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1.
Cien Saude Colet ; 29(7): e03672024, 2024 Jul.
Article in Portuguese, English | MEDLINE | ID: mdl-38958325

ABSTRACT

This article aimed to know a Shelter for women in situations of intimate partner violence at imminent risk of death located in the state of Rio de Janeiro from the perception of its professionals. To this end, this qualitative research adopted semi-structured interviews with seven professionals directly involved with the care and assistance to the Shelter's user population. The findings were interpreted through Bardin's thematic content analysis. Moreover, the profile of the women and children sheltered in 2021 was drawn based on the data provided by the institution. In conceptual terms, this work focused on intersectional feminist theoretical references. Among the results, we argue that the shelter is permeated by contradictions, from its normative idealizations to institutional practices: on the one hand, the shelter represents the possibility of salvation, that is, of interrupting the escalation of violence and, therefore, preventing femicide. However, on the other hand, it appears as an upside-down prison, which "incarcerates" the victims. We highlight the importance of thinking about new ways to ensure protection for women who need this shelter.


O artigo teve como objetivo conhecer uma casa-abrigo para mulheres em situação de violência por parceiros íntimos (VPI) em risco iminente de morte localizada no estado do Rio de Janeiro a partir da percepção de seus profissionais. Para tanto, a pesquisa teve abordagem qualitativa e foram realizadas entrevistas semiestruturadas com sete profissionais envolvidos/as diretamente no atendimento e na assistência às mulheres atendidas pela casa-abrigo. A interpretação dos achados se deu por meio da técnica de análise de conteúdo temática preconizada por Bardin. Além disso, foi traçado o perfil das mulheres e crianças abrigadas no ano de 2021, com base nos dados disponibilizados pela instituição. Em termos conceituais, este trabalho debruçou-se sobre referenciais teóricos feministas interseccionais. Entre os resultados, argumenta-se que a casa-abrigo está permeada por contradições, desde suas normativas às práticas institucionais: por um lado, representa uma possibilidade de "salvação", isto é, de interrupção da escalada da violência e, portanto, de impedimento do feminicídio, mas, por outro, aparece como uma prisão "às avessas", que "prende" as vítimas. Aponta-se a importância e a urgência de pensar novas formas de garantir proteção às mulheres que necessitam desse tipo de abrigamento.


Subject(s)
Interviews as Topic , Intimate Partner Violence , Prisons , Qualitative Research , Humans , Female , Brazil , Intimate Partner Violence/prevention & control , Prisoners/psychology , Adult , Crime Victims/psychology , Feminism
3.
Chem Biol Interact ; 398: 111073, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38823538

ABSTRACT

Cancer is a complex and multifaceted group of diseases with a high mortality rate characterized by uncontrolled proliferation of abnormal cells. Dysregulation of normal signalling pathways in cancer contributes to the different hallmarks of this disease. The signalling pathway of which phosphatidylinositol 3-kinase (PI3K) is a part is not an exception. In fact, dysregulated activation of PI3K signalling pathways can result in unbridled cellular proliferation and enhanced cell survival, thereby fostering the onset and advancement of cancer. Therefore, there is substantial interest in developing targeted therapies specifically aimed at inhibiting the PI3K enzyme and its associated pathways. Also, the therapeutic interest on pyrazoles and indazoles has been growing due to their various medicinal properties, namely, anticancer activity. Derivatives of these compounds have been studied as PI3K inhibitors, and they showed promising results. There are already some PI3K inhibitors approved by Food and Drug Administration (FDA), such as Idelalisib (Zydelig®) and Alpelisib (Piqray®). In this context, this review aims to address the importance of PI3K in cellular processes and its role in cancer. Additionally, it aims to report a comprehensive literature review of PI3K inhibitors, containing the pyrazole and indazole scaffolds, published in the last fifteen years, focusing on structure-activity relationship aspects, thus providing important insights for the design of novel and more effective PI3K inhibitors.


Subject(s)
Antineoplastic Agents , Indazoles , Neoplasms , Phosphoinositide-3 Kinase Inhibitors , Pyrazoles , Humans , Indazoles/chemistry , Indazoles/pharmacology , Indazoles/therapeutic use , Pyrazoles/chemistry , Pyrazoles/pharmacology , Pyrazoles/therapeutic use , Neoplasms/drug therapy , Phosphoinositide-3 Kinase Inhibitors/pharmacology , Phosphoinositide-3 Kinase Inhibitors/chemistry , Phosphoinositide-3 Kinase Inhibitors/therapeutic use , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Animals , Phosphatidylinositol 3-Kinases/metabolism , Phosphatidylinositol 3-Kinases/chemistry , Phosphatidylinositol 3-Kinase/metabolism , Signal Transduction/drug effects
4.
Phys Chem Chem Phys ; 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38922674

ABSTRACT

Chemical processes taking place on ice-grain mantles are pivotal to the complex chemistry of interstellar environments. In this study, we conducted a comprehensive analysis of the catalytic effects of an amorphous solid water (ASW) surface on the reaction between ammonia (NH3) and formaldehyde (H2CO) to form aminomethanol (NH2CH2OH) using density functional theory. We identified potential catalytic sites based on the binding energy distribution of NH3 and H2CO reactants, on a set-of-clusters surface model composed of 22 water molecules and found a total of 14 reaction paths. Our results indicate that the catalytic sites can be categorized into four groups, depending on the interactions of the carbonyl oxygen and the amino group with the ice surface in the reactant complex. A detailed analysis of the reaction mechanism using Intrinsic Reaction Coordinate and reaction force analysis, revealed three distinct chemical events for this reaction: formation of the C-N bond, breaking of the N-H bond, and formation of the O-H hydroxyl bond. Depending on the type of catalytic site, these events can occur within a single, concerted, albeit asynchronous, step, or can be isolated in a step-wise mechanism, with the lowest overall transition state energy observed at 1.3 kcal mol-1. A key requirement for the low-energy mechanism is the presence of a pair of dangling OH bonds on the surface, found at 5% of the potential catalytic sites on an ASW porous surface.

5.
Int J Biochem Cell Biol ; 172: 106599, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38797495

ABSTRACT

Elevated levels of prostaglandin E2 have been implicated in the pathophysiology of various diseases. Anti-inflammatory drugs that act through the inhibition of cyclooxygenase enzymatic activity, thereby leading to the suppression of prostaglandin E2, are often associated with several side effects due to their non-specific inhibition of cyclooxygenase enzymes. Consequently, the targeted suppression of prostaglandin E2 production with innovative molecules and/or mechanisms emerges as a compelling therapeutic strategy for the treatment of inflammatory-related diseases. Therefore, in this study, a systematic analysis of 28 pyrazole derivatives was conducted to explore their potential mechanisms for reducing prostaglandin E2 levels. In this context, the evaluation of these derivatives extended to examining their capacity to reduce prostaglandin E2in vitro in human whole blood, inhibit cyclooxygenase-1 and cyclooxygenase-2 enzymes, modulate cyclooxygenase-2 expression, and suppress oxidative burst in human leukocytes. The results enabled the establishment of significant structure-activity relationships, elucidating key determinants for their activities. In particular, the 4-styryl group on the pyrazole moiety and the presence of chloro substitutions were identified as key determinants. Pyrazole 8 demonstrated the capacity to reduce prostaglandin E2 levels by downregulating cyclooxygenase-2 expression, and pyrazole-1,2,3-triazole 18 emerged as a dual-acting agent, inhibiting human leukocytes' oxidative burst and cyclooxygenase-2 activity. Furthermore, pyrazole 26 demonstrated effective reduction of prostaglandin E2 levels through selective cyclooxygenase-1 inhibition. These results underscore the multifaceted anti-inflammatory potential of pyrazoles, providing new insights into the substitutions and structural frameworks that are beneficial for the studied activity.


Subject(s)
Cyclooxygenase 1 , Cyclooxygenase 2 , Dinoprostone , Leukocytes , Pyrazoles , Respiratory Burst , Humans , Pyrazoles/pharmacology , Pyrazoles/chemistry , Dinoprostone/metabolism , Respiratory Burst/drug effects , Leukocytes/drug effects , Leukocytes/metabolism , Cyclooxygenase 2/metabolism , Cyclooxygenase 1/metabolism , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Structure-Activity Relationship , Cyclooxygenase Inhibitors/pharmacology
6.
Mol Biochem Parasitol ; 259: 111629, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38750697

ABSTRACT

Leishmaniases comprise a group of infectious parasitic diseases caused by various species of Leishmania and are considered a significant public health problem worldwide. Only a few medications, including miltefosine, amphotericin B, and meglumine antimonate, are used in current therapy. These medications are associated with severe side effects, low efficacy, high cost, and the need for hospital support. Additionally, there have been occurrences of drug resistance. Additionally, only a limited number of drugs, such as meglumine antimonate, amphotericin B, and miltefosine, are available, all of which are associated with severe side effects. In this context, the need for new effective drugs with fewer adverse effects is evident. Therefore, this study investigated the anti-Leishmania activity of a dichloromethane fraction (DCMF) extracted from Arrabidaea brachypoda roots. This fraction inhibited the viability of L. infantum, L. braziliensis, and L. Mexicana promastigotes, with IC50 values of 10.13, 11.44, and 11.16 µg/mL, respectively, and against L. infantum amastigotes (IC50 = 4.81 µg/mL). Moreover, the DCMF exhibited moderate cytotoxicity (CC50 = 25.15) towards RAW264.7 macrophages, with a selectivity index (SI) of 5.2. Notably, the DCMF caused damage to the macrophage genome only at 40 µg/mL, which is greater than the IC50 found for all Leishmania species. The results suggest that DCMF demonstrates similar antileishmanial effectiveness to isolated brachydin B, without causing genotoxic effects on mammalian cells. This finding is crucial because the isolation of the compounds relies on several steps and is very costly while obtaining the DCMF fraction is a simple and cost-effective process. Furthermore, In addition, the potential mechanisms of action of brachydins were also investigated. The computational analysis indicates that brachydin compounds bind to the Triosephosphate isomerase (TIM) enzyme via two main mechanisms: destabilizing the interface between the homodimers and interacting with catalytic residues situated at the site of binding. Based on all the results, DCMF exhibits promise as a therapeutic agent for leishmaniasis due to its significantly reduced toxicity in comparison to the adverse effects associated with current reference treatments.


Subject(s)
Antiprotozoal Agents , Bignoniaceae , Flavonoids , Leishmania , Molecular Docking Simulation , Plant Extracts , Bignoniaceae/chemistry , Antiprotozoal Agents/pharmacology , Antiprotozoal Agents/chemistry , Antiprotozoal Agents/isolation & purification , Flavonoids/pharmacology , Flavonoids/chemistry , Animals , Leishmania/drug effects , Leishmania/genetics , Plant Extracts/pharmacology , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Mice , Inhibitory Concentration 50 , Macrophages/drug effects , Macrophages/parasitology , RAW 264.7 Cells
7.
Article in English | MEDLINE | ID: mdl-38602265

ABSTRACT

The 2018 LUCAS (Land Use and Coverage Area frame Survey) Soil Pesticides survey provides a European Union (EU)-scale assessment of 118 pesticide residues in more than 3473 soil sites. This study responds to the policy need to develop risk-based indicators for pesticides in the environment. Two mixture risk indicators are presented for soil based, respectively, on the lowest and the median of available No Observed Effect Concentration (NOECsoil,min and NOECsoil,50) from publicly available toxicity datasets. Two further indicators were developed based on the corresponding equilibrium concentration in the aqueous phase and aquatic toxicity data, which are available as species sensitivity distributions. Pesticides were quantified in 74.5% of the sites. The mixture risk indicator based on the NOECsoil,min exceeds 1 in 14% of the sites and 0.1 in 23%. The insecticides imidacloprid and chlorpyrifos and the fungicide epoxiconazole are the largest contributors to the overall risk. At each site, one or a few substances drive mixture risk. Modes of actions most likely associated with mixture effects include modulation of acetylcholine metabolism (neonicotinoids and organophosphate substances) and sterol biosynthesis inhibition (triazole fungicides). Several pesticides driving the risk have been phased out since 2018. Following LUCAS surveys will determine the effectiveness of substance-specific risk management and the overall progress toward risk reduction targets established by EU and UN policies. Newly generated data and knowledge will stimulate needed future research on pesticides, soil health, and biodiversity protection. Integr Environ Assess Manag 2024;00:1-15. © 2024 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

8.
Enferm. glob ; 23(74): 1-13, abr.2024. graf
Article in Spanish | IBECS | ID: ibc-232275

ABSTRACT

Objetivo: Examinar la actividad investigadora de los enfermeros en atención primaria de salud y conocer su divulgación. Metodología: Se trata de un estudio transversal descriptivo realizado entre el 27 mayo hasta el 29 de junio de 2022, en un Área de Gestión Sanitaria a través de un cuestionario electrónico autoadministrado. Contestaron el cuestionario 242 enfermeros. Un 5.2% posee el grado de Máster y ninguno el de Doctor. Un 8.3% ha colaborado en algún proyecto de investigación financiado, siendo la suscripción a grupos del Plan Andaluz de Investigación, Desarrollo e Innovación (PAIDI) de un 0,4%. La participación es principalmente colaborativa con sólo 1 caso como IP en proyectos financiados. La aportación a congresos u otras actividades de divulgación es de un 23% para comunicaciones orales y de un 26,1 % para comunicaciones escritas. Resultados: Sobre la publicación de resultados, un 16,5%, han publicado al menos 1 artículo científico, siendo un 1,3% en revistas de impacto (ninguna en Q1 y Q2). La temática de las publicaciones es muy diversa. La colaboración en investigaciones realizadas con otras disciplinas ha sido de un 10,4 % y en estudios de investigación realizados con otras instituciones o servicios de salud de un 11,3%. Conclusión: Se concluye que la actividad investigadora realizada en atención primaria es de bajo nivel y calidad. Existe dispersión tanto en la temática como en los perfiles enfermeros que desarrollan actividad investigadora, lo que implica inexistencia de una red consolidada en investigación en cuidados que sustente la práctica asistencial basada en la evidencia científica. (AU)


Aim: The aim of this study is to examinate the research activity of nurses in primary health care and to know his dissemination. Method: It is a descriptive cross-sectional study carried out between May 27 and June 29, 2022, in a Health Management Area Through a self-administrated questionnaire. A total of 242 nurses answered the questionnaire. A total of 5,2% have a Master ́s degree and none have a PhD. Some 8,3% have collaborated in a funded research project, with 0,4% subscribing to PAIDI groups. Participation is mostly collaborative with only 1 case as PI in funded projects. Contribution to congresses or other dissemination activities is 18.7% for oral communications and 16,5% for written communications. Results: Regarding the publication of results, 16,5% have published at least 1 scientific article, 1,3% in impact journals (none in Q1 or Q2). The subject matter of the publications is very diverse. Collaboration in research with other disciplines was 10,4%, and in research studies carried out with other institutions or health services are 11,3%. Conclusion: It is concluded that the research activity carried out in primary care is of low level and quality. There is dispersion both in the subject matter and in the nursing profiles that carry out research activity, which implies the lack of a consolidated network in research in care that supports care practice based on scientific evidence. (AU)


Subject(s)
Humans , Nursing Research , Primary Care Nursing , Health Services Research , Nurses, Male , Sanitary Management , Cross-Sectional Studies , Epidemiology, Descriptive
9.
Environ Sci Technol ; 58(15): 6744-6752, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38568876

ABSTRACT

During the growing season of 2021, 201 soil samples from conventionally and organically managed fields from 10 European countries and 8 cropping systems were taken, and 192 residues of synthetic pesticides were analyzed. Pesticide residues were found in 97% of the samples, and 88% of the samples contained mixtures of at least 2 substances. A maximum of 21 substances were found in conventionally managed fields, and a maximum of 12 were found in organically managed fields. The number and concentration of pesticide residues varied significantly between conventional and organic fields in 70 and 50% of the case study sites, respectively. Application records were available for a selected number of fields (n = 82), and these records were compared to the detected substances. Residues from 52% of the applied pesticides were detected in the soils. Only 21% of the pesticide residues detected in the soil samples were applied during the 2021 growing season. From the application data, predicted environmental concentrations of residues in soil were calculated and compared to the measured concentrations. These estimates turned out not to be accurate. The results of this study show that most European agricultural soils contain mixtures of pesticide residues and that current calculation methods may not reliably estimate their presence.


Subject(s)
Pesticide Residues , Pesticides , Soil Pollutants , Pesticide Residues/analysis , Pesticide Residues/chemistry , Soil/chemistry , Agriculture , Pesticides/analysis , Europe
10.
Water Res ; 254: 121419, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38484551

ABSTRACT

Freshwater ecosystems face a particularly high risk of biodiversity loss compared to marine and terrestrial systems. The use of pesticides in agricultural fields is recognized as a relevant stressor for freshwater environments, exerting a negative impact worldwide on the overall status and health of the freshwater communities. In the present work, part of the Horizon 2020 funded SPRINT project, the occurrence of 193 pesticide residues was investigated in 64 small water bodies of distinct typology (creeks, streams, channels, ditches, rivers, lakes, ponds and reservoirs), located in regions with high agricultural activity in 10 European countries and in Argentina. Mixtures of pesticide residues were detected in all water bodies (20, median; 8-40 min-max). Total pesticide levels found ranged between 6.89 and 5860 ng/L, highlighting herbicides as the dominant type of pesticides. Glyphosate was the compound with the highest median concentration followed by 2,4-D and MCPA, and in a lower degree by dimethomorph, fluopicolide, prothioconazole and metolachlor(-S). Argentina was the site with the highest total pesticide concentration in water bodies followed by The Netherlands, Portugal and France. One or more pesticides exceeded the threshold values established in the European Water Framework Directive for surface water in 9 out of 11 case study sites (CSS), and the total pesticide concentration surpassed the reference value of 500 ng/L in 8 CSS. Although only 5 % (bifenthrin, dieldrin, fipronil sulfone, permethrin, and terbutryn) of the individual pesticides denoted high risk (RQ > 1), the ratios estimated for pesticide mixtures suggested potential environmental risk in the aquatic compartment studied.


Subject(s)
Pesticide Residues , Pesticides , Water Pollutants, Chemical , Water , Ecosystem , Argentina , Water Pollutants, Chemical/analysis , Environmental Monitoring , Pesticides/analysis , Rivers/chemistry
11.
J Zoo Wildl Med ; 55(1): 125-135, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38453495

ABSTRACT

The present study characterized the filamentous and yeast-like fungal microbiota of the nasal cavity and rectum of Amazonian manatees (Trichechus inunguis) undergoing rehabilitation at the Laboratory of Aquatic Mammals, National Institute of Amazonian Research, Manaus, Amazonas, and determined the antifungal susceptibility of these organisms. Nasal and rectal swabs were collected from 22 calves and three juveniles. The samples were seeded in Sabouraud agar supplemented with chloramphenicol 10%, incubated at 26°C, and observed daily for up to 7 d. The growth of different filamentous and yeast-like fungi was observed among the two anatomical sites. Filamentous fungi were categorized by macro- and microscopic characteristics of the colonies. Representatives of each group were selected for molecular identification based on the internal transcribed spacer region. Yeast identification was performed using MALDI-TOF MS and molecular analyses. Thirteen genera of filamentous fungi and six genera of yeasts were isolated and identified. The dominant filamentous species were Fusarium spp., Aspergillus spp., and Cochliobolus lunatus in the nostril samples and Aspergillus melleus in the rectal samples. Candida was the dominant genus among the identified yeasts at both anatomical sites. In the antifungal susceptibility test, 28 isolates showed resistance to fluconazole (78%), itraconazole (39%), and nystatin (42%). The knowledge of fungal microbiota composition of Amazonian manatees provides information that assists in monitoring the health status of individuals maintained in captivity, as these organisms can behave either as opportunists or as primary pathogens. Moreover, the composition and resistance of these organisms may vary among different rehabilitation institutions or different time frames of search, reinforcing the importance of constant in loco surveillance of these microorganisms. This study provides new perspectives on the fungal diversity in the microbiota of manatees and supports future studies concerning the clinical and epidemiological aspects and the impacts of these agents on the health of Amazonian manatees undergoing rehabilitation.


Subject(s)
Mycobiome , Trichechus inunguis , Animals , Cattle , Antifungal Agents/pharmacology , Brazil/epidemiology , Rectum , Nasal Cavity , Saccharomyces cerevisiae , Trichechus , Fungi
12.
Biochem Pharmacol ; 221: 116045, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38336156

ABSTRACT

Cancer is a disease with a high mortality rate characterized by uncontrolled proliferation of abnormal cells. The hallmarks of cancer evidence the acquired cells characteristics that promote the growth of malignant tumours, including genomic instability and mutations, the ability to evade cellular death and the capacity of sustaining proliferative signalization. Poly(ADP-ribose) polymerase-1 (PARP1) is a protein that plays key roles in cellular regulation, namely in DNA damage repair and cell survival. The inhibition of PARP1 promotes cellular death in cells with homologous recombination deficiency, and therefore, the interest in PARP protein has been rising as a target for anticancer therapies. There are already some PARP1 inhibitors approved by Food and Drug Administration (FDA), such as Olaparib and Niraparib. The last compound presents in its structure an indazole core. In fact, pyrazoles and indazoles have been raising interest due to their various medicinal properties, namely, anticancer activity. Derivatives of these compounds have been studied as inhibitors of PARP1 and presented promising results. Therefore, this review aims to address the importance of PARP1 in cell regulation and its role in cancer. Moreover, it intends to report a comprehensive literature review of PARP1 inhibitors, containing the pyrazole and indazole scaffolds, published in the last fifteen years, focusing on structure-activity relationship aspects, thus providing important insights for the design of novel and more effective PARP1 inhibitors.


Subject(s)
Neoplasms , Poly (ADP-Ribose) Polymerase-1 , Pyrazoles , Adenosine Diphosphate Ribose , Cell Cycle , Indazoles/pharmacology , Indazoles/therapeutic use , Neoplasms/drug therapy , Neoplasms/enzymology , Pyrazoles/pharmacology , Pyrazoles/therapeutic use , United States , Humans , Animals , Poly (ADP-Ribose) Polymerase-1/antagonists & inhibitors , Poly (ADP-Ribose) Polymerase-1/metabolism
13.
Environ Int ; 181: 108280, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37924602

ABSTRACT

Intensive and widespread use of pesticides raises serious environmental and human health concerns. The presence and levels of 209 pesticide residues (active substances and transformation products) in 625 environmental samples (201 soil, 193 crop, 20 outdoor air, 115 indoor dust, 58 surface water, and 38 sediment samples) have been studied. The samples were collected during the 2021 growing season, across 10 study sites, covering the main European crops, and conventional and organic farming systems. We profiled the pesticide residues found in the different matrices using existing hazard classifications towards non-target organisms and humans. Combining monitoring data and hazard information, we developed an indicator for the prioritization of pesticides, which can support policy decisions and sustainable pesticide use transitions. Eighty-six percent of the samples had at least one residue above the respective limit of detection. One hundred residues were found in soil, 112 in water, 99 in sediments, 78 in crops, 76 in outdoor air, and 197 in indoor dust. The number, levels, and profile of residues varied between farming systems. Our results show that non-approved compounds still represent a significant part of environmental cocktails and should be accounted for in monitoring programs and risk assessments. The hazard profiles analysis confirms the dominance of compounds of low-moderate hazard and underscores the high hazard of some approved compounds and recurring "no data available" situations. Overall, our results support the idea that risk should be assessed in a mixture context, taking environmentally relevant mixtures into consideration. We have uncovered uncertainties and data gaps that should be addressed, as well as the policy implications at the EU approval status level. Our newly introduced indicator can help identify research priority areas, and act as a reference for targeted scenarios set forth in the Farm to Fork pesticide reduction goals.


Subject(s)
Pesticide Residues , Pesticides , Humans , Farmers , Crops, Agricultural , Dust , Soil , Water , Environmental Monitoring
14.
Food Res Int ; 173(Pt 1): 113291, 2023 11.
Article in English | MEDLINE | ID: mdl-37803604

ABSTRACT

Enteric endothelial cells are the first structure to come in contact with digested food and may suffer oxidative damage by innumerous exogenous factors. Although peptides derived from whey digestion have presented antioxidant potential, little is known regarding antioxidant pathways activation in Caco-2 cell line model. Hence, we evaluated the ability to form whey peptides resistant to simulated gastrointestinal digestive processes, with potential antioxidant activity on gastrointestinal cells and associated with sequence structure and activity. Using the INFOGEST method of simulated static digestion, we achieved 35.2% proteolysis, with formation of peptides of low molecular mass (<600 Da) evaluated by FPLC. The digestion-resistant peptides showed a high proportion of hydrophobic and acidic amino acids, but with average surface hydrophobicity. We identified 24 peptide sequences, mainly originated from ß-lactoglobulin, that exhibit various bioactivities. Structurally, the sequenced peptides predominantly contained the amino acids lysine and valine in the N-terminal region, and tyrosine in the C-terminal region, which are known to exhibit antioxidant properties. The antioxidant activity of the peptide digests was on average twice as potent as that of the protein isolates for the same concentration, as evaluated by ABTS, DPPH and ORAC. Evaluation of biological activity in Caco-2 intestinal cells, stimulated with hydrogen peroxide, showed that they attenuated the production of reactive oxygen species and prevented GSH reduction and SOD activity increase. Caco-2 cells were not responsive to nitric oxide secretion. This study suggests that whey peptides formed during gastric digestion exhibit biological antioxidant activity, without the need for previously hydrolysis with exogenous enzymes for supplement application. The study's primary contribution was demonstrating the antioxidant activity of whey peptides in maintaining the gastrointestinal epithelial cells, potentially preventing oxidative stress that affects the digestive system.


Subject(s)
Antioxidants , Whey , Humans , Antioxidants/chemistry , Caco-2 Cells , Whey/metabolism , Endothelial Cells/metabolism , Whey Proteins/chemistry , Peptides/chemistry , Digestion
15.
Nucl Med Biol ; 126-127: 108390, 2023.
Article in English | MEDLINE | ID: mdl-37804561

ABSTRACT

This study aimed to evaluate the repeatability of brown adipose tissue (BAT) activation measured by [18F]FDG-PET after beta3-adrenergic stimuli with CL316243 in mice. METHODS: Male C57BL/6 mice underwent [18F]FDG-PET at baseline without stimulation (T0-NS), on three consecutive days after intravenous administration of the selective ß3-adrenergic agonist CL316243 (T1-CL, T2-CL, T3-CL), and without stimuli after 1 and 2 weeks (T7-NS and T14-NS). The standardized uptake value (SUVmax), BAT metabolic volume (BMV), and total BAT glycolysis (TBG) were measured in each scanning session, with statistical groupwise comparisons by ANOVA and post hoc Tukey test. RESULTS: SUVmax, BMV, and TBG values showed no significant differences between the three PET scans without stimuli, but were significantly higher after CL316243 administration (p < 0.0001). The mean coefficient of variation (CoV) of PET within individuals was 49 % at baseline but only 9 % with pharmacological stimulation. CONCLUSIONS: The study demonstrated that administration of the selective ß3-adrenergic receptor agonist CL316243 (CL) in mice leads to consistent metabolic activation of brown adipose tissue (BAT), as measured by [18F]FDG-PET. We also demonstrated metabolic activation by repeated pharmacological challenge, without evidence of hysteresis. Thus, the methods used in the current work should serve for further studies on BAT metabolism in experimental animals, with translational value for clinical research.


Subject(s)
Adipose Tissue, Brown , Fluorodeoxyglucose F18 , Male , Mice , Animals , Fluorodeoxyglucose F18/metabolism , Adipose Tissue, Brown/diagnostic imaging , Adrenergic Agents/metabolism , Adrenergic Agents/pharmacology , Mice, Inbred C57BL , Positron-Emission Tomography/methods , Disease Models, Animal , Adipose Tissue/metabolism
16.
Sci Total Environ ; 905: 167797, 2023 Dec 20.
Article in English | MEDLINE | ID: mdl-37838044

ABSTRACT

Pesticides are widely used as plant protection products (PPPs) in farming systems to preserve crops against pests, weeds, and fungal diseases. Indoor dust can act as a chemical repository revealing occurrence of pesticides in the indoor environment at the time of sampling and the (recent) past. This in turn provides information on the exposure of humans to pesticides in their homes. In the present study, part of the Horizon 2020 funded SPRINT project, the presence of 198 pesticide residues was assessed in 128 indoor dust samples from both conventional and organic farmworker households across Europe, and in Argentina. Mixtures of pesticide residues were found in all dust samples (25-121, min-max; 75, median). Concentrations varied in a wide range (<0.01 ng/g-206 µg/g), with glyphosate and its degradation product AMPA, permethrin, cypermethrin and piperonyl butoxide found in highest levels. Regarding the type of pesticides, insecticides showed significantly higher levels than herbicides and fungicides. Indoor dust samples related to organic farms showed a significantly lower number of residues, total and individual concentrations than those related to conventional farms. Some pesticides found in indoor dust were no longer approved ones (29 %), with acute/chronic hazards to human health (32 %) and with environmental toxicity (21 %).


Subject(s)
Air Pollution, Indoor , Pesticide Residues , Pesticides , Humans , Pesticide Residues/analysis , Environmental Monitoring , Dust/analysis , Farmers , Argentina , Pesticides/analysis , Europe , Air Pollution, Indoor/analysis
17.
Molecules ; 28(15)2023 Aug 04.
Article in English | MEDLINE | ID: mdl-37570842

ABSTRACT

Pyrazole and its derivatives are considered privileged N-heterocycles with immense therapeutic potential [...].

19.
ChemMedChem ; 18(17): e202300264, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37392377

ABSTRACT

A multistep and diversity-oriented synthetic route aiming at the A3 coupling/domino cyclization of o-ethynyl anilines, aldehydes and s-amines is described. The preparation of the corresponding precursors included a series of transformations, such as haloperoxidation and Sonogashira cross-coupling reactions, amine protection, desilylation and amine reduction. Some products of the multicomponent reaction underwent further detosylation and Suzuki coupling. The resulting library of structurally diverse compounds was evaluated against blood and liver stage malaria parasites, which revealed a promising lead with sub-micromolar activity against intra-erythrocytic forms of Plasmodium falciparum. The results from this hit-to-lead optimization are hereby reported for the first time.


Subject(s)
Antimalarials , Antimalarials/pharmacology , Indoles , Aldehydes , Amines , Aniline Compounds , Cyclization , Catalysis
20.
Ciênc. Saúde Colet. (Impr.) ; 28(6): 1643-1653, jun. 2023.
Article in Portuguese | LILACS-Express | LILACS | ID: biblio-1439853

ABSTRACT

Resumo Este artigo é parte da pesquisa "As violências no contexto da COVID-19: desafios e vulnerabilidades globais", que propõe uma reflexão crítica acerca das situações de violências de gênero potencializadas pelos protocolos de distanciamento social requeridos pela pandemia de COVID-19. A partir de levantamento bibliográfico do ano de 2020, analisamos recomendações de pesquisadores e instituições de diferentes partes do mundo, com o objetivo de sistematizar e disseminar estratégias para lidar com este cenário. O material está organizado em dois eixos temáticos: políticas de gênero e ações intersetoriais; e estratégias de enfrentamento às violências contra mulheres e crianças no campo da saúde e da assistência social. As recomendações estão centradas no desenvolvimento de ações por Estados/governos, redes de atendimento e sociedade em geral. Parte das recomendações sugere aumentar ou adequar as ações de vigilância já existentes, e parte contribui com propostas criativas, norteando ações promotoras e preventivas em nível individual e coletivo. A adoção de teleatendimento, campanhas midiáticas de conscientização de que a violência é injustificável e desenvolvimento de estratégias de denúncia por meio de sinais e códigos foram reiteradas pela literatura.


Abstract This article is an integral part of the research "Violence in the context of COVID-19: global challenges and vulnerabilities", which proposes a critical reflection on situations of gender-based violence increased by social distancing protocols, required by the COVID-19 pandemic. Based on a 2020 literature survey, we have analyzed recommendations made by researchers and institutions from different countries around the world, with the aim of systematizing and disseminating strategies to deal with this scenario. The material is organized into two thematic areas, namely: gender policies and intersectoral actions; and strategies to face violence against women and children in the health and social work field. The recommendations are focused on the development of actions by States/governments, service networks and society in general. Part of the recommendations suggest increasing or adapting existing surveillance actions and part of them contribute with creative proposals, guiding promotional and preventive actions at an individual and collective level. The adoption of teleassistance, media campaigns raising awareness that violence is unjustifiable and the development of reporting strategies through signs and codes have been reiterated in the literature.

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