Background: The increased vascular permeability seen after burn contribute to morbidity and mortality as it interferes with organ function and the healing process. Large efforts have been made to explore underlying pathophysiological mechanisms that generate increased vascular permeability after burns. Many different substances have been proposed as mediators of which histamine, serotonin and oxygen radicals are claimed most important. However, no specific blocker has convincingly been shown to be clinically effective. Early work has claimed increased histamine plasma-concentrations in humans after burn and data from animal models pointed at histamine as an important mediator. Modern human clinical studies investigating the role of histamine as a mediator of the generalized post burn increase in vascular permeability are lacking. less thanbrgreater than less thanbrgreater thanMethod: We examined histamine turnover by measuring the urinary excretion of histamine and methyl histamine for 48 h after burns in 8 patients (mean total burn surface area 24%). less thanbrgreater than less thanbrgreater thanResults: Over time, in this time frame and compared to healthy controls we found a small increase in the excretion of histamine, but no increase of its metabolite methylhistamine. less thanbrgreater than less thanbrgreater thanConclusion: Our findings do not support that histamine is an important mediator of the increased systemic vascular permeability seen after burn. / <p>Funding Agencies|Research and Development Unit, Jamtland County Council, Sweden||</p>

Bone marrow oedema is a term used to define the appearance of regions of low signal on T1 weighted and high signal on T2 weighted fat-suppressed magnetic resonance images. The potential association between bone marrow oedema and prognosis in pathologies such as osteoarthritis is becoming increasingly recognised through clinical studies. A limited number of clinical studies have linked bone marrow oedema to altered bone density or altered bone marrow perfusion. The principal aims of this study were to investigate these findings in vitro, using the equine forelimb. The presence of bone marrow oedema within the equine forelimb was initially confirmed by undertaking magnetic resonance imaging scans. Bone samples were selected from 10 animals, 5 exhibiting the presence of bone marrow oedema-type abnormalities (BMOA) at the distal metacarpal. Raman microspectroscopy was used to determine the chemical composition of bone and projection radiography to provide a measure of bone density. Micro computed x-ray tomography was undertaken on a subset of three bone samples exhibiting BMOA. A second component of the study utilised contrast enhanced magnetic resonance imaging to enable comparison of perfusion to bone marrow with and without evidence of oedema. A saline flushing agent containing Evan’s blue was used so that subsequent sectioning of the bone would enable visualisation of the distribution of contrast agent as part of a histological examination of the oedematous region. An initial observation was that the majority of bone marrow oedema that was observed in the distal metacarpal appeared in a consistent location, namely the postero-inferior aspect of the bone, corresponding to the point of greatest load thereby suggesting a potential relationship to forces upon the joint. The principal observations were that there appears to be increased bone volume densities in those bone samples with evidence of bone marrow oedema. The Raman microspectroscopy did not demonstrate any statistically significant differences in the chemical composition of bone. Hence the overall impression is that bone marrow oedema is associated with a greater volume of bone, although of similar maturity and composition. There was limited evidence of increased perfusion (suggestive of increased vascularity and / or hyperpermeability) in those samples with bone marrow oedema. This work suggests that these particular bone marrow oedema lesions are associated with bone changes and potentially vascular changes although the aetiology is currently unclear. Further work is needed to determine the clinical significance and prognosis associated with these particular lesions, and whether these findings can be replicated for bone marrow oedema demonstrated at other anatomical locations.

Introduction. The glial cell water channel aquaporin-4 (AQP4) plays an important ro le in brain oedema, astrocyte migration and neuronal excitability. Current theories of AQP4 function are based largely on experiments using AQP4 -1- mice. These mice have only been partially characterized. I therefore undertook a detailed investigation of baseline brain properties in AQP4 -1- mice. In the second part of my experiments I investigated the role of AQP4 in brain oedema in a mouse model of subarachnoid haemorrhage. Method. Gross anatomical measurements included estimates of brain and ventricle size. Neurons, astrocytes and oligodendrocytes were assessed using the neuronal nuclear marker NeuN, the astrocyte marker GFAP, and the myelin stain Luxol Fast Blue. The blood brain barrier was studied by electron microscopy and the horseradish peroxidase extravasation technique. A mouse model in which 30~1 of autologous blood was injected into the basal cisterns was used to reproduce subarachnoid haemorrhage. Brain water content, intracranial pressure and neurological score were compared in wildtype and AQP4 -/- mice. I also measured blood brain barrier permeability and the osmotic permeability of the glia lim itans, one of the routes of oedema elimination.

Aims: Thiazolidinediones have been advocated as second or third line insulin sensitizing agents in the management of type 2 diabetes (T2DM). Their widespread use has been hampered by concerns about their cardiovascular safety, including fluid retention. Metformin is established as first-line glucose-lowering pharmacotherapy in T2DM. It has also been suggested that it may have benefits in alleviating insulin resistance in type 1 diabetes (T1DM). This thesis examined: (i) cardiovascular, renal and metabolic differences between individuals with T2DM ‘tolerant’ or ‘intolerant’ of TZDs; (ii) risk factors for TZD-associated oedema in T2DM; and (iii) the potential for metformin as adjunct therapy in T1DM. Methods: (i) A small clinical study characterising TZD tolerant and intolerant individuals with T2DM; (ii) A population-based epidemiological study of TZD induced oedema in individuals with T2DM in Tayside, Scotland (using incident loop diuretic prescription as a surrogate); (iii) A systematic review and meta-analysis of published studies of adjunct metformin in T1DM. Results (i) During a five-day high sodium diet, two known TZD-intolerant individuals with T2DM had reductions in haematocrit, aldosterone, and diastolic BP and increases in ANP and central and peripheral augmentation indices which were outwith reference ranges derived from nine TZD-tolerant individuals; (ii) Predictors of time to loop diuretic prescription included age, body mass index, systolic BP, haematocrit, ALT and macrovascular disease but rates of this outcome did not differ by therapy: 4.3% (TZDs) vs 4.7% (other agents) [unadjusted OR 0.909 (95% CI 0.690, 1.196); p = 0.493]; (iii) In meta-analysis of nine small studies in T1DM (192.8 patient-years of follow-up), metformin was associated with a reduction in total daily insulin dose (6.6 units/day; p < 0.001) but no studies examined cardiovascular surrogates or outcomes. Conclusions: Hypotheses were generated for several potential biomarkers predictive of TZD-induced oedema but the clinical importance of TZDs as a risk factor for oedema in individuals with T2DM was questioned. As there is some evidence for the safety of metformin as an adjunct therapy in T1DM but little evidence of efficacy, larger studies are warranted.

The primary aim of this research is to test the therapeutic potential of certain new generation corticosteroid drugs in order to develop safe and effective treatment for eye diseases that result in oedema, or swelling. The rising incidence of diabetes and the ageing population of developed countries mean that the prevalence of uveitis, diabetic retinopathy and age related macular degeneration will rise. Often, oedema is one of the reasons for vision loss. Corticosteroids are often used to reduce inflammation. Inflammation is one of several sources of oedema. Glucocorticoids, a class of corticosteroids that have anti-inflammatory properties, are thus used to treat ocular oedema. There is an unmet need to support clinical experience of the efficacy of steroids for ocular inflammation and oedema with more substantial scientific evidence. None of the drugs under investigation, with the exceptions of dexamethasone and triamcinolone, have been used for any ocular therapeutic purpose before. This thesis investigates “repurposing” fludrocortisone to the ophthalmic area. 11-Desoxycorticosterone (11D) and Deoxycorticosterone (DCS), other potentially valuable mineralocorticoids, remain completely untested. Lastly, Kenacort ®, or triamcinolone acetonide (TCA), is only used off-label by ophthalmologists. Methods: In the first study, corticosteroids, and especially mineralocorticoids, were investigated for their treatment efficacy in experimental uveitis, or intraocular inflammation (using a model known as endotoxin induced uveitis). In the second study, endothelial cells from choroidal blood vessels in the back of the eye were used in vitro to study whether corticosteroids reduce paracellular (between cells) permeability. Lastly, since endophthalmitis due to frequent injections is a side effect of corticosteroid use, the pharmacokinetics of different size formulations of corticosteroids were studied in an effort to find a formula that would have a prolonged dwell time within the eye.

Objective: To investigate the experiences of ambulance nurses when using Boussignac CPAPcompared to their previous model, and their suggestions for possible improvements in the use of CPAP in the care of patients with pulmonary oedema. Method: A qualitative study with a descriptive and exploratory approach. Data was collected through ten semi-structured interviews with ambulance nurses, seven men and three women. The analysis was conducted using Lundman and Graneheim’s content analysis. Results: Three categories were identified: Usage, Treatment and Development. Boussignac CPAP is described as easy to use and with fewer elements than the previous model. With this model it is particularly appreciated to have the opportunity to be able to regulate the resistance without fixed settings. Boussignac CPAP is regarded as more convenient in the handover of the patient. The potential for increased use, with the possibility of adjustment without fixed settings of resistance for Boussignac CPAP, is not perceived to be fully realized. Conclusion: Boussignac CPAP is, by the ambulance nurses, perceived to have made the handling of equipment easier and increased quality of care. To make further use of the potential of Boussignac CPAP more training and changes in the guidelines may be needed. / Syfte: Att undersöka ambulanssjuksköterskors upplevelser av Boussignac CPAP jämfört med deras föregående modell, samt ambulanssjuksköterskors eventuella förslag till möjliga förbättringar vid användandet av CPAP i vården av patienter med lungödem. Metod: En kvalitativ studie med deskriptiv och utforskande ansats. Data utgörs av tio semistrukturerade intervjuer med ambulanssjuksköterskor, sju män och tre kvinnor. Materialet har analyserats med Lundman och Graneheims innehållsanalys. Resultat: Tre kategorier identifierades: Användning, Behandling samt Utveckling. Boussignac CPAP beskrivs som lättanvänd och med färre moment än föregående modell. Med modellen uppskattas särskilt möjligheten att steglöst reglera motståndet. Boussignac CPAP upplevs som lättare då masken eller dess delar inte behöver plockas av patienten vid överlämnandet från ambulansverksamheten. Förutsättningarna till ökat användningsområde, i och med möjligheten att steglöst ändra motståndet för Boussignac CPAP upplevs inteutnyttjas fullt ut. Slutsats: Boussignac CPAP upplevs av ambulanssjuksköterskorna ha underlättat hanteringen av utrustningen samt ökat vårdkvaliteten för patienten. För att vidare kunna utnyttja potentialen med Boussignac CPAP kan mer utbildning och förändringar i riktlinjer behövas.

Darbo tikslas: įvertinti šunų gerklų edemų etiotropinius faktorius, taikomas diagnostikos priemones bei gydymo ypatumus. Darbo uždaviniai: 1. Apžvelgti literatūroje pateikiamus duomenis apie gerklų edemų šunims etiologiją. 2. Išanalizuoti patologinio proceso pagrindinius ir pagalbinius diagnozavimo metodus. 3. Išanalizuoti gerklų edemų gydymui taikomas priemones, pateikti patologinio proceso prevencijos būdus. Buvo renkami duomenys 2005–2012 m. pacientų, kurie sirgo ligomis, sukeliančiomis gerklų edemą. Nuo 2005–2008 m. analizuotos tik pacientų ligos istorijos, kuriems buvo diagnozuota gerklų edema (n=133), o nuo 2008–2012 m. – gyvūnai (n=163) tirti kartu su veterinarijos gydytojais, dalyvauta atliekant diagnostines procedūras bei paskiriant gydymą. Išnagrinėti gerklų edemos etiologiniai veiksniai, jų diagnozavimo ir gydymo būdai. Tyrimų rezultatai ir išvados: išanalizavus surinktus duomenis apie pacientus, sergančius ligomis, kurios iššaukia gerklų edemą, nustatyta, kad pagrindiniai etiologiniai veiksniai, sukėlę gerklų edemą šunims, buvo laringitas (54 proc. arba 159 atvejai, p>0,05), laringotracheitas (27 proc. arba 78 atvejai, p>0,05), trachėjos kolapsas (11 proc. arba 34 atvejai, p<0,05), brachicefalinis sindromas (6 proc. arba 19 atvejų, p<0,05), navikai gerklų srityje (1 proc. arba 4 atvejai, p>0,05), vabzdžių įgėlimai (0,3 proc. arba 1 atvejis, p>0,05) ir šunidžių kosulys (0,3 proc. arba 1 atvejis, p>0,05). Gerklų edema dažniau diagnozuota patinams (58 proc. arba 17... [toliau žr. visą tekstą] / The objective of the research–to understand factors about dogs laryngeal oedema, laryngeal oedema diagnostic and treatment. Task of the research: 1. To analyze information about dogs laryngeal edema in literature. 2. To identify pathological process main and supporting diagnostic procedures. 3. To analyze treatment and ways of prevention of the laryngeal edema in dogs. 2005–2012 years, the information was picked about pacients, who had diseases, which stimulate laryngeal edema, from 2005–2008 information was picked about patients who has diseases which stimulate laryngeal edema, and from 2008–2012, the pacients were researched with vet doctor near abay. Were identifyied 296 pacients and their causes and treatment of laryngeal edema. Results and conclusions: main etiology factors of laryngeal edema in dogs were: laringytis (54 percent or 159 cases, p>0,05), laringotracheitis (27 percent or 78 cases, p>0,05), collapse of trachea (11 percent. or 34 cases, p<0,05), brachicefalic syndrome (6 percent. or 19 cases, p<0,05), tumours (1 percent or 1 case, p>0,05), bite of insect (0,3 % or 1 case, p>0,05) and kennel cough (0,3 % or 1 case, p>0,05). laryngeal edema,was identified more in males (58 percent or 172 cases), than females (42 percent or 124 cases). The patient average age was from 5,2±1,17 years old. Laryngeal edema diagnosed more in pedigreed dogs (72 percent or 214 cases) than in hybrids (28 percent or 82 cases). Major pedigreed dogs had ilnesses, who were from 1 to 5... [to full text]

More than 15 million people worldwide will suffer a stroke each year two thirds will die or be left permanently disabled. Accordingly, stroke represents an enormous financial burden on the community, due to the cost of hospitalisation, treatment and rehabilitation of stroke patients. Despite the significance of this public health problem, a safe and widely applicable stroke therapeutic remains elusive. Cerebral oedema is widely recognised as a common and often fatal complication of stroke that is associated with worsened outcome. However, the exact mechanisms of oedema formation remain unclear, with current therapies largely ineffective in addressing the mechanisms of cerebral swelling, and also being associated with their own negative side-effect profile. This thesis characterises the role of neurogenic inflammation and the neuropeptide, substance P (SP), in mediating the development of blood brain barrier breakdown, cerebral oedema and resultant functional deficits following stroke, using a rodent model of reversible cerebral ischaemia. The findings of this thesis demonstrate that increased SP immunoreactivity, particularly of the penumbral tissue vasculature, is a feature of tissue perfusion following stroke, but not in non-reperfused infarcts. The central role for SP in the breakdown of the BBB following stroke and the associated deleterious effects of such breakdown was confirmed by studies using an NK₁ receptor antagonist. These antagonists conferred a profound attenuation of BBB breakdown, cerebral oedema formation, neuronal death and injury, and the associated development of functional deficits following reversible stroke. Similarly, depletion of all neuropeptides by capsaicin pre-treatment also reduced both histological abnormalities and functional deficits following stroke, confirming the central role of neuropeptides in the secondary injury process after stroke. The NK₁ receptor antagonist was able to be safely combined with the currently approved treatment for stroke, tPA, producing a synergistic effect of greater protection from the ischaemic insult. In particular, histological and functional outcome were markedly improved, as well as a reduction in the risk of intracerebral haemorrhage and death. Furthermore, the NK₁ receptor antagonist was effective even when administered up to 8 h following the onset of ischaemia, and in a variety of stroke severities. We conclude that SP plays a central role in the secondary injury that occurs following stroke, in particular, the genesis of BBB breakdown and cerebral oedema. Accordingly, combination therapy of tPA and an NK₁ receptor antagonist may offer a novel therapeutic strategy for the clinical management of ischaemic stroke of varying severity. / http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1298280 / Thesis (Ph.D.) -- The University of Adelaide, School of Medical Sciences, 2007

More than 15 million people worldwide will suffer a stroke each year two thirds will die or be left permanently disabled. Accordingly, stroke represents an enormous financial burden on the community, due to the cost of hospitalisation, treatment and rehabilitation of stroke patients. Despite the significance of this public health problem, a safe and widely applicable stroke therapeutic remains elusive. Cerebral oedema is widely recognised as a common and often fatal complication of stroke that is associated with worsened outcome. However, the exact mechanisms of oedema formation remain unclear, with current therapies largely ineffective in addressing the mechanisms of cerebral swelling, and also being associated with their own negative side-effect profile. This thesis characterises the role of neurogenic inflammation and the neuropeptide, substance P (SP), in mediating the development of blood brain barrier breakdown, cerebral oedema and resultant functional deficits following stroke, using a rodent model of reversible cerebral ischaemia. The findings of this thesis demonstrate that increased SP immunoreactivity, particularly of the penumbral tissue vasculature, is a feature of tissue perfusion following stroke, but not in non-reperfused infarcts. The central role for SP in the breakdown of the BBB following stroke and the associated deleterious effects of such breakdown was confirmed by studies using an NK₁ receptor antagonist. These antagonists conferred a profound attenuation of BBB breakdown, cerebral oedema formation, neuronal death and injury, and the associated development of functional deficits following reversible stroke. Similarly, depletion of all neuropeptides by capsaicin pre-treatment also reduced both histological abnormalities and functional deficits following stroke, confirming the central role of neuropeptides in the secondary injury process after stroke. The NK₁ receptor antagonist was able to be safely combined with the currently approved treatment for stroke, tPA, producing a synergistic effect of greater protection from the ischaemic insult. In particular, histological and functional outcome were markedly improved, as well as a reduction in the risk of intracerebral haemorrhage and death. Furthermore, the NK₁ receptor antagonist was effective even when administered up to 8 h following the onset of ischaemia, and in a variety of stroke severities. We conclude that SP plays a central role in the secondary injury that occurs following stroke, in particular, the genesis of BBB breakdown and cerebral oedema. Accordingly, combination therapy of tPA and an NK₁ receptor antagonist may offer a novel therapeutic strategy for the clinical management of ischaemic stroke of varying severity. / http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1298280 / Thesis (Ph.D.) -- The University of Adelaide, School of Medical Sciences, 2007

Made available in DSpace on 2015-05-14T12:59:24Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 1952542 bytes, checksum: cbb5dfafac619fd1f5d9b4ef4efbccf2 (MD5) Previous issue date: 2011-02-28 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Enantiomers are asymmetric compounds that present mirror images of each other, not overlapping and different behaviors in chiral environments, resulting in esterioseletiva discrimination and different biological effects. The carvone is a monoterpene, a constituent of many essential oils found in nature as two enantiomers, (S)-(+)-carvone and (R)-(−)-carvone. The inflammation, a physiological response of the organism, when it occurs exaggerated or inappropriated ways may promote tissue damage and associated pathologies. An example of inflammatory disease is asthma, an immediate hypersensitivity process of the airways and the conventional treatments have significant adverse effects. The aim of this study was to evaluate the carvone enantiomers in experimental models of inflammation and hypersensitivity of the airways. To investigate the effect anti-inflammatory the following parameters were evaluated: NO production by cells J774.A1, paw oedema formation induced by carrageenan, zymosan, compound 48/80 and histamine, cell migration and cytokines production (TNF-α and IL-1β) in the experimental model of peritonitis induced by zymosan in Swiss mice. To evaluate the anti-asthmatic activity of these enantiomers, it was used the experimental model of asthma induced by ovalbumin and the following parameters were analyzed: bronchoalveolar lavage (BAL), mucus production, OVA-specific IgE synthesis, cytokine production (IL-13, IFN-γ and IL-10). The results showed that both enantiomers were able to reduce NO production, inhibit the paw oedema induced by phlogistic agents and inhibit cell migration to the peritoneum, but only the (R)-(−)-carvone was able to reduce levels of TNF-α. In the murine model of asthma, the (R)-(−)-carvone, was able to reduce the cellularity of the BAL, modulate the OVA-specific IgE production, reduce the cell infiltration and mucus in the lungs and further increase the IL-10. However, although the (S)-(+)-carvone has reduced the BAL cellularity and increased IFN-γ levels, it was unable to reduce the cell infiltration in the lung and increase the mucus production. Therefore, both enantiomers of carvone showed anti-inflammatory effect, although only the (R)-(−)-carvone showned potential anti-asthmatic. Additionally, the results presented by (S)-(+)-carvone, revealed a potential adverse effect of this enantiomer in the experimental model of asthma. / Enantiômeros são compostos assimétricos que apresentam a particularidade de serem imagens especulares um do outro, não sobreponíveis e por terem comportamentos diferentes em ambientes quirais, resultando frequentemente na discriminação esterioseletiva e diferentes efeitos biológicos. A carvona é um monoterpeno, constituinte de muitos óleos essenciais e encontrada na natureza na forma de dois enantiômeros: (S)-(+)-carvona e (R)-(-)-carvona. A inflamação uma resposta fisiológica do organismo, quando ocorre de forma exacerbada ou inapropriada pode promover dano tecidual e patologias associadas. Um exemplo de doença inflamatória importante é a asma, um processo hipersensibilidade imediata nas vias aéreas e que tratamentos convencionais apresentam efeitos colaterais importantes. O objetivo desse trabalho foi avaliar os enantiômeros da carvona em modelos de inflamação e de hipersensibilidade das vias aéreas. Para investigar a atividade anti-inflamatória das substâncias os seguintes parâmetros foram avaliados: produção de NO por células J774.A1, formação de edema de pata induzido por carragenina, zimosan, composto 48/80 e histamina, migração de células e produção das citocinas (TNF-α e IL-1β) no modelo de peritonite induzida por zimosan, em camundongos Swiss. Para avaliar a atividade anti-asmática dos enantiômeros, foi utilizado o modelo de asma experimental induzido por ovalbumina e analisado os seguinte parâmetros: celularidade do lavado bronco alveolar (BAL), produção de muco, síntese de IgE OVA-específica, produção de citocinas (IL-13, IFN-γ e IL-10). Os resultados demonstraram que ambos os enantiômeros foram capazes de reduzir a produção de NO, inibir o edema de pata induzido pelos agentes flogísticos utilizados e inibir a migração de células para o peritônio, porém apenas a (R)-( )-carvona foi capaz de reduzir os níveis de TNF-α. No modelo murino de asma alérgica, a (R)-(−)-carvona, foi capaz de reduzir a celularidade do BAL, modular a produção de IgE OVA-específica, reduzir o infiltrado de células e muco no pulmão e ainda, aumentar os níveis de IL-10. Porém, embora a (S)-(+)-carvona, tenha reduzido a celularidade do BAL e aumentado os níveis de IFN-γ, ela não foi capaz de reduzir o infiltrado de células no pulmão e ainda, aumentou a produção de muco. Portanto, ambos enantiômeros da carvona apresentaram efeito anti-inflamatório, embora apenas a (R)-(-)-carvona tenha apresentado potencial anti-asmático e ainda, os resultados apresentados pela (S)-(+)-carvona, revelaram um potencial efeito adverso desse enantiômero em modelo experimental de asma.