Vibration sensor dataset for estimating fan coil motor health.

To enhance the field of continuous motor health monitoring, we present FAN-COIL-I, an extensive vibration sensor dataset derived from a Fan Coil motor. This dataset is uniquely positioned to facilitate the detection and prediction of motor health issues, enabling a more efficient maintenance scheduling process that can potentially obviate the need for regular checks. Unlike existing datasets, often created under controlled conditions or through simulations, FAN-COIL-I is compiled from real-world operational data, providing an invaluable resource for authentic motor diagnosis and predictive maintenance research. Gathered using a high-resolution 32 KHz sampling rate, the dataset encompasses comprehensive vibration readings from both the forward and rear sides of the Fan Coil motor over a continuous two-week period, offering a rare glimpse into the dynamic operational patterns of these systems in a corporate setting. FAN-COIL-I stands out not only for its real-world applicability but also for its potential to serve as a reliable benchmark for researchers and practitioners seeking to validate their models against genuine engine conditions.

Nebulized enriched heparin improves respiratory parameters in patients with COVID-19: a phase I/II randomized and triple-blind clinical trial.

To evaluate the safety and the potential antiviral treatment of inhaled enriched heparin in patients with COVID-19. The specific objectives were to investigate the anticoagulation profile, antiviral and anti-inflammatory effects, and respiratory evolution of inhaled enriched heparin. We conducted a randomized, triple-blind, placebo-controlled Phase I/II clinical trial in hospitalized adults with COVID-19 receiving inhalation of enriched heparin or saline (placebo) every 4 h for 7 days. Among the 27 patients who completed the study, no changes in blood coagulation parameters were observed, indicating the safety of inhaled enriched heparin. The group receiving enriched heparin showed a significant reduction in the need for supplemental oxygen and improvement in respiratory parameters, such as the PaO2/FiO2 ratio. Inhalation of enriched heparin is shown to be safe and has also demonstrated potential therapeutic benefits for patients with COVID-19. These promising results justify the continuation of the study to the next phase, Phase II/III, to further evaluate the therapeutic efficacy of inhaled enriched heparin in the treatment of COVID-19-associated viral pneumonia.Trial registration: ClinicalTrials.gov. 08/02/2021. Identifier: NCT04743011.

Inhibitors and activators for myotoxic phospholipase A2-like toxins from snake venoms - A structural overview.

Snakebite envenomations result in acute and chronic physical and psychological health effects on their victims, leading to a substantial socio-economic burden in tropical and subtropical countries. Local necrosis is one of the serious effects caused by envenomation, primarily induced by snake venoms from the Viperidae family through the direct action of components collectively denominated as myotoxins, including the phopholipase A2-like (PLA2-like) toxins. Considering the limitations of antivenoms in preventing the rapid development of local tissue damage caused by envenomation, the use of small molecule therapeutics has been suggested as potential first-aid treatments or as adjuvants to antivenom therapy. In this review, we provide an overview of the structural interactions of molecules exhibiting inhibitory activity toward PLA2-like toxins. Additionally, we discuss the implications for the myotoxic mechanism of PLA2-like toxins and the molecules involved in their activation, highlighting key differences between activators and inhibitors. Finally, we integrate all these results to propose a classification of inhibitors into three different classes and five sub-classes. Taking into account the structural and affinity information, we compare the different inhibitors/ligands to gain a deeper understanding of the structural basis for the effective inhibition of PLA2-like toxins. By offering these insights, we aim to contribute to the search for new and efficient inhibitor molecules to complement and improve current therapy by conventional antivenoms.

BthTX-I, a phospholipase A2-like toxin, is inhibited by the plant cinnamic acid derivative: chlorogenic acid.

Snakebite is a significant health concern in tropical and subtropical regions, particularly in Africa, Asia, and Latin America, resulting in more than 2.7 million envenomations and an estimated one hundred thousand fatalities annually. The Bothrops genus is responsible for the majority of snakebite envenomings in Latin America and Caribbean countries. Accidents involving snakes from this genus are characterized by local symptoms that often lead to permanent sequelae and death. However, specific antivenoms exhibit limited effectiveness in inhibiting local tissue damage. Phospholipase A2-like (PLA2-like) toxins emerge as significant contributors to local myotoxicity in accidents involving Bothrops species. As a result, they represent a crucial target for prospective treatments. Some natural and synthetic compounds have shown the ability to reduce or abolish the myotoxic effects of PLA2-like proteins. In this study, we employed a combination approach involving myographic, morphological, biophysical and bioinformatic techniques to investigate the interaction between chlorogenic acid (CGA) and BthTX-I, a PLA2-like toxin. CGA provided a protection of 71.8% on muscle damage in a pre-incubation treatment. Microscale thermophoresis and circular dichroism experiments revealed that CGA interacted with the BthTX-I while preserving its secondary structure. CGA exhibited an affinity to the toxin that ranks among the highest observed for a natural compound. Bioinformatics simulations indicated that CGA inhibitor binds to the toxin's hydrophobic channel in a manner similar to other phenolic compounds previously investigated. These findings suggest that CGA interferes with the allosteric transition of the non-activated toxin, and the stability of the dimeric assembly of its activated state.

An in silico molecular modeling approach of halolactone derivatives as potential inhibitors for human immunodeficiency virus type-1 reverse transcriptase enzyme.

Acquired Immune Deficiency Syndrome (AIDS) is an infectious disease caused by Human Immunodeficiency Virus (HIV) infection and its replication requires the Reverse Transcriptase (RT) enzyme. RT plays a key role in the HIV life cycle, making it one of the most important targets for designing new drugs. Thus, in order to increase therapeutic options against AIDS, halolactone derivatives (D-halolactone) that have been showed as potential non-nucleoside inhibitors of the RT enzyme were studied. In the present work, a series of D-halolactone were investigated by molecular modeling studies, combining Three-dimensional Quantitative Structure-Activity Relationship (3 D-QSAR), molecular docking and Molecular Dynamics (MD) techniques, to understand the molecular characteristics that promote biological activity. The internal and external validation parameters indicated that the 3 D-QSAR model has good predictive capacity and statistical significance. Contour maps provided useful information on the structural characteristics of compounds for anti-HIV-1 activity. The docking results showed that D-halolactone present good complementarity by the RT allosteric site. In MD simulations it was observed that the formation of enzyme-ligand complexes were favorable, and from the free energy decomposition it was found that Leu100, Val106, Tyr181, Try188, and Trp229 are key residues for stabilization in the enzymatic site. Thus, the results showed that the proposed models can be used to design promising HIV-1 RT inhibitors. Communicated by Ramaswamy H. Sarma.

Structural and functional studies of a snake venom phospholipase A2-like protein complexed to an inhibitor from Tabernaemontana catharinensis.

Snake envenomation is an ongoing global health problem and tropical neglected disease that afflicts millions of people each year. The only specific treatment, antivenom, has several limitations that affects its proper distribution to the victims and its efficacy against local effects, such as myonecrosis. The main responsible for this consequence are the phospholipases A2 (PLA2) and PLA2-like proteins, such as BthTX-I from Bothrops jararacussu. Folk medicine resorts to plants such as Tabernaemontana catharinensis to palliate these and other snakebite effects. Here, we evaluated the effect of its root bark extract and one of its isolated compounds, 12-methoxy-4-methyl-voachalotine (MMV), against the in vitro paralysis and muscle damage induced by BthTX-I. Secondary and quaternary structures of BthTX-I were not modified by the interaction with MMV. Instead, this compound interacted in an unprecedented way with the region inside the toxin hydrophobic channel and promoted a structural change in Val31, loop 58-71 and Membrane Disruption Site. Thus, we hypothesize that MMV inhibits PLA2-like proteins by preventing entrance of fatty acid into the hydrophobic channel. These data may explain the traditional use of T. catharinensis extract and confirm MMV as a promising candidate to complement antivenom or a structural guide to develop more effective inhibitors.

Analysis of the Reduction of Ergonomic Risks through the Implementation of an Automatic Tape Packaging Machine.

Many industrial sectors still lack automation resources to optimize their production processes, aiming to make manufacturing leaner and offer better working conditions to operators. Without these improvements, workers can suffer physical and even psychological damage from the ergonomic risks of the activities performed. Thus, the aim of this paper is to present the ergonomic evaluation of packaging tapes workstation before and after the implementation of an automatic packaging machine, called Guzzetti. In the Guzzetti context, the paper shows the implementation of an electrical system based on controlling a mechanical device powered by servomotors and controlled by a PLC is necessary. For ergonomic evaluation, the paper presents the application of three methods: Suzanne Rodger, Strain Index, called Moore and Garg and REBA (Rapid Entire Body Assessment). With the results collection, was possible to obtain improvements in ergonomic risks that changed from the intermediate level to low level in all methods.

Identification of potential inhibitors of Schistosoma mansoni purine nucleoside phosphorylase from neolignan compounds using molecular modelling approaches.

Schistosomiasis is a parasitic disease that is part of the neglected tropical diseases (NTDs), which cause significant levels of morbidity and mortality in millions of people throughout the world. The enzyme purine nucleoside phosphorylase from Schistosoma mansoni (SmPNP) represents a potential target for discovering new agents, and neolignans stand out as an important class of compounds. In this work, molecular modeling studies and biological assays of a set of neolignans were conducted against the PNP enzymes of the parasite and the human homologue (HssPNP). The results of the molecular docking described that the neolignans showed good complementarity by the active site of SmPNP. Molecular dynamics (MD) studies revealed that both complexes (Sm/HssPNP - neolignan compounds) were stable by analyzing the root mean square deviation (RMSD) values, and the binding free energy values suggest that the selected structures can interact and inhibit the catalytic activity of the SmPNP. Finally, the biological assay indicated that the selected neolignans presented a better molecular profile of inhibition compared to the human enzyme, as these ligands did not have the capacity to inhibit enzymatic activity, indicating that these compounds are promising candidates and that they can be used in future research in chemotherapy for schistosomiasis.Communicated by Ramaswamy H. Sarma.

Nebulized enriched heparin to treat no critical patients with Sars-Cov-2: Triple-blind clinical trial.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a viral respiratory disease that spreads rapidly, reaching pandemic status, causing the collapse of numerous health systems, and a strong economic and social impact. The treatment so far has not been well established and there are several clinical trials testing known drugs that have antiviral activity, due to the urgency that the global situation imposes. Drugs with specific mechanisms of action can take years to be discovered, while vaccines may also take a long time to be widely distributed while new virus variants emerge. Thus, drug repositioning has been shown to be a good strategy for defining new therapeutic approaches. Studies of the effect of enriched heparin in the replication of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) in vitro assays justify the advance for clinical tests. METHODS AND ANALYSIS: A phase I/II triple-blind parallel clinical trial will be conducted. Fifty participants with radiological diagnosis of grade IIA pneumonia will be selected, which will be allocated in 2 arms. Participants allocated in Group 1 (placebo) will receive nebulized 0.9% saline. Participants allocated in Group 2 (intervention) will receive nebulized enriched heparin (2.5 mg/mL 0.9% saline). Both groups will receive the respective solutions on a 4/4 hour basis, for 7 days. The main outcomes of interest will be safety (absence of serious adverse events) and efficacy (measured by the viral load).Protocols will be filled on a daily basis, ranging from day 0 (diagnosis) until day 8.

Gallic acid anti-myotoxic activity and mechanism of action, a snake venom phospholipase A2 toxin inhibitor, isolated from the medicinal plant Anacardium humile.

Snakebite envenoming is the cause of an ongoing health crisis in several regions of the world, particularly in tropical and neotropical countries. This scenario creates an urgent necessity for new practical solutions to address the limitations of current therapies. The current study investigated the isolation, phytochemical characterization, and myotoxicity inhibition mechanism of gallic acid (GA), a myotoxin inhibitor obtained from Anacardium humile. The identification and isolation of GA was achieved by employing analytical chromatographic separation, which exhibited a compound with retention time and nuclear magnetic resonance spectra compatible with GA's commercial standard and data from the literature. GA alone was able to inhibit the myotoxic activity induced by the crude venom of Bothrops jararacussu and its two main myotoxins, BthTX-I and BthTX-II. Circular dichroism (CD), fluorescence spectroscopy (FS), dynamic light scattering (DLS), and interaction studies by molecular docking suggested that GA forms a complex with BthTX-I and II. Surface plasmon resonance (SPR) kinetics assays showed that GA has a high affinity for BthTX-I with a KD of 9.146 × 10-7 M. Taken together, the two-state reaction mode of GA binding to BthTX-I, and CD, FS and DLS assays, suggest that GA is able to induce oligomerization and secondary structure changes for BthTX-I and -II. GA and other tannins have been shown to be effective inhibitors of snake venoms' toxic effects, and herein we demonstrated GA's ability to bind to and inhibit a snake venom PLA2, thus proposing a new mechanism of PLA2 inhibition, and presenting more evidence of GA's potential as an antivenom compound.

Analysis of the prison population's mental health in Sars-Cov-2 pandemic: Qualitative analysis.

This study aimed to analyze the possible impacts on the prison population's mental health in the context of the new COVID-19 pandemic. Qualitative study was carried out following a lexical and content analysis using the software IRaMuTeQ, version 0.7 alpha 2, in the speech of the short communication and headlines from newspapers. Three groups emerged from the analysis: "spatial conditions for infection" (39.2% of the text segments); "disease outbreaks in prisons" (30,4%) and "public responsibility" (30,4%). Precarious conditions of prisons, high rate of infections and psychiatric illnesses, and lack of government assistance are issues that should be given special attention in order to formulate health promotion and prevention policies focusing on mental health in prison population.

In-solution structural studies involving a phospholipase A2-like myotoxin and a natural inhibitor: Plasticity of oligomeric assembly affects mechanisms of inhibition.

Snakebite envenomation has been categorized by World Health Organization as a category A neglected tropical disease, since it causes chronic psychological disorders, physical disablement and death. Ophidian accidents may cause local myonecrosis that cause drastic sequelae, which are not efficiently neutralized via serum therapy. Phospholipase A2-like (PLA2-like) myotoxins have a major role in the local effects caused by several snake venoms. We previously demonstrated that chicoric acid (CA) is an efficient inhibitor of the BthTX-I myotoxin and solved the X-ray structure of complex. Herein, we assess the oligomeric behavior of the BthTX-I/CA complex in solution under different physical-chemical conditions and using toxin obtained by two different biochemical methodologies to fully elucidate structural bases of inhibition of myotoxins by CA. We demonstrated the ability of PLA2-like proteins to form different oligomeric assemblies in the presence of certain inhibitors, which can also be modulated by buffer polarity change. In the presence of ethanol, BthTX-I/CA remains predominantly in a monomeric conformation, which prevents it from being in its active form (dimeric conformation). In contrast, in the absence of ethanol, the tetramer assembly was observed, which hid key regions of the protein responsible for docking and disruption of the muscle membrane. Therefore, the "plasticity" of these proteins with regard to their abilities to form oligomeric assemblies is a key issue for the future development of therapeutic agents to complement of serum therapy.

Perfil dos pacientes com infecções relacionadas à assistência à saúde em unidade de terapia intensiva de um hospital público / Profile of patients presenting hospital infection at public hospital's intensive care units / Perfil de pacientes con infección hospitalar en la unidad de terapia intensiva de un hospital público

Justificativa e Objetivo: A Unidade de Terapia Intensiva (UTI) desempenha atualmente um papel decisivo na chance de sobrevida de pacientes gravemente enfermos, sejam eles vítimas de trauma ou de qualquer outra condição clínica extremamente grave. Em contrapartida, se tornou o principal local de ocorrência das infecções hospitalares que aumentam a morbimortalidade e os custos assistenciais, o que vem representando, nos últimos anos, um importante agravo de saúde pública. Deste modo, este estudo objetiva conhecer o perfil dos pacientes com infecções relacionadas à assistência à saúde na UTI Adulto de um hospital público do Distrito Federal, Brasil. Método: Estudo do tipo retrospectivo, de caráter descritivo, com abordagem quantitativa. Os dados foram coletados diretamente do prontuário eletrônico dos pacientes. Resultados: Foram encontrados 51 pacientes com infecção hospitalar, predominantemente do sexo masculino, idosos, entre os quais 24 eram oriundos do próprio hospital, 21 de outros hospitais e 6 das Unidades de Pronto Atendimento. O principal motivo da internação foi clínico, com percentual de 76,4%. Em relação à topografia, 23 pacientes apresentaram quadro de pneumonia e 18 tiveram infecções do trato urinário. O tempo médio de internação foi de 31 dias e o índice de mortalidade foi de 37,2%. Conclusão: Tão importante quanto o investimento em tecnologia de ponta em tratamento intensivo, o conhecimento do perfil dos doentes críticos é uma necessidade que se impõe, pois pode auxiliar o enfermeiro nas diretrizes das admissões, diagnóstico de enfermagem e altas dessa unidade.(AU)

Background and objective Intensive Care Unit (ICU) currently plays a decisive role in the chance of survival of critically ill patients, whether they are victims of trauma or any other extremely serious clinical condition; on the other hand, it has become the main place of occurrence of hospital infections that result in increased morbidity, mortality, health care costs and has, in recent years, represented an important public health problem. Thus, this study aims to know the profile of patients with infections related to health care in the Adult ICU of a public hospital in the Federal District ­ Brazil. Method: Retrospective, descriptive study with a quantitative approach. Data were collected directly from patients' electronic medical records. Results: 51 patients with nosocomial infection were found, predominantly male, elderly, with 24 patients coming from the hospital itself, 21 from other hospitals and 06 from the Emergency Care Units. The main reason for hospitalization was clinical, with a percentage of 76.4%. Regarding the topography, 23 patients had pneumonia and 18 urinary tract infections. The average hospital stay was 31 days, the mortality rate was 37.2%. Conclusion: As important as the investment in cutting-edge technology in intensive care, knowledge of the profile of critically ill patients is an imperative that can help the nurse in the guidelines of admissions, nursing diagnosis and discharge from this unit.(AU)

Justificación y objetivo: La unidad de terapia intensiva -UTI desempeña actualmente un papel decisivo en la posibilidad de supervivencia de pacientes gravemente enfermos, ya sean víctimas de trauma o de cualquier otra condición clínica extremadamente grave, en contrapartida se ha convertido en el principal lugar de ocurrencia de las infecciones hospitalarias que resultan en el aumento de la morbimortalidad y de los costos asistenciales y viene representando en los últimos años un importante agravio de salud pública de este modo, este estudio objetiva conocer el perfil de los pacientes con infección hospitalaria en la Unidad de Terapia Intensiva Adulto de un hospital público del DF. Métodos: Estudio de carácter retrospectivo, descriptivo, con enfoque cuantitativo. Los datos fueron recogidos directamente de los registros médicos electrónicos de pacientes. Resultados: Se encontraron 51 pacientes con infección nosocomial, masculina predominante, más viejo, y 24 pacientes están llegando desde el hospital y otros 21 hospitales y 6 de la UPM. La razón principal para la admisión fue clínico, con un porcentaje de 76,4%. En cuanto a la topografía, 23 pacientes tenían neumonía y sepsis. La duración media de la estancia fue de 31 días, la tasa de mortalidad fue del 37,2%. Conclusion: Tan importante como la inversión en tecnología de cuidados intensivos, el conocimiento del perfil de los pacientes críticamente enfermos es una necesidad para imponer y puede ayudar a las enfermeras en las directrices de admisión, ealtas diagnóstico de enfermería de esta unidad.(AU)

The allosteric activation mechanism of a phospholipase A2-like toxin from Bothrops jararacussu venom: a dynamic description.

The activation process of phospholipase A2-like (PLA2-like) toxins is a key step in their molecular mechanism, which involves oligomeric changes leading to the exposure of specific sites. Few studies have focused on the characterization of allosteric activators and the features that distinguish them from inhibitors. Herein, a comprehensive study with the BthTX-I toxin from Bothrops jararacussu venom bound or unbound to α-tocopherol (αT) was carried out. The oligomerization state of BthTX-I bound or unbound to αT in solution was studied and indicated that the toxin is predominantly monomeric but tends to oligomerize when complexed with αT. In silico molecular simulations showed the toxin presents higher conformational changes in the absence of αT, which suggests that it is important to stabilize the structure of the toxin. The transition between the two states (active/inactive) was also studied, showing that only the unbound BthTX-I system could migrate to the inactive state. In contrast, the presence of αT induces the toxin to leave the inactive state, guiding it towards the active state, with more regions exposed to the solvent, particularly its active site. Finally, the structural determinants necessary for a molecule to be an inhibitor or activator were analyzed in light of the obtained results.

Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19.

BACKGROUND: Hydroxychloroquine and azithromycin have been used to treat patients with coronavirus disease 2019 (Covid-19). However, evidence on the safety and efficacy of these therapies is limited. METHODS: We conducted a multicenter, randomized, open-label, three-group, controlled trial involving hospitalized patients with suspected or confirmed Covid-19 who were receiving either no supplemental oxygen or a maximum of 4 liters per minute of supplemental oxygen. Patients were randomly assigned in a 1:1:1 ratio to receive standard care, standard care plus hydroxychloroquine at a dose of 400 mg twice daily, or standard care plus hydroxychloroquine at a dose of 400 mg twice daily plus azithromycin at a dose of 500 mg once daily for 7 days. The primary outcome was clinical status at 15 days as assessed with the use of a seven-level ordinal scale (with levels ranging from one to seven and higher scores indicating a worse condition) in the modified intention-to-treat population (patients with a confirmed diagnosis of Covid-19). Safety was also assessed. RESULTS: A total of 667 patients underwent randomization; 504 patients had confirmed Covid-19 and were included in the modified intention-to-treat analysis. As compared with standard care, the proportional odds of having a higher score on the seven-point ordinal scale at 15 days was not affected by either hydroxychloroquine alone (odds ratio, 1.21; 95% confidence interval [CI], 0.69 to 2.11; P = 1.00) or hydroxychloroquine plus azithromycin (odds ratio, 0.99; 95% CI, 0.57 to 1.73; P = 1.00). Prolongation of the corrected QT interval and elevation of liver-enzyme levels were more frequent in patients receiving hydroxychloroquine, alone or with azithromycin, than in those who were not receiving either agent. CONCLUSIONS: Among patients hospitalized with mild-to-moderate Covid-19, the use of hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days as compared with standard care. (Funded by the Coalition Covid-19 Brazil and EMS Pharma; ClinicalTrials.gov number, NCT04322123.).

Neutralization of a bothropic PLA2-like protein by caftaric acid, a novel potent inhibitor of ophidian myotoxicity.

Envenoming by snakebite is an important global health issue that has received little attention, leading the World Health Organization to naming it as neglected tropical disease. Several snakebites present serious local symptoms manifested on victims that may not be efficiently neutralized by serum therapy. Phospholipase A2-like (PLA2-like) toxins are present in Viperidae venoms and are responsible for local myotoxic activity. Herein, we investigated the association between BthTX-I toxin and caftaric acid (CFT), a molecule present in plants. CFT neutralized neuromuscular blocking and muscle-damaging activities promoted by BthTX-I. Calorimetric and light-scattering assays demonstrated that CFT inhibitor interacted with dimeric BthTX-I. Bioinformatics simulations indicated that CFT inhibitor binds to the toxin's hydrophobic channel (HCh). According to the current myotoxic mechanism, three different regions of PLA2-like toxins have specific tasks: protein allosteric activation (HCh), membrane dockage (MDoS), and membrane rupture (MDiS). We propose CFT inhibitor interferes with the allosteric activation, which is related to the conformation change leading to the exposure/alignment of MDoS/MDiS region. This is the first report of a PLA2-like toxin fully inhibited by a compound that interacts only with its HCh region. Thus, CFT is a novel candidate to complement serum therapy and improve the treatment of snakebite.

Design of Inhibitors for Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH) Enzyme of Leishmania mexicana.

BACKGROUND: Leishmaniosis is a neglected tropical disease and glyceraldehyde 3- phosphate dehydrogenase (GAPDH) is a key enzyme in the design of new drugs to fight this disease. OBJECTIVE: The present study aimed to evaluate potential inhibitors of GAPDH enzyme found in Leishmania mexicana (L. mexicana). METHODS: A search for novel antileishmanial molecules was carried out based on similarities from the pharmacophoric point of view related to the binding site of the crystallographic enzyme using the ZINCPharmer server. The molecules selected in this screening were subjected to molecular docking and molecular dynamics simulations. RESULTS: Consensual analysis of the docking energy values was performed, resulting in the selection of ten compounds. These ligand-receptor complexes were visually inspected in order to analyze the main interactions and subjected to toxicophoric evaluation, culminating in the selection of three compounds, which were subsequently submitted to molecular dynamics simulations. The docking results showed that the selected compounds interacted with GAPDH from L. mexicana, especially by hydrogen bonds with Cys166, Arg249, His194, Thr167, and Thr226. From the results obtained from molecular dynamics, it was observed that one of the loop regions, corresponding to the residues 195-222, can be related to the fitting of the substrate at the binding site, assisting in the positioning and the molecular recognition via residues responsible for the catalytic activity. CONCLUSION: The use of molecular modeling techniques enabled the identification of promising compounds as inhibitors of the GAPDH enzyme from L. mexicana, and the results obtained here can serve as a starting point to design new and more effective compounds than those currently available.

Search for efficient inhibitors of myotoxic activity induced by ophidian phospholipase A2-like proteins using functional, structural and bioinformatics approaches.

Ophidian accidents are considered an important neglected tropical disease by the World Health Organization. Particularly in Latin America, Bothrops snakes are responsible for the majority of the snakebite envenomings that are not efficiently treated by conventional serum therapy. Thus, the search for simple and efficient inhibitors to complement this therapy is a promising research area, and a combination of functional and structural assays have been used to test candidate ligands against specific ophidian venom compounds. Herein, we tested a commercial drug (acetylsalicylic acid, ASA) and a plant compound with antiophidian properties (rosmarinic acid, RA) using myographic, crystallographic and bioinformatics experiments with a phospholipase A2-like toxin, MjTX-II. MjTX-II/RA and MjTX-II/ASA crystal structures were solved at high resolution and revealed the presence of ligands bound to different regions of the toxin. However, in vitro myographic assays showed that only RA is able to prevent the myotoxic effects of MjTX-II. In agreement with functional results, molecular dynamics simulations showed that the RA molecule remains tightly bound to the toxin throughout the calculations, whereas ASA molecules tend to dissociate. This approach aids the design of effective inhibitors of PLA2-like toxins and, eventually, may complement serum therapy.

New records of Niceforo's big-eared bat, Trinycterisnicefori (Sanborn, 1949) (Chiroptera, Phyllostomidae), from the state of Maranhão, Brazil.

Niceforo's big-eared bat, Trinycterisnicefori (Sanborn, 1949), is a monotypic species which has been recorded in a number of Brazilian states, but has a disjunct distribution in this country. This study presents the first record of T.nicefori in the Brazilian state of Maranhão. The specimens were collected in the municipalities of Godofredo Viana and Cândido Mendes, in fragments of the Amazon forest. One male (forearm: 38.00 mm, weight: 6 g) and one female (39.68 mm, 8 g) specimens were collected. The specimens presented chestnut-colored fur, and a chin with a pair of dermal pads arranged in a V-shape, without a central papilla. The COI gene sequences were plotted in the BOLD Systems platform, which confirmed the morphological identification of the species, with a 99.1% similarity in the male, and 99.4% in the female to existing sequences. This record extends the known distribution of T.nicefori in Brazil by approximately 310 km to the most eastern part of the Amazon Biome.

Structural basis of phospholipase A2-like myotoxin inhibition by chicoric acid, a novel potent inhibitor of ophidian toxins.

BACKGROUND: Specific compounds found in vegetal species have been demonstrated to be efficient inhibitors of snake toxins, such as phospholipase A2-like (PLA2-like) proteins. These particular proteins, present in several species of vipers (Viperidae), induce a severe local myotoxic effect in prey and human victims, and this effect is often not efficiently neutralized by the regular serum therapy. PLA2-like proteins have been functionally and structurally studied since the early 1990s; however, a comprehensive molecular mechanism was proposed only recently. METHODS: Myographic and histological techniques were used to evaluate the inhibitory effect of chicoric acid (CA) against BthTX-I myotoxin. Isothermal titration calorimetry assays were used to measure the affinity between the inhibitor and the toxin. X-ray crystallography was used to reveal details of this interaction. RESULTS: CA prevented the blockade of indirectly evoked muscle contraction and inhibited muscle damage induced by BthTX-I. The inhibitor binds to the toxin with the highest affinity measured for a natural compound in calorimetric assays. The crystal structure and molecular dynamics simulations demonstrated that CA binds at the entrance of the hydrophobic channel of the toxin and binds to one of the clusters that participates in membrane disruption. CONCLUSIONS: CA prevents the myotoxic activity of the toxin, preventing its activation by simultaneous binding with two critical regions. GENERAL SIGNIFICANCE: CA is a potential myotoxic inhibitor to other PLA2-like proteins and a possible candidate to complement serum therapy.