Development of a high pressure liquid chromatographic method for the simultaneous analysis of sulphamethoxazole and trimethoprim and its application to biological fluids and dissolution rate studies on solid oral dosage forms
- Authors: Gochin, Rosa
- Date: 1980
- Subjects: High performance liquid chromatography , Body fluids -- Analysis , Drugs -- Dosage forms
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3735 , http://hdl.handle.net/10962/d1001524
- Description: Co-trimoxazole, a combination of a 5-to-l ratio of Sulphamethoxazole (SMZ) and Trimethoprim (TMP) , is a highly effective, broad-spectrum antibacterial agent. Since its introduction in 1968, it has been extensively used in infections of the respiratory and urinary tracts. Co-trimoxazole was developed by the systematic investigation of a series of compounds whose mechanism of action was already known. As early as 1950 synergy between sulphonamides and 2,4-diaminopyrimidines was reported. This was to be expected as both groups of drugs exert their antibacterial activity by interfering with the same biochemical pathway in bacteria. TMP was chosen from among many 2,4-diaminopyrimidines tested because of its good antibacterial activity and low toxicity. SMZ was chosen from the sulphonamides available for combination with TMP because of similarity of their biological half-lives. The widespread use of the combination coupled with the fact that monitoring of the levels of all drugs in the body is becoming increasingly important has stimulated research into rapid and efficient methods for the analysis of TMP and SMZ in biological fluids. Another consequence of the immense popularity of the combination is the appearance on the market of several generic preparations of Co-trimoxazole. It is now generally recognized that drug products from different manufacturers which are chemically equivalent may not be therapeutically equivalent. This is due to the fact that the absorption rate and/or bioavailability (extent of absorption) of a poorly soluble drug may be markedly affected by its release rate from the product and by its subsequent dissolution rate in gastrointestinal fluids. Hence bioequivalence of these various products should be established
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- Date Issued: 1980
The effects of sustained attention, workload and task-related fatigue on physiological measures and performance during a tracking task
- Authors: De Gray Birch, Casey
- Date: 2012
- Subjects: Fatigue -- Physiological aspects -- Research , Attention -- Physiological aspects -- Research , Human engineering -- Research
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:5120 , http://hdl.handle.net/10962/d1005198 , Fatigue -- Physiological aspects -- Research , Attention -- Physiological aspects -- Research , Human engineering -- Research
- Description: Despite extensive research into the concept of mental fatigue there is as yet no “gold standard” definition or measurement technique available. Because of this a large amount of fatigue-related errors are still seen in the workplace. The complexity of the problem lies with the inability to directly measure mental processes as well as the various endogenous and exogenous factors that interact to produce the experienced fatigue. Fatigue has been divided into sleep-related and task-related fatigue; however the task-related aspect is evident both during normal waking hours as well as during periods of sleep deprivation, therefore this aspect is considered important in the understanding of fatigue in general. The concept of task-related fatigue has further been divided into active and passive fatigue states; however differentiation between the two requires careful consideration. Various physiological measures have been employed in an attempt to gain a better understanding of the mechanisms involved in the generation of fatigue, however often studies have produced dissociating results. The current study considered the task-related fatigue elicited by a tracking task requiring sustained attention, in order to evaluate the usefulness of various cardiovascular and oculomotor measures as indicators of fatigue. A secondary aim was to determine whether the behavioural and physiological parameter responses could be used to infer the type of fatigue incurred (i.e. an active versus passive fatigue state) as well as the energetical mechanisms involved during task performance. A simple driving simulator task was used as the main tracking task, requiring constant attention and concentration. This task was performed for approximately two hours. Three experimental groups (consisting of 14 subjects each) were used: a control group that performed the tracking task only, a group that performed a five minute auditory memory span task concurrently with the driving task after every 20 minutes of pure driving, and a group that performed a visual choice reaction task for five minutes following every 20 minute driving period. The secondary tasks were employed in order to evaluate the extent of resource allocation as well as arousal level. Performance measures included various driving performance parameters, as well as secondary task performance. Physiological measures included heart rate frequency (HR) and various time- and frequency-domain heart rate variability (HRV)parameters, pupil dilation, blink frequency and duration, fixations, and saccadic parameters as well as critical flicker fusion frequency (CFFF). The Borg CR-10 scale was used to evaluate subjective fatigue during the task, and the NASA-TLX was completed following the task. A decline in driving performance over time was supplemented by measures such as HR, HRV and pupil dilation indicating an increase in parasympathetic activity (or a reduction in arousal). An increase in blink frequency was considered as a sign of withdrawal of attentional resources over time. Longer and faster saccades were also evident over time, coupled with shorter fixations. With regards to the secondary task influence, the choice RT task did not affect any behavioural or physiological parameters, thereby contesting the active fatigue theory of resource depletion, as well as implying that the increase in demand for the same resources used by the primary task was insufficient to affect the state of the subjects. The increased load elicited by the memory span task improved driving performance and increased measures of HR, HRV, pupil dilation and blink frequency. Some of these measures produced opposite effects to what was expected; an attempt to explain the dissociation of the various physiological parameters was expressed in terms of arousal, effort and resource theories. Overall, the results indicate that the fatigue and/or reduced arousal accompanying a monotonous sustained attention task can, to some degree, be alleviated through intermittent performance of a secondary task engaging mental resources other than the ones used for the primary task. The degree to which such a task is beneficial, however, requires careful consideration as while an immediate increase in arousal and primary task performance is noted, the impact of the task on general attentional resources may be detrimental in the case of reacting should an emergency situation occur.
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- Date Issued: 2012