O objetivo deste trabalho foi avaliar os efeitos do monossialogangliosídio (GM1), da câmara de oxigenoterapia hiperbárica e de ambos no tratamento da lesão medular experimental em ratos. Trinta e dois ratos Wistar com lesão medular foram divididos em 4 grupos: um grupo recebeu o monossialogangliosídio (GM1), um segundo foi submetido à oxigenoterapia hiperbárica, um terceiro recebeu os dois tratamentos e um quarto não recebeu tratamento (controle). Não houve diferença significativa entre os grupos na análise histológica, em todas as variáveis (necrose, hemorragia, hiperemia e degeneração cística, p>0,06). Também não houve nenhuma diferença na comparação entre os lados direito e esquerdo nos testes funcionais (p>0,06 para todos). Não foram encontradas diferenças nos testes motores, na comparação entre os grupos após 2, 7 21 e 28 dias de lesão medular. Mas, na avaliação após 14 dias, o Grupo 3, o qual recebeu a terapia combinada, mostrou um escore BBB significantemente maior que os outros grupos (p=0,015). Na avaliação de 28 dias, houve uma tendência dos Grupos 1 (GM1) e 3 (terapia combinada) apresentarem um escore BBB maior que o do Grupo 4 (controle), embora sem significância estatística (p=0,057). Concluiu-se que, quanto aos índices motores, a utilização do GM-1 tem efeito benéfico, embora sem diferença estatisticamente significante e que o efeito benéfico do GM-1 é antecipado através da utilização concomitante da oxigênio terapia hiperbárica. / The objectives were to evaluate the effect of GM1 ganglioside, hyperbaric oxygen, and both in combination, in the treatment of experimental spinal cord lesions in rats. Thirty-two Wistar rats with spinal cord lesions were divided into four groups: one group received GM1 ganglioside, one was submitted to hyperbaric oxygen therapy, the third received both treatments, and the fourth received no treatment (control). There were no significant differences between the groups in the histological analysis, for any of the variables (necrosis, hemorrhage, hyperemia, cystic degeneration, p > 0.06). Neither were there any significant differences in the comparison of left and right sides in the functional tests (p > 0.06 for all). No significant differences were found in the locomotor ratings, in the comparison of groups at 2 days, 7 days, 21 days and 28 days after the surgical procedure. However, in the evaluation on day 14, Group 3, which received the combined therapy, showed a significantly higher BBB score than the other groups (p = 0.015). In the evaluation on day 28, there was a trend to Group 1 (GM1) and 3 (combined therapy) showed a higher BBB score than the group 4 (control), but with no significance (p=0,057). In conclusion, the is a benefit in the use of GM1 ganglioside, but with no significance and the therapeutic effect of GM1 in locomotor evaluation of rats submitted to spinal cord lesion is anticipated by hyperbaric oxygen therapy.

Objetivo: Avaliar o efeito da oxigenoterapia hiperbárica na cicatrização da anastomose esôfagojejunal em ratos gastrectomizados. Material e Métodos: Foram operados 40 ratos Wistar, adultos machos, com peso entre 322g e 506g. Os animais foram divididos aleatoriamente em dois grupos. No grupo A (controle), 20 ratos foram submetidos à gastrectomia total. No grupo B, 20 ratos foram igualmente gastrectomizados e receberam tratamento pósoperatório com oxigenoterapia hiperbárica por 90 minutos/dia durante sete dias. Todos os ratos foram sacrificados no oitavo dia de pós-operatório e avaliados de acordo com as seguintes variáveis em estudo:a) presença ou não de fístula anastomótica; b) avaliação da cicatrização da anastomose esôfagojejunal através da medida da força de ruptura à tração na linha da sutura segundo Hendriks & Mastboom; c) determinação da concentração de colágeno na anastomose, pelos critérios de Kovács. Para análise estatística comparativa entre os grupos foi utilizado o teste t de Student, considerando-se como significativo p <0,05. Resultados: Houve 20% de óbitos na amostra, sendo cerca de 60% no grupo A e os 40% restantes no grupo B (p=N.S.) . Ocorreu apenas uma fístula anastomótica em cada grupo, sendo que em ambos não houve morbidade relacionada ou óbito. As medidas de força de ruptura à tração na linha da sutura entre os grupos (p=0,528) e a determinação da concentração de colágeno na anastomose esôfagojejunal (p=0,89) não mostraram diferença estatisticamente significativa nos dois grupos. Conclusões: Utilizando parâmetros clínicos, mecânicos e bioquímicos para avaliar a anastomose esôfagojejunal, concluímos que no presente estudo a oxigenoterapia hiperbárica não interferiu no processo de cicatrização desta anastomose. / Purpose: To evaluate the effect of the hyperbaric oxygen therapy on the healing of the esophagojejunal anastomosis in gastrectomized rats. Material and Methods: 40 Wistar rats male adults with weighing between 322g to 506g were operated. The animals were divided in two ramdom groups.20 rats from group A (control group), were submitted to total gastrectomy. In group B, 20 rats were equally gastrectomized and received postoperative treatment with hyperbaric oxygen for 90 minutes/day during seven days. All rats were sacrificed on the eighth postoperative day and evaluated according to the following study variables :a) whether there were any anastomotic fistula or not; b) evaluating esophagojejunal anastomosis healing by measuring breaking strength at the suture line as per Hendriks & Mastboom; c) determining of the collagen concentration on the anastomosis, as per Kovács criteria. For the comparative statistical analyses between the groups, Student’s “t” test was used, whereas p<0,05 was significant. Results: There was a 20% rate of deceasing in the sample, whereas 60% occurred in group A and 40% in group B (p=N.S.). There was only one anastomotic fistula in each group, and in neither one occurred any morbidity or deaths related. Breaking strength measured at the suture line (p=0,528) and collagen concentration determined at the esophagojejunal anastomosis (p=0,89) did not present any significant statistical difference in either group. Conclusions: By using clinical, mechanical and biochemical parameters to evaluate the esophagojejunal anastomosis, it was possible to conclude that, in this study, hyperbaric oxygen therapy did not interfere with the healing process of the anastomosis.

Au cours de cette thèse, nous avons rapporté que la combinaison unique de l'hexafluoroisopropanol (HFIP), utilisé comme solvant, et des conditions hyperbares (10-15 kbar) permet une addition sans précédent de nucléophiles-1,4 pauvres, comme les amines aromatiques, sur des récepteurs Michael encombrés, sans promoteur externe. De plus, l'addition d'hétéro-Michael d'anilines fonctionnellement substituées sur des esters insaturés-α,β est définie par la différence d'acidité entre le solvant et l'amine. La réaction avec des anilines plus basiques se déroule facilement dans le méthanol. En revanche, les solvants protiques très polaires comme les alcools fluorés (HFIP et TFE) favorisent l'addition d'aza-Michael de nucléophiles plus faibles. Enfin, une méthode verte et sans catalyseur de construction de nouveaux dérivés d'acides aminés contenant des fragments d'adamantane et d'aziridine a été développée. Et il est prouvé que la réaction d'aza-Michael initie la formation de l’hétérocycle. / Along this PhD work, we have reported that the unique combination of hexafluoroisopropanol (HFIP), employed as solvent, and hyperbaric conditions (10-15 kbar) allows unprecedented 1,4-addition of poor nucleophiles such as aromatic amines onto sluggish (cumbersome) Michael acceptors without any promoter nor work-up. Moreover, The hetero-Michael addition of functionally substituted anilines to α,β-unsaturated esters is significantly defined by the difference of acidity between the solvent and the amine. Reaction with more basic anilines proceeds smoothly in methanol. In contrast, very polar protic solvent such as fluorinated alcohols (HFIP and TFE) favor the aza-Michael addition of more weak nucleophiles. Finally, green and catalyst-free method of new amino acid derivatives construction containing adamantane and aziridine fragments was developed. And it is proved that aza-Michael reaction initiates the formation of heterocycle.

<p>Magnetic resonance spectroscopy (MRS) is a non-invasive diagnostic technique that provides unique information about the biochemical composition of the human body. By excluding the overwhelming signals from water and fat, clinically relevant biomarkers such as lactate, N-acetyl aspartate, choline, creatine, glutamate/glutamine (Glx), gamma-aminobutyric acid (GABA), glutathione, and myoinositol can be reliably quantified. MRS has diverse applications in investigating the metabolic window of a wide range of biochemical processes. </p> <p>Here, we have utilized MRS to better understand chemical changes associated with neurological disorders and treatment response. We have investigated neurometabolic imbalances in brain regions related to post-traumatic stress disorder (PTSD). MRS was applied to better understand the neurobiological processes of hyperbaric oxygen therapy in military veterans with clinically diagnosed traumatic brain injury and/or PTSD.</p>

Thesis (MScMedSc)-- Stellenbosch University, 2014. / ENGLISH ABSTRACT: Diving medical doctors frequently make use of Hyperbaric Facilities without fully realising their legal and ethical responsibilities towards the safety of their patients and their staff. Few have specific training in the technical or operational aspects of these facilities; this deficiency is exacerbated when these are established in remote areas. The potential dangers are real and the results can be devastating. Most current regulatory, manufacturing, safety and operational guidance documents are not flexible enough to be applied universally, nor do they offer practical guidance on the recognition and the mitigation of the unique and relevant hazards at a given facility. The goal of integrated safety is rarely achieved. The Risk Assessment Guide (RAG) was developed by the investigator as a tool to qualify the actual safety status of a hyperbaric facility and to offer guidance on how to improve and maintain it. Although the RAG has been subject to extensive peer review and field implementation over the past 13 years, it has not been subject to scientific validation. Therefore, the objective of this thesis was to do so by (1) retrospectively reviewing the most common safety concerns affecting facility status as identified by the RAG; (2) using the data derived from the analysis to produce a predictive model of likely safety status for un-assessed facilities; and (3) consolidating the results in the form of specific recommendations to improve and maintain safety status. Data collected from a consistent application of the RAG over a period of 13 years, covering 105 applicable facilities, was analysed to determine the common safety concerns, particularly those affecting safety status by means of a consolidated Risk Assessment Score (RAS). The RAS values permitted comparisons between the facilities assessed. The various factors associated with a higher RAS were determined by means of a multivariate regression. Thereupon, the most significant determinant factors were built into a predictive model for the likely safety status of an un-assessed facility. Finally, the most common safety concerns were identified and summarised so that medical practitioners are empowered to determine, improve and maintain the safety status of a given facility. The conclusions of this project are that: (1) the RAG is an appropriate tool to assess facilities for risk elements relevant to their safety status while simultaneously filling the knowledge gaps to equip medical practitioners and staff to improve and maintain safety; (2) reliable predictions on unknown facilities can be made to provide medical practitioners with the necessary information on whether a given facility is appropriate for patient referral; and (3) the RAG is a suitable benchmark for determining hyperbaric facility safety; the review of its application has provided objective data that will permit the formulation of future safety guidelines based on empirical rather than arbitrary information. / AFRIKAANSE OPSOMMING: Duikmediese dokters maak dikwels gebruik van hiperbariese fasiliteite sonder om die wetlike en etiese verantwoordelikhede ten opsigte van die veiligheid van hul pasiënte en personeel te besef. Weinig het spesifieke opleiding in die tegniese of operasionele aspekte van hierdie fasiliteite; hierdie tekort is gewoonlik erger in afgeleë gebiede. Die potensiële gevare is wesenlik en die gevolge kan verwoestend wees. Meeste van die huidige regulatoriese-, vervaardigings-, veiligheids en operasionele leidingsdokumente is nie buigsaam genoeg om in die algemeen toegepas te kan word nie. Hulle bied ook nie praktiese leiding oor die erkenning en die versagting van unieke en relevante gevare by 'n gegewe fasiliteit nie. Die doelwit van geïntegreerde veiligheid word selde bereik. Die “Risk Asssessment Guide” (RAG) is voorheen deur die navorser ontwikkel as 'n instrument om die werklike veiligheidsstatus van 'n hiperbariese fasiliteit te kwantifiseer en leiding te bied oor hoe om dit te verbeter en in stand te hou. Alhoewel die RAG onderhewig was aan uitgebreide eweknie hersiening en praktiese uitvoering oor die afgelope 13 jaar, was dit nie voorheen onderhewig aan wetenskaplike validasie nie. Die doelwit van hierdie tesis is dus om hierdie te bewerkstellig deur (1) die mees algemene veiligheidskommernisse wat fasiliteitstatus beïnvloed, soos deur die RAG geïdentifiseer, retrospektiewelik te hersien; (2) die data wat deur die hersiening verkry is te gebruik om 'n model te ontwikkel vir onbeoordeelde fasiliteite, wat die waarskynlike veiligheidsstatus kan voorspel, en (3) die resultate te konsolideer in die vorm van spesifieke aanbevelings om veiligheidsstatus te verbeter en in stand te hou. Die data wat ingesamel is deur die konsekwente toepassing van die RAG oor 'n tydperk van 13 jaar en wat 105 fasiliteite gedek het, is ontleed om die algemene veiligheidskommernisse, veral die wat die veiligheidsstatus beïnvloed, deur middel van 'n gekonsolideerde Risikoassesserings waarde (RAW) te bepaal. Die duidelike en aangepaste RAW laat toe om vergelykings tussen die fasiliteite te tref. Faktore wat verband hou met 'n hoër RAW was deur middel van 'n meervoudige regressie bepaal. Daarna is die belangrikste determinante in 'n voorspellende model gebou om die waarskynlike veiligheidsstatus van 'n onbeoordeelde fasiliteit te bepaal. Ten slotte was die mees algemene veiligheidskommernisse geïdentifiseer en opgesom om sodoende mediese praktisyns te bemagtig om die veiligheidsstatus van 'n gegewe fasiliteit vas te stel, te verbeter en in stand te hou. Die gevolgtrekkings van hierdie projek is dat: (1) die RAG 'n geskikte instrument is om fasiliteite te evalueer vir risiko-elemente wat relevant is tot hul eie veiligheidsstatus en terselfdertyd die kennisgapings te vul om geneeshere en personeel toe te rus om veiligheid te verbeter en in stand te hou; (2) redelik betroubare voorspellings oor onbekende fasiliteite kan gemaak word om vir mediese praktisyns die nodige inligting te verskaf aangaande die geskiktheid van 'n gegewe fasiliteit vir pasiënt-verwysing, en (3) dat die RAG 'n geskikte maatstaf is vir die bepaling van hiperbariese fasiliteit veiligheid. Die hersiening van die toepassing het objektiewe data voorsien wat die formulering van toekomstige veiligheidsriglyne, geskoei op empiriese eerder as arbitrêre inligting, sal toelaat.

Introdução: O conhecimento da fisiopatogênese da Doença Inflamatória Intestinal (DII) tem evoluído nas últimas décadas. No entanto, apesar das terapias terem evoluído, 2/3 dos casos ainda necessitam de drogas alternativas e terapias de suporte. A busca constante de tratamentos alternativos e modalidades mais eficazes tem gerado algumas abordagens promissoras, tais como a utilização do oxigênio hiperbárico (HBO). O uso dessa terapia cresceu rapidamente nos anos 90 mostrando bons resultados e poucos efeitos colaterais sendo, posteriormente \"esquecida\" ante a eficácia apresentada pelo uso das terapias biológicas. Objetivos: Os objetivos deste trabalho foram avaliar os efeitos do tratamento com HBO em camundongos com colite induzida quimicamente pelo ácido 2,4,6 trinitro benzeno sulfônico 2,5% (TNBS), sobre a avaliação dos animais, a análise histológica, o perfil inflamatório através das citocinas IL-4, IL-10, IL-12, IL-13, IL-17, fator de necrose tumoral alfa (TNFalfa) e Interferon y e da atividade das enzimas antioxidantes superóxido dismutase (SOD), glutationa peroxidase (GPx) e glutationa redutase (GR) em intestino de camundongos. Metodologia: Camundongos machos foram divididos em 6 grupos. No grupo 1, a colite foi induzida por TNBS 2,5% + Etanol 35%, sendo chamado de grupo TNBS; o grupo 2 também recebeu TNBS 2,5% + Etanol 35% seguido do tratamento com o HBO, sendo chamado de grupo TNBS+HBO; o grupo 3 recebeu apenas o veículo etanólico a 35%, sendo chamado de grupo ÁLCOOL; o grupo 4 também recebeu o veículo etanólico a 35% associado ao HBO, sendo chamado de grupo ÁLCOOL+HBO; o grupo 5 recebeu apenas solução salina (NaCl 0,9%), sendo chamado de grupo SALINA; e o grupo 6 recebeu a solução salina associado ao HBO, sendo chamado de grupo SALINA+HBO. Durante o tratamento os animais foram avaliados diariamente. O tratamento com HBO foi realizado por 4 dias e, ao final, as amostras da porção final do intestino foram retiradas e armazenadas para análise histológica, enzimas antioxidantes e citocinas. Resultados: A avaliação mostrou que o HBO promoveu uma melhora significativa no quadro clínico desses animais. A aplicação do ácido 2,4,6 trinitro benzeno sulfônico nos animais do grupo TNBS resultou na perda de 12,71% do peso corpóreo dos animais após 24 horas e, ao final do período experimental uma perda de peso total de 14,63%. Por outro lado, os animais que também receberam 2,4,6 trinitro benzeno sulfônico associado ao tratamento com o HBO (TNBS+HBO) tiveram uma perda de apenas 7,52% nas primeiras 24 horas, apresentando uma recuperação de 5,58% de seu peso no final do período experimental. A avaliação do quadro histológico mostrou uma melhora significativa entre o grupo TNBS+HBO quando comparado com o grupo TNBS. O tratamento com HBO aumentou a atividade das enzimas antioxidantes SOD e GPx em todos os grupos, sendo somente significativo entre os grupos TNBS vs TNBS+HBO, não sendo observado diferença da GR entre os grupos. Com relação ao perfil inflamatório foi observado que o tratamento com o HBO promoveu a diminuição das citocinas pró-inflamatórias INFy, IL-12, IL-17 e TNF? e o aumento das citocinas anti-inflamatórias IL-4 e IL-10, e não houve alteração da IL-13. Em modelo experimental, esses dados representam, o potencial efeito anti-inflamatório e o do aumento das defesas antioxidantes enzimáticas promovido pelo HBO / Introduction: The Knowledge about the physiopathogenesis of inflammatory bowel disease (IBD) has evolved over the last decades. However, although therapies have improved, 2/3 of the cases still need alternative drugs and support therapy. The constant search for alternative treatments and more effective modalities has brought to light some promising strategies, as the use of hyperbaric oxygen (HBO). The use of such therapy surged rapidly in the 90´s showing good results and few side effects being, later on, \"forgotten\" due to the efficacy shown by the use of biological therapies. Objective: This study aimed to evaluate the effects of HBO treatment in mice with chemically induced colitis, using 2,4,6 trinitrobenzene sulfonic acid 2,5% (TNBS) over the evaluation of the animals, histological analysis, inflammatory profile through cytokines IL-4, IL-10, IL-12, IL-13, IL-17, TNF- alfa and interferon y, and also the activity of the antioxidant enzymes superoxide dismutase (SOD), gluthatione peroxidase (GPx) and gluthatione reductase (GR) in intestine of mice. Methodology: Male mice were divided into 6 groups, in group 1, colitis was induced by TNBS 2,5%+ Ethanol 35%, named as TNBS, group 2 also received TNBS 2,5%+ Ethanol 35% + HBO, named as TNBS+HBO, group 3 received only Ethanol 35%, named as ALCOHOL, group 4 received Ethanol 35% associated with HBO, named as ALCOHOL+HBO, group 5 received Saline (NaCl 0,9%), named as SALINE and group 6 received Saline combined with HBO, named as SALINE+HBO. During the treatment the animals were evaluated daily. The treatment with HBO was performed for 4 days and at the end, the samples of the final portion of the bowel were removed and stored for histological, antioxidant enzymes and cytokines analysis. Results: This study has shown that the HBO promoted a significant improve on these animals clinical status. The group which received TNBS showed a 12,71% body weight loss after 24 hours, and by the end of the experimental period the average weight loss was 14,63%. On the other hand, the animals treated with HBO showed only 7,52% weight loss during the first 24 hours, having recovered the weight lost in 5,58% by the end of the experimental period. The histological evaluation of the TNBS+HBO group presented a significant improvement when compared with TNBS group. The treatment with HBO increased the activity of the antioxidant enzymes SOD and GPx in all groups, being only significant among the groups TNBS vs TNBS+HBO, difference in the activity of GR was not observed among the groups. Regarding the inflammatory profile, it was observed that the treatment with HBO promoted the decrease of pro-inflammatory cytokines INFy, IL-12, IL-17 and TNFalfa, as well as the increase of anti-inflammatory cytokines IL-4 and IL-10, while IL-13 was not affected. These data represents, in experimental model, the potential anti-inflammatory effect and the increase of the enzymatic antioxidant defenses promoted by the HBO

Introdução: O conhecimento da fisiopatogênese da Doença Inflamatória Intestinal (DII) tem evoluído nas últimas décadas. No entanto, apesar das terapias terem evoluído, 2/3 dos casos ainda necessitam de drogas alternativas e terapias de suporte. A busca constante de tratamentos alternativos e modalidades mais eficazes tem gerado algumas abordagens promissoras, tais como a utilização do oxigênio hiperbárico (HBO). O uso dessa terapia cresceu rapidamente nos anos 90 mostrando bons resultados e poucos efeitos colaterais sendo, posteriormente \"esquecida\" ante a eficácia apresentada pelo uso das terapias biológicas. Objetivos: Os objetivos deste trabalho foram avaliar os efeitos do tratamento com HBO em camundongos com colite induzida quimicamente pelo ácido 2,4,6 trinitro benzeno sulfônico 2,5% (TNBS), sobre a avaliação dos animais, a análise histológica, o perfil inflamatório através das citocinas IL-4, IL-10, IL-12, IL-13, IL-17, fator de necrose tumoral alfa (TNFalfa) e Interferon y e da atividade das enzimas antioxidantes superóxido dismutase (SOD), glutationa peroxidase (GPx) e glutationa redutase (GR) em intestino de camundongos. Metodologia: Camundongos machos foram divididos em 6 grupos. No grupo 1, a colite foi induzida por TNBS 2,5% + Etanol 35%, sendo chamado de grupo TNBS; o grupo 2 também recebeu TNBS 2,5% + Etanol 35% seguido do tratamento com o HBO, sendo chamado de grupo TNBS+HBO; o grupo 3 recebeu apenas o veículo etanólico a 35%, sendo chamado de grupo ÁLCOOL; o grupo 4 também recebeu o veículo etanólico a 35% associado ao HBO, sendo chamado de grupo ÁLCOOL+HBO; o grupo 5 recebeu apenas solução salina (NaCl 0,9%), sendo chamado de grupo SALINA; e o grupo 6 recebeu a solução salina associado ao HBO, sendo chamado de grupo SALINA+HBO. Durante o tratamento os animais foram avaliados diariamente. O tratamento com HBO foi realizado por 4 dias e, ao final, as amostras da porção final do intestino foram retiradas e armazenadas para análise histológica, enzimas antioxidantes e citocinas. Resultados: A avaliação mostrou que o HBO promoveu uma melhora significativa no quadro clínico desses animais. A aplicação do ácido 2,4,6 trinitro benzeno sulfônico nos animais do grupo TNBS resultou na perda de 12,71% do peso corpóreo dos animais após 24 horas e, ao final do período experimental uma perda de peso total de 14,63%. Por outro lado, os animais que também receberam 2,4,6 trinitro benzeno sulfônico associado ao tratamento com o HBO (TNBS+HBO) tiveram uma perda de apenas 7,52% nas primeiras 24 horas, apresentando uma recuperação de 5,58% de seu peso no final do período experimental. A avaliação do quadro histológico mostrou uma melhora significativa entre o grupo TNBS+HBO quando comparado com o grupo TNBS. O tratamento com HBO aumentou a atividade das enzimas antioxidantes SOD e GPx em todos os grupos, sendo somente significativo entre os grupos TNBS vs TNBS+HBO, não sendo observado diferença da GR entre os grupos. Com relação ao perfil inflamatório foi observado que o tratamento com o HBO promoveu a diminuição das citocinas pró-inflamatórias INFy, IL-12, IL-17 e TNF? e o aumento das citocinas anti-inflamatórias IL-4 e IL-10, e não houve alteração da IL-13. Em modelo experimental, esses dados representam, o potencial efeito anti-inflamatório e o do aumento das defesas antioxidantes enzimáticas promovido pelo HBO / Introduction: The Knowledge about the physiopathogenesis of inflammatory bowel disease (IBD) has evolved over the last decades. However, although therapies have improved, 2/3 of the cases still need alternative drugs and support therapy. The constant search for alternative treatments and more effective modalities has brought to light some promising strategies, as the use of hyperbaric oxygen (HBO). The use of such therapy surged rapidly in the 90´s showing good results and few side effects being, later on, \"forgotten\" due to the efficacy shown by the use of biological therapies. Objective: This study aimed to evaluate the effects of HBO treatment in mice with chemically induced colitis, using 2,4,6 trinitrobenzene sulfonic acid 2,5% (TNBS) over the evaluation of the animals, histological analysis, inflammatory profile through cytokines IL-4, IL-10, IL-12, IL-13, IL-17, TNF- alfa and interferon y, and also the activity of the antioxidant enzymes superoxide dismutase (SOD), gluthatione peroxidase (GPx) and gluthatione reductase (GR) in intestine of mice. Methodology: Male mice were divided into 6 groups, in group 1, colitis was induced by TNBS 2,5%+ Ethanol 35%, named as TNBS, group 2 also received TNBS 2,5%+ Ethanol 35% + HBO, named as TNBS+HBO, group 3 received only Ethanol 35%, named as ALCOHOL, group 4 received Ethanol 35% associated with HBO, named as ALCOHOL+HBO, group 5 received Saline (NaCl 0,9%), named as SALINE and group 6 received Saline combined with HBO, named as SALINE+HBO. During the treatment the animals were evaluated daily. The treatment with HBO was performed for 4 days and at the end, the samples of the final portion of the bowel were removed and stored for histological, antioxidant enzymes and cytokines analysis. Results: This study has shown that the HBO promoted a significant improve on these animals clinical status. The group which received TNBS showed a 12,71% body weight loss after 24 hours, and by the end of the experimental period the average weight loss was 14,63%. On the other hand, the animals treated with HBO showed only 7,52% weight loss during the first 24 hours, having recovered the weight lost in 5,58% by the end of the experimental period. The histological evaluation of the TNBS+HBO group presented a significant improvement when compared with TNBS group. The treatment with HBO increased the activity of the antioxidant enzymes SOD and GPx in all groups, being only significant among the groups TNBS vs TNBS+HBO, difference in the activity of GR was not observed among the groups. Regarding the inflammatory profile, it was observed that the treatment with HBO promoted the decrease of pro-inflammatory cytokines INFy, IL-12, IL-17 and TNFalfa, as well as the increase of anti-inflammatory cytokines IL-4 and IL-10, while IL-13 was not affected. These data represents, in experimental model, the potential anti-inflammatory effect and the increase of the enzymatic antioxidant defenses promoted by the HBO

The caudal solitary complex (cSC) is a cardiorespiratory integrative center in the dorsal medulla oblongata that plays a vital role in the central CO2-chemoreceptive network. Neurons in this area respond to hypercapnic acidosis (HA) by a depolarization of the membrane potential and increase in firing rate, however a definitive mechanism for this response remains unknown. Likewise, CO2-chemoreceptive neurons in the cSC respond to hyperoxia in a similar fashion, but via a free radical mediated mechanism. It remains unknown if the response to increased pO2 is merely an increase in redox signaling, or if it’s the result of a pathological state of redox stress. Importantly, free radical production is known to be stimulated by increasing pO2, and can be exacerbated downstream by the addition of CO2 and its subsequent acidosis. Conditions of hyperoxia in combination with HA can therefore become detrimental in several scenarios, including O2 toxicity seizures in divers and stranded submariners, as well as in cases of ischemia-reperfusion injury and sleep apneas. As such, we sought to not only determine how O2 and CO2 interact to affect cellular excitability in the cSC, but also if these cells exhibited increases in redox signaling and/or stress. We employed sharp-electrode intracellular electrophysiology to study whole-cell electrical responses to varied combinations of hyperoxia (0.4 0.95/1.95 ATA O2) and HA (0.05 0.1 ATA CO2). Additionally, we used fluorescence microscopy under similar conditions to study changes in the production rates of various free radicals, including superoxide (˙O2-), nitric oxide (˙NO), and a downstream aggregate pool of CO2/H+-dependent reactive oxygen and nitrogen species (RONS). Finally, we used several colorimetric assays to measure markers of oxidative and nitrosative stress, including malondialdehyde, 3-nitrotyrosine, and protein carbonyls. Our hypothesis for these experiments was that hyperoxia and HA alone could produce effects, but would be more pronounced when used together. As such, we saw that ~89% of cells tested that were sensitive to both hyperoxia and HA showed larger firing rate responses to HA during an increased background O2 (0.9 and/or 1.9 ATA) after showing a smaller response or no response to HA during control levels O2 (0.4 ATA). Additionally, we noted that the rate of ˙O2- fluorescence increased in response to hyperoxia, but only during pharmacological inhibition of its reactions with ˙NO and SOD. Likewise, the rate of ˙NO fluorescence increased during hyperoxia compared to control O2, but only during pharmacological scavenging of ˙O2-. Downstream, our aggregate pool of RONS showed increased rates of fluorescence during both hyperoxia alone and HA in control O2, however the most prominent increases were seen during hypercapnic hyperoxia. Finally, no significant effects were seen when probing for markers of redox stress in response to hyperoxia and hypercapnic hyperoxia. Overall, these results suggest that the increased excitability seen in cSC neurons during hypercapnic hyperoxia is the result of physiological redox signaling rather than pathological redox stress. Further research needs to be done to determine how this redox mechanism is specifically resulting in increased cellular excitability.

Vital components are more or less prone to fail in a diving apparatus. This thesis examines the performance of oxygen sensors, carbon dioxide scrubber monitoring and composite gas cylinders. A partial pressure of oxygen sensor authentication is suggested in a published patent and poster, weaknesses in carbon dioxide scrubber monitoring systems near surface are revealed in a published paper and potential harmful gas permeability properties of a composite gas cylinder, altering the gas composition and decreases the oxygen fraction, is measured and determined in a submitted paper.The importance of adequately and thoroughly performed safety tests that are standardized becomes even more relevant when managing personal protective equipment. The European Committee for Standardization have ratified relevant standard for the work in this thesis;EN-14143 Respiratory equipment – Self-contained re-breathing diving apparatus,EN-12245:2009+A1:2011 Transportable gas cylinders – Fully wrapped composite cylinders, andISO 11119-3:2013 Gas cylinders – Refillable composite gas cylinders and tubes – Design, construction and testing.These tests form a base-line for the methods, tests and result evaluations performed here and are considered safe; however improvements to the tests and standards can be made and are here suggested.

Made available in DSpace on 2014-07-29T15:07:41Z (GMT). No. of bitstreams: 1 Dissertacao Ana Carolina Vasques Villela.pdf: 1200187 bytes, checksum: e80340dfd98ca2e1e517f50dcd0bef34 (MD5) Previous issue date: 2012-02-24 / A anestesia local se popularizou na medicina veterinária no século XX, mas alguns de seus recursos, como o cateter epidural e as soluções hiperbáricas, bastante utilizados no homem atualmente ainda são pouco estudados e aplicados em animais. Em seguida, outro estudo verificou a qualidade da anestesia epidural toracolombar com lidocaína a 2% ou hiperbárica a 5% e a influência do decúbito e o do tempo de permanência do cateter epidural na qualidade deste bloqueio. Para isso foram usados sete cães machos, adultos, pesando 12,76 +/-2,59 kh. Com os animais até o espaço T13-L1, tendo seu dispositivo sepultado no tecido subcutâneo. Em seguida, administrou-se 4 mg/kg de lidocaína isobárica a 2% com os animais em posição quadrupedal(IQ4) ou em decúbito lateral (IL4); 3 mg/kg de lidocaína hiperbárica a 5% em posição quadrupedal (HQ3) ou em decúbito lateral (HL3); e 4 mg/kg de lidocaína hiperbárica a 5% em posição quadupedal (HQ4) ou em decúbito lateral (HL4). Foram avaliadas a viabilidade da técnica de implantação; a ocorrência de complicações após a implantação ou retirada do cateter epidural; o tempo de permanência do cateter epidural; os efeitos da administração de lidocaína a 2% ou hiperbárica a 5% sobre a FC, , PAS, SPO2 e TR; a a qualidade do bloqueio anestésico (latência, extensão, simetria e duração do bloqueio anestésico); influência do decúbito e do tempo de permanência do cateter na qualidade do bloqueio anestésico. A implantação do cateter epidural foi viável e isenta de complicações; houve redução significativa somente nos valores de e TR em relação ao valor basal nos grupos IQ4, IL4, HQ3, HL3,HQ4. Não foram observadas diferenças significativas na FC, PAS, SPO2, latência, duração e extensão do bloqueio entre os grupos. O decúbito não influenciou significativamente a qualidade do bloqueio. O tempo de permanência do cateter no espaço epidural influenciou significativamente a duração máxima do bloqueio sensitivo. Em conclusão, o modelo descrito para implantação do cateter epidural é viável, porém o tempo que o cateter permaneceu no espaço epidural influenciou a duração do bloqueio anestésico e a lidocaína hiperbárica a 5% não mostrou vantagens em relação ao uso da lidocaína isobárica a 2% na anestesia epidural toracolombar.