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There are many public health organizations with guidelines concerning the best first-aid treatment for burn injuries. The Australian and New Zealand Burn Association recommends that a burn wound should be cooled with tap water (8-20°C) for 20 minutes, up to three hours after the injury has occurred. However, the evidence that these guidelines are based on is inconclusive and contradictory. As a result of the conflicting published data, there is controversy over whether ice water or ice may confer any beneficial wound healing effects, and what temperature of water is optimal. In the wider community there are also many different alternative therapies believed to be beneficial for the treatment of burn injuries which do not have much evidence to support their use. In this study, patients were found to use agents such as Aloe vera, tea tree oil dressings, butter, toothpaste, papaya ointment and moisturizer on the burn wound. The aim of this work was to review the current field of first-aid treatment for burn injuries and obtain evidence for the optimum first aid treatment using a good animal model, with clinically relevant assessments of wound healing and scar formation. The mechanisms behind the best first aid treatment were also investigated in an effort to better understand and identify the factors involved in optimal wound healing. Studies showed that cool running water at 15°C and 2°C improved the speed of wound healing, gave a better cosmetic outcome and decreased amounts of scar tissue compared to untreated controls. Other treatments Aloe vera, tea tree oil dressings, ice and saliva did not improve wound healing compared to untreated controls. All cold treatments acted to decrease the subdermal temperature, however as the running water was beneficial for wound healing whereas the ice was not, this suggests that the running water acts through other non-thermal mechanisms. Further studies showed that immediate treatment with 15°C water for 20 minutes duration significantly improved the re-epithelialization for 2 weeks post-burn and decreased the distribution of scar tissue compared to untreated controls, however durations as short as 10 minutes and delays of treatment for 1 hour (and perhaps longer) were also beneficial. An audit of first aid used by pediatric patients demonstrated that although 86.1% of patients used first aid, only 12.1% applied the recommended first aid treatment of cold water for 20 or more minutes. For those that did use correct first aid, re-epithelialization time and number of hospital visits were significantly reduced for children with contact and flame burns, respectively. Inadequate first aid treatment was also found to be more common for children <3.5 years old and for friction burn injuries. These studies provide compelling evidence that correct first aid treatment of burn injuries results in improved clinical outcomes, which benefit the patient as well as health care providers. There is a definite need for greater public awareness concerning the correct first aid treatment to use for burn injuries.

Title page, table of contents and abstract only. The complete thesis in print form is available from the University of Adelaide Library. / The aim of the work described in this thesis was initially to screen the ethanol extracts of eleven Indonesian ginger species (Zingiberaceae family) for anticancer activity. MCF-7 breast and HT-29 colon cancer cells were used for the investigations. Extracts of Zingiber aromaticum and Boesenbergia pandurata were found to be the most active species, similar to that of Curcuma langa which has been shown to possess anticancer activity in vitro and in vivo (Aruna and Sivaramakrishnan, 1992; Azuine and Bhide, 1992). These two active species were then further investigated. Bioactive compounds from the species were isolated and identified using various chromatography procedures and nuclear magnetic resonance (NMR) and their anticancer activities were further tested on MCF-7 breast and HT-29 colon cancer cells including cell cycle analysis and measurements of apoptosis. The ethanol extracts of these two active species were also investigated using the AOM-induced colon cancer model in rats. The antiinflammatory activity of the ethanol extract of Z. aromaticum was also investigated using dextran sulfate sodium (DSS) induced ulcerative colitis (UC) in rats. The inhibitory activity of ethanol extracts of rhizomes of 11 ginger species was initially tested against MCF-7 breast and HT-29 colon cancer cells using colorimetric tetrazolium salt (MTT) assay. Ethanol extracts of eight species (Amommum cardamomum, C. longa, C. mangga, C. xanthorrhiza, Boesenbergia pandurata, Zingiber aromaticum, Z. officinale, Z. cassumunar) showed a strong inhibitory effect on the growth of the cancer cells with the IC50 concentrations between 100-100 g/ml. The ethanol extract of Curcuma aeruginosa was less active (IC5o between 100-120 g/ml) and extracts of Kaempferia galangal and K. rotunda had no effect on the growth of either cell lines at concentrations up to 250 g/ml. Ethanol extract of C. longa was used as a comparison since curcumin, an active compound isolated from this species, has had demonstrated its anticancer activity in vitro, in vivo and is currently undergoing clinical trial against colon cancer (Greenwald, et al., 2001; Sharma et al., 2001). Extracts of Z. aromaticum and B. pandurata had very strong inhibitory activity similar to the extract of C. longa. Curcumin was not detectable in either Z. aromaticum or B. pandurata. The ethanol extracts of the active species were not toxic on human skin fibroblast cells (SF 3169). The ethanol extracts of Z. aromaticum and B. pandurata were further fractionated using two different solvents by reversed phase preparative HPLC. Fraction A was eluted with a mobile phase containing 5% vlv aqueous methanol containing 0.025% v/v trifluoroacetic acid (TFA) and fraction B was eluted with 100% methanol. The inhibitory activity of fractions was then investigated against HT-29 colon cancer cells and assayed using the MTT assay. Zerumbone, a sesquiterpenoid compound was isolated from fraction B of the extract of Z. aromaticum and a chalcone derivative, panduratin A was isolated from fraction B of the extract of B. pandurata. Curcumin was in fraction A of extract of C. longa. The anticancer activity of zerumbone and panduratin A was investigated using MCF-7 breast. HT-29 and CaCo-2 colon cancer cells. The inhibitory activity of the active compounds was assessed using the MTT assay. The ICso of zerumbone in each of the cell lines was about 10 uM and of curcumin on HTU29 cells was 25 uM. The IC50 of panduratin A in HT-29 cells was 16 uM and in MCF-7 cells was 9 uM. Zerumbone and panduratin A showed antiproliferative effects by alteration of the DNA distribution in the cell cycle and induction of apoptosis. HT-29 cells treated with zerumbone at concentrations of 10 -25 uM or panduratin A at concentrations of 9 -65 uM for 24 h were stained with propidium iodide (PI) to determine cell cycle distribution and analysed using FACScan flow cytometry. The proportion of cells in the S phase was reduced from 18.7% in untreated cells to 10.2% in HT-29 cells after treatment with zerumbone at 10 uM to 3.1% at 25 uM. Cells in the G2 phase increased from 18.5% at 10 uM to 40% at a concentration of 25 uM. Panduratin A increased the proportion of cells in the GO/G1 phase from 33% of untreated cells to 71% after treatment with 65 uM for 24 h. Panduratin A slightly reduced the proportion of cells in S phase and cells in G2/M phase also decreased from 36,8% in untreated cells to 15.4% at 65 M. Apoptosis was determined using double labelled (Annexin-V-Fluos and PI) and then evaluated using FACScan Flow Cytometry. Morphological features of apoptosis were also examined using DiffQuick stain and fluorescent Hoechst 3355 and 4,6-diamino-2-phenylindole (DAPI). Zerumbone induced apoptosis in HT-29 cells in a dose dependent rnanner, At 48 h, 2% of cells treated with 10 M of zerumbone underwent apoptosis, which increased to 8% when treated with 50 M, Panduratin A at 28 M increased the number of cells undergoing apoptosis from 2,2% to 16.7% when treated with a concentration of 65 M. The ethanolic extracts of Z. aromaticum and B. pandurata were also investigated using the azoxymethane (AOM) induced aberrant crypt foci (ACF) model of colon cancer in rats in a short and long term study. Ethanolic extracts of C. tonga and curcumin were used as comparison. The basal diet used throughout all animal studies in this thesis was a semi-purified AIN-93 G diet (Reeves et aI., 1993). ACF were induced by two doses (15 mg/kg BW) subcutaneously of AOM one week apart and ACF were visualised in the formalin fixed colon using methylene blue stain. The ACF study was run over a short (5 weeks) and long (13 weeks) experiments. Diets containing ethanol extracts prepared from the equivalent of 2% (w/w) dried rhizome of Z. aromaticum, B. pandurate or C. tonga in a short term study did not affect the formation of ACF in rats compared to those in the control diet group. The ACF formation in a short term study was dominated by small numbers of aberrant crypts (1 or 2) per focus. It is suggested that large ACF (4 or more ACs/focus) are better predictors of colon cancer (Uchida et aI., 1997; Jenab et aI., 2001). Diets containing ethanol extracts of the equivalent of 4% by weight of dried rhizomes of Z. aromaticum, B. pandurata, C. longa were investigated over 13 week study, Total ACF were significantly reduced by Z. aromaticum extract (0.34%) in the diet (down 21%, p<0.05) relative to rats fed the control diet. A similar reduction was observed with C, longa extract (0.86%) in the diet (down 24%, p<0.01) and with 2000 ppm curcumin. There was no significant different in small ACFs (1-2 ACs/ focus) between dietary treatments. The number of foci containing 3-4 ACs/focus was significantly reduced (35%, p<0,001) in animals fed the Z. aromaticum extract and 34% (p<0.001) of animals fed the C. tonga extract. The total number of ACF containing 5 or more ACs per focus of animals fed 0.34% Z. aromaticum extract was 41 % lower than control (p<0.05) and for 0.86 % C. tonga extract was 22% (not significant). A diet containing extract (0.56%) of B. pandurata did not significantly affect the formation of ACF compared to the control AIN group. The concentration of zerumbone in the Z.aromaticum extract diet was assayed at 300 ppm, and of curcumin in the C. tonga extract diet was also 300 ppm. The concentration of panduratin A was not assayed in the diet due to late identification of the active compound. The antiinflammatory activity of ethanol extract of Z. aromaticum was investigated using dextran sulfate sodium (DSS) induced ulcerative colitis in rats. Sulfasalazine, a widely used compound to treat inflammatory bowel disease (IBD) in humans was used as the positive control. Diets containing ethanol extracts (0.34% and 0.68%) prepared from the equivalent of 4% and 8% by weight of dried rhizomes of Z. aromaticum were given to the animals throughout the experiment. On day three, rats were given 2% DSS in drinking water for 5 d and then just water for 3 d and then were killed. During the DSS treatment rats were maintained in metabolic cages, body weight, food and fluid intake and clinical symptoms such as consistency of stools and blood in faeces were recorded daily. There was slight but not significant reduction in the body weight of rats fed 0.68% extract of Z. aromaticum in the diet due to reduced food consumption. The extract of Z. aromaticum (0.34%) and sulfasalazine suppressed clinical signs of ulcerative colitis. Eleven percent of the controls were hemoccult positive on day 2 after DSS administration, which progressed further by day three with 67% being hemoccult positive and 100 % on day five. By comparison, blood appeared on day 3 of rats treated with diet containing 0.34% and 0.68% extract of Z. aromaticum and 0.05% sulfasalazine, and only 33%, 67% and 22%, of rats being hemoccult positive on day 5 respectively. The disease activity index (DAI) of rats fed diet containing 0.34% extract of Z. aromaticum was about 0.4 and similar to those which were fed with diet containing sulfasalazine. The DAI of untreated rats was 1.4. The crypt score of rats fed the extract of Z. aromaticum was slightly reduced but it was not significantly different from those of untreated rats. Other histological scores were not significantly different between dietary treatments. Extract of Z. aromaticum significantly decreased the content of PGE-2 in colon tissue compared to that of untreated animals. There was a reduction of TX8-2 content in colonic tissue of rats fed with extracts of Z. aromaticum but this was not significant. The activity of myeloperoxidase (MPO) activity in the colonic tissue of rats fed with sulfasalazine was significantly lower than that of the untreated controls and those which fed with extracts of Z. aromaticum. The results from the studies performed in this thesis showed that extract of Z. aromaticum which contains an active sesquiterpenoid zerumbone have anticancer and antiinflammatory activity suggesting that the extract may have benefits as a chernopreventative agent. However further studies are needed to elucidate their other pharmacological actions. Panduratin A showed potential anticancer activity in cell culture in vitro. However an extract of B. pandurata did not have effect on the AOM-induced colon cancer model. Different cancer models such as breast and prostate cancer could be used to further investigate the anticancer activity of extract of B. pandurata and panduratin A and to elucidate their mechanism. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1097849 / Thesis (Ph.D.) -- University of Adelaide, Dept of Medicine, 2003

Thesis (MNutr)--Stellenbosch University, 2012. / ENGLISH ABSTRACT: Background: Nausea and vomiting during pregnancy (NVP) is a common medical condition. Due to possible harmful side-effects that conventional medicine may pose to the fetus, many mothers choose not to use it, and are left helpless against NVP. There is a need for alternative treatment to relieve NVP symptoms. Objectives: This systematic review (SR) investigated current evidence regarding ginger for the treatment of NVP. The primary objective was to assess the effectiveness of ginger in treating NVP. The secondary objective was to assess the safety of ginger during pregnancy, by identifying adverse events or side-effects. Search strategy: Electronic search of bibliographic databases (1966-February 2011). Selection criteria: Randomized controlled trials (RCTs) of the efficacy of ginger by any route, as treatment for NVP in pregnant women regardless of their age or stage of pregnancy. Data collection and analysis: The principal investigator and independent reviewer individually identified relevant studies, extracted data and assessed trial quality. Data analysis was performed using the RevMan5 software. Differences at the level of p<0.05 were considered to be statistically significant. Results: Eleven RCTs involving 1176 pregnant women were included. The quality of evidence was low, hence the high risk of bias and imprecision of results. Ginger significantly improved the symptoms of nausea when compared to placebo, when comparing the results of this SR to past SRs, and taking into account a meta-analysis performed on two relatively large included studies (mean difference (MD) 1.20, 95% confidence interval (CI) 0.56-1.84, p=0.0002, I2=0%). However, another meta-analysis on two smaller studies indicated no significant improvement in nausea. Ginger did not significantly improve nausea when compared to vitamin B6 (MD 0.34, 95% CI -1.52-2.20, p=0.7, I2=91%). Similarly, ginger did not significantly reduce the number of vomiting episodes during NVP, when compared to placebo, although there was a trend towards improvement (MD 0.72, 95% CI -0.03-1.46, p=0.06, I2=71%). Subgroup analyses performed seemed to favor the lower daily dosage of <1500mg ginger to possibly be more effective for the relief of nausea. Ginger did not pose a significant risk for spontaneous abortion when compared to placebo (RR 3.14, 95% CI 0.65-15.11, p=0.15; I2=0%), or to vitamin B6 (RR 0.49, 95% CI 0.17-1.42, p=0.19, I2=40%). Similarly, ginger did not pose a significant risk for the side effects of heartburn or drowsiness when compared to placebo or vitamin B6. When compared to dimenhydrinate, ginger posed a smaller risk for drowsiness (RR 0.08, 95% CI 0.03-0.18) and no increased risk for heartburn. Conclusions: This review suggests potential benefits of ginger in reducing nausea symptoms in pregnancy (bearing in mind the limited number of studies, variable outcome reporting and quality of evidence). Ginger did not have a significant impact on vomiting episodes, nor pose a risk for side effects or adverse events during pregnancy. Based on evidence from this SR, ginger could be considered a harmless and possibly effective alternative option for women suffering from the symptoms of NVP. Large RCTs are necessary to confirm the possible benefit of ginger as treatment for NVP. / AFRIKAANSE OPSOMMING: Agtergrond: Naarheid en vomering tydens swangerskap (NVS) is ‘n algemene mediese toestand. As gevolg van moontlike skadelike newe-effekte wat konvensionele medikasie kan veroorsaak vir die fetus, vermy baie moeders dit en word hulpeloos gelaat teen NVS. Dus is daar behoefte aan alternatiewe behandeling vir NVS. Doelwitte: Hierdie sistematiese literatuuroorsig (SO) het huidige literatuur ondersoek wat verband hou met gemmer vir behandeling van NVS. Die primêre doelwit was om effektiwiteit van gemmer as behandeling vir NVS te assesseer. Die sekondêre doelwit was om veiligheid van gemmer tydens swangerskap te assesseer, deur ongunstige gebeure en newe-effekte te identifiseer. Soektogstrategie: Elektroniese soektog van bibliografiese databasisse (1966-Februarie 2011). Seleksiekriteria: Verewekansigde gekontrolleerde proewe (RCTs) van gemmer deur enige roete as behandeling van NVS, in swanger vroue ongeag ouderdom of stadium van swangerskap. Dataversameling en –analise: Die hoof navorser en ‘n onafhanklike hersiener het individueel relevante studies geidentifiseer, data ekstraksie onderneem en studie-kwaliteit geassesseer. Data-analise is uitgevoer deur die RevMan5 sagteware te gebruik. Verskille by die vlak van p<0.05 was beskou as statisties betekenisvol. Hoof resultate: Elf RCTs waarby 1176 swanger vroue betrokke was, is ingesluit. Die studie-kwaliteit was swak, dus die hoë risiko vir sydigheid en onakkuraatheid van resultate. Gemmer het beduidend die simptome van naarheid verbeter in vergelyking met plasebo, wanneer die resultate van hierdie SO met vorige SO’s vergelyk word, en die meta-analise in ag geneem word wat op twee relatiewe groot ingeslote studies uitgevoer is (gemiddelde verskil (MD) 1.20, 95% vertrouens interval (VI) 0.56-1.84, p=0.0002,I2=0%). Kontrasterend, het ‘n ander meta-analise van twee kleiner studies geen beduidende verbetering in naarheid aangedui nie. Gemmer het nie beduidend naarheid verbeter wanneer dit met vitamien B6 vergelyk word nie (MD 0.34, 95% VI -1.52-2.20, p=0.7, I2=91%). Soortgelyk, het gemmer nie die aantal vomerings-episodes verminder, in verglyking met plasebo nie, maar daar was wel ‘n neiging na verbetering (MD 0.72, 95% VI -0.03-1.46, p=0.06, I2=71%). Die subgroup-analise blyk ten gunste te wees van die laer daaglikse dosis van <1500mg gemmer om meer effektief te wees vir die behandeling van naarheid. Gemmer het nie ‘n beduidende risiko ingehou vir spontane aborsie, wanneer dit vergelyk word met plasebo (relatiewe risiko (RR) 3.14, 95% VI 0.65-15.11,p=0.15;I2=0%), of vitamien B6 nie (RR 0.49, 95% VI 0.17-1.42,p=0.19;I2=40%). Soortgelyk, het gemmer nie ‘n beduidende risiko ingehou vir newe-effekte van sooibrand of duiseligheid, wanneer dit vergelyk word met plasebo of vitamien B6 nie. Wanneer dit vergelyk word met dimenhidrinaat, het gemmer ‘n kleiner risiko ingehou vir duiseligheid (RR 0.08, 95% VI 0.03-0.18) en geen verhoogde risiko vir sooibrand nie. Gevolgtrekkings: Hierdie SO dui ‘n potensiële voordeel van gemmer aan in vermindering van naarheid tydens swangerskap (inagnemend van die klein hoeveelheid studies, wisselende uitkomste-rapportering en studie-kwaliteit). Gemmer het nie ‘n beduidnede impak gehad op vomerings-episodes nie, en ook nie ‘n risiko ingehou vir newe-efekte of ongunstige gebeure tydens swangerskap nie. Volgens bewyse uit hierdie SO, kan gemmer beskou word as ‘n skadelose en moontlike effektiewe alternatiewe opsie vir vroue wat lei aan NVP. Grootskaalse RCTs is nodig om die moontlike voordeel van gemmer as behandeling vir NVS te bevestig.