Intestines of fifty-six albino rats of the Holtzman strain were removed and perfused with Krebs bicarbonate buffered solutions containing caffeine. After one hour of absorbtion, caffeine was extracted from the serosal fluids in chloroform and concentrations were determined spectrophotometrically. It was found that all portions of the small intestine transported caffeine against a concentration gradient. This transport mechanism demonstrated saturation kinetics and was inhibited by ouabain. It was concluded that the movement of caffeine from the mucosa to the serosa of the small intestine cannot be the result of simple diffusion. Possible mechanisms by which the absorption of caffeine takes place are discussed.

<p> Chapter 1-4 focuses on investigating whether forced copulations occur in teneral females, and how the female responds. There has only been one paper to report mating in newly eclosed (teneral) female matings in fruit flies (Drosophila melanogaster), and it was suggested to be forced. The focus of this thesis is to determine whether teneral matings are forced and how this may affect the future remating and reproductive success of females. Within the thesis, chapter 1 and 4 results suggest that teneral matings occur in both Canton-S and wild caught females, and occur in females less than 30 minutes post eclosion. Chapter 3 compared the male/female interaction of teneral females vs. immature females that successfully reject male mating attempts. Males were more aggressive with teneral females, and females displayed more rejection behaviours during courtship and mating. Chapter 4, was aimed at investigating what the reproductive consequences are, and results suggest that a teneral mating yields less progeny than a mature mating, and 68% of tenerally mated females remate at maturity.</p> <p> Chapter 5 and 6 focuses on investigating whether situational caffeine tolerance can be developed in fruit flies. Chapter 5 results indicate that caffeine causes a rest disruption, and a general tolerance to the rest disrupting effects can be gained over 6 days of repeated administration. The experiments in chapter 6 used various protocols to investigate whether a situational tolerance will develop, using odours and colours as associative cues. No conclusive results were found.</p> / Thesis / Master of Science (MSc)

The burden of neurocognitive diseases, such as Alzheimer’s, is of global concern and points to an urgent need for accurate detection and prevention strategies. This thesis investigated dietary components, in particular those that affect vitamin B levels, such as white fish consumption and veganism, which have the potential to alter cognitive outcomes in the population. Also investigated were external factors, significantly caffeine consumption, time of day, and quantity of sleep, not associated with age-related impairment, that can alter neuropsychological test performance. The literature reveals that short, multi-domain cognitive tests are commonly used for dementia screening; this study has focused exclusively on cognitive domains associated with the early stages of Alzheimer’s disease. Cognitively healthy adults were assessed using a cognitive test battery that focused on memory and processing speed. Memory test scores improved by 0.03 points for every gram of white fish consumed, whilst participants following a vegan diet scored significantly worse on tests of composite memory than their omnivorous counterparts. Interaction tests showed that prior caffeine consumption improved short-term memory test scores up to age 70. Participants of all ages performed best at their age-optimal times and further improved for immediate word recall tests with prior caffeine consumption. Processing speed scores increased linearly with hours of sleep. The results of this thesis suggest that nutrition and external factors have a significant impact on cognitive test performance. These novel findings have implications for research, diagnosis and prevention of chronic neurological disease, and public health guidance relating to cognitive function, for all ages.

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Caffeine is the most widely used psychoactive substance in the world. While findings suggest that chronic caffeine exerts negligible effects on cognition in adults, the effects of chronic caffeine on cognition in children and adolescents are not well understood. The hippocampus, a brain region important for learning and memory, undergoes extensive structural and functional modifications during pre-adolescence and adolescence. As a result, chronic caffeine may have differential effects on hippocampus-dependent learning and memory in pre-adolescents and adolescents compared to adults. The present study characterized the effects of chronic caffeine and withdrawal from chronic caffeine on hippocampus-dependent (contextual) and hippocampus-independent (cued) fear conditioning in pre-adolescent, adolescent, and adult mice. In addition, we investigated whether exposure to chronic caffeine during pre-adolescence, adolescence, or adulthood had long-lasting effects on conditioning in adulthood. Results indicate that exposure to chronic caffeine during pre-adolescence and adolescence either enhances or impairs contextual conditioning in a concentration-dependent manner. However, withdrawal from chronic caffeine impairs contextual conditioning in pre-adolescent mice only. In addition, exposure to chronic caffeine during pre-adolescence either enhances or impairs retention of contextual memories in adulthood in a concentration-dependent manner. In contrast, exposure to chronic caffeine during adolescence impairs cued conditioning in adulthood. These findings support the hypothesis that exposure to chronic caffeine during pre-adolescence and adolescence compromises hippocampus-dependent learning and memory. Furthermore, exposure to chronic caffeine during adolescence may produce long-lasting deficits in learning and memory in adulthood. / Psychology

Yes / We report that performance on neuropsychological tests used in the diagnosis of dementia can be influenced by external factors such as time of day (TOD) and caffeine. This study investigates TOD effects on cognitive performance in the elderly. The optimal TOD at which an individual is at their maximal arousal alters with age and in the elderly typically occurs in the morning. Neuropsychological test scores from healthy elderly participants were analysed to determine whether TOD affected performance. Interactions between caffeine and TOD were also investigated. Across two data sets that were analysed, significant TOD effects were noted for Pattern Comparison Speed (PCS), Letter Comparison Speed (LCS), Trail Making Test Part A, Mini Mental State Examination (MMSE) and the Graded Naming Test (GNT), revealing a decline in test scores as TOD increases. Significant interactions between TOD, age and the PCS, LCS and Trail Making part A were noted in data set one. In data set two, where caffeine intake had been controlled for, significant interactions between caffeine, TOD and scores on the MMSE and GNT were found. The TOD and caffeine effects highlight the need to control for these external factors when scoring the assessments. This conclusion has implications for the clinical procedure of diagnosis and treatment of dementia and Alzheimer’s.

Polyelectrolyte complexes (PECs) between chitosan, a mucoadhesive, intestinal mucosal permeability-enhancing polysaccharide, and cellulose nanocrystals, rod-like cellulose nanoparticles with sulfate groups on their surface, have potential applications in oral drug delivery. The purpose of this research was to develop an understanding of the formation and properties of chitosan–cellulose nanocrystal PECs and determine their in vitro drug release properties, using caffeine and ibuprofen as model drugs. Cellulose nanocrystals were prepared by sulfuric acid hydrolysis of bleached wood pulp. Chitosans with three different molecular weights (81, 3·103, 6·103 kDa) and four different degrees of deacetylation (77, 80, 85, 89%) were used. PEC formation was studied by turbidimetric titration. PEC particles were characterized by FT-IR spectroscopy, scanning electron microscopy, dynamic light scattering, and laser Doppler electrophoresis. The formation and properties of chitosan–cellulose nanocrystal PEC particles were governed by the strong mismatch in the densities of the ionizable groups. The particles were composed primarily of cellulose nanocrystals. Particle shape and size strongly depended on the mixing ratio and pH of the surrounding medium. The ionic strength of the surrounding medium, and the molecular weight and degree of deacetylation of chitosan had a minor effect. Release of caffeine from the chitosan–cellulose nanocrystal PEC particles was rapid and uncontrolled. Ibuprofen-loaded PEC particles showed no release in simulated gastric fluid and rapid release in simulated intestinal fluid. Further evaluation studies should focus on the expected mucoadhesive and permeability-enhancing properties of chitosan–cellulose nanocrystal PEC particles. / Ph. D.

Crystal engineering study using spray dryer was performed for scale-up and rapid, continuous crystallisation of co-crystals from solution. The study emphasise on developing co-crystals of two structurally similar compounds, caffeine (CAF) and theophylline (THEO) with various di-carboxylic acids. The incongruently soluble pair of CAF and THEO with di-carboxylic acids acquires large solubility difference which is important to consider for its utility in product development. Based on previous assumption that maleic acid (MAL) elevates CAF’s solubility; solubility of the two similar compounds was tested in various dicarboxylic acids. Other solubility enhancement strategies such as introduction of surfactant and binary solvents were also scrutinised. A kinetically similar bench-scale technique, rotary evaporator (rotavap) was investigated as a pre-screening tool for the production of co-crystals via spray drying. Furthermore, various process parameters within the spray dryer were optimised to control the kinetic conditions which influence co-crystallisation and quality of the product. Another polymorphic co-crystal pair, CBZ (carbamazepine) and SAC (saccharin) was examined in various solvents and its degradation was evaluated over a period of few months. In this study, a two-step conversion of CBZ into its degradate was hypothesised. Rotavap delivered a true reflection of co-crystal favoured via spray drying apart from co-crystal pairs depicting polymorphism. Spray dryer offered a unique environment favouring metastable forms of co-crystals irrespective of the starting component stoichiometry; generating CAF:MAL 2:1. However, due to process limitation and solubility constraint, the impurity of CAF in CAF:MAL 2:1 co-crystals could not be abolished.

Several studies have shown that the loss in tension during fatigue can be virtually reversed by exposure of the muscle to agents which evoke Ca²⁺ release from the SR. The purpose of this study was to determine whether the SR Ca²⁺ release mechanism of fatigued muscle is less sensitive to caffeine than that of rested muscle. Following a fatigue bout of electrically evoked tetanic pulses, the functioning of the SR of chemically skinned muscle fibers was determined by the sensitivity of the SR to increasing concentrations of caffeine. Measurements of tension and rate of tension development were made at the maximal Ca²⁺ activated contracture(pCa4.5), the maximal caffeine(25mM) activated contracture and at the caffeine threshold for contraction. All tension and rate values were normalized per cross sectional area and expressed as percents of the maximal calcium activated values. Results of the maximal Ca²⁺ and caffeine data suggest that the both control and fatigue fibers are similar in maximal tension and Ca²⁺ loading characteristics. While no differences were found between rested or fatigued maximal Ca²⁺ or caffeine contractures, significant difference was found at the caffeine threshold (p<.05) with the fatigued muscle tending to contract at a higher caffeine concentration. This suggests that fatigued muscle is less sensitive to the caffeine stimulus for Ca²⁺ release from the SR. / Master of Science