Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Thesis (M.Tech.: Chiropractic)-Dept. of Chiropractic, Durban Institute of Technology, 2003 65 leaves / Low back pain is one of the largest known causes of disability in western society. The purpose of this study was to evaluate the relative effectiveness of combined spinal manipulation and interferential current therapy versus combined oral meloxicam and interferential current therapy in the treatment of acute mechanical low back pain.

Dissertation completed in partial compliance with the requirements for the Master's Degree in Technology: Chiropractic, Durban University of Technology, 2012. / Background:Myofascial Pain Syndrome is characterized by localized muscle pain, in which affected muscles are in a chronically-shortened state and contain trigger points.It is the single most common source of musculoskeletal pain that is encountered in clinical practice. Modalities such as electrotherapy, cryotherapy, thermal therapy, dry-needling and ultrasound are used in its management. The use of phonophoresis has generated much interest; and literature around this modality continues to accumulate. Numerous studies have demonstrated the efficacy of phonophoresis with an anti-inflammatory in the treatment of musculoskeletal disorders, attributing the efficacy to the penetration of the coupling medium by means of the ultrasonic waves. Traumeel®S, is a homeopathic anti-inflammatory, that has successfully been used in the treatment of musculoskeletal injuries.It has anti-oedematous, anti-exudative, anti-inflammatory and analgesic properties. Its efficacy as a coupling agent in phonophoresis has not been tested for myofascial pain syndrome. Methodology:This study was designed as a prospective, double-blinded, randomized, and controlled experimental investigation. Sixty subjects were randomly allocated to three groups of 20 subjects each. Group Areceived active phonophoresis with Traumeel® S gel;Group B received sham phonophoresis with Traumeel® S gel; Group C received an application of Traumeel® S gel only.Algometer and Numerical Pain Rating Scale 101 (NRS) readings were taken immediately before treatment at visit one and thereafter at visits three and four. Results:Repeated measures ANOVA testing was used to examine the intra-group effect of time and the inter-group effect of treatment on the outcomes of NRS and algometer readings. Profile plots were used to assess the direction and trends of the effects. An intra-group analysis revealed that, objectively and subjectively, all groups responded positively to treatment over time, with no significant time-group interaction. It was noted that there was a higher rate of improvement in Group A over time; however, this difference was not statistically significant. Conclusion:The results from this study revealed that all three treatment groups responded favorably to the alleviation of pain. It was concluded that phonophoresis with Traumeel® gel had no significant additional beneficial effects.

Submitted in partial compliance with the requirements for the Master's degree in technology in Technology : Homeopathy, Durban University of Technology, Durban, South Africa, 2015. / Introduction There is no proper definition of acute mechanical neck pain (AMNP) but it has been theorized that it has a sudden onset pain and lasts for a relatively short time. It occurs with or without injury and presents with pain in the shoulder and upper arm. Acute mechanical neck pain should not be accompanied by an inflammatory disease, neurological disease, fracture, dislocation, neoplasm or infection AIM The purpose of this study was to compare the relative effectiveness of homoeopathic Simillimum against Traumeel® (a commercial homoeopathic complex) in the treatment of acute mechanical neck pain using the neck disability scale, range of motion measurements and a subjective observation. METHODOLOGY This study was a double blind, quantitative, comparative; clinical trial that involved two treatment groups: Half the participants received the homoeopathic Simillimum and the other half received oral Traumeel® drops. Patients self-selected homoeopathic treatment. Patients were screened and only those who fit the inclusion criteria of suffering from AMNP of maximal two weeks duration, were English conversant and between the ages of 18 and 55 were included. Those suffering with AMNP were required to sign an informed consent form after the procedure was explained thoroughly. Each patient read through the procedure of the clinical trial and were informed that their participation was on a voluntary basis and they could withdraw at any time. Convenience sampling was utilised in which an independent person, using a simple sampling method, randomly allocated the patients into the respective groups. Of the 30 patients, 15 received Traumeel® and 15 received homoeopathic Simillimum. It was hypothesized that the homoeopathic Simillimum treatment would be more effective in the treatment of acute mechanical neck pain than oral Traumeel®. The treatment protocol consisted of three homoeopathic consultations within a seven day period, with the consultations scheduled on days one, three and seven. Subjective and objective measurements were taken at each of the three consultations, Durban University of Technology Homoeopathic Day Clinic, Steve Biko Campus. A Simillimum treatment was prescribed for every patient based on full homoeopathic case history. This Simillimum was confirmed by the co-supervisor. Half of the patients were dispensed the Simillimum and the other half received Traumeel® according to the randomisation list. At the first follow up, on day three, the patients were reassessed according to their progress, perception and their range of motion, and the progress of the patient was analysed. In the last consultation on day seven, the progress of the patient was analysed using the perceptive questionnaire of the Neck Disability Index and the objective cervical range of motion. Full physical examinations were carried out during all three consultations. Upon collection of data, the statistical package SPSS 22.0 was used to record and analyse the data. Non parametric statistical tests were used as the data were non parametric - it does not follow any distribution, was ordinal (not relying on numbers but rather a ranking order of sorts). Inter-group comparisons were made using Mann-Whitney U-test. RESULTS The effectiveness of Traumeel® and homoeopathic Simillimum was measured firstly, in terms of the patients’ perception of the responses to the treatment applying the Neck Disability Index and secondly the increase in degree of movement in the range of motion of the cervical region. When applying an ANOVA with repeated measures with a Greenhouse-Geisser correction, the mean scores between groups were statistically not significantly different (p = 0.112). CONCLUSION Both the Traumeel® and Simillimum treatments were effective in the treatment of acute mechanical neck pain, but there was no evidence that one treatment was more beneficial than the other. The p-values (sig.) reported were greater than 0.05, thus implying that there is no significant difference between the groups.

Cathelicidins are cationic host defence peptides (CHDP) with essential roles in the innate defence system. These peptides have antimicrobial potential and the capacity to modulate innate immunity and inflammatory processes. Neutrophils (PMN) are the main reservoir of cathelicidins and play key roles in first line defence against infection. The appropriate regulation of PMN function, death, and clearance is critical to innate immunity, and the efferocytosis of apoptotic PMN, in contrast to necrotic cells, is proposed to promote the resolution of inflammation. In this thesis I demonstrate that the human cathelicidin LL-37 rapidly induced secondary necrosis of apoptotic human PMN and identify the essential C-terminal region of LL-37 required for this activity. In addition to the induction of secondary necrosis, higher concentrations of LL-37 also promoted PMN granule contents release. LL-37-induced secondary necrosis did not affect PMN ingestion by human monocyte-derived macrophages and, in contrast to expectation, was not proinflammatory. Interestingly, the anti-inflammatory effects of apoptotic PMN on activated macrophages were retained and even potentiated where LL-37-mediated secondary necrosis induced anti-inflammatory granule content release. Consistent with the results of in vitro studies, in vivo murine sterile peritonitis model revealed the same phenomenon: LL-37-induced secondary necrosis diminished inflammatory responses with decreased PMN influx. I also present data on LL-37- mediated modulation of innate immune effector cell cytokines responses to inflammatory signals. I propose that during acute inflammation LL-37 can modulate innate immune responses through its activity on cytokine production, and that LL-37-mediated secondary necrosis of apoptotic PMN has anti-inflammatory effects, but may also mediate host damage by promoting the release of potentially harmful intracellular contents under chronic or dysregulated conditions.

Inflammation plays a key role in the underlying pathogenesis of obesity and its associated health risks, with increased markers of inflammation evident in both liver and adipose tissue. In parallel, there is dysregulation of glucocorticoid metabolism in obesity, with increased adipose levels of the glucocorticoid-regenerating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) and increased hepatic levels of 5α-reductase type 1 (5αR1), which catalyses the reduction of glucocorticoids. Both the mechanisms and consequences of this glucocorticoid metabolism dysregulation remain unclear, however, there is evidence that it may be related to inflammation. In vitro studies have demonstrated that pro-inflammatory markers upregulate 11βHSD1 expression in adipocytes, potentially explaining increased expression of this enzyme in obesity. Previous work has also demonstrated that the glucocorticoid metabolites produced by 5αR1 lack the metabolic effects of the parent glucocorticoid, but retain its anti-inflammatory properties, indicating that increased expression of hepatic 5αR1 may serve to dampen down inflammation in the liver. The hypotheses addressed in this thesis are that in obesity, inflammation regulates adipose glucocorticoid metabolism through 11βHSD1, and that hepatic glucocorticoid metabolism regulates the inflammatory state of the liver through 5αR1. The role of inflammation in the regulation of 11βHSD1 was assessed in vivo in mice treated with the anti-inflammatory compound sodium salicylate (salicylate). In diet-induced obese mice, salicylate downregulated 11βHSD1 expression and activity selectively in visceral adipose tissue, alongside improved glucose tolerance, reduced plasma non-esterified fatty acids, and changes in adipose lipid metabolism. 11βHSD1-deficient mice fed a high-fat diet were resistant to the insulin sensitising effects of salicylate treatment. These results indicate a novel role for 11βHSD1 down-regulation in mediating the insulin sensitising effect of anti-inflammatory treatment. The mechanisms underpinning the anti-inflammatory properties of 5α-reduced glucocorticoids were explored in vitro and in vivo. In lipopolysaccharide-stimulated murine macrophages, both 5α-reduced glucocorticoid metabolites tested, namely 5α-dihydrocorticosterone (5αDHB) and 5α-tetrahydrocorticosterone (5αTHB), suppressed tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6) release, although to a lesser extent than corticosterone (B). Similar to B, both 5αDHB and 5α THB suppressed phosphorylation of intra-cellular inflammatory signalling mitogen-activated protein kinases (MAPK) proteins c-Jun N-terminal kinase (JNK) and p38, as well as increasing protein expression of MAPK phosphatase-1 (MKP-1). Treatment of phorbol ester-stimulated HEK293 kidney cells with these 5α-metabolites revealed that 5αDHB suppressed nuclear factor κB (NFκB) and activator protein-1 (AP-1) activation to a similar extent to that of B, whilst 5αTHB increased activation of these pro-inflammatory transcription factors, indicating cell-specific effects of 5αTHB. In conclusion, reduced intra-adipose glucocorticoid regeneration by 11βHSD1 mediates the insulin sensitising effects of salicylate, suggesting that altered glucocorticoid metabolism may reflect altered intra-adipose inflammation in obesity. Furthermore, these data support the concept that this enzyme provides a therapeutic target in obesity-related metabolic disorders. 5α-reduced metabolites of glucocorticoids have similar anti-inflammatory properties to the parent glucocorticoid, indicating that the elevated hepatic levels of 5α-reductase in obesity may be a protective mechanism to limit the adverse metabolic effects of glucocorticoids upon the liver, but maintain the beneficial anti-inflammatory properties. These 5α-reduced glucocorticoid metabolites may provide a potential therapeutic treatment as selective glucocorticoid receptor modulators for inflammatory conditions.

Thesis (MSc)--Stellenbosch University, 2015. / ENGLISH ABSTRACT: Chronic inflammation is suggested to contribute to cancer development and therefore a potential target for chemoprevention. In the skin, keratinocytes and macrophages play an integral part in acute and chronic inflammation, with interleukin 1-α (IL-1α) and tumor necrosis factor α (TNF-α) as key cytokines governing this process. Green tea (Camellia sinensis) and the South African herbal teas, rooibos (Aspalathus linearis) and honeybush (Cyclopia spp.) displayed antiinflammatory effects in mouse and human skin. To further investigate the antiinflammatory properties of green tea and the herbal teas, rooibos and honeybush (C. subternata and C. maculata) herbal teas, suitable cell culture models were developed and validated utilising human keratinocytes (HaCaT) and monocyte (THP- 1) derived macrophages. Aqueous extracts of the green tea and unfermented herbal teas were prepared and their chemical composition determined by high performance liquid chromatography (HPLC) and the antioxidant activity characterised utilising different antioxidant assays. Green tea and rooibos exhibited similar antioxidant activities while C. maculata displayed the lowest overall antioxidant activity of all the extracts, despite possessing the highest mangiferin level, the major polyphenol in honeybush. The modulation of cytokine release was studied in (i) an UVB-induced pre-exposure HaCaT model monitoring the accumulation of IL-1α and (ii) a LPS stimulated THP-1 macrophage model monitoring the TNF-α release, utilising both a pre-exposure and co-exposure extract regimens. In the pre-exposure HaCaT inflammatory model the UVB-induced IL-1α was decreased by the green tea extract while a far weaker response was obtained with the rooibos extract. Both the honeybush extracts displayed a significant effect in the reduction of IL-1α with C. subternata exhibiting a slight increased protection at a lower extract concentration. In the pre-exposure THP-1 derived macrophage model, green tea and the herbal tea extracts inhibited TNF-α release in a dose dependent manner in the absence of an overt loss in cell viability and apoptosis at lower extract concentrations, suggesting a typical anti-inflammatory effect. In the co-exposure model, the different extracts also exhibited an anti-inflammatory effect at the lowest concentrations in the absence of apoptosis while at higher extract concentrations the effect was masked by a decrease in cell viability and increased apoptosis. C. maculata exhibit differential effects when considering the inhibition of cytokine production and, depending on the cell model, either exhibited a weaker or stronger effect when compared to C. subternata and rooibos. Phenolic diversity of the different teas is likely to explain the differential effects in the antioxidant assays and cell culture models with respect to the regulation of the production of the inflammatory markers. Proposed mechanism for the anti-inflammatory effects include the modulation of oxidative stress via various pathways and the subsequent down regulation of nuclear factor kappa β (NFκB) and activated protein-1 (AP-1) which are key regulators of cytokine production governing the inflammatory response. / AFRIKAANSE OPSOMMING: Kroniese inflammasie van die vel kan bydra tot die ontwikkeling van kanker en is dus ’n potensiële area om te teiken in die voorkoming van velkanker. Keratinosiete en makrofage speel ’n integrale rol in akute en chroniese inflammasie van die vel en TNF-α en IL-1α is die belangrikste sitokiene wat hierdie proses inisieer. Dit is bekend dat ekstrakte van groen tee (Camellia sinensis) en die Suid-Afrikaanse kruietees, rooibos (Aspalathus linearis) en heuningbos (Cyclopia spp.) ‘n anti-inflammatoriese effek op die vel van muise en mense het. Om die anti-inflammatoriese aktiwitieit van groen tee, rooibos en 2 heuningbos kruietees (C. subternata en C. maculata) verder te ondersoek en te definieer is geskikte selkultuurmodelle ontwikkel en gevalideer deur gebruik te maak van menslike keratinosiete (HaCaT) en monosiet (THP-1) afgeleide makrofage. Water ekstrakte van groen tee en ongefermenteerde kruietees is voorberei en die chemiese samestelling deur hoë druk vloeistof chromatografie (HDLC) bepaal. ‘n Verskeidenheid van antioksidant bepalingstoetse is gebruik om die antioksidant aktiwiteit van die ekstrakte te meet. Groen tee en rooibos het soortgelyke antioksidant aktiwiteite getoon, terwyl C. maculata die swakste algehele aktiwiteit getooon het, ten spyte van die teenwoordigheid van hoёr vlakke van mangiferin, die belangrikste polifenoliese verbinding in heuningbos. Modulasie van sitokiene is verder bestudeer in (i) ’n UVB-geïnduseerde vooraf-blootstelling HaCaT model, waartydens akkumulering van IL-1α gemonitor is en (ii) ‘n lipopolisakkaried (LPS)-gestimuleerde THP-1 makrofaag model, waar die vrystelling van TNF-α gemonitor is. Vir die THP-1 model is beide die voor en gelyktydige blootstelling benaderings vir die ekstrakte met LPS gebruik. In die keratinosiet model, waar die selle aan ekstrakte blootgestel is voor UVB bestraing, is IL-1α beduidend verlaag deur die groen tee ekstrak, terwyl ’n swakker reaksie gesien is met rooibos. Beide heuningbos ekstrakte het ’n beduidende invloed in die vermindering van IL-1α getoon, waar C. subternata ’n effense verhoogde beskerming teen selsterfte by ‘n laer ekstrakkonsentrasie toon. Blootstelling van die makrofage aan al vier ekstrakte voor LPS stimulasie (vooraf-blootstelling), het gelei tot inhibisie van TNF-α vrystelling op ’n dosis afhanklike wyse en die afwesigheid van apoptose en selsterftes by lae ekstrak konsentrasievlakke. Hierdie waarnemings dui op ’n tipiese antiinflammatoriese effek. In die gelyktydige-blootstelling model verlaag al die ekstrakte TNF-α vrystelling teen die laagste ekstrak konsentrasievlakke, in die afwesigheid van apoptose en met geen effek op seldood nie. Hoёr ekstrak konsentrasievlakke het sitotoksisiteit en verhoogde apoptose getoon, dus was die anti-inflammatoriese effek gemaskeer. C. maculata toon ‘n variërende effek met betrekking tot antioksidant aktiwiteit en die bekamping van sitokien produksie, afhangend van die model wat bestudeer is. Die verskeidenheid fenoliese verbindings teenwoordig in die verskillende tee ekstrakte is waarskynlik die rede vir die effekte wat waargeneem is tydens antioksidant toetsing en selkultuurmodelle. Die anti-inflammatoriese meganismes wat deur hierdie studie voorgestel word sluit die modulasie van oksidatiewe stres via verskeie metaboliese paaie in. Modulasie van oksidatiewe stres lei tot af-regulering van kernfaktor-kappaB (NF-κB) en aktiveerderproteïen- 1(AP-1), wat sleutel reguleerders van sitokien produksie tydens inflammatoriese respons is.

published_or_final_version / abstract / Medicine / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / Medicine / Master / Doctor of Medicine

published_or_final_version / Chemistry / Master / Master of Philosophy