Antiinflamatórios não-esteroidais (AINEs) são muito utilizados para o alívio da dor. Estudos indicam que 1 em 7 pacientes com doenças inflamatórias crônicas usam AINEs e que 1 em 5 pessoas usam AINEs para dores agudas. Os AINEs inibem a cicloxigenase (COX-1 e COX-2) ou seletivamente a COX-2, e apesar de sua excelente ação antiinflamatória e analgésica, muitos são os efeitos colaterais. Problemas gastrointestinais (GI) são a queixa mais comum para os AINEs convencionais, que também são associados a apoptose de diferentes tipos celulares. Os COX-2 seletivos apresentam menos problemas GI, mas seu uso tem sido questionado pelo risco de trombose e enfarto do miocárdio. Todos os AINEs parecem interferir no processo de cicatrização, embora os resultados dos estudos realizados apresentem-se conflitantes. Uma vez que os AINEs são utilizados por grande número de pessoas, o objetivo do nosso trabalho foi avaliar os efeitos dessa medicação sobre o tecido epitelial e durante o processo de cicatrização. Ratos Wistar foram tratados diariamente com AINEs convencional (diclofenaco, 3mg/Kg) ou um COX-2 seletivo (Celecoxibe, 1mg/Kg) por períodos de 7 e 14 dias. O controle foi feito com animais da mesma idade e peso não submetidos ao tratamento com AINEs. Após 7 dias, em todos os animais, controles e tratados, foram realizadas feridas cirúrgicas (4cm de diâmetro) no dorso depilado, sob anestesia com Tribromoetanol. Foram analisados, histológica e histometricamente, os epitélios da mucosa bucal, e a área de cicatrização (3 e 7 dias pós-cirurgia). Os resultados obtidos foram tabelados para avaliação estatística apropriada. No geral foi possível observar que todos os AINEs provocaram alterações com o seu uso agudo, no entanto para os inibidores seletivos da COX- 2 houve uma tendência à normalização com o uso crônico, não observada com o uso do AINE convencional. Na avaliação da cicatrização foi possível observar que os AINEs convencionais provocaram um pequeno atraso no processo de cicatrização, o que não foi observado com o uso de AINE seletivo para COX-2. Foi possível concluir que é necessário cautela em pacientes que fazem uso de AINEs, por provocarem alterações significativas no epitélio bucal, sendo os convencionais os que apresentam alterações mais significativas principalmente a longo prazo / Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for pain relief mostly in inflammatory chronic diseases. One in 7 patients with chronic inflammatory diseases uses NSAIDs, 1 in 5 uses NSAIDs for acute pain. NSAIDs may inhibit cyclooxygenase (COX-1 and COX-2) or COX-2 selectively, and despite their excellent anti-inflammatory and analgesic action, there are many side effects related. Gastrointestinal (GI) problems are the most commmon complaint for conventional NSAIDs, wich are also associated with different cell types apoptosis. The COX-2 selective NSAIDs have less GI problems, but may be associated to risks of cardiovascular events. All of NSAIDs seems to interfere with wound healing, although studies results may show conflicting results. Since NSAIDs are used by large numbers of people, the aim of this study was to evaluate the effects of this medication on the epithelial tissue and during wound healing process. Wistar rats were treated daily with conventional NSAIDs (diclofenac, 3mg/Kg) or selective COX-2 (celecoxib, 1mg/Kg) for a period of 7-14 days. The control group was animals of similar age and weight not treated with NSAIDs. After 7 days in all the animals, control and treated, were made surgical wounds (4cm in diameter) on the shaved back under anesthesia with Tribromoethanol. Oral mucosa and wound healing were histological and histometrically analyzed (3 and 7 days after surgery). The results received appropriated statistical evaluation. It was possible to observe that both NSAIDs lead to changes with acute use, but only selective COX-2 inhibitors tends to get back to normal parameters with long lasting use. Related to wound healing, it was possible to verify that conventional NSAIDs was associated to a slightly delay in wound healing process, which was not observed with selective COX-2 NSAIDs use. It was possible to conclude that caution is needed with the use of NSAIDs. They cause significant changes in oral epithelium and the convenional one causes most signifcant changes with long term use

Submitted by Sandro Camargo (sandro.camargo@unipampa.edu.br) on 2015-05-08T02:37:18Z No. of bitstreams: 1 127110041.pdf: 1450512 bytes, checksum: bbda08f02d9cddbd1397c133ddee4bbe (MD5) / Made available in DSpace on 2015-05-08T02:37:18Z (GMT). No. of bitstreams: 1 127110041.pdf: 1450512 bytes, checksum: bbda08f02d9cddbd1397c133ddee4bbe (MD5) Previous issue date: 2014 / A utilização de produtos naturais na medicina popular como recurso terapêutico é uma tendência generalizada pela população brasileira. Esta tendência tem contribuído significativamente para o consumo não só de produtos naturais, como também de medicamentos fitoterápicos. Neste contexto, o Manjericão (Ocimum basilicum L.) surge como um destes recursos terapêuticos, sendo amplamente utilizado como planta ornamental e como condimento. Originário da Ásia tropical, hoje é cultivado no mundo todo. Entre os usos populares do O. basilicum L., está o emprego como antioxidante, anti-inflamatório, anti-cancerígeno, antimicrobiano, agente cardiovascular, fatores associados ao envelhecimento, dentre outros. Diversos metabólitos secundários com atividade antioxidante e anti-inflamatória já foram identificados nesta espécie e trabalhos relatam que o Ácido Rosmarínico é o composto biologicamente mais ativo. Sabendo da importância econômica e da enorme difusão mundial de seus usos, tanto na culinária, quanto na medicina popular, torna-se importante a comprovação dos efeitos do Manjericão, visando garantir sua eficácia e sua segurança, já que estudos de toxicidade para esta espécie são raros e usualmente não abordam aspectos genéticos. Este trabalho, portanto, teve como objetivo a avaliação da atividade antioxidante pelo teste da peroxidação lipídica, conteúdo de proteína carbonilada, vitamina C; atividade das enzimas Superóxido dismutase (SOD) e Catalase (CAT); análise dos parâmetros inflamatórios pela da avaliação de citocinas anti- inflamatórias e pró-inflamatórias, e a toxicidade genética do extrato hidroalcoólico frente a leucócitos humanos em cultura celular, através da viabilidade e proliferação celular, ensaio cometa, teste de micronúcleo e instabilidade cromossômica. Observou-se que o extrato etanólico de O. basilicum agiu como agente antioxidante reduzindo/revertendo os efeitos causados pelo peróxido de hidrogênio, ações essas que podem ser explicadas pela composição rica em polifenois e flavonoides do extrato, além de seu conteúdo de ácido rosmarínico, um importante antioxidante com atividade comprovada e descrita na literatura. Em relação aos parâmetros genotoxicológicos, para todos os testes, os resultados foram dose-dependentes. Enquanto que para os parâmetros inflamatórios, o extrato apresentou capacidade anti-inflamatória, onde o possível mecanismo envolvido ocorre pela interação de inibição das citocinas mediadoras pró- inflamatórias e o estímulo de citocinas mediadoras anti-inflamatórias. / The use of natural products in folk medicine as a treatment method is a genereal ternd for the Brazilian population. This trend has contributed significantly to the consumption not only of natural products, as well as herbal medicines. In this context, Basil (Ocimum basilicum L.) arises as one of these therapeutical resources. Basil is widely used as an ornamental plant and as a condiment. Original in tropical Asia, is now grown worldwide. Among the popular uses of Ocimum basilicum L., its employment as an antioxidant, anti-inflammatory, anti-carcinogenic, anti-microbial, cardiovascular agent, factors associated with aging, between others. Several secondary metabolites with antioxidant and anti-inflammatory activity have been identified in this species and several studies have reported that rosmarinic acid is the most biologically active compound. Knowing the economic importance and worldwide dissemination of their uses, both in cooking, as in folk medicine, it is important to prove the effects of Basil, to ensure its efficacy and safety, as toxicicty studies for this species are rare and usually do not approach genetic aspects. This study evaluated the antioxidant activity by testing lipid peroxidation, protein carbonyl content, vitamin C; activity of superoxide dismutase (SOD) and catalase (CAT); analysis of inflammatory parameters for the evaluation of anti-inflammatory and pro-inflammatory cytokines, and genetic toxicity of the hydroalcoholic extract in human white blood cells (WBC) using cell culture, through the analysis of cell viability and cellular proliferation, chromosome instability, comet assay and micronucleus test. With our results it is possible to verify that O. basilicum extract acts as an antioxidant and effectively reverts or subjugates the effects of a high oxidizing agent as hydrogen peroxide and, these actions are explained because its composition, which is rich in polyphenols and flavonoids besides several compound as Rosmarinic Acid, who have a well-known antioxidant activity. In toxicological tests, all results were dose-dependent. In the anti-inflammatory aspect, we show that our extract actually presents these properties and the mechanism involved in these particular actions are a composed interaction between the inhibition of pro-inflammatory mediator and the stimulation of anti-inflammatory cytokines.

Submitted by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2016-04-04T17:31:47Z No. of bitstreams: 1 Marcelo Gomes de Gomes.pdf: 1949846 bytes, checksum: c4472edd9df88ec1d4f0e86bd59fafa9 (MD5) / Made available in DSpace on 2016-04-04T17:31:47Z (GMT). No. of bitstreams: 1 Marcelo Gomes de Gomes.pdf: 1949846 bytes, checksum: c4472edd9df88ec1d4f0e86bd59fafa9 (MD5) Previous issue date: 2015-03-02 / O lipopolissacarídeo (LPS) associado com a D-galactosamina (D-GalN), tetracloreto de carbono (CCl4) e o paracetamol (PCM), são modelos animais de hepatite fulminante aguda amplamente utilizados. O gama orizanol (γ-ORY) é uma mistura de 10 ésteres de ácido trans ferúlico e é encontrado no óleo do farelo de arroz. O objetivo deste estudo foi avaliar o efeito hepatoprotetor do γ-ORY nos diferentes modelos animais de hepatite fulminante aguda em camundongos. O experimento foi realizado através do tratamento com γ-ORY (50 mg/kg, por via oral, p.o.) durante uma semana, após uma hora do último tratamento foi administrado por via intraperitoneal o LPS (50 mg/kg) e D-GalN (500 mg/kg), foi utilizado silimarina como controle positivo. O γ-ORY foi administrado oralmente (50 mg/kg) durante uma semana, após 1 hora da última administração o dano foi induzido por uma única dose de CCI4 (1 mg/kg i.p.), a silimarina foi utilizada como controle positivo. Os animais receberam γ-ORY durante dois dias em duas doses (10 mg e 50 mg/kg p.o.), no terceiro dia o PCM (2 g/kg, p.o.). Após 24 horas os animais foram submetidos à eutanásia. Foram feitas as seguintes determinações bioquímicas: marcadores de estresse oxidativo (TBARS, NPSH, 4-HNE), defesas antioxidantes enzimáticas (CAT, SOD, GPx), marcadores de dano hepático (AST, ALT, GGT), marcadores de funcionalidade hepática (bilirrubina), marcadores inflamatórios (TNF-α, IL-1β), marcadores de apoptoses (Caspase 3 e 9) e análise histológica. O γ-ORY foi capaz de proteger significantemente em todas as determinações analisadas, podendo ser comparado ao um fármaco utilizado para o tratamento da hepatite fulminante aguda que é a silimarina. Portanto, sugerimos que o γ-ORY pode ser uma alternativa para o tratamento da hepatite fulminante aguda, pois ficou comprovado seu efeito hepatoprotetor está associado com sua capacidade antioxidante, anti-inflamatória e anti-apoptótica. / The lipopolysaccharide (LPS) associated with D-galactosamine (D-GalN), carbon tetrachloride (CCl4) and paracetamol (PCM) are acute fulminant hepatitis widely used animal models. The gamma oryzanol (γ-ORY) is a mixture of 10 esters of trans-ferulic acid and is found in rice bran oil. The objective was to assess the potential hepatoprotective effect of γ-ORY on mechanisms involved in different animal models of acute fulminant hepatitis in mice. The animals were divided into different groups depending on the experiment. γ-ORY treatment (50 mg/kg, per oral, p.o.) for a week after an hour of the last treatment before the administration by intraperitoneal of LPS (50 mg/kg) and D-GalN (500 mg/kg). γ-ORY was administered orally (50 mg/kg) for one week, after 1 hour of the last administration damage was induced by a single dose of CCl4 (1 mg /kg i.p.). The animals received γ-ORY for two days in two doses (10mg and 50mg /kg p.o.), on the third day PCM (2 g/ kg, p.o.). After 24 hours the animals were euthanized. The following biochemical determinations were made: non-enzymatic antioxidant defenses, defenses enzymatic antioxidants, liver damage markers, liver function markers, inflammatory markers, apoptosis markers and histological analysis. The γ-ORY was able to significantly protect in all analyzed determinations, and can be compared to a drug used for acute fulminant hepatitis. Therefore, we suggest that the γ-ORY can be an alternative for the treatment of acute fulminant hepatitis, as was proved its hepatoprotective effect is associated with its antioxidant capacity, anti-inflammatory and anti-apoptotic effect.

O uso de produtos anti-inflamatórios e antioxidantes sintéticos representa uma grande preocupação nos dias atuais para a população. Importante destacar alguns aspectos relevantes quanto às dificuldades encontradas no tratamento, como o aumento da resistência aos fármacos e os efeitos colaterais da terapia convencional, que apresenta como consequência o desencadeamento de doenças graves, prejudicando e comprometendo a saúde humana. Os óleos voláteis têm sido alvo na busca de novas substâncias, por apresentarem como potencial fonte de novos agentes antioxidantes e anti-inflamatórios. Dentre as espécies vegetais caracterizadas pela produção deste metabólito secundário, estão aquelas pertencentes ao gênero Schinus, da família Anacardiaceae, de ampla ocorrência do Rio Grande do Sul. Nesse contexto, o presente trabalho objetivou analisar e identificar a composição química e avaliar as atividades biológicas a partir da extração do óleo volátil das espécies de Schinus weinmannifolius e Schinus polygamus, nativas do Rio Grande do Sul. Assim, o óleo volátil foi obtido por hidrodestilação de diversas coletas de folhas e frutos de S. weinmannifolius e folhas de S. polygamus. A análise química, realizada por cromatografia à gás acoplada à espectrometria de massas (CG-EM), demonstrou grande variedade de compostos presentes nas amostras, com predominância dos sesquiterpenos β-cariofileno, germacreno D, biciclogermacreno, germacreno A, δ-cadineno, espatulenol, óxido de cariofileno e α-cadinol para folhas e frutos de S. weinmannifolius e predominância do composto alifático n-nonano para S. polygamus. Os óleos obtidos foram submetidos aos ensaios de reação com 2,2-difenil-1-picrilidrazila (DPPH) e substâncias reativas ao ácido tiobarbitúrico (TBARS) para avaliação da atividade antioxidante, sendo esta ação apenas observada para as amostras de folhas de S. weinmannifolius coletadas no outono e inverno de 2016 pelo ensaio de TBARS. No método de DPPH as amostras de folhas de S. weinmannifolius coletadas no outono de 2015 e 2016 apresentaram baixa atividade antioxidante, na concentração de 100 μg/mL. A ação anti-inflamatória foi inicialmente avaliada pela técnica in vitro da câmara de Boyden, nas concentrações de 0,001 a 10 μg/mL. Todas as amostras apresentaram inibição significativa da migração leucocitária em relação ao controle, avaliada no ensaio de antiquimiotaxia. A avaliação da atividade anti-inflamatória in vivo, realizada pelo método de edema de pata, foi conduzida apenas para a amostra que melhor resultado obteve no ensaio in vitro, folhas de S. weinmannifolius, verificando-se inibição significativa do edema na segunda hora de tratamento, na dose de 100 mg/kg. Os resultados encontrados suportam o uso tradicional dos óleos de Schinus como agentes anti-inflamatórios. / The use of synthetic anti-inflammatory and antioxidant products represents a major worry these days for the population. It is important to highlight some aspects relevant concerning the difficulties of the treatment, such as the increase in drug resistance and the side effects of conventional medication, leading to the development of serious diseases, impairing and compromising human health. Volatile oils have been the target of this search for new substances, as they are potential sources of new antioxidant and anti-inflammatory agents. Among the plant species characterized by the production of this chemical group, are those belonging to the Schinus genus, from the Anacardiaceae family, of large occurrence in Rio Grande do Sul. In this context, the present work aimed to analyze and identify the chemical composition and to evaluate the biological activities from the extraction of volatile oil from species of Schinus weinmannifolius and Schinus polygamus, native from Rio Grande do Sul. Thus, the volatile oil was obtained by hydrodistillation of several leaves and fruit collections of S. weinmannifolius and S. polygamus leaves. The chemical analysis, performed by gas chromatography coupled with mass detector (GC-MS), demonstrated great variety of compounds present in the samples, with predominance β-caryophyllene, germacrene D, bicyclogermacrene, germacrene A, δ-cadinene, espatulenol, caryophyllene oxide and α-cadinol for leaves and fruits of S. weinmannifolius and predominance of the compound aliphatic n-nonane for S. polygamus. The obtained oils were submitted to the reaction with 2,2-diphenyl-1-picrylhydrazyl (DPPH) and thiobarbituric acid reactive substances (TBARS) assays to evaluate the antioxidant activity, being this action only observed for leaves samples of S. weinmannifolius collected in autumn and winter of 2016 by the TBARS assay. In the DPPH method, leaves samples of S. weinmannifolius collected in the autumn of 2015 and 2016 presented low antioxidant activity at the concentration of 100 μg/mL. The anti-inflammatory potential was initially performed by the in vitro technique of the Boyden chamber, at concentrations 0,001 to 10 μg/mL. All samples showed significant inhibition of leukocyte migration in relation to the control, evaluated in the antichemotactic assay. The evaluation of in vivo anti-inflammatory activity by the paw edema method was conducted only for the sample that obtained the best result in the in vitro test, S. weinmannifolius oil, with significant inhibition of edema in the second hour of treatment, at dose 100 mg/kg. The results found support the traditional use of Schinus oils as anti-inflammatory agent.

Commiphora species (from which myrrh is obtained) has been a source of several novel and bio-active natural compounds. Traditionally, Commiphora (Burseraceae) is used in southern Africa for the treatment of ulcers, fevers, and as a remedy for snake and scorpion bites. In western Africa, the macerated stem is used in the treatment of rheumatic conditions. The resin of some Commiphora species is applied topically to aid in wound healing. Documented uses include antibacterial and antifungal properties, as well as cytotoxic, cytostatic and anti-oxidant activity. The botanical diversity of this genus in South Africa warrants a study of this plant group, to provide scientific evidence for the traditional use of Commiphora species in African healing rites. Ten Commiphora species were investigated. Fresh plant material of the selected species were identified and collected from natural populations in the Limpopo Province. Active compounds, viz. kaempferol and dihydrokaempferol, in C. glandulosa (stem) were isolated using bioassay-guided fractionation and identified using nuclear magnetic resonance spectroscopy. The stem and leaf extracts of each species were analysed for in vitro anti-oxidant, antimicrobial, anti-inflammatory, anticancer activity, as well as cytotoxicity. The anti-oxidant activity of the extracts was investigated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and the 2,2’-azino-bis(3-ethyl-benzthiazoline-6-sulfonic acid) (ABTS) assays. Extracts generally exhibited poor anti-oxidant activity in the DPPH assay, with the exception of C. schimperi (stem), C. neglecta (stem), C. tenuipetiolata (stem and leaf), and C. edulis (stem), which possessed IC50 values ranging between 7.31 μg/ml and 10.81 μg/ml. Isolated compounds were subjected to the DPPH assay to determine the anti-oxidant potential of each compound, separately and in combination to establish possible synergistic, antagonistic or additive effects. The flavonol, kaempferol (IC50 = 3.32 μg/ml) showed exceptional radical scavenging activity, in contrast to the low activity displayed by dihydrokaempferol (IC50 = 301.57 μg/ml), their combination being antagonistic. Greater anti-oxidant activity was observed for most species in the ABTS assay when compared to the results obtained in the DPPH assay. The best activity was observed for the stem extracts of C. neglecta (IC50 = 7.28 μg/ml) and C. mollis (IC50 = 8.82 μg/ml). In vitro antimicrobial efficacy was determined against Gram-positive and Gram-negative bacteria as well as yeasts using the MIC microtiter plate assay. A greater selectivity was exhibited by the extracts against the Gram-positive bacteria and yeast than against the Gram-negative bacteria. Using death kinetics studies (time-kill studies), the rate at which the antimicrobial agent kills pathogens over a 24-hour period was determined. The antibacterial activity of Commiphora marlothii (stem) was observed to begin at ca. 30 min of the exposure of S. aureus to the different concentrations of plant extract. All concentrations exhibited antibacterial activity, with a complete bactericidal effect achieved by all test concentrations by the 24th hour. Commiphora pyracanthoides (stem) displayed anti-inflammatory activity through good inhibition of the 5-LOX enzyme (IC50 = 27.86 μg/ml). The ability of extracts and kaempferol to inhibit the in vitro growth of three human cancer cell lines, namely the colon adenocarcinoma (HT-29), breast adenocarcinoma (MCF-7), and the neuronal glioblastoma (SF-268), was evaluated using the sulforhodamine (SRB) antiproliferative assay. The most active Commiphora species against the HT-29 cells were C. glandulosa (leaf and stem) and C. marlothii (leaf). The MCF-7 cell line was the most sensitive to indigenous Commiphora species, with C. edulis (leaf and stem), C. glandulosa (leaf and stem), C. marlothii (leaf), C. pyracanthoides (leaf and stem), C. schimperi (stem), and C. viminea (stem) all possessing an inhibition greater than 80% at 100 μg/ml. Commiphora glandulosa (leaf and stem) and C. pyracanthoides (leaf and stem) were the two most active species against the SF-268 cells, with IC50 values ranging between 68.50 μg/ml and 71.45 μg/ml. The inhibition of the cancer cell proliferation by kaempferol in all three-cancer cell lines was determined, with IC50 values of 9.78 μg/ml in HT-29 cells, 20.21 μg/ml in MCF-7 cells and 43.83 μg/ml in SF-268 cells. The microculture tetrazolium cellular viability (MTT) assay was used to determine the cellular toxicity of the extracts against transformed human kidney epithelium (Graham) cells. Commiphora glandulosa (stem) proved to be most toxic (IC50 = 30.5 μg/ml). The IC50 values for all other extracts were in excess of 95 μg/ml suggesting low in vitro toxicity for the majority of the species. A phytochemical investigation of the non-volatile constituents of the leaf and stems was conducted using high performance liquid chromatography (HPLC). The HPLC profiles and UV spectra of the stem extracts, and the representative flavonoid patterns in the leaf extracts of the species indicate that a similarity exists in their chemical fingerprint.

No description available.

Abstract not available

Asthma is a chronic inflammatory disease of the airways. Using a murine model which replicates many characteristic features of human asthma, this study evaluated the effects of treatment with anti-inflammatory drugs on the lesions of chronic asthma, and investigated potential underlying molecular mechanisms. Treatment with dexamethasone, a glucocorticoid, was compared with roflumilast, a novel phosphodiesterase-4 (PDE4) inhibitor. BALB/c mice sensitised to ovalbumin were challenged with a low mass concentration of aerosolised antigen for 30 min/day, 3 days/week for 6 weeks. In weeks 5 and 6, groups of animals were treated with either dexamethasone or roflumilast. Assessment included changes in acute-on-chronic inflammation, structural remodelling of the airways and airway hyper-responsiveness to a bronchoconstrictor stimulus. These were correlated with the expression of pro-inflammatory cytokines and growth factors. Compared to vehicle-treated control animals, dexamethasone- and roflumilast-treated mice exhibited reduced accumulation of intra-epithelial eosinophils and chronic inflammatory cells, including CD3+ T-lymphocytes in the airways. Similarly, both drugs inhibited subepithelial fibrosis and airway epithelial thickening, although only dexamethasone inhibited goblet cell hyperplasia/metaplasia. Airway hyper-reactivity was not diminished by either drug. Both treatments suppressed production of Th2 cytokines by ovalbumin-restimulated peribronchial lymph node cells. In selectively dissected airway tissue from vehicletreated animals, increased expression of mRNA for several pro-inflammatory cytokines (TNF-α, GM-CSF, IL-6) and cytokines characteristic of Th1 (IFN-γ), Th2 (IL-5, IL-13)and Th17 (IL-17A) cells was demonstrated using real-time PCR. Enhanced expression of growth factors (TGF-β1 and FGF-2) was also demonstrated in airway epithelium isolated by laser capture microdissection. Interestingly, whereas treatment with dexamethasone significantly inhibited expression of mRNA for all of the inflammationrelated cytokines examined, roflumilast inhibited only IL-17A, TNF-α, GM-CSF and IL-6. Both drugs inhibited mRNA expression of growth factors by epithelial cells. Because roflumilast was as effective as dexamethasone in suppressing inflammation and most changes of remodelling, the selective suppression of IL-17A, TNF-α, GM-CSF and IL-6 suggests that these mediators, or the cells that produce them, may have critical roles in pathogenesis. Furthermore, they may be particularly appropriate therapeutic targets in chronic asthma.

Bibliography: leaves 161-204 / xv, 204 leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (M.D.)--University of Adelaide, Dept. of Medicine and Pathology, 1985

Loss of physiological function, uncomfortable symptoms and various disease processes are thought to be directly related to the formation of scar tissue following tissue damage. Between ten and thirty percent of patients requiring spinal surgery suffer from failed back surgery syndrome. The pain and instability resulting from failed back syndrome often requires medical treatment and may even require additional surgeries to alleviate its associated symptoms. Following surgery, scar tissue forms that often becomes adherent to the dura and entangled in the ganglia and nerve fibers of the spinal nerves. This scar tissue is considered to play a major role in the development of failed back syndrome. Following tissue injury, excessive oxidative stress and inflammation are considered to be the primary stimulators behind increased fibroblast proliferation and activation, resulting in abundant extracellular matrix deposition. The excessive laying down of extracellular matrix ultimately leads to abundant scar tissue formation. I hypothesized that reducing oxidative stress and inflammation will mitigate scar tissue formation and produce a better outcome after spinal surgeries. Quercetin is a dietary flavonoid with anti-oxidant and anti-inflammatory properties that has been shown to improve the outcome following injury to the spinal cord and reduce the proliferation of fibroblasts. L-2-Oxothiazolidine-4-carboxylate (OTC) also minimizes inflammation and protects against oxidative stress by promoting the synthesis of the potent antioxidant and anti-inflammatory agent glutathione. OTC reduces airway inflammation in asthma models and is potentially capable of modulating extracellular matrix production. <p>Treatment with these two agents was hypothesized to decrease oxidative stress and inflammation, thereby causing an amelioration of scar tissue formation following spinal surgery and improve the outcome. Morphological changes observed initially indicated that improvements in wound healing were occurring in the experimentally treated tissues. In addition, the scar tissue area and the lateral widths of the peridural scar forming between the muscular tissue areas suggested a reduction in the scar size. Although inflammatory cell numbers increased slightly in the experimental treatment groups, particularly during the initial three day post laminectomy time point, this increase was not statistically significant. <p>While quercetin and OTC did not appear to inhibit the influx of inflammatory cells following laminectomy, they did appear to induce a more beneficial wound healing environment. It is possible that these agents are affecting parameters of wound healing not considered by these studies. For instance the myriad of processes mediated by growth factors and cytokines involved in wound healing process may play a much greater role than the inflammatory cells themselves. In conclusion, reducing oxidative stress and inflammation by these agents to ameliorate scar tissue formation following spinal laminectomy was supported by the observed morphology, but not supported by the quantification of inflammatory cells. Additional studies investigating the efficacy of quercetin and OTC on the wound healing process are needed to further understand the role they play in repair and scar tissue formation.