The purification and biochemical characterization of the substance P (SP) hydrolyzing enzyme, substance P endopeptidase (SPE), have been carried out; with subsequent orientation in neurobiological fundamental processes involved in opioid dependence, withdrawal, and heat-stress. SPE was purified from rat spinal cord, human spinal cord and cerebrospinal fluid (CSF), rat ventral tegemental area (VTA), and rat hippocampus. The enzyme activity was found to release the biologically active fragments SP(1-7) and SP(1-8) as major products. The purified enzymes were characterized with regard to their biochemical and kinetic properties. The typical SPE is neither inhibited by phosphoramidon nor captopril nor phenylmethanesulfonylflourid (PMSF). In comparison to other known proteases SPE differed in characteristics regarding substrate specificity, inhibition-profile, cleavage pattern, and other kinetic parameters. The technically very delicate approach of micro purification of SPE from the rat ventral tegemental area (VTA) (this is a very small tissue), turned out to be possible with the ÄKTA™-purifier system. Studies revealed a crucial role of SPE in a series of clinically important neuropathological conditions, such as opioid tolerance, and withdrawal (SPE, increased); and heat-stress (SPE, increased). These findings emerged from assessment of enzyme activity in hypothalamus, nucleus accumbens (NAc) periaqueductal gray (PAG), pituitary, striatum, substantia nigra (SN), VTA, spinal cord. Viewing the role of SPE in morphine tolerance, it was possible to note regional differences with a decrease in PAG, and striatum, whereas an increase was seen in SN, and VTA. After heat-stress treatment, SPE was raised in several regions (cerebral cortex, hippocampus, diencephalon, cerebellum, spinal cord), and the most precise observation of this was located to the hippocampus structure.

The melanocortin (MC) receptors are G-protein coupled receptors thatparticipate in several important physiological functions such as the regulation of the energy balance. This thesis focuses on the evolutionary aspect of the MC receptors and their pharmacology. One MC4 receptor and two MC5 receptor subtypes were found in a teleost fish, zebrafish. This indicates that the MC receptor subtypes arose very early in vertebrate evolution. Important pharmacological and functional properties, as well as gene structure and syntenic relationships have been highly conserved over a period of more than 400 million years implying that these receptors participate in vital physiological functions. Moreover, we found a MC4 receptor from a shark, spiny dogfish that represents the most distant MC receptor gene cloned to date. We also characterized the pharmacology of a MC4 receptor in goldfish. The conserved central expression pattern and physiological role in regulation of food intake of the MC4 receptor suggests that neuronal pathways of the melanocortin system may be important for regulation of energy homeostasis in most vertebrates. We determined the chromosomal position of the chicken MC receptors genes and found conserved synteny of the MC2, MC5, and MC4 receptor genes. These results suggest that there exist a clustering of these genes that is ancient. Analysis of conserved synteny with mammalian genomes and paralogon segments prompted us to predict an ancestral gene organization that may explain how this family has been formed through both local duplication and tetraploidization processes. There are several common point mutations in the human MC1 receptor that are over represented in North European red-heads, and in individuals with pale skin. We pharmacologically characterised four naturally occurring human MC1 receptor variants providing molecular explanation to the respective phenotype. The MC receptor subtypes have highly diverse physiological functions despite having relative high similarities in their primary structure. Our studies on the structural and functional properties of the MC receptor subtypes have provided insight into the molecular mechanism of how the specification of these receptors may have occurred.

G protein-coupled receptors (GPCRs) are one of the largest protein families in mammals. GPCRs are instrumental for hormonal and neurotransmitter signalling and are important in all major physiological systems of the body. Paper I describes the repertoire of GPCRs in Branchiostoma floridae, which is one of the species most closely related species to vertebrates. Mining and phylogenetic analysis of the amphioxus genome showed the presence of at least 664 distinct GPCRs distributed among all the main families of GPCRs; Glutamate (18), Rhodopsin (570), Adhesion (37), Frizzled (6) and Secretin (16). Paper II contains studies of the Adhesion, Methuselah and Secretin GPCR families in nine genomes. The Adhesion GPCRs are the most complex gene family among GPCRs with large genomic size, multiple introns and a fascinating flora of functional domains. Phylogenetic analysis showed Adhesion group V (that contains GPR133 and GPR144) to be the closest relative to the Secretin family among the groups in the Adhesion family, which was also supported by splice site setup and conserved motifs. Paper III examines the repertoire of human transmembrane proteins. These form key nodes in mediating the cell’s interaction with the surroundings, which is one of the main reasons why the majority of drug targets are membrane proteins. We identified 6,718 human membrane proteins and classified the majority of them into 234 families of which 151 belong to the three major functional groups; Receptors (63 groups, 1,352 members), Transporters (89 groups, 817 members) or Enzymes (7 groups, 533 members). In addition, 74 Miscellaneous groups were shown to include 697 members. Paper IV clarifies the hierarchy of the main families and evolutionary origin of majority of the metazoan GPCR families. Overall, it suggests common decent of at least 97% of the GPCRs sequences found in humans, including all the main families.

Patienter med kronisk obstruktiv lungsjukdom (KOL) upplever ofta oro relaterat till dyspné. Syftet med studien var att undersöka vilka icke-farmakologiska åtgärder som kan vidtas för att lindra patienters oro relaterat till dyspné vid KOL.  En litteraturstudie genomfördes där vetenskapliga artiklar granskades och sammanställdes. Resultatet visade att det finns ett flertal icke-farmakologiska åtgärder så som andningstekniker, fysisk träning, avledning, nutrition och kommunikation som sjuksköterskan kan undervisa och informera om för att lindra oro relaterad till dyspné. Åtgärderna bör vara individanpassade, eftersom varje patient är unik. Sjuksköterskan bör själv eller tillsammans med andra vårdinstanser försäkra sig om att patienten får den information och utbildning om sin sjukdom som krävs för att lindra patientens oro i möjligast mån. Informationen och utbildningen bör vara omfattande, för att patienten ska kunna finna de strategier och hjälpmedel som hjälper just dem vid oro. Lungrehabiliteringsprogram visade sig vara av betydelse för patienternas möjlighet att finna strategier för att lindra oro relaterad till dyspné. Ytterligare forskning men även utbildning av sjuksköterskor behövs angående specifika icke-farmakologiska åtgärder som kan lindra oro relaterad dyspné. Det behövs även forskning om vilka icke-farmakologiska åtgärder som bör ingå i ett lungrehabiliteringsprogram. / Patients with chronic obstructive pulmonary disease (COPD) often experience anxiety related to dyspnea. The purpose of this study was to investigate the non-pharmacological interventions that can be performed to alleviate patients' anxiety related dyspnea. A literature review was conducted and scientific articles were reviewed and summarized. The results showed that there are several non-pharmacological interventions that nurses can conduct to relieve anxiety related dyspnea, such as breathing techniques, physical exercise, diversion, nutrition and communication. Every patient is unique and therefore should the nurse interventions be individualized. It is the nurse task together with other health care professionals to ensure that the patients receives and understands the information that is given. The information and education should be extensive so that the patient will be able to find the right strategies that will help them to alleviate their anxiety. Pulmonary rehabilitation programs proved to be of great importance to patients' ability to find strategies to relieve anxiety related to dyspnea. Further research and education to nurses are needed on specific non- pharmacological interventions that can relieve anxiety related dyspnea. Research is also needed on which non-pharmacological interventions that should be part of a pulmonary rehabilitation program.

Syzygium cordatum is a medicinal plant indigenous to South Africa and Mozambique, commonly used to treat stomach aches, diabetes, respiratory problems and tuberculosis. In spite of the folklore use, adequate scientific data to credit its widespread traditional use is lacking. The objectives of this study were: to evaluate and validate scientifically the successful therapeutic claims by traditional medicine practitioners that Syzygium cordatum is effective in treating diarrhoea and diabetes / to determine the effects of the plant extract on gastrointestinal transit of a charcoal meal in mice / to determine the effects on castor oilinduced intestinal fluid accumulation / to determine the safety profile of the plant by carrying out acute toxicology study and to carry out preliminary screening of the active compounds present in the plant using standard phytochemical analytical procedures. The aqueous leaf extract of Syzygium cordatum (3.125 -50mg/kg, p.o) significantly reduced the faecal output caused by castor oil (0.7ml). All the doses used, reduced faecal output from 100% produced by castor oil to between 40 and 61%. S.cordatum (6.25 &ndash / 50mg/kg, p.o) significantly and in a dose dependent manner, delayed the onset of castor oil-induced diarrhoea.

Dissertation submitted in partial compliance with the requirements for a Masters Degree in Tehcnology: Chiropractic, Durban University of Technology, 2009. / Background: The aim of this study was to determine the knowledge, perception and utilisation of vitamins and minerals, natural medicines and pharmacological agents as adjuncts to Chiropractic practice in South Africa. Method: This study was a population based cross sectional survey utilising a descriptive, quantitative questionnaire study design. The questionnaire was distributed to all practicing qualified Chiropractors (n=388) and masters Chiropractic students (n=102) in South Africa. Results: The results obtained (30.4% response rate), indicated that the majority of the respondents (62.8%) felt qualified to advise patients on vitamins and mineral supplements and had a positive view of the use of vitamins and minerals as part of Chiropractic patient management (86.6%). The majority of the practitioners were aware that topical substances are part of the scope of practice and males were nearly twice as likely as females to use them. The majority thought biopuncture should be available to Chiropractors (82%) and felt that Chiropractors should challenge the legislation to incorporate biopuncture as part of the scope of practice (77.5%). Most respondents agreed with the statement indicating that NSAIDS should be part of Chiropractic scope of practice and 71% of respondents felt that being able to use NSAIDS in non-emergency situations would enhance patient retention. This study revealed that amongst the student population the majority, if allowed, would consider administering pharmacological agents in practice (55.1%). Conclusion: A correlation exists between the perception, knowledge and utilisation of vitamins and minerals, natural medicines and pharmacological agents in the Chiropractic profession with respect to the demographic data and there is a significant difference in opinion between qualified Chiropractors and Chiropractic masters students regarding perception, knowledge and utilisation of these adjuncts to practice.

Made available in DSpace on 2015-05-14T12:59:41Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 679492 bytes, checksum: 3252c196788de3bae30bf110b0d94cce (MD5) Previous issue date: 2009-10-09 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Fibromyalgia is a chronic painful syndrome that affects up to 5% of the population worldwide. It may be associated with sleep or mood disorders and fatigue, and progresses with functional disability. Its pathogenesis consists of disorders of central pain modulation, involvement of the descending inhibitory system and substance P hyperactivity. The drug most commonly used for treatment of this syndrome is amitriptyline, which leads to an improvement in up to 50% of cases. Patients are interested in trying alternative or complementary medicine for the treatment of fibromyalgia. Panax ginseng C.A. Meyer is an herb that has been used for hundreds of years in oriental medicine. Preclinical studies have confirmed the antinociceptive effect of its active metabolites (ginsenosides) on substance P-induced pain, demonstrating an ability to inhibit calcium channels in dorsal medullary neurons. Clinical trials have shown an improvement in quality of life and fatigue with the use of ginseng. The study had as objective to evaluate the therapeutic efficacy of the extract of P. ginseng roots in controlling pain, fatigue, sleep quality, anxiety and quality of life in fibromyalgia. Fifty-two women of 21-60 years of age, who fulfilled the inclusion criteria of the study, were selected. A randomized, double-blind, controlled clinical trial was carried out over 12 weeks to compare the effect of P. ginseng (100 mg/day) with amitriptyline (25 mg/day) and placebo. Variables evaluated were pain, fatigue, sleep quality and anxiety using a visual analogue scale (VAS); pain was evaluated using a tender points count and quality of life using the Fibromyalgia Impact Questionnaire (FIQ). The patients were evaluated at six follow-up visits and results were expressed as means ± standard error (SE) of the mean using analysis of variation (ANOVA) and Tukey s post-hoc test. Thirty-eight women with a mean age of 43 years concluded the study. There were no statistically significant differences between the three groups with respect to baseline characteristics. VAS revealed a reduction in pain in the ginseng group (p<0.0001) with an improvement ≥ 30% from the sixth week of treatment onwards, an improvement in fatigue (p<0.0001) with a reduction ≥ 25% on the sixth week and ≥ 40% on the ninth week; and an improvement in sleep (p=0.0003) with a reduction ≥ 40% in the frequency of this complaint by the 6th week of treatment. The VAS evaluation of pain, fatigue and sleep detected an improvement compared to baseline values; however, there was no statistically significant difference between the three groups. With respect to anxiety, an improvement occurred in the ginseng group compared to baseline (p<0.0001); however, amitriptyline treatment resulted in a significantly greater improvement (p<0.05). Ginseng reduced the number of tender points and improved patients quality of life, as evaluated by the FIQ, compared to baseline in both cases (p<0.0001); however, no difference was found between the groups. Treatment with ginseng resulted in an improvement in all the parameters evaluated compared to baseline; however, there was no difference between this group of patients and those using placebo and amitriptyline, and this one was more effective than placebo or ginseng in improving anxiety. The beneficial effect on all parameters evaluated suggests that further studies should be performed with larger sample sizes and/or higher doses of ginseng to evaluate this herb for future use as a complementary therapy for fibromyalgia. / A fibromialgia é uma síndrome dolorosa crônica que afeta até 5% da população mundial. Pode associar-se com distúrbios do sono, do humor e fadiga, e cursar com incapacidade funcional. Sua patogênese envolve distúrbio de modulação central da dor, comprometimento do sistema inibitório descendente e hiperatividade da substância P. O fármaco mais utilizado na sua terapia farmacológica é a amitriptilina, com melhora em até 50% dos casos. Há muito interesse dos pacientes sobre a medicina alternativa e complementar na terapia da fibromialgia. O Panax ginseng C.A. Meyer é uma erva utilizada pela medicina oriental há centenas de anos. Estudos pré-clínicos comprovaram a ação antinociceptiva dos seus metabólitos ativos (ginsenosídeos) sobre a dor induzida pela substância P, e demonstraram sua capacidade de inibir canais de cálcio nos neurônios da região dorsal medular. Ensaios clínicos sugeriram melhora da qualidade de vida e da fadiga com uso do ginseng. O estudo teve como objetivos: avaliar a eficácia terapêutica do extrato das raízes do P. ginseng no controle da dor, fadiga, qualidade do sono e ansiedade, e qualidade de vida na fibromialgia. Foram selecionadas 52 mulheres, com idades entre 21 e 60 anos, após preencherem os critérios de inclusão para o estudo. Foi desenvolvido um ensaio clínico, randômico, duplo-cego, controlado, por 12 semanas, comparando a ação do P. ginseng (100 mg/dia) com amitriptilina (25 mg/dia) e placebo. Variáveis avaliadas: dor, fadiga, qualidade do sono e ansiedade, por escala visual analógica (EVA); dor, por contagem dos pontos dolorosos; e melhora da qualidade de vida, por meio do Fibromyalgia impact questionnaire (FIQ). As pacientes foram avaliadas em 6 visitas, e os resultados foram dados em média ± EPM, utilizando ANOVA e pós-teste de Tukey. Trinta e oito mulheres concluíram o estudo, com média de idade de 43 anos. Não houve diferença significante nas características basais médias nos três grupos. Na EVA, observou-se: redução da dor no grupo do ginseng (p<0,0001), com melhora ≥ 30% a partir da 6ª semana de terapia; melhora da fadiga (p<0,0001), com redução ≥ 25% a partir da 6ª semana, e ≥ 40% na 9ª semana; e melhora do sono (p= 0,0003), reduzindo ≥ 40% a partir da 6ª semana de terapia. Nas três variáveis avaliadas na EVA, houve melhora em relação ao período basal, mas não houve diferença entre os três grupos. Com relação à ansiedade, o ginseng mostrou-se melhor em relação ao período basal (p<0,0001), mas foi inferior à amitriptilina (p<0,05), na comparação entre os grupos. O ginseng reduziu o número de pontos dolorosos e melhorou a qualidade de vida das pacientes (FIQ), ambos em relação ao período basal (p<0,0001), mas não houve diferença entre os grupos. O ginseng foi capaz de melhorar todos os parâmetros avaliados em relação ao período basal, mas não foi diferente do placebo ou da amitriptilina, e esta foi superior ao placebo e ao ginseng na melhora da ansiedade. Sua atuação benéfica nos parâmetros avaliados sugere a realização de novos ensaios clínicos, com amostras maiores, e/ou com dose maior do ginseng, para uma futura indicação como terapia complementar na fibromialgia.

Background: Persons with dementia diseases are today a large group that will increase significantly over the next few years. Behavioral and Psychological Symptoms of Dementia (BPSD) are very common and can cause major suffering. For dementia care professionals, persons with dementia suffering from BPSD may induce stress in the caregiving situation. With proper training and support, this stress may be reduced. In the BPSD register, the dementia care professionals may get information, advice and help suggesting non-pharmacological interventions that can help the person with dementia. Aim: The aim of the study was to investigate caregivers opportunities and experiences in implementing BPSD registration and follow up of non-pharmacological interventions in the caregiving situation within residential care for dementia. Furthermore, the aim was to compare if the dementia caregivers experience had significance for the experienced value of BPSD registration in Behavioral and Psychological Symptoms of Dementia. Method: A quantitative survey was conducted on residential care for dementia, N=5. The study- specific questionnaire covered possibility for BPSD- registration and interventions, considered value of BPSD estimation, and if non-pharmacological interventions are performed followed up, and considered to reduce BPSD. The results are presented using tables and diagrams. Kruskal Wallis test was used to compare variables between subgroups with varying working experience. Result: Most dementia caregivers considered that they had possibility to conduct BPSD registration 50% (n=28). They expressed 88% (n=49) that the non-pharmacological interventions that were initiated and performed decreased BPSD. Further they experienced BPSD follows up being important, 100% (n=56). There were no statistically significant differences between number of professional years and the compared variables (p-values ranged 0,266-0,981). Conclusion:The study found that dementia care professionals considered having possibilities to perform BPSD estimation, non-pharmacological interventions and follow- up. BPSD registration was experienced to be a helping tool for the dementia providers; and the length of the working experience had no significant relation to how they graded the value of the BPSD estimation.

Summaries in Afrikaans and English / Text in Afrikaans / Tourettesindroom is 'n lewenslange versteuring wat gekenmerk word deur motoriese en vokale trekkings saam met moontlik ook komorbiede simptome soos aandagtekort-hiperaktiwiteitsversteuring, obsessief-kompulsiewe versteuring, aggressie en depressie. Die sindroom kom in hoe mate in Suid-Afrika voor en die pastor kan dus heel moontlik daarmee te doen kry. Die beste behandeling vir die sindroom is medikasie saam met gedrags- en gesinsterapie toegedien deur 'n multidissiplinere span. Die pastor het 'n rol om te vervul in hierdie span probleme het aangesien persone met Tourettesindroom dikwels in hulle verhoudings met God, hulleself en ander mense. Vir effektiewe pastorale berading aan sodanige persone, moet die pastor deeglike kennis he van die sindroom en die simptome daarvan, asook van sy of haar invalshoek as pastor. 'n Moontlike kernmoment van die sindroom wat deur die pastor aangespreek kan word, is die verlies aan beheer wat deur dje lyer ervaar word. Die sindroom kan as 'n verskoning gedrag en gebruik word vir negatiewe en onverantwoordelike die pastor sal die lyer dus moontlik eties moet konfronteer op 'n medemenslike wyse. / Tourette Syndrome is a lifelong disorder. Symptoms are motoric and vocalic tics with possible comorbid symptoms such as attention deficit disorder with hyperactivity, obsessive-compulsive disorder, and depression. It is frequent among South Africans and the pastor will probably be confronted with persons struggling with the syndrome. The best therapy for Tourette Syndrome is medication in conjunction with behaviour and family therapy administered by a multi-disciplinary team. Persons with Tourette Syndrome have problems maintaining relationships with God, themselves and others. The pastor therefore has a definite role to play in the team. Knowledge of the syndrome and its symptoms, and of pastoral care are essential for succesful pastoral counseling. A possible central theme of the syndrome is the loss of control experienced by the person with the syndrome. The syndrome can become an excuse for negative and irresponsible behaviour and ethical confrontation may be necessary. / Philosophy, Practical and Systematic Theology / M. Th. (Praktiese Teologie)

Bakgrund: Smärta är en subjektiv upplevelse och ett flerdimensionellt begrepp som berör fysiska, psykiska, psykosociala och existentiella dimensioner av människan. Inom den palliativa vården är smärta ett vanligt förekommande symtom. För att uppnå en individanpassad smärtlindring bör sjuksköterskor ta hänsyn till smärtans olika dimensioner. Smärtlindring i palliativ vård anses som otillräcklig och berör främst åtgärder i ett medicinskt perspektiv. Sjuksköterskor kan bemöta patienterna som lider av smärta med icke- farmakologiska omvårdnadsåtgärder. Syfte: Att belysa icke- farmakologiska omvårdnadsåtgärder och dess betydelse i relation till smärta inom palliativ vård. Metod: Litteraturöversikten är grundad i tio vårdvetenskapliga artiklar; två kvalitativa, fyra kvantitativa och tre med mixad metod. Artiklarnas innehåll granskades och analyserades utifrån Katie Erikssons omvårdnadsbegrepp ansa, leka och lära. Resultat: Utifrån de tre begreppen visade resultatet från ansa att icke- farmakologiska omvårdnadsåtgärder som innefattades av fysisk beröring gav upphov till smärtlindring. Resultatet från kategorin leka visade att icke- farmakologiska omvårdnadsåtgärder berörde den psykiska dimensionen av patienternas smärta där sociala sammanhang kan påverka smärtlindringen. I kategorin lära påvisades att sjuksköterskors och patienters attityder samt förhållningssättet till icke- farmakologiska omvårdnadsåtgärder kan påverka smärtlindringen positivt och negativt. Diskussion: Resultatdiskussionen knyts an till Katie Erikssons omvårdnadsteori kring ansa, leka och lära. I diskussionen stärker och kritiserar författarna sitt resultat kopplat till sjuksköterskans kompetensbeskrivning. / Background: Pain is a subjective experience and a multi-dimensional concept based on physical, psychological, psychosocial and existential dimensions. Within palliative care, pain is a symptom that is regularly occurring. To achieve pain relief that is individually adapted, the nurses should have the different dimensions of pain in regard. Pain relief in palliative care is seen as inadequate and touches mostly on actions from a medical perspective. The nurses can respond to patients with non-pharmacological nursing measures to treat symptoms of pain. Aim: To illuminate non-pharmacological nursing measures and its meaning with pain in palliative care. Method: The literature review is based on ten articles in nursing science; two qualitative, four quantitative and three articles based on both methods. The content of the articles has been reviewed and analyzed with Katie Erikssons nursing theory by categories tend to, play and learn. Results: From these three concepts the results from the category tend to demonstrated that the non-pharmacological nursing measures which included physical touch gave rise to pain relief. Results from the category play demonstrated that non-pharmacological nursing measures affected the psychological aspect of the patients' pain where social interactions can affect pain relief. From the category learn it was shown that nurses and patients attitudes and approach to non-pharmacological nursing measures can affect the pain relief both positively and negatively. Discussion: The result is discussed and linked to Katie Erikssons theory of nursing tend to, play and learn. The writers also reinforces and critiques the result tied to the nursing skills description