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The aim of this study was to select the best exopolysaccharide (EPS) producer among the Enterococcus strains to optimize, characterize, and evaluate its biological properties. Among the eleven strains, Enterococcus faecium KT990028 was selected, and the production conditions were optimized: 16.3â¯% (w/v) sucrose, 0.70â¯% (w/v) yeast extract, 8.3â¯% (w/v) reconstituted skimmed milk, at 38⯰C in 15â¯h of incubation, producing 2.880â¯g/L of EPS. High performance anion exchange chromatography (HPAEC) analysis revealed that the molecular weight was 166.98â¯kDa. HPAEC, spectroscopy (FTIR), and nuclear magnetic resonance (1H NMR) analyses revealed that the EPS was a heteropolysaccharide composed of galactose (37.74â¯%), rhamnose (19.79â¯%), arabinose (17.71â¯%), glucose (9.50â¯%), fucose (7.93â¯%), and mannose (7.33â¯%). Scanning electron microscopy showed a three-dimensional microstructure in the form of decompressed plates, with wrinkles, and pores. By means of dynamic light scattering (DLS), the EPS showed an average size varying from 135.25⯱â¯10.56â¯nm and 410.60⯱â¯45.20â¯nm, as the concentration was increased from 0.5â¯mg/mL to 2.0â¯mg/mL, respectively. X-ray diffraction revealed that the EPS has an amorphous and crystalline nature, while thermogravimetric analysis indicated stability up to 400⯰C. The antioxidant effect (5â¯mg/mL) against DPPH, ABTS, OH, and O2 was 64.50⯱â¯0.71â¯%, 47.50⯱â¯0.10â¯%, 68.36⯱â¯0.59â¯%, and 44.83⯱â¯0.86â¯%, respectively. It was also able to inhibit and biofilm disruption of Escherichia coli ATCC 25922 and Enterococcus faecalis ATCC 6057 and had an antimicrobial effect from 50â¯mg/mL for the strains of against Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Listeria monocytogenes ATCC 19117, Staphylococcus aureus ATCC 6538, and Enterococcus faecalis ATCC 6057. Cell cytotoxicity carried out using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay revealed that the EPS was safe and promoted the proliferation of Vero cells. Thus, the results indicated that the EPS from E. faecium KT990028 is a promising functional biopolymer for possible applications in the food and pharmaceutical fields.
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Due to the increasing incidence of cancer, the consumption of highly toxic oncological drugs is continuously growing. Given the current lack of efficient technologies to remove/treat these toxic drugs in wastewater treatment plants, the environmental quality is compromised, and aquatic organisms are at risk. To address this critical environmental burden, a new strategy based on supported ionic liquids (SILs) for the simultaneous removal of oncologic drugs and toxicity reduction of aqueous samples is here proposed. Silica-based SILs functionalized with imidazolium-based and quaternary ammonium-based ILs were designed and kinetics and isotherm adsorption studies performed. Aiming to develop an adsorbent able to reduce the toxicity of aqueous samples contaminated with oncological drugs, the toxicity reduction was appraised using the model organism Danio rerio. The obtained results disclose that among the studied SILs, the [Si][N3888]Cl (silica functionalized with propyltrioctylammonium chloride) is the best adsorption material (maximum adsorption capacity, qmax = 67.64 mg g-1), with a fast adsorption rate (<20 min). Furthermore, [Si][N3888]Cl was able to remove the toxicity of the treated aqueous samples towards D. rerio embryos, as assessed by lethal and several sublethal endpoints, demonstrating that this material holds remarkable potential for oncological drugs pollution remediation.
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Herein we demonstrate the formation of new stimuli-responsive aqueous biphasic systems (ABS), able to respond simultaneously to temperature and pH, or just to one stimulus, therefore allowing the design of more sustainable separation processes. This dual behavior is achieved with ABS formed by mono or dicationic protic ionic liquids as phase-forming components, being defined by the ionic liquid cation chemical structure or its basicity. While ABS comprising monocationic ionic liquids only respond to the effect of temperature, systems comprising dicationic ionic liquids are simultaneously affected by both temperature and pH variations. Dicationic ionic liquids are here identified as the key to unlock a double response to stimuli, which is due to the presence of two pKa values afforded by the cation. The reported findings contribute to increase the customizability of double stimuli-responsive ABS based on ionic liquids, whose development was up to date limited to ionic liquids bearing pH-responsive anions, opening the door towards the development of more sustainable separation processes.
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BACKGROUND: Autism spectrum disorder (ASD) is often accompanied by comorbid conditions such as attention deficit hyperactivity disorder and epilepsy. In this context, patients are often treated with psychostimulants in an attempt to control behavioral symptoms. This study aims to understand the behavioral effects of psychostimulants in children with ASD and investigate if interictal epileptiform discharges on electroencephalogram (EEG) can act as a modifying factor in this behavior. METHODS: Sixty-eight patients with ASD who were being accompanied in the Department of Child and Adolescent Psychiatry of the Centro Hospitalar Universitário de São João and had previously done an EEG assessment answered a questionnaire regarding their behavioral response to psychostimulants. RESULTS: In total, 47.4% of patients reported improved agitation, 56.1% enhanced concentration, and 8.8% improved sleep. Conversely, 28.1% experienced worsened agitation, 15.8% worsened concentration, and 17.5% worsened sleep. The remaining reported no alterations. The age of diagnosis correlated significantly with improved agitation, with a higher diagnosis age being associated with a higher probability of improvement. Extended-release methylphenidate and genetic variations were significantly associated with worsening of agitation. Regarding speech, 86% exhibited no changes, while 14% showed alterations, mostly, 87.5%, characterized as negative. For other behavioral alterations, 45.6% reported negative changes, 3.5% reported positive changes, and 50.9% reported no additional alterations. Female gender was significantly associated with other negative behavioral changes. A significant correlation was found between treatment duration and the probability of improvement in agitation, concentration, and other behavioral changes.
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Neonatal immune activation (NIA) through exposure to lipopolysaccharide (LPS) induces adult behavioral changes in rodents that resemble symptoms of developmental disorders, such as autism spectrum disorder. The neonatal timing of LPS exposure appears to play a crucial role in determining the nature and extent of long-term changes. This study aims to explore whether a 3-day LPS-NIA triggers sex- and age-related changes in gut function, potentially linking LPS-NIA to gastrointestinal dysfunction. Male and female Swiss mice received intraperitoneal injections of LPS or saline on postnatal days (PN) 3, 5, and 7. At PN35 (juvenile) and PN70 (adult), gut inflammation and oxidative stress were evaluated in addition to assessments of working memory, depressive-like symptoms, sociability, and repetitive behavior. Gut examination showed elevated C-X-C motif chemokine receptor 3 (CXCR3) in LPS-NIA mice, while MyD88 and Zonulin expressions were significantly higher only in adult LPS-NIA females. Interleukin (IL)-23 expression increased in juvenile and adult male and juvenile female LPS-NIA mice. Oxidative changes included decreased duodenal reduced glutathione (GSH) in juvenile females and ileal GSH in adult females exposed to LPS-NIA. Regarding behavioral alterations, adult LPS-NIA females exhibited depressive-like behavior. Working memory deficits were observed across all LPS-NIA groups. Only juvenile LPS-NIA females increased grooming, while rearing was higher in adult LPS-NIA mice of both sexes. The findings imply that LPS-NIA impacts intestinal barrier function and causes gut inflammatory alterations that are sex- and age-specific. These findings pave the way for exploring potential mechanisms that could contribute to LPS-induced gastrointestinal disturbances among individuals with ASD.
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Animais Recém-Nascidos , Lipopolissacarídeos , Caracteres Sexuais , Animais , Lipopolissacarídeos/toxicidade , Feminino , Camundongos , Masculino , Fatores Etários , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Envelhecimento/imunologia , Envelhecimento/fisiologiaRESUMO
We propose an innovative approach to address the pressing need for efficient and transparent evaluation techniques to assess extraction processes' sustainability. In response to society's growing demand for natural products and the consequent surge in biomass exploration, a critical imperative arises to ensure that these processes are genuinely environmentally friendly. Extracting natural compounds has traditionally been regarded as a benign activity rooted in ancient practices. However, contemporary extraction methods can also significantly harm the environment if not carefully managed. Recognizing this, we developed a novel metric, Path2Green, tailored specifically and rooted in 12 new principles of a green extraction process. Path2Green seeks to provide a comprehensive framework beyond conventional metrics, offering a nuanced understanding of the environmental impact of extraction activities from biomass collection/production until the end of the process. By integrating factors such as resource depletion, energy consumption, waste generation, and biodiversity preservation, Path2Green aims to offer a holistic assessment of sustainability of an extraction approach. The significance of Path2Green lies in its ability to distill complex environmental data into a simple, accessible metric. This facilitates informed decision-making for stakeholders across industries, enabling them to prioritize greener extraction practices. Moreover, by setting clear benchmarks and standards, Path2Green incentivizes innovation and drives continuous improvement in sustainability efforts, being a new user-friendly methodology.
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Anethole is a terpenoid with antioxidant, anti-inflammatory, and neuronal blockade effects, and the present work was undertaken to study the neuroprotective activity of anethole against diabetes mellitus (DM)-induced neuropathy. Streptozotocin-induced DM rats were used to investigate the effects of anethole treatment on morphological, electrophysiological, and biochemical alterations of the sciatic nerve (SN). Anethole partially prevented the mechanical hyposensitivity caused by DM and fully prevented the DM-induced decrease in the cross-sectional area of the SN. In relation to electrophysiological properties of SN fibers, DM reduced the frequency of occurrence of the 3rd component of the compound action potential (CAP) by 15%. It also significantly reduced the conduction velocity of the 1st and 2nd CAP components from 104.6 ± 3.47 and 39.8 ± 1.02 to 89.9 ± 3.03 and 35.4 ± 1.56 m/s, respectively, and increased the duration of the 2nd CAP component from 0.66 ± 0.04 to 0.82 ± 0.09 ms. DM also increases oxidative stress in the SN, altering values related to thiol, TBARS, SOD, and CAT activities. Anethole was capable of fully preventing all these DM electrophysiological and biochemical alterations in the nerve. Thus, the magnitude of the DM-induced neural effects seen in this work, and the prevention afforded by anethole treatment, place this compound in a very favorable position as a potential therapeutic agent for treating diabetic peripheral neuropathy.
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Derivados de Alilbenzenos , Anisóis , Diabetes Mellitus Experimental , Estresse Oxidativo , Nervo Isquiático , Animais , Derivados de Alilbenzenos/farmacologia , Nervo Isquiático/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Ratos , Anisóis/farmacologia , Anisóis/uso terapêutico , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Neuropatias Diabéticas/tratamento farmacológico , Neuropatias Diabéticas/prevenção & controle , Neuropatias Diabéticas/metabolismo , Potenciais de Ação/efeitos dos fármacos , Antioxidantes/farmacologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêuticoRESUMO
Sleep is a vital process that impacts biological functions such as cell renewal, bone regeneration, and immune system support. Disrupted sleep can interrupt erythropoiesis, leading to fewer red blood cells, reduced haemoglobin concentration, and decreased haematocrit levels, potentially contributing to haematological disorders. This is particularly concerning for shift workers for example firefighters. While previous studies have explored sleep's adverse effects on various professions, research specific to firefighters is limited. This study investigates the relationship between sleep quality and haematological parameters among firefighters in Northeast Portugal. From a sample of 201 firefighters, variations in red blood cells, haemoglobin, and haematocrit values were linked to sleep quality. The study utilised non-parametric tests (Wilcoxon-Mann-Whitney, Spearman's correlation) to explore the connection between sleep quality and haematological profile. The impact of covariates on haematological parameters was assessed using non-parametric ANCOVA (Quade's). A multiple regression analysis was employed to further understand how sleep quality and various confounding variables impact haematological levels. Findings suggest a negative link between sleep quality and haematological levels, meaning that as sleep quality deteriorates, there is a tendency for haematological levels to decrease, as indicated by Spearman's correlation (rRBC = -0.157, pRBC = 0.026; rHb = -0.158, pHb = 0.025; rHCT = -0.175, pHCT = 0.013). As observed in scientific literature, the correlation found suggests a possible inhibition of erythropoiesis, the process responsible for red blood cell production. Despite firefighters presenting a haematological profile within the reference range (RBC: 5.1 × 106/mm3 (SD ± 0.4), Hb: 15.6 g/dL (SD ± 1.3), 47% (SD ± 1.0), there is already an observable trend towards lower levels. The analysis of co-variables did not reveal a significant impact of sleep quality on haematological levels. In conclusion, this study underscores the importance of sleep quality in determining haematological parameters among firefighters. Future research should investigate the underlying mechanisms and long-term implications of poor sleep quality on firefighter health. Exploring interventions to enhance sleep quality is vital for evidence-based strategies promoting firefighter well-being.
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Com muita alegria, apresentamos a vocês, leitoras e leitores, uma das primeiras produções oficiais da 17ª Conferência Nacional de Saúde (17ª CNS), realizada em Brasília (DF), em julho de 2023. Este livro é uma coletânea que reúne diversos capítulos das monitoras e monitores formados pelo curso "'Fazendo manhãs' para a saúde e a democracia: participação social e políticas de saúde" e que atuaram na etapa prática da 17ª CNS. Os capítulos são, na verdade, narrativas que discorrem sobre a vivência na conferência que, dentre muitas características, foi marcada pelo retorno da democracia. Nunca é excessivo ou tarde demais lembrar que superamos as tentativas nefastas que ameaçaram e colocaram em risco todas as vidas no período de 2019 a 2022. Superar a crise humanitária causada pela covid-19 e o governo fascista do período mencionado, responsável pela disseminação de "fake news", ódio e incitação à violência, são fatos lembrados pelos diversos autores do livro, desde a apresentação. Viver em sociedade implica necessariamente em viver politicamente, pois cada interação e decisão que tomamos contribui para a estruturação do ambiente social e para a busca contínua do bem-estar comum. Essa compreensão ampliada, apresentada de diversas formas nos capítulos, nos ajuda a reconhecer as esferas da vida e a assumir o nosso papel como agentes ativos na construção de comunidades mais justas e coesas e na defesa do SUS e da democracia.
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Humanos , Masculino , FemininoRESUMO
This study aimed to compare and relate the body composition (obtained through anthropometry with the pentacompartmental model and the tricompartmental model by DXA) with bone mineral density and biochemical and nutritional parameters in Chilean adults with overweight/obesity and normal weight from La Araucanía region, Chile. A case-control study was conducted with 116 adults and volunteers from the PURE cohort, collecting sociodemographic data, BMI assessment, waist-to-hip ratio (WHR), and body composition using the pentacompartmental model (5CM) and tricompartmental model (3CM) by DXA, as well as bone mineral density (BMD). Blood biochemical parameters (fasting glucose and lipid profile), physical activity (PA) measured by GPAQ, and average dietary habits (R24h) were measured. In the overweight/obesity group, the 5CM and 3CM adipose mass were indirectly and moderately correlated with PA (p < 0.05), except in the male 5CM group. In the overweight/obesity group, muscle and fat-free mass (FFM) of the 5CM and 3CM correlated directly and moderately with blood fasting glucose (BFG) and BMD (p < 0.05), except in females, where FFM was not related to BMD but was related to residual mass (p < 0.01). Independent of gender and BMI, bone mineral content was positively and highly correlated with BMD (p < 0.0000). In the male overweight/obesity group, bone, skin, and residual mass were correlated with BFG (p < 0.05). In conclusion, for the assessment of non-athletic adult populations, more routine use of the 5CM in clinical practice is recommended.
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Composição Corporal , Densidade Óssea , Obesidade , Sobrepeso , Humanos , Masculino , Feminino , Chile , Adulto , Obesidade/sangue , Estudos de Casos e Controles , Pessoa de Meia-Idade , Sobrepeso/sangue , Estado Nutricional , Absorciometria de Fóton , Glicemia/metabolismo , Índice de Massa Corporal , Exercício Físico/fisiologiaRESUMO
Cancer remains a significant global health concern, with mortality rates steadily rising and prompting an urgent search for effective treatments. This study focuses on the medicinal properties of plants from the Phyllanthus genus, specifically Phyllanthus amarus and Phyllanthus niruri, which have shown promise in traditional medicine. Through bioguided fractionation using preparative high-performance liquid chromatography (HPLC), bioactive compounds were isolated and identified using ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-QTOF-MSE) and nuclear magnetic resonance (NMR) spectroscopy. Chemometric analyses such as principal component analysis (PCA) aided in understanding metabolite distribution. Biological assays demonstrated cytotoxic activities of specific fractions against cancer cell lines, notably the PhyN 4n fraction from P. niruri, which induced S-phase cell cycle arrest and apoptosis in HL60 cells. These findings underscore the anticancer potential of Phyllanthus species and lay the groundwork for future drug development efforts. The study's integration of advanced analytical techniques, chemometrics, and biological assays provides valuable insights for harnessing natural products in the fight against cancer.
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Antineoplásicos Fitogênicos , Apoptose , Ensaios de Seleção de Medicamentos Antitumorais , Metabolômica , Phyllanthus , Phyllanthus/química , Humanos , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a DrogaRESUMO
Atrazine is an herbicide with a high soil leaching capacity, contaminating subsurface water sources. Once the water table is contaminated, riparian species can be exposed to atrazine. In this way, understanding the impacts of this exposure must be evaluated for planning strategies that minimize the effects of this herbicide on native forest species. We aimed to evaluate forest species' sensitivity and antioxidant response to exposure to subsurface waters contaminated with atrazine, as well the dissipation this herbicide. The experiment was conducted in a greenhouse in a completely randomized design, with three replications and one plant per experimental unit. The treatments were arranged in a 2 × 10 factorial. The first factor corresponded to the presence or absence (control) of the atrazine in the subsurface water. The second factor comprised 10 forest species: Amburana cearensis, Anadenanthera macrocarpa, Bauhinia cheilantha, Enterolobium contortisiliquum, Hymenaea courbaril, Libidibia ferrea, Mimosa caesalpiniifolia, Mimosa tenuiflora, Myracrodruon urundeuva, and Tabebuia aurea. The forest species studied showed different sensitivity levels to atrazine in subsurface water. A. cearensis and B. cheilantha species do not have efficient antioxidant systems to prevent severe oxidative damage. The species A. macrocarpa, E. contortisiliquum, L. ferrea, and M. caesalpiniifolia are moderately affected by atrazine. H. courbaril, M. urundeuva, and T. aurea showed greater tolerance to atrazine due to the action of the antioxidant system of these species, avoiding membrane degradation events linked to the production of reactive oxygen species (ROS). Among the forest species, H. courbaril has the most significant remedial potential due to its greater tolerance and reduced atrazine concentrations in the soil.
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Antioxidantes , Atrazina , Florestas , Herbicidas , Plântula , Poluentes Químicos da Água , Atrazina/análise , Herbicidas/análise , Antioxidantes/metabolismo , Antioxidantes/análise , Poluentes Químicos da Água/análise , Plântula/efeitos dos fármacos , Poluentes do Solo/análise , Solo/químicaRESUMO
Açaí seed extract (ASE) is obtained from Euterpe oleracea Mart. (açaí) plant (Amazon region) has high nutritional and functional value. ASE is rich in polyphenolic compounds, mainly proanthocyanidins. Proanthocyanidins can modulate the immune system and oxidative stress by inhibiting the toll-like receptor-4 (TLR-4)/myeloid differentiation primary response 88 (MyD88)/nuclear factor-κB (NF-κB) pathway. A great deal of evidence suggests that inflammatory cytokines and oxidative stress contribute to the pathogenesis of intestinal mucositis, and these events can lead to intestinal dysmotility. We hypothesized that ASE acts as an anti-inflammatory and antioxidant compound in intestinal mucositis induced by 5-fluorouracil (5-FU) through modulation of the TLR-4/MyD88/phosphatidylinositol-3-kinase α/mechanistic target of rapamycin/NF-κBp65 pathway. The animals were divided into linear 5-FU (450 mg/kg) and 5-FU + ASE (10, 30, and 100 mg/kg) groups. The weight loss of the animals was evaluated daily. Samples from duodenum, jejunum, and ileum were obtained for histopathological, biochemical, and functional analyses. ASE reduced weight loss, inflammatory parameters (interleukin-1ß; tumor necrosis factor-α; myeloperoxidase activity) and the gene expression of mediators involved in the TLR-2/MyD88/NF-κB pathway. ASE prevented histopathological changes with beneficial effects on gastrointestinal transit delay, gastric emptying, and intestinal absorption/permeability. In conclusion, ASE protects the integrity of the intestinal epithelial barrier by inhibiting the TLR/MyD88/PI3K/mechanistic target of rapamycin/NF-κBp65 pathway.
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Euterpe , Fluoruracila , Mucosite , Fator 88 de Diferenciação Mieloide , Extratos Vegetais , Polifenóis , Sementes , Transdução de Sinais , Serina-Treonina Quinases TOR , Receptor 4 Toll-Like , Animais , Receptor 4 Toll-Like/metabolismo , Mucosite/induzido quimicamente , Mucosite/tratamento farmacológico , Mucosite/prevenção & controle , Mucosite/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Transdução de Sinais/efeitos dos fármacos , Extratos Vegetais/farmacologia , Sementes/química , Polifenóis/farmacologia , Masculino , Euterpe/química , Camundongos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Fator de Transcrição RelA/metabolismo , Antioxidantes/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , NF-kappa B/metabolismoRESUMO
The leaching of herbicides into the soil is essential to control germinating seeds and parts of vegetative weeds. However, herbicide transportation to deeper soil layers can result in groundwater contamination and, consequently, environmental issues. In this research, our objective was to investigate differences in herbicide leaching between commercial formulations and analytical standards using three different soils. Leaching experiments were carried out for diuron, hexazinone, and sulfometuron-methyl herbicides isolated and in binary and ternary mixtures. The herbicide residue quantification was performed by ultra-high-performance liquid chromatography coupled to a mass spectrometer (LC-MS/MS). Diuron had less mobility in soils and was retained in the most superficial layers. Hexazinone and sulfometuron-methyl were more mobile and leached into deeper layers. The leaching process was more intense for hexazinone and sulfometuron-methyl. The additives present in the commercial formulation favored the leaching in soils of diuron, hexazinone, and sulfometuron-methyl herbicides isolated and mixture compared to the analytical standard. This fact highlights the importance of considering these effects for the positioning of herbicides in the field to increase the efficiency of weed control and minimize the potential for environmental contamination.
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Mania is associated with disturbed dopaminergic transmission in frontotemporal regions. D-amphetamine (AMPH) causes increased extracellular DA levels, considered an acknowledged mania model in rodents. Doxycycline (DOXY) is a second-generation tetracycline with promising neuroprotective properties. Here, we tested the hypothesis that DOXY alone or combined with Lithium (Li) could reverse AMPH-induced mania-like behavioral alterations in mice by the modulation of monoamine levels in brain areas related to mood regulation, as well as cytoprotective and antioxidant effects in hippocampal neurons. Male Swiss mice received AMPH or saline intraperitoneal (IP) injections for 14 days. Between days 8-14, mice receive further IP doses of DOXY, Li, or their combination. For in vitro studies, we exposed hippocampal neurons to DOXY in the presence or absence of AMPH. DOXY alone or combined with Li reversed AMPH-induced risk-taking behavior and hyperlocomotion. DOXY also reversed AMPH-induced hippocampal and striatal hyperdopaminergia. In AMPH-exposed hippocampal neurons, DOXY alone and combined with Li presented cytoprotective and antioxidant effects, while DOXY+Li also increased the expression of phospho-Ser133-CREB. Our results add novel evidence for DOXY's ability to reverse mania-like features while revealing that antidopaminergic activity in some brain areas, such as the hippocampus and striatum, as well as hippocampal cytoprotective effects may account for this drug's antimanic action. This study provides additional rationale for designing clinical trials investigating its potential as a mood stabilizer agent.
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Antioxidantes , Doxiciclina , Hipocampo , Mania , Neurônios , Animais , Masculino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Camundongos , Antioxidantes/farmacologia , Mania/induzido quimicamente , Mania/tratamento farmacológico , Doxiciclina/farmacologia , Comportamento Animal/efeitos dos fármacos , Células Cultivadas , Anfetamina/farmacologia , Anfetamina/toxicidade , Modelos Animais de Doenças , Estimulantes do Sistema Nervoso Central/toxicidade , Monoaminas Biogênicas/metabolismo , Dextroanfetamina/farmacologia , Dextroanfetamina/toxicidade , Antimaníacos/farmacologia , Fármacos Neuroprotetores/farmacologiaRESUMO
Objetivo: Analisar a atuação do enfermeiro perfusionista na cirurgia cardíaca. Método: Estudo exploratório com abordagem qualitativa, desenvolvida em ambiente virtual no período de 1 a 30 de junho de 2022. Amostra intencional, não probabilística, constituída de 14 enfermeiros perfusionistas. Os dados foram analisados por meio da análise de conteúdo de Bardin. Resultados: Emergiram duas categorias temáticas: Atuação do enfermeiro perfusionista na circulação extracorpórea e A relevância da interação do enfermeiro com os membros da equipe durante a cirurgia cardíaca com circulação extracorpórea. Os relatos identificaram que o enfermeiro perfusionista realiza inúmeras atribuições que vão desde o histórico de enfermagem, até o preparo e a escolha de materiais, circuitos, dispositivos e maquinários para a condução da circulação extracorpórea. Destaca-se a interação desse profissional com os demais membros da equipe no tocante à comunicação a fim de minimizar riscos e obter resultado cirúrgico positivo para o paciente. Conclusão: A atividade do enfermeiro perfusionista é complexa e necessita de um rigoroso preparo teórico-prático, especializações reconhecidas pelos órgãos competentes, bem como frequentes atualizações mesmo já sendo um profissional experiente. (AU)
Objective: To analyze the role of the perfusionist nurse in cardiac surgery. Method: Exploratory study with a qualitative approach, conducted in a virtual environment from June 1st to June 30th, 2022. The sample consisted of 14 perfusionist nurses, selected intentionally and non-probabilistically. Data were analyzed through Bardin's content analysis. Results: Two thematic categories emerged: the role of the perfusionist nurse in extracorporeal circulation and the relevance of the nurse's interaction with team members during cardiac surgery with extracorporeal circulation. The reports identi-fied that the perfusionist nurse performs numerous tasks ranging from nursing history to the preparation and selection of materials, circuits, devices, and machinery for extracorporeal circulation. The interaction of this professional with other team members regarding communication stands out, aiming to minimize risks and achieve positive surgical outcomes for the patient. Conclusion: The activity of the perfusionist nurse is complex and requires rigo-rous theoretical-practical preparation, recognized specializations by competent bodies, as well as frequent updates even for experienced professionals
Objetivo: Analizar el papel del enfermero de perfusión en la cirugía cardíaca. Método: Estudio exploratorio con enfoque cualitativo, desarrol-lado en ambiente virtual durante el período del 1 al 30 de junio de 2022. Muestra intencional, no probabilística, compuesta por 14 enfermeros de perfu-sión. Los datos fueron analizados mediante el análisis de contenido de Bardin. Resultados: Surgieron dos categorías temáticas: El papel del enfermero perfusionista en circulación extracorporea y la relevancia de la interacción del enfermero con los miembros del equipo durante la cirugía cardíaca con circulación extracorporea. Los informes identificaron que el enfermero perfusionista desempeña numerosas atribuciones que van desde el historial de enfermería hasta la preparación y elección de materiales, circuitos, dispositivos y maquinaria para la conducción de la circulación extracorporea. Se des-taca la interacción de este profesional con los demás miembros del equipo en lo que respecta a la comunicación para minimizar riesgos y obtener resulta-dos quirúrgicos positivos para el paciente. Conclusión: La actividad del enfermero de perfusión es compleja y requiere una preparación teórico-práctica rigurosa, especializaciones reconocidas por los órganos competentes, así como actualizaciones frecuentes incluso siendo un profesional experimentado
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Humanos , Papel do Profissional de Enfermagem , Procedimentos Cirúrgicos Cardíacos/enfermagem , Cirurgia Torácica/instrumentação , Circulação Extracorpórea/enfermagemRESUMO
Fear-related pathologies are among the most prevalent psychiatric conditions, having inappropriate learned fear and resistance to extinction as cardinal features. Exposure therapy represents a promising therapeutic approach, the efficiency of which depends on inter-individual variation in fear extinction learning, which neurobiological basis is unknown. We characterized a model of extinction learning, whereby fear-conditioned mice were categorized as extinction (EXT)-success or EXT-failure, according to their inherent ability to extinguish fear. In the lateral amygdala, GluN2A-containing NMDAR are required for LTP and stabilization of fear memories, while GluN2B-containing NMDAR are required for LTD and fear extinction. EXT-success mice showed attenuated LTP, strong LTD and higher levels of synaptic GluN2B, while EXT-failure mice showed strong LTP, no LTD and higher levels of synaptic GluN2A. Neurotrophin 3 (NT3) infusion in the lateral amygdala was sufficient to rescue extinction deficits in EXT-failure mice. Mechanistically, activation of tropomyosin receptor kinase C (TrkC) with NT3 in EXT-failure slices attenuated lateral amygdala LTP, in a GluN2B-dependent manner. Conversely, blocking endogenous NT3-TrkC signaling with TrkC-Fc chimera in EXT-success slices strengthened lateral amygdala LTP. Our data support a key role for the NT3-TrkC system in inter-individual differences in fear extinction in rodents, through modulation of amygdalar NMDAR composition and synaptic plasticity.
Assuntos
Tonsila do Cerebelo , Extinção Psicológica , Medo , Individualidade , Camundongos Endogâmicos C57BL , Plasticidade Neuronal , Neurotrofina 3 , Receptor trkC , Receptores de N-Metil-D-Aspartato , Animais , Medo/fisiologia , Extinção Psicológica/fisiologia , Tonsila do Cerebelo/metabolismo , Tonsila do Cerebelo/fisiologia , Camundongos , Plasticidade Neuronal/fisiologia , Masculino , Receptores de N-Metil-D-Aspartato/metabolismo , Receptor trkC/metabolismo , Neurotrofina 3/metabolismo , Potenciação de Longa Duração/fisiologia , Transdução de Sinais/fisiologia , Condicionamento Clássico/fisiologiaRESUMO
INTRODUCTION: Anastomotic leakage (AL) is one of the most feared postoperative complications in colon cancer surgery due to an association with increased morbidity and mortality, although its impact on long-term survival is not consensual. The aim of this study was to investigate the influence of AL on long-term survival of patients undergoing curative colon cancer resection. METHODS: A single-centre retrospective cohort study was designed. Clinical records of all consecutive patients undergoing surgery at our institution between 01/01/2010 and 12/31/2019 were reviewed. Survival analysis was performed by Kaplan-Meier method to estimate overall and conditional survival and Cox regression to search for risk factors impacting survival. RESULTS: A total of 2351 patients submitted to colorectal surgery were screened for eligibility, of which 686 with colon cancer were included. AL occurred in 57 patients (8,3%) and was associated with higher postoperative morbidity and mortality, length of stay and early readmissions (P < 0,05). Overall survival was inferior in the leakage group (Hazard Ratio 2,08 [1,02-4,24]). Conditional overall survival at 30, 90 days and 6 months was also inferior in the leakage group (P < 0,05), but not at 1 year. Risk factors independently associated with reduced overall survival included AL occurrence, higher ASA classification and delayed/missed adjuvant chemotherapy. AL did not impact local and distant recurrence (P > 0,05). CONCLUSION: AL has a negative impact on survival. Its effect is more pronounced on short-term mortality. AL does not appear to be associated with disease progression.
Assuntos
Neoplasias do Colo , Procedimentos Cirúrgicos do Sistema Digestório , Humanos , Fístula Anastomótica/epidemiologia , Fístula Anastomótica/etiologia , Estudos Retrospectivos , Neoplasias do Colo/cirurgia , Neoplasias do Colo/complicações , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversosRESUMO
General anxiety disorders are among the most prevalent mental health problems worldwide. The emergence and development of anxiety disorders can be due to genetic (30-50%) or non-genetic (50-70%) factors. Despite medical progress, available pharmacotherapies are sometimes ineffective or can cause undesirable side effects. Thus, it becomes necessary to discover new safe and effective drugs against anxiety. This study evaluated the anxiolytic effect in adult zebrafish (Danio rerio) of a natural pyrroloformamide (PFD), N-(4,5-dihydro-5-oxo-1,2-dithiolo-[4,3,b]-pyrrole-6-yl)-N-methylformamide, isolated from a Streptomyces sp. bacterium strain recovered from the ascidian Eudistoma vannamei. The complete structure of PFD was determined by a detailed NMR analysis, including 1H-13C and 1H-15N-HBMC data. In addition, conformational and DFT computational studies also were performed. A group of fishes (n = 6) was treated orally with PFD (0.1, 0.5 and 1.0 mg/mL; 20 µL) and subjected to locomotor activity and light/dark tests, as well as, acute toxicity 96 h. The involvement of the GABAergic and serotonergic (5-HT) systems was investigated using flumazenil (a silent modulator of GABA receptor) and 5-HT1, 5-HT2A/2C and 5-HTR3A/3B receptors antagonists, known as pizotifen, granisetron and cyproheptadine, respectively. PFD was nontoxic, reduced locomotor activity and promoted the anxiolytic effect in zebrafish. Flumazenil did not inhibit the anxiolytic effect of the PFD via the GABAergic system. This effect was reduced by a pretreatment with pizotifen and granisetron, and was not reversed after treatment with cyproheptadine. Molecular docking and dynamics studies confirmed the interaction of PFD with the 5-HT receptor.Communicated by Ramaswamy H. Sarma.
Pyrroloformamide (PFD), isolated from the marine Streptomyces sp. associated ascidian Eudistoma vannamei, showed no toxicity in adult zebrafish but reduced its locomotor activity.The structural elucidation of PFD was determined by the analysis of 1D and 2D NMR and HRESIMS data.The density functional theory (DFT) study confirmed the existence of two conformers as determined by NMR spectra.The serotonergic system modulated the anxiolytic effect of PFD via the 5-HT receptor in adult zebrafish.Molecular docking and dynamics studies confirmed the interaction of PFD with the 5-HT receptor.