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Comparação dos efeitos da ressuscitação com Ringer lactato, solução salina hipertônica e terlipressina sobre a perfusão e oxigenação cerebral em modelo experimental de choque hemorrágico / Comparison of the effects of lactated Ringer\'s solution, hypertonic saline solution and terlipressin resuscitation on cerebral tissue oxygenation and perfusion in an experimental model of haemorrhagic shockKeila Kazue Ida 15 June 2015 (has links)
INTRODUÇÃO: A ressuscitação de baixo volume com solução salina hipertônica (SSH) ou terlipressina pode ser uma alternativa à administração de grandes volumes de cristaloides no tratamento do choque hemorrágico. O objetivo deste estudo foi avaliar os efeitos da HHS e terlipressina sobre a perfusão e oxigenação cerebral e investigar os mecanismos cerebrais envolvidos na microcirculação, função mitocondrial, atividade eletrocortical e vias apoptóticas cerebrais durante choque hemorrágico. MÉTODOS: Animais anestesiados com isofluorano foram submetidos ao choque hemorrágico [grupo Hemo; pressão arterial média (PAM) de 40 mmHg por 30 minutos] e tratados com Ringer lactato (RL) (3RL; 3x volume de sangue removido), terlipressina (grupo Terli; bolus) ou SSH (grupo SSH; 4 mL/kg bolus) e comparados ao grupo Sham. Um modelo porcino (n = 56) foi utilizado para avaliação da pressão de perfusão cerebral (PPC) e de oxigênio tecidual (PbtO2), e da expressão cerebral de marcadores teciduais da regulação de água (aquaporina-4), sódio (cotransportador-1 de Na-K-2Cl), estresse oxidativo (substâncias reativas ao ácido tiobarbitúrico e superóxido dismutase dependente de manganês) e apoptose. Um modelo murino (n = 179) foi utilizado para avaliação da microcirculação (fluorescência de FITC-dextrano) e função mitocondrial (potencial redox e de membrana mitocondrial, utilizando-se a fluorescência de flavoproteínas endógenas e do tetrametilrodamina metil éster, respectivamente) no córtex cerebral, utilizando-se a microscopia confocal in vivo, e para avaliação da atividade eletrocortical cerebral, por meio da monitorização do potencial evocado somatossensorial. No modelo murino foram avaliados três grupos adicionais, constituídos pela associação da terlipressina ao RL (1x, 2x ou 3x volume removido). RESULTADOS: No grupo Hemo porcino, houve uma redução significativa da PPC e PbtO2, associada ao aumento na expressão cerebral de marcadores da regulação do transporte de água e sódio, estresse oxidativo e apoptose em relação ao Sham. No modelo murino, a hipotensão induzida pelo choque hemorrágico foi correlacionada à diminuição na densidade vascular cortical e às disfunções mitocondriais e da atividade eletrocortical cerebral. No grupo 3RL porcino, a infusão de grandes volumes de RL recuperou a PbtO2, mas não a PPC, e foi acompanhada por uma maior expressão cerebral de marcadores da regulação de água, estresse oxidativo e apoptose comparada ao Sham. Nos ratos, a ressuscitação volêmica agressiva não recuperou a densidade vascular cortical, que foi correlacionada às disfunções mitocondrial e da atividade eletrocortical. No grupo Terli porcino, o aumento na PAM foi associado à restauração da PPC, PbtO2 e expressão dos marcadores da regulação de água e sódio, estresse oxidativo e apoptose no cérebro. Nos ratos tratados com terlipressina, associada ou não a 1x ou 2x RL, houve uma correlação positiva entre a recuperação da densidade vascular cortical e a restauração das funções mitocondrial e atividade eletrocortical cerebral. A SSH não promoveu melhora em nenhum dos modelos. CONCLUSÕES: RL e terlipressina recuperaram a oxigenação no córtex cerebral, mas apenas a terlipressina recuperou a perfusão cerebral, revertendo as disfunções mitocondrial e eletrocortical no cérebro e o aumento no transporte de água e sódio, estresse oxidativo e apoptose induzidos pelo choque hemorrágico. A SSH não recuperou a perfusão e oxigenação cerebral / INTRODUCTION: Small-volume resuscitation with hypertonic saline solution (HSS) or terlipressin can be an alternative to the administration of large amounts of crystalloids in haemorrhagic shock. The aim of this study was to evaluate the effects of HSS and terlipressin on cerebral perfusion and oxygenation and investigate the cerebral mechanisms associated with microcirculation, mitochondrial function, electrocortical activity and apoptotic pathways during haemorrhagic shock. METHODS: Isoflurane-anaesthetised animals were submitted to haemorrhagic shock [Haemo group; mean arterial pressure (MAP) of 40 mmHg for 30 minutes] and treated with lactated Ringer\'s solution (LR) (3LR group; 3x volume bled), terlipressin (Terli group; bolus) or HSS (HSS group; bolus 4 mL/kg) and were compared with a Sham group. A porcine model (n = 56) was used to assess the cerebral perfusion pressure (CPP) and tissue oxygenation (PbtO2) and the expression of tissue markers of water (aquaporin-4), sodium (Na-K-2Cl cotransporter-1), oxidative stress (thiobarbituric acid reactive substances and manganese superoxide dismutase) and apoptosis in cerebral samples. A murine model (n = 179) was used to assess microcirculation (FITC-dextran fluorescence) and mitochondrial function (redox and membrane potential, using the fluorescence of endogenous flavoproteins and tetramethylrhodamine methyl ester, respectively) in the cerebral cortex by using in vivo confocal microscopy, and to assess the electrocortical brain activity by monitoring the somatosensory evoked potential. In the murine model, three additional groups were evaluated, which received terlipressin associated to LR (1x, 2x or 3x blood withdrawn). RESULTS: In the porcine Hemo group, there was a significant decrease in the CPP and PbtO2, which were associated to an increased cerebral expression of markers of water and sodium transport, oxidative stress and apoptosis compared with Sham. In the murine model, the haemorrhagic shock-induced hypotension was correlated to a decrease in the cortical vascular density and to dysfunctions on brain mitochondria and electrocortical activity. In the porcine 3LR group, the infusion of large volumes of LR recovered the PbtO2, but not the CPP, and was accompanied by an increased cerebral expression of markers of water and sodium transport, oxidative stress and apoptosis compared with Sham. In the rats, the aggressive fluid resuscitation did not recover the cortical vascular density, which was correlated to the brain mitochondrial and electrocortical dysfunctions. In the porcine Terli group, the increase in the MAP was associated with the recovery of CPP, PbtO2, and expression of markers of water and sodium regulation, oxidative stress and apoptosis within the brain. In the rats treated with terlipressin, associated or not with 1x or 2x LR, there was a positive correlation between the recovery of the cortical vascular density and the recovery of the brain mitochondrial and electrocortical functions. Such improvements were not observed in none of the models treated with HSS. CONCLUSIONS: LR and terlipressin recovered tissue oxygenation in the cerebral cortex, but only terlipressin recovered the cerebral perfusion, reversing the brain mitochondrial and electrocortical dysfunctions and the increase in the markers of water and sodium transport, oxidative stress, and apoptosis induced by haemorrhagic shock. The HSS did not recover cerebral perfusion and oxygenation
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Intérêts et limites du clampage endovasculaire de l'aorte thoracique en situation de choc hémorragique non contrôlé lié à un traumatisme abdominal sur un modèle animalAvaro, Jean-Philippe 18 April 2011 (has links)
La traumatologie est la première cause de mortalité chez les sujets de moins de 40 ans dans les pays industrialisés. Le choc hypovolémique lié à une hémorragie du tronc est une cause fréquente de décès, à la fois sur les lieux de l’accident mais également pendant la prise en charge pré-hospitalière et intra-hospitalière. L’existence d’un hémopéritoine est un facteur de sous estimation du traumatisé grave.Le contrôle lésionnel, mieux connu sous les anglicismes « damage control ressucitation » et « damage control surgery », est le paradigme moderne de la prise en charge du choc hémorragique d’origine traumatique. Il comprend une mise en condition minimaliste privilégiant la réalisation d’une hémostase chirurgicale précoce et rapide, suivie d’une réanimation intensive associant transfusion massive, réchauffement et optimisation de la coagulation. Le traitement chirurgical exhaustif des lésions traumatiques est différé au delà de la période d’instabilité.Chez le blessé hémorragique agonique, la thoracotomie de ressuscitation avec clampage de l’aorte thoracique est une pratique courante mais dont les bases factuelles ne sont pas bien établies. En revanche en pathologie artérielle, la voie d’abord endovasculaire a très largement fait preuve de son efficacité.Nous avons émis l’hypothèse qu’un clampage aortique endovasculaire de l’aorte thoracique par voie rétrograde est possible et que cette technique améliore le profil hémodynamique dans le territoire myocardique et cérébral tout en augmentant la survie en cas de choc hémorragique lié à un traumatisme abdominal.Nos résultats suggèrent que cette technique de sauvetage est efficace, même s’il semble exister des limites corrélées à la durée de l’ischémie/reperfusion viscérale et médullaire. / Trauma is the leading cause of mortality in industrialized countries for people aged below 40 years. Fifty percent of the pre hospital and in hospital mortality from severe blunt and penetrating abdominal traumas is due to an hemorrhagic shock. Peritoneal bloody effusion is the main reason to under estimate the seriousness of trauma.Damage control resuscitation (DCR) and damage control surgery (DCS) typify the current paradigm of hemorrhagic torso trauma management. Damage control includes a basic pre operative management before a short surgical control of bleeding followed by intensive resuscitation care based on massive blood transfusion, palliation of hypothermia and correction of biological coagulation disorders. According to this strategy, the curative surgical treatment is postponed until the patient has been stabilized.Some authors have reported on the efficacy of resuscitation thoracotomy with aortic crossclamping in the emergency room in patients with severe abdominal trauma . However, the end results of such a procedure are contrasted and its use is still debated. More recently, endovascular approach has emerged in the management algorithm of some vascular emergencies. We hypothesized that an endovascular retrograde occlusion of the thoracic aorta would be a safe and efficient to preserve hemodynamic profile in cardiac and cerebral area, and to improve survival in case of uncontrolled hemorrhagic shock caused by an abdominal trauma.Our results sustain this hypothesis, even if its benefits seem time-limited, according to the medullar and visceral side-effects of ischemia/reperfusion.
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Serological and genetic characterisation of putative new serotypes of bluetongue virus and epizootic haemorrhagic disease virus isolated from an Alpaca / Isabella Maria WrightWright, Isabella Maria January 2014 (has links)
Alpacas were first introduced into South Africa during the year 2000. They are valuable
because of the fine quality wool they produce which has much better insulation properties
than that of merino wool fibres. Alpacas are also used to act as guards of sheep herds
against predators.
During 2008, blood samples from an alpaca that died acutely with severe lung oedema,
respiratory distress and froth exuding from the nose were received at Elsenburg Veterinary
Laboratory. The alpaca was from a herd of 23 alpacas of a British veterinarian in the
Montagu district in the western Cape. Virus isolation attempts on the blood produced
infrequent embryo mortalities. Embryonated chicken egg (ECE) material was send to the
Virology Department at the Onderstepoort Veterinary Institute (OVI). A bluetongue virus
(BTV) PCR performed at the diagnostic PCR laboratory at OVI on the ECE material was
positive. Further intra-venous (IV) inoculations in ECE produced embryo mortalities on two
consecutive days, the 8th and 9th November. The dead embryos were harvested separately
and named and treated as two separate virus samples, Alp8 and Alp9 which were further
passaged on baby hamster kidney (BHK) cells.
The BTV virus neutralisation tests (VNT) performed at the Office International des Epizooties
(OIE) Laboratory on both Alp8 and Alp9 were negative. Because of the close serological
relationship between BTV and epizootic haemorrhagic disease virus (EHDV), an EHDV VNT
was also performed and was also negative.
In the light of the negative VNT and the positive BTV PCR results, more in-depth molecular
analyses were performed. RNA was purified from tissue culture material and agarose gel
electrophoresis (AGE) performed. Both Alp8 and Alp9 had a typical orbiviral electrophoretic
profile, but their respective profiles were different.
A sequence-independent reverse transcriptase PCR amplification method generated ample
complementary DNA (cDNA) of both samples for sequencing. Sanger sequencing was used
to partially sequence genome segments 5 (NS1) and 2 (VP2). BLAST analysis of the partial
information of the genome segments 5 (NS1) of Alp8 confirmed it as being a BTV and Alp9
as being an EHDV. BLAST analysis of the deduced amino acid sequence generated of VP2
of both Alp8 and Alp9 established that these samples were possibly new serotypes of BTV
and EHDV respectively. The complete genome of both Alp8 and Alp9 was sequenced with
next generation 454 Pyrosequencing. This confirmed the partial sequencing results. BLAST analysis of the complete sequence of S2 (VP2) of Alp8 showed that it has 73 % nucleotide
and 77 % deduced amino acid identity to BTV15. In contrast the nucleic acid sequence of
genome segment S2 (VP2) of Alp9 had no nucleotide sequence identity to any virus, but its
deduced amino acid sequence had 71 % amino acid identity to EHDV2.
Hyper immune guinea pig (GP) serum prepared against the putative new BT (Alp8) and EHD
(Alp9) virus serotypes were tested for serological cross-reactivity against the 24 OIE
reference antigen strains of BTV and the 8 OIE reference antigen strains of EHDV. Alp8 had
a neutralising antibody (NAb) titre of > 32 against BTV15. Alp9 did not cross react with any of
the OIE BTV and EHDV strains.
Six out of the remaining 22 alpacas on the farm had NAbs to a greater or lesser extend
against Alp8 (BTV) and Alp9 (EHDV) viruses, which confirmed that the viruses were also
present in other alpacas in the herd. Very few cases of EHDV in alpacas have ever been
reported in literature.
A small scale pilot vector susceptibility study showed that vector competence of C. imicola
for both Alp8 and Alp9 was low, below 2 %. The fact that neutralising antibodies to Alp8 and
Alp9 were detected in other alpacas in the herd raises the question as to whether there are
other Culicoides species circulating in the area that could vector the viruses.
In conclusion, the results from the serological and virological analyses as well as the nucleic
acid sequence data of the genomes of two virus samples, Alp8 and Alp9, from an alpaca that
died in the Montagu district in the western Cape identified Alp9 as a definite new serotype of
EHDV and Alp8 as a possible new serotype of BTV most closely related to BTV15. / MSc (Biochemistry), North-West University, Potchefstroom Campus, 2014
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Ergebnisse paläopathologischer Untersuchungen zu meningealen Reaktionen an Kinderskeleten präkolumbischer Populationen aus dem südöstlichen Nordamerika (USA), dem zentralmexikanischen Hochland und dem östlichen Tiefland Yucatáns (Mexiko) / Results of palaeopathological studies on meningeal reactions of children's skeletons from pre-Columbian Populations from the southeastern North America (USA), the Central Mexican highlands and the eastern lowlands of Yucatán (Mexico)Rabani, Shabnam 19 September 2019 (has links)
No description available.
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Serological and genetic characterisation of putative new serotypes of bluetongue virus and epizootic haemorrhagic disease virus isolated from an Alpaca / Isabella Maria WrightWright, Isabella Maria January 2014 (has links)
Alpacas were first introduced into South Africa during the year 2000. They are valuable
because of the fine quality wool they produce which has much better insulation properties
than that of merino wool fibres. Alpacas are also used to act as guards of sheep herds
against predators.
During 2008, blood samples from an alpaca that died acutely with severe lung oedema,
respiratory distress and froth exuding from the nose were received at Elsenburg Veterinary
Laboratory. The alpaca was from a herd of 23 alpacas of a British veterinarian in the
Montagu district in the western Cape. Virus isolation attempts on the blood produced
infrequent embryo mortalities. Embryonated chicken egg (ECE) material was send to the
Virology Department at the Onderstepoort Veterinary Institute (OVI). A bluetongue virus
(BTV) PCR performed at the diagnostic PCR laboratory at OVI on the ECE material was
positive. Further intra-venous (IV) inoculations in ECE produced embryo mortalities on two
consecutive days, the 8th and 9th November. The dead embryos were harvested separately
and named and treated as two separate virus samples, Alp8 and Alp9 which were further
passaged on baby hamster kidney (BHK) cells.
The BTV virus neutralisation tests (VNT) performed at the Office International des Epizooties
(OIE) Laboratory on both Alp8 and Alp9 were negative. Because of the close serological
relationship between BTV and epizootic haemorrhagic disease virus (EHDV), an EHDV VNT
was also performed and was also negative.
In the light of the negative VNT and the positive BTV PCR results, more in-depth molecular
analyses were performed. RNA was purified from tissue culture material and agarose gel
electrophoresis (AGE) performed. Both Alp8 and Alp9 had a typical orbiviral electrophoretic
profile, but their respective profiles were different.
A sequence-independent reverse transcriptase PCR amplification method generated ample
complementary DNA (cDNA) of both samples for sequencing. Sanger sequencing was used
to partially sequence genome segments 5 (NS1) and 2 (VP2). BLAST analysis of the partial
information of the genome segments 5 (NS1) of Alp8 confirmed it as being a BTV and Alp9
as being an EHDV. BLAST analysis of the deduced amino acid sequence generated of VP2
of both Alp8 and Alp9 established that these samples were possibly new serotypes of BTV
and EHDV respectively. The complete genome of both Alp8 and Alp9 was sequenced with
next generation 454 Pyrosequencing. This confirmed the partial sequencing results. BLAST analysis of the complete sequence of S2 (VP2) of Alp8 showed that it has 73 % nucleotide
and 77 % deduced amino acid identity to BTV15. In contrast the nucleic acid sequence of
genome segment S2 (VP2) of Alp9 had no nucleotide sequence identity to any virus, but its
deduced amino acid sequence had 71 % amino acid identity to EHDV2.
Hyper immune guinea pig (GP) serum prepared against the putative new BT (Alp8) and EHD
(Alp9) virus serotypes were tested for serological cross-reactivity against the 24 OIE
reference antigen strains of BTV and the 8 OIE reference antigen strains of EHDV. Alp8 had
a neutralising antibody (NAb) titre of > 32 against BTV15. Alp9 did not cross react with any of
the OIE BTV and EHDV strains.
Six out of the remaining 22 alpacas on the farm had NAbs to a greater or lesser extend
against Alp8 (BTV) and Alp9 (EHDV) viruses, which confirmed that the viruses were also
present in other alpacas in the herd. Very few cases of EHDV in alpacas have ever been
reported in literature.
A small scale pilot vector susceptibility study showed that vector competence of C. imicola
for both Alp8 and Alp9 was low, below 2 %. The fact that neutralising antibodies to Alp8 and
Alp9 were detected in other alpacas in the herd raises the question as to whether there are
other Culicoides species circulating in the area that could vector the viruses.
In conclusion, the results from the serological and virological analyses as well as the nucleic
acid sequence data of the genomes of two virus samples, Alp8 and Alp9, from an alpaca that
died in the Montagu district in the western Cape identified Alp9 as a definite new serotype of
EHDV and Alp8 as a possible new serotype of BTV most closely related to BTV15. / MSc (Biochemistry), North-West University, Potchefstroom Campus, 2014
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Relationship between lactate values and mortality in patients with haemorrhagic shock in an emergency unitZarrabi, Eleonora Natali 23 November 2011 (has links)
Introduction : Trauma is the leading cause of death in patients between the ages of 1-44 years in South Africa. Taking these statistics into consideration it is essential to better resuscitation strategies in order to improve outcome of trauma patients. Compensated and uncompensated haemorrhagic shock is frequently under diagnosed in trauma patients, which has a definitive effect on mortality. Concerns about inadequate monitoring of patients through the use of only physiological end points are raised. Methods : A comprehensive literature review was conducted on resuscitation strategies for patients presenting with haemorrhagic shock. Physiological and metabolic end points of resuscitation were identified to guide resuscitation strategies. A quantitative, retrospective, non-experimental, descriptive, correlational and crosssectional research design was chosen for this study. Data was collected by using biophysical measures, namely clinical audit checklists. Results : Lactate was identified as a good indicator to predicting mortality in patients presenting with shock caused by haemorrhage. Special consideration to patients’ age and physiological status should be made during resuscitation. The consequence of delayed resuscitation in haemorrhagic shock patients is associated with an increase in mortality that can be prevented. It is found that serum blood lactate levels taken over time are good predictors of patient survival rates. Patients presenting with a raised serum blood lactate level for more than 24-hours has an increase in mortality rate. Conclusion : Emergency nurse practitioners are responsible for the monitoring of patients admitted to the emergency unit with haemorrhagic shock. The use of serum lactate levels during the first 24-hours of the resuscitation of patients with haemorrhage can assist with the implementation of strategies to reverse the effect haemorrhagic shock on cellular level in these patients. / Dissertation (MCur)--University of Pretoria, 2011. / Nursing Science / unrestricted
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Rift Valley fever : consequences of virus-host interactionsBaudin, Maria January 2016 (has links)
Rift Valley fever virus (RVFV) is a mosquito-borne virus which has the ability to infect a large variety of animals including humans in Africa and Arabian Peninsula. The abortion rate among these animals are close to 100%, and young animals develop severe disease which often are lethal. In humans, Rift Valley fever (RVF) presents in most cases as a mild illness with influenza-like symptoms. However, in about 8% of the cases it progresses into a more severe disease with a high case fatality rate. Since there is such a high abortion rate among infected animals, a link between human miscarriage and RVFV has been suggested, but never proven. We could in paper I for the first time show an association between acute RVFV infection and miscarriage in humans. We observed an increase in pregnant women arriving at the Port Sudan Hospital with fever of unknown origin, and several of the patients experienced miscarriage. When we analysed their blood samples for several viral diseases we found that many had an acute RVFV infection and of these, 54% experienced a miscarriage. The odds of having a miscarriage was 7 times higher for RVFV patients compared to the RVFV negative women of which only 12% miscarried. These results indicated that RVFV infection could be a contributing factor to miscarriage. RVFV is an enveloped virus containing the viral glycoproteins n and c (Gn and Gc respectively), where Gn most likely is responsible for the initial cellular contact. The protein DC-SIGN on dendritic cells and the glycosaminoglycan heparan sulfate has been suggested as cellular receptors for RVFV, however other mechanisms are probably also involved in binding and entry. Charge is a driving force for molecular interaction and has been shown to be important for cellular attachment of several viruses, and in paper II we could show that when the charge around the cells was altered, the infection was affected. We also showed that Gn most likely has a positive charge at a physiological pH. When we added negatively charged molecules to the viral particles before infection, we observed a decreased infection efficiency, which we also observed after removal of carbohydrate structures from the cell surface. Our results suggested that the cellular interaction partner for initial attachment is a negatively charged carbohydrate. Further investigations into the mechanisms of RVFV cellular interactions has to be undertaken in order to understand, and ultimately prevent, infection and disease. There is currently no vaccine approved for human use and no specific treatments for RVF, so there is a great need for developing safe effective drugs targeting this virus. We designed a whole-cell based high-throughput screen (HTS) assay which we used to screen libraries of small molecular compounds for anti-RVFV properties. After dose-response and toxicity analysis of the initial hits, we identified six safe and effective inhibitors of RVFV infection that with further testing could become drug candidates for treatment of RVF. This study demonstrated the application of HTS using a whole-cell virus replication reporter gene assay as an effective method to identify novel compounds with potential antiviral activity against RVFV.
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Implication de l’acide urique dans l’atteinte du système nerveux central d’un modèle murin de choc hémorragique réaniméL'Écuyer, Sydnée 12 1900 (has links)
Les traumatismes graves sont une cause principale d’hospitalisations et peuvent induire des handicaps physiques et psychologiques. Dans ce travail, nous nous intéressons au choc hémorragique (CH), défini par une perte sanguine de plus de 30% menant à une ischémie systémique causant de la mort cellulaire et la libération de médiateurs circulants. Parmi ces médiateurs, notre groupe a déjà démontré l’augmentation en circulation de l’acide urique (AU) après le CH et son rôle dans l’atteinte d’organes ; un effet qui est prévenu par l’utilisation d’une uricase, qui métabolise l’AU circulant. Notre objectif actuel est de démontrer le rôle de l’AU dans l’altération du système nerveux central. Pour ce faire nous utilisons un modèle murin de CH reperfusé avec 3 groupes expérimentaux : SHAM (contrôle), CH et CH+U (uricase IP au moment de la reperfusion). Nos résultats démontrent que l’altération de la perméabilité de la barrière hématoencéphalique (augmentation significative de la perméabilité à la fluorescéine de sodium (NaF)) et de l’expression de ICAM-1 après le CH peut être prévenu par l’administration d’uricase. Les résultats sont les mêmes pour la mesure de la neuroinflammation (activité de la myéloperoxidase (neutrophiles) ainsi que astrocytes et microglie activés) et de l’apoptose/dégérescence neuronale (caspase-3, coloration TUNEL et fluorojade). En conséquence à l’atteinte neuroinflammatoire et apoptotiques, nous observons une augmentation significative des comportements anxieux après le CH, détectés par le test de nage forcée, le labyrinthe en croix surélevé et l’intéraction sociale, et qui sont prévenus par le traitement avec uricase. En conclusion, ce projet permet de confirmer que l’AU joue un rôle important dans l’atteinte cérébrale et l’altération des comportements, après le CH reperfusé. / Polytrauma is one of the main causes of hospitalisations and can lead to physical and psychological handicaps. This work focuses on hemorrhagic shock (HS), defined by a blood-loss of at least 30%, leading to systemic ischemia, cell death and the release of various mediators in circulation. The importance of one of these mediators, uric acid (UA), in multiple organ failure after HS and the improvement by the use of an uricase, which can destroy UA, was already demonstrated by our lab. Our objective is to illustrate the implication of UA in central nervous system alterations after HS. To reach this goal, we use a murine model which is assigned to one of our 3 experimental groups: SHAM (control), HS and HS+U (IP injection of uricase at reperfusion). Our results show an altered blood-brain barrier permeability (significant infiltration of NaF in the brain after HS), an increased expression of ICAM-1 after HS and a prevention of both these results by uricase treatment. The same results are observed for neuroinflammation (myeloperoxidase activity (neutrophils), astrocytes and microglia) and for neuronal apoptosis/degeneration (caspase-3, TUNEL staining and FluoroJade staining). Furthermore, anxiety is increased after HS compared to SHAM but prevented with uricase treatment. The tests used to reach this conclusion are the elevated plus maze, the forced swim test and social interaction. In conclusion, this project confirms the central role of UA in brain lesions and subsequent behavioral alterations after resuscitated HS.
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Lassa fever epidemic outbreak causing maternal mortality on pregnant women : A statistical and systematic review on prevalence and occurrence of maternal mortality in NigeriaOffor, Joy January 2020 (has links)
Introduction/background: Epidemics of infectious diseases (ID) are re-occurring now more often and spreads faster into many different parts of the world due to globalization. The increasing evidence of climate change and man-made events have shown impacts to increase the emergency and re-emerging of animal- borne IDs. Studies claims that background factors of these IDs are biological, environmental and human-lifestyle related changes. The pathogen Lassa fever virus (LASV) is a zoonotic organismthat circulates in rodent reservoirs, and the animal´s hosts are rodent species (rats) of the genus Mastomys natalensis. Mastomys natalensis is primarily the reservoir species of the animal-borne disease of Lassa fever (LF) which is most prevalent in west Africa, particularly in Nigeria. Lassa fever (LF) has limited information with under-documented cases, its health effect on pregnant women especially in Nigeria is within the rural areas of Edo, Ondo, Delta, Ebony, Bauchi, Taraba and Plateau states where maternal mortalities are higher. Aim: The overarching aim of this thesis is to analyse and discuss the health effects of Lassa fever occurrence and outcomes on pregnant women in Nigeria, with emphasis on the maternal mortality and fatality during pregnancy. Method: A statistical and systematic review was performed from retrospective studies of case series, case-control, observational and cohort studies of patients in Nigeria (pregnant women with gestation ages of pregnancy from 2 weeks –32 weeks) that tested positive to LASV. Publication status and publication date was applied for the inclusion of respective studies by electronic searches via Web of Science, Google scholar, MEDLINE and PubMed. Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines (PRISMA) was used to illustrate the flow of relevant articles in my study. R-commander and R-Studio software was used to analyze the data and to find the causal significant relationship between LF and maternal mortality using “Linear regression and linear model plot”. Result: The total number of full-text and Peer-view publications on Lassa fever virus cases was 1 609 articles. 94 articles out of the 1 609 articles were eligible for full text revision. Exclusion criteria finally yielded 6 studies that were relatively relevant to my study. However, 3 out of the 6 articles were statistically reviewed to know the influence of Lassa fever and the risk of maternal mortality during pregnancy. Conclusion: Lassa fever occurrence have significantly shown potential increase in the severity of maternal mortality, and is predominant among pregnant women from 39 - 45 years old in Nigeria especially within the risk endemic areas of Ondo, Edo, Ebony and Bauchi states showing significant long-term diseases on LF affected pregnant women, such as encephalopathy, acute kidney dysfunction and acute kidney failure that leads to further health problems or complications like coma and sensorineural deafness.
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