Academic literature on the topic 'Physiology (medical)'

The blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) signal is one of the most recently developed imaging techniques used to identify localized changes in brain activity. The BOLD signal is a function of cerebral blood flow (CBF), the cerebral metabolic rate of oxygen consumption (CMRO2), and cerebral blood volume (CBV). Normally coupled changes in these physiological parameters during regional increases in neural activity will result in BOLD signal increases. This makes the BOLD signal useful as a tool for identifying areas of increased neural activity. Moreover, it can also be used to infer changes in neurophysiology as a response to certain stimuli in the healthy brain, in individuals with certain neurological conditions affecting the cerebrovasculature and under the effect of some types of drugs. There is a major challenge to be faced when using the BOLD signal to study neurophysiological changes that occur under the effect of certain drugs or in the case of neurovascular disease. Under these circumstances, the underlying physiology and normally coupled vascular/metabolic response to a stimulus will be altered. Consequently, changes seen in the BOLD signal during regional increases in neural activity may not be associated with the same neurovascular changes that would occur in the healthy brain. Caffeine is an example of a widely used drug which has been shown to elicit such changes in the neurophysiological state. Two experiments were performed on a group of healthy volunteers in order quantify the effects of caffeine on both baseline neurophysiology and the BOLD signal changes evoked during a visual stimulus. The first involved the measurement of the oxygen extraction fraction(OEF) by performing venous blood magnetic resonance (MR) relaxometry and the second, the measurement of the BOLD and CBF response to a visual stimulus. The results obtained demonstrate that after caffeine consumption there is an increase in baseline OEF (OEF0) and a decrease in baseline CBF (CBF0), but a non-significant change in baseline CMRO2 (CMRO2,0). The caffeine-induced change in the individual BOLD and CBF response to a visual stimulus was found to correlate negatively with individual caffeine-induced change in CBF0. However, the average percent change in visually evoked BOLD and CBF signals across all subjects remained unaltered following caffeine consumption, whereas the CMRO2 response to a visual stimulus was found to increase.<br>L'effet BOLD (blood oxygenation level dependent) est l'une des plus récentes techniques d'imagerie par résonance magnetique (IRM) utilisée pour identifier les changements localisés d'activité cérébrale. Le signal BOLD varie en fonction de la circulation sanguine cérébrale (CBF), du taux métabolique cérébral de la consommation d'oxygène (CMRO2), et du volume sanguin cérébral (CBV). Les changements normalement-couplés de ces paramètres physiologiques lors d'une augmentation régionale d'activité neurale causeront une augmentation du signal BOLD. Cela rend le signal BOLD utile comme outil pour identifier les régions d'augmentation de l'activité neuronale. Deplus, le signal BOLD permet de déterminer quels changements neurophysiologiques suivent certains stimulus dans les cas suivants : le cerveau sain; le cerveau de personnes atteintes d'affections neurologiques affectant la cérébrovasculature; et le cerveau sous l'effet de certains types de médicaments. Un défi majeur se présente lorsque le signal BOLD est utilisé pour étudier les changements neurophysiologiques se produisant sous l'effet de certains médicaments ou en cas de maladie neuro-vasculaire. Lors de ce type d'utilisation, la physiologie sous-jacente et la réponse normalement-couplée vasculaire/métabolique à un stimulus est altérée. Par conséquent, les changements observés dans le signal BOLD au cours des augmentations régionales d'activité neuronale ne correspondent pas aux changements neurovasculaires qui se produisent normalement dans le cas du cerveau sain. La caféine est un médicament couramment utilisé qui a suscité de tels changements dans l'état neurophysiologique. Deux expériences ont été réalisées sur un groupe de volontaires sains dans le but de quantifier les effets de la caféine sur la neurophysiologie de base et les changements évoqués sur le signal BOLD lorsd'un stimulus visuel. La première expérience mesure la fraction de l'extraction d'oxygène (OEF) en effectuant de la relaxométrie par résonance magnetique sur le sang veineux. La deuxième expérience mesure la réponse du signal BOLD et CBFà un stimulus visuel. Les résultats montrent que, après la consommation de caféine il y a une augmentation de l'OEF, une augmentation de la réponse du CMRO2 au stimulus visuel, une diminution de la CBF de base (CBF0) et un changement non-significatif du CMRO2 de base (CMRO2,0). On observe une corrélation négative entre les changements générés par la consommation de caféine sur les réponses du signal BOLD et de la CBF au stimulus visuel et les changements générés par la consommation de caféine sur la CBF0. Néanmoins, en moyenne, la consommation de caféine ne génére aucun changement sur la réponse du signal BOLD et de la CBF au stimulus visuel.

The experiments described in this thesis comprise a series of related, yet independent investigations examining the physiological and metabolic responses of well-trained amateur cyclists under conditions designed to mimic actual competitive situations, during individual and mass start races. In Section A the physiological responses to constant load and steady state exercise are determined. In Section B, the metabolic factors associated with constant and variable load cycling performance are examined.

Bibliography<br>Thesis (MScMedSc (Biomedical Sciences. Medical Physiology))--University of Stellenbosch, 2010.<br>ENGLISH ABSTRACT: Male infertility is often associated with impaired sperm motility and morphology (asthenoteratozoospermia) for which there is no specific therapeutic treatment. It has come to light that the modification and expression of human sperm proteins play a crucial role in sperm function. In the present study, we present proteomic data of human spermatozoa in the context of sperm dysfunction. Novel techniques have been used to successfully isolate and identify differences in protein expression on a cellular level associated with asthenoteratozoospermia. In the first part of the study, differences in protein expression within the total sperm proteome were investigated between immature and mature sperm populations. Semen was collected from healthy donors (n=23) and separated into mature and immature sperm populations by 3-layer Percoll gradient centrifugation. Cells were washed and motility and morphology were measured by computer assisted sperm analysis (CASA). For the proteomic investigation cells were lysed and proteins separated by means of two-dimensional gel electrophoresis (2D electrophoresis). PD-Quest was used to identify the differentially expressed proteins. The protein spots of interest were excised and subjected to in-gel digestion. Peptides were separated by High Pressure Liquid Chromatography (HPLC) analysis and amino acid sequences determined by mass spectrophotometry. Proteins were identified by Mascot, using the Swiss Prot database. The results show that the motility (immature; 26.1±1.75% total motile cells vs. mature; 60.93±3.24% total motile cells; p<0.001) and morphology parameters (immature; 64.1±2.75% normal head morphology vs. mature; 87.63±3.24% normal head morphology; p<0.001) of the two populations differed significantly. After 2D electrophoresis, 16 differentially expressed protein spots were identified within the total sperm proteome between the immature and mature sperm populations. 56% of the differentially expressed proteins were more abundant in the immature sperm population compared to the mature sperm population. Functions have been ascribed to these proteins of which only four proteins, namely Tubulin -3C/D chain, Tubulin -2C chain, Outer dense fibre protein 2 and A-Kinase anchoring protein 4 precursor, were directly related to sperm motility and morphology. In the second part of the study the expression of nuclear proteins in human spermatozoa was investigated between immature and mature sperm populations. Semen was collected from healthy donors (n=156) and further separated from the seminal plasma by PureSperm® gradient centrifugation. The immature and mature sperm populations were retrieved and used during further analysis. For the proteomic analysis of nuclear proteins, cells were fractionated into four different subcellular protein fractions, instead of analyzing the whole sperm proteome. The results show that the motility (immature; 32.33±0.51% total motile cells vs. mature; 88.67±0.85% total motile cells; p<0.0001) and morphology parameters (immature; 13.51±0.87% normal head morphology vs. mature; 20.89±1.20% normal head morphology; p<0.0001) of the two populations differ significantly. After 2D electrophoresis, 21 differentially expressed nuclear proteins were identified between the immature and mature sperm populations. 95% of the differentially expressed nuclear proteins were less abundant in the immature population compared to the mature population. Only one nuclear protein namely 78kDa Glucose regulated protein was more abundant in the immature population compared to the mature population. Functions ascribed to these individual proteins were directly related to sperm motility, morphology and energy metabolism. In conclusion,In conclusion, in the current study novel techniques have been employed to investigate protein differences between immature and mature sperm populations. From these results it is evident that protein expression in the total sperm proteome and nuclear protein fraction is significantly different and incomplete in the immature population, compared to mature population. Based on these findings, it is recommended that further studies should be done on human spermatozoa to validate the role of the individual proteins in sperm function. Proteomics is an ideal tool to identify idiopathic causes of male infertility, as it can help to identify novel receptors (and signal transduction pathways) that can be used in the screening of drugs to alleviate sperm dysfunction.<br>AFRIKAANSE OPSOMMING: Manlike infertiliteit word dikwels geassosieer met verlaagde sperm motiliteit en morfologie (asthenoteratozoospermia) waarvoor daar tot dusver nog geen spesifieke terapeutiese behandeling is nie. Dit het aan die lig gekom dat die modifisering en uitdrukking van menslike sperm proteïene ‘n belangrike rol speel in spermfunksie. In die huidige studie stel ons data voor van proteiene in menslike sperme in die konteks van abnormale spermfunksie. Unieke tegnieke was gebruik om verskille in proteïen uitdrukking op sellulêre vlak suksesvol te isoleer en identifiseer wat verband hou met asthenoteratozoospermia. Tydens die eerste deel van die studie was verskille in proteïen uitdrukking binne die totale spermproteoom tussen onvolwasse en volwasse spermpopulasies ondersoek. Sperme van gesonde skenkers (n=23) is geskei in twee spermpopulasies (onvolwasse en volwasse sperme) deur middel van ‘n 3-laag Percoll gradiënt sentrifugasie tegniek. Selle is gewas en sperm motiliteit en morfologie is gemeet deur rekenaar geassisteerde sperm analise (CASA). Vir proteomiese analise is selle geliseer en proteïene geskei deur twee dimensionele gel elektroforese (2D-elektroforese). PD-Quest sagteware is gebruik om statisties beduidende proteïen verskille aan te dui. Die proteïene van belang is uitgesny en onderwerp aan in-gel vertering. Peptiede is geskei met behulp van hoë druk vloeistof chromatografie (HPLC) analise en aminosuurvolgordes is bepaal deur massa spektrofotometrie. Proteïene is geïdentifiseer met behulp van Mascot deur van die Swiss Prot databasis gebruik te maak. Die resultate toon dat die sperm motiliteit (onvolwasse; 26.1±1.75% totale motiele selle vs. volwasse; 60.93±3.24% totale motiele selle; p <0,001) en morfologiese parameters (onvolwasse; 64.1±2.75% normale kop morfologie vs. volwasse; 87.63±3.24% normale kop morfologie; p <0,001) tussen die twee populasies beduidend verskil. Na 2Delektroforese is 16 proteïen kolle geïdentifiseer wat beduidend verskil het, tussen die totale sperm proteoom van onvolwasse spermpopulasies en volwasse spermpopulasies. 56% van die proteïene wat beduidend verskil het, was meer uitgedruk in die onvolwasse spermpopulasie ten opsigte van die volwasse sperm populasie. Funksies is toegeskryf aan hierdie proteïene waarvan net vier proteïene naamlik Tubulin -3C/D ketting, Tubulin -2C ketting, Buite digte vesel proteïen 2 en A-Kinase anker proteïen 4 voorloper direk verband hou met sperm motiliteit en morfologie. In die tweede deel van die studie is die uitdrukking van nukluêre proteïene in menslike spermatozoa tussen onvolwasse en volwasse spermpopulasies ondersoek. Sperme was van gesonde skenkers (n=156) versamel en verder geskei van seminale plasma deur middel van ‘n PureSperm® gradiënt sentrifugasie tegniek. Vir die proteomiese analise van nukluêre proteïene is selle gefraksioneer in vier verskillende sub-sellulêre proteïen fraksies, in plaas van analise van die totale spermproteoom. Die resultate toon aan dat die sperm motiliteit (onvolwasse; 32.33±0.51% totale motiele selle vs. volwasse; 88.67±0.85% totale motiele selle; p <0,001) en morfologiese parameters (onvolwasse; 13.51±0.87% normale kop morfologie vs. volwasse; 20.89±1.20% normale kop morfologie; p <0,001) tussen die twee populasies beduidend verskil. Na 2D-elektroforese is 21 kern proteïen kolle geïdentifiseer wat betekenisvol uitgedruk was tussen onvolwasse en volwasse spermpopulasies. 95% van die nukluêre proteïene wat beduidend verskil het, was minder uitgedruk in die onvolwasse spermpopulasie ten opsigte van die volwasse spermpopulasie. Slegs een kern proteïen naamlik 78kDa Glukose gereguleerde proteïen was meer uitgedruk in die onvolwasse spermpopulasie in vergelyking met die volwasse spermpopulasie. Funksies is toegeskryf aan hierdie proteïene wat direk verband hou met sperm motiliteit, morfologie en energie metabolisme. Ten slotte, in die huidige studie is unieke tegnieke geïmplementeer om proteïen verskille tussen onvolwasse en volwasse spermpopulasies te ondersoek. Uit hierdie resultate is dit duidelik dat proteïen uitdrukking in die totale sperm proteoom en in die kern proteïen fraksie beduidend verskil en onvolledig is in die onvolwasse spermpopulasie ten opsigte van die volwasse spermpopulasie. Op grond van hierdie bevindinge word aanbeveel dat verdere studies op menslike sperme gedoen moet word ten einde die rol van individuele proteïene in sperm funksie te kan bepaal. Proteomika is ‘n ideale tegniek om die iodiopatiese oorsake van manlike infertiliteit te identifiseer, aangesien dit kan help in die identifisering van unieke reseptore (en seintransduksie paaie) wat gebruik kan word om sperm disfunksie te verbeter deur farmaseutiese behandeling.

Several factors may determine the rate. at which exogenous carbohydrate (CHO) is utilised by the human working muscles during prolonged (> 90 min moderate-intensity (63% of peak sustained power output [PPO]) exercise. These include i) the rate of gastric emptying of an ingested fluid, ii) the rate of digestion, absorption and subsequent transport of glucose into the systemic circulation, and iii) the rate of glucose uptake and oxidation by the working muscles. To test the hypothesis that the rate of gastric emptying is the primary factor limiting the rate of CHO delivery to the working muscles during exercise, uniformly labelled ¹⁴carbon (U-¹⁴C) tracer techniques were used in association with conventional gas exchange measurements and post-exercise gastric aspiration to compare the rates of gastric emptying, intestinal CHO delivery and ingested CHO oxidation from 15 g/100 ml solutions of glucose, maltose, a 22 chain-length glucose polymer, and an isocaloric 'soluble' starch preparation. Two groups of six highly-trained male cyclists or triathletes each ingested two of the test drinks which were given as a 400 ml loading bolus immediately before and then as eight 100 ml feedings at 10 min intervals during 90 min of continuous cycling at a work rate of 63% of PPO (~70% of maximal oxygen consumption [VO₂ₘₐₓ]).

Students Learn when they are actively engaged and thinking in class. The activities in this book are the primary classroom materials for teaching Anatomy and Physiology, sing the POGIL method. The result is an "I can do this" attitude, increased retention, and a feeling of ownership over the material.<br>https://dc.etsu.edu/etsu_books/1027/thumbnail.jpg

Ca2+-binding proteins (CaBP) alter Ca2+ signals, triggering cellular processes such as gene transcription regulation in neurons. CaBP1/CD is a calmodulin (CaM)-like Ca2+ binding protein that may regulate neuronal functions through interactions with effectors such as voltage-gated Ca2+ (Cav) channels and inositol trisphosphate receptors (InsP3Rs). To gain insight into the potential cellular functions of CaBP1/CD, we analyzed the expression and localization of CaBP1/CD variants in mouse brain. Of the three CaBP1/CD splice variants that have been characterized (CaBP1-S, CaBP1-L, and caldendrin (CD)), CD was the major variant expressed in mouse brain by western blot and quantitative polymerase chain reaction. These results reflected the expression of CaBP1/CD since they were not reproduced in mice with targeted disruption of the gene encoding CaBP1/CD (CaBP1 knock-out). By immunoperoxidase labeling, CaBP1/CD was localized in multiple cell-types including pyramidal cells in the cerebral cortex and hippocampal CA3 neurons and inhibitory neurons in the cerebellum. In the cerebellum, CaBP1/CD was not detected in Purkinje neurons but strongly colocalized with voltage-sensitive Shaker-type potassium channel, Kv1.2, in the pinceau formation formed between basket cells and the Purkinje cell axon initial segment. We conclude that CaBP1/CD is expressed in a subset of principal neurons where it may regulate Ca2+ signaling and neuronal excitability.

Exercise-induced muscle damage (EIMD) is known to be produced by novel or unaccustomed exercise, especially high force eccentric contractions. Histological myofibre disruption, force loss and muscle soreness are associated with EIMD and have implications for sporting performance. Traditional practices of assessing the extent of disruption to the myofibres is by performing needle biopsies and subsequently analysing the histology of the fibres. Recently there has been interest in investigating whether changes in force production and contractile properties of muscle following damaging exercise correlate strongly with the magnitude of disruption to the myofibres. The main aim of this study was to investigate whether changes in force production and contractile properties of muscle following damaging eccentric exercise correlated with myofibre disruption. In order to test the hypotheses set down in the study 56 mice (C57 BU/10 strain) were randomly assigned to two groups (active and passive). Each main group was then divided into 5 subgroups. Anaesthetised mice performed either 120 active (eccentric contractions) or passive (no muscle contraction) lengthening repetitions after which they were allowed to recover. The right foot was fixed to a foot plate housing a force transducer which was directly attached to the axle of a stepping motor. A stimulating electrode was surgically placed around the peroneal nerve and P. and 1/ 150 Hz ratios were determined. Animals in the active group then performed 5 bouts of 24 stimulated lengthening repetitions at 0.3 amps with a stimulation frequency of IOO Hz. The passive group's protocol was identical with the exception that no stimulation was provided. One repetition for both active and passive groups consisted of a 300 millisecond plantar flexion movement of the foot plate and a 4.7 second dorsi flexion recovery movement to the starting position. Active and passive subgroups were terminated at 3, 6, 10, 15 and 20 days following exercise, prior to which P. and 1/ 150 Hz ratio were determined. Tibialis anterior (TA) muscles were excised at this time from both exercised and contralateral limbs and prepared for later histological examination. Significant differences were evident between the two groups for Po following each bout of 24 lengthening repetitions, 10 minutes following lengthening and on days 3 and 20 of recovery. The only significant differences between the groups in 1/ 150 Hz ratio occurred 10 minutes following lengthening and at day six of recovery (p

Thesis (PhD (Biomedical Sciences. Medical Physiology))--University of Stellenbosch, 2010.<br>ENGLISH ABSTRACT: Psychosocial stressors have frequently been associated with an increased risk for developing The contributions of the cholinergic (Lobeline) and opioid (Naltrexone) systems in place preference behaviour were determined by employing a post-methamphetamine pharmacological treatment strategy. These two treatments failed to reverse the methamphetamine-induced place preference. However, administration of the drugs did lead to alterations in striatal dopamine and serotonin levels which may infer beneficial effects against the biochemical alterations induced by methamphetamine. We used both 2-D gel-based proteomics and isobaric tagging for relative and absolute quantitation (iTRAQ) to identify proteins in the frontal cortex, and nucleus accumbens shell and core of rats that were subjected to maternal separation, methamphetamine or both regimes. The proteins were associated with cytoskeletal modifications, altered energy metabolism, degenerative processes, interruptions in normal neurotransmission and enhanced intracellular signalling. We found that more proteins were quantitatively expressed in rats that were exposed to maternal separation followed by methamphetamine treatment than those animals subjected to the individual interventions independently. Additional proteins recruited by the combination of MS followed by MA which remained unchanged with independent treatments included malate dehydrogenase, V-type proton ATPase subunit E1, beta-synuclein, brevican core protein, eukaryotic translation initiation factor 4H, histidine triad nucleotide binding protein 1 and stress-induced phosphoprotein in the nucleus accumbens shell subregion. Additional proteins recruited in the core subregion with the combination treatment included thymosin beta-4, calretinin, Arpp-21 protein, alpha-synuclein, ubiquitin carboxylterminal hydrolase isozyme L1, cytochrome c, brain acid soluble protein 1, prosaposin and stress-induced phosphoprotein 1. Although, on a behavioural level via the use of CPP we found that MS did not exacerbate the rewarding effects of MA, the proteomic data does infer a role played by early life stress by the recruitment of additional proteins. We therefore propose that the molecular mechanisms by which early adverse events predispose animals to the addictive state may involve a complex assembly of cellular processes within the brain. depression, anxiety or substance abuse in adult life. Animal studies have also suggested that stressful experiences may result in altered behavioural responses to drugs of abuse as evidenced by enhanced cocaine self-administration and psychostimulant-induced hyperlocomotor activity. The main aim of our study was to establish whether adversity early in life would render individuals more vulnerable to later drug usage. We adopted maternal separation as our animal model of early life adversity and treated these animals with methamphetamine during the adolescent stage of their life. A conditioned place preference (CPP) paradigm was subsequently used to determine the rewarding effects of methamphetamine. To obtain an understanding of the underlying molecular mechanisms of methamphetamine-induced behaviour, we measured neurochemical changes on a neuroendocrine, neurotrophic, neurotransmitter and proteome level. Firstly, we established that methamphetamine-induced place preference behaviour lasted for at least 2 weeks after the last methamphetamine administration. Contrary to expectation, this behaviour was not affected by prior exposure to maternal separation. However, rats subjected to maternal separation caused a decrease in apomorphine-induced locomotor behaviour in methamphetamine-treated rats. Maternal separation therefore preferentially affected the behavioural repertoire of the dorsal striatum rather than that of the ventral striatum. A general down regulation of neuroendocrine activity (ACTH and corticosterone levels) was observed in animals subjected to maternal separation or methamphetamine treatment, as well as those subjected to the combination of the two interventions. Increased concentrations of plasma prolactin levels in maternally separated as well as normally reared animals subjected to methamphetamine-CPP were found which suggested a reduction in dopamine inhibition. Maternal separation resulted in increased NGF levels in the ventral hippocampus of methamphetamine treated rats. This suggested that the ventral hippocampus may particularly be vulnerable to the effects of early life stress. The increased neurotrophin concentrations may reflect a compensatory response to stress and drug exposure.<br>AFRIKAANSE OPSOMMING: Psigososiale stressors word gereeld geassosieer met ‘n verhoogde risiko vir die ontwikkeling van depressie, angs en dwelm misbruik in volwassenheid. Diere studies het ook al bewys dat vroeë lewensstres in die vorm van moederlike skeiding lei tot veranderde gedrag teenoor dwelm misbruik. Hierdie veranderde gedrag veroorsaak deur moederlike skeiding sluit die verhoodge kokaïne toediening en psigostimulant geinduseerde verhoging in lokomotoriese aktiwiteit in. Die hoofdoel van die studie was om vas te stel of vroeë lewensstres mense meer vatbaar laat vir latere dwelm misbruik. ‘n Moederlike skeidings diere model was gebruik om vroeë lewensstres voor te stel and het verder hierdie diere behandel met metamfetamiene gedurende adolesensie. Die gekondisioneerde plek voorkeur model was gebruik om die euforiese / verslawende effekte van metamfetamiene te bepaal. Om die onderliggende molekulêre meganismes van metamfetamien geinduseerde gedrag te verstaan het ons neurochemiese veranderinge op ‘n neuroendokriene, neurotrofiese, neurotransmissie en proteinvlak vasgestel. Eerstens het ons was gestel dat metamfetamien geinduseerde plek voorkeur vir ten minste twee weke na die laaste metafetamien toediening voortduur. In teenoorstelling met verwagting, het moederlike skeiding nie metamfetamien geinduseerde plek voorkeur beinvloed nie, maar eerder apo-morfien geinduseerde lokomotoriese aktiwiteit geaffekteer. Moederlike skeiding stres het by voorkeur die gedrags funksie van die dorsale striatum beinvloed eerder as die ventrale gedragsfunksie. ‘n Algemene afregulering van neuroendokriene aktiwiteit was waargeneem (adrenokortikotrofiene en kortikosteroon vlakke) in diere wat aan moederlike skeiding of metafetamien behandeling sowel as die kombinasie behandeling blootgestel was. Verhoogde plasma prolaktien vlakke was gevind in moederlike skeidings rotte sowel as kontrole diere wat verder blootgestel is aan metamfetamien behandeling wat ‘n inhibisie van die dopamiene sisteem toon. Moederlike skeiding het ook ‘n verhooging in neurotrofiene (NGF) in die ventrale hippokampus van metamfetamien behandelde rotte veroorsaak. Hierdie bevinding stel voor dat die ventrale hippokampus veral vatbaar is vir die effekte van vroeë lewensstres. ‘n Verhoging in neurotrofien konsentrasies mag ‘n kompenserende teenslag van die brein wees teen stres en dwelm blootstelling. Die bydrae van die cholinergiese (Lobeline) en opiaat (Naltrexone) sisteme in plek voorkeur gedrag was bepaal deur farmaseutiese behandeling te volg na metamftemien toediening. Lobeline en naltrexone was egter nie suksesvol om die metamfetamien geinduseerde plek voorkeur te wysig nie. Alhoewel die toediening van die twee behandelings het tot veranderinge in neurotransmissie (dopamiene en serotoniene) gelei wat moontlik tot voordelige effekte teen die biochemiese veranderinge van metamfetamien kan lei. Om veranderinge op proteinvlak in die frontale korteks en nukleus akkumbens middel en buitenste subareas vas te stel het ons gebruik gemaak van twee-dimensie gel elektroforese en isobariese merkers vir relatiewe en absolute kwantifisering (iTRAQ) gevolg deur massa spektrofotometrie. Geindentifiseerde proteine was geassosieer met sitoskeletale modifikasies, veranderde energie metabolisme, afbrekende prosesse, onderbrekings met normale neurotransmissie en intrasellulêre seintransduksie. Meer proteine was beduidend in die diere wat aan beide moederlike skeiding en metamfetamien behandeling blootgestel was. Addisionele proteine wat deur die kombinasie behandeling geaffekteer is in die buitenste subarea van die nukleus akkumbens sluit ‘malate dehydrogenase’, ‘V-type proton ATPase subunit E1’, ‘beta-synuclein’, ‘brevican core protein’, ‘eukaryotic translation initiation factor 4H’, ‘histidine triad nucleotide binding protein 1’ en ‘stress-induced phosphoprotein’ in. Additionele proteine geaffekteer in die middelste subarea van die nukleus akkumbens sluit ‘thymosin beta-4’, ‘calretinin’, ‘Arpp-21 protein’, ‘alpha-synuclein’, ‘ubiquitin carboxylterminal hydrolase isozyme L1’, ‘cytochrome c’, ‘brain acid soluble protein 1’, ‘prosaposin’ en ‘stress-induced phosphoprotein 1’ in. Vanuit ‘n gedrags benadering deur die gebruik van metamfetamien geinduseerde plek voorkeur het moederlike skeiding nie diere meer vatbaar gemaak vir die effekte van metamfetamien nie, maar die protein data wys wel dat vroeë lewens stres ‘n rol speel deur dat meer proteine geaffekteer word deur die kombinasie van moederlike skeiding gevolg deur later metamfetamien toediening. Ons stel voor dat die molekulêre meganismes waardeur vroeë lewensstres diere meer vatbaar maak vir die verslawende effekte van stimulante behels ‘n komplekse samestelling van sellulêre prosesse in die brein.

African runners dominate distance running both in South Africa and internationally. Therefore, the aim of this thesis was to compare selected exercise and skeletal muscle characteristics in well-trained African and Caucasian 10 km runners to determine if evidence exists of differences between these groups with respect to these physiological and biochemical characteristics. Furthermore, the relationship between exercise and skeletal muscle characteristics was investigated. Sedentary individuals from each population group were also studied to determine if differences existed in untrained skeletal muscle between groups. Maximal oxygen consumption and peak treadmill speed were measured using an incremental treadmill protocol whilst submaximal exercise characteristics were measured during a specifically designed protocol consisting of four sequential submaximal workloads relative to the peak treadmill speed of the individual. The final workload was maintained until fatigue with resistance to fatigue defined as total test time. Running economy was measured at a treadmill speed of 16.1 km/hr. Race pace characteristics were measured directly at race pace. Characteristics measured during exercise tests were oxygen uptake, minute ventilation, respiratory exchange ratio and heart rate whilst plasma lactate concentration was determined immediately after exercise. Skeletal muscle characteristics were determined by needle biopsy of the vastus lateralis muscle. Skeletal muscle enzymes citrate synthase, phosphofructokinase, 3-hydroxyacyl CoA dehydrogenase, hexokinase and carnitine palmityl transferase were assayed spectrophotometrically. Skeletal muscle buffering capacity was measured using by titration and fibre type proportions were analysed histochemically. Comparisons between groups were made with the Student's t-test for unpaired data whilst the relationships between variables were analysed using the Pearson's correlation coefficient. The first major finding was that when exercising at the same relative percentage of individual maximal treadmill velocity, African distance runners were able to exercise for longer than the Caucasians (1376±227 vs 1137±126 sec, p<0.01) with lower plasma lactate accumulation (4.8±3.2 vs 7.7±2.8 mmol/l,p<0.05). Time to fatigue was significantly related to a lower plasma lactate concentration (r=-0.63) and a lower respiratory exchange ratio (r=-0.53). The second major finding indicated that African runners were able to race 10 km at a higher percentage of their maximal oxygen uptake (93.5 vs 86.0%, p<0.005), whilst eliciting only a comparable plasma lactate concentration and respiratory exchange ratio. The third main finding was that the African runners were more economical than the Caucasian runners (p<0.05). The fourth main finding is that the African runners had a 50% greater activity of citrate synthase (p<0.005) and 3-hydroxyacyl CoA dehydrogenase (p<0.01) in the vastus lateralis than the Caucasians and this could not be explained by fibre type proportions, because the proportion of type I fibres was lower in the African runners (p<0.05). Citrate synthase activity, was related to the runners' ability to resist fatigue at high intensity relative to their individual peak treadmill velocity (r=0.70, p<0.05). A higher CS activity was related to a lower plasma lactate concentration and a lower RER. The sixth main finding of this thesis was that skeletal muscle buffering capacity of the Caucasian runners was higher than that of the African runners (p<0.05). A methodological study of buffering capacity in rats showed the buffering capacity was largely dependent upon fibre type and protein concentration, however these parameters could not explain the difference observed between the African and Caucasian runners. Furthermore, despite the differences in skeletal muscle characteristics observed between African and Caucasian runners in the current thesis, there was no evidence of these differences being inherently present in sedentary African and Caucasian individuals. In conclusion, the current series of studies do provide evidence of differences in selected exercise and skeletal muscle characteristics between African and Caucasian distance runners, with the African runners possessing exercise and skeletal muscle profiles that are considered to be more advantageous for endurance performance.