Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Estudo da dinâmica populacional e das estratégias de manejo da população canina no município de Itabirito, MG, Brasil de 2007 a 2011

Exportado OPUSMade available in DSpace on 2019-08-12T22:43:41Z (GMT). No. of bitstreams: 1 tese_ana_liz_f._bastos.pdf: 3921018 bytes, checksum: 10ef9187797a0b40f3b24500bd5cae1e (MD5) Previous issue date: 21O objetivo deste trabalho foi estudar a dinâmica populacional canina e avaliar as estratégias de manejo populacional aplicadas nesta população no município de Itabirito, MG, durantes os anos de 2007 a 2011. Os dados foram obtidos por meio de dois estudos transversais aplicados com intervalos de um ano, em 10% da população canina, amostrada de forma aleatória sistemática em todos os bairros da zona urbana do município. Foram analisados ainda dados secundários provenientes do Serviço de Controle de Zoonoses e da entidade de proteção animal do Município. O impacto da esterilização na densidade populacional canina foi realizado por meio de modelagem matemática. Verificou-se a existência de 5,2 cães por habitante, 0,47 cão por imóvel e (2,25 - 1,85) cães por imóvel com a presença deles em 2010 e 2011 respectivamente. Os cães estiveram presentes em 72,8% do total de imóveis pesquisados, dos quais 42,09% possuíam dois animais. A maioria (93,86%) possuíam barreiras físicas que continham os animais. A idade mediana dos animais foi 3,5 anos e a razão macho/fêmea (1,11:1 - 0,98:1) em 2010 e 2011 respectivamente. A taxa de natalidade foi 19,39%, a taxa de mortalidade 20,86% e a taxa de abandono foi de 3,6%. A média de filhotes nascidos vivos por gestação foi de 3,7 e a mortalidade neonatal foi de 31,4%. A proporção de animais esterilizados foi 15% - 21,78% em 2010 e 2011 respectivamente. Quanto à raça, 56,41% dos cães não tinham raça definida, 41,71% foram considerados de porte pequeno e 66,67% tinham como finalidade a companhia. Quanto à forma de aquisição, 47,46% dos cães foram recebidos de doação e 42,38% nunca saíam para passear. Em relação ao controle reprodutivo, aproximadamente 17% da população foi esterilizada durante os anos de 2007 a 2011, sendo esses animais provenientes de todos os bairros da zona urbana do Município. As taxas de esterilização anuais empregadas na população domiciliada não foram eficazes para promover uma diminuição significativa na densidade populacional canina, ao longo de dez anos, porém o impacto dessa estratégia na densidade canina foi maior na presença do abandono. O recolhimento seletivo de cães nas ruas foi realizado de forma humanitária, porém o número de cães recolhidos foi baixo em relação ao número total de animais no Município, sendo a eutanásia desses animais o destino mais frequente. A campanha de adoção promovida pela entidade de proteção animal possui números expressivos de adoção, mas é ineficiente quanto ao monitoramento dos cães após a adoção. A população canina se encontra em equilíbrio, e esse fato pode estar associado às intervenções promovidas pelo homem. As taxas de esterilização, eutanásia e adoção obtidas mostraram valores próximos e juntas podem ter influenciado a situação de equilíbrio que a população canina se encontrava, durante o período estudado. Entretanto, foi detectado o problema de abandono desses animais, influenciados por condições sociais, econômicas e culturais da população humana. Diante do cenário encontrado, recomendou-se a implantação de ações educativas no Município para dar sustentabilidade às ações de manejo populacional canino, para aumentar o nível da guarda responsável da população e diminuir o abandono dos cães no Município.This paper aimed at studying the canine population dynamics and evaluate its population management strategies in Itabirito county, Minas Gerais State, from 2007 to 2011. Data were collected through two cross-sectional studies applied at intervals of one year, 10% of the canine population, randomly sampled systematically in all neighborhoods of the urban area, and by obtaining secondary data from the Zoonosis Service Control and the Department of animal protection in the county. The impact of population density in canine sterilization was performed by means of mathematical modeling. The results revealed the existence of 5.2 dogs per capita, 0.47 dogs per property (2.25 to 1.85) dogs per property with their presence. The dogs were present in 72.8% of the surveyed properties, which 42.09% contained two animals and 93.86% had physical barriers blocking them. The average age of the animals was 3.5 and the ratio male / female was (1,1105:1 - 0,98:1). The birth rate was 19.39%, the mortality rate was around 20.86% and abandonment dog´s rate was over 3.6%. The average number of pups born alive was 3.7 per pregnancy and neonatal mortality was 31.4%. The proportion of sterilized animals was (15% - 21.78%). As for the breed, 56.41% of the dogs had not defined breed, 41.71% were considered as small size and 66.67% were aimed at companionship. In additional, 47.46% of the dogs were welcomed by donation and 42.38% never left to wander. Regarding reproductive control, around 17% of the dog´s population that had come from all the neighborhoods in the urban area, were sterilized through the years 2007 to 2011. The annual rates of sterilization used in the resident population were not effective in promoting a significant decrease in canine population density over ten years, however in the presence of abandoning the impact of this strategy on canine density was higher. The selective collection of dogs on the streets was done humanely, but the number of dogs collected was lower compared to the total number of animals in the city, and the euthanasia of these animals were the most frequent destination. The campaign promoted by the animal protection entity presented a significant number of adoptions, but was inefficient as tracking dogs after adoption. The dog´s population was in equilibrium, and this may has been associated with interventions promoted by man. The rates of sterilization, euthanasia and adoption presented close values and together may have influenced the equilibrium in the dog´s population. However, the abandonment problem of these animals was detected and It was influenced by social, economic and cultural conditions, that leaded to the implementation of educational activities in the county as a strategy to increase the level of the guard in charge of the dog´s population and reduce the abandoned dogs and provide sustainability for management actions in canine population in Itabirito

Experimental skin wound treatment with Copaifera langsdorffii Desf Kuntze (Leguminosae) extract and oil-resin in horses

Copaifera langsdorffii é uma planta nativa brasileira usada para cicatrização de feridas e como agente anti-inflamatório. As feridas que não cicatrizam são um importante problema de saúde em equinos, devido à possibilidade de afastamento da carreira atlética ou até mesmo levar à morte. Além disso, os cavalos respondem às feridas com resposta inflamatória crônica e intensa granulação, atrasando o processo cicatricial. Dessa forma, o presente trabalho avaliou o potencial do extrato hidroalcoólico (EH) e cremes de óleo resina (OR) de Copaifera langsdorffii em feridas cutâneas de equinos. Quatro feridas de 2 cm foram realizadas bilateralmente na região lombar de seis equinos e tratadas diariamente com: solução salina, veículo, creme EH 10% ou creme OR 10%. Diariamente foi efetuada a análise macroscópica das feridas e planimetria para mensurar a área da ferida. Em quatro períodos experimentais diferentes (3, 7, 14 e 21 dias), as biópsias foram realizadas e utilizadas para análises microscópicas. As análises microscópica e clínica indicaram melhor resposta cicatricial nas feridas tratadas com HE e OR em comparação com os controles. O grupo OR apresentou melhor qualidade de cicatrização, especificamente após sete dias de tratamento. Portanto, as formulações de Copaifera langsdorffii utilizadas apresentaram potencial de cicatrização de feridas em lesões de pele de cavalo, exibindo uma melhora nos parâmetros macro e microscópicos.Copaifera langsdorffii is a Brazilian native plant that is used for wound healing or as an anti-inflammatory agent. Non-healing wounds are an important health problem, particularly in horses, because they can cause the animal invalidity or even lead to death. In addition, horses respond to skin wounds with chronic inflammatory response and intense wound granulation, thereby delaying the healing process. By this way, our aim was to evaluate the healing potential of Copaifera langsdorffii hydroalcoholic extract (HE) and oil-resin creams (OR) in horse skin wounds. Four wounds were performed bilaterally in the lumbar region of six horses with a 2 cm punch and treated daily with the respective treatments: saline solution, vehicle, 10% HE creams or 10% OR cream. Daily planimetry analyses were performed to measure the wound area and clinical parameters. In four different experimental periods (3, 7, 14 and 21 d), wound biopsies were removed and used for microscopic analyses. SS wounds presented a significant small area at day 3 and 7, OR wounds presented significant small area in comparison with HE at 14 d, and no significant difference was observed between treatments at 21 d. A better microscopic and clinical healing activity of HE and OR was identified in comparison with the controls. The OR group showed better healing quality, specifically after 7 d of treatment. Therefore, Copaifera langsdorffii formulations demonstrated their wound healing potential in horse skin lesions, exhibiting an improvement of the macro- and microscopic parameters

Lycopene from Red Guava (<i>Psidium guajava</i> L.): From Hepatoprotective Effect to Its Use as Promising Self-Emulsifying Drug Delivery System for Anti-Inflammatory and Antioxidant Applications

Lycopene is a carotenoid with potential use in the treatment of chronic illnesses. Here, different formulations of lycopene were studied: lycopene-rich extract from red guava (LEG), purified lycopene from red guava (LPG) and a self-emulsifying drug delivery system loaded with LPG (nanoLPG). The effects of administering orally various doses of LEG to hypercholesterolemic hamsters were evaluated regarding the liver function of the animals. The cytotoxicity of LPG in Vero cells was analyzed by a crystal violet assay and by fluorescence microscopy. In addition, nanoLPG was employed in stability tests. LPG and nanoLPG were tested for their cytotoxic effect on human keratinocytes and antioxidant capacity on cells in an endothelial dysfunction model in an isolated rat aorta. Finally, the effect of different nanoLPG concentrations on the expression of immune-related genes (IL-10, TNF-α, COX-2 and IFN-γ) from peripheral blood mononuclear cells (PBMC) using real-time PCR was also analyzed. Results suggest that LEG, despite not being able to improve blood markers indicative of liver function in hypercholesterolemic hamsters, reduced hepatic degenerative changes. Additionally, LPG did not show cytotoxicity in Vero cells. In relation to nanoLPG, the effects produced by heat stress evaluated by Dynamics Light Scattering (DLS) and visually were loss of color, texture change and phase separation after 15 days without interfering with the droplet size, so the formulation proved to be efficient in stabilizing the encapsulated lycopene. Although LPG and nanoLPG showed moderate toxicity to keratinocytes, which may be related to cell lineage characteristics, both revealed potent antioxidant activity. LPG and nanoLPG showed vasoprotective effects in aortic preparations. The gene expression assay indicates that, although no significant differences were observed in the expression of IL-10 and TNF-α, the PBMCs treated with nanoLPG showed a reduction in transcriptional levels of IFN-γ and an increased expression of COX-2. Thus, the work adds evidence to the safety of the use of lycopene by humans and shows that tested formulations, mainly nanoLPG due to its stability, stand out as promising and biosafe products for the treatment of diseases that have oxidative stress and inflammation in their etiopathology