In silico evaluation of pharmacokinetics properties of withanolides and simulation of their biological activities against Alzheimer's disease.

The withanolides are naturally occurring steroidal lactones found mainly in plants of the Solanaceae family. The subtribe Withaninae includes species like Withania sominifera, which are a source of many bioactive withanolides. In this work, we selected and evaluate the ADMET-related properties of 91 withanolides found in species of the subtribe Withaninae computationally, to predict the relationship between their structures and their pharmacokinetic profiles. We also evaluated the interaction of these withanolides with known targets of Alzheimer's disease (AD) through molecular docking and molecular dynamics. Withanolides presented favorable pharmacokinetic properties, like high gastrointestinal absorption, lipophilicity (logP ≤ 5), good distribution and excretion parameters, and a favorable toxicity profile. The specie Withania aristata stood out as an interesting source of the promising withanolides classified as 5-ene with 16-ene or 17-ene. These withanolides presented a favourable pharmacokinetic profile and were also highlighted as the best candidates for inhibition of AD-related targets. Our results also suggest that withanolides are likely to act as cholinesterase inhibitors by interacting with the catalytic pocket in an energy favorable and stable way.Communicated by Ramaswamy H. Sarma.

Multi-Parameter Optical Monitoring Solution Applied to Underground Medium-Voltage Electric Power Distribution Networks.

This work presents a multi-parameter optical fiber monitoring solution applied to an underground power distribution network. The monitoring system demonstrated herein uses Fiber Bragg Grating (FBG) sensors to measure multiple parameters, such as the distributed temperature of the power cable, external temperature and current of the transformers, liquid level, and intrusion in the underground manholes. To monitor partial discharges of cable connections, we used sensors that detect radio frequency signals. The system was characterized in the laboratory and tested in underground distribution networks. We present here the technical details of the laboratory characterization, system installation, and the results of 6 months of network monitoring. The data obtained for temperature sensors in the field tests show a thermal behavior depending on the day/night cycle and the season. The temperature levels measured on the conductors indicated that in high-temperature periods, the maximum current specified for the conductor must be reduced, according to the applied Brazilian standards. The other sensors detected other important events in the distribution network. All the sensors demonstrated their functionality and robustness in the distribution network, and the monitored data will allow the electric power system to have a safe operation, with optimized capacity and operating within tolerated electrical and thermal limits.

Determination of Pesticides in Soybean Seeds Incorrectly Discarded Near a Spring of the Paranaíba River, GO-Brazil.

The objective of this research was to evaluate the contamination of pesticides of carbamate and benzimidazole classes in soil, water and soybean seeds, incorrectly discarded near a spring in the state of Goiás-Brazil. The Solid-Liquid and Liquid-Liquid Extraction with Low Temperature Partition (SLE/LTP or LLE/LTP) methods were used for pesticide extraction and the analyses were performed by HPLC-UV. A high resolution mass spectrometer was used to confirm the identity of the compounds present in the seeds. The results showed that the soybeans were treated with the pesticide carbendazim and the dosage was three times higher than established by Brazilian legislation. In the soil and water analyzed there was no presence of the pesticides researched, nor of the carbendazim detected in the seeds. Since this was an environmental crime due to incorrect disposal, it is not known how long ago it occurred. Thus, depending on how long the seeds had been exposed there, the pesticide could have leached out, and caused contamination in the spring and soil. Thus, we conclude that the incorrect disposal of seeds treated with pesticides can be a risk to the permanence of life on the site.

Potential of Ficus carica extracts against Euschistus heros: Toxicity of major active compounds and selectivity against beneficial insects.

BACKGROUND: Using plant-based extracts and their constituents has been suggested as an alternative tool to replace or integrate with the synthetic compounds used to manage insect pests. Here, we evaluated the potential of extracts obtained from Ficus carica Linn (Moraceae) branches and leaves against the Neotropical brown stink bug, Euschistus heros, one of the most prevalent insect pests in soybean fields. We further isolated and evaluated the toxicity of the extracts' major components against E. heros. Additionally, by using computational docking analysis and toxicological approaches, we assessed the physiological basis for the selectivity of these extracts against beneficial insects such as pollinator bees (i.e. Apis mellifera and the Neotropical stingless bee Partamona helleri), ladybeetles (Eriopis connexa and Coleomegilla maculata), and lacewings (Chrysoperla externa). RESULTS: Our results demonstrate that branch (LC50  = 5.9 [4.7-7.1] mg mL-1 ) and leaf (LC50  = 14.1 [12.5-15.4] mg mL-1 ) extracts exhibited similar toxicity against E. heros. Our phytochemical analysis revealed psoralen and bergapten furanocoumarins as the major components of the extract. Based on our computational predictions, these molecules' differential abilities to physically interact with the acetylcholinesterases of E. heros and beneficial insects play relevant roles in their selectivity actions. The estimated LC90 values of branch (30.0 mg mL-1 ) and leaf (30.0 mg mL-1 ) extracts killed less than 12% of the beneficial insects. CONCLUSION: Overall, our findings revealed that furanocoumarin-rich extracts obtained from F. carica extracts have the potential to be used as alternative tools in the integrated management of stink bug pests. © 2021 Society of Chemical Industry.

Tebuconazole-induced toxicity and the protective effect of Ficus carica extract in Neotropical fruit-eating bats.

Tebuconazole (TEB) is a triazole fungicide widely used in agriculture known to cause metabolic and endocrine disorders in mammals. Several plant extracts have shown to be beneficial against pesticide effects due to their hepatoprotective, antioxidant and anti-inflammatory properties. As fruit bats play a critical role in rainforest regeneration and are constantly exposed to pesticides, we aimed at evaluating TEB-induced toxicity and the possible protective effect of the Ficus carica plant extract in Neotropical fruit-eating bats (Artibeus lituratus). Bats were captured and assigned to 4 experimental groups, offered: 1) CTL (n = 6): papaya; 2) DMSO (n = 6): papaya treated with 1.25% dimethyl sulfoxide (DMSO); 3) TEB (n = 6): papaya treated with tebuconazole (commercial formulation) 0.1%; and 4) TEBFC (n = 6): papaya treated with tebuconazole 0.1% and Ficus carica extract (20%) in DMSO (1.25%). After seven days of exposure, TEB bats showed increased lipid peroxidation, increased superoxide dismutase (SOD) and catalase (CAT) activities, vascular congestion and inflammatory infiltrate in the liver, and increased serum transaminase enzyme activities. We found the same alterations in oxidative stress parameters in the breast muscles of TEB-exposed bats. In the testes, all oxidative stress markers were increased in TEB bats and corroborate findings of histopathological and increased serum testosterone levels observed following TEB exposure. The co-administration of the fungicide with the F. carica plant extract attenuated most oxidative stress markers in exposed bats' liver and testes and decreased liver damage, but failed to revert the steroid imbalance caused by the fungicide exposure.

Diagnostic Accuracy of Next Generation Sequencing Panel using Circulating Tumor DNA in Patients with Advanced Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND/OBJECTIVES: Until now, no meta-analysis has been published to evaluate the diagnostic performance of next-generation sequencing (NGS) panel using circulating tumor (ctDNA) in patients with advanced non-small cell lung cancer (aNSCLC). The aim of the study was to carry out a systematic review and a meta-analysis in order to determine the accuracy of NGS of ctDNA to detect six oncogenic driver alterations: epidermal growth factor receptor (EGFR); anaplastic lymphoma kinase (ALK); ROS proto-oncogene 1, receptor tyrosine kinase (ROS-1); serine/threonine-protein kinase B-RAF (BRAF); RET proto-oncogene (RET); and MET proto-oncogene, receptor tyrosine kinase (MET) exon 14 in patients with aNSCLC. METHODS: MEDLINE/PubMed, Cochrane Library, Latin American and Caribbean Health Sciences Literature (LILACS), and Centre for Reviews and Dissemination databases and articles obtained from other sources were searched for relevant studies that evaluate the accuracy (sensitivity and specificity) of NGS using ctDNA in patients with aNSCLC. The studies were eligible when NGS of ctDNA was compared with tissue tests to detect at least one of the six oncogenic driver alterations. Diagnostic measures (sensitivity and specificity) were pooled with a bivariate diagnostic random effect. All statistical analyses were performed with software R, v.4.0.0. RESULTS: Ten studies were eligible for data extraction. The overall pooled estimates of sensitivity and specificity were 0.766 (95% CI: 0.678-0.835); 0.999 (95% CI: 0.990-1.000), respectively. CONCLUSIONS: The analysis has demonstrated that the NGS panel using ctDNA has a high accuracy to identify the six actionable oncogenic driver alterations in patients with aNSCLC. Therefore, it can be considered a reliable alternative to guide the patients with aNSCLC to the right treatment who cannot undergo an invasive procedure or have insufficient tissue material for molecular tests.

Deleterious effects of Pfaffia glomerata (Spreng.) Pedersen hydroalcoholic extract on the seminiferous epithelium of adult Balb/c mice.

Several plant species such as Pfaffia glomerata are widely used in traditional Brazilian medicine as stimulants and aphrodisiacs. In this regard, the aim of our study was to explore the effects of the long-term intake of the hydro-alcoholic root extract of P glomerata on the germ and somatic cells within the seminiferous tubules in adult Balb/c mice. The experimental groups were placed as: controls (water and DMSO), and treated with 300 and 400 mg/kg of the root extract. The number of germ and somatic cells, the proportion of pathological seminiferous tubules, and the germ cell apoptotic levels were evaluated. The volume and proportion of the seminiferous epithelium was decreased after the extract intake due to the increased germ cell apoptotic levels. Vacuolization of Sertoli cell cytoplasm was observed widely in pathological tubules, along with fully disorganized epithelia, showing multinucleated cells, which lead to decreased daily sperm production. Taken together, our results indicate that long-term intake of the P glomerata caused deleterious effects on spermatogenesis by inducing apoptosis and altering the seminiferous tubule's epithelial dynamics.

Tyrosol 1,2,3-triazole analogues as new acetylcholinesterase (AChE) inhibitors.

The present work proposed the preparation of triazolic analogues of tyrosol, a biophenol found in olive oil and whose wide range of bioactivities has been the target of many studies. We obtained fifteen novel tyrosol derivatives and the compounds of the series were later evaluated as acetylcholinesterase (AChE) inhibitors. The study of AChE inhibition is important for the development of new drugs and pesticides, and especially the research for managing Alzheimer's disease. The most active compound, namely 7-({1-[2-(4-hydroxyphenyl)ethyl]-1H-1,2,3-triazol-4-yl}methoxy)-4-methyl-2H-chromen-2-one (30), showed IC50 value of 14.66 ±â€¯2.29 µmol L-1. Docking experiments corroborated by kinetic assay are suggestive of a competitive inhibition mechanism. Derivatives interacted with amino acids from the AChE active site associated to the development of Alzheimer's disease. The results indicate that the compounds synthesized have a high potential as prototypes for the development of new acetylcholinesterase inhibitors.

Parasitological and immunological evaluation of a novel chemotherapeutic agent against visceral leishmaniasis.

AIMS: Treatment for visceral leishmaniasis (VL) is hampered by the toxicity and/or high cost of drugs, as well as by emergence of parasite resistance. Therefore, there is an urgent need for new antileishmanial agents. METHODS AND RESULTS: In this study, the antileishmanial activity of a diprenylated flavonoid called 5,7,3,4'-tetrahydroxy-6,8-diprenylisoflavone (CMt) was tested against Leishmania infantum and L amazonensis species. Results showed that CMt presented selectivity index (SI) of 70.0 and 165.0 against L infantum and L amazonensis promastigotes, respectively, and of 181.9 and 397.8 against respective axenic amastigotes. Amphotericin B (AmpB) showed lower SI values of 9.1 and 11.1 against L infantum and L amazonensis promastigotes, respectively, and of 12.5 and 14.3 against amastigotes, respectively. CMt was effective in the treatment of infected macrophages and caused alterations in the parasite mitochondria. L infantum-infected mice treated with miltefosine, CMt alone or incorporated in polymeric micelles (CMt/Mic) presented significant reductions in the parasite load in distinct organs, when compared to the control groups. An antileishmanial Th1-type cellular and humoral immune response were developed one and 15 days after treatment, with CMt/Mic-treated mice presenting a better protective response. CONCLUSION: Our data suggest that CMt/Mic could be evaluated as a chemotherapeutic agent against VL.

A new approach for the achievement of stable aqueous dispersions of carbon nanotubes.

A novel methodology to prepare stable aqueous dispersions of raw single- and multi-walled carbon nanotubes is reported, based on dispersions previously prepared in tetrahydrofuran containing a phenol that donates electrons to nanotubes and provides colloidal stability through electrostatic repulsion. A proposed mechanism for the stabilization of the dispersions is presented. Conductive and transparent thin films are prepared through a liquid/liquid interfacial route starting from these dispersions.

Hepatitis C in Brazil: lessons learned with boceprevir and telaprevir.

In 2012, the first-generation protease inhibitors telaprevir (TVR) and boceprevir (BOC) were introduced in the Brazilian health system for treatment of chronic hepatitis C, after their approval by the National Committee for Health Technology Incorporation (CONITEC). However, these medicines were discontinued in 2015. The short period of use in therapy and their high cost require a discussion about the consequences for patients and for the health system of the early incorporation of new therapies. The article presents a qualitative analysis of the incorporation process of both medications in Brazil and the results of a multicenter study that included patients treated with BOC or TVR between January 2011 and December 2015 in five Brazilian cities. The study included 855 patients (BOC: n=247) and (TVR: n=608). The document analysis showed that CONITEC's decision to incorporate BOC and TVR was based on results of phase III clinical trials that compared sustained virologic response (SVR) rates of patients treated with BOC and TVR with rates of those that received placebo. However, these studies included a low percentage of cirrhotic patients. The SVR rates observed in this multicenter study were worse than clinical trials pointed out (BOC: 45.6%; TVR: 51.8%), but similar to those achieved with previously adopted therapies. The discontinuation rate due to adverse events was (BOC: 15.4%; TVR: 12.7%). Based on these unsatisfactory results, the study brings a discussion that goes beyond the therapy outcomes, exploring the incorporation of these high-cost medicines and the related decision-making process, contributing to future decisions in medicine policies and in the treatment of chronic hepatitis C.

Electrostatic stabilization of multi-walled carbon nanotubes dispersed in nonaqueous media.

Dispersing carbon nanotubes is an easy and low-cost way to manipulate these solids and allows the preparation of more complex materials or devices, so it is fundamental for further uses that these dispersions have controlled properties and high colloidal stability. In this work we report the spontaneous electrical charge build-up in pristine multi-walled carbon nanotubes dispersed in common organic solvents such as chloroform and tetrahydrofuran and the achievement of dispersions stable for long periods without adding passivant agents or functional groups on nanotubes surface. Results from electrokinetics, homo- and heterocoagulation provided macroscopic evidences that carbon nanotubes acquire electric charges after dispersion in some organic liquids and we confirmed this process by measuring in situ Raman spectra of the nanotubes dispersions with higher surface electric potentials. We also show that the signal of electric potential of the dispersions can be predicted by the acid-base behaviour of the dispersing medium, corroborating previously reports for other dispersions of carbon nanomaterials.

Structural aspects of graphitic carbon modified SBA-15 mesoporous silica and biological interactions with red blood cells and plasma proteins.

Functional mesoporous materials have been worldwide studied for different applications. Mesoporous silicas are highlighted due to the synthetic possibilities for the preparation of such materials with different particle sizes and morphologies, and controlled pores sizes and structures. Moreover, the silica superficial silanol groups are explored in several chemical modifications, leading to functional materials with tuned functionalities and properties. In this work, an organo-functionalization and pyrolysis synthetic procedure is used to obtain graphitic carbon modified mesoporous SBA-15 silica. The carbon content was tuned during the functionalization step, and the graphitic nanodomains were formed in the pores surface and particles outer surface. Textural and small angle X-ray diffraction analysis accessed the presence of the carbon nanostructures inside the SBA-15 mesopores. Advanced microanalysis using electron energy loss spectroscopy coupled to a transmission electron microscope had confirmed the carbon distribution along the silica pores, which gives higher hydrophobicity and changed the interaction of the mesoporous material with biological systems. Finally, the influence of the surface modification with graphitic carbon species over the interaction with human red blood cells (hemolysis) and human blood plasma (protein corona formation) was elucidated for the very first time for this kind of functional materials. It was observed that the graphitic carbon species considerably reduced the hemolytic effect of the silica particles, and was responsible for modulating the loading and composition of the hard corona plasma proteins. This work deepness the fundamental knowledge on the interaction between such nanomaterials and biological systems, one step further the use of these modified silicas in biomedical applications.

Skeletal age and explosive strength in young volleyball players / Idade óssea e força explosiva de jovens praticantes de voleibol

Abstract Identifying different anthropometric, physiological and motor aspects is essential to obtain success in sports practice. However, these components may be developed in same age subjects differently, in part due biological development. The aim of the study was compare and correlate the explosive strength to biological maturation by sex, obtained by estimation of skeletal age based on anthropometric variables. The sample consisted of 239 subjects of both sexes, aged 10 to 13 years. Maturation was assessed by skeletal age predictive equation and upper and lower limbs explosive strength using medicine ball throw test and vertical jump, respectively. Skeletal age was assessed by skeletal age using a predictive anthropometrical based equation. Upper and lower limbs explosive strength were evaluated by medicine ball throwing test and vertical jump test, respectively. Post hoc analysis showed delayed biological development subjects had worst medicine ball throwing test performance than accelerated boys (p=0.001; d=0.96) and girls (p< 0.01; d= 2.01); regarding to vertical jump test, worst performance was also detected to maturational delayed boys when compared to accelerated ones (p=0.24; d=1.1) and girls (p=0.007; d=0.75). Regression analysis showed skeletal age explained variance of 36% and 19.2% for boys and 45.2% and 16.1% for girls upper and lower limbs explosive strength. Skeletal age is positively related to upper and lower limbs explosive strength and show higher performance for accelerated biological development young players when compared to delayed ones, independently from sex.

Resumo Para se alcançar o sucesso no esporte, a identificação de diferentes aspectos antropométricos, motores e fisiológicos são imprescindíveis. Porém, esses componentes podem se desenvolver diferentemente em indivíduos na mesma faixa etária, em parte pelo desenvolvimento biológico. O objetivo do estudo foi comparar e relacionar a força explosiva com a maturação biológica de acordo com o sexo. A amostra foi composta por 239 sujeitos, com idades entre 10 a 13 anos. A idade óssea foi estimada por uma equação preditora baseada em variáveis antropométricas. A força explosiva de membros superiores e inferiores foram avaliadas através do teste de arremesso de medicine ball e de salto vertical, respectivamente. A análise de post hoc mostrou que os sujeitos com desenvolvimento biológico atrasado obtiveram o pior desempenho no teste de arremesso de medicine ball quando comparados com o grupo acelerado dos meninos (p=0.001; d=0.96) e meninas (p< 0.01; d= 2.01); em relação ao teste de salto vertical, desempenho inferior também foi observado para o estágio atrasado quando comparado com o grupo acelerado dos meninos (p=0.24; d=1.1) e meninas (p= 0.007; d=0.75). Análise de regressão demonstrou que 36% e 19,2% da variância no desempenho da força explosiva de membros superiores e inferiores foi compartilhada pela idade óssea dos meninos, e 45,2% e 16,1%, respectivamente, nas meninas. Conclui-se que a força explosiva de membros superiores e inferiores se relaciona de forma positiva com a idade óssea, sendo o desempenho destes componentes superiores em jovens com desenvolvimento biológico acelerado, quando comparados com o desenvolvimento atrasado, independente do sexo.

Antileishmanial activity and mechanism of action from a purified fraction of Zingiber officinalis Roscoe against Leishmania amazonensis.

In recent years, considerable attention has been given to identify new antileishmanial products derived from medicinal plants, although, to date, no new effective compound has been recently applied to treat leishmaniasis. In the present study, the antileishmanial activity of a water extract from Zingiber officinalis Roscoe (ginger) was investigated and a purified fraction, named F10, was identified as responsible by this biological activity. The chemical characterization performed for this fraction showed that it is mainly composed by flavonoids and saponins. The water extract and the F10 fraction presented IC50 values of 125.5 and 49.8 µg/mL, respectively. Their selectivity indexes (SI) were calculated and values were seven and 40 times higher, respectively, in relation to the value found for amphotericin B, which was used as a control. Additional studies were performed to evaluate the toxicity of these compounds in human red blood cells, besides of the production of nitrite, as an indicator of nitric oxide (NO), in treated and infected macrophages. The results showed that both F10 fraction and water extract were not toxic to human cells, and they were able to stimulate the nitrite production, with values of 13.6 and 5.4 µM, respectively, suggesting that their biological activity could be due to macrophages activation via NO production. In conclusion, the present study shows that a purified fraction from ginger could be evaluated in future works as a therapeutic alternative, on its own or in association with other drugs, to treat disease caused by L. amazonensis.

The cranial morphology of the Botocudo Indians, Brazil.

The Botocudo Indians were hunter-gatherer groups that occupied the East-Central regions of Brazil decimated during the colonial period in the country. During the 19th century, craniometric studies suggested that the Botocudo resembled more the Paleoamerican population of Lagoa Santa than typical Native Americans groups. These results suggest that the Botocudo Indians might represent a population that retained the biological characteristics of early groups of the continent, remaining largely isolated from groups that gave origin to the modern Native South American variation. Moreover, recently, some of the Botocudo remains have been shown to have mitochondrial and autosomal DNA lineages currently found in Polynesian populations. Here, we explore the morphological affinities of Botocudo skulls within a worldwide context. Distinct multivariate analyses based on 32 craniometric variables show that 1) the two individuals with Polynesian DNA sequences have morphological characteristics that fall within the Polynesian and Botocudo variation, making their assignation as Native American specimens problematic, and 2) there are high morphological affinities between Botocudo, Early Americans, and the Polynesian series of Easter Island, which support the early observations that the Botocudo can be seen as retaining the Paleoamerican morphology, particularly when the neurocranium is considered. Although these results do not elucidate the origin of the Polynesian DNA lineages among the Botocudo, they support the hypothesis that the Botocudo represent a case of late survival of ancient Paleoamerican populations, retaining the morphological characteristics of ancestral Late Pleistocene populations from Asia.

The energy density of laser light differentially modulates the skin morphological reorganization in a murine model of healing by secondary intention.

This study investigates the influence of gallium-arsenide (GaAs) laser photobiostimulation applied with different energy densities on skin wound healing by secondary intention in rats. Three circular wounds, 10 mm in diameter, were made on the dorsolateral region of 21 Wistar rats weighting 282.12 ± 36.08 g. The animals were equally randomized into three groups: Group SAL, saline solution 0.9%; Group L3, laser GaAs 3 J/cm(2); Group L30, laser GaAs 30 J/cm(2). Analyses of cells, blood vessels, collagen and elastic fibres, glycosaminoglycans and wound contraction were performed on the scar tissue from different wounds every 7 days for 21 days. On day 7, 14 and 21, L3 and L30 showed higher collagen and glycosaminoglycan levels compared to SAL (P < 0.05). At day 21, elastic fibres were predominant in L3 and L30 compared to SAL (P < 0.05). Type-III collagen fibres were predominant at day 7 in both groups. There was gradual reduction in these fibres and accumulation of type-I collagen over time, especially in L3 and L30 compared with SAL. Elevated density of blood vessels was seen in L30 on days 7 and 14 compared to the other groups (P < 0.05). On these same days, there was higher tissue cellularity in L3 compared with SAL (P < 0.05). The progression of wound closure during all time points investigated was higher in the L30 group (P < 0.05). Both energy densities investigated increased the tissue cellularity, vascular density, collagen and elastic fibres, and glycosaminoglycan synthesis, with the greater benefits for wound closure being found at the density of 30 J/cm(2).

Bark extract of Bathysa cuspidata attenuates extra-pulmonary acute lung injury induced by paraquat and reduces mortality in rats.

This study investigated the effect of the bark extract of Bathysa cuspidata on paraquat (PQ)-induced extra-pulmonary acute lung injury (ALI) and mortality in rats. ALI was induced with a single dose of PQ (30 mg/kg, i.p.), and animals were treated with B. cuspidata extract (200 and 400 mg/kg). Analyses were conducted of survival, cell migration, lung oedema, malondialdehyde, proteins carbonyls, catalase, superoxide dismutase, histopathology and the stereology of lung tissue. Rats exposed to PQ and treated with 200 and 400 mg of the extract presented lower mortality (20% and 30%), compared with PQ alone group (50%). Furthermore, lung oedema, septal thickening, alveolar collapse, haemorrhage, cell migration, malondialdehyde and proteins carbonyl levels decreased, and catalase and superoxide dismutase activity were maintained. These results show that the bark extract of B. cuspidata reduced PQ-induced extra-pulmonary ALI and mortality in rats and suggest that these effects may be associated with the inhibition of oxidative damage.

Leishmanicidal activity of the Agaricus blazei Murill in different Leishmania species.

Leishmaniasis is a major public health problem, and the alarming spread of parasite resistance underlines the importance of discovering new therapeutic products. The present study aims to investigate the in vitro leishmanicidal activity of an Agaricus blazei Murill mushroom extract as compared to different Leishmania species and stages. The water extract proved to be effective against promastigote and amastigote-like stages of Leishmania amazonensis, L. chagasi, and L. major, with IC(50) (50% inhibitory concentration) values of 67.5, 65.8, and 56.8 µg/mL for promastigotes, and 115.4, 112.3, and 108.4 µg/mL for amastigotes-like respectively. The infectivity of the three Leishmania species before and after treatment with the water extract was analyzed, and it could be observed that 82%, 57%, and 73% of the macrophages were infected with L. amazonensis, L. major, and L. chagasi, respectively. However, when parasites were pre-incubated with the water extract, and later used to infect macrophages, they were able to infect only 12.7%, 24.5%, and 19.7% of the phagocytic cells for L. amazonensis, L. chagasi, and L. major, respectively. In other experiments, macrophages were infected with L. amazonensis, L. chagasi, or L. major, and later treated with the aforementioned extract, presented reductions of 84.4%, 79.6%, and 85.3% in the parasite burden after treatment. A confocal microscopy revealed the loss of the viability of the parasites within the infected macrophages after treatment with the water extract. The applied extract presented a low cytotoxicity in murine macrophages and a null hemolytic activity in type O(+) human red blood cells. No nitric oxide (NO) production, nor inducible nitric oxide syntase expression, could be observed in macrophages after stimulation with the water extract, suggesting that biological activity may be due to direct mechanisms other than macrophage activation by means of NO production. In conclusion, the results demonstrate that the A. blazei Murill water extract can potentially be used as a therapeutic alternative on its own, or in association with other drugs, to treat Visceral and Cutaneous Leishmaniasis.

Contribuição ao estudo farmacobotânico da Echinodorus macrophyllus (Kunth) Micheli (chapéu-de-couro) - Alismataceae / Contribution to the pharmacobotanical study of Echinodorus macrophyllus (Kunth) Micheli (chapéu-de-couro) - Alismataceae

A Echinodorus macrophyllus (Kunth) Micheli - Alismataceae, conhecida como chapéu-de-couro, chá-mineiro, erva-de-pantâno, erva-de-bugre, congonha-do-brejo e erva-do-brejo, ocorre em Minas Gerais e São Paulo. Embora tenha importância terapêutica, comercial e estar inscrita nas duas primeiras edições da Farmacopéia Brasileira (1924, 1959), são poucos os estudos que a contemplam. Este presente trabalho teve como objetivo estudar a morfoanatomia foliar e do pecíolo da E. macrophyllus, a fim de ampliar o seu conhecimento farmacognóstico, visando o controle de qualidade. A descrição macroscópica foi realizada à vista desarmada, com recursos óticos e as dimensões, com paquímetro. As características anatômicas foram determinadas, após a colheita, nos fragmentos de folhas e pecíolos fixos, seccionados à mão livre e fixados em glicerina, azul-de-astra ou fucsina. O estudo morfo-anatômico da folha e do pecíolo da E. macrophyllus contribuiu para ampliar e aprofundar as informações contidas nas Farmacopéias Brasileiras (1924, 1959). As características estruturais assinaladas auxiliam na identificação da espécie e fornece parâmetros que poderão ser aplicados futuramente no controle de qualidade farmacognóstico. E, inseriu no contexto da descrição anatômica, a presença de pêlos tectores e de células diafragmáticas, estruturas chaves no diagnóstico da espécie, não descritas pelas Farmacopéias Brasileiras (1929, 1959).

Echinodorus macrophyllus (Kunth) Micheli - Alismataceae, known as "chapéu-de-couro", "chá-mineiro", "erva-de-pântano", "erva-de-bugre", "congonha-do-brejo", "erva-do-brejo", occurs in Minas Gerais and São Paulo. Although it has therapeutic and commercial importance and is described in the two first editions of the Brazilian Pharmacopoeia (1924, 1959), there are few studies that contemplate it. This present work had the objective to study the leaf and petiole morpho-anatomy of A. macrophyllus, in order to extend its pharmacognosy knowledge, aiming at the quality control. The macroscopic description was carried through disarmed sight, with optical resources and the dimensions with a caliper. The anatomical c haracteristics had been determined, after the harvest, in the fragments of leaves and fixed petioles, freehand sectioned and stained either in glycerin, astra-blue or fuchsine. The morpho-anatomical study of the leaf and petiole of A. macrophyllust contributed to extend and deepen the information contained in the Brazilian Pharmacopoeia (1924, 1959). The designated structural characteristics assist in the identification of the species and supply parameters that could be applied in the pharmacognosy quality control in the future. And, the presence of non-glandular trichomes in the midribs (adaxial and abaxial surface) and the petiole exhibits diaphragm (specialized cells), key structures in the diagnosis of the species, that are not described in the Brazilian Pharmacopoeia (1924, 1959), were inserted in the context of the anatomical description.