Assessment of sleep and stress level in individuals with chronic pain.

Introduction: The experience of living with chronic pain allows for the appearance of changes in sleep patterns, mood, and stress levels. Objective: To describe the phases of stress and the quality of sleep in patients with chronic pain. Material and Methods: Cross-sectional study carried out at the pain clinic of the HUPES Complex, Salvador-Bahia. Data collection between March 2016 and November 2017. Instruments: Sociodemographic questionnaire, Numerical Pain Scale (EVN), Mini-Sleep Questionnaire (MSQ), and Stress Symptoms Inventory for LIPP adults (ISSL). Categorical variables were expressed by absolute and relative frequency and quantitative variables by means and standard deviation (SD). The comparison of categorical variables was performed using the chi-square test. Values of p<0.05 were considered statistically significant. Results: Mean age (standard deviation) of 50.0 (10) years, 89.6% of whom were female. Predominance of people with a partner, with religion, high school, and unemployed or removed by the INSS. They have severe sleep disorders, severe pain, and the presence of stress in the resistance phase. Most subjects reveal that they have improved with the treatment and have moderate self-esteem and personal satisfaction, despite the presence of anxious and depressive symptoms. Conclusion: Chronic pain has a very significant impact on life, increasing the level of stress, compromising and limiting daily activities, and showing more presence of anxious and depressive symptoms in people who suffer from chronic pain.

LPS Response Is Impaired by Urban Fine Particulate Matter.

Fine particulate matter (PM2.5) is a complex mixture of components with diverse chemical and physical characteristics associated with increased respiratory and cardiovascular diseases mortality. Our study aimed to investigate the effects of exposure to concentrated PM2.5 on LPS-induced lung injury onset. BALB/c male mice were exposed to either filtered air or ambient fine PM2.5 in an ambient particle concentrator for 5 weeks. Then, an acute lung injury was induced with nebulized LPS. The animals were euthanized 24 h after the nebulization to either LPS or saline. Inflammatory cells and cytokines (IL-1ß, IL-4, IL-5, IL-6, IL-10, IL-17, TNF) were assessed in the blood, bronchoalveolar lavage fluid (BALF), and lung tissue. In addition, lung morphology was assessed by stereological methods. Our results showed that the PM+LPS group showed histological evidence of injury, leukocytosis with increased neutrophils and macrophages, and a mixed inflammatory response profile, with increased KC, IL-6, IL-1ß, IL-4, and IL-17. Our analysis shows that there is an interaction between the LPS nebulization and PM2.5 exposure, differently modulating the inflammatory response, with a distinct response pattern as compared to LPS or PM2.5 exposure alone. Further studies are required to explain the mechanism of immune modulation caused by PM2.5 exposure.

scFv-Anti-LDL(-)-Metal-Complex Multi-Wall Functionalized-Nanocapsules as a Promising Tool for the Prevention of Atherosclerosis Progression.

Atherosclerosis can be originated from the accumulation of modified cholesterol-rich lipoproteins in the arterial wall. The electronegative LDL, LDL(-), plays an important role in the pathogenesis of atherosclerosis once this cholesterol-rich lipoprotein can be internalized by macrophages, contributing to the formation of foam cells, and provoking an immune-inflammatory response. Herein, we engineered a nanoformulation containing highly pure surface-functionalized nanocapsules using a single-chain fragment variable (scFv) reactive to LDL(-) as a ligand and assessed whether it can affect the LDL(-) uptake by primary macrophages and the progression of atherosclerotic lesions in Ldlr -/- mice. The engineered and optimized scFv-anti-LDL(-)-MCMN-Zn nanoformulation is internalized by human and murine macrophages in vitro by different endocytosis mechanisms. Moreover, macrophages exhibited lower LDL(-) uptake and reduced mRNA and protein levels of IL1B and MCP1 induced by LDL(-) when treated with this new nanoformulation. In a mouse model of atherosclerosis employing Ldlr -/- mice, intravenous administration of scFv-anti-LDL(-)-MCMN-Zn nanoformulation inhibited atherosclerosis progression without affecting vascular permeability or inducing leukocytes-endothelium interactions. Together, these findings suggest that a scFv-anti-LDL(-)-MCMN-Zn nanoformulation holds promise to be used in future preventive and therapeutic strategies for atherosclerosis.

Prodigiosin Modulates the Immune Response and Could Promote a Stable Atherosclerotic Lession in C57bl/6 Ldlr-/- Mice.

Atherosclerosis is a chronic inflammatory disease, whose progression and stability are modulated, among other factors, by an innate and adaptive immune response. Prodiginines are bacterial secondary metabolites with antiproliferative and immunomodulatory activities; however, their effect on the progression or vulnerability of atheromatous plaque has not been evaluated. This study assessed the therapeutic potential of prodigiosin and undecylprodigiosin on inflammatory marker expression and atherosclerosis. An in vitro and in vivo study was carried out. Migration, low-density lipoprotein (LDL) uptake and angiogenesis assays were performed on cell types involved in the pathophysiology of atherosclerosis. In addition, male LDL receptor null (Ldlr-/-) C57BL/6J mice were treated with prodigiosin or undecylprodigiosin for 28 days. Morphometric analysis of atherosclerotic plaques, gene expression of atherogenic factors in the aortic sinus and serum cytokine quantification were performed. The treatments applied had slight effects on the in vitro tests performed, highlighting the inhibitory effect on the migration of SMCs (smooth muscle cells). On the other hand, although no significant difference in atherosclerotic plaque progression was observed, gene expression of IL-4 and chemokine (C-C motif) ligand 2 (Ccl2) was downregulated. In addition, 50 µg/Kg/day of both treatments was sufficient to inhibit circulating tumor necrosis factor alpha (TNF-α), interleukin-2 (IL-2) and interferon-gamma (IFN-γ) in serum. These results suggested that prodigiosin and undecylprodigiosin modulated inflammatory markers and could have an impact in reducing atherosclerotic plaque vulnerability.

Air pollution impairs recovery and tissue remodeling in a murine model of acute lung injury.

Evidence regarding the impact of air pollution on acute respiratory distress syndrome (ARDS) is limited, and most studies focus on ARDS onset. Our study aimed to evaluate whether exposure to fine particulate matter interferes with lung recovery and remodeling in a murine model of acute lung injury. Forty-eight mice received nebulized LPS or the vehicle (controls). Blood, BALF, lungs and spleen were collected after 5 weeks of exposure to either PM2.5 (PM and LPS + PM group) or filtered air (control and LPS5w groups). Inflammatory cells and cytokines were assessed in the blood, BALF, lungs and spleen. Stereological analyses and remodeling assessments were performed by histology. The LPS + PM group showed increased BALF leukocytes, characterized by increased macrophages, increased IL-1ß and IL-6 levels, anemia and thrombocytopenia. Moreover, we also observed septal thickening, decreased alveolar air space total volume and, septa surface density. Finally, regarding tissue remodeling, we observed elastosis of the lung parenchyma, and unlike in the LPS5w group, we did not observe fibrosis in the LPS + PM group. In conclusion, the delayed inflammation resolution due to subchronic exposure to PM2.5 could be influenced by low systemic and local lymphocyte counts, which lead to impaired lung injury recovery and tissue remodeling.

Notifiable Diseases Information System (SINAN): main features of tuberculosis notification and data analysis. / Sistema de Informação de Agravos de Notificação (Sinan): principais características da notificação e da análise de dados relacionada à tuberculose.

The Notifiable Diseases Information System (SINAN) enables knowledge of the profile of people with active tuberculosis (TB) in a country of continental dimensions such as Brazil. Available in all Brazilian municipalities and states, the system enables continuous consolidation of data, evaluation and monitoring of actions related to TB control in the country. The purpose of this paper is to present the specificities of SINAN-Net related to TB, including the follow-up screen, the record linkage and the follow-up report. Additionally, we describe the main variables and indicators and the challenges and limitations of the system.

O Sistema de Informação de Agravos de Notificação (Sinan) possibilita conhecer o perfil das pessoas com tuberculose (TB) ativa em um país continental como o Brasil. Disponível em todos os municípios e estados, o sistema permite contínua consolidação dos dados, avaliação e monitoramento das ações relacionadas ao controle da doença no país. O objetivo deste estudo foi apresentar as especificidades do Sinan-Net referentes à TB, entre elas a tela de acompanhamento, a rotina de vinculação e o boletim de acompanhamento. Adicionalmente, são descritas as principais variáveis e indicadores, os desafios e limitações do sistema.

El Sistema de Información de Agravamientos de Notificación (Sinan) posibilita conocer el perfil de las personas con tuberculosis (TB) activa en un país continental como Brasil. Disponible en todos los municipios y estados, el sistema posibilita una continua consolidación de los datos, evaluación y monitoreo de las acciones relacionadas al control de la enfermedad en el país. El objetivo de este trabajo es presentar las especificidades del Sinan-Net con relación a la TB, entre ellas la pantalla de acompañamiento, la rutina de vinculación y el boletín de acompañamiento. Adicionalmente, describimos las principales variables e indicadores y los desafíos y limitaciones del sistema.

Minimally Invasive Cardiac Surgery versus Sternotomy - Pain Investigation

Abstract Background: Treatment of postoperative (PO) pain is essential after surgery, as it contributes to a faster rehabilitation. Assessment of PO pain after minimally invasive (MI) surgery has not been regularly addressed, especially when compared with median sternotomy (MS). Objective: This study aims to evaluate the intensity of thoracic pain in the PO period in patients subjected to MI surgery and MS. Methods: This study compared the intensity of thoracic pain in 34 patients subjected to minimally invasive (MI; n = 17) and median sternotomy (MS; n = 17) from June 2015 to June 2016. The intensity and sites of pain in the PO period, assessed using the visual numeric pain scale, and the need for pain medications were analyzed using the Student's t-test and the z test, with confidence level of 95% (p < 0.05). Results: Almost all patients reported pain on the third PO day (MS = 94.1% and MI = 88.2%; p = 0.5410). On the seventh PO day, there were significantly more patients free of pain in the group of patients subjected to the MI procedure (MS = 94.1% and MI = 64.7%; p = 0.0341). also, these patients reported fewer pain sites (3rd PO day: MS = 3.2 ± 1.5; MI = 1.5 ± 1.2; p = 0.001; 7th PO day: MS = 3.1 ± 1.4; MI = 0.9 ± 0.9; p = 0.000). Patients undergoing MS reported higher pain intensity and longer lasting pain (3rd PO: MS = 4.8 ± 2.2; MI = 3.0 ± 1.6; 7th PO: MS = 5.3 ± 2.0; MI = 1.2 ± 1.3; p = 0.001), with no difference in pain intensity between the third and the seventh PO days (p = 0.4931). In addition, patients subjected to MI procedure had a significant decrease in pain intensity from the third to the seventh PO days (p = 0.001). Conclusion: According to these results, we concluded that a MI procedure leads to lower intensity of pain in the PO period (from the third PO day on) when compared to a MS; also, patients undergoing MI patients reported fewer pain sites.

Proinflammatory Action of a New Electronegative Low-Density Lipoprotein Epitope.

The electronegative low-density lipoprotein, LDL (-), is an endogenously modified LDL subfraction with cytotoxic and proinflammatory actions on endothelial cells, monocytes, and macrophages contributing to the progression of atherosclerosis. In this study, epitopes of LDL (-) were mapped using a phage display library of peptides and monoclonal antibodies reactive to this modified lipoprotein. Two different peptide libraries (X6 and CX8C for 6- and 8-amino acid-long peptides, respectively) were used in the mapping. Among all tested peptides, two circular peptides, P1A3 and P2C7, were selected based on their high affinities for the monoclonal antibodies. Small-angle X-ray scattering analysis confirmed their structures as circular rings. P1A3 or P2C7 were quickly internalized by bone marrow-derived murine macrophages as shown by confocal microscopy. P2C7 increased the expression of TNFα, IL-1 ß and iNOS as well as the secretion of TNFα, CCL2, and nitric oxide by murine macrophages, similar to the responses induced by LDL (-), although less intense. In contrast, P1A3 did not show pro-inflammatory effects. We identified a mimetic epitope associated with LDL (-), the P2C7 circular peptide, that activates macrophages. Our data suggest that this conformational epitope represents an important danger-associated molecular pattern of LDL (-) that triggers proinflammatory responses.

Early and late pulmonary effects of nebulized LPS in mice: An acute lung injury model.

BACKGROUND AND OBJECTIVE: Acute respiratory distress syndrome (ARDS) has a high mortality rate of 35-46% depending on its severity. Animal models are crucial to better understand the pathophysiology of diseases, including ARDS. This study presents a feasible animal model of acute lung injury (ALI) using nebulized lipopolysaccharide (LPS) in a non-invasive approach, focusing on its short and long-term effects. METHODS: Mice received nebulized LPS or vehicle only (control group). Blood, BALF and lung tissue were collected 24 hours (LPS 24h) or 5 weeks (LPS 5w) after the nebulized LPS-induced lung injury. Inflammatory cytokines were assessed in the blood serum, BALF and lung tissue. Stereological analyses and remodeling changes were assessed by histology and immunohistochemistry at the specified time points. RESULTS: The LPS 24h group showed increased pro-inflammatory cytokine levels, intense cell influx, increased total septal volume, septal thickening and decreased surface density of the alveolar septa. The LPS 5w group showed persistent lung inflammation, septal thickening, increased total lung volume, accentuated collagen deposition, especially of collagen type I, and decreased MMP-2 protein expression. CONCLUSION: We present a feasible, reproducible and non-invasive nebulized-LPS animal model that allows the assessment of both the acute and late phases of acute lung injury. The presence of lung remodeling with collagen deposition after 5 weeks makes it useful to study the pathophysiology, complications, and possible therapeutic intervention studies that aim to understand and reduce pulmonary fibrosis in the late phases of ALI.

A nanoformulation containing a scFv reactive to electronegative LDL inhibits atherosclerosis in LDL receptor knockout mice.

Atherosclerosis is a chronic inflammatory disease responsible for the majority of cases of myocardial infarction and ischemic stroke. The electronegative low-density lipoprotein, a modified subfraction of native LDL, is pro-inflammatory and plays an important role in atherogenesis. To investigate the effects of a nanoformulation (scFv anti-LDL(-)-MCMN-Zn) containing a scFv reactive to LDL(-) on the inhibition of atherosclerosis, its toxicity was evaluated in vitro and in vivo and further it was also administered weekly to LDL receptor knockout mice. The scFv anti-LDL(-)-MCMN-Zn nanoformulation did not induce cell death in RAW 264.7 macrophages and HUVECs. The 5mg/kg dose of scFv anti-LDL(-)-MCMN-Zn did not cause any typical signs of toxicity and it was chosen for the evaluation of its atheroprotective effect in Ldlr(-/-) mice. This nanoformulation significantly decreased the atherosclerotic lesion area at the aortic sinus, compared with that in untreated mice. In addition, the Il1b mRNA expression and CD14 protein expression were downregulated in the atherosclerotic lesions at the aortic arch of Ldlr(-/-) mice treated with scFv anti-LDL(-)-MCMN-Zn. Thus, the scFv anti-LDL(-)-MCMN-Zn nanoformulation inhibited the progression of atherosclerotic lesions, indicating its potential use in a future therapeutic strategy for atherosclerosis.

Polyphenols from Chilean Propolis and Pinocembrin Reduce MMP-9 Gene Expression and Activity in Activated Macrophages.

Polyphenols from diverse sources have shown anti-inflammatory activity. In the context of atherosclerosis, macrophages play important roles including matrix metalloproteinases synthesis involved in degradation of matrix extracellular components affecting the atherosclerotic plaque stability. We prepared a propolis extract and pinocembrin in ethanol solution. Propolis extract was chemically characterized using LC-MS. The effect of treatments on gene expression and proteolytic activity was measured in vitro using murine macrophages activated with LPS. Cellular toxicity associated with both treatments and the vehicle was determined using MTT and apoptosis/necrosis detection assays. MMP-9 gene expression and proteolytic activity were measured using qPCR and zymography, respectively. Thirty-two compounds were identified in the propolis extract, including pinocembrin among its major components. Treatment with either ethanolic extract of propolis or pinocembrin inhibits MMP-9 gene expression in a dose-dependent manner. Similarly, an inhibitory effect was observed in proteolytic activity. However, the effect showed by ethanolic extract of propolis was higher than the effect of pinocembrin, suggesting that MMP-9 inhibition results from a joint contribution between the components of the extract. These data suggest a potential role of polyphenols from Chilean propolis in the control of extracellular matrix degradation in atherosclerotic plaques.

Conhecimento e atitude dos profissionais de enfermagem sobre avaliação e tratamento da dor neonatal / Nursing professionals' knowledge and attitude related to assessment and treatment of neonatal pain

Objetivo do estudo foi verificar o conhecimento e atitude dos profissionais de enfermagem de uma unidade neonatal quanto à avaliação e tratamento da dor aguda em recém-nascidos. Estudo descritivo exploratório realizado com 26 profissionais de enfermagem de uma unidade neonatal no Centro-Oeste, Brasil. A maioria dos profissionais identificou ao menos uma escala de avaliação da dor neonatal (76,9%). As estratégias para alívio da dor selecionadas pelos profissionais foram diminuição de ruído e luminosidade (84,6%), posição canguru (76,9%) e colo (76,9%). Menos da metade (28,0%) dos profissionais afirmou registrar sempre ou frequentemente o escore de dor no plantão, e 64,0% referiu utilizar estratégias de alívio da dor. A maioria dos profissionais demonstrou conhecimento quanto ao manejo da dor, apesar de existirem lacunas. A aplicação das escalas e medidas de alívio da dor mostrou-se inadequada, seja pelo pouco uso, não utilização da melhor evidência disponível ou falta de registro

The objective of the study was to verify the knowledge and attitude of nursing professionals from a neonatal unit regarding assessment and treatment of acute procedural pain in newborns. We conducted an exploratory descriptive study with 26 nursing professionals from aneonatal unit at the Center-Western region of Brazil. Most professionals identified at least one assessment scale for neonatal pain (76.9%). Strategies to relieve pain chosen by professionals were decrease of noise and light (84.6%), kangaroo position (76.9%) and rocking (76.9%). Less than half (28.0%) of professionals affirmed to always or frequently register pain scores during their shift, and 64.0% referred to use pain relief strategies. Most professionals seemed knowledgeable regarding pain management despite of gaps. The application of scales and measures for pain relief seemed inadequate due to its little use, lack of use of the best evidence available or, by the lack of documentation.

Efeitos do fragmento variável de cadeia única anti-LDL eletronegativa vetorizado em nanocápsulas na aterosclerose experimental / Effects of an anti-LDL(-) single chain fragment variable vectorized in nanocapsules in experimental atherosclerosis

As doenças cardiovasculares são a principal causa de mortalidade no mundo. A aterosclerose é a base fisiopatológica dessas doenças, sendo definida como um processo crônico-inflamatório multifatorial, resultando da interação de diferentes células como linfócitos, macrófagos, células endoteliais e células musculares lisas na parede arterial. A lipoproteína de baixa densidade eletronegativa [LDL(-)], uma subfração modificada da LDL nativa, desempenha um papel-chave na aterosclerose, uma vez que as modificações sofridas por esta partícula são capazes de induzir o acúmulo de ésteres de colesterol em macrófagos e a subsequente formação de células espumosas. O sistema imunológico é crucial no processo aterogênico e estratégias terapêuticas direcionadas à imunoregulação deste processo têm sido utilizadas como novas alternativas tanto na prevenção do desenvolvimento quanto da progressão desta doença. Dentre essas estratégias, destaca-se o uso de fragmentos de anticorpos como o scFv (do inglês, single chain fragment variable), que podem ainda estar conjugados a nanopartículas com o intuito de aumentar sua eficiência de ação no organismo. Diante do papel da LDL(-) na aterosclerose, este projeto objetivou avaliar os efeitos in vitro e in vivo de um sistema nanoestruturado contendo fragmentos scFv anti-LDL(-) derivatizados na superfície de nanocápsulas sobre macrófagos murinos e humanos primários e em camundongos knockout para o gene do receptor da LDL (Ldlr-/-) no desenvolvimento e na progressão dessa doença. Demonstrou-se que o tratamento de macrófagos com a formulação scFv anti-LDL(-)-MCMN-Zn diminuiu de forma significativa a captação de LDL(-), assim como a expressão de IL-1ß (mRNA e proteína) e MCP-1 (mRNA). Foi demonstrada a internalização da nanoformulação pelos macrófagos via diferentes mecanismos de endocitose, demonstrando seu potencial uso como carreador de fármacos. In vivo, a nanoformulação diminuiu de forma significativa a área da lesão aterosclerótica em camundongos Ldlr-/- submetidos à avaliação pela técnica de tomografia por emissão de pósitrons (do inglês, PET), utilizando o radiotraçador 18F-FDG (18F-desoxiglicose), associada à tomografia computadorizada (CT) com agente de contraste iodado, além da análise morfométrica das lesões no arco aórtico. O conjunto dos resultados obtidos evidenciou a ação ateroprotetora da formulação scFv anti-LDL(-)-MCMN-Zn, reforçando seu potencial como estratégia terapêutica na aterosclerose

Cardiovascular diseases are the leading cause of mortality worldwide. Atherosclerosis is the pathophysiological basis of these diseases, defined as a chronic inflammatory multifactorial process, resulting from the interaction of several cells such as lymphocytes macrophages, endothelial cells and smooth muscle cells within the arterial wall. The electronegative low-density lipoprotein [LDL(-)], a modified subfraction of native LDL, plays a key role in atherosclerosis, since its modifications are capable of inducing the accumulation of cholesteryl esters in macrophages and the subsequent foam cells formation. The immune system is crucial in atherogenic process and therapeutic strategies directed to the immunoregulation of this process have been used as a new alternative in the prevention of the development as well as the progression of this disease. Among these strategies, it is the use of antibody fragments such as scFv (single chain fragment variable), which may be also conjugated to nanoparticles in order to increase their efficiency in the body. Given the role of LDL(-) in atherosclerosis, the aim of this project was to evaluate the in vitro and in vivo effects of a nanostructured system containing scFv anti-LDL(-) fragments derivatized on the surface of nanocapsules on murine and human primary macrophages and in the development and progression of the disease in LDL receptor knockout mice (Ldlr-/-). It was demonstrated that the treatment of macrophages with scFv anti-LDL(-)-MCMN-Zn formulation significantly decreases the uptake of LDL(-) and the expression IL-1ß (mRNA and protein) and MCP-1 (mRNA). Moreover, the internalization of the nanoformulation by macrophages through different endocytosis mechanisms was shown, demonstrating its potential use as a nanocarrier. In vivo, the nanoformulation decreased the area of atherosclerotic lesions in Ldlr-/- mice evaluated by positron emission tomography with 18F-FDG associated with computed tomography with iodinated contrast agent (PET/CT), besides the lesion morphometric analysis at the aortic arch Thus, these data provide evidence of the atheroprotection action of the ateroprotection action of the scFv anti-LDL(-)-MCMN-Zn formulation, suggesting its promising use as a therapeutic strategy for atherosclerosis

AMP-Activated Protein Kinase Interacts with the Peroxisome Proliferator-Activated Receptor Delta to Induce Genes Affecting Fatty Acid Oxidation in Human Macrophages.

AMP-activated protein kinase (AMPK) maintains energy homeostasis by suppressing cellular ATP-consuming processes and activating catabolic, ATP-producing pathways such as fatty acid oxidation (FAO). The transcription factor peroxisome proliferator-activated receptor δ (PPARδ) also affects fatty acid metabolism, stimulating the expression of genes involved in FAO. To question the interplay of AMPK and PPARδ in human macrophages we transduced primary human macrophages with lentiviral particles encoding for the constitutively active AMPKα1 catalytic subunit, followed by microarray expression analysis after treatment with the PPARδ agonist GW501516. Microarray analysis showed that co-activation of AMPK and PPARδ increased expression of FAO genes, which were validated by quantitative PCR. Induction of these FAO-associated genes was also observed upon infecting macrophages with an adenovirus coding for AMPKγ1 regulatory subunit carrying an activating R70Q mutation. The pharmacological AMPK activator A-769662 increased expression of several FAO genes in a PPARδ- and AMPK-dependent manner. Although GW501516 significantly increased FAO and reduced the triglyceride amount in very low density lipoproteins (VLDL)-loaded foam cells, AMPK activation failed to potentiate this effect, suggesting that increased expression of fatty acid catabolic genes alone may be not sufficient to prevent macrophage lipid overload.

New strategy to surface functionalization of polymeric nanoparticles: one-pot synthesis of scFv anti-LDL(-)-functionalized nanocapsules.

PURPOSE: In general, the surface functionalization of polymeric nanoparticles is carried out by covalently bounding ligands to the nanoparticle surface. This process can cause a lack or decrease of the ligand specificity to its target receptor, besides the need of purification steps. We proposed a ligand-metal-chitosan-lecithin complex as a new strategy to functionalize the surface of biodegradable nanoparticles. METHODS: One pot synthesis of scFv anti-LDL(-)-functionalized nanocapsules was carried out by self-assembly and interfacial reactions. Particle sizing techniques, lipid peroxidation and molecular recognition by enzyme linked immuno sorbent assays were carried out. RESULTS: The selected formulation had unimodal size distribution with mean diameter of about 130 nm. The metals in the complex did not enhance the oxidative stress, and the scFv anti-LDL(-)-functionalized nanocapsules recognized LDL(-) and did not react with native LDL indicating the maintenance of the active site of the fragment. CONCLUSIONS: The one pot synthesis, using the ligand-metal-chitosan-lecithin complex to functionalize the surface of the biodegradable nanocapsules, maintained the active site of the antibody fragment making the device interesting for applications in nanomedicine.

Identification of microRNAs involved in the modulation of pro-angiogenic factors in atherosclerosis by a polyphenol-rich extract from propolis.

New vessel formation plays a critical role in the progression and vulnerability of atherosclerotic lesions. It has been shown that polyphenols from propolis attenuate the progression of atherosclerosis and also exert inhibitory effects on angiogenic factors. However, the mechanisms underlying these effects are not completely understood. Thus, this study aimed to identify microRNAs (miRNAs) involved in the modulation of pro-angiogenic factors in the atherosclerotic plaques of LDL receptor gene knockout mice treated with a polyphenol-rich extract of Chilean propolis. The progression of the atherosclerotic lesions was significantly attenuated in treated mice compared with control mice. Using microarray analysis and a bioinformatic approach, we identified 29 differentially expressed miRNAs. Many of these miRNAs were involved in biological processes associated with angiogenesis, such as the cell cycle, cell migration, cell growth and proliferation. Among them, three miRNAs (miR-181a, miR-106a and miR-20b) were over-expressed and inversely related to the expression of Vegfa (vascular endothelial growth factor A) and Hif1a (hypoxia inducible factor 1 alpha). In addition, VEGF-A protein expression was attenuated in histological sections obtained from the aortic sinuses of treated mice. VEGFA is a key pro-angiogenic factor in atherosclerotic plaques, and Hif1a, which is expressed in the necrotic nucleus of the atheroma, is its main inducer. We found a correlation between the over-expression of miR-181a, miR-106a and miR-20b and their target genes, Hif1a and Vegfa, which is consistent with attenuation of the atherosclerotic lesion. In conclusion, our data analysis provides evidence that the anti-angiogenic effects of polyphenols from Chilean propolis can be modulated by miRNAs, in particular miR-181a, miR-106a and miR-20b.

Cloning and expression of an anti-LDL(-) single-chain variable fragment, and its inhibitory effect on experimental atherosclerosis.

The in vivo modified forms of low-density lipoprotein (LDL) are important for the formation of foam cells and as mediators of the immuno-inflammatory process involved in the progression of atherosclerosis. Electronegative LDL, LDL(-), is a LDL subfraction with pro-inflammatory properties that is present in human blood. To investigate possible atheroprotective effects, an anti-LDL(-) single-chain variable fragment (scFv) was expressed in the methylotrophic yeast Pichia pastoris and its activity was evaluated in vitro against macrophages and in experimental atherosclerosis in Ldlr(-/-) mice. The recombinant 2C7 scFv was produced in a yield of 9.5 mg of protein/L. The specificity and affinity of purified 2C7 scFv against LDL(-) was confirmed by ELISA. To assess the activity of 2C7 scFv on foam cell formation, RAW 264.7 macrophages were exposed to LDL(-) in the presence or absence of 2C7 scFv. The 2C7 scFv inhibited the uptake of LDL(-) by macrophages in a dose-dependent manner, and internalization of LDL(-) by these cells was found to be mediated by the CD36 and CD14 receptor. In addition, compared with untreated cells, lipid accumulation in macrophages was decreased, and the expression of Cd36, Tlr-4 and Cox-2 was downregulated in macrophages treated with 2C7 scFv. Importantly, compared with untreated mice, the treatment of Ldlr(-/-) mice with 2C7 scFv decreased the atherosclerotic lesion area at the aortic sinus. In conclusion, our data show that 2C7 scFv inhibits foam cell formation and atherosclerotic plaque development by modulating the expression of genes relevant to atherogenesis. These results encourage further use of this antibody fragment in the development of new therapeutic strategies that neutralize the pro-atherogenic effects of LDL(-).

Análise da retirada de registros repetidos de tuberculose nos indicadores epidemiológicos da I regional de saúde do estado de Pernambuco / Analysis of the removal of duplicate records of tuberculosis epidemiological markers of I regional health state of Pernambuco

A tuberculose é um importante e preocupante problema de saúde pública no Brasil. O país é responsável por 35 por cento dos casos de tuberculose notificados anualmente na Região das Américas. O estado de Pernambuco ocupa o 3º lugar em taxa de incidência no âmbito nacional. O estudo tem por objetivo analisar o resultado da retirada de registros repetidos de tuberculose nos indicadores epidemiológicos da I regional de saúde do estado de Pernambuco, identificando os municípios que apresentam maior número de registros repetidos no seu banco de dados. Foram analisados todos os registros de casos de tuberculose notificados no período de janeiro de 2001 a julho de 2010 presentes no relatório de duplicidade, no banco de dados congelado em julho/2010 do Sistema de Informações de Agravos de Notificação. Do total de registros repetidos (1.476), 94,3 por cento eram casos com duplos registros, 4,9 por cento notificações em triplos registros e 0,8 por cento casos agrupados em quádruplos registros. Do resultado das rotinas executadas 33 por cento foi de exclusão de fichas, 29,3 por cento de vinculações e 37,7 por cento da rotina de não listar. Nas taxas de incidência anuais de TB observou-se redução ao longo dos anos estudados em grande parte dos municípios. Na I regional, os anos de 2001, 2002 e 2003 apresentaram as maiores reduções nas taxas de incidência, 2,9 por cento; 1,4 por cento e 1,7 por cento, respectivamente. Os anos de 2005 e 2007 apresentaram as menores reduções, ambos com 0,3 por cento. Os resultados sugerem que os dados estudados são uma representação confiável da realidade do agravo na I regional de saúde de Pernambuco, o que leva a ótica da problematização dos baixos indicadores no estado para outros campos, que não apenas o sistema de informação. Recomenda-se a execução da análise de duplicidades como rotina, visto a necessidade de dados epidemiológicos confiáveis para a tomada de decisões prioritárias para os programas de controle da tuberculose...

Profile of audiometric thresholds and tympanometric curve of elderly patients.

AIM: to analyze the audiological profile of elderly patients seen in a clinic from an audiology school clinic in the city of Belo Horizonte. METHODS: we studied all the charts from the patients who underwent audiologic assessment from April of 2004 and August of 2007 in an audiology clinic in the city of Belo Horizonte. RESULTS: We studied the 313 audiological tests from patients 60 years of age or over. The results from the audiological evaluations as to the type of hearing loss were: auditory thresholds within normal standards - 22.28%; sensorineural hearing loss - 60.62%; mixed hearing loss - 14.70%, conductive hearing loss - 2.40%. The level varied between normal and profound. As to the tympanometry, 83.22% had the type A curve, and the other types of curves obtained made up a total of 16.3%. The percentage of individuals who did not undergo the test was 0.48%. 1.76% of the patients who had unilateral hearing loss and 98.24% had bilateral hearing loss. CONCLUSIONS: we found a greater prevalence of sensorineural hearing loss, and the degree of the loss varied from mild to profound, with a prevalence of the moderate degree.

Perfil dos limiares audiométricos e curvas timpanométricas de idosos / Profile of audiometric thresholds and tympanometric curve of elderly patients

OBJETIVO: Traçar o perfil audiológico dos idosos atendidos em uma clínica escola da cidade de Belo Horizonte. MÉTODOS: Foram analisados todos os prontuários de pacientes que realizaram avaliação audiológica no período de Abril de 2004 a Agosto de 2007 em um Centro Clínico de Fonoaudiologia da cidade de Belo Horizonte. RESULTADOS: Foram analisados 313 exames audiológicos de pacientes acima de 60 anos de idade. Os resultados das avaliações audiológicas quanto ao tipo da perda auditiva foram: limiares auditivos dentro dos padrões de normalidade - 22,28 por cento; perda auditiva neurossensorial - 60,62 por cento; perda auditiva mista - 14,70 por cento, perda auditiva condutiva - 2,40 por cento. O grau variou de normal a profundo. Quanto à timpanometria, prevaleceu com 83,22 por cento a curva tipo A, sendo que os demais tipos de curvas obtiveram um total de 16,3 por cento. A porcentagem dos indivíduos que não realizou o exame foi de 0,48 por cento. Dos pacientes que apresentaram perda auditiva foram unilaterais 1,76 por cento e 98,24 por cento bilaterais. CONCLUSÕES: Foi constatada uma maior prevalência de perda auditiva do tipo neurossensorial, sendo que o grau de perda variou de leve a profundo, com maior prevalência do grau moderado.

AIM: to analyze the audiological profile of elderly patients seen in a clinic from an audiology school clinic in the city of Belo Horizonte. METHODS: we studied all the charts from the patients who underwent audiologic assessment from April of 2004 and August of 2007 in an audiology clinic in the city of Belo Horizonte. RESULTS: We studied the 313 audiological tests from patients 60 years of age or over. The results from the audiological evaluations as to the type of hearing loss were: auditory thresholds within normal standards - 22.28 percent; sensorineural hearing loss - 60.62 percent; mixed hearing loss - 14.70 percent, conductive hearing loss - 2.40 percent. The level varied between normal and profound. As to the tympanometry, 83.22 percent had the type A curve, and the other types of curves obtained made up a total of 16.3 percent. The percentage of individuals who did not undergo the test was 0.48 percent. 1.76 percent of the patients who had unilateral hearing loss and 98.24 percent had bilateral hearing loss. CONCLUSIONS: we found a greater prevalence of sensorineural hearing loss, and the degree of the loss varied from mild to profound, with a prevalence of the moderate degree.