Spontaneous subarachnoid hemorrhage (SAH) is a form of hemorrhagic stroke that accounts for approximately 7% of all strokes worldwide. Recently, researchers have gained insight into some possible genetic influences involved in the response to SAH. The goal of this study was to investigate the potential contribution of different mouse genetic backgrounds to brain injury after SAH. SAH was induced in 7 inbred strains of mice, and the degree of large artery vasospasm and brain injury was assessed. After 48 hours, SAH mice showed a significant reduction in middle cerebral artery diameter and increased neuronal injury in the cerebral cortex compared to sham controls. The degree of vasospasm and brain injury varied across strains. This data suggests that vasospasm and neuronal injury may not correlate, and that different genetic factors may influence each one. Future investigations may provide invaluable insight into the causes of these inter-strain differences and potential genetic contributors.

Purpose: To investigate venous total retinal blood flow (TRBF) and retinal blood flow (RBF) in the superior and the inferior retinal hemifields in primary open angle glaucoma (POAG) patients with, and without, disc hemorrhage (DH). Methods: RBF measurements were obtained from 10 POAG with DH and 19 POAG without DH using Doppler SD-OCT (RTVue) as well as bi-directional laser Doppler flowmetry (CLBF). Results: RBF was not different between the superior and inferior hemifields for either of the two groups. Venous TRBF in the POAG with DH group was significantly lower than in the age-matched stable POAG without DH group (p=0.009). In the POAG with DH group, venous TRBF was significantly lower in the DH eye compared to contralateral eye without DH (p=0.015). Conclusions: Venous TRBF was significantly lower in the POAG with DH group compared to both the POAG without DH group and the contralateral eye of the POAG with DH group.

Purpose: To investigate venous total retinal blood flow (TRBF) and retinal blood flow (RBF) in the superior and the inferior retinal hemifields in primary open angle glaucoma (POAG) patients with, and without, disc hemorrhage (DH). Methods: RBF measurements were obtained from 10 POAG with DH and 19 POAG without DH using Doppler SD-OCT (RTVue) as well as bi-directional laser Doppler flowmetry (CLBF). Results: RBF was not different between the superior and inferior hemifields for either of the two groups. Venous TRBF in the POAG with DH group was significantly lower than in the age-matched stable POAG without DH group (p=0.009). In the POAG with DH group, venous TRBF was significantly lower in the DH eye compared to contralateral eye without DH (p=0.015). Conclusions: Venous TRBF was significantly lower in the POAG with DH group compared to both the POAG without DH group and the contralateral eye of the POAG with DH group.

Diss. (sammanfattning) Göteborg : Univ., 2008. / Härtill 5 uppsatser.

Thesis (M. D.)--University of Hong Kong, 2008. / Includes bibliographical references (leaves 177-207) Also available in print.

El texto completo de este trabajo no está disponible en el Repositorio Académico UPC por restricciones de la casa editorial donde ha sido publicado. / Background: Various randomized-controlled clinical trials (RCTs) have investigated the neuroprotective role of minocycline in acute ischemic stroke (AIS) or acute intracerebral hemorrhage (ICH) patients. We sought to consolidate and investigate the efficacy and safety of minocycline in patients with acute stroke. Methods: Literature search spanned through November 30, 2017 across major databases to identify all RCTs that reported following efficacy outcomes among acute stroke patients treated with minocycline vs. placebo: National Institute of Health Stroke Scale (NIHSS), Barthel Index (BI), and modified Rankin Scale (mRS) scores. Additional safety, neuroimaging and biochemical endpoints were extracted. We pooled mean differences (MD) and risk ratios (RR) from RCTs using random-effects models. Results: We identified 7 RCTs comprising a total of 426 patients. Of these, additional unpublished data was obtained on contacting corresponding authors of 5 RCTs. In pooled analysis, minocycline demonstrated a favorable trend towards 3-month functional independence (mRS-scores of 0–2) (RR = 1.31; 95% CI 0.98–1.74, p = 0.06) and 3-month BI (MD = 6.92; 95% CI − 0.92, 14.75; p = 0.08). In AIS subgroup, minocycline was associated with higher rates of 3-month mRS-scores of 0–2 (RR = 1.59; 95% CI 1.19–2.12, p = 0.002; I2 = 58%) and 3-month BI (MD = 12.37; 95% CI 5.60, 19.14, p = 0.0003; I2 = 47%), whereas reduced the 3-month NIHSS (MD − 2.84; 95% CI − 5.55, − 0.13; p = 0.04; I2 = 86%). Minocycline administration was not associated with an increased risk of mortality, recurrent stroke, myocardial infarction and hemorrhagic conversion. Conclusions: Although data is limited, minocycline demonstrated efficacy and seems a promising neuroprotective agent in acute stroke patients, especially in AIS subgroup. Further RCTs are needed to evaluate the efficacy and safety of minocycline among ICH patients. / Revisión por pares / Revisión por pares

Background: Primary subarachnoid hemorrhage (1°SAH) is an important disease that causes significant morbidity and mortality. The sparse Canadian epidemiologic literature on 1° SAH is outdated and relies on diagnostic coding for case ascertainment which misses true cases and incorrectly labels non-cases. Objectives: Primary objective was to identify all patients with 1° SAH presenting to the Ottawa Hospital (TOH) between July 1, 2002 and June 30, 2011 by deriving and validating a search algorithm using an enriched administrative database. Secondary objectives included: 1) determine incidence and case-fatality rates (CFR) of 1° SAH at TOH; and 3) derive and validate a method to identify 1° SAH using routinely collected administrative data. Methods: A cohort of 1° SAH patients were identified with a case-defining algorithm that was derived and validated using a combination of cerebrospinal fluid analysis results and text-search algorithms of both cranial imaging and post-mortem reports. The incidence of 1° SAH was calculated using the total number of hospital encounters over the same time period. CFR was calculated by linking to vital statistic data of hospitalized patients at discharge. An optimal1° SAH prediction model was derived and validated using binomial recursive partitioning built with independent variables obtained from routinely collected administrative data. Results: Using the case-defining algorithm, 831 patients were identified with a 1° SAH over the study period. Hospital incidence of 1° SAH was 17.2 events per 10,000 inpatient encounters (or 0.17% of encounters) with a case-fatality rate of 18.1%. A validated SAH prediction model based on administrative data using a recursive partitioning model had a sensitivity of 96.5% (95% CI 93.9-98.0), a specificity of 99.8% (95%CI 99.6-99.9), and a +LR of 483 (95% CI 254-879). This results in a post-test probability of disease of 45%. Conclusion: We identified almost all cases of 1° SAH at our hospital using an enriched administrative data. Accurately identifying such patients with routinely collected health administrative data is possible, providing important opportunities to examine and study this patient population. Further studies, involving multiple centres are needed to reproduce these results.

Made available in DSpace on 2014-06-11T19:31:10Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-12-05Bitstream added on 2014-06-13T20:41:29Z : No. of bitstreams: 1 biava_js_dr_botfmvz.pdf: 534119 bytes, checksum: 45998dd63bee23a93b62bdf28d26cd12 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O termo hemorragia pulmonar induzida por exercício (HPIE) tem sido usado para descrever o sangramento de origem pulmonar associado à atividade física intensa. HPIE é considerada um dos maiores problemas em cavalos atletas devido ao grande impacto econômico causado pelo uso indiscriminado de produtos farmacológicos, custos com veterinários e descarte do animal. Esta síndrome mundialmente conhecida tem sido objeto de intensa discussão devido sua etiopatogenia incerta e tratamento controverso. O exame endoscópico é essencial instrumento no diagnóstico da HPIE e deve ser realizado 30 a 120 minutos após esforço físico intenso, tempo necessário para o sangue ser eliminado das vias aéreas distais. O objetivo deste estudo foi mensurar potenciais marcadores plasmáticos de lesão pulmonar como a enzima conversora de angiotensina (ECA) e endotelina tipo 1 (ET-1), antes de iniciar condicionamento físico (M0); e depois do teste de esforço máximo (M1) e depois de 15 minutos após fadiga (M15) em esteira de alta velocidade em cavalos de trote com e sem HPIE. Oito cavalos de trote (4 fêmeas e 4 machos castrados) com idade de 3 a 5 anos (média de 4 anos de idade) foram incluidos neste estudo. A severidade da HPIE foi estabelecida em graus de 0 a 4 depois de 15, 30, 60, 90 e 120 minutos após fadiga, pelo exame traqueobrônquico por endoscopia, e pela contagem manual de hemácias e concentração de hemoglobina no lavado broncoalveolar (LBA) coletado 90 minutos após fadiga, na 13° semana do experimento. A endoscopia determinou o grupo positivo e negativo para HPIE, sendo que três cavalos foram positivos para HPIE em três exames endoscópicos.A contagem de hemácias e a concentração de hemoglobina estavam aumentadas no grupo positivo para RESUMO HPIE quando comparadas ao grupo negativo ajudando... / The term Exercise-Induced Pulmonary Hemorrhage (EIPH) has been used to describe the bleeding of pulmonary origin associated with physical activities of high-intensity. EIPH is considered one of the greatest problems in athlete horses due to the high economical impact caused by the indiscriminate use of pharmaceutical products, veterinary costs and disposal of the animal. This worldwide syndrome has been object of intense discussions because of its unclear etiopathogeny and controversial treatment. Endoscopic exam is an essential instrument to diagnose HPIE and it must be performed 30 to 120 minutes after intense physical exercise, the necessary amount of time for the blood to be eliminated from distal airways. The objective of the present study was to measure potential markers of lung injury such as angiotensin-converting enzym (ACE) and endothelin-1 (ET- 1), before the beginning of training (M0); and after maximum effort testing on the treadmill (M1); and 15 minutes after fatigue (M15) on high speed treadmill in Standardbred horses with and without HPIE. Eight Standardbred horses (4 fillies and 4 geldings) aged 3 to 5 years old (average 4 years old) were included in this study. The severity of EIPH was scored in degrees from 0 to 4 after 15, 30, 60, 90 and 120 minutes after fatigue by tracheobronchoscopy exam and red blood cell count and hemoglobin concentration in BALF collected 90 minutes after fatigue on the 13th week of the experiment. The endoscopy determined positive and negative group for EIPH and three horses were EIPH positive upon three endoscopic exams. The red blood cell count and hemoglobin concentration were increased in positive group for EIPH when compared to negative group which helped... (Complete abstract click electronic access below)

Orientador: Roberto Calderon Gonçalves / Banca: Simone Biagio Chiacchio / Banca: Rogério Martins Amorim / Banca: Ivan Roque de Barros Filho / Banca: Wilson Roberto Fernandes / Resumo: O termo hemorragia pulmonar induzida por exercício (HPIE) tem sido usado para descrever o sangramento de origem pulmonar associado à atividade física intensa. HPIE é considerada um dos maiores problemas em cavalos atletas devido ao grande impacto econômico causado pelo uso indiscriminado de produtos farmacológicos, custos com veterinários e descarte do animal. Esta síndrome mundialmente conhecida tem sido objeto de intensa discussão devido sua etiopatogenia incerta e tratamento controverso. O exame endoscópico é essencial instrumento no diagnóstico da HPIE e deve ser realizado 30 a 120 minutos após esforço físico intenso, tempo necessário para o sangue ser eliminado das vias aéreas distais. O objetivo deste estudo foi mensurar potenciais marcadores plasmáticos de lesão pulmonar como a enzima conversora de angiotensina (ECA) e endotelina tipo 1 (ET-1), antes de iniciar condicionamento físico (M0); e depois do teste de esforço máximo (M1) e depois de 15 minutos após fadiga (M15) em esteira de alta velocidade em cavalos de trote com e sem HPIE. Oito cavalos de trote (4 fêmeas e 4 machos castrados) com idade de 3 a 5 anos (média de 4 anos de idade) foram incluidos neste estudo. A severidade da HPIE foi estabelecida em graus de 0 a 4 depois de 15, 30, 60, 90 e 120 minutos após fadiga, pelo exame traqueobrônquico por endoscopia, e pela contagem manual de hemácias e concentração de hemoglobina no lavado broncoalveolar (LBA) coletado 90 minutos após fadiga, na 13° semana do experimento. A endoscopia determinou o grupo positivo e negativo para HPIE, sendo que três cavalos foram positivos para HPIE em três exames endoscópicos.A contagem de hemácias e a concentração de hemoglobina estavam aumentadas no grupo positivo para RESUMO HPIE quando comparadas ao grupo negativo ajudando ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract:The term Exercise-Induced Pulmonary Hemorrhage (EIPH) has been used to describe the bleeding of pulmonary origin associated with physical activities of high-intensity. EIPH is considered one of the greatest problems in athlete horses due to the high economical impact caused by the indiscriminate use of pharmaceutical products, veterinary costs and disposal of the animal. This worldwide syndrome has been object of intense discussions because of its unclear etiopathogeny and controversial treatment. Endoscopic exam is an essential instrument to diagnose HPIE and it must be performed 30 to 120 minutes after intense physical exercise, the necessary amount of time for the blood to be eliminated from distal airways. The objective of the present study was to measure potential markers of lung injury such as angiotensin-converting enzym (ACE) and endothelin-1 (ET- 1), before the beginning of training (M0); and after maximum effort testing on the treadmill (M1); and 15 minutes after fatigue (M15) on high speed treadmill in Standardbred horses with and without HPIE. Eight Standardbred horses (4 fillies and 4 geldings) aged 3 to 5 years old (average 4 years old) were included in this study. The severity of EIPH was scored in degrees from 0 to 4 after 15, 30, 60, 90 and 120 minutes after fatigue by tracheobronchoscopy exam and red blood cell count and hemoglobin concentration in BALF collected 90 minutes after fatigue on the 13th week of the experiment. The endoscopy determined positive and negative group for EIPH and three horses were EIPH positive upon three endoscopic exams. The red blood cell count and hemoglobin concentration were increased in positive group for EIPH when compared to negative group which helped... (Complete abstract click electronic access below) / Doutor

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / Envenenamentos por serpentes sÃo um importante problema de saÃde muito difundido em paÃses tropicais. Entre as espÃcies mais perigosas da AmÃrica do Sul encontra-se o gÃnero Bothrops. Acidentes ofÃdicos causados por espÃcies Bothrops podem desenvolver rapidamente dano tecidual local grave, incluindo edema, hemorragia, mionecrose, ulceraÃÃo de pele e dor. A soroterapia tradicional tem eficÃcia limitada contra esses efeitos. Compostos naturais isolados de plantas, principalmente a partir de espÃcies usadas na medicina popular para tratar envenenamentos de serpente, podem ser uma boa alternativa para encontrar novos compostos para melhorar o tratamento do envenenamento e minimizar as sequelas das vÃtimas. Atividade antiofÃdica dos novos alcalÃides esteroidais: 1 -22,23-epoxi-solanida-1,4,9-trien-3-ona (1), 2-22,23-epoxi-solanida-1,4-dien-3-ona (2) 3-3,9-dihidroxi-22,23-epoxi-9-10-secosolanida-1,3,5(10)-trieno (3) isolados das folhas de Solanum campaniforme foram testados atravÃs da inibiÃÃo da atividade fosfolipÃsica, atividade proteolÃtica, miotoxicidade, hemorragia e necrose induzidas pelo veneno de Bothrops pauloensis. Os trÃs compostos foram capazes de inibir completamente a liberaÃÃo de creatina quinase de mÃsculos estriados esquelÃticos e minimizar as alteraÃÃes histolÃgicas sem inibir a atividade fosfolipÃsica A2 do veneno total de B. pauloensis. A inibiÃÃo da miotoxicidade parece ser independente da atividade catalÃtica de fosfolipase (PLA2) e pode estar relacionada à inibiÃÃo da PLA2 Lys 49, enzimaticamente inativas, e / ou uma aÃÃo indireta sobre metaloproteinases. Houve tambÃm, a inibiÃÃo da atividade proteolitica do veneno em diferentes substratos com os trÃs alcaloides A hemorragia, bem como a necrose de pele, ambas induzidas por metaloproteases presentes no veneno, foram reduzidas na presenÃa dos alcalÃides 1 e 2, mas nÃo com o alcalÃide 3. A inibiÃÃo das atividades proteolÃticas e a reduÃÃo dos efeitos hemorrÃgicos e necrosantes induzidas pelo vBp, principalmente atribuÃdos aos alcalÃides 1 e 2, podem estar associadas com a interaÃÃo destes compostos com as metaloproteases presentes no veneno e/ou com Ãons metÃlicos bivalentes necessÃrios para sua aÃÃo. / Snake envenoming is an important health problem widespread in tropical countries. Among the most dangerous species in South America is the Bothrops genus. Snakebites accidents caused by Bothrops species quickly develop severe local tissue damage, including swelling, hemorrhage, myonecrosis, skin ulceration and pain. The traditional serum therapy has limited effectiveness against these effects. Natural compounds isolated from plants, mainly from species used in folk medicine to treat snakebite, are a good choice to find new lead compounds to improve the snakebite treatment and minimize the sequelae of the victims. Antiophidic activity of the new steroidal alkaloids: 22-epoxy-solanide-1,4,9-trien-3-one (1), 22-epoxy-solanide-1,4-dien-3-one (2) and 3,9-dihydroxy-22,23-epoxy-9,10-secosolanida-1,3,5(10)-triene (3) isolated from leaves of Solanum campaniforme was tested through inhibition of phospholipasic activity, proteolytic activity, myotoxicity, hemorrhage and necrosis induced by Bothrops pauloensis venom. The three compounds were able to complete inhibit the creatine kinase release from skeletal muscles and minimize the histological changes, without inhibiting the phospholipasic A2 activity of whole venom. The inhibition of myotoxicity appears to be independent of catalytic activity of phospholipase A2 (PLA2) and may be related to inhibition of PLA2 Lys 49, enzymatically inactive, and / or an indirect action on metalloproteinases. There was also, the inhibition of proteolytic activity of the venom on different substrates with three alkaloids. Hemorrhage as well as skin necrosis, both induced by metalloproteases present in the venom, were reduced in the presence of alkaloids 1 and 2 , but not with the alkaloid 3. Inhibition of proteolytic activities and the reduction of hemorrhagic and necrotizing effects induced by vBp, mainly attributed to the alkaloids 1 and 2, may be associated with the interaction of these compounds with the metalloproteases present in the venom and / or divalent metal ions required for their action.