Orientador: Lea Rodrigues Simioni / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-03T18:21:12Z (GMT). No. of bitstreams: 1 Durigon_AndreMarchi_M.pdf: 4253171 bytes, checksum: d40a5c4577ed52c635254ee0ab159b13 (MD5) Previous issue date: 2003 / Resumo: No presente estudo, os efeitos farmacológicos do veneno de Bothrops neuwiedi pauloensis foram estudados em preparações nervo frêniCCHiiafragma de camundongo e biventer cervicis de pintainho. Em preparações biventer cervicis de pintainho, na temperatura de 37°C, o veneno, (1,5, 10,50 e 100 J1g/ml) produziu bloqueio neuromuscular progressivo e dependente da concentração. Em baixas concentrações (1,5, 10 e 20 J1g1m1), as respostas ao KCI (13,4 mM), aplicado ao banho, foram parcialmente inibidas, enquanto que as respostas à ACh (110 mM ou concentrações cumulativas de 10-6 - 10-2 mM) permaneceram após a incubação com o veneno, e na vigência de bloqueio total. Em altas concentrações (50 - 100 J1g1ml), o veneno causou contratura, inibiu as respostas à ACh, ao KCI e as contrações em resposta à estimulação elébica direta. Estes efeitos não foram observados à temperatura ambiente (20 - 24° C), quando COf11)8rados aos obtidos a 37°C. Na preparação hemidiafragma de camundongo, na concentração de 20 p.gImI, o veneno inibiu irreversivelmente (60 :t 10 % de bloqueio; p < 0,05; n = 6) as respostas à estimulação elétrica indireta. Na mesma preparação a concentração de 50 J1g1ml do veneno determinou bloqueio completo das contrações musculares em resposta à estimulação elétrica indireta (n = 5) e direta (n = 6). Na ausência do ea2+ (1,8 mM), substituído pelo s.-2+ (4 mM), o p < 0,05; n = 3) após 120 min de incubação. O registro eletrofisiológico demonstrou um aumento na freqüência dos pptms (562 :t 3%; p < 0,05), após 120 min de incubação. O veneno (20 f.1g1ml) determinou um aumento (25 :t 2%; p<0,05) na freqüência dos potenciais gigantes em 9 das 10 placas examinadas após 30 min de observação (LEE et ai., 1985). O registro do potencial de repouso mostrou que após 90 min de incubação com o veneno (20 f.1g/ml) houve uma redução no valor médio do potencial de membrana de -81 :t 1,4 mV para - 41,3 :t 3,6 mV (24 fibras; p < 0.01; n = 4) em regiões de placa terminal e de -77,4 :t 1,4 mV para - 44,6 :t 3,9 mV (24 fibras; p < 0.01; n = 4) em regiões distantes da placa. Estes resultados indicam que o veneno de Bothrops neuwiedi pauloensis exibe neurotoxicidade em preparações neuromusculares isoladas e sugerem uma ação preferencial em sítios pré-sinápticos. Além disso, uma atividade enzimática parece estar envolvida na indução de seus efeitos farmacológicos, pois mostrou ser cálcio-dependente / Abstract: In the present study, the phannacological effects of Bothrops neuwiedi pauloensis venom were studied in mouse phrenic nerve-diaphragm and chick biventer cervicis preparations. In chick preparations, venom (1, 5, 10,50 and 100 J.1g1ml) produoed progressive, concentration-dependent neuromuscular blockade. At low venom concentrations (1, 5, 10 and 20 J.1g1m1) , the responses to exogenously applied KCI (13.4 mM) were inhibited whereas those to acetylcholine (ACh, 110 mM alone or cumulative concentrations of 10-6-10-2 M) were unaffected. At high venom concentrations (50 and 100 J.1g1ml) , there was pronounoed muscle contracture with inhibition of the responses to ACh, KCI and direct stimulation. These activities were not observed at 20-24°C compareci to 37°C. At 20 J.1g1m1, the venom irreversibly inhibited indirectly evoked twitches in mouse phrenic nerve-diaphragm preparations (60 ::t 10% inhibition, mean ::t SEM; p<0.05; n = 6). At 50 J.1g1m1, the venom blocked indirectly (n = 5) and directly (n=6) evoked twitches in mouse hernidiaphragms. When Ca2+ (1.8 mM) was replaced by S~ (4 mM), the venom (50 J.1g/ml) produoed only partial blockade (40.3:t 7.8% inhibition; p<0.05; n = 3) after 120 mino The venom (20 J.1g1m1) inaeased the number of miniature end-plate potentials by a maximum of 562::t 3%, (p<0.05) after 120 min, and also increased the frequency of giant miniature end-plate potentials (25 ::t 2%, 1><0.05) in 9 out of 10 end-plates -41.3:t 3.6 mV (24 fibers; p<O.01; n = 4) in the end-plate region, and trom - 77.4 :t 1.4 to -44.6 :t 3.9 mV (24 fibers; p<O.01; n = 4) in regions distant trom the end-plate. These results indicate that B. n. pauloensis venom is neurotoxic and has a presynaptic adion. They also suggest that enzymatic activity may be involved in this phannacological action / Mestrado / Mestre em Farmacologia

Orientadores: Maria Alice da Cruz-Hofling, Lea Rodrigues-Simioni / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-07-24T21:59:09Z (GMT). No. of bitstreams: 1 Costa_PatriciaDourado_M.pdf: 12162774 bytes, checksum: bc20d738d02786ba6422eeb6cadaf073 (MD5) Previous issue date: 1999 / Resumo: Várias são as motivações que levam ao estudo de substâncias naturais podendo ser citadas, a caracterização dos seus princípios ativos e dos seus efeitos biológicos. Dentre estas, ocupam lugar de destaque os venenos ofídicos, uma vez que é freqüente o envenenamento acidental causado por picada de serpentes, nos países de clima tropical. No Brasil, os acidentes ofídicos representam problema de Saúde Pública, sendo o gênero Bothrops responsável por cerca de 90% dos casos. Dentre os efeitos sistêmicos e locais, destaca-se a mionecrose que se manifesta rapidamente, é de difícil controle e merece atenção especial nas estratégias de tratamento. A mionecrose é provocada por proteínas miotóxicas que atuam especificamente no sítio da picada. Frente à escassez de estudos quanto à ação biológica do veneno da serpente Bothrops pirajai ("jararacussu da Bahia") uma espécie rara e exclusiva do estado da Bahia e nordeste de Minas Gerais, o presente trabalho foi proposto com o objetivo de investigar as possíveis atividades miotóxica e neurotóxica do seu veneno total e de suas frações isoladas, Piratoxina-I (prTX- I) e Piratoxina-III (PrTX-III). Para o estudo, foram utilizadas preparações neuromusculares, nervo frênico-diafragma (NFD) e extensor longo dos dedos (EDL) de camundongos. Os parâmetros utilizados foram a técnica miográfica, a determinação de creatinoquinase (CK), análise histológica e ultraestrutural. O veneno total e a fração PrTX-III nas doses de 10, 25 e 50 µg/ml causaram bloqueio dose-dependente da resposta contrátil do músculo EDL, alterações morfológicas e ultraestrututais com elevada liberação da enzima creatinoquinase (CK) na cuba. A miotoxina PrTX-I provocou bloqueio dose-dependente (doses de 5, 10 e 20 µg/ml) da resposta contrátil do músculo diafragma de camundongo e severa mionecrose constatada pela análise histológica do tecido. No entanto, esta fração não provocou alterações miográficas ou histológicas no músculo EDL. Essas diferenças quanto à sensibilidade foram provavelmente devidas às diferenças entre o EDL e o diafragma, que diferem quanto às quantidades de fibras de contração rápida e lenta. Nossos resultados sugerem que a miotoxina PrTX-I e a fração PrTX-III do veneno total de B. pirajai seriam os componentes responsáveis pela atividade miotóxica do veneno, muito embora haja evidência de que seus modos de ação podem ser distintos. Além disso, os resultados preliminares com a fração PrTX-III apontam para uma potente ação neurotóxica, fato observado também com o veneno total. / Abstract: Several reasons can be cited which motivate the study of natural substances such as the characterization of the active principles and its biological effects. Among them, the ophidic venoms stand out because it is common the occurrence of accidental envenomation after snake bites in tropical countries. In Brazil, ophidic accidents account for a major part in the context of Public Health were the genus Bothrops is responsable for about 90% of them. Myonecrosis is one ofthe local effects whose rapid onset is difficult to control and deserves special attention in the treatment approaches after envenomation. Myonecrosis is triggred by myotoxic proteins specifical1y acting in muscle fibers at the bite site. Due to the scarcity of studies about the biological actions of Bothrops pirajai (li jararacussu of Bahia") snake venom, arare and exclusive specimen living in Bahia and northeastrn of Minas Gerais, the present work was proposed viewing to investigate miotoxic and neurotoxic activities of crude venom and its fractions Piratoxin-I (PrTX-I) and Piratoxin-III (PrTX-III). The studies were performed in mice isolated muscle preparations of the extensor'digitorum longus (EDL) and phrenic nerve-diaphragm (PND) muscles through myographic, histological and ultrastructural analysis and determination of creatinokinase (CK) in the incubation bath. The venom and the fraction PrTX-III (10, 25 and 50 µg/ml) caused a dose-dependent twitch-tension blockade of the EDL muscle fibers, histological and ultrastructural changes of muscle cells and nerve endings culminating in complete necrosis of both and increased CK release in the bath. PrTX-I caused a dose dependent blockade (5, 10 and 20 µg/ml) onhe twitch tension in PND muscle fibers and severe myonecrosis. However, PrTX-I did not affect muscle fibers nor caused alter(!.tions on the twitch tension responses in EDL. These differences could be accounted for a distinct sensitivity of EDL and PND muscle fibers to the venom and PrTX-I possibly related to the amount of slow- and fast-contracting fibers present in each one. Our results suggest that PrTX-I and PrTX-III of B. pirajai venom would be the components accounting for the myotoxic activity of venom despite a distinct mechanism of action could be implied. Additionally, these preliminary results suggest a potent neurotoxic activity, also observed with the whole venom. / Mestrado / Farmacologia / Mestre em Ciências

I dagens elektroniska samhälle, e-samhället, har invånare hög förväntan och höga krav när det kommer till kvalitet på elektroniska offentliga tjänster, så kallade offentliga e-tjänster. För att uppfylla invånarnas förväntan och krav krävs det att e-tjänsterna utvärderas utifrån kvalitet. Eftersom offentliga e-tjänster nyttjas av t ex invånare i en kommun är det viktigt att invånarna involveras i utvärderingen eftersom det är invånarna som är användaren av e-tjänsten. Kvalitetsramverket COBRA är en metod som används för att mäta kvalitet på offentliga e-tjänster och som involverar användaren. COBRA är ett kvantitativt ramverk och i denna studie kommer COBRA att användas kvalitativt med hjälp av intervjuer för att mäta kvalitet på en specifik offentlig e-tjänst. Syftet med studien är att ta reda på hur COBRA kan tillämpas kvalitativt och hur resultatet av det kommer bli. Resultatet av studien visar hur COBRA kan tillämpas kvalitativt och det som har gjorts i denna studie är att tillämpa en intervjuguide utifrån COBRA. Intervjuguiden har genomförts på Skövde kommuns e-tjänst ”jämförelsetjänst”. Resultatet visar resultatet från intervjuerna, hur COBRA har tillämpats kvalitativt samt hur COBRAs kvantitativa frågor har blivit kvalitativa.

This essay explores Operation Cobra based on a social constructivist perspective, according to social constructivist Ian Hacking. To do this, I examined newspaper articles from that event. The purpose of this paper was to examine how the border between extortioners and terrorists was constructed during the Swedish 80's and to examine why the perpetrator was constructed as a extortion and not a terrorist. I also examined how a terrorist from the eighties differs from the present-day terrorist. My result shows that the limits of what the perpetrator is being constructed depends on the newspaper articles and how the journalists have described him. He was designed as a terrorist, extortionist, correct, pedant, and also a madman. Operation Cobra took place in Sweden in 1983-1985 and has been described as Sweden's biggest extortion event.

Orientadores: Lea Rodrigues Simioni, Maria Alice da Cruz-Holing / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-04T01:17:53Z (GMT). No. of bitstreams: 1 Moura_PriscilaRandazzode_M.pdf: 4111122 bytes, checksum: 4edbe32ec7d6b0ac303c94e564c0a4e6 (MD5) Previous issue date: 2004 / Resumo: Os efeitos miotóxicos dos venenos botrópicos são inquestionáveis pela exuberante manifestação clínica e são extensivamente relatados na literatura. Já os efeitos neurotóxicos têm sido descritos sob condições in vitro, em preparações neuromusculares, com pouca ou nenhuma evidência clínica. O objetivo do presente trabalho foi o de contribuir para o conhecimento sobre a farmacologia da bothropstoxina-I (BthTX-I), o principal componente do veneno de Bothrops jararacussu, em suas dimensões pré- e pós-sinápticas. Esta toxina reproduz os mesmos efeitos in vitro do veneno bruto, quais sejam, bloqueio neuromuscular e mionecrose. Como ferramenta farmacológica utilizou-se o íon manganês ('Mn POT.2+¿), capaz de prevenir o efeito bloqueado r da BthTX-I, mas não ainda investigado o seu efeito protetor sobre a miotoxicidade da BthTX-I. Para isso foram utilizadas as preparações nervo frênico-diafragma (NFD) e extensor digitorum longus (EDL) de camundongos. A neurotoxicidade foi avaliada pelas técnicas mio gráfica e eletrofisiológica, enquanto a miotoxicidade pelas técnicas histológica (determinação da porcentagem das fibras lesadas e determinação da área transversal das fibras musculares) e bioquímica (determinação da creatinoquinase, CK). ... Observação: O resumo, na íntegra, poderá ser visualizado no texto completo da tese digital / Abstract: Various Bothrops snake venoms produce neuromuscular blockade in avian and mammalian nerve-muscle preparations in vitro that is partly mediated by myotoxins. Bothropstoxin-I (BthTX-I) is the principal myotoxin present in Bothrops jararacussu venom and contributes to the neuromuscular blockade and myonecrosis caused by the venom in vitro. In this work, we investigated the ability of manganese (Mn2+) to prevent the neuromuscular blockade caused by BthTX-I in mouse phrenic nerve-diaphragm (pND) and extensor digitorum longus (EDL) preparations. Conventional electrophysiological and myographic techniques were used to study the neurotoxicity while myotoxicity was assessed based on the release of creatine kinase (CK) and on histological analysis. ... Note: The complete abstract is available with the full electronic digital thesis or dissertations / Mestrado / Farmacologia / Mestre em Farmacologia

Orientadores: Lea Rodrigues Simioni, Maria Alice Cruz-Hofling / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-07-20T06:55:13Z (GMT). No. of bitstreams: 1 Cogo_JoseCarlos_D.pdf: 14244533 bytes, checksum: f92b7d3b01d031de9913d42d8deaa4ea (MD5) Previous issue date: 1995 / Resumo: Duas frações com atividade fosfolipásica ('PLA IND. 2¿) foram isoladas do veneno total de Bothrops insularis através de 2 processos de fracionamento: gel de Sephadex G-75 em tampão formato de amônio 50 mM, pH 3,5 e gel de Sephadex G-150 em tampão fosfato salina (PBS) 0,1M, pH 7,2 seguido por cromatografia de troca iônica em DEAE Sephadex em tampão bicarbonato de amônio 0,01 M, pH 8,0. A fração isolada em pH ácido mostrou-se menos efetiva que a fração obtida em pH neutro. Esta última reproduziu todos os efeitos farmacológicos observados com o veneno total. Estes foram associados apenas à atividade ('PLA IND. 2¿) pois a fração é desprovida de atividades esterásica, coagulante e caseinolítica. Utilizando técnicas de eletrofisiologia, miografia, determinação dos níveis de creatino quinase (CQ) e estudos das alterações morfológicas (músculos incubados com r- a fração ('PLA IND. 2¿) ou injetados com o veneno e fração ('PLA IND. 2¿) e comparando nossos resultados com aqueles existentes na literatura, chegamos às seguintes conclusões: 1) Alterações miográficas induzidas pela fração ('PLA IND. 2¿) isolada em pH neutro,caracterizam-se pela facilitação da neurotransmissão (aumento da amplitude de contração muscular e aumento da freqüência dos potenciais em miniatura da placa terminal) seguida por bloqueio das contrações musculares. O bloqueio induzido por esta fração, mostrou-se dose-tempo dependente e irreversível após a lavagem da preparação. A ('PLA IND. 2¿) isolada em pH ácido promoveu a facilitação da neurotransmissão mas não promoveu o bloqueio das contrações musculares. 2) Os efeitos da redução da temperatura de incubação e da substituição de Ca2+por Sr2+ no meio nutritivo, inibindo o efeito bloqueador da fração ('PLA IND. 2¿), sugere a existência de uma relação entre as atividades enzimática e farmacológica. 3) A ('PLA IND. 2¿) foi capaz de liberar CQ dos músculos biventer cervicis incubados, em consonância com os efeitos observados diretamente nos músculos incubados tanto em microscopia óptica como nos músculos injetados, analisados com microscopia eletrônica. 4) O soro anti-botrópico (comercial) neutralizou apenas parcialmente a liberação de CQ e bloqueio das contrações musculares. A existência de componentes específicos, que não se encontram nos venenos botrópicos utilizados na imunização, põe novamente em destaque a alta especialização alcançada pela Bothrops insularis. 5) As alterações ultraestruturais induzidas pelo veneno bruto atingem a junção neuromuscular, os axônios mielínicos e as fibras musculares. Incluem também alterações vasculares e vasculotóxicas com conseqüente efeitos hemorrágicos. 6) As alterações ultraestruturais induzidas pela fração ('PLA IND. 2¿) são mais brandas. Atingem tanto a porção pré-sináptica, como a porção do músculo. No músculo afetam principalmente o retículo sarcoplasmático (distúrbio iônico provável), o túbulo T (em menor grau), e a organização miofibrilar. Células musculares mionecróticas são em menor número do que as afetadas pelo veneno bruto. Por outro lado, os efeitos hemorrágicos parecem ser mais proeminentes / Doutorado / Fisiologia / Doutor em Ciências Biológicas

Im Rahmen eines vom BMBF/BMWi geförderten WTZ-Vorhabens wurde dem Institute for Nuclear Research and Nuclear Energy (INRNE) in Sofia der Programmcode DYN3D sowie der gekoppelte Programmkomplex ATHLET-DYN3D verfügbar gemacht. Dabei stellt dieser Programmkomplex eine Anbindung des im FZR entwickelten 3D Kernmodells DYN3D an den thermohydraulischen Systemcode ATHLET der GRS dar. Zur Validierung dieser Programmcodes wurde eine Messdatensammlung zu einem Inbetriebnahmeexperiment am Block 6 des KKW Kozloduj (WWER-1000/320) erstellt. Die Ergebnisse der durchgeführten Validierungsrechnungen wurden mit den Messwerten aus der Datensammlung verglichen. In den Programmcode DYN3D wurde von den bulgarischen Experten ein vereinfachtes Modell zur Simulation von Querströmungen zwischen den Brennelementen integriert. Dieses Querströmungsmodell ermöglicht es, Prozesse mit asymmetrischen Randbedingungen realistischer zu betrachten. Eine erste Bewertung des implementierten Strömungsmodells erfolgt durch Vergleichsrechnungen zwischen dem modifizierten DYN3D Code und dem Unterkanalanalyse-Code COBRA-4I sowie auf der Grundlage von verfügbaren Messdaten aus dem KKW Kozloduj.

Snake envenomations are often medical emergencies and occur regularly in dogs. Snake venom contains hundreds of enzymes, proteins and peptides that assist in paralysing, killing and digesting prey, or as a defence against predators. Multiple snake venom components affect haemostasis in the victim. Inadvertent activation of coagulation may also result from expression of large amounts of tissue factor (TF) from injured tissues at the envenomation site, especially with potent cytotoxic venoms. The purpose of this study was to investigate the haemostatic functions in dogs envenomed by two South African snakes (Bitis arietans and Naja annulifera) using thromboelastography and traditional plasma-based coagulation assays. This prospective study included 18 client-owned dogs, of which nine dogs were envenomed by African puffadder and nine by snouted cobra. Blood was collected at presentation and at 24 hours post-envenomation. Complete blood count, thromboelastography (TEG), prothrombin time (PT), activated partial thromboplastin time (aPTT), antithrombin (AT) activity and C-reactive protein (CRP) and fibrinogen (Fib) concentrations were measured. Ten healthy client-owned dogs served as controls. These dogs were presented for routine ovariohysterectomy, castration or blood donation. Haematologic and haemostatic assay results at presentation were compared between groups using ANCOVA (analysis of covariance), and results over time between the puffadder and cobra groups were compared using linear mixed models at 5% significance. At presentation, the mean TEG R-time was significantly prolonged in the puffadder group when compared to the cobra and control groups (P=0.01 and 0.05, respectively). Visual appraisal of the thromboelastograms at presentation revealed that 5/9 (56%) of puffadder-envenomed dogs had hypocoagulable thromboelastograms as was demonstrated by prolonged R-time and decreased Angle (á), maximal amplitude (MA) and global clot strength (G). Despite this observation of hypocoagulability, none of the other TEG parameters (á, MA or G) were significantly decreased when compared to the cobra and control groups. This finding of hypocoagulability was surprising, because puffadder venom is cytotoxic, often inducing severe tissue necrosis and potentially leading to limb loss and disability in people. It therefore seems that certain components in puffadder venom affect the thromboelastograph by either interfering with or consuming coagulation factors, resulting in a hypocoagulable tracing. It is also possible that this is a dose-dependent effect, with only dogs with a significant amount of envenoming demonstrating this phenomenon. This effect appears to be transient, as 6/8 dogs (one fatality) envenomed by puffadders reverted to a severely hypercoagulable state at 24 hours post-envenomation. One dog was still hypocoagulable and one dog that was hypocoagulable became normocoagulable but still had a prolonged R-time. In the cobra-envenomed group hypercoagulable thromboelastograms were observed in 5/9 (56%) dogs at presentation as was demonstrated by increased MA and G. At 24 hours post-envenomation all cobra-envenomed dogs demonstrated hypercoagulable thromboelastograms. This hypercoagulability at presentation and 24 hours post-envenoming was not statistically significant between groups. This hypercoagulable state was likely due to tissue factor-activated coagulation promoted by inflammation at the envenomation site. At presentation, marked thrombocytopenia was evident in the puffadder-envenomed dogs when compared to the cobras and controls (P=0.04 and 0.001, respectively). Thrombocytopenia following puffadder envenomation has been reported in dogs and baboons. Components have been identified in puffadder venom that interfere with platelet function either by inhibiting or promoting aggregation. At 24 hours post-envenomation mean platelet count (Plt) was mildly increased compared to its value at presentation in the puffadder-envenomed dogs. There were Plt abnormalities in the cobra-envenomed dogs at presentation or at 24 hours post-envenomation. Marked leucocytosis was detected in the puffadder-envenomed dogs at presentation when compared to the cobras and controls (P=0.003 and 0.001, respectively) and was more severe at 24 hours post-envenomation when compared to the cobra group (P=0.01). Leucocytosis has been reported in different types of snake envenoming including puffadder-envenomed dogs. C-reactive protein (CRP) concentration at presentation was below the lowest detection limit for most dogs (14/18) in this study. At 24 hours post-envenoming all but two dogs (one each in the puffadder and cobra groups) had severely elevated CRP. This increase in CRP was statistically significant in both puffadder and cobra-envenomed dogs when compared to its concentration at presentation (P=0.04 and 0.001, respectively). Fibrinogen (Fib) concentration was not elevated in any envenomed dogs at presentation, but increased 24 hours post-envenoming. Although this increase was not statistically significant, an increase would suggest activation of the inflammatory response, as both Fib and CRP are positive acute phase proteins. Elevated CRP, neutrophilic leucocytosis and increases in cytokine IL-6 and IL-8 has been documented in four human patients bitten by Bothrops and Crotalus snakes (two each) in Brazil. CRP levels were low immediately post-envenoming, peaked at two days post-envenoming and dropped to within normal limits four days post-envenoming. These findings demonstrated a typical acute-phase response and it is likely that a similar acute phase response occurred after puffadder and cobra envenoming in our study. Mean antithrombin (AT) activity was mildly decreased in both the puffadder- and cobra-envenomed dogs compared to the controls (P=0.002 and 0.004, respectively), suggesting that the activation of haemostasis led to some AT consumption. Mean PT and mean aPTT were prolonged in the cobra-envenomed dogs compared to the controls (P=0.03 for both), but were within their reference intervals (RI). At 24 hours post envenomation mean haematocrit (Ht) was significantly decreased in the puffadder group compared to the cobra group (P=0.01), but was within RI. The Ht was significantly lower at 24 hours post envenomation compared to presentation values in both these groups (P<0.001 and 0.02, respectively). At presentation, marked thrombocytopenia, leucocytosis and prolonged clot initiation were common features in puffadder-envenomed dogs and were likely venom-induced. Snouted cobra-envenomed dogs were normo- to hypercoagulable at presentation. Both puffadder- and cobra-envenomed dogs equally showed hypercoagulability at 24 hours post-envenomation and this was more pronounced compared to their coagulability at presentation. TEG proved to be a useful tool to detect abnormal haemostasis in all envenomed dogs in this study. TEG also provided additional insights into certain aspects of snake envenomation (such as hypercoagulability) that has not been reported on previously and cannot be assessed using traditional coagulation assays. TEG may serve as a differentiating tool in early envenomation between these two types of snake envenoming in scenarios where the identity of the snake species involved is not known. / Dissertation (MMedVet)--University of Pretoria, 2012. / Companion Animal Clinical Studies / unrestricted

Metabolic Syndrome (MetS) is a cluster of metabolic disorders that substantially increase the risk of developing other chronic diseases such as cardiovascular disease and type II diabetes. Diet is known to play a crucial role in the development of MetS and dietary intervention studies are a useful tool to investigate the effect of diet on MetS. However, the slow onset of MetS and difficulties associated with adhering to new diets, especially for long-term, makes it challenging to perform extensive dietary intervention studies on humans. To overcome this limitation, we sought to investigate the impact of diet on the risk of MetS by taking an in silico systems biology approach. We employed a whole-body model (WBM) of metabolism that accounts for 26 organs, including six sex organs, to computationally evaluate, at genome-scale, the effect of ten different diets on the serum levels of five key metabolites implicated in MetS namely glucose, triacylglycerides (TAG), LDL-C, HDL-C, and palmitoyl-CoA. We performed separate simulations for males and females using the sex specific WBMs. Our analyses elucidated molecular mechanisms that support the current hypothesis that an unhealthy diet can significantly elevate the risk of developing MetS while a healthy diet helps promote metabolic homeostasis. Furthermore, our investigation uncovered novel insights into the contribution of specific organs and tissues to the risk of MetS under these diets in males and females. For example, we found that glucose and TAG secretion by adipocytes into the blood are substantially lower and higher, respectively, under the unhealthy diet compared to other diets. Striking differences were also observed between the unhealthy diet and other diets for LDL-C, HDL-C, and palmitoyl-CoA in males. In females, we observed patterns that resembled those in males although other organs, such as the breast or uterus, also contributed to the serum levels of these key metabolites. Our study offers a promising strategy for investigating the effect of various dietary regimens on human metabolism and MetS at organ-level resolution. This paves the way for the in silico design of new dietary interventions to treat MetS. / 2026-02-12T00:00:00Z

Um dos parâmetros termo-hidráulicos de segurança mais importantes no projeto e operação de reatores a água pressurizada é o fluxo de calor crítico (FCC). O FCC ocorre quando se atinge uma região de instabilidade na mudança de mecanismo de transferência de calor de uma parede aquecida para um fluido, aumentado drasticamente a temperatura da parede. Transientes em um reator nuclear podem afetar a taxa de geração de calor ou a fluxo de refrigerante no núcleo, prejudicando a retirada de calor das varetas combustíveis. Conhecer o FCC nestas condições é essencial para evitar danos às varetas e, consequentemente, a liberação de material radioativo. O objetivo deste trabalho é analisar o FCC para o LABGENE (Laboratório de Geração Nucleoelétrica) por meio do planejamento experimental e da simulação de seções de teste em condições de operação utilizando o código COBRAIIIc/MIT-1 e a correlação EPRI para o FCC. Considerou-se primeiramente seções de teste 3×3 de dois tamanhos distintos e os resultados para 100 pontos experimentais foram mostrados por meio de superfícies de resposta, a fim de melhor visualizar e analisar o comportamento de FCC para cada condição. Dois pontos importantes são os valores máximo e mínimo do FCC encontrados. O valor máximo (1,038 MBtu/hr.ft2 ou 3,27 MW/m2) indica o fluxo de calor necessário para a realização dos experimentos e o mínimo (0,162 MBtu/hr.ft2 ou 0,51 MW/m2) indica a pior condição de operação, a qual estaria mais próxima do ponto de ebulição. As simulações e modificações no código foram verificadas utilizando o banco de dados da Universidade de Columbia. Foram selecionados 2718 pontos experimentais referentes a seções de teste 5×5 com perfil de potência uniforme. Os resultados foram apresentados pela razão entre o valor predito e o valor experimental (DNBR) e os limites de tolerância unilateral 95/95 foram calculados, estando dentro dos valores esperados. / One of the most important thermal-hydraulic safety parameters for pressurized water reactor design and operation is the critical heat flux (CHF). The CHF occurs when a region of instability reached in the change of heat transfer mechanism from a hot wall to a fluid is reached, dramatically increasing the wall temperature. Transients in a nuclear reactor can affect the heat generation rate or the coolant flow in the core, impairing the removal of heat from the fuel rods. Knowledge of the CHF on these conditions is essential to prevent fuel rod damages and therefore the release of radioactive material. The main goal of this work is to analyze the CHF for LABGENE (Nuclear-electrical Generation Laboratory) by an experimental design and test sections simulation in operating conditions by using COBRAIIIc/MIT-1 code and the EPRI correlation for CHF. 3x3 test sections were initially considered for two different heights and outcomes for 100 experimental points were shown by means of response surfaces in order to better visualize and analyze the behavior of CHF for each condition. Two important points are the maximum and minimum values of the CHF found. The maximum value (1.038 MW/m2 or 3.27 MBtu/hr.ft2) indicates the power required for the experiments and the minimum one (0.162 MBtu/hr.ft2 or 0.51 MW/m2) indicates the worst operation condition, which would be closer to the boiling point. Code simulations and modifications were verified using the CHF database of Columbia University. 2718 data points pertaining to test sections 5×5 with uniform power profile were selected. The results were presented by the ratio between the predicted value and the experimental value (DNBR) and the limits of unilateral tolerance 95/95 were calculated, being within the expected values.