Spelling suggestions: "subject:"nonpharmacological"" "subject:"onpharmacological""
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Classification, Evolution, Pharmacology and Structure of G protein-coupled ReceptorsLagerström, Malin C January 2006 (has links)
G protein-coupled receptors (GPCR) are integral membrane proteins with seven α-helices that translate a remarkable diversity of signals into cellular responses. The superfamily of GPCRs is among the largest and most diverse protein families in vertebrates. We have searched the human genome for GPCRs and show that the family includes approximately 800 proteins, which can divided into five main families; Glutamate, Rhodopsin, Adhesion, Frizzled/Taste2 and Secretin. This study represents one of the first overall road maps of the GPCR family in a mammalian genome. Moreover, we identified eight novel members of the human Adhesion family which are characterized by long N-termini with various domains. We also investigated the GPCR repertoire of the chicken genome, where we manually verified a total of 557 chicken GPCRs. We detected several specific expansions and deletions that may reflect some of the functional differences between human and chicken. Substantial effort has been made over the years to find compounds that can bind and activate the melanocortin 4 receptor (MC4R). This receptor is involved in food intake and is thus an important target for antiobesity drugs. We used site-directed mutagenesis to insert micromolar affinity binding sites for zinc between transmembrane (TM) regions 2 and 3. We generated a molecular model of the human MC4R which suggests that a rotation of TM3 is important for activation of the MC4R. Furthermore, we present seven new vertebrate prolactin releasing hormone receptors (PRLHRs) and show that they form two separate subtypes, PRLHR1 and PRLHR2. We performed a pharmacological characterization of the human PRLHR which showed that the receptor can bind neuropeptide Y (NPY) related ligands. We propose that an ancestral PRLH peptide has coevolved with a redundant NPY binding receptor, which then became PRLHR. This suggests how gene duplication events can lead to novel peptide ligand/receptor interactions and hence spur the evolution of new physiological functions.
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Farmakologisk omvårdnad hos äldre / Pharmacological care in the elderlyLundberg, Linda, Storck, Carina January 2013 (has links)
Av de läkemedel som förskrivs i Sverige, konsumerar de äldre över 65 år ca 40 %. Anledningen är att denna grupp drabbas av många sjukdomar och behandlas med fler läkemedel. Äldre får generellt sett annorlunda och fler biverkningar än yngre. Syftet med uppsatsen var att beskriva hur sjuksköterskan kan säkerställa en god farmakologisk omvårdnad hos äldre och uppmärksamma de konsekvenser som uppstår till följd av polyfarmaci. Studien utfördes som en litteraturstudie där 22 vetenskapliga artiklar granskades och analyserades varefter två teman framträdde. Dessa båda teman var förutsättningar för god farmakologisk omvårdnad och konsekvenser vid polyfarmaci. Läkemedelsrelaterade problem är en vanlig orsak till sjukhusinläggningar och fördröjer ofta utskrivningen. Läkemedelsbiverkningarna ökar med antalet konsumerade läkemedel. Den farmakologiska kunskapen upplevs som bristfällig bland sjuksköterskorna. Även kortare utbildningar ger ökad kunskap vilket leder till att fler läkemedelsrelaterade problem upptäcks och biverkningar rapporteras i högre grad. Utbildning och användande av bedömningsmallar kan därför förbättra den farmakologiska omvårdnaden. / Elderly often have several diseases and treated with many drugs. They use about 40 percent of all prescribed medications in the country and get different and more adverse events than younger. The aim of the study was to describe how the nurse can ensure a good pharmacological nursing in the elderly and pay attention to the consequences that arise as a result of polypharmacy. The study was conducted as a litterature study there 22 scientific articles were reviewed and analyzed whereafter two themes were found. Those were conditions for pharmacological care and polypharmacy consequences. Drug related problems are a common cause of hospital admissions and delays often discharge. Adverse drug reactions increases with the number consumed medicines. The pharmacological knowledge is perceived as deficient among nurses. Shorter courses provide increased knowledge leading to more drug-related problems were discovered and side effects were reported more often. Education and use of assessment templates leads to improved pharmacological care.
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Det var höjdpunkten under hans dag : Musikens inverkan på människor med demenssjukdom och deras vårdgivare.Tapper, Karin, Wickström, Linn January 2012 (has links)
Bakgrund: Personer med demens har en försämrad förmåga att förstå och kommunicera med omgivningen och därför kan det vara svårt och krävande att vårda personer med demens. Agitation är ett vanligt beteendeproblem vid demenssjukdom och är påfrestande för såväl personen med demens, som för vårdgivaren. Personer med demens behandlas främst farmakologiskt trots de biverkningar som läkemedelsbehandlingen orsakar och därför behövs andra behandlingsstrategier och omvårdnadsåtgärder för att öka välbefinnandet och minska deras lidande. Syfte: Att beskriva musikens inverkan på människor med demenssjukdom och deras vårdgivare. Metod: En systematisk litteraturöversikt av fjorton kvalitativa och kvantitativa vetenskapliga artiklar som sedan analyserades och sammanställdes i ett resultat. Resultat: Musik visade sig ha en övervägande positiv inverkan på personer med demenssjukdom och deras vårdgivare. De demenssjuka personernas agitation minskade, deras möjlighet att kommunicera förbättrades och de fick en ökad livskvalitet. Vårdgivarnas samarbete med den demenssjuka personen förbättrades och de blev mer närvarande i omvårdnaden. Slutsats: Musiken inverkade på ett övervägande positivt sätt i omvårdnaden av demenssjuka personer och gav även en positiv inverkan på de demenssjuka personernas vårdgivare. Resultatet visar att musik kan vara användbart för att förbättra vården av personer med demens och kan förmodligen fungera som en icke-farmakologisk behandling i omvårdnaden. / Background: People with dementia have an impaired ability to understand and communicate with their environment and it can be difficult and demanding to care for people with dementia. Agitation is a common behavior problem in dementia and this is stressful for both the person with dementia, as for the caregiver. People with dementia are treated primarily pharmacological despite the many side effects that drug therapy induced and therefore requires other treatments strategies and nursing interventions to improve wellbeing and to reduce their suffering. Aim: To describe the impact of music on people with dementia and their caregivers. Method: A systematic literature review of fourteen qualitative and quantitative research articles that then were analyzed and summarized in the result. Results: Music was found to have a predominantly positive impact on people with dementia and their caregivers. The dementia person’s agitation decreased, their ability to communicate improved and they had an improved quality of life. The caregiver’s cooperation with the dementia persons was improved and they became more present in the care. Conclusion: The music had a mainly positive impact in the care of persons with dementia and also gave a positive impact on the caregivers. The results show that music probably can be useful for improving the care of people with dementia and can act as a non-pharmacological treatment in the care.
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Sömn, depressionssymtom, livskvalitet och Alzheimers sjukdom / Sleep, Depression, Quality of Life and Alzheimer´s DiseaseDjupdalen, Rhiannon January 2012 (has links)
Background: Sleep-disturbances in persons with Alzheimer´s disease are prevalent. They are characterized as increased frequency and duration of awakenings, decreased slow-wave sleep, REM-sleep and increase of day-time napping. Depression and lower quality of life are associated with sleep-disturbances. Altogether a significant source of stress for caregivers and an important factor in institutionalization. Non-pharmacological treatment alternatives are rare. Method: Single-case A-B-C design, with non-concurrent multiple baselines, a pilotstudy. Aim: To explore if an educational program on sleep, sleep disturbances and behavioural change directed towards caregivers improved sleep, depression and quality of life in persons with Alzheimer´s disease living at home. A second aim was to test program and method. Result: Three patients/cases were included and in one case sleep was improved. Depression and quality of life outcome varied in all cases. The program and method has the potential of being useful after some adjustments. Conclusion: Non-pharmacological treatments are needed and this study shows that a behavioural program is a feasible way to improve sleep in patients with Alzheimer´s disease. More research is needed to develop method and increase overall knowledge within the area. Knowledge of sleep and non-pharmacological treatments for sleep problems are scarce in clinical environment and nurses have an important task.
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Sjuksköterskors erfarenhet av att använda icke-farmakologisk behandling vid procedursmärta hos barn : En litteraturstudieLarsson, Madelene, Persson, Erika January 2015 (has links)
Background: Most procedures in healthcare were described to cause the child pain. Anxiety was also strongly linked to pain and painful experience can generate future consequences for the child in contact with health services. Administering medication to children was considered difficult to adapt while non-pharmacological treatment is considered to be both time- and cost efficient. Purpose: To describe nurses' use of non-pharmacological treatment of procedural pain in children and to examine the included articles research group.Method: This descriptive literature studies results was based on 15 articles sought in the databases Cinahl, PsycINFO and PubMed. Eight of the included articles were qualitative studies, four were quantitative studies and three were studies with mixed approach. Main Results: Non-pharmacological treatment of procedural pain in children was considered effective when it was formed based on each unique child and occasion. The nurses described distraction as a useful method that can be performed in several ways, ranging from the child's needs. The importance of a good relationship, a working cooperation and that the nurse had the ability to get the child's confidence was described as key elements in non-pharmacology. The research group characteristics were examined and in all articles the participants profession consists in the majority of nurses. Conclusion: Non-pharmacological treatment of procedural pain should be adjusted based on the unique child and the situation. Distraction was considered by the majority of nurses to be a positive and useful non-pharmacological treatment of procedural pain in children and can be performed by both nurses and parents to reduce the child's pain and future fears. / Bakgrund: Ett flertal procedurer inom vården beskrevs kunna orsaka barnet smärta. Oro var vidare starkt kopplat till smärta och en tidigare smärtsam upplevelse kan komma att generera framtida konsekvenser för barnet i kontakt med sjukvården. Administreringen utav läkemedel till barn ansågs vara svårt att anpassa samtidigt som icke-farmakologisk behandling anses vara både tids- och kostnadseffektiv. Syfte: Att beskriva sjuksköterskors användning av icke-farmakologisk behandling vid procedursmärta hos barn, samt att granska de inkluderade artiklarnas undersökningsgrupp. Metod: Denna beskrivande litteraturstudies resultat grundades på 15 artiklar eftersökta i databaserna Cinahl, PsycINFO och PubMed. Åtta av studiens inkluderade artiklar hade kvalitativ ansats, fyra hade kvantitativ ansats och tre var studier med mixad ansats. Huvudresultat: Icke-farmakologisk behandling vid procedursmärta hos barn ansågs effektivt när den formades utifrån varje unikt barn och tillfälle. Sjuksköterskorna beskrev distraktion som en användbar metod som kan utföras på flertalet sätt, allt utifrån barnets behov. Vikten av en fungerande relation, ett fungerande samarbete och att sjuksköterskan hade förmåga att få barnets förtroende beskrevs vidare som centrala delar inom icke-farmakologin. Artiklarnas beskrivning av undersökningsgrupp granskades och deltagarnas yrkeskategori utgjordes i majoritet av sjuksköterskor i samtliga fall. Slutsats: Icke-farmakologisk behandling vid procedursmärta bör anpassas utifrån det unika barnet och situationen. Distraktion ansågs av majoriteten sjuksköterskor vara en positiv och användbar icke-farmakologisk behandling vid procedursmärta hos barn och kan utföras av både sjuksköterskor och föräldrar för att minska barnets smärta och framtida rädslor.
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Hjärtsviktspatienters följsamhet till, samt beskrivningar och upplevelser av, att följa icke-farmakologiska behandlingsriktlinjer – en litteraturstudieBergström, Filippa, Granevåg, Anna January 2014 (has links)
Bakgrund: Hjärtsvikt är vanligt förekommande i den svenska befolkningen och är den vanligaste orsaken till sjukhusinläggning. Bristande följsamhet till den farmakologiska hjärtsviktbehandlingen är idag ett stort problem inom sjukvården. Detta bidrar till ökade sjukhusinläggningar samt ökad dödlighet hos hjärtsviktspatienterna. Icke-farmakologisk behandling har dock kunnat ses som ett komplement till den farmakologiska behandlingen. Syfte: Syftet med denna litteraturstudie var att beskriva patienters följsamhet till, samt beskrivningar och upplevelser av, att följa icke-farmakologiska riktlinjer i samband med hjärtsvikt. En granskning av kvaliteten beträffande de inkluderade studiernas undersökningsgrupp utfördes även. Metod: En beskrivande litteraturstudie där 12 vetenskapliga artiklar inkluderades. Artiklarna söktes vid databaserna Pubmed och Cinahl. Delar från studiernas resultat plockades ut och analyserades. Dessa delades sedan upp under kategorier och underkategorier passande för att svara till litteraturstudiens frågeställningar. Resultat: Generellt var följsamheten till de icke-farmakologiska behandlingsriktlinjerna bristande. Flest antal hinder identifierades beträffande riktlinjer gällande saltrestriktioner. Törst, glömska, samt fysiska symtom var även de stora hinder till en följsam icke-farmakologisk behandling. De största fördelarna som identifierades till en följsam behandling var ökat välmående samt minskade sjukhusinläggningar. Slutsats: En generellt bristande följsamhet till de icke-farmakologiska behandlingsriktlinjerna gällande salt- och vätskerestriktioner, regelbunden vägning samt träning förekommer bland hjärtsviktspatienter. Många hinder till en följsam behandling identifierades, men även fördelar till att vara följsam till icke-farmakologiska behandlingsriktlinjer beskrevs i studierna. / Background: Heart failure is a common disease among the Swedish population today and it is also the number one cause of hospitalisation. A lack of compliance with the pharmacological treatment for heart failure is a big issue within the medical services today. This significantly contributes to increased hospitalisation as well as higher mortality rates among Heart failure patients. However, non-pharmacological treatments have been found to be a rather good complement to the pharmacological treatment. Aim: The purpose of this literature study was to describe patients’ compliance with, as well as their experiences and accounts of, following non-pharmacological guidelines in connection to heart failure. An examination of the included studies’ focus groups and their quality was done as well. Method: A descriptive literature study where twelve scientific articles were included. The articles were found on the databases Pubmed and Cinahl. Parts of the study’s results were selected and analysed. These were then divided into categories and subcategories that suited the literature study’s research questions. Result: The compliance with the non-pharmacological treatment guidelines was generally inadequate. The most obstacles were found concerning the guidelines the patients got regarding the restrictions on salt. Thirst, forgetfulness, and physical symptoms were also big obstacles for complying with a non-pharmacological treatment. The biggest advantages of complying with the treatment that were identified were an increased sense of well-being and decreased hospitalisation. Conclusion: A general lack of compliance with the non-pharmacological treatment guidelines concerning the restrictions on salt and fluid, regular weigh-ins, and exercise occur among heart failure patients. Many obstacles to complying with treatment were identified, but the advantages of complying with non-pharmacological treatment guidelines were also described in the study.
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Cerebral blood flow in the non-human primate : an in vivo model and drug interventions / Douglas W. OliverOliver, Douglas William January 2003 (has links)
Cerebral blood flow dynamics is an essential component for preserving
cerebral integrity. Cerebral blood flow abnormalities are often seen in patients
with central nervous system pathologies such as epilepsy, migraine,
Alzheimer's Disease, vascular dementia, stroke, and even HIV/AIDS. There is
increasing clinical and experimental evidence implicating cerebral
hypoperfusion during ageing. The determination of cerebral perfusion has
therefore become an important objective in physiological, pathological,
pharmacological, and clinical investigations. The knowledge of regional
cerebral blood flow further provides useful diagnostic information and/or data
for a better understanding of the complex clinical presentations in patients with
neurological and psychiatric disorders. Several cerebrovasoactive drugs have
found application in the clinical setting of cerebrovascular diseases such as
migraine and dementia.
Due to the similarities between humans and non-human primates with
respect to their brains, both structurally and behaviourally, numerous studies
have been conducted and several non-human primate models have been
developed for physiological, pathological, pharmacological, and clinical studies,
amongst others in Parkinson's disease and diabetes. The relatively large size
of the Cape baboon Papio Ursinus with a weight of 27-30 kg for a large male,
makes this primate especially suitable for in vivo brain studies using
radiotracers and Single Photon Emission Computed Tomography (SPECT).
The main aim of the current study was therefore to develop a suitable
radiotracer (99m Tc-hexamethylpropylene amine oxime (HMPAO) or 99m Tc_ethyl_cysteinatedimer (ECD) or 123l-iodoamphetamine (IMP)) for adapted in vivo
cerebral blood flow measurements in a non-human primate (Papio ursinus) as
an investigative model. The model was to be validated and applied in various
drug studies for the evaluation of pharmacological interventions. The study
design made use of split-dose methodology, whereby the radiopharmaceutical
(radiotracer) was administered twice during each study. The first administration
was injected soon after the induction of the anaesthesia, and was followed by
the first SPECT data acquisition. The second administration of the radioligand,
a double dose of radioactivity with respect to the first radioligand injection, was
done at a specific time during the study, which took into account the
pharmacodynamics of the drug. A second SPECT data acquisition followed
subsequently. The drugs that were included in the study were acetazolamide,
a carbonic acid anhydrase inhibitor (often used in nuclear medicine to
determine cerebral reserve); sumaptriptan, a 5-HT (serotonin) agonist used for
treatment of migraine; sodium valproate (an anti-epileptic drug); nimodipine, a
calcium channel blocker and nitro-glycerine, a vasodilator used for angina.
Arterial blood pressures were recorded from a catheter in the femoral artery
and heart rates were concurrently monitored.
The split-dose method was successfully applied to develop a non-human
primate cerebral blood flow model under anaesthesia. The model showed
differences in cerebral perfusion of the different anaesthesia regimes. These
anaesthesia data sets were suitable as control/baseline results for drug
intervention studies. Acetazolamide evaluation through the split-dose method
in the baboon confirmed the sensitivity of the model by presenting comparable
perfusion. This result compared to those already familiar prompted the model
to be applied in pharmacological intervention studies. Subsequent results of
these investigations showed increases in perfusion for single drug nimodipine
treatment (25%). However, nimodipine attenuated the increases in perfusion
when administered in combination with acetazolamide. Sumatriptan was able
to decrease and normalise the increased perfusion after long duration
anaesthesia. Decreased cerebral blood flow was observed for combinations of
nimodipine with sodium valproate suggesting drug-drug interaction with
important clinical implications. Similar decreases were found also for
sumatriptan and nitro-glycerine when administered in combination with
nimodipine.
Studies with the various tracers (99m Tc_HMPAO or 99m Tc_ECD or 123l_IMP)
showed clear differences in the perfusion data, confirming variation in the
biochemical performance of the tracers. These differences, if not taken into
consideration, caution for inappropriate clinical conclusions and subsequent
erroneous therapeutic decisions. Improvement of radiotracer efficacy was
subsequently attempted through application of the cyclodextrine complexation
approach. Although cyciodextrine technology did not markedly improve the
brain disposition of the 99m Tc-ECD, protection of the tracer against degradation
was demonstrated. This study encouraged further exploration of this method for
protection of the tracer against chemical and metabolic degradation.
The current study was aimed to develop and effectively apply a non-human
primate model with nuclear medicine technology for cerebral blood flow
determinations after pharmacological interventions. This was achieved through
the split-dose method and dedicated computer programming, which yielded a
successful model with the non-human primate under anaesthesia. The model
was validated with the application of acetazolamide to confirm familiar
cerebrovascular reserve results, indicating that the model is sensitive to CBF
changes. The model was also effectively applied in several pharmacological
intervention studies, whereby cerebropharmacodynamics of selected drugs
were investigated and established.
This unique model of a non-human primate, Papio ursinus for cerebral blood
flow determinations has served pharmacological research successfully during
the past 12 years and could do so in the future, with scope to investigate new
frontiers with improved technologies. / Thesis (Ph.D. (Pharmacology))--North-West University, Potchefstroom Campus, 2004.
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A biophysical study of intranuclear herpes simplex virus type 1 DNA during lytic infectionLacasse, Jonathan J Unknown Date
No description available.
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Nöjd och glad : Icke - farmakologiska omvårdnadsåtgärder i demensvårdZerom, Senait, Yuldasheva, Nodira January 2014 (has links)
abstract Background: Dementia affected patients have increasing problems with memory , impaired language ability, which affects communication and behaviour is considerable. These difficulties may provide an outlet for aggression, agitation and anxiety, and are common in dementia, which is exhausting for patients and their relatives and carers. Behavioural changes are common condition in patients with dementia and affects quality of life and cause unnecessary suffering . Pharmacological treatment that is inserted to relieve these symptoms have many side effects. Printed out more knowledge about non- pharmacological nursing interventions that can facilitate care for patients , relatives and carers are great. Aim: To describe non- pharmacological nursing interventions in dementia care . Method: A general literature review of thirteen scientific papers compiled and described in a result. Results: Compilation resulted in two themes, Music in dementia care and Stimulation in dementia care and four subthemes, Singing in the care, Listening to music, Activities and Consolation and fillip that showed a dominant positive effect on dementia affected patients and carers and there by create opportunities for caring in dementia care . Conclusion: The different nursing interventions may be useful in dementia care when they show a dominant positive effect on various behavioural changes, it seems memory stimulant and promotes communication between patients and carers which favours caring . Keywords: Agitated behaviour, dementia, non- pharmacological, literature review, nursing. / Sammanfattning Bakgrund: Demensdrabbade patienter har tilltagande besvär med minnet, försämrad språkförmåga, vilket påverkar kommunikationen och beteende avsevärd. Dessa svårigheter kan ge utlopp till aggressivitet, oro och ångest och är vanliga vid demenssjukdomar vilket är ansträngande för både patienter, anhöriga och vårdare. Beteendeförändringar är vanligt förekommande tillstånd hos patienter med demens och påverkar livskvalitet och medför onödigt lidande. Farmakologisk behandling som sätts in för att lindra dessa symtom har många biverkningar. Behov utav ökad kunskap kring icke- farmakologiska omvårdnadsåtgärder som kan underlätta omvårdnaden för både patienter, anhöriga och vårdarna är stor. Syfte: Att beskriva icke- farmakologiska omvårdnadsåtgärder i demensvård. Metod: En allmän litteraturöversikt av tretton vetenskapliga artiklar som sammanställdes och beskrivs i ett resultat. Resultat: Sammanställningen resulterade i 2 teman, Musik i demensvård och Stimulans i demensvård och 4 subteman, Sång i omvårdnaden, Att lyssna på musik, Aktivitet och Tröst och stumulans som påvisade en dominerande positiv effekt på demensdrabbade patienter samt vårdarna och därigenom gynnande för vårdandet i demensvård. Slutsats: De olika omvårdnadsåtgärder kan vara användbara inom demensvården då dem visar på en dominerande positiv påverkan på olika beteendeförändringar, verkar minnesstimulerande samt främjar kommunikation mellan patienter och vårdare vilket gynnar vårdandet. Nyckelord: Agiterat beteende, demens, icke- farmakologisk, litteraturöversikt, omvårdnad
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Cerebral blood flow in the non-human primate : an in vivo model and drug interventions / Douglas W. OliverOliver, Douglas William January 2003 (has links)
Cerebral blood flow dynamics is an essential component for preserving
cerebral integrity. Cerebral blood flow abnormalities are often seen in patients
with central nervous system pathologies such as epilepsy, migraine,
Alzheimer's Disease, vascular dementia, stroke, and even HIV/AIDS. There is
increasing clinical and experimental evidence implicating cerebral
hypoperfusion during ageing. The determination of cerebral perfusion has
therefore become an important objective in physiological, pathological,
pharmacological, and clinical investigations. The knowledge of regional
cerebral blood flow further provides useful diagnostic information and/or data
for a better understanding of the complex clinical presentations in patients with
neurological and psychiatric disorders. Several cerebrovasoactive drugs have
found application in the clinical setting of cerebrovascular diseases such as
migraine and dementia.
Due to the similarities between humans and non-human primates with
respect to their brains, both structurally and behaviourally, numerous studies
have been conducted and several non-human primate models have been
developed for physiological, pathological, pharmacological, and clinical studies,
amongst others in Parkinson's disease and diabetes. The relatively large size
of the Cape baboon Papio Ursinus with a weight of 27-30 kg for a large male,
makes this primate especially suitable for in vivo brain studies using
radiotracers and Single Photon Emission Computed Tomography (SPECT).
The main aim of the current study was therefore to develop a suitable
radiotracer (99m Tc-hexamethylpropylene amine oxime (HMPAO) or 99m Tc_ethyl_cysteinatedimer (ECD) or 123l-iodoamphetamine (IMP)) for adapted in vivo
cerebral blood flow measurements in a non-human primate (Papio ursinus) as
an investigative model. The model was to be validated and applied in various
drug studies for the evaluation of pharmacological interventions. The study
design made use of split-dose methodology, whereby the radiopharmaceutical
(radiotracer) was administered twice during each study. The first administration
was injected soon after the induction of the anaesthesia, and was followed by
the first SPECT data acquisition. The second administration of the radioligand,
a double dose of radioactivity with respect to the first radioligand injection, was
done at a specific time during the study, which took into account the
pharmacodynamics of the drug. A second SPECT data acquisition followed
subsequently. The drugs that were included in the study were acetazolamide,
a carbonic acid anhydrase inhibitor (often used in nuclear medicine to
determine cerebral reserve); sumaptriptan, a 5-HT (serotonin) agonist used for
treatment of migraine; sodium valproate (an anti-epileptic drug); nimodipine, a
calcium channel blocker and nitro-glycerine, a vasodilator used for angina.
Arterial blood pressures were recorded from a catheter in the femoral artery
and heart rates were concurrently monitored.
The split-dose method was successfully applied to develop a non-human
primate cerebral blood flow model under anaesthesia. The model showed
differences in cerebral perfusion of the different anaesthesia regimes. These
anaesthesia data sets were suitable as control/baseline results for drug
intervention studies. Acetazolamide evaluation through the split-dose method
in the baboon confirmed the sensitivity of the model by presenting comparable
perfusion. This result compared to those already familiar prompted the model
to be applied in pharmacological intervention studies. Subsequent results of
these investigations showed increases in perfusion for single drug nimodipine
treatment (25%). However, nimodipine attenuated the increases in perfusion
when administered in combination with acetazolamide. Sumatriptan was able
to decrease and normalise the increased perfusion after long duration
anaesthesia. Decreased cerebral blood flow was observed for combinations of
nimodipine with sodium valproate suggesting drug-drug interaction with
important clinical implications. Similar decreases were found also for
sumatriptan and nitro-glycerine when administered in combination with
nimodipine.
Studies with the various tracers (99m Tc_HMPAO or 99m Tc_ECD or 123l_IMP)
showed clear differences in the perfusion data, confirming variation in the
biochemical performance of the tracers. These differences, if not taken into
consideration, caution for inappropriate clinical conclusions and subsequent
erroneous therapeutic decisions. Improvement of radiotracer efficacy was
subsequently attempted through application of the cyclodextrine complexation
approach. Although cyciodextrine technology did not markedly improve the
brain disposition of the 99m Tc-ECD, protection of the tracer against degradation
was demonstrated. This study encouraged further exploration of this method for
protection of the tracer against chemical and metabolic degradation.
The current study was aimed to develop and effectively apply a non-human
primate model with nuclear medicine technology for cerebral blood flow
determinations after pharmacological interventions. This was achieved through
the split-dose method and dedicated computer programming, which yielded a
successful model with the non-human primate under anaesthesia. The model
was validated with the application of acetazolamide to confirm familiar
cerebrovascular reserve results, indicating that the model is sensitive to CBF
changes. The model was also effectively applied in several pharmacological
intervention studies, whereby cerebropharmacodynamics of selected drugs
were investigated and established.
This unique model of a non-human primate, Papio ursinus for cerebral blood
flow determinations has served pharmacological research successfully during
the past 12 years and could do so in the future, with scope to investigate new
frontiers with improved technologies. / Thesis (Ph.D. (Pharmacology))--North-West University, Potchefstroom Campus, 2004.
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