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1.
J Pediatr ; 274: 114216, 2024 Jul 27.
Article de Anglais | MEDLINE | ID: mdl-39074734

RÉSUMÉ

Discordance in perception of disease activity between adolescent patients with lupus and their providers may influence disease outcomes. We found that patients endorsed higher perceptions of disease activity than providers. Discordance was present at all levels of disease activity, particularly in patients with high activity, nephritis, and/or taking corticosteroids or mycophenolate mofetil.

2.
Proteomics ; 24(18): e2100313, 2024 Sep.
Article de Anglais | MEDLINE | ID: mdl-38850190

RÉSUMÉ

Evolutionary relationships among parasites of the subfamily Leishmaniinae, which comprises pathogen agents of leishmaniasis, were inferred based on differential protein expression profiles from mass spectrometry-based quantitative data using the PhyloQuant method. Evolutionary distances following identification and quantification of protein and peptide abundances using Proteome Discoverer and MaxQuant software were estimated for 11 species from six Leishmaniinae genera. Results clustered all dixenous species of the genus Leishmania, subgenera L. (Leishmania), L. (Viannia), and L. (Mundinia), sister to the dixenous species of genera Endotrypanum and Porcisia. Placed basal to the assemblage formed by all these parasites were the species of genera Zelonia, Crithidia, and Leptomonas, so far described as monoxenous of insects although eventually reported from humans. Inferences based on protein expression profiles were congruent with currently established phylogeny using DNA sequences. Our results reinforce PhyloQuant as a valuable approach to infer evolutionary relationships within Leishmaniinae, which is comprised of very tightly related trypanosomatids that are just beginning to be phylogenetically unraveled. In addition to evolutionary history, mapping of species-specific protein expression is paramount to understand differences in infection processes, tissue tropisms, potential to jump from insects to vertebrates including humans, and targets for species-specific diagnostic and drug development.


Sujet(s)
Leishmania , Phylogenèse , Trypanosomatina , Leishmania/génétique , Leishmania/métabolisme , Leishmania/classification , Trypanosomatina/génétique , Trypanosomatina/métabolisme , Trypanosomatina/classification , Évolution moléculaire , Animaux , Protéines de protozoaire/génétique , Protéines de protozoaire/métabolisme , Protéomique/méthodes , Protéome/génétique , Protéome/analyse , Protéome/métabolisme , Crithidia/génétique , Crithidia/métabolisme
3.
Inflammopharmacology ; 31(6): 3227-3241, 2023 Dec.
Article de Anglais | MEDLINE | ID: mdl-37806984

RÉSUMÉ

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes cartilage damage. Anti-inflammatories are widely used in the management of RA, but they can have side effects such as gastrointestinal and/or cardiovascular disorders. Studies published by our group showed that the synthesis of hybrid triazole analogs neolignan-celecoxib containing the substituent groups sulfonamide (L15) or carboxylic acid (L18) exhibited anti-inflammatory activity in an acute model of inflammation, inhibited expression of P-selectin related to platelet activation and did not induce gastric ulcer, minimizing the related side effects. In continuation, the present study evaluated the anti-inflammatory effects of these analogs in an experimental model of arthritis and on the functions of one of the important cells in this process, macrophages. Mechanical hyperalgesia, joint edema, leukocyte recruitment to the joint and damage to cartilage in experimental arthritis and cytotoxicity, spread of disease, phagocytic activity and nitric oxide (NO) and hydrogen peroxide production by macrophages were evaluated. Pre-treatment with L15 and L18 reduced mechanical hyperalgesia, joint edema and the influx of leukocytes into the joint cavity after different periods of the stimulus. The histological evaluation of the joint showed that L15 and L18 reduced cartilage damage and there was no formation of rheumatoid pannus. Furthermore, L15 and L18 were non-cytotoxic. The analogs inhibited the spreading, the production of NO and hydrogen peroxide. L15 decreased the phagocytosis. Therefore, L15 and L18 may be potential therapeutic prototypes to treat chronic inflammatory diseases such as RA.


Sujet(s)
Arthrite expérimentale , Polyarthrite rhumatoïde , Lignanes , Animaux , Célécoxib/effets indésirables , Zymosan , Lignanes/usage thérapeutique , Hyperalgésie/traitement médicamenteux , Peroxyde d'hydrogène , Arthrite expérimentale/induit chimiquement , Arthrite expérimentale/traitement médicamenteux , Polyarthrite rhumatoïde/traitement médicamenteux , Anti-inflammatoires/usage thérapeutique , Oedème/traitement médicamenteux
4.
Chem Biol Interact ; 382: 110622, 2023 Sep 01.
Article de Anglais | MEDLINE | ID: mdl-37442286

RÉSUMÉ

The A-series is the most recent generation of chemical warfare nerve agents (CWA) which act directly on the inhibition of the human acetylcholinesterase (HssAChE) enzyme. These compounds lack accurate experimental data on their physicochemical properties, and there is no evidence that traditional antidotes effectively reactivate HssAChE inhibited by them. In the search for potential antidotes, we employed virtual screening, molecular docking, and molecular dynamics (MD) simulations for the theoretical assessment of the performance of a library of Mannich phenols as potential reactivators of HssAChE inhibited by the Novichok agents A-230, A-232, and A-234, in comparison with the commercial oximes pralidoxime (2-PAM), asoxime (HI-6), trimedoxime (TMB-4), and obidoxime. Following the near-attack conformation (NAC) approach, our results suggest that the compounds assessed would face difficulties in triggering the proposed nucleophilic in-line displacement mechanism. Despite this, it was observed that certain Mannich phenols presented similar or superior results to those obtained by reference oximes against A-232 and A-234 model, suggesting that these compounds can adopt more favourable conformations. Additional binding energy calculations confirmed the stability of the model/ligands complexes and the reactivating potential observed in the molecular docking and MD studies. Our findings indicate that the Mannich phenols could be alternative antidotes and that their efficacy should be evaluated experimentally against the A-series CWA.


Sujet(s)
Armes chimiques , Réactivateurs de la cholinestérase , Agents neurotoxiques , Humains , Antidotes/pharmacologie , Réactivateurs de la cholinestérase/pharmacologie , Acetylcholinesterase/métabolisme , Simulation de docking moléculaire , Anticholinestérasiques/pharmacologie , Anticholinestérasiques/composition chimique , Oximes/pharmacologie , Oximes/composition chimique , Trimédoxime/composition chimique , Trimédoxime/pharmacologie , Armes chimiques/pharmacologie , Composés de pyridinium/pharmacologie
5.
J Mol Model ; 29(6): 183, 2023 May 22.
Article de Anglais | MEDLINE | ID: mdl-37212923

RÉSUMÉ

CONTEXT: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19 infection and responsible for millions of victims worldwide, remains a significant threat to public health. Even after the development of vaccines, research interest in the emergence of new variants is still prominent. Currently, the focus is on the search for effective and safe drugs, given the limitations and side effects observed for the synthetic drugs administered so far. In this sense, bioactive natural products that are widely used in the pharmaceutical industry due to their effectiveness and low toxicity have emerged as potential options in the search for safe drugs against COVID-19. Following this line, we screened 10 bioactive compounds derived from cholesterol for molecules capable of interacting with the receptor-binding domain (RBD) of the spike protein from SARS-CoV-2 (SC2Spike), responsible for the virus's invasion of human cells. Rounds of docking followed by molecular dynamics simulations and binding energy calculations enabled the selection of three compounds worth being experimentally evaluated against SARS-CoV-2. METHODS: The 3D structures of the cholesterol derivatives were prepared and optimized using the Spartan 08 software with the semi-empirical method PM3. They were then exported to the Molegro Virtual Docking (MVD®) software, where they were docked onto the RBD of a 3D structure of the SC2Spike protein that was imported from the Protein Data Bank (PDB). The best poses obtained from MVD® were subjected to rounds of molecular dynamics simulations using the GROMACS software, with the OPLS/AA force field. Frames from the MD simulation trajectories were used to calculate the ligand's free binding energies using the molecular mechanics - Poisson-Boltzmann surface area (MM-PBSA) method. All results were analyzed using the xmgrace and Visual Molecular Dynamics (VMD) software.


Sujet(s)
Produits biologiques , COVID-19 , Humains , SARS-CoV-2 , Produits biologiques/pharmacologie , Simulation de dynamique moléculaire , Bases de données de protéines , Simulation de docking moléculaire , Antiviraux/pharmacologie
6.
medRxiv ; 2023 May 11.
Article de Anglais | MEDLINE | ID: mdl-37214968

RÉSUMÉ

Background: NVX-CoV2373, an adjuvanted, recombinant SARS-CoV-2 spike (rS) protein vaccine, consistently demonstrated protective efficacy against COVID-19 in clinical trials and has received regulatory authorizations or approvals worldwide. Methods: PREVENT-19 (NCT04611802) is a phase 3, randomized, observer-blinded, placebo-controlled trial evaluating safety, immunogenicity, and efficacy of NVX-CoV2373 in ≈30 000 participants ≥18 years in the United States and Mexico. Vaccine humoral immune response (ie, serum immunoglobulin [IgG] antibodies, hACE2 receptor binding inhibition antibodies, and neutralizing antibodies to SARS-CoV-2) (ancestral strain) was assessed in 1200 participants randomly selected and equally divided between participants 18-64 and ≥65 years. Results: In the per protocol analysis, NVX-CoV2373 induced vigorous serum antibody responses among the 1063 analyzed participants who were SARS-CoV-2 seronegative at baseline, received both doses of study treatment, and had serology results available 2 weeks after dose 2. Geometric mean (GM) responses in both younger and older adults were higher among recipients of vaccine versus placebo for IgG (64 259 vs 121 and 37 750 vs 133 ELISA units, respectively), hACE2 receptor binding inhibition GM titers (GMTs) (222 vs 5 and 136 vs 5, respectively), and neutralizing antibody GMTs (1303 vs 11 and 900 vs 11, respectively). Humoral responses were 30-40% lower in participants ≥65 years or HIV-positive; however, seroconversion rates were high and comparable between the age cohorts, regardless of HIV serostatus. Conclusions: NVX-CoV2373 elicited robust humoral immune responses against ancestral SARS-CoV-2 virus 2 weeks following the second vaccination in adult PREVENT-19 participants, consistent with previously reported high vaccine efficacy.

7.
J Biomol Struct Dyn ; 40(12): 5309-5319, 2022 08.
Article de Anglais | MEDLINE | ID: mdl-33410376

RÉSUMÉ

Ricin is a potent cytotoxin with no available antidote. Its catalytic subunit, RTA, damages the ribosomal RNA (rRNA) of eukaryotic cells, preventing protein synthesis and eventually leading to cell death. The combination between easiness of obtention and high toxicity turns ricin into a potential weapon for terrorist attacks, urging the need of discovering effective antidotes. On this context, we used computational techniques, in order to identify potential ricin inhibitors among approved drugs. Two libraries were screened by two different docking algorithms, followed by molecular dynamics simulations and MM-PBSA calculations in order to corroborate the docking results. Three drugs were identified as potential ricin inhibitors: deferoxamine, leucovorin and plazomicin. Our calculations showed that these compounds were able to, simultaneously, form hydrogen bonds with residues of the catalytic site and the secondary binding site of RTA, qualifying as potential antidotes against intoxication by ricin.Communicated by Ramaswamy H. Sarma.


Sujet(s)
Ricine , Antidotes , Repositionnement des médicaments , Simulation de docking moléculaire , Simulation de dynamique moléculaire , Ricine/composition chimique , Ricine/métabolisme , Ricine/pharmacologie
8.
J Biomol Struct Dyn ; 40(11): 5229-5242, 2022 07.
Article de Anglais | MEDLINE | ID: mdl-33416020

RÉSUMÉ

The acute respiratory syndrome caused by the SARS-CoV-2, known as COVID-19, has been ruthlessly tormenting the world population for more than six months. However, so far no effective drug or vaccine against this plague have emerged yet, despite the huge effort in course by researchers and pharmaceutical companies worldwide. Willing to contribute with this fight to defeat COVID-19, we performed a virtual screening study on a library containing Food and Drug Administration (FDA) approved drugs, in a search for molecules capable of hitting three main molecular targets of SARS-CoV-2 currently available in the Protein Data Bank (PDB). Our results were refined with further molecular dynamics (MD) simulations and MM-PBSA calculations and pointed to 7 multi-target hits which we propose here for experimental evaluation and repurposing as potential drugs against COVID-19. Additional rounds of docking, MD simulations and MM-PBSA calculations with remdesivir suggested that this compound can also work as a multi-target drug against SARS-CoV-2.Communicated by Ramaswamy H. Sarma.


Sujet(s)
Traitements médicamenteux de la COVID-19 , SARS-CoV-2 , Protéases 3C des coronavirus , Cysteine endopeptidases , Humains , Simulation de docking moléculaire , Simulation de dynamique moléculaire , Préparations pharmaceutiques , Inhibiteurs de protéases
9.
J Enzyme Inhib Med Chem ; 36(1): 1370-1377, 2021 Dec.
Article de Anglais | MEDLINE | ID: mdl-34148470

RÉSUMÉ

Organophosphorus poisoning caused by some pesticides and nerve agents is a life-threating condition that must be swiftly addressed to avoid casualties. Despite the availability of medical countermeasures, the clinically available compounds lack a broad spectrum, are not effective towards all organophosphorus toxins, and have poor pharmacokinetics properties to allow them crossing the blood-brain barrier, hampering cholinesterase reactivation at the central nervous system. In this work, we designed and synthesised novel isatin derivatives, linked to a pyridinium 4-oxime moiety by an alkyl chain with improved calculated properties, and tested their reactivation potency against paraoxon- and NEMP-inhibited acetylcholinesterase in comparison to the standard antidote pralidoxime. Our results showed that these compounds displayed comparable in vitro reactivation also pointed by the in silico studies, suggesting that they are promising compounds to tackle organophosphorus poisoning.


Sujet(s)
Acetylcholinesterase/effets des médicaments et des substances chimiques , Réactivateurs de la cholinestérase/pharmacologie , Isatine/pharmacologie , Pyridines/pharmacologie , Simulation numérique , Techniques in vitro
10.
Chest ; 159(4): 1517-1530, 2021 04.
Article de Anglais | MEDLINE | ID: mdl-33031832

RÉSUMÉ

BACKGROUND: Management of patients with interstitial lung disease (ILD) requires subspecialized, comprehensive, multidisciplinary care. The Pulmonary Fibrosis Foundation established the Care Center Network (CCN) in 2013 with identified criteria to become a designated CCN site. Despite these criteria, the essential components of an ILD clinic remain unknown. RESEARCH QUESTIONS: How are ILD clinics within the CCN structured? What are the essential components of an ILD clinic according to ILD physician experts, patients, and caregivers? STUDY DESIGN AND METHODS: This study had three components. First, all 68 CCN sites were surveyed to determine the characteristics of their current ILD clinics. Second, an online, three-round modified Delphi survey was conducted between October and December 2019 with 48 ILD experts participating in total. Items for round 1 were generated using expert interviews. During rounds 1 and 2, experts rated the importance of each item on a 5-point Likert scale. The a priori threshold for consensus was more than 75% of experts rating an item as important or very important. In round 3, experts graded items that met consensus and ranked items deemed essential for an ILD clinic. Third, ILD patient and caregiver focus groups were conducted and analyzed for content to determine their perspectives of an ideal ILD clinic. RESULTS: Forty items across four categories (members, infrastructure, resources, and multidisciplinary conference) achieved consensus as essential to an ILD clinic. Patient and caregiver focus groups identified three major themes: comprehensive, patient-centered medical care; expanded access to care; and comprehensive support for living and coping with ILD. INTERPRETATION: The essential components of an ILD clinic are well-aligned between physician experts and patients. Future research can use these findings to evaluate the impact of these components on patient outcomes and to inform best practices for ILD clinics throughout the world.


Sujet(s)
Établissements de soins ambulatoires/organisation et administration , Pneumopathies interstitielles/thérapie , Modèles d'organisation , Colorado , Méthode Delphi , Groupes de discussion , Humains , États-Unis
11.
Toxins (Basel) ; 12(12)2020 11 26.
Article de Anglais | MEDLINE | ID: mdl-33256167

RÉSUMÉ

Ricin is a toxin found in the castor seeds and listed as a chemical weapon by the Chemical Weapons Convention (CWC) due to its high toxicity combined with the easiness of obtention and lack of available antidotes. The relatively frequent episodes of usage or attempting to use ricin in terrorist attacks reinforce the urge to develop an antidote for this toxin. In this sense, we selected in this work the current RTA (ricin catalytic subunit) inhibitor with the best experimental performance, as a reference molecule for virtual screening in the PubChem database. The selected molecules were then evaluated through docking studies, followed by drug-likeness investigation, molecular dynamics simulations and Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) calculations. In every step, the selection of molecules was mainly based on their ability to occupy both the active and secondary sites of RTA, which are located right next to each other, but are not simultaneously occupied by the current RTA inhibitors. Results show that the three PubChem compounds 18309602, 18498053, and 136023163 presented better overall results than the reference molecule itself, showing up as new hits for the RTA inhibition, and encouraging further experimental evaluation.


Sujet(s)
Ricine/antagonistes et inhibiteurs , Ricine/composition chimique , Algorithmes , Sites de fixation , Armes chimiques/composition chimique , Découverte de médicament , Liaison hydrogène , Ligands , Conformation moléculaire , Simulation de docking moléculaire , Simulation de dynamique moléculaire , Structure moléculaire
12.
Article de Anglais | LILACS-Express | LILACS | ID: biblio-1437994

RÉSUMÉ

The Sete Cidades National Park is located in the Brazilian municipalities of Piracuruca and Brasileira, Piauí state, in a transitional zone between the Caatinga and Cerrado biomes. Studies on its herpetofauna were limited to anuran distribution notes and a snake checklist. Thus, here we present an unpublished species list of anurans from Sete Cidades National Park, Piauí state, northeastern Brazil. We recorded one of the two highest species richness for all northeastern National Parks, and also increased the geographic distribution of one species in the state of Piauí. Most species observed are common of both Caatinga and Cerrado biomes or have wide distribution in Brazil. The anuran assemblage of Sete Cidades National Park is more similar to those registered at the Delta do Parnaíba Environmental Protection Area, Ceará, Piauí and Maranhão states, and Ubajara National Park, Ceará state. These results increase our knowledge on anuran diversity in northeastern Brazil, providing basic information for management and conservation actions of an important Brazilian National Park.


O Parque Nacional de Sete Cidades está localizado nos municípios de Piracuruca e Brasileira, Estado do Piauí, em uma zona de transição entre os biomas Caatinga e Cerrado. Os estudos sobre sua herpetofauna estão limitados a notas de distribuição de anfíbios e um inventário de serpentes. Portanto, aqui apresentamos uma lista inédita de espécies de anuros do Parque Nacional de Sete Cidades, Estado do Piauí, Nordeste do Brasil. Nós registramos uma das duas maiores riquezas de espécies dentre todos os Parques Nacionais do Nordeste, além de aumentar a distribuição geográfica de uma espécie para o estado. A maioria das espécies observadas são comuns em ambos os biomas da Caatinga e Cerrado ou têm ampla distribuição no Brasil. A assembleia de anuros do Parque Nacional de Sete Cidades é mais similar àquela registrada na Área de Proteção Ambiental do Delta do Parnaíba, estados do Ceará, Piauí e Maranhão, e no Parque Nacional de Ubajara, estado do Ceará. Estes resultados aumentam nosso conhecimento sobre a diversidade de anuros no Nordeste do Brasil, fornecendo subsídios para ações de gestão e conservação de um importante Parque Nacional do Brasil.

13.
Molecules ; 25(1)2019 Dec 23.
Article de Anglais | MEDLINE | ID: mdl-31878010

RÉSUMÉ

Organophosphorus compounds (OP) are chemicals widely used as pesticides in different applications such as agriculture and public health (vector control), and some of the highly toxic forms have been used as chemical weapons. After application of OPs in an environment, they persist for a period, suffering a degradation process where the biotic factors are considered the most relevant forms. However, to date, the biodegradation of OP compounds is not well understood. There are a plenty of structure-based biodegradation estimation methods, but none of them consider enzymatic interaction in predicting and better comprehending the differences in the fate of OPs in the environment. It is well known that enzymatic processes are the most relevant processes in biodegradation, and that hydrolysis is the main pathway in the natural elimination of OPs in soil samples. Due to this, we carried out theoretical studies in order to investigate the interactions of these OPs with a chosen enzyme-the phosphotriesterase. This one is characteristic of some soils' microorganisms, and has been identified as a key player in many biodegradation processes, thanks to its capability for fast hydrolyzing of different OPs. In parallel, we conducted an experiment using native soil in two conditions, sterilized and not sterilized, spiked with specific amounts of two OPs with similar structure-paraoxon-ethyl (PXN) and O-(4-nitrophenyl) O-ethyl methylphosphonate (NEMP). The amount of OP present in the samples and the appearance of characteristic hydrolysis products were periodically monitored for 40 days using analytical techniques. Moreover, the number of microorganisms present was obtained with plate cell count. Our theoretical results were similar to what was achieved in experimental analysis. Parameters calculated by enzymatic hydrolysis were better for PXN than for NEMP. In soil, PXN suffered a faster hydrolysis than NEMP, and the cell count for PXN was higher than for NEMP, highlighting the higher microbiological toxicity of the latter. All these results pointed out that theoretical study can offer a better comprehension of the possible mechanisms involved in real biodegradation processes, showing potential in exploring how biodegradation of OPs relates with enzymatic interactions.


Sujet(s)
Dépollution biologique de l'environnement , Composés organiques du phosphore/composition chimique , Pesticides/composition chimique , Sol/composition chimique , Agriculture , Guerre chimique , Humains , Hydrolyse , Insecticides/composition chimique , Insecticides/métabolisme , Composés organiques du phosphore/métabolisme , Paraoxon/analogues et dérivés , Paraoxon/composition chimique , Pesticides/toxicité , Santé publique , Pyrrolidines/composition chimique
14.
Biomolecules ; 9(10)2019 10 08.
Article de Anglais | MEDLINE | ID: mdl-31597234

RÉSUMÉ

Casualties caused by organophosphorus pesticides are a burden for health systems in developing and poor countries. Such compounds are potent acetylcholinesterase irreversible inhibitors, and share the toxic profile with nerve agents. Pyridinium oximes are the only clinically available antidotes against poisoning by these substances, but their poor penetration into the blood-brain barrier hampers the efficient enzyme reactivation at the central nervous system. In searching for structural factors that may be explored in future SAR studies, we evaluated neutral aryloximes as reactivators for paraoxon-inhibited Electrophorus eel acetylcholinesterase. Our findings may result into lead compounds, useful for development of more active compounds for emergencies and supportive care.


Sujet(s)
Acetylcholinesterase/métabolisme , Electrophorus/métabolisme , Réactivateurs d'enzymes/pharmacologie , Oximes/pharmacologie , Paraoxon/toxicité , Animaux , Réactivateurs d'enzymes/composition chimique , Protéines de poisson/métabolisme , Techniques in vitro , Structure moléculaire , Oximes/composition chimique , Relation structure-activité
15.
Chaos ; 29(7): 073115, 2019 Jul.
Article de Anglais | MEDLINE | ID: mdl-31370401

RÉSUMÉ

We consider the problem of global synchronization in a large random network of Kuramoto oscillators where some of them are subject to an external periodically driven force. We explore a recently proposed dimensional reduction approach and introduce an effective two-dimensional description for the problem. From the dimensionally reduced model, we obtain analytical predictions for some critical parameters necessary for the onset of a globally synchronized state in the system. Moreover, the low dimensional model also allows us to introduce an optimization scheme for the problem. Our main conclusion, which has been corroborated by exhaustive numerical simulations, is that for a given large random network of Kuramoto oscillators, with random natural frequencies ωi, such that a fraction of them is subject to an external periodic force with frequency Ω, the best global synchronization properties correspond to the case where the fraction of the forced oscillators is chosen to be those ones such that |ωi-Ω| is maximal. Our results might shed some light on the structure and evolution of natural systems for which the presence or the absence of global synchronization is a desired property. Some properties of the optimal forced networks and their relation to recent results in the literature are also discussed.

16.
An Acad Bras Cienc ; 91(suppl 1): e20180097, 2019.
Article de Anglais | MEDLINE | ID: mdl-31017187

RÉSUMÉ

INTRODUCTION: In some Amazonian river basins, hair mercury concentration is above the recommended levels. We evaluated the influence of birth geographical location in the hair mercury level of Amazonian riverine children. MATERIALS AND METHODS: Hair mercury concentration was measured in 219 children living in four Amazonian riverine communities: Tapajós River (São Luiz do Tapajós and Barreiras villages, n = 110), Tocantins River (Limoeiro do Ajurú village, n = 61), and Caeté River (Caratateua village, n = 48). We used Poisson regression analysis to evaluate the association between native and non-native children from each village and its hair mercury concentration. RESULTS: Higher mercury exposure was found in native children from São Luiz do Tapajós (range = 0.81-22.38 µg/g) followed by native children from Barreiras (range = 0.48-13.46 µg/g), non-native children from São Luiz do Tapajós (range = 0.26-22.18 µg/g), non-native children from Barreiras (range = 0.43-20.76 µg/g), followed by the children from Caeté and Tocantins river basins. We observed that Tapajós villages' native children had higher prevalence of mercury exposure children than other children (p < 0.05). CONCLUSIONS: Birth geographical location has association to mercury levels in the hair of children who lived in a same community with history of mercury exposure.


Sujet(s)
Développement de l'enfant , Exposition environnementale/analyse , Géographie médicale , Mercure/analyse , Adolescent , Adulte , Brésil , Enfant , Femelle , Poils/composition chimique , Humains , Mâle , Grossesse , Effets différés de l'exposition prénatale à des facteurs de risque/diagnostic , Effets différés de l'exposition prénatale à des facteurs de risque/étiologie , Rivières , Polluants chimiques de l'eau/effets indésirables
17.
J Biomol Struct Dyn ; 37(8): 2041-2048, 2019 May.
Article de Anglais | MEDLINE | ID: mdl-29749305

RÉSUMÉ

Aflatoxins are secondary metabolites of the fungi Aspergillus flavus and A. parasiticus. Among them, aflatoxin B1 (AFB1) is the most frequent type in nature and the most carcinogenic for mammals. It can contaminate many kinds of food like seeds, oil, olives, milk, dairy products, corn and meat, causing acute and chronic damages to the organism, especially in the liver, being, for this reason, considered highly hepatotoxic. AFB1 is also a mixed inhibitor of the enzyme acetylcholinesterase (AChE). This fact, together with its high toxicity and carcinogenicity, turns AFB1 into a potential chemical and biological warfare agent, as well as its metabolites. In order to investigate this, we performed inedited molecular modeling studies on the interactions of AFB1 and its metabolites inside the peripheral anionic site of human AChE (HssAChE), to verify their stability, suggest the preferential ways of inhibition, and compare their behavior to each other. Our results suggest that all metabolites can be better inhibitors of HssAChE than AFB1 and that AFBO and AFM1, the most toxic and carcinogenic metabolites of AFB1, are also the most effective HssAChE inhibitors among the AFB1 metabolites. Communicated by Ramaswamy H. Sarma.


Sujet(s)
Acetylcholinesterase/composition chimique , Acetylcholinesterase/métabolisme , Aflatoxine B1/composition chimique , Aflatoxine B1/métabolisme , Métabolome , Modèles moléculaires , Anions , Humains , Liaison hydrogène , Ligands , Simulation de docking moléculaire , Simulation de dynamique moléculaire , Thermodynamique
18.
Molecules ; 23(11)2018 Nov 12.
Article de Anglais | MEDLINE | ID: mdl-30424582

RÉSUMÉ

The present work aimed to compare the small, neutral and monoaromatic oxime, isatin-3-oxime (isatin-O), to the commercial ones, pralidoxime (2-PAM) and obidoxime, in a search for a new potential reactivator for acetylcholinesterase (AChE) inhibited by the pesticide paraoxon (AChE/POX) as well as a novel potential scaffold for further synthetic modifications. The multicriteria decision methods (MCDM) allowed the identification of the best docking poses of those molecules inside AChE/POX for further molecular dynamic (MD) studies, while Ellman's modified method enabled in vitro inhibition and reactivation assays. In corroboration with the theoretical studies, our experimental results showed that isatin-O have a reactivation potential capable of overcoming 2-PAM at the initial moments of the assay. Despite not achieving better results than obidoxime, this molecule is promising for being an active neutral oxime with capacity of crossing the blood⁻brain barrier (BBB), to reactivate AChE/POX inside the central and peripheral nervous systems. Moreover, the fact that isatin-O can also act as anticonvulsant makes this molecule a possible multipotent reactivator. Besides, the MCDM method showed to be an accurate method for the selection of the best docking poses generated in the docking studies.


Sujet(s)
Anticholinestérasiques/pharmacologie , Réactivateurs de la cholinestérase/composition chimique , Réactivateurs de la cholinestérase/pharmacologie , Modèles moléculaires , Oximes/composition chimique , Oximes/pharmacologie , Paraoxon/composition chimique , Paraoxon/pharmacologie , Érythrocytes/effets des médicaments et des substances chimiques , Érythrocytes/enzymologie , Simulation de docking moléculaire , Simulation de dynamique moléculaire , Structure moléculaire
19.
Hig. aliment ; 32(284/285): 51-55, out. 30, 2018.
Article de Portugais | LILACS | ID: biblio-965436

RÉSUMÉ

As Unidades de Alimentação e Nutrição (UAN) são todos os estabelecimentos onde ocorre a manipulação e processamento de alimentos e deverá fornecer uma alimentação, nutricionalmente equilibrada e segura do ponto de vista higienicossanitário. Uma das ferramentas utilizadas para avaliar a aplicação das Boas Práticas de Fabricação em áreas de produção de alimentos, é a ficha de inspeção ou checklist. Esta ferramenta é empregada para verificar as porcentagens de não conformidades referentes à legislação em vigor, Portaria CVS 5/2013. O objetivo do presente trabalho foi realizar um diagnóstico das condições higienicossanitárias em duas Unidades de Alimentação e Nutrição Hospitalar (UANH), por meio da aplicação de checklist, para verificação da conformidade aos itens avaliados. As duas UANs foram classificadas como satisfatórias, após aplicação do checklist, por meio do qual foram encontrados 81% de adequação na Unidade A e 74% na Unidade B, sendo possível verificar que há o controle na produção de alimentos nos locais estudados e que os pontos críticos citados são falhas pontuais na adoção e controle das boas práticas e infraestrutura dos locais.


The Food and Nutrition Units (FNU) are all the establishments where food manipulation and processing occurs and should provide a nutritionally balanced and safe nutrition from the hygienic and sanitary point of view. One of the tools used to achieve good Practices in food productions areas is the Inspection or check list. This tool is used to verify the percentages of non-conformities referring to the current legislation CVS 5 of 2013.The objective of the present study was to perform the diagnosis of the hygienic-sanitary conditions of a. Hospital. Food and Nutrition Unit (UANH) a A check list based on the country's legislation is used countrywide to detect non-conformities by the Unit. The two FNU were classified as satisfactory after application of the checklist where 81% of suitability was found in unit A and 74% in unit B, being possible to verify that there is hygienic-sanitary control, and the critical points are Punctual failures in the adoption and control of the good practices and infrastructure of the sites.


Sujet(s)
Surveilance de Santé , Production Alimentaire , Hygiène Alimentaire , Pratiques de Bonne Fabrication , Manipulation des aliments , Perfectionnement du personnel , Liste de contrôle/méthodes , Alimentation et nutrition , Hôpitaux
20.
Hig. aliment ; 32(284/285): 51-55, Set.-Out.2018.
Article de Portugais | VETINDEX | ID: vti-20891

RÉSUMÉ

As Unidades de Alimentação e Nutrição (UAN) são todos os estabelecimentos onde ocorre a manipulação e processamento de alimentos e deverá fornecer uma alimentação, nutricionalmente equilibrada e segura do ponto de vista higienicossanitário. Uma das ferramentas utilizadas para avaliar a aplicação das Boas Práticas de Fabricação em áreas de produção de alimentos, é a ficha de inspeção ou checklist. Esta ferramenta é empregada para verificar as porcentagens de não conformidades referentes à legislação em vigor, Portaria CVS 5/2013. O objetivo do presente trabalho foi realizar um diagnóstico das condições higienicossanitárias em duas Unidades de Alimentação e Nutrição Hospitalar(UANH), por meio da aplicação de checklist, para verificação da conformidade aos itens avaliados. As duas UANs foram classificadas como satisfatórias, após aplicação do checklist, por meio do qual foram encontrados 81% de adequação na Unidade A e 74% na Unidade B, sendo possível verificar que há o controle na produção de alimentos nos locais estudados e que os pontos críticos citados são falhas pontuais na adoção e controle das boas práticas e infraestrutura dos locais.(AU)


The Food and Nutrition Units (FNU) are all the establishments where food manipulation and processing occurs and should provide a nutritionally balanced and safe nutrition from the hygienic and sanitary point of view. One of the tools used to achieve good Practices in food productions areas is the Inspection or check list. This tool is used to verify the percentages of non-conformities referring to the current legislation CVS 5 of 2013. The objective of the present study was to perform the diagnosis of the hygienic-sanitary conditions of a. Hospital. Food and Nutrition Unit (UANH) a A check list based on the country's legislation is used countrywide to detect non-conformities by the Unit. The two FNU were classified as satisfactory after application of the checklist where 81% of suitability was found in unit A and 74% in unit B, being possible to verify that there is hygienic-sanitary control, and the critical points are Punctual failures in the adoption and control of the good practices and infrastructure ofthe sites.(AU)


Sujet(s)
Sciences de la nutrition/enseignement et éducation , Manipulation des aliments/classification , Manipulation des aliments/méthodes , Contrôle des aliments
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