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This dissertation aims at determining the possible effects of alcoholic hangover on human behaviour by examining the effects of acute alcohol consumption (> 1g/kg) 14-16 hours following alcohol ingestion on simple and choice reaction times, divided attention tasks and driving skills. The hypotheses are that cognitive and behavioural functioning is impaired even after the blood alcohol concentration level has returned to zero The California Computerised Assessment Package (CALCAP) together with selected driving skills tasks, repeated breath analysis measures, a biographical questionnaire, a subjective hangover rating scale, and blood glucose tests were administered to a group of 63 mixed gender student volunteers. The experimental group and was tested prior to, and during hangover. The control group was pre- and post-tested in order to determif.le the impact of practice effects. Results indicate that hangover individuals performed less well than control subjects on measures of reaction time and driving precision. Further more, the findings show that subjective experience of hangover is not a good predictor of reaction time or driving performance, and that the absence of hangover symptoms does not guarantee full mental recovery. Statistical analysis of the data showed that post-test findings could not be attributed to a gender effect. / Thesis (M.A.)-University of Natal, Pietermaritzburg, 2000.

Brugia malayi is one of the causative agents of the disabling and disfiguring disease known as Lymphatic Filariasis (LF). This infection is a well-established ailment in tropical and subtropical countries and recently the drug ivermectin has been introduced for the LF control programs. Ivermectin (IVM) is an excellent microfilaricide, but is not markedly macrofilaricidal. However, it causes a long-lasting reduction in the production of new larvae by female worms, suggesting that adult stages are affected. However, the mechanism by which IVM produces such effect in the adult worm is not well understood. One major reason is our incomplete understanding about the biological effect of IVM on adult stages. The present study was carried out to examine the in vitro effects of IVM on B. malayi adult worms using Brugia-gerbil animal model. And also to have some leads in understanding the drug-uptake and location of probable targets in the worm body by using fluorescent labeled IVM and confocal microscopy. / The antifilarial effects of IVM were examined using three parameters: mf release by female worms, and motility, and viability in both male and female worms. The results reported in this study demonstrate that although IVM did not kill the adult worm, but showed significant antifilarial effects on B. malayi adult stages when examined in an in vitro system. Confocal microscopy images of the worms incubated in bodipy FITC-IVM showed strong specific localization signal in the anterior cephalic region of both male and female worms. These observations suggest the early/initial interactions of the drug with its probable receptors that could be located specifically in the head region.

This thesis examined how pharmacological treatment and cortical injury during development affects brain plasticity. Rats were given either a low dose of perinatal fluoxetine or a mild postnatal day 7 Hypoxic‐Ischemic (HI) injury, both, or neither. The functional outcome was assessed using a series of behavioral tasks and anatomical measures. To assess how HI affects the development of motor maps, forelimb motor maps were evoked at P19. The findings indicate that fluoxetine treatment or HI injury mostly negatively affected functional outcome. The combined treatment with fluoxetine and HI injury only interacted on a limited number of measures. There was no delay in the emergence of evoked motor movements, or change in map location in the HI animals. These results suggest that the pharmacological treatment and cortical injury described in this thesis may have different mechanisms whereby plastic changes are induced and the interaction between these two mechanisms is limited. / xii, 169 leaves : ill. ; 29 cm.

The behavioural and electrophysiological consequences of two newly developed aniracetam analogues were investigated in male Long-Evans rats. Results indicate that an intraperitoneal (i.p.) injection of LD38.2 significantly improved retention in a two odour olfactory discrimination task. However, three different dosages of LN1 did not facilitate memory in the task. In rats with chronically implanted electrodes, both compounds rapidly crossed the blood brain barrier (BBB) after an i.p. injection and influenced several parameters of the field excitatory postsynaptic potential (EPSP) in the CA1 and dentate gyrus regions of the hippocampus. The enhancement of the field EPSP following LD38.2 administration may be related to the drug's ability to facilitate memory in the olfactory discrimination task. Compounds, like LD38.2, that enhance both hippocampal transmission and performance in learning/memory tasks in laboratory rodents may have implications for the treatment of clinical memory disorders.

There is relatively little known about the fate of human pharmaceuticals once they are released into the aquatic environment and what adverse impacts these compounds have on exposed aquatic organisms. Both of these factors are essential in defining the potential risk pharmaceuticals pose in the aquatic environment. For this project up to 14 human therapeutic agents were selected as representative compounds to assess both their fate and effects within model aquatic systems. Considering sediments often serve as a repository for aquatic contaminants, the interaction of the selected pharmaceuticals with sediment was assessed. The sorption of the selected pharmaceuticals was found to be highly variable. Furthermore, the solution pH and ionic strength, due to Ca2+, were found to exert a large degree of influence on the extent of sorption observed. These solution parameters, among others, may therefore make it difficult to predict the fate of pharmaceuticals, in terms of their association with sediments, using standardised assessment methods alone. There is an extensive pool of knowledge on pharmaceuticals, in terms of their pharmacological profile, so their distribution within the human body (using the volume of distribution or VD) was compared with their distribution within a sediment / water system (using the partition coefficient or Kd). The correlation between the VD and Kd indicated this relationship provided a reasonable basis for estimating the distribution of drugs within the test sediment / water systems. This finding suggests that further exploration of the use of pharmacological data in understanding the potential fate of pharmaceuticals in aquatic systems is warranted. The extent of the pharmaceuticals respective desorption values was also found to be highly variable within a standard test system. Further analysis on the desorption of carbamazepine, an anti-epileptic drug, was undertaken using an isotopic dilution technique. Observations from the isotopic dilution study indicated that both contact time with sediment and the quality of organic carbon could play an important role in the potential for sediments to irreversibly sorb carbamazepine present in aquatic systems. The desorption hysteresis observed for the other pharmaceuticals also indicates considerable effort is still required to address the issue of whether sediments can be a means of reducing exposure of pharmaceuticals to aquatic organisms (a “sink”) or a means of increasing exposure to sediment-dependent organisms (a “source”). The necessity for further work on investigating the role that sorption with sediments may play in the fate and effects of human pharmaceuticals was highlighted by a series of ecotoxicological assays in both sediment and solution-only systems. Sediment-dwelling freshwater midges, Chironomus tepperi, were exposed to carbamazepine in both short- and long-term assays. Wet weight was found to be significantly reduced during short-term assays, while the development of C. tepperi larvae was found to be significantly inhibited when exposed to spiked sediment, over a longer exposure period. For these assays, the aqueous phase may have been a more important route of exposure of carbamazepine for the midges. This study has indicated that sediments are likely to play an important role in the fate of pharmaceuticals and, subsequently, their effects. However, considerably more effort is required to assess the role sediments have and how this knowledge can be linked with current regulatory ecological risk assessments. / http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1298389 / Thesis (Ph.D.) -- University of Adelaide, School of Earth and Environmental Sciences, 2007

There is relatively little known about the fate of human pharmaceuticals once they are released into the aquatic environment and what adverse impacts these compounds have on exposed aquatic organisms. Both of these factors are essential in defining the potential risk pharmaceuticals pose in the aquatic environment. For this project up to 14 human therapeutic agents were selected as representative compounds to assess both their fate and effects within model aquatic systems. Considering sediments often serve as a repository for aquatic contaminants, the interaction of the selected pharmaceuticals with sediment was assessed. The sorption of the selected pharmaceuticals was found to be highly variable. Furthermore, the solution pH and ionic strength, due to Ca2+, were found to exert a large degree of influence on the extent of sorption observed. These solution parameters, among others, may therefore make it difficult to predict the fate of pharmaceuticals, in terms of their association with sediments, using standardised assessment methods alone. There is an extensive pool of knowledge on pharmaceuticals, in terms of their pharmacological profile, so their distribution within the human body (using the volume of distribution or VD) was compared with their distribution within a sediment / water system (using the partition coefficient or Kd). The correlation between the VD and Kd indicated this relationship provided a reasonable basis for estimating the distribution of drugs within the test sediment / water systems. This finding suggests that further exploration of the use of pharmacological data in understanding the potential fate of pharmaceuticals in aquatic systems is warranted. The extent of the pharmaceuticals respective desorption values was also found to be highly variable within a standard test system. Further analysis on the desorption of carbamazepine, an anti-epileptic drug, was undertaken using an isotopic dilution technique. Observations from the isotopic dilution study indicated that both contact time with sediment and the quality of organic carbon could play an important role in the potential for sediments to irreversibly sorb carbamazepine present in aquatic systems. The desorption hysteresis observed for the other pharmaceuticals also indicates considerable effort is still required to address the issue of whether sediments can be a means of reducing exposure of pharmaceuticals to aquatic organisms (a “sink”) or a means of increasing exposure to sediment-dependent organisms (a “source”). The necessity for further work on investigating the role that sorption with sediments may play in the fate and effects of human pharmaceuticals was highlighted by a series of ecotoxicological assays in both sediment and solution-only systems. Sediment-dwelling freshwater midges, Chironomus tepperi, were exposed to carbamazepine in both short- and long-term assays. Wet weight was found to be significantly reduced during short-term assays, while the development of C. tepperi larvae was found to be significantly inhibited when exposed to spiked sediment, over a longer exposure period. For these assays, the aqueous phase may have been a more important route of exposure of carbamazepine for the midges. This study has indicated that sediments are likely to play an important role in the fate of pharmaceuticals and, subsequently, their effects. However, considerably more effort is required to assess the role sediments have and how this knowledge can be linked with current regulatory ecological risk assessments. / http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1298389 / Thesis (Ph.D.) -- University of Adelaide, School of Earth and Environmental Sciences, 2007

There is relatively little known about the fate of human pharmaceuticals once they are released into the aquatic environment and what adverse impacts these compounds have on exposed aquatic organisms. Both of these factors are essential in defining the potential risk pharmaceuticals pose in the aquatic environment. For this project up to 14 human therapeutic agents were selected as representative compounds to assess both their fate and effects within model aquatic systems. Considering sediments often serve as a repository for aquatic contaminants, the interaction of the selected pharmaceuticals with sediment was assessed. The sorption of the selected pharmaceuticals was found to be highly variable. Furthermore, the solution pH and ionic strength, due to Ca2+, were found to exert a large degree of influence on the extent of sorption observed. These solution parameters, among others, may therefore make it difficult to predict the fate of pharmaceuticals, in terms of their association with sediments, using standardised assessment methods alone. There is an extensive pool of knowledge on pharmaceuticals, in terms of their pharmacological profile, so their distribution within the human body (using the volume of distribution or VD) was compared with their distribution within a sediment / water system (using the partition coefficient or Kd). The correlation between the VD and Kd indicated this relationship provided a reasonable basis for estimating the distribution of drugs within the test sediment / water systems. This finding suggests that further exploration of the use of pharmacological data in understanding the potential fate of pharmaceuticals in aquatic systems is warranted. The extent of the pharmaceuticals respective desorption values was also found to be highly variable within a standard test system. Further analysis on the desorption of carbamazepine, an anti-epileptic drug, was undertaken using an isotopic dilution technique. Observations from the isotopic dilution study indicated that both contact time with sediment and the quality of organic carbon could play an important role in the potential for sediments to irreversibly sorb carbamazepine present in aquatic systems. The desorption hysteresis observed for the other pharmaceuticals also indicates considerable effort is still required to address the issue of whether sediments can be a means of reducing exposure of pharmaceuticals to aquatic organisms (a “sink”) or a means of increasing exposure to sediment-dependent organisms (a “source”). The necessity for further work on investigating the role that sorption with sediments may play in the fate and effects of human pharmaceuticals was highlighted by a series of ecotoxicological assays in both sediment and solution-only systems. Sediment-dwelling freshwater midges, Chironomus tepperi, were exposed to carbamazepine in both short- and long-term assays. Wet weight was found to be significantly reduced during short-term assays, while the development of C. tepperi larvae was found to be significantly inhibited when exposed to spiked sediment, over a longer exposure period. For these assays, the aqueous phase may have been a more important route of exposure of carbamazepine for the midges. This study has indicated that sediments are likely to play an important role in the fate of pharmaceuticals and, subsequently, their effects. However, considerably more effort is required to assess the role sediments have and how this knowledge can be linked with current regulatory ecological risk assessments. / http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1298389 / Thesis (Ph.D.) -- University of Adelaide, School of Earth and Environmental Sciences, 2007

Doctorat en sciences psychologiques / info:eu-repo/semantics/nonPublished

Despite the current interventions to avert contagions and AIDS-related deaths, sub-Saharan Africa is still the region most severely affected by the HIV/AIDS pandemic, where clade C is the dominant circulating HIV-1 strain. The pol-encoded HIV-1 protease enzyme has been extensively exploited as a drug target. Protease inhibitors have been engineered within the framework of clade B, the commonest in America, Europe and Australia. Recent studies have attested the existence of sequence and catalytic disparities between clades B and C proteases that could upset drug susceptibilities. Emergence of drug-resistant associated mutations and combinatorial explosions due to recombination thwarts the attempt to stabilize the current highly active antiretroviral therapy (HAART) baseline. The project aimed at identifying the structural and molecular mechanisms hired by mutants to affect the efficacies of both FDA approved and Rhodes University (RU)-synthesized inhibitors, in order to define how current and or future drugs ought to be modified or synthesized with the intent of combating drug resistance. The rationale involved the generation of homology models of the HIV-1 sequences from the South African infants failing treatment with two protease inhibitors: lopinavir and ritonavir (as monitored by alterations in surrogate markers: CD4 cell count decline and viral load upsurge). Consistent with previous studies, we established nine polymorphisms: 12S, 15V, 19I, 36I, 41K, 63P, 69K, 89M, and 93L, linked to subtype C wild-type; some of which are associated with protease treatment in clade B. Even though we predicted two occurrence patterns of M46I, I54V and V82A mutations as V82A→I54V→M46I and I54V→V82A→M46V, other possibilities might exist. Mutations either caused a protracted or contracted active site cleft, which enforced differential drug responses. The in silico docking indicated susceptibility discordances between clades B and C in certain polymorphisms and non-polymorphisms. The RU-synthesized ligands displayed varied efficacies that were below those of the FDA approved protease inhibitors. The flaps underwent a wide range of structural motions to accommodate and stabilize the ligands. Computational analyses unravelled the need for these potential drugs to be restructured by (de novo) drug engineers to improve their binding fits, affinities, energies and interactions with multiple key protease residues in order to target resilient HIV-1 assemblages. Accumulating evidences on contrasting drug-choice interpretations from the Stanford HIVdb should act as an impetus for the customization of a HIVdb for the sub-Saharan subcontinent.