Anti-Inflammatory Effect of Topiramate in a Chronic Model of TNBS-Induced Colitis.

Inflammatory bowel disease (IBD) is characterized by a chronic and relapsing inflammatory response in the gastrointestinal tract, resulting in severe symptoms such as abdominal pain, vomiting, diarrhea, bloody stools, and weight loss. Currently, there is no cure, and the pharmacological treatment includes drugs that induce and keep the patient in remission, not reversing the underlying pathogenic mechanism. These therapies, in the long term, may cause various side effects and complications, which has increased the need to investigate new, more effective, and safer pharmacological approaches. In preclinical studies, topiramate has demonstrated a potential anti-inflammatory effect by inhibiting the production of several pro-inflammatory cytokines. This study aimed to investigate the effect of topiramate in a chronic TNBS-induced colitis model in rodents. Experimental colitis was induced by four intrarectal administrations of 1% TNBS in female CD-1 mice. Topiramate 10 and 20 mg were administered intraperitoneally for 14 days. Several parameters were evaluated, such as bodyweight, alkaline phosphatase (ALP), fecal hemoglobin, fecal calprotectin, tumor necrosis factor (TNF)-α, and interleukin (IL)-10. Topiramate reduces TNBS-induced colonic damage in a model of chronic experimental colitis and normalizes the stool consistency and anus appearance. Additionally, topiramate significantly reduced the concentration of ALP, fecal hemoglobin, fecal calprotectin, TNF-α, and IL-10, demonstrating it to be a promising pharmacological approach for the treatment of IBD in the future.

Higher oral efficacy of ravuconazole in self-nanoemulsifying systems in shorter treatment in experimental chagas disease.

We investigated the in vitro activity and selectivity, and in vivo efficacy of ravuconazole (RAV) in self-nanoemulsifying delivery system (SNEDDS) against Trypanosoma cruzi. Novel formulations of this poorly soluble C14-α-demethylase inhibitor may improve its efficacy in the experimental treatment. In vitro activity was determined in infected cardiomyocytes and efficacy in vivo evaluated in terms of parasitological cure induced in Y and Colombian strains of T. cruzi-infected mice. In vitro RAV-SNEDDS exhibited significantly higher potency of 1.9-fold at the IC50 level and 2-fold at IC90 level than free-RAV. No difference in activity with Colombian strain was observed in vitro. Oral treatment with a daily dose of 20 mg/kg for 30 days resulted in 70% of cure for RAV-SNEDDS versus 40% for free-RAV and 50% for 100 mg/kg benznidazole in acute infection (T. cruzi Y strain). Long-term treatment efficacy (40 days) was able to cure 100% of Y strain-infected animals with both RAV preparations. Longer treatment time was also efficient to increase the cure rate with benznidazole (Y and Colombian strains). RAV-SNEDDS shows greater efficacy in a shorter time treatment regimen, it is safe and could be a promising formulation to be evaluated in other pre-clinical models to treat T. cruzi and fungi infections.

Nitrotriazole-Based Compounds as Antichagasic Agents in a Long-Treatment In Vivo Assay.

3-Nitrotriazole-based compounds belonging to various chemical subclasses were found to be very effective against Chagas disease both in vitro and in vivo after a short administration schedule. In this study, five compounds with specific characteristics were selected to be administered for longer periods of time to mice infected with the virulent Trypanosoma cruzi Y strain to further evaluate their effectiveness as antichagasic agents and whether or not potential adverse effects occur. Benznidazole was included for comparison purposes. Complete parasitemia depletion, weight gain, 100% survival, and a lack of myocardial inflammation were observed with four of the compounds and benznidazole administered intraperitoneally at 15 or 20 mg/kg of body weight/day for 40 days. There was a significant reduction in the number of treatment days (number of doses) necessary to induce parasitemia suppression with all four compounds compared to that required with benznidazole. Partial cures were obtained with only one compound tested at 15 mg/kg/day and on the schedule mentioned above but not with benznidazole. Taken together, our data suggest that these compounds demonstrate potent trypanocidal activity comparable to or better than that of the reference drug, benznidazole, when they are administered at the same dose and on the same schedule.

Vasoactive intestinal peptide reduces the inflammatory profile in mice infected with Trypanosoma cruzi.

Vasoactive intestinal peptide (VIP) has gained great prominence because of its therapeutic potential, which is ascribed to its ability to regulate innate immunity, inhibit antigen-specific Th1 cell responses, and generate T regulatory cells. Additionally, VIP may act as a natural antimicrobial peptide, killing bacteria, fungi, and infective forms of Trypanosoma brucei. Despite the possible relevance of VIP during the course of Chagas disease, studies regarding this in human and experimental Trypanosoma cruzi infections remain poorly characterized. In this work, we evaluated the effects of VIP on systemic and cardiac immune responses during experimental acute infection. C57BL/6 mice were infected with 5000 trypomastigotes of the VL-10 strain of T. cruzi and treated with intraperitoneal VIP injection every other day for one month. After 30 days, we observed no reduction in parasitemia levels. However, we observed a reduction in serum levels of IFN-gamma and IL-2 and an increase in that of IL-4. These data suggest that VIP treatment modified immune responses to favor the Th2 response, which had no impact on parasitemia levels although the serum level of IFN-gamma was reduced. However, this change in immune balance reduced heart damage, as noted by the smaller cardiac volume and the moderate inflammatory infiltrate observed in VIP-treated mice. Our results indicate that VIP treatment reduced the inflammatory response at the cardiac site of mice that were experimentally infected with T. cruzi. These data suggest a protective role for VIP in the heart of infected mice.

The Pharmacological Effect of Hemin in Inflammatory-Related Diseases: A Systematic Review.

BACKGROUND: Hemin is clinically used in acute attacks of porphyria; however, recent evidence has also highlighted its capability to stimulate the heme oxygenase enzyme, being associated with cytoprotective, antioxidant, and anti-inflammatory effects. Indeed, current preclinical evidence emphasizes the potential anti-inflammatory role of hemin through its use in animal models of disease. Nevertheless, there is no consensus about the underlying mechanism(s) and the most optimal therapeutic regimens. Therefore, this review aims to summarize, analyze, and discuss the current preclinical evidence concerning the pharmacological effect of hemin. METHODS: Following the application of the search expression and the retrieval of the articles, only nonclinical studies in vivo written in English were considered, where the potential anti-inflammatory effect of hemin was evaluated. RESULTS: Forty-nine articles were included according to the eligibility criteria established. The results obtained show the preference of using 30 to 50 mg/kg of hemin, administered intraperitoneally, in both acute and chronic contexts. This drug demonstrates significant anti-inflammatory and antioxidant activities considering its capacity for reducing the expression of proinflammatory and oxidative markers. CONCLUSIONS: This review highlighted the significant anti-inflammatory and antioxidant effects of hemin, providing a clearer vision for the medical community about the use of this drug in several human diseases.

Glucans: A Therapeutic Alternative for Sepsis Treatment.

Sepsis treatment is a challenging condition due to its complexity, which involves host inflammatory responses to a severe and potentially fatal infection, associated with organ dysfunction. The aim of this study was to analyze the scientific literature on the immunomodulatory effects of glucans in a murine model of systemic infection induced by cecal ligation and puncture. This study comprises an integrative literature review based on systematic steps, with searches carried out in the PubMed, ScienceDirect, Scopus, Web of Science, and Embase databases. In most studies, the main type of glucan investigated was ß-glucan, at 50 mg/kg, and a reduction of inflammatory responses was identified, minimizing the occurrence of tissue damage leading to increased animal survival. Based on the data obtained and discussed in this review, glucans represent a promising biotechnological alternative to modulate the immune response and could potentially be used in the clinical management of septic individuals.

Correction: The Efficacy, Safety, and Efficiency of the Off-Label Use of Bevacizumab in Patients Diagnosed With Age-Related Macular Degeneration: Protocol for a Systematic Review and Meta-Analysis.

[This corrects the article DOI: 10.2196/38658.].

The Efficacy, Safety, and Efficiency of the Off-Label Use of Bevacizumab in Patients Diagnosed With Age-Related Macular Degeneration: Protocol for a Systematic Review and Meta-Analysis.

BACKGROUND: Age-related macular degeneration (AMD) is recognized as the leading cause of vision loss in older people. Considering the phenomenon of aging societies worldwide, the prevalence of AMD is expected to increase gradually in the future. AMD can be divided into early, intermediate, and late stages, with the early and intermediate stages being mainly asymptomatic, and the late stage being classified as geographic atrophy, neovascular AMD, or both. Current pharmacological treatments for neovascular AMD include anti-vascular endothelial growth factor agents, such as ranibizumab, pegaptanib, and aflibercept. Additionally, it has been reported that the off-label use of intravitreally administered bevacizumab is effective. It is also lower cost than other agents, which makes it an interesting pharmacological approach. OBJECTIVE: This review aims to evaluate the efficacy, safety, and efficiency of bevacizumab for the treatment of neovascular AMD. METHODS: This review will only consider randomized controlled clinical trials that compare the use of bevacizumab with another pharmacological agent or a placebo in patients aged 50 years and older who are diagnosed with vascular AMD. It will exclude studies that include participants diagnosed with polypoidal choroidal vasculopathy or retinal angiomatous proliferation. To identify and select relevant articles, we will develop a highly sensitive search strategy and apply it in MEDLINE via the PubMed platform. Upon selection of the studies and analysis of the titles, abstracts, and full texts, the results will be presented according to the Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The analysis and extraction of the data will be performed by 2 independent reviewers. Risk of bias will be evaluated with the Critical Appraisal Skills Programme (CASP) checklist. Finally, the same reviewers will also perform a quality assessment of the included studies with the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) tool. RESULTS: The search strategy, after the application of the inclusion and exclusion criteria, identified 15 randomized clinical trials, which are currently being analyzed. This project has no funding and it has been developed by a multidisciplinary research team of pharmacologists and orthoptists. The study was initiated in May 2021 and it is expected to conclude by the end of 2023. CONCLUSIONS: This review will provide a synthesis of current information and underlying evidence about the off-label use of bevacizumab in neovascular AMD. It will provide a clearer vision of a possible new pharmacological approach, as well as the most suitable treatment designs, for the treatment of neovascular AMD. TRIAL REGISTRATION: PROSPERO CRD42021244931; https://tinyurl.com/p6m5ycpk. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/38658.

The Pharmacological Effect of Hemin in Inflammatory-Related Diseases: Protocol for a Systematic Review.

BACKGROUND: Hemin is a commonly used drug in the treatment of acute attacks of porphyria, due to its capability of restoring normal levels of hemoproteins and respiratory pigments. In addition, this drug has demonstrated the capacity to induce the heme oxygenase (HO) enzyme. At the moment, there are 3 known HO isoenzymes in mammals: HO-1, HO-2, and HO-3. The first of these shows cytoprotective, antioxidant, and anti-inflammatory effects. Currently, medicines used in inflammatory disorders have increased toxicity, especially over longer time frames, which highlights the need to investigate new, safer options. Indeed, the current nonclinical evidence demonstrates the potential that hemin has a significant anti-inflammatory effect in several animal models of inflammation-related diseases, such as experimental colitis, without significant side effects. However, the underlying mechanism(s) are still not fully understood. In addition, past nonclinical studies have applied different therapeutic regimens, making it relatively difficult to understand which is optimal. According to the literature, there is a lack of review articles discussing this topic, highlighting the need for a summary and analysis of the available preclinical evidence to elucidate the abovementioned issues. Therefore, a qualitative synthesis of the current evidence is essential for the research and medical communities. OBJECTIVE: This systematic review aims to summarize and analyze currently available nonclinical data to ascertain the potential anti-inflammatory effect of hemin in animal models. METHODS: Throughout the development of this protocol, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. The comprehensive search strategy will be carried out in MEDLINE (PubMed), Web of Science, and Scopus without any filters associated with publication date. Only in vivo, nonclinical studies that evaluated the potential anti-inflammatory effect of hemin will be included. The evaluated outcomes will be the observed clinical signs, inflammatory and other biochemical markers, and macroscopic and microscopic evaluations. To analyze the potential risk of bias, we will use the risk of bias tool developed by the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE). RESULTS: Currently, it is not possible to disclose any results since the project is still in initial steps. More specifically, we are currently engaged in the identification of eligible articles through the application of the inclusion and exclusion criteria. The work was initiated in April 2023, and it is expected to be finished at the end of 2023. CONCLUSIONS: Concerning the major gap in the literature regarding the underlying mechanism(s) and treatment-related properties, this systematic review will be essential to clearly summarize and critically analyze the nonclinical data available, promoting a clearer vision of the potential anti-inflammatory effect of hemin. TRIAL REGISTRATION: PROSPERO CRD42023406160; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=406160. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/48368.

Effect of Carbamylated Erythropoietin in a Chronic Model of TNBS-Induced Colitis.

BACKGROUND: Inflammatory bowel disease (IBD) is a public health issue with a growing prevalence, which can be divided into two phenotypes, namely Crohn's disease (CD) and ulcerative colitis (UC). Currently, used therapy is based only on symptomatic and/or palliative pharmacological approaches. These treatments seek to induce and maintain remission of the disease and ameliorate its secondary effects; however, they do not modify or reverse the underlying pathogenic mechanism. Therefore, it is essential to investigate new potential treatments. Carbamylated erythropoietin (cEPO) results from the modification of the Erythropoietin (EPO) molecule, reducing cardiovascular-related side effects from the natural erythropoiesis stimulation. cEPO has been studied throughout several animal models, which demonstrated an anti-inflammatory effect by decreasing the production of several pro-inflammatory cytokines. AIM: This study aimed to evaluate the efficacy and safety of cEPO in a chronic TNBS-induced colitis model in rodents. METHODS: Experimental colitis was induced by weekly intrarectal (IR) administrations of 1% TNBS for 5 weeks in female CD-1 mice. Then, the mice were treated with 500 IU/kg/day or 1000 IU/kg/day of cEPO through intraperitoneal injections for 14 days. RESULTS: cEPO significantly reduced the concentration of alkaline phosphatase (ALP), fecal hemoglobin, tumor necrosis factor (TNF)-α, and interleukin (IL)-10. Also, it demonstrated a beneficial influence on the extra-intestinal manifestations, with the absence of significant side effects of its use. CONCLUSION: Considering the positive results from cEPO in this experiment, it may arise as a new possible pharmacological approach for the future management of IBD.

Therapeutic Potential of Punica granatum and Isolated Compounds: Evidence-Based Advances to Treat Bacterial Infections.

Punica granatum Linn has been known for its nutritional and medicinal value since ancient times and is used in the treatment of various pathologies owing to its antibacterial properties. This review reports the results of the most recent studies on the antibacterial effects of P. granatum and its isolated compounds on bacteria of clinical interest. A search in the PubMed, Scopus, Science Direct, and Science Citation Index Expanded (Web of Science) databases was performed, which included articles that evaluated the antibacterial activity of P. granatum extracts and excluded articles that analyzed other microorganisms or nonpathogenic bacteria, as well as theses, dissertations, duplicate articles, and those not fully available. The literature suggests that P. granatum extracts can act on bacteria, such as methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), Streptococcus mutans, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. In addition, fruit peel was the most commonly used pharmacogen and methanol, ethanol, and water were the most common solvents for the extraction of bioactive compounds. The antibacterial potential of the methanolic extract of pomegranate peel could be attributed to the presence of active compounds, such as 5-hydroxymethylfurfural, punicic acid, gallic acid, and punicalagin. Thus, there is evidence that these plant extracts, having high polyphenol content, can disrupt the bacterial plasma membrane and inhibit the action of proteins related to antimicrobial resistance. P. granatum shows antibacterial activity against Gram-positive and Gram-negative bacteria, with great potential against multidrug-resistant strains. Further research is needed to clarify the mechanism of action related to this biological activity and investigate the isolated substances that may be responsible for the antibacterial effects.

The Immunomodulatory Activity of Punica granatum L. Peel Extract Increases the Lifespan of Mice with Lethal Sepsis.

Sepsis is an organ dysfunction syndrome associated with high mortality. To date, no effective treatment is available to combat this disease. Punica granatum L. is a potential alternative treatment due to its anti-inflammatory, antimicrobial, and antioxidant properties. Thus, this study aimed to evaluate the effects of a hydroalcoholic crude extract from the peels of P. granatum (HCEPg) in mice with lethal sepsis. Lethal polymicrobial sepsis was induced in female Swiss mice via cecal ligation and puncture (CLP). Initially, the animals were divided into three groups: Sham (false-operated), CLP-control (phosphate-buffered saline), and CLP-HCEPg (single dose, 5 mg/kg, subcutaneous administration). Treatment was initiated immediately after the induction of sepsis, and survival was evaluated every 12 hr for 5 days. Those who survived were euthanized. Serum cytokine levels were measured using a cytometric bead array Mouse Inflammatory Cytokine Kit. The number of colony-forming units, as well as the number of cells in the lymphoid organs and their activation markers, were analyzed. Results showed that treatment with HCEPg increased lifespan and reduced bacterial counts in the peritoneum, bloodstream, and spleen. HCEPg also decreased hydrogen peroxide secretion by phagocytes and augmented serum IL-10 levels, indicating its systemic anti-inflammatory effects. Additionally, treatment with HCEPg attenuated infection-induced lung hemorrhage. Overall, P. granatum extract improved the lifespan of septic mice, possibly due to its antimicrobial, anti-inflammatory, and immunomodulatory effects, thereby regulating bacterial load and translocation, as well as controlling the systemic inflammation induced by sepsis.

Knowledge and use of personal protective equipment by nursing professionals during the Covid-19 pandemic.

OBJECTIVE: To explore the knowledge and use of personal protective equipment by nursing professionals of Primary Health Care during the Covid-19 pandemic. METHOD: This is an exploratory study of a non-probabilistic sample developed in Basic Health Units in the city of Picos, Piauí, Brazil. Data were collected between June and August 2020, by phone call, following a semi-structured script, with responses recording and transcription. For material analysis, the software IRaMuTeQ was used for statistical textual analyses: Descending Hierarchical Classification, similarity analysis, and word cloud. RESULTS: From the corpus of 6,873 words and 832 lexical units, three categories were created: (1) motivations and barriers for use (20.9%); (2) handling of personal protective equipment (classes 5 and 4) with 25% and 21.6%, respectively, and (3) measures to protect users and health professionals (classes 3 and 5) with 17.6% and 14.9%. CONCLUSION: The nursing professionals interviewed demonstrated that they did not have sufficient knowledge for the proper use of the equipment, which could compromise their integrity and that of the patient as a subject who receives unsafe care.

A cell surface 230 kDa protein from murine melanoma involved with tumor malignancy.

Because melanoma incidence has increased at a dramatic rate, it is relevant to identify novel melanoma antigens for diagnosis and develop monoclonal antibodies recognizing such molecules. Some monoclonal antibodies (mAbs), raised against murine melanoma, identify molecules correlated with carcinogenesis. Herein, we describe a murine melanoma-associated 230 kDa molecule, expressed only in tumorigenic cell lines. Moreover, its expression is higher in more metastatic than less metastatic cells. G12F2 mAb, produced against this antigen, inhibited in vitro proliferation of both murine and human melanoma cells and enhanced in vitro complement activity. It also affected in vivo tumor growth and lung metastases formation. This 230kDa molecule represents an important target for experimental melanoma studies and may become a potential diagnostic marker for malignancy as well as a useful tool for immunotherapeutic approaches.

Chronic exercise induces pathological left ventricular hypertrophy in adrenaline-deficient mice.

Adrenaline-deficient phenylethanolamine-N-methyltransferase-knockout mice (Pnmt-KO) have concentric heart remodeling and though their resting blood pressure is normal, it becomes higher during acute exercise. The aim of this study was to evaluate cardiac morphological, functional and molecular alterations after chronic exercise in adrenaline-deficient mice. Genotypes at the Pnmt locus were verified by polymerase chain reaction (PCR) of ear samples of Pnmt-KO and wild-type (WT) mice. These mice were submitted to chronic exercise training during 6weeks. Blood pressure was determined by a photoelectric pulse detector. Mice were anesthetized and cardiac morphology and function were evaluated by echocardiography and hemodynamics. IGF-1, IGF-1R, ANP and BNP mRNA were quantified by real-time PCR in left ventricle (LV) samples. Pnmt-KO mice showed increased systolic blood pressure compared with WT mice. A significant increase was found in LV mass, and LV posterior wall thickness in trained Pnmt-KO compared to trained WT mice, without significant differences in LV volumes. Acute ß1-adrenergic stimulation with dobutamine increased systolic function indexes in WT mice, but not in Pnmt-KO mice. LV expression of IGF-1 and ANP was increased in trained Pnmt-KO mice when compared to trained WT mice. In conclusion, in response to chronic exercise adrenaline-deficient Pnmt-KO mice show concentric LV hypertrophy and impaired response to dobutamine, suggesting an initial stage of pathological cardiac hypertrophic remodeling. These results support the need for an efficient partial conversion of noradrenaline into adrenaline for prevention of blood pressure overshoot and thus pathological cardiac hypertrophic remodeling in chronic exercise.

Higiene de las manos basada en indicadores de rendimiento / Hand Hygiene Based on Performance Indicators

Introducción: Las manos de los profesionales son el vehículo más común para la transmisión de microorganismos de un paciente a otro. En ese contexto, la higiene de las manos se considera una medida primaria muy relevante para controlar las infecciones asociadas a la atención sanitaria. Objetivo: Verificar la adherencia a las prácticas de higiene de las manos entre los profesionales de la salud en la Unidad de Cuidados Intensivos de un Hospital Universitario. Métodos: Estudio descriptivo de corte transversal con abordaje cuantitativo, realizado en la Unidad de Cuidados Intensivos de un Hospital Universitario Brasileiro en el año 2020. La población del estudio estuvo formada por 121 profesionales de la salud. La recogida de datos se produjo mediante la consulta de la base de datos puesta a disposición por el Comité de Control de Infecciones Hospitalarias del hospital. El análisis estadístico se procesó en el Statistical Package for the Social Sciences-SPSS versión 22, a través de estadísticas descriptivas simples. Resultados: La tasa de adherencia al saneamiento fue superior a 78,04 por ciento. Los residentes de enfermedades tuvieron la tasa de depresión más alta, 96,72 por ciento. Por otro lado, los médicos tuvieron solo 57,29 por ciento de su atención con higiene. Estos eventos indican que los profesionales de la salud de la Unidad de Cuidados Intensivos pueden estar preocupados por el riesgo de que se realicen los procedimientos, debido a la exposición a fluidos corporales y regiones contaminadas. Conclusiones: Se encontró adherencia insatisfactoria al saneamiento para todas las categorías profesionales durante el período de demostración de la investigación(AU)

Introduction: The hands of professionals are the most common vehicle for the transmission of microorganisms from one patient to another. In this setting, hand hygiene is considered a very relevant primary measure for controlling healthcare-associated infections. Objective: To verify adherence to hand hygiene practices among healthcare professionals in the intensive care unit of a university hospital. Methods: Descriptive and cross-sectional study, with a quantitative approach, carried out in 2020 in the intensive care unit of a Brazilian university hospital. The study population consisted of 121 health professionals. Data collection was done by consulting the database available under the committee for hospital infection control at the institutional level. The statistical analysis was done with the Statistical Package for the Social Sciences (SPSS), version 22, using simple descriptive statistics. Results: The sanitation adherence rate was over 78.04 percent. Internal Medicine residents had the highest depression rate, accounting for 96.72 percent. On the other hand, physicians had only 57.29 percent of their care with sanitation. These events indicate that healthcare professionals in the intensive care unit may be concerned about the risk of procedures being performed due to exposure to body fluids and contaminated areas. Conclusions: Unsatisfactory adherence to sanitation was found in all professional categories during the research demonstration period(AU)

Conhecimento de profissionais da saúde sobre segurança do paciente: revisão integrativa / Health professionals' knowledge about patient safety: an integrative review

Objetivo: Analisar na literatura o conhecimento dos profissionais da saúde sobre segurança do paciente. Métodos: Revisão integrativa com busca e seleção em cinco bases eletrônicas de dados: MEDLINE, CINAHL, Web of Science, LILACS e BDENF, utilizando descritores controlados e não controlados indexados nos vocabulários DeCS e MESH. Foram incluídos estudos primários, sem delimitação temporal ou de idioma e excluídos os duplicados, editoriais, teses e dissertações. Para análise e síntese, utilizou-se a classificação do nível de evidência baseadas nas recomendações do Oxford Centre for Evidence-based Medicine e os métodos descritivos.Resultados: Foram selecionados 11 artigos desenvolvidos em contexto nacional e internacional, de nível de evidência2C. O nível de conhecimentos gerais sobre segurança do paciente entre os profissionais de saúde foi considerado baixo, envolvendo limitações significativas no entendimento dos conceitos e definições, assim como na aplicação dos pressupostos teóricos na prática assistencial. Nas categorias investigadas,observou-se variação desse nível de conhecimento. Conclusão: Existem lacunas importantes no conhecimento de profissionais de saúde sobre segurança do paciente, que apresentam nível baixo de conhecimento. Destaca-se então,a educação permanente como uma estratégia para promover melhorias. Descritores: Segurança do paciente. Pessoal de saúde. Conhecimento. Enfermagem. Educação continuada.

Objective: To analyze, in the literature, health professionals' knowledge about patientsafety.Methods: An integrative review with searches and selection in five electronic databases: MEDLINE, CINAHL, Web of Science, LILACS and BDENF, using controlled and non-controlled descriptors indexed in the DeCS and MESH vocabularies. Primary studies with no time or language restrictions were included, with exclusion of duplicates, editorials, theses and dissertations. For analysis and synthesis purposes, the level of evidenceclassification based on the Oxford Centre for Evidence-based Medicinerecommendations and the descriptive methods was used. Results: Eleven articles with level of evidence2C and developed in the national and international contexts were selected. The level of general knowledge about patient safety among health professionals was considered low, involving significant limitations in the understanding of concepts and definitions, as well as in the application of theoretical assumptions in the care practice. Inthe categories investigated, certain variation of this knowledge level was observed. Conclusion: There are important gaps in health professionals' knowledge about patient safety, with the subjects presenting low knowledge levels. Therefore, permanent education stands out as a strategy to promote improvements. Descriptors: Patient Safety. Health Personnel. Knowledge. Nursing. Education Continuing

Instrumentos de medida para avaliação do conhecimento de estudantes de Enfermagem sobre segurança do paciente / Measurement instruments to evaluate Nursing students' knowledge about patient safety / Instrumentos de medición para evaluar los conocimientos de los estudiantes de Enfermería sobre la seguridad del paciente

Objetivo: Analisar as evidências científicas relacionadas aos instrumentos utilizados para avaliar o conhecimento de estudantes de enfermagem sobre Segurança do Paciente. Métodos: Revisão integrativa realizada nas bases de dados MEDLINE, CINAHL, WOS, LILACS e BDENF. A amostra foi composta por 11 estudos primários, publicados entre os anos de 2008 a 2017, nos idiomas português, espanhol ou inglês e que responderam à questão de pesquisa. Resultados: Houve predomínio de estudos transversais, no idioma inglês. O instrumento mais utilizado para avaliação do conhecimento em segurança do paciente foi o Health Professional Education in Patient Safety Survey (H-PEPSS). Dentre os fatores que limitaram o processo de aprendizagem destacou-se a inexperiência dos alunos. Simulações clínicas e aproximação precoce com o tema representaram as intervenções que favorecem o desenvolvimento do conhecimento e de competências. Conclusão: A avaliação do conhecimento em segurança do paciente pode auxiliar no desenvolvimento de programas e ensino, bem como refletir diretamente na qualidade da assistência, surgindo, assim, a necessidade da criação, adaptação e validação de instrumentos de medida. (AU)

Objective: To analyze the scientific evidence related to the instruments used to evaluate nursing students' knowledge about patient safety. Methods: Integrative review performed in the electronic databases MEDLINE, CINAHL, WOS, LILACS and BDENF. The sample consisted of 11 primary studies, published between the years 2008 and 2017, in Portuguese, Spanish or English, and which answered the research question. Results: There studies were predominant cross-sectional, and in English. The synthesis of knowledge was divided into three categories: The use of measurement instruments to assess knowledge in patient safety; Interventions that contribute to learning about patient safety; Factors that limit learning about patient safety. Conclusion: The assessment of patient safety knowledge can assist in the development of programs and teaching, as well as directly reflect on the quality of care, thus arising the need for the creation, adaptation and validation of instruments measure. (AU)

Objetivo: Analizar las evidencias científicas relacionadas con los instrumentos utilizados para evaluar el conocimiento de estudiantes de enfermería sobre seguridad del paciente. Métodos: Revisión integrativa realizada en las bases electrónicas de datos MEDLINE, CINAHL, WOS, LILACS y BDENF. La muestra consistió en 11 estudios primarios publicados entre los años 2008 a 2017, en portugués, español o Inglés y que respondieron a la pregunta de investigación. Resultados: Hubo predominios de estudios transversales, en el idioma inglés. La síntesis del conocimiento se dividió en tres categorías: el uso de instrumentos de medida para la evaluación del conocimiento en seguridad del paciente; Intervenciones que contribuyen al aprendizaje sobre Seguridad del paciente; Factores que limitan el aprendizaje sobre seguridad del paciente. Conclusión: La evaluación de los conocimientos sobre seguridad del paciente puede ayudar en el desarrollo de programas y docencia, así como reflejar directamente la calidad de la atención, surgiendo así la necesidad de la creación, adaptación y validación de instrumentos la medida. (AU)

Low epinephrine levels and selective deficiency of ß2-adrenoceptor vasodilation at birth.

AIMS: Epinephrine is unique among biogenic catecholamines as a potent agonist of ß2-adrenoceptors. The ß2-adrenoceptor mediated effects during development might be linked to the increase of epinephrine synthesis. Our purpose was to characterize ß-adrenoceptor-mediated relaxation in the aorta of newborn and young rabbits (3 to 4months old), and to relate those responses with the epinephrine content of the adrenal gland. MAIN METHODS: The epinephrine levels and the tyrosine hydroxylase activity were determined in adrenal glands of newborn and young rabbits. Also, concentration-response curves to phenylephrine (selective α1-adrenoceptor agonist), dobutamine (selective ß1-adrenoceptor agonist), terbutaline (selective ß2-adrenoceptor agonist), and CL 316243 (selective ß3-adrenoceptor agonist) were determined in isolated aortic rings obtained from both groups. KEY FINDINGS: The adrenal gland content and the plasma concentrations of epinephrine were lower in newborn than in young rabbits. In contrast, the tyrosine hydroxylase activity was higher in newborn than in young rabbits. On the other hand, the maximal response to phenylephrine was lower in newborn than in young rabbits. Terbutaline at concentrations selective for ß2-adrenoceptors had no relaxing effects in neonates, in contrast to young rabbits. The potency and the maximal response of neither dobutamine nor CL 316243 were significantly different between the two groups. SIGNIFICANCE: In rabbits, as well as in humans, ß2-adrenoceptor-mediated responses and epinephrine synthesis are both immature at birth. On the other hand, the ß1 and ß3-adrenoceptor-mediated responses are fully developed. We conclude that epinephrine may influence the development of the ß2-adrenoceptor-mediated responses at birth and the rabbit is an excellent model to study these issues.

Efeitos psicossociais do distanciamento social durante as infecções por coronavírus: revisão integrativa / Efectos psicosociales del distanciamiento social durante las infecciones por coronavirus: revisión integradora / Psychosocial effects of social distancing during coronavirus infections: integrative review

Resumo Objetivo: Analisar na literatura os efeitos psicossociais do isolamento e do distanciamento social adotados como estratégia para prevenção e controle das infecções por coronavírus. Métodos: Revisão integrativa fundamentada no referencial teórico proposto por Whittemore e Knafl e executada em sete recursos informacionais: MEDLINE, SCOPUS, Embase, Web of Science, LILACS, IBECS e BDENF. A amostra foi constituída por 14 estudos primários, sem delimitação temporal ou de idioma e a análise foi realizada de forma descritiva. Utilizou-se a classificação do nível de evidência para caracterização das produções. Resultados: As repercussões psicossociais decorrentes das medidas de isolamento e distanciamento social foram frequentes em diferentes países, indicando impactos negativos na saúde mental e na qualidade de vida. Os comprometimentos psicológicos foram expressos por instabilidades de humor, níveis elevados de ansiedade, situação de estresse, frustração, solidão, raiva e alteração de padrão de sono. Fatores associados à duração prolongada da medida, às possibilidades de contágio, às instabilidades econômicas, ao desconhecimento e às incertezas que permeiam a doença foram determinantes para o grau de sofrimento psíquico. Conclusão: As medidas de distanciamento e isolamento social apesar de contribuírem para o controle epidemiológico em surtos, epidemias e pandemia por coronavírus, geraram comprometimentos na saúde mental da população, em que a duração da medida, as possibilidades de contágio, o medo e as instabilidades financeiras foram determinantes para o grau de sofrimento psíquico.

Resumen Objetivo: Analizar en la literatura los efectos psicosociales del aislamiento y del distanciamiento social adoptados como estrategia de prevención y control de las infecciones por coronavirus. Métodos: Revisión integradora fundamentada en el marco referencial teórico propuesto por Whittemore y Knafl y ejecutada en siete recursos informativos: MEDLINE, SCOPUS, Embase, Web of Science, LILACS, IBECS y BDENF. La muestra estuvo compuesta por 14 estudios primarios, sin delimitación temporal ni de idioma, y el análisis se realizó de forma descriptiva. Se utilizó la clasificación del nivel de evidencia para la caracterización de las producciones. Resultados: Las repercusiones psicosociales resultantes de las medidas de aislamiento y distanciamiento social fueron frecuentes en diferentes países e indicaron impactos negativos en la salud mental y en la calidad de vida. Las consecuencias psicológicas expresadas fueron humor inestable, niveles elevados de ansiedad, situación de estrés, frustración, soledad, enojo y cambios en el patrón de sueño. Factores asociados a la duración prolongada de la medida, a las posibilidades de contagio, a la inestabilidad económica, al desconocimiento y a la incertidumbre que provoca la enfermedad fueron determinantes para el nivel de sufrimiento psíquico. Conclusión: Las medidas de distanciamiento y aislamiento social, a pesar de contribuir con el control epidemiológico en brotes, epidemias y pandemia por coronavirus, generan consecuencias en la salud mental de la población; y la duración prolongada de la medida, las posibilidades de contagio, el miedo y la inestabilidad económica fueron determinantes para el nivel de sufrimiento psíquico.

Abstract Objective: To analyze the literature regarding the psychosocial effects of isolation and social distancing measures adopted as strategy for the prevention and control of coronavirus infections. Methods: Integrative review of the literature based on the theoretical framework proposed by Whittemore and Knafl and conducted on seven databases: MEDLINE, SCOPUS, Embase, Web of Science, LILACS, IBECS and BDENF. The sample consisted of 14 primary studies, with no time or language restriction and the analysis was descriptive. The level of evidence classification was used to characterize the studies. Results: Psychosocial repercussions of isolation and social distancing measures were frequent in different countries, with a negative impact on mental health and quality of life. Psychological impairments included mood instability, high levels of anxiety, stress, frustration, loneliness, anger and altered sleep patterns. Factors related to the prolonged duration of the measure, possibilities of contagion, economic instability, lack of knowledge and the uncertainties related to the disease were associated with psychological distress. Conclusion: Isolation and social distancing measures contribute to the epidemiological control of outbreaks, epidemics and pandemics of coronavirus; however, they compromise the population's mental health. The duration of the measure, the possibilities of contagion, fear and financial instability were determining factors for the degree of psychological distress.