No description available.

No description available.

No description available.

ABSTRACT All members registered on the managed care database for the chronic condition Rheumatoid Arthritis (RA), for the period 01 January 2003 to 30 June 2003, were evaluated to determine the prescribing pattern of the cyclo-oxygenase (COX) II inhibitors and non-selective non-steroidal anti-inflammatory (NSAIDs). A total of 2818 members were registered on the managed care database of the chronic condition RA and 1372 members were identified as using COX II inhibitors and 827 members were using nonsteroidal anti-inflammatory (NSAIDs). The prescribing frequency determined for the COX II inhibitors were 48.60% and 29.35% for the NSAIDs. The members identified as either using a COX II inhibitor or a NSAIDs were divided into two groups. The prescribing patterns of each group such as age, gender, co-morbid conditions, concomitant medication use and frequency were analysed and compared to the national institute of clinical excellence (NICE) and the South African Rheumatism and Arthritis Association (SARAA) guidelines for the appropriate prescribing of the COX II inhibitors. Celecoxib was the most frequently prescribed COX II inhibitor accounting for 46% of all the COX II inhibitors identified and diclofenac was the most frequently prescribed NSAID accounting for 34% of all the NSAIDs prescriptions. COX II inhibitors were prescribed more frequently to females with a mean age of 55 years than males. A similar prescribing trend was found with the NSAIDs. The COX II inhibitors were frequently prescribed to patients over the age of 56 with co morbid gastro-oesophageal disease and concomitant warfarin and steroid use. The prescribing patterns found in the managed care environment were similar to those recommended by the NICE and SARAA guidelines. The managed care data showed that the COX II inhibitors, which are supposed to have less gastric adverse side effects, were frequently used in combination with gastroprotective agents (GPA’s). This study indicates that even though COX II inhibitors were prescribed more frequently than NSAIDs in the managed care environment the recommended clinical guidelines and protocols employed by the managed care environment were adhered to. However, there v is a need to closely monitor patients on concomitant GPA’s treatment and COX II inhibitors. This study helped to evaluate the current prescribing patterns of COX II inhibitors in the managed health care environment. This study confirmed that guidelines and protocols were adhered to. These are excellent tools to be used in the managed health care environment to ensure effective and appropriate prescribing.

Pharmaceutical drugs are used extensively by humans and domestic animals. The detection of compounds such as non-steroidal anti-inflammatory drugs (NSAIDs) in effluents of sewage treatment plants and surface waters has raised concerns about whether these drugs have the potential to impact aquatic organisms. However, little is known about either the mechanism of action of NSAIDs or their impact on aquatic organisms. A key indicator of animal stress performance is the elevation in plasma cortisol levels, the primary circulating corticosteroid in teleosts, and the associated metabolic changes in response to stressor exposure. The secretion of cortisol is under the control of the hypothalamus-pituitary-interrenal (HPI) axis with the terminal step involving the activation of interrenal steroidogenesis by adrenocorticotropic hormone (ACTH) from the pituitary gland. Cortisol, predominantly via glucocorticoid receptor (GR) activation, is involved in a wide array of animal functions, including growth and metabolism, osmo- and iono-regulation, stress and immune function and reproduction, all of which play a role in regaining homeostasis after stressor insult. The overall objective of this thesis was to investigate the role of NSAIDs in impacting the evolutionarily-conserved adaptive stress response in a model teleost fish, the rainbow trout (Oncorhynchus mykiss). Specifically, the impact of NSAIDs on stress coping mechanisms was investigated by examining: i) interrenal steroid biosynthetic capacity and cortisol production, ii) target tissue GR function, iii) cellular heat shock protein response, iv) tissue-specific metabolic response to stressors, and iv) ionoregulatory performance in seawater. The experimental approach involved a series of whole animal in vivo and in vitro studies, using rainbow trout interrenal cell preparations, with two NSAIDs, salicylate and ibuprofen, commonly detected in our surface waters. Fish were subjected to stressors of varying intensity and duration, including handling disturbance, heat shock and salinity exposures, to identify targets impacted by NSAIDs in fish. NSAIDs did not affect resting plasma cortisol levels but disrupted the acute ACTH-stimulated corticosteroidogenesis in vitro and stressor-induced plasma cortisol response in vivo. The mode of action of NSAIDs in disrupting cortisol production involves inhibition of the key rate-limiting step, the steroidogenic acute regulatory protein (StAR), in steroidogenesis. Also, tissue (brain, liver and gill) GR protein content is a target for endocrine disruption by NSAIDs leading to abnormal negative feedback regulation of plasma cortisol levels and reduced target tissue responsiveness to cortisol after stressor exposure. The drugs also clearly affected the cellular stress response in rainbow trout by perturbing the expression of heat shock protein 70 (hsp70), a highly conserved stress coping mechanism. This impaired heat shock response with NSAIDs corresponded with an altered tissue metabolic capacity suggesting disturbances in biochemical adjustments to stressor. Specifically, the dynamics of glucose, the primary fuel to cope with the enhanced tissue metabolic demand, was disrupted in a drug-specific manner in rainbow trout. Exposure to NSAIDs also disrupted the ionoregulatory mechanisms critical for seawater acclimation in rainbow trout. The targets for ionoregulatory disturbance in seawater by NSAIDs include the major ion transporter gill Na+/K+-ATPase as well as gill GR, a key signaling protein for Na+/K+-ATPase upregulation in fish. Altogether, NSAIDs disrupt the adaptive endocrine and metabolic stress coping mechanisms in rainbow trout. The targets for endocrine disruption by NSAIDs include multiple sites along the HPI axis as well as target tissue response to cortisol action in fish. Specifically, the mode of action of NSAIDs involves disruption of StAR and GR, two key proteins critical for cortisol production and target tissue responsiveness to this steroid, respectively. While the work presented here identified the mechanism(s) of action of NSAIDs, the environmental relevance of this finding, specifically the impact of concentrations of NSAIDs present in our waterways on fish stress performance, remains to be explored.

Pharmaceutical drugs are used extensively by humans and domestic animals. The detection of compounds such as non-steroidal anti-inflammatory drugs (NSAIDs) in effluents of sewage treatment plants and surface waters has raised concerns about whether these drugs have the potential to impact aquatic organisms. However, little is known about either the mechanism of action of NSAIDs or their impact on aquatic organisms. A key indicator of animal stress performance is the elevation in plasma cortisol levels, the primary circulating corticosteroid in teleosts, and the associated metabolic changes in response to stressor exposure. The secretion of cortisol is under the control of the hypothalamus-pituitary-interrenal (HPI) axis with the terminal step involving the activation of interrenal steroidogenesis by adrenocorticotropic hormone (ACTH) from the pituitary gland. Cortisol, predominantly via glucocorticoid receptor (GR) activation, is involved in a wide array of animal functions, including growth and metabolism, osmo- and iono-regulation, stress and immune function and reproduction, all of which play a role in regaining homeostasis after stressor insult. The overall objective of this thesis was to investigate the role of NSAIDs in impacting the evolutionarily-conserved adaptive stress response in a model teleost fish, the rainbow trout (Oncorhynchus mykiss). Specifically, the impact of NSAIDs on stress coping mechanisms was investigated by examining: i) interrenal steroid biosynthetic capacity and cortisol production, ii) target tissue GR function, iii) cellular heat shock protein response, iv) tissue-specific metabolic response to stressors, and iv) ionoregulatory performance in seawater. The experimental approach involved a series of whole animal in vivo and in vitro studies, using rainbow trout interrenal cell preparations, with two NSAIDs, salicylate and ibuprofen, commonly detected in our surface waters. Fish were subjected to stressors of varying intensity and duration, including handling disturbance, heat shock and salinity exposures, to identify targets impacted by NSAIDs in fish. NSAIDs did not affect resting plasma cortisol levels but disrupted the acute ACTH-stimulated corticosteroidogenesis in vitro and stressor-induced plasma cortisol response in vivo. The mode of action of NSAIDs in disrupting cortisol production involves inhibition of the key rate-limiting step, the steroidogenic acute regulatory protein (StAR), in steroidogenesis. Also, tissue (brain, liver and gill) GR protein content is a target for endocrine disruption by NSAIDs leading to abnormal negative feedback regulation of plasma cortisol levels and reduced target tissue responsiveness to cortisol after stressor exposure. The drugs also clearly affected the cellular stress response in rainbow trout by perturbing the expression of heat shock protein 70 (hsp70), a highly conserved stress coping mechanism. This impaired heat shock response with NSAIDs corresponded with an altered tissue metabolic capacity suggesting disturbances in biochemical adjustments to stressor. Specifically, the dynamics of glucose, the primary fuel to cope with the enhanced tissue metabolic demand, was disrupted in a drug-specific manner in rainbow trout. Exposure to NSAIDs also disrupted the ionoregulatory mechanisms critical for seawater acclimation in rainbow trout. The targets for ionoregulatory disturbance in seawater by NSAIDs include the major ion transporter gill Na+/K+-ATPase as well as gill GR, a key signaling protein for Na+/K+-ATPase upregulation in fish. Altogether, NSAIDs disrupt the adaptive endocrine and metabolic stress coping mechanisms in rainbow trout. The targets for endocrine disruption by NSAIDs include multiple sites along the HPI axis as well as target tissue response to cortisol action in fish. Specifically, the mode of action of NSAIDs involves disruption of StAR and GR, two key proteins critical for cortisol production and target tissue responsiveness to this steroid, respectively. While the work presented here identified the mechanism(s) of action of NSAIDs, the environmental relevance of this finding, specifically the impact of concentrations of NSAIDs present in our waterways on fish stress performance, remains to be explored.

A number of studies have indicated that individuals with arthritis have a decreased risk for Alzheimer's disease (AD). Inflammatory processes are implicated in the neurodegeneration associated with AD and the reduced risk associated with arthritis may be due to the anti-inflammatory (AI) drugs used by these individuals. The present project used magnetic resonance imaging (MRI) to assess the integrity of gray and white brain matter in AI users compared to controls not taking AIs. Thirty six female AI users were compared to thirty three controls. All participants underwent extensive neuropsychological testing. MRI scans included diffusion-weighted imaging, sensitive to the microstructural integrity of brain matter, high resolution anatomical imaging for the determination of brain volume, and T2 fluid attenuated inversion recovery (FLAIR) imaging, sensitive to white matter damage that is seen as hyperintense regions on this type of image. AI users showed increased brain integrity in the frontal lobes and in the corpus callosum, compared to controls indicated by diffusion imaging. Volumetric analysis indicated that AI users and controls have different relationships between brain volume and age. AI users showed greater brain volume than controls at higher ages, particularly in frontal and parietal brain regions, and in the cingulate. White matter hyperintensity volume did not differ between AI users and controls. Finally, the data indicated that non-steroidal anti-inflammatory drug (NSAID) use, but not methotrexate use, had a beneficial effect on cognitive function, particularly in the domain of memory function.

No description available.

Dissertation submitted in partial compliance with the requirements for the Masters Degree in Technology: Chiropractic, Durban University of Technology, 2010. / The 1 year overall prevalence of Episodic Tension-Type Headache (ETTH) is 38.3%; with lifetime prevalence at 46% for TTH. Little literature exists to support the effectiveness of spinal manipulation in the treatment of ETTH. Therefore aim of this study was to determine the relative effectiveness of cervical spine manipulation and a Nonsteroidal Anti-inflammatory drug (NSAID) (Ibuprofen®) in the treatment of ETTH. Method: This study was a prospective randomised clinical trial with two intervention groups (N=32, n1=16 and n2=16). The allocation of participants to the two groups was completed by means of simple randomization. Group one were treated using cervical spine manipulation. Group two were treated using Ibuprofen. Subjective measurements included the Numerical Rating Scale 101 Questionnaire (NRS-101), Short Form McGill Pain Questionnaire (SF-MPQ), CMCC Neck Disability Index (CMCC) and Headache Diary. A p value <0.05 was considered as statistically significant. Results: The subjective measurements of the NRS-101, SF-MPQ and CMCC showed a significant time effect in both treatment groups. Several of the subjective Headaches Diary outcomes followed this trend with significant time effect in both groups. There was a significant treatment effect for the NRS-101. Several subject outcomes from the Headache Diary showed a significant treatment effect in favour of manipulation, namely frequency and duration of headaches. Conclusion: The findings in this study have shown that cervical spine manipulation is more effective than Ibuprofen® for the treatment of ETTH in terms of several subjective outcomes namely: pain intensity (NRS-101), and the frequency and the duration of headache per day.

Det finns många läkemedel som höjer blodtrycket eller interagerar med antihypertensiva läkemedel vilket motverkar en blodtryckssänkning. Den vanligaste interaktionen är en försämring av de antihypertensiva läkemedlens effekt på grund av intag av non steroidal anti-inflammatory drugs, NSAIDs (7). Syftet med denna litteraturstudie är att försöka besvara: Hur påverkas olika grupper av antihypertensiva läkemedel? Hur påverkar traditionella NSAID preparat respektive COX-2 hämmare effekten av antihypertensiva läkemedel? Hur allvarliga är interaktionerna? Vilken dos behövs för att en interaktion mellan NSAIDs och antihypertensiva läkemedel ska uppstå? Vilka typer av patienter utgör riskgrupper? Nio randomiserade kontrollerade kliniska studier inkluderades i detta examensarbete. Studierna undersökte sju olika NSAIDs; diklofenak, ibuprofen, indometacin, piroxikam, sulindac, celecoxib och rofecoxib, och representerade flertalet olika typer av antihypertensiva läkemedelsbehandlingar. Ingen signifikant påverkan på blodtrycket sågs då NSAIDs kombinerades med kalciumantagonister. En signifikant ökning av blodtrycket sågs för ACE-hämmare, ARBs, betablockare och diuretika. Ingen av studierna visade någon signifikant skillnad på interaktionskänslighet mellan ACE-hämmare, ARBs, betablockare eller diuretika. Blodtrycksökningar sågs för diklofenak, ibuprofen, indometacin, piroxikam, och rofecoxib. Celecoxib undersöktes i tre studier och påverkade inte blodtrycket i någon av dem. Slutsatser: Den individuella kardiovaskulära risken för olika NSAIDs beror på flera olika faktorer förutom COX-2 specificitet. Risken är svårbedömd och ännu kan inga NSAIDs klassas som säkra vad gäller kardiovaskulär risk. Dock tycks celecoxib sakna blodtryckhöjande effekter och skulle kunna vara ett bra alternativ för de hypertoniker som behöver samtidig behandling med NSAID preparat. Trots detta kan inga slutsatser dras om celecoxibs kardiovaskulära risk då preparatet skulle kunna påverka andra riskfaktorer förutom blodtryck. Interaktionsmekanismen mellan NSAIDs och antihypertensiva läkemedel är fortfarande oklar och fler studier på detta område behövs. Men troliga teorier är att NSAIDs hämning prostaglandinsyntesen ger en ökad perifer resistens samt en ökad volymretention. Båda dessa effekter ger ett ökat blodtryck. Interaktionen ger relativt små blodtrycksökningar men dessa är kliniskt relevanta då de kvarstår en längre tid. Hos hypertonipatienter där samtidig behandling med NSAIDs är nödvändigt bör blodtrycket och njurfunktion stå under noggrann övervakning.