the cyano group normally located at the 3-position of the pyrazole ring with an amino group will change the binding potency of the phenylpyrazoles. Changes in binding produced by the changes introduced in molecular structure can create more information about the GABA receptor.Synthesis of our target compounds starts with production of monosubstituted malononitriles. Conventionally a two-step process, our research developed a new, efficient one-step process using borohydride as the only reagent. We utilized this method in the synthesis of desired monosubstituted malononitriles. These were converted to unsymmetrical disubstituted malononitriles, and to our target fiprole compounds, through a 4-alkyl-3,5-diaminopyrazole intermediate. / Department of Chemistry

The recognition of MHC-peptide ligands by the T cell receptor (TCR) is central to the induction of the adaptive immune response. This thesis describes the development of a bioassay for TCR recognition which was then used to undertake a molecular analysis of the TCR/MHC-peptide interaction. 1. A TCR-CD3ϛ chimeric receptor was stably expressed in the cell line RBL-2H3 to give the transfectant RBL-008. RBL-008 was shown to exhibit MHC-restricted peptide-specific responses to both cellular and multimerised recombinant HLA-A2-pol peptide targets (Chapter 3). 2. By competitively inhibiting the response of RBL-008 to HLAA2 pol complexes with monovalent soluble recombinant MHCpeptide complexes it was confirmed that the TCR makes significant contact with both the MHC and peptide parts of its ligand. Furthermore it was found that only a few peptides in a random mixture can prevent contact between the TCR and HLA-A2. This has implications for positive selection since it supports evidence suggesting that some TCRs can be selected on a wide range of unrelated peptides (Chapter 4). 2. The bioassay was used to examine the flexibility of TCRpeptide interactions using a panel of variant peptides designed on the basis of the previously published HLA-A2-pol peptide structure (Chapter 5). Several variant peptides were recognised by the TCR and interestingly one of these altered peptide ligands was actually recognised better than the index peptide, raising the prospect of designing 'improved epitopes'. 3. By mutating the β chain of TCR-CD3ϛ chimeric receptor it was shown that allelic variation in the TCR genes can have a significant effect on antigen recognition and may therefore be disease susceptibility candidates genes (Chapter 6). 4. The structural relationship between the V and C domains of the TCR was examined and found to be of considerable functional significance since disruption of this relationship resulted in loss of expression of the TCR-CD3ϛ receptor.

No description available.

I studied how glutamate receptor-mediated responses, spatial arrangements, intrinsic properties and molecular specificity of cells serve cortical functions. I tested whether two somatosensory submodalities in the primary somatosensory (SI) cortex can be distinguished by glutamate receptor involvement in vivo. Low-threshold responses evoked by innocuous stimuli had a short-duration and long-duration component. The short-duration responses were mostly mediated by AMPA/kainate receptors and the long-duration responses involved the additional recruitment of NMDA receptors. High-threshold responses evoked by noxious stimuli were unimodal and mediated by both AMPA/kainate and NMDA receptors throughout the entire response. During noxious stimulus trials, an increase in baseline activity in SI cortical cells was observed. I attribute the changes in baseline activity to cells in the medial thalamic nuclei, which project to the SI cortex and are involved in the affective-motivational aspects of nociceptive signalling. To gain insight into the influence of synaptic organisation of a well-defined cortical area, I studied in vitro whether the intrinsic properties of two anatomically well-defined nonpyramidal cells in the hippocampus can provide clues into the modulation of neuronal signalling. During a depolarising current pulse, O-LM and O-Bi cells were distinguished by their accommodation of action potentials depending on the early or late part of the response. Also, during a hyperpolarising current pulse, O-LM cells displayed a prominent voltage 'sag' as compared to O-Bi cells. Both cell types contain somatostatin and I showed that O-LM cells express the metabotropic glutamate receptor type 1α. Although O-LM and O-Bi cells have a similar somatodendritic position their different axonal arbours imply that they are involved in the feedback modulation of the entorhinal and CA3 glutamatergic influences, respectively. I also found that contrary to previous reports not only somatostatin but also vasoactive intestinal polypeptide containing cells express mGluR1α, which might facilitate their oscillatory responses. To relate the action potential discharge of specific cortical cell classes to behaviourally relevant network activity, I also sought to identify hippocampal cells following in vivo recording. Novel information was provided for both the temporal and anatomical properties of cells not recorded previously. In particular, a putative interneuron targeting nonpyramidal cell and backprojection cell was recorded in relation to theta field events. A novel nonpyramidal projection cell was recorded in relation to sharp wave field events. A remarkable specificity was found in the dendritic and axonal patterns of these cells. The results show that distinct types of glutamate receptors are differentially involved in cortical function. The intrinsic properties and expression of mGluR1α in particular is highly specific in distinct nonpyramidal cell classes.

No description available.

Bisphenol A (BPA) is an estrogen receptor binding chemical, widely used in the plastics industry, and as such commonly encountered from plastic containers etc. Even at very low doses, BPA is believed to induce obesity and to have various endocrine disruptive effects. The purpose of this study was to determine possible gene expression changes in gonadal and inguinal adipose tissue from rats perinatally exposed to BPA. The method used was quantitative real-time PCR, and genes found to be up-regulated were PLZF, adiponectin, RXRa and Tcf21, while down-regulated genes were PPARγ, Tmem26, EsR1, Resistin, LPL, Chemerin, Serpina6, TFAM and Ahr. This is so far largely unsupported by other studies, and more research is needed.

Buprenorphine is a promising medication for the treatment of opiate abuse. The pharmacology of buprenorphine has been studied in vitro using radioligand binding and [³⁵S]GTPγS assays, and in vivo using assays of antinociception in rodents. A number of compounds with potential similar pharmacology have also been characterised. These are an iso-morphinan pyrrolidine derivative, and long-lasting 14-aminomorphinones and codeinones, in particular clocinnamox (C-CAM), a pure μ-antagonist and methoclocinnamox (MC-CAM), which has some agonist properties.

Pontomesencephalic tegmental cholinergic neurons were destroyed in cats by local injections of kainic acid in order to assess the role of these neurons in sleep-wakefulness states and in the defining variables of these states: EEG (electroencephalographic) and EMG (electromyographic) amplitude, PGO (ponto-geniculo-occipital) spike rate, REMs (rapid eye movements) and (OBS) olfactory bulb spindles. Loss of cholinergic innervation to forebrain and brainstem structures was also assessed by histochemistry. Histological and histochemical analysis of the brains after the lesion showed a major destruction of the pontomesencephalic cholinergic neurons and a major loss of innervation to thalamic nuclei and brainstem regions, including the reticular formation. Whereas the states of waking and slow wave sleep were relatively unaffected, paradoxical sleep (PS) was reduced or eliminated immediately following the lesions. Two to three weeks later, incipient PS-like episodes returned with a reduced PGO spike rate and REMs, and an elevated EMG amplitude, marking the loss of muscle atonia. Such results suggest pontomesencephalic cholinergic neurons and their projections to thalamic and brainstem regions are important for the expression of PS and its defining variables.

CAR (for C&barbelow;oxsackievirus and A&barbelow;denovirus R&barbelow;eceptor) is a novel member of the Ig superfamily, which has recently been identified as a high affinity receptor for both Coxsackievirus and certain adenovirus (AV) serotypes. Virus bound by CAR is believed to be passed to integrins which bind an RGD (Arg-Gly-Asp) sequence in the viral penton base protein and act as secondary receptors responsible for virus internalization. / Recent studies have shown that, in integrin-expressing cells, CAR-mediated AV uptake does not require the cytoplasmic (CP) domain of CAR, presumably because virus bound to the CAR extracellular (EC) domain can be passed to integrins for subsequent internalization. It has however also been reported that CAR can directly mediate AV uptake in the absence of penton base RGD-alphav integrin interactions. I therefore attempted to determine whether the CP domain of CAR is required for CAR-mediated AV uptake in cells which do not express integrins, or in which integrin function has been blocked by RGD-containing peptide. / As CAR is the primary AV receptor and integrins are secondary AV receptors I investigated the possibility that these proteins associate in a functional complex in the cell membrane. (Abstract shortened by UMI.)