Atractylenolide III alleviates sepsis-mediated lung injury via inhibition of FoxO1 and VNN1 protein

ABSTRACT Purpose: To evaluate the influence of atractylenolide (Atr) III on sepsis-induced lung damage. Methods: We constructed a mouse sepsis model through cecal ligation and puncture. These mice were allocated to the normal, sepsis, sepsis + Atr III-L (2 mg/kg), as well as Atr III-H (8 mg/kg) group. Lung injury and pulmonary fibrosis were accessed via hematoxylin-eosin (HE) and Masson's staining. We used terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and flow cytometry for detecting sepsis-induced lung cell apoptosis. The contents of the inflammatory cytokines in lung tissue were measured via enzyme-linked immunosorbent assay (ELISA). Results: Atr III-H did not only reduce sepsis-induced lung injury and apoptosis level, but also curbed the secretion of inflammatory factors. Atr III-H substantially ameliorated lung function and raised Bcl-2 expression. Atr III-H eased the pulmonary fibrosis damage and Bax, caspase-3, Vanin-1 (VNN1), as well as Forkhead Box Protein O1 (FoxO1) expression. Conclusions: Atr III alleviates sepsis-mediated lung injury via inhibition of FoxO1 and VNN1 protein.

Development and Characterization of Poly-ε -caprolactone Nanocapsules Containing β -carotene Using the Nanoprecipitation Method and Optimized by Response Surface Methodology

Abstract Nanoparticles demonstrate an important role in the protection of bioactive compounds from external factors such as temperature, oxygen and light. In this study, poly-ε-caprolactone (PCL) nanoparticles entrapped β-carotene was produced using the nanoprecipitation method. Firstly, was evaluated the lipophilic surfactant effect and carrier agent of the active compound in the nanocapsules formulation. After choosing the most stable formulation, the nanocapsules production was optimized using β-carotene, caprylic/capric triglycerides (CCT) and soybean lecithin. Response surface methodology (RSM) was adopted to evaluate the influence of soy lecithin concentration, volume of CCT and β-carotene concentration in the particle size, zeta potential, polydispersity index (PDI), encapsulation efficiency and recovery. Formulations containing soy lecithin and CCT demonstrated better stability comparing to the other formulations tested. The nanoparticle formulations presented an optimized particle size below 200 nm, PDI lower than 0.1 and encapsulation efficiency above 95%. Based on the results obtained, the optimum conditions to prepare PCL nanocapsules were 0.2160 mg/mL of β-carotene, 232.42 μL of CCT and 2.59 mg/mL of soy lecithin, suggesting an applicability to promote controlled released of β-carotene in food system.

Relationship Between Parameters of Development and Functional Compounds of Yacon Leaves

Abstract Yacon is a tuberous root from the Andean region being increasingly grown across the world due to the low caloric values of their roots and the functional properties of extractions of its leaves. However, there is still a gap in the knowledge of how the plant develops, and if physical and chemical changes are noticed regarding maturity. The subject of this work was to investigate the dynamics of a group of parameters and to establish correlations across them. To achieve this goal, leaves collected from three different parts of the plant in three months were assessed regarding size (plant height and leaf area), color and the presence of sesquiterpene lactones. Different methods of extraction were also studied and the total phenolic content was analyzed. The analysis of the results revealed different patterns in the quantity, size and leaf distribution according to the age of the plant. From three different methods of extraction studied, decoction seems to be the most appropriate one to obtain phenolic compounds with greater yield and safety. Besides, the greenness of yacon leaves showed a linear correlation to the total phenolic content, being a simple and promising estimator of the corresponding bioactive group. Sesquiterpene lactones were identified in all extracts, indicating the ease of their extractability even in simple procedures of tea-making.

Cardioprotective effect of lipstatin derivative orlistat on normotensive rats submitted to cardiac ischemia and reperfusion

Abstract Purpose: To evaluate in vivo animal model of cardiac ischemia/reperfusion the cardioprotective activity of pancreatic lipase inhibitor of the orlistat. Methods: Adult male Wistar rats were anesthetized, placed on mechanical ventilation and underwent surgery to induce cardiac I/R by obstructing left descending coronary artery followed by reperfusion to evaluation of ventricular arrhythmias (VA), atrioventricular block (AVB) and lethality (LET) with pancreatic lipase inhibitor orlistat (ORL). At the end of reperfusion, blood samples were collected for determination of triglycerides (TG), very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL), lactate dehydrogenase (LDH), creatine kinase (CK), and creatine kinase-MB (CK-MB). Results: Treatment with ORL has been able to decrease the incidence of VA, AVB and LET. Besides that, treatment with ORL reduced serum concentrations of CK and LDL, but did not alter the levels of serum concentration of TG, VLDL and HDL. Conclusion: The reduction of ventricular arrhythmias, atrioventricular block, and lethality and serum levels of creatine kinase produced by treatment with orlistat in animal model of cardiac isquemia/reperfusion injury suggest that ORL could be used as an efficient cardioprotective therapeutic strategy to attenuate myocardial damage related to acute myocardial infarction.

Effect of phospholipase A2 inhibitors during infection caused by Leishmania (Leishmania) amazonensis

Lipid metabolites play an important role in parasite differentiation and virulence. Studies have revealed that Leishmania sp. uses prostaglandins to evade innate barriers, thus enabling the parasites to survive inside immune cells. Despite the role of the enzyme Phospholipase A2 (PLA2) in prostaglandins production, few studies have investigated the role of parasite PLA2 during the interaction between L. (L.) amazonensis and the host (in vitro and in vivo) immune cells. Methods: In the present work, the leishmanicidal effect of PLA2 inhibitors, methyl arachidonyl fluorophosphonate (MAFP), bromoenol lactone (BEL) and aristolochic acid (AA) were investigated in vitro (promastigote and intracellular amastigote forms of L. (L.) amazonensis) and during in vivo infection using BALB/c mice. Results: The aforementioned inhibitors were deleterious to promastigote and amastigote forms of the L. (L.) amazonensis and were non-toxic to peritoneal macrophages from BALB/c mice. L. (L.) amazonensis-infected BALB/c mice treated with the inhibitor BEL presented decreased lesion size and skin parasitism; however, BEL treatment induced hepatotoxicity in BALB/c mice. Conclusions: Results presented herein suggested that PLA2 inhibitors altered L. (L.) amazonensis viability. In spite of liver toxicity, treatment with BEL was the most selective compound in vitro, as well in vivo, resulting in lower skin parasitism in the infected mice. These findings corroborate the role of PLA2 in parasite virulence and maintenance in vertebrate hosts, and suggest that molecules structurally related to BEL should be considered when planning compounds against Leishmania sp.(AU)

Effect of γ-lactones and γ-lactams compounds on Streptococcus mutans biofilms

Abstract Considering oral diseases, antibiofilm compounds can decrease the accumulation of pathogenic species such as Streptococcus mutans at micro-areas of teeth, dental restorations or implant-supported prostheses. Objective To assess the effect of thirteen different novel lactam-based compounds on the inhibition of S. mutans biofilm formation. Material and methods We synthesized compounds based on γ-lactones analogues from rubrolides by a mucochloric acid process and converted them into their corresponding γ-hydroxy-γ-lactams by a reaction with isobutylamine and propylamine. Compounds concentrations ranging from 0.17 up to 87.5 μg mL-1 were tested against S. mutans. We diluted the exponential cultures in TSB and incubated them (37°C) in the presence of different γ-lactones or γ-lactams dilutions. Afterwards, we measured the planktonic growth by optical density at 630 nm and therefore assessed the biofilm density by the crystal violet staining method. Results Twelve compounds were active against biofilm formation, showing no effect on bacterial viability. Only one compound was inactive against both planktonic and biofilm growth. The highest biofilm inhibition (inhibition rate above 60%) was obtained for two compounds while three other compounds revealed an inhibition rate above 40%. Conclusions Twelve of the thirteen compounds revealed effective inhibition of S. mutans biofilm formation, with eight of them showing a specific antibiofilm effect.

Squamocin, an annonaceous acetogenin, enhances naphthalene degradation mediated by Bacillus atrophaeus CN4 / Squamocin, una acetogenina annonácea, estimula la degradación de naftaleno mediada por Bacillus atrophaeus CN4

Squamocin belongs to a group of compounds called annonaceous acetogenins. They are secondary products of Annonaceae metabolism and can be isolated from Annona cherimolia seeds. This paper deals with the stimulation of biofilm formation of Bacillus atrophaeus CN4 by employing low squamocin concentrations to increase naphthalene degradation. Bacillus atrophaeus CN4, isolated from contaminated soil, has the ability to degrade naphthalene as the only source of carbon and energy. In the absence of additional carbon sources, the strain removed 69% of the initial concentration of naphthalene (approx. 0.2 mmol/l) in the first 12 h of incubation. The addition of squamocin in LB medium stimulated Bacillus atrophaeus CN4 biofilm formation and enhanced naphthalene removal. Squamocin (2.5 pg/ml) does not affect planktonic growth and therefore, the observed increases are solely due to the stimulation of biofilm formation.

Squamocin pertenece a un grupo de compuestos llamados acetogeninas annonáceas (ACG). Las ACG son productos secundarios del metabolismo de plantas de la familia Annonaceae y se pueden aislar a partir de semillas de Annona cherimola. Este artículo trata de la estimulación de la formación de biofilm de Bacillus atrophaeus CN4 mediante el empleo de bajas concentraciones de squamocin para optimizar la degradación de naftaleno. B. atrophaeus CN4, aislado de suelo contaminado, tiene la capacidad de emplear naftaleno como única fuente de carbono y energía. En ausencia de fuentes de carbono adicionales, la cepa degradó el 69% de la concentración inicial de naftaleno (aprox. 0,2 mmol/l) en las primeras 12h de incubación. La adición de squamocin en medio LB estimula la formación de biofilm y la remoción naftaleno de B. atrophaeus CN4. Squamocin (2,5 µg/ml) no afecta al crecimiento planctónico y, por lo tanto, los incrementos observados se deben únicamente a la estimulación de la formación de biofilm.

Climate conditions associated with the occurrence of antimicrobial and macrocyclic lactone residues in bulk tank milk / Condições climáticas associadas à ocorrência de resíduos de antimicrobianos e lactonas macrocíclicas em amostras de leite de tanque

The present study aimed to identify the climate condition parameters that are associated with the occurrence of antimicrobial and macrocyclic lactone residues in bulk tank milk using a multivariate principal components analysis (PCA). A total of 132 raw milk samples were collected at dairy farms in Minas Gerais State in Brazil and analyzed for 35 analytes, comprising macrocyclic lactones and antibacterials, using liquid chromatography coupled with mass spectrometry in tandem mode spectrometry. Of the 132 samples, 34 (25.76%) bulk tank milk samples were positive for at least one analyte. PCA showed that antimicrobial residues in bulk tank milk occurred less frequently on days with a higher average temperature, maximum temperature and temperature-humidity index. In contrast, relative humidity was inversely associated with antimicrobial residues in raw milk. The PCA showed that daily milk production was also related to macrocyclic lactone residues, while rainfall showed an inverse association. Thus, some climate conditions, such as average temperature, maximum temperature and temperature-humidity index, can predict the moments with lower risk of occurrence of antimicrobial residues in bulk tank milk, in contrast to relative humidity. Furthermore, the risk of macrocyclic lactone residues in bulk tank milk was higher in months with less rainfall.(AU)

O presente trabalho objetivou identificar fatores climáticos associados à ocorrência de resíduos de antimicrobianos e lactonas macrocíclicas em amostras de leite de tanque por análise multivariada de componentes principais (ACP). Para o presente trabalho, 132 amostras de leite cru foram coletadas em fazendas leiteiras localizadas no estado de Minas Gerais (Brasil) e analisadas por cromatografia líquida de alta eficiência e espectrometria de massas in tandem para detecção de 35 analitos, incluindo antimicrobianos e lactonas macrocíclicas. Das 132 amostras de leite analisadas, detectou-se pelo menos um analito em 34 (25,76%) amostras. A ACP demonstrou que a presença de resíduos de antimicrobianos no leite de tanque ocorreu menos frequentemente nos dias com maior temperatura média, temperatura máxima e índice de temperatura e umidade. Por outro lado, a umidade relativa foi inversamente associada à presença de resíduos antimicrobianos no leite. A ACP demonstrou associação entre a presença de resíduos de lactonas macrocíclicas no leite e a produção diária de leite, e a presença de resíduos de lactonas macrocíclicas ocorreu menos frequentemente nos meses com maiores índices pluviométricos. Dessa forma, conclui-se que alguns índices climáticos, como temperatura média, temperatura máxima e índice de temperatura e umidade, podem predizer períodos com maior risco de ocorrência de resíduos de antimicrobianos, em contraste com a umidade relativa. Além disso, o risco de resíduos de lactonas macrocíclicas no leite de tanque foi maior nos meses com menores índices pluviométricos.(AU)

7-epi-griffonilide, a new lactone from Bauhinia pentandra: complete 1H and 13C chemical shift assignments

ABSTRACT A new lactone, 7-epi-griffonilide (1), and six known compounds, 2, 3a - 3c, 4a and 4b, were isolated from the leaves of Bauhinia pentandra (Fabaceae). The structures elucidation of 1 and 2 were based on detailed 2D NMR techniques and spectral comparison with related compounds, leading to complete assignment of the 1H and 13C NMR spectra.

Survey of pyrethroid, macrocyclic lactone and antibacterial residues in bulk milk tank from Minas Gerais State, Brazil / Resíduos de piretróides, lactonas macrocíclicas e antimicrobianos em amostras de leite de tanque no estado de Minas Gerais

A survey of veterinary drug residues in bulk milk tank from Minas Gerais State, Brazil, was carried out through a broad scope analysis. Here, 132 raw milk samples were collected at 45 dairy farms in Minas Gerais from August 2009 to February 2010, and analyzed for 42 analytes, comprising pyrethroids, macrocyclic lactones and antibacterials, using liquid chromatography coupled with mass spectrometry in tandem mode and gas chromatography with electron capture detection. Within all milk samples, at least one veterinary drug residue was identified in 40 milk samples (30.30%) by confirmatory tests, whereas 16 samples (12.12%) showed the presence of at least two residues. With regard to the Brazilian maximum residue levels, 11 milk samples (8.33%) were non-compliant according to Brazilian Legislation. The veterinary drugs detected in the non-compliant milk samples include penicillin V (one sample), abamectin (one sample) and cypermethrin (nine samples). Furthermore, the antibacterial screening methods failed to identify most of the positive samples that were detected by confirmatory tests, leading to a large discrepancy between the screening and confirmatory antimicrobial tests. Thus, the present study indicated that the veterinary drugs residues still represents a great concern for the milk production chain.(AU)

Avaliou-se a presença de 42 analitos, incluindo piretróides, lactonas macrocíclicas e antimicrobianos em 132 amostras de leite de tanque proveniente de 45 propriedades leiteiras localizadas no Estado de Minas Gerais. Para tal, utilizou-se a cromatografia líquida acoplada a espectrofotometria de massas tandem e cromatografia gasosa com detector com captura de elétrons. Dentre todas as amostras de leite, 40 (30,30%) amostras de leite de tanque apresentaram a presença de pelo menos um analito, enquanto 16 amostras (12,12%) de leite demonstraram a presença de pelo menos dois analitos. Considerando os limites estabelecidos pela legislação brasileira, 11 amostras de leite (8,33%) seriam consideradas como não conforme. Ademais, os testes de triagem para detecção de antimicrobianos no leite não conseguiram identificar a maioria das amostras positivas nos testes confirmatórios, levando a grande discrepância entre estes testes. Desta forma, os resultados do presente estudo indicam que os períodos de descarte do leite, especialmente para piretróides, não foram plenamente respeitados por todos os produtores de leite. Além disto, uma discrepância entre os resultados dos testes confirmatórios e os testes de triagem foi observada.(AU)

Dung removal by dung beetles (Coleoptera: Scarabaeidae) and macrocyclic lactone use on cattle ranches of Yucatan, Mexico / Remoción de estiércol por escarabajos estercoleros (Coleoptera: Scarabaeinae) y uso de lactonas macrocíclicas en ranchos ganaderos de Yucatán, México

Abstract:The expanded use of macrocyclic lactones (ML) to treat endo- and ectoparasites in cattle in tropical regions, can reduce dung beetle populations, and thus interrupt the dung removal process in cattle pasture ecosystems. During the reproductive period (the rainy season) of two functional groups of dung beetles (paracoprid and telocoprid Scarabaeinae), we compared dung removal amount in ranches where ML are and are not used in Yucatan, Mexico, through exclusion traps baited with 500 g of ML-free cow dung. On each ranch, two transects (separated by 500 m) with six traps each, were set up for 24 hours. After this time, all the dung remnants in each trap were obtained and weighed in order to record the dung removal. Results showed that dung removal amounts were similar in ranches with and without ML use. Dung beetles removed 40.1 % of all cow dung weighed. Paracoprids removed 87.46 % and telocoprids 12.54 % of all the dung that was removed. Our results indicated that the ecological function of dung beetles in the pastures studied, does not seem to be affected by the ML use, and that paracoprid species removed most of the dung. For both types of ranch, further studies that take into account the population dynamics and movement of the most important dung beetle species in the region are required, coupled with laboratory studies evaluating the effect of ML on their reproductive success. This could give some light on the effect of ML on the ecological function of this important insect group in the sustainability of cattle production systems. Rev. Biol. Trop. 64 (3): 945-954. Epub 2016 September 01.

ResumenLa expansión en el uso de lactonas macrocíclicas (LM) para el tratamiento de endo y ectoparásitos del ganado en las regiones tropicales puede reducir las poblaciones de escarabajos del estiércol, interrumpiendo así el proceso de eliminación de estiércol de ganado en los pastizales. Durante el período reproductivo (época de lluvias) de dos grupos funcionales de escarabajos coprófagos (paracópridos y telecópridos), se comparó la cantidad removida de estiércol usando trampas de exclusión cebadas con 500 g de estiércol de vaca libre de LM en dos ranchos donde se usan y en dos donde no se usan LM, en la península de Yucatán, México. En cada rancho se establecieron dos transectos (separados por 500 m) con seis trampas cada uno, las cuales estuvieron activas durante 24 horas. Después de este tiempo, todos los restos de estiércol en cada trampa se pesaron para registrar la remoción. Los resultados mostraron que las cantidades de remoción fueron similares en ranchos con y sin uso de LM. Los escarabajos estercoleros removieron 40.1 % del peso total del excremento. Los paracópridos removieron 87.46 % y los telecópridos 12.54 % del total de excremento removido. Los resultados indican que la función ecológica de los escarabajos estercoleros en los potreros estudiados no parece verse afectada por el uso de LM y que las especies paracórpidas remueven la mayor parte del excremento. Se requiere hacer más estudios en ambos tipos de ranchos, en los que se tome en cuenta la dinámica poblacional y el movimiento de las especies más importantes de la región, acoplados a estudios de laboratorio que evalúen el efecto de las LM sobre el éxito reproductivo, y de esta manera esclarecer el efecto de las LM sobre la función ecológica de este grupo de insectos tan importante para la sustentabilidad de los sistemas ganaderos.

Effects of budlein A on human neutrophils and lymphocytes

ABSTRACT Sesquiterpene lactones (SLs) are the active constituents of a variety of medicinal plants used in traditional medicine for the treatment of inflammatory diseases and other ailments. Objective In this study, we evaluated whether budlein A modulates the activation of innate and adaptive immune cells such as neutrophils and lymphocytes. Material and Methods Our research group has investigated several plant species and several compounds have been isolated, identified, and their medical potential evaluated. Budlein A is a SL isolated from the species Aldama buddlejiformis and A. robusta (Asteraceae) and shows anti-inflammatory and anti-nociceptive activities. Advances in understanding how plant-derived substances modulate the activation of innate and adaptive immune cells have led to the development of new therapies for human diseases. Results Budlein A inhibited MPO activity, IL-6, CXCL8, IL-10, and IL-12 production and induces neutrophil apoptosis. In contrast, budlein A inhibited lymphocyte proliferation and IL-2, IL-10, TGF-β, and IFN-γ production, but it did not lead to cell death. Conclusions Collectively, our results indicate that budlein A shows distinct immunomodulatory effects on immune cells.

Alternariol 9-methyl ether from the endophytic fungus Alternaria sp. Samif01 and its bioactivities

Abstract One bioactive compound, identified as alternariol 9-methyl ether, was isolated from the crude extract of the endophytic fungus Alternaria sp. Samif01 residing in the roots of Salvia miltiorrhiza Bunge. Alternariol 9-methyl ether was active against bacteria with minimum inhibitory concentration values ranging from 25 to 75 µg/mL and median inhibitory concentration (IC50) values ranging from 16.00 to 38.27 µg/mL. The IC50 value of alternariol 9-methyl ether against spore germination of Magnaporthe oryzae was 87.18 µg/mL. Alternariol 9-methyl ether also showed antinematodal activity against Bursaphelenchus xylophilus and Caenorhabditis elegans with IC50 values of 98.17 µg/mL and 74.62 µg/mL, respectively. This work is the first report on alternariol 9-methyl ether and its biological activities from the endophytic fungus Alternaria sp. Samif01 derived from S. miltiorrhiza Bunge. The results indicate the potential of Alternaria sp. Samif01 as a source of alternariol 9-methyl ether and also support that alternariol 9-methyl ether is a natural compound with high potential bioactivity against microorganisms.

Social determinants of health, inequality and social inclusion among people with disabilities / Determinantes sociais da saúde, iniquidades e inclusão social entre pessoas com deficiência / Determinantes sociales de la salud, iniquidades e inclusión social entre personas con deficiencia

OBJECTIVE: to analyze the socio-familial and community inclusion and social participation of people with disabilities, as well as their inclusion in occupations in daily life. METHOD: qualitative study with data collected through open interviews concerning the participants' life histories and systematic observation. The sample was composed of ten individuals with acquired or congenital disabilities living in the region covered by a Family Health Center. The social conception of disability was the theoretical framework used. Data were analyzed according to an interpretative reconstructive approach based on Habermas' Theory of Communicative Action. RESULTS: the results show that the socio-familial and community inclusion of the study participants is conditioned to the social determinants of health and present high levels of social inequality expressed by difficult access to PHC and rehabilitation services, work and income, education, culture, transportation and social participation. CONCLUSION: there is a need to develop community-centered care programs in cooperation with PHC services aiming to cope with poverty and improve social inclusion. .

OBJETIVO: analisar a inclusão sociofamiliar e comunitária e a participação social de pessoas com deficiência, bem como sua inserção em ocupações na vida cotidiana. MÉTODO: estudo qualitativo, com coleta de dados por meio de entrevistas abertas sobre história de vida e observação sistemática. A amostra foi composta por dez pessoas com deficiência, adquirida ou congênita, moradoras de região adstrita a um Núcleo de Saúde da Família. O referencial teórico foi a concepção social da deficiência. Os dados foram analisados segundo abordagem interpretativa reconstrutiva, fundamentada no referencial da Teoria da Ação Comunicativa de Habermas. RESULTADOS: os resultados evidenciaram que a inclusão sociofamiliar e comunitária dos sujeitos do estudo condiciona-se a determinantes sociais da saúde, apresentando índices de iniquidades sociais, expressos pela dificuldade de acesso a serviços de Atenção Primária à Saúde e de reabilitação, trabalho e renda, educação, cultura, transporte e participação social. CONCLUSÃO: conclui-se a necessidade da elaboração de programas de atenção centrados na comunidade, voltados ao enfrentamento da pobreza e à inclusão social, em articulação com serviços de Atenção Primaria à Saúde. .

OBJETIVO: analizar la inclusión social familiar y comunitaria, y la participación social de personas con deficiencia, así como su inserción en ocupaciones en la vida cotidiana. MÉTODO: estudio cualitativo, con recolección de datos por medio de entrevistas abiertas sobre historia de vida y por observación sistemática. La muestra estuvo compuesta por diez personas con deficiencia, adquirida o congénita, habitantes de una región adscrita a un Núcleo de Salud de la Familia. El referencial teórico fue la concepción social de la deficiencia. Los datos fueron analizados según abordaje interpretativo reconstructivo, fundamentado en el referencial de la Teoría de la Acción Comunicativa de Habermas. RESULTADOS: los resultados evidenciaron que la inclusión social familiar y comunitaria de los sujetos del estudio se condiciona a determinantes sociales de la salud, presentando índices de iniquidades sociales, expresados por la dificultad de acceso a servicios de Atención Primaria de la Salud y de rehabilitación, trabajo y renta, educación, cultura, transporte y participación social. CONCLUSIÓN: se concluye que existe la necesidad de elaborar programas de atención centrados en la comunidad, dirigidos al enfrentamiento de la pobreza y a la inclusión social, en articulación con servicios de Atención Primaria a la Salud. .

Efectos adversos cardíacos de la domperidona en pacientes adultos: revisión sistemática / Cardiac adverse effects of domperidone in adult patients: a systematic review

Background: Domperidone is widely prescribed in patients with gastrointestinal disorders but some cardiac adverse effects have been recently reported. Aim: To evaluate the risk of QT prolongation, ventricular arrhythmias and sudden cardiac death associated with the use of oral domperidone in adults without cancer. Material and Methods: Systematic searches in MEDLINE, LILACS, SciELO, the Cochrane Library and regulatory agencies websites were performed, followed by a manual search of cited references. The search strategy consisted of combining free and indexed text words without any date or language restriction. Results: Three case-control studies met the inclusion criteria; none of them evaluated QT interval prolongation. With low risk of bias, each study quantified the risk of ventricular arrhythmia or sudden cardiac death (VA/SCD). The odds ratios for these events in these studies were 4.7 (95% confidence interval (CI): 1.4-16), 1.59 (95% CI: 1.28-1.98) and 11.02 (95% CI: 2.02-62.3) respectively. A significantly increased risk was observed in patients older than 60 years of age or receiving doses > 30 mg/day. Conclusions: Heterogeneity between selected studies did not allow the computation of a summary measure. However, evidence was found that an increased risk of VA/SCD is associated with the use of oral domperidone in adults.

Cytotoxicity, nitric oxide and acetylcholinesterase inhibitory activity of three limonoids isolated from Trichilia welwitschii (Meliaceae)

BACKGROUND: Limonoids are highly oxygenated compounds with a prototypical structure. Their occurrence in the plant kingdom is mainly confined to plant families of Meliaceae and Rutaceae. Owing to their wide range of pharmacological and therapeutic properties, this study was aimed at investigating the potential nitric oxide (NO) and acetylcholinesterase (AChE) inhibitory activity and the cytotoxicity of three limonoids: trichilia lactone D5 (1), rohituka 3 (2) and dregeanin DM4 (3), isolated from Trichilia welwitschii C.DC. RESULTS: Results indicated that the three limonoids had low cytotoxicity towards Vero cells with LC50 values ranging from 89.17 to 75.82 µg/mL. Compounds (2) and (3) had lower cytotoxicity compared to puromycin and doxorubicin used as reference cytotoxic compounds. Compound (1) (LC50 of 23.55 µg/mL) had good antiproliferative activity against RAW 264.7 cancer cells. At the lowest concentration tested (0.5 µg/mL), compound (2) and (3) released the lowest amount of nitric oxide (2.97 and 2.93 µM, respectively). The three limonoids had anti-AChE activity with IC50 values ranged of 19.13 µg/mL for (1), 34.15 µg/mL for (2) and 45.66 µg/mL for (3), compared to galantamine (IC50 of 8.22 µg/mL) used as positive control. CONCLUSION: The limonoid compounds studied in this work inhibited nitric oxide production in LPS-stimulated macrophages and had anti-AChE activity. Trichilia lactone D5 had potential antiproliferative activity against RAW 264.7 cancer cells. The limonoids had low cytotoxicity towards Vero cells lines. This study provided further examples of the importance of limonoids compounds as potential AChE inhibitors and anti-inflammatory agents targeting the inhibition of NO production.

Diagnostic accuracy of respiratory diseases in primary health units / Precisão diagnóstica de doenças respiratórias em unidades primárias de saúde.

Respiratory diseases are responsible for about a fifth of all deaths worldwide and its prevalence reaches 15% of the world population. Primary health care (PHC) is the gateway to the health system, and is expected to resolve up to 85% of health problems in general. Moreover, little is known about the diagnostic ability of general practitioners (GPs) in relation to respiratory diseases in PHC. This review aims to evaluate the diagnostic ability of GPs working in PHC in relation to more prevalent respiratory diseases, such as acute respiratory infections (ARI), tuberculosis, asthma and chronic obstructive pulmonary disease (COPD). 3,913 articles were selected, totaling 30 after application of the inclusion and exclusion criteria. They demonstrated the lack of consistent evidence on the accuracy of diagnoses of respiratory diseases by general practitioners. In relation to asthma and COPD, studies have shown diagnostic errors leading to overdiagnosis or underdiagnosis depending on the methodology used. The lack of precision for the diagnosis of asthma varied from 54% underdiagnosis to 34% overdiagnosis, whereas for COPD this ranged from 81% for underdiagnosis to 86.1% for overdiagnosis. For ARI, it was found that the inclusion of a complementary test for diagnosis led to an improvement in diagnostic accuracy. Studies show a low level of knowledge about tuberculosis on the part of general practitioners. According to this review, PHC represented by the GP needs to improve its ability for the diagnosis and management of this group of patients constituting one of its main demands.

As doenças respiratórias acometem 15% da população do planeta e respondem por 1/5 dos óbitos no mundo. Espera-se que a atenção primária à saúde (APS), primeira instância da assistência médica, solucione até 85% dos problemas de saúde em geral. Pouco se sabe a respeito da habilidade de médicos generalistas da APS em relação ao diagnóstico das doenças respiratórias. Esta revisão refere-se à habilidade diagnóstica de médicos generalistas que atuam na APS em relação às doenças respiratórias mais prevalentes, como doenças respiratórias agudas (IRA), tuberculose, asma e doença pulmonar obstrutiva crônica (DPOC). Dentre 3.913 artigos, 30 foram selecionados após aplicação dos critérios de inclusão e exclusão. Ficou demonstrada a carência de dados consistentes sobre a acurácia dos diagnósticos de doenças respiratórias elaborados por generalistas. Em relação à asma e à DPOC, os estudos demonstram erros diagnósticos que levam ao sobrediagnóstico ou ao subdiagnóstico, dependendo da metodologia usada. A imprecisão do diagnóstico de asma variou de 54% de subdiagnóstico a 34% de sobrediagnóstico; para DPOC, houve variação de 81% de subdiagnóstico a 86,1% de sobrediagnóstico; para IRA, verificou-se que a inclusão de exame complementar de auxílio diagnóstico melhora sua acurácia. Os estudos demonstram um baixo nível de conhecimento sobre tuberculose por parte dos generalistas. De acordo com esta revisão, a APS, na figura do médico generalista, necessita aprimorar sua capacidade de diagnóstico e o manejo desse grupo de pacientes, que constitui uma de suas principais demandas.

Rhipicephalus (Boophilus) microplus resistant to acaricides and ivermectin in cattle farms of Mexico / Rhipicephalus (Boophilus) microplus resistentes aos acaricidas e ivermectina nas fazendas de gado do México

Ticks and the diseases they transmit cause great economic losses to livestock in tropical countries. Non-chemical control alternatives include the use of resistant cattle breeds, biological control and vaccines. However, the most widely used method is the application of different chemical classes of acaricides and macrocyclic lactones. Populations of the cattle tick, Rhipicephalus (Boophilus) microplus, resistant to organophosphates (OP), synthetic pyrethroids (SP), amitraz and fipronil have been reported in Mexico. Macrocyclic lactones are the most sold antiparasitic drug in the Mexican veterinary market. Ivermectin-resistant populations of R. (B.) microplus have been reported in Brazil, Uruguay and especially in Mexico (Veracruz and Yucatan). Although ivermectin resistance levels in R. (B.) microplus from Mexico were generally low in most cases, some field populations of R. (B.) microplus exhibited high levels of ivermectin resistance. The CHPAT population showed a resistance ratio of 10.23 and 79.6 at lethal concentration of 50% and 99%, respectively. Many field populations of R. (B.) microplus are resistant to multiple classes of antiparasitic drugs, including organophosphates (chlorpyrifos, coumaphos and diazinon), pyrethroids (flumethrin, deltamethrin and cypermethrin), amitraz and ivermectin. This paper reports the current status of the resistance of R. (B.) microplus to acaricides, especially ivermectin, in Mexican cattle.

Carrapatos e as doenças por eles transmitidas causam grandes perdas econômicas ao gado dos países tropicais. Alternativas não-químicas incluem o uso de raças de gado que sejam resistentes, controle biológico e vacinas. No entanto, o método mais utilizado é a aplicação de diferentes classes químicas de acaricidas e lactonas macrocíclicas. Populações de piolhos de gado, Rhipicephalus (Boophilus) microplus, resistentes aos organofosfatos (OP), piretoides sintéticos (SP), amitraz e fipronil, foram descritas no México. Lactonas macrocíclicas são as drogas antiparasitárias mais vendidas no mercado veterinário mexicano. Populações de R. (B.) microplus resistentes à irvemectina foram relatadas no Brasil, Uruguai e especialmente no México (Veracruz e Yucatan). Embora os níveis de resistência à ivermectina no R. (B.) microplus do México tenha sido relativamente baixa, na maioria dos casos, algumas populações campestres de R. (B.) microplus mostraram altos níveis de resistência à ivermectina. A população CHPAT mostrou uma razão de resistência de 10,23 e 79,6 na concentração letal de 50% e 99%, respectivamente. Muitas populações campestres de R. (B.) microplus são resistentes a múltiplas classes de drogas antiparasitárias, incluindo organofosfatos (clorpirifós, coumafos e diazinon), piretoides (flumetrina, deltametrina e cipermetrina), amitraz e ivermectina. Este artigo relata o estado atual de resistência do R. (B.) microplus aos acaricidas, especialmente ivermectina, no gado mexicano.

In Vitro Antitumor Activity of Sesquiterpene Lactones from Lychnophora trichocarpha / Atividade antitumoral in vitro de lactonas sesquiterpenicas de Lychnophora

The sesquiterpene lactones lychnopholide and eremantholide C were isolated from Lychnophora trichocarpha Spreng. (Asteraceae), which is a plant species native to the Brazilian Savannah or Cerrado and popularly known as arnica. Sesquiterpene lactones are known to present a variety of biological activities including antitumor activity. The present paper reports on the evaluation of the in vitro antitumor activity of lychnopholide and eremantholide C, in the National Cancer Institute, USA (NCI, USA), against a panel of 52 human tumor cell lines of major human tumors derived from nine cancer types. Lychnopholide disclosed significant activity against 30 cell lines of seven cancer types with IC100 (total growth concentration inhibition) values between 0.41 µM and 2.82 µM. Eremantholide C showed significant activity against 30 cell lines of eight cancer types with IC100 values between 21.40 µM and 53.70 µM. Lychnopholide showed values of lethal concentration 50% (LC50) for 30 human tumor cell lines between 0.72 and 10.00 µM, whereas eremantholide C presented values of LC50 for 21 human tumor cell lines between 52.50 and 91.20 µM. Lychnopholide showed an interesting profile of antitumor activity. The α-methylene-γ-lactone present in the structure of lychnopholide, besides two α,β- unsaturated carbonyl groups, might be responsible for the better activity and higher cytotoxicity of this compound in relation to eremantholide C.

As lactonas sesquiterpênicas licnofolida e eremantolida C foram isoladas de Lychnophora trichocarpha Spreng. (Asteraceae), espécie vegetal nativa do cerrado brasileiro e popularmente conhecida por arnica brasileira. As lactonas sesquiterpênicas são conhecidas por apresentarem variadas atividades biológicas, incluindo atividade antitumoral. O presente artigo relata a avaliação da atividade antitumoral in vitro de licnofolida e eremantolida C frente a um painel de 52 linhagens de células tumorais, provenientes de tumores humanos referentes a nove principais tipos de câncer. Os testes foram conduzidos no National Cancer Institute, USA (NCI, USA). Licnofolida apresentou atividade significativa frente a 30 linhagens de células tumorais referentes a sete tipos de câncer, com valores de CI100 (concentração que inibe 100% do crescimento celular) entre 0,41 µM e 2,82 µM. Eremantolida C mostrou atividade significativa frente a 30 linhagens de células tumorais referentes a oito tipos de câncer, com valores de CI100 entre 21,40 µM e 53,70 µM. Licnofolida apresentou valores de concentração letal 50% (CL50) para 30 linhagens de células tumorais humanas entre 0,72 e 10,00 µM, enquanto eremantolida C mostrou valores de CL50 para 21 linhagens entre 52,50 e 91,20 µM. Licnofolida apresentou um interessante perfil de atividade antitumoral. A presença na estrutura química da licnofolida de uma α-metileno-γ-lactona, além de dois grupos ésteres α,β-insaturados, podem ser responsáveis pela melhor atividade e maior citotoxicidade desta substância em relação à eremantolida C.

Arnica montana: una revisión bioquímica y homeopática / Arnica montana: A biochemical and homeopathic review

El Arnica montana es uno de los medicamentos que se emplean con mayor frecuencia en la práctica homeopática. Comúnmente, es la primera elección en la atención de traumatismos, contusiones y golpes, especialmente de partes blandas. También se emplea en torceduras, fracturas, esfuerzos exagerados, enfermedades reumáticas, traumas emocionales y para mejorar la recuperación de los pacientes que se someten a intervenciones quirúrgicas. Debido al interés que genera, el Arnica montana ha sido objeto de numerosos estudios en diferentes áreas para comprobar su alcance y determinar sus mecanismos de acción. A continuación se presenta una revisión de algunos artículos publicados sobre este medicamento; unos versan sobre sus principios activos y otros analizan diversos experimentos que se han efectuado.

Arnica montana is one of the most often used drugs in homeopathic practice. Commonly, it is the first choice in the trauma care, bruises and bumps, especially soft tissue. Also used in sprains, fractures, exaggerated efforts, rheumatic diseases and emotional trauma to improve recovery of patients who undergo surgery. Due to the interest generated, Arnica montana has been the subject of numerous studies in different areas to check their range and determine their mechanisms of action. Below is a review of some articles published on this medication, some deal with other active principles and discusses various experiments that have been conducted.