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Neuronal cell types are the nodes of neural circuits that determine the flow of information within the brain. Neuronal morphology, especially the shape of the axonal arbor, provides an essential descriptor of cell type and reveals how individual neurons route their output across the brain. Despite the importance of morphology, few projection neurons in the mouse brain have been reconstructed in their entirety. Here we present a robust and efficient platform for imaging and reconstructing complete neuronal morphologies, including axonal arbors that span substantial portions of the brain. We used this platform to reconstruct more than 1,000 projection neurons in the motor cortex, thalamus, subiculum, and hypothalamus. Together, the reconstructed neurons constitute more than 85 meters of axonal length and are available in a searchable online database. Axonal shapes revealed previously unknown subtypes of projection neurons and suggest organizational principles of long-range connectivity.
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Encéfalo/citologia , Encéfalo/diagnóstico por imagem , Neuritos/fisiologia , Tratos Piramidais/fisiologia , Animais , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microscopia de Fluorescência por Excitação Multifotônica/métodos , Software , TransfecçãoRESUMO
Cocaine and antidepressants rank high globally in substance consumption, emphasizing their impact on public health. The determination of these compounds and related substances in biological samples is crucial for forensic toxicology. This study focused on developing an innovative analytical method for the determination of cocaine, antidepressants, and their related metabolites in postmortem blood samples, using unmodified commercial Fe3O4 nanoparticles as a sorbent for dispersive magnetic solid-phase extraction (m-d-SPE), coupled with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analysis. An aliquot of 100 µL of whole blood and 5 µL of the internal standard pool were added to 30 mg of nanoparticles. The nanoparticles were separated from the sample using a neodymium magnet inserted into a 3D-printed microtube rack. The liquid was then discarded, followed by desorption with 300 µL of 1/1/1 acetonitrile/methanol/ethyl acetate. The sample was vortexed and separated, and 1.5 µL of the organic supernatant was injected into the LC-MS/MS. The method was acceptably validated and successfully applied to 263 postmortem blood samples. All samples evaluated in this study were positive for at least one substance. The most frequent analyte was benzoylecgonine, followed by cocaine and cocaethylene. The most common antidepressants encountered in the analyzed samples were citalopram and fluoxetine, followed by fluoxetine's metabolite norfluoxetine. This study describes the first report of this sorbent in postmortem blood analysis, demonstrating satisfactory results for linearity, precision, accuracy, and selectivity for all compounds. The method's applicability was confirmed, establishing it as an efficient and sustainable alternative to traditional techniques for forensic casework.
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Antidepressivos , Cocaína , Toxicologia Forense , Nanopartículas de Magnetita , Extração em Fase Sólida , Espectrometria de Massas em Tandem , Humanos , Cocaína/sangue , Cocaína/análogos & derivados , Antidepressivos/sangue , Espectrometria de Massas em Tandem/métodos , Toxicologia Forense/métodos , Extração em Fase Sólida/métodos , Nanopartículas de Magnetita/química , Cromatografia Líquida/métodos , Limite de Detecção , Detecção do Abuso de Substâncias/métodos , Masculino , Feminino , AdultoRESUMO
In pharmaceutics, ingredients are classified as active ingredients and excipients. In topical/transdermal phytomedicines, an ingredient may serve both functions. Published information on these dual-purpose ingredients and their pharmacological relevance is limited. An intriguing scenario arises in traditional Chinese medicine (TCM) formulations, where active ingredients and excipients are undifferentiated. This study analyzes ingredients in TCM topical/transdermal formulations, aiming at harmonization of understanding of TCMs. The most commonly recorded ingredients from such formulations in the Chinese pharmacopoeia 2020 (ChP 2020) are reviewed, aiming at developing innovative topical/transdermal phytomedicines. Current editions of Chinese historical documents were reviewed to explore the principles underlying the use of these ingredients. TCM formulations containing botanical drugs for topical/transdermal application were selected from the ChP 2020. The use of botanical materials in TCM formulations is guided by the "Jun-Chen-Zuo-Shi" principle rooted in Yin-Yang and the five elements' theories. In the ChP 2020, 155 botanical drugs, along with 40 excipients (from the "procedure" section, focusing on processing and technical parameters), were identified from 34 botanical formulations intended for topical/transdermal application. Pungent and aromatic botanical materials were the most frequently recorded. Adhesive plasters were the most commonly recorded TCM dosage form, employing specific matrix blends. This new perspective of study reveals the prevalence of pungent and aromatic botanical materials, the common use of adhesive plasters, multifunctional properties of botanical oils, and formulation adaptability in TCM topical/transdermal products. These insights should inform novel formulation designs for both pharmaceutical and phytopharmacological research.
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The reconstruction of bones following tumor excision and radiotherapy remains a challenge. Our previous study, performed using polysaccharide-based microbeads that contain hydroxyapatite, found that these have osteoconductivity and osteoinductive properties. New formulations of composite microbeads containing HA particles doped with strontium (Sr) at 8 or 50% were developed to improve their biological performance and were evaluated in ectopic sites. In the current research, we characterized the materials by phase-contrast microscopy, laser dynamic scattering particle size-measurements and phosphorus content, before their implantation into two different preclinical bone defect models in rats: the femoral condyle and the segmental bone. Eight weeks after the implantation in the femoral condyle, the histology and immunohistochemistry analyses showed that Sr-doped matrices at both 8% and 50% stimulate bone formation and vascularization. A more complex preclinical model of the irradiation procedure was then developed in rats within a critical-size bone segmental defect. In the non-irradiated sites, no significant differences between the non-doped and Sr-doped microbeads were observed in the bone regeneration. Interestingly, the Sr-doped microbeads at the 8% level of substitution outperformed the vascularization process by increasing new vessel formation in the irradiated sites. These results showed that the inclusion of strontium in the matrix-stimulated vascularization in a critical-size model of bone tissue regeneration after irradiation.
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Regeneração Óssea , Polímeros , Ratos , Animais , Hidroxiapatitas/química , Osteogênese , Estrôncio/químicaRESUMO
This research aims to determine whether the combination of epidemiological and clinical features can predict malaria. Diagnostic investigation detected 22.3% of individuals with Plasmodium vivax (P. vivax) malaria, with significant predominance of the male gender. The malaria triad (fever, chills and headache) had a more expressive frequency (81.1%) in individuals with positive thick blood than those with negative thick blood smear (65.1%), although there was no statistical significance. Among the variables analysed as predictive for positive thick blood smear, it was observed that personal history of travel to an endemic malaria area and past malaria infection (PMI) were significantly associated with malaria, even in multiple logistic regression. Fever had the higher sensitivity (94.6%) and past malaria history had the greater specificity (68.2%), with accuracy of 23.5% and 67.5%, respectively. In combined analysis, fever with chills had the highest sensitivity (91.9%), but low accuracy (38.5%). High specificity (91.5%) was found in the association of malaria triad, PMI and history of travel to endemic malaria area (which along with anorexia, was higher 94.6%), with good accuracy (80.7%), suggesting that the screening of patients for performing thick blood smear can be based on these data. The epidemiological features and the malaria triad (fever, chills and headache) can be predictors for identification of malaria patients, concurring to precocious diagnosis and immediate treatment of individuals with malaria.
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Malária Falciparum , Malária Vivax , Malária , Brasil/epidemiologia , Humanos , Malária/diagnóstico , Malária/epidemiologia , Malária Falciparum/epidemiologia , Malária Vivax/diagnóstico , Malária Vivax/epidemiologia , Masculino , Plasmodium vivax , ViagemRESUMO
BACKGROUND: Surgical Tray Rationalization (STR) consists of a systematic reduction in the number of surgical instruments to perform specific procedures without compromising patient safety while reducing losses in the sterilization and assembly of trays. STR is one example of initiatives to improve process performance that have been widely reported in industrial settings but only recently have gained popularity in healthcare organizations. METHODS: We conduct a scoping review of the literature to identify and map available evidence on surgical tray management. Five methodological stages are implemented and reported; they are: identifying research questions, identifying relevant studies, study selection, charting the data, and collating, summarizing and reporting the results. RESULTS: We reviewed forty-eight articles on STR, which were grouped according to their main proposed approaches: expert analysis, lean practices, and mathematical programming. We identify the most frequently used techniques within each approach and point to their potential contributions to operational and economic dimensions of STR. We also consolidate our findings, proposing a roadmap to STR with four generic steps (prepare, rationalize, implement, and consolidate) and recommended associated techniques. CONCLUSIONS: To the best of our knowledge, ours is the first study that reviews and systematizes the existing literature on the subject of STR. Our study closes with the proposition of future research directions, which are presented as nine research questions associated with the four generic steps proposed in the STR roadmap.
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Racionalização , Instrumentos Cirúrgicos , Humanos , EsterilizaçãoRESUMO
BACKGROUND: Recent physiological and experimental data highlight the role of the sensory nervous system in bone repair, but its precise role on angiogenesis in a bone regeneration context is still unknown. Our previous work demonstrated that sensory neurons (SNs) induce the osteoblastic differentiation of mesenchymal stem cells, but the influence of SNs on endothelial cells (ECs) was not studied. METHODS: Here, in order to study in vitro the interplay between SNs and ECs, we used microfluidic devices as an indirect co-culture model. Gene expression analysis of angiogenic markers, as well as measurements of metalloproteinases protein levels and enzymatic activity, were performed. RESULTS: We were able to demonstrate that two sensory neuropeptides, calcitonin gene-related peptide (CGRP) and substance P (SP), were involved in the transcriptional upregulation of angiogenic markers (vascular endothelial growth factor, angiopoietin 1, type 4 collagen, matrix metalloproteinase 2) in ECs. Co-cultures of ECs with SNs also increased the protein level and enzymatic activity of matrix metalloproteinases 2 and 9 (MMP2/MMP9) in ECs. CONCLUSIONS: Our results suggest a role of sensory neurons, and more specifically of CGRP and SP, in the remodelling of endothelial cells extracellular matrix, thus supporting and enhancing the angiogenesis process. Video abstract.
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Células Endoteliais/metabolismo , Matriz Extracelular/metabolismo , Gânglios Espinais/metabolismo , Células Receptoras Sensoriais/metabolismo , Animais , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Células Endoteliais/ultraestrutura , Matriz Extracelular/ultraestrutura , Feminino , Gânglios Espinais/ultraestrutura , Regulação da Expressão Gênica , Metaloproteinases da Matriz/biossíntese , Microfluídica , Modelos Biológicos , Neuritos/metabolismo , Osteogênese , Ratos Wistar , Células Receptoras Sensoriais/ultraestrutura , Substância P/metabolismoRESUMO
In this study, essential oil extracted from Syagrus coronata seeds (SCEO) was evaluated for antibacterial and antibiofilm activities against Staphylococcus aureus; in addition, Galleria mellonella model was used as an in vivo infection model. SCEO was mainly composed by fatty acids (89.79%) and sesquiterpenes (8.5%). The major components were octanoic acid, dodecanoic acid, decanoic acid and γ-eudesmol. SCEO showed bactericidal activity (minimal bactericidal concentration from 312 to 1250⯵g/mL) against all tested S. aureus clinical isolates, which showed distinct biofilm-forming and multiple drug resistance phenotypes. SCEO weakly reduced biomass but remarkably decreased cell viability in pre-formed biofilms of S. aureus isolate UFPEDA-02 (ATCC-6538). Electron microscopy analysis showed that SCEO treatments decreased the number of bacterial cells (causing structural alterations) and lead to loss of the roughness in the multiple layers of the three-dimensional biofilm structure. In addition, overproduction of exopolymeric matrix was observed. SCEO at 31.2â¯mg/kg improved the survival of G. mellonela larvae inoculated with UFPEDA-02 isolate and reduced the bacterial load in hemolymph and melanization. In conclusion, SCEO is an antibacterial agent against S. aureus strains with different resistance phenotypes and able to disturb biofilm architecture. Our results show SCEO as a potential candidate to drug development.
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Antibacterianos/farmacologia , Arecaceae/química , Biofilmes/efeitos dos fármacos , Lepidópteros/microbiologia , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Staphylococcus/efeitos dos fármacos , Animais , Antibacterianos/química , Biofilmes/crescimento & desenvolvimento , Brasil , Modelos Animais de Doenças , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Óleos Voláteis/química , Extratos Vegetais/química , Sementes/química , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimentoRESUMO
Currently, titanium and its alloys are the most used materials for biomedical applications. However, because of the high costs of these metals, new materials, such as niobium, have been researched. Niobium appears as a promising material due to its biocompatibility, and excellent corrosion resistance. In this work, anodized niobium samples were produced and characterized. Their capacity to support the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) was also tested. The anodized niobium samples were characterized by SEM, profilometry, XPS, and wettability. BM-MSCs were cultured on the samples during 14 days, and tested for cell adhesion, metabolic activity, alkaline phosphatase activity, and mineralization. Results demonstrated that anodization promotes the formation of a hydrophilic nanoporous oxide layer on the Nb surface, which can contribute to the increase in the metabolic activity, and in osteogenic differentiation of BM-MSCs, as well as to the extracellular matrix mineralization.
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Diferenciação Celular/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Nióbio/farmacologia , Osteogênese/efeitos dos fármacos , Alicerces Teciduais , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/fisiologia , Células Cultivadas , Eletrólise , Feminino , Temperatura Alta , Teste de Materiais , Células-Tronco Mesenquimais/fisiologia , Nióbio/química , Oxirredução , Ratos , Ratos Endogâmicos SHR , Propriedades de Superfície , Alicerces Teciduais/químicaRESUMO
Prioritizing watershed management interventions relies on delineating homogeneous precipitation regions. In this study, we identify these regions in the Brazilian Legal Amazon based on the magnitude of Sen's Slope trends using annual precipitation data from September to August, employing the Google Earth Engine platform. Utilizing the silhouette method, we determine four distinct clusters representing zones of homogeneous precipitation patterns. Cluster 0 exhibits a significant median increase in precipitation of 3.20 mm year-1 over the period from 1981 to 2020. Cluster 1 shows a notable increase of 8.13 mm year-1, while Clusters 2 and 3 demonstrate reductions in precipitation of - 1.61 mm year-1 and - 3.87 mm year-1, respectively, all statistically significant. Notably, the region known as the arc of deforestation falls within Cluster 2, indicating a concerning trend of reduced precipitation. Additionally, our analysis reveals significant correlations between Sea Surface Temperature (SST) in various oceanic regions and precipitation patterns over the Brazilian Legal Amazon. Particularly noteworthy is the strong positive correlation with SST in the South Atlantic, while negative correlations are observed with SST in the South Pacific and North Atlantic. These findings provide valuable insights for enhancing climate adaptation strategies in the Brazilian Legal Amazon region.
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INTRODUCTION: The revised international standards for neurological classification of spinal cord injury (ISNCSCI) have facilitated the documentation of non-spinal cord injury-related impairments, such as chronic peripheral nerve injuries and muscle weakness due to immobility. This advancement addresses potential biases in muscle strength examinations. Utilizing electrically evoked contractions from paralyzed muscles, enhanced by electrodiagnosis, holds promise in identifying false-negative diagnoses of non-responsiveness to neuromuscular electrical stimulation. This concept prompts the exploration of polyneuromyopathy arising from nonuse in paralyzed muscles. CASE SERIES PRESENTATION: To substantiate our hypothesis, we recruited nine participants for a case series aimed at elucidating the potential benefits of incorporating the stimulus electrodiagnostic test (SET) to mitigate non-responsiveness during preparation for functional electrical stimulation (FES)-assisted cycling. In our convenience sample (n = 5), we conducted neurological mapping based on ISNCSCI and applied SET on the quadriceps. The SET guided optimal dosimetry for evoking contractions and revealed responses similar to those observed in peripheral neuropathies, with α coefficients equal to or lower than 2.00. This observation is likely attributable to nonuse of paralyzed muscles, indicative of an ongoing polyneuropathy in individuals with chronic spinal cord injury (SCI). DISCUSSION: Among the nine initially recruited subjects, seven exhibited responsiveness to neuromuscular electrical stimulation (78% responsiveness), with two participants excluded based on exclusion criteria. In the final five reported cases, all displayed α coefficient values indicating impaired neuromuscular accommodation, and one presented no α coefficient within the normal range. The inclusion of electrodiagnosis appears effective in averting non-responsiveness, suggesting the presence of ongoing polyneuropathies in paralyzed muscles.
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Eletrodiagnóstico , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Polineuropatias/diagnóstico , Estimulação Elétrica , Traumatismos da Medula Espinal/diagnóstico , Traumatismos da Medula Espinal/reabilitação , Traumatismos da Medula Espinal/complicações , Eletromiografia , Contração Muscular/fisiologia , Debilidade Muscular/diagnóstico , Idoso , Músculo EsqueléticoRESUMO
Despite progress in bone tissue engineering, reconstruction of large bone defects remains an important clinical challenge. Here, a biomaterial designed to recruit bone cells, endothelial cells, and neuronal fibers within the same matrix is developed, enabling bone tissue regeneration. The bioactive matrix is based on modified elastin-like polypeptides (ELPs) grafted with laminin-derived adhesion peptides IKVAV and YIGSR, and the SNA15 peptide for retention of hydroxyapatite (HA) particles. The composite matrix shows suitable porosity, interconnectivity, biocompatibility for endothelial cells, and the ability to support neurites outgrowth by sensory neurons. Subcutaneous implantation leads to the formation of osteoid tissue, characterized by the presence of bone cells, vascular networks, and neuronal structures, while minimizing inflammation. Using a rat femoral condyle defect model, longitudinal micro-CT analysis is performed, which demonstrates a significant increase in the volume of mineralized tissue when using the ELP-based matrix compared to empty defects and a commercially available control (Collapat). Furthermore, visible blood vessel networks and nerve fibers are observed within the lesions after a period of two weeks. By incorporating multiple key components that support cell growth, mineralization, and tissue integration, this ELP-based composite matrix provides a holistic and versatile solution to enhance bone tissue regeneration.
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Regeneração Óssea , Elastina , Engenharia Tecidual , Animais , Elastina/química , Ratos , Engenharia Tecidual/métodos , Regeneração Óssea/efeitos dos fármacos , Humanos , Alicerces Teciduais/química , Durapatita/química , Durapatita/farmacologia , Osso e Ossos , Ratos Sprague-Dawley , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Microtomografia por Raio-XRESUMO
Driving under the influence of cannabis (DUIC) is increasing worldwide, and cannabis is the most prevalent drug after alcohol in impaired driving cases, emphasizing the need for a reliable traffic enforcement strategy. ∆9 -tetrahydrocannabinol (THC) detection in oral fluid has great potential for identifying recent cannabis use; however, additional data are needed on the sensitivities, specificities, and efficiencies of different oral fluid devices for detecting cannabinoids at the roadside by police during routine traffic safety enforcement efforts. At the roadside, 8945 oral fluid THC screening tests were performed with four devices: AquilaScan®, Dräger DrugTest®, WipeAlyser Reader®, and Druglizer®. A total of 530 samples screened positive for THC (5.9%) and were analyzed by liquid chromatography-tandem mass spectrometry at multiple cutoff concentrations (2 ng/mL, 10 ng/mL, and manufacturers' recommended device cutoffs) to investigate device performance. Results varied substantially, with sensitivities of 0%-96.8%, specificities of 89.8%-98.5%, and efficiencies of 84.3%-97.8%. The Dräger DrugTest® outperformed the other devices with a 96.8% sensitivity, 97.1% specificity, and 97.0% efficiency at a 5-ng/mL LC-MS/MS confirmation cutoff. The WipeAlyser Reader® had good performance with a 91.4% sensitivity, 97.2% specificity, and 96.4% efficiency. AquilaScan® and Druglizer® had unacceptable performance for cannabinoid detection, highlighted by sensitivity <13%. The choice of roadside oral fluid testing device must offer good analytical performance for cannabinoids because of its high prevalence of use and impact on road safety.
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Urine toxicological analysis is a relevant tool in both clinical and forensic scenarios, enabling the diagnosis of acute poisonings, elucidation of deaths, verification of substance use in the workplace and identification of drug-facilitated crimes. For these analyses, the dilute-and-shoot technique associated with liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS) is a promising alternative since it has demonstrated satisfactory results and broad applicability. This study developed and validated a comprehensive LC-MS-MS screening method to analyze 95 illicit drugs and medicines in urine samples and application to clinical and forensic Brazilian cases. The dilute-and-shoot protocol was defined through multivariate optimization studies and was set using 100 µL of sample and 300 µL of solvent. The total chromatographic run time was 7.5 min. The method was validated following the recommendations of the ANSI/ASB Standard 036 Guideline. The lower limits of quantification varied from 20 to 100 ng/mL. Within-run and between-run precision coefficient of variations% were <20%, and bias was within ± 20%. Only 4 of the 95 analytes presented significant ionization suppression or enhancement (>25%). As proof of applicability, 839 urine samples from in vivo and postmortem cases were analyzed. In total, 90.9% of the analyzed samples were positive for at least one substance, and 78 of the 95 analytes were detected. The most prevalent substances were lidocaine (40.2%), acetaminophen (38.0%) and benzoylecgonine (31.5%). The developed method proved to be an efficient and simplified alternative for analyzing 95 therapeutic and illicit drugs in urine samples. Additionally, the results obtained from sample analysis are essential for understanding the profile of Brazilian substance use, serving as a valuable database for the promotion of health and safety public policies.
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Toxicologia Forense , Drogas Ilícitas , Detecção do Abuso de Substâncias , Espectrometria de Massas em Tandem , Humanos , Drogas Ilícitas/urina , Brasil , Detecção do Abuso de Substâncias/métodos , Cromatografia Líquida , Toxicologia Forense/métodos , Reprodutibilidade dos Testes , Limite de Detecção , Espectrometria de Massa com Cromatografia LíquidaRESUMO
BACKGROUND: Previously, we demonstrated that trans fatty acid ingestion during pregnancy and lactation caused a pro-inflammatory effect on the newborn. The opposite effect was described for gestational prebiotic intake. In the present study, we examined whether supplementation of the diet of the dams with 10% of oligofructose with or without hydrogenated vegetable fat during pregnancy and lactation affected the pro-inflammatory status on the pups at age 21 days. METHODS: On the first day of pregnancy, rats were divided into four groups, each of which received one of four diets: a control diet (C group), a control diet supplemented with 10% oligofructose (CF group), a diet enriched with hydrogenated vegetable fat containing trans fatty acids (T group) or a diet enriched with hydrogenated vegetable fat containing trans fatty acids supplemented with 10% oligofructose (TF group). The pups were weighed at birth and at 7, 14 and 21 days of life and were euthanized on post-natal day 21. The serum glucose, insulin and adiponectin concentrations were analyzed. The IL-6, IL-10 and TNF-α contents of the retroperitoneal white adipose tissue, liver, soleus and extensor digital longus muscles were analyzed by ELISA. The results are presented as the means ± standard error of the mean. Statistical significance was assessed using two-way ANOVA, followed by Tukey's test and considered significant at p < 0.05 RESULTS: The body weights of the 21-day old pups in the CF and TF groups were significant lower than those of the C (27% and 21%) and T (25% and 19%, respectively) groups. The serum levels of adiponectin in the CF, T and TF groups were lower than in the C group (41%; 34% and 31%, respectively). In the retroperitoneal adipose tissue, the IL-6 content was increased in TF group relative to the C and CF groups (74% for both), and the TNF-α content was higher in the T and TF groups than in the C group (62% and 98%, respectively). In the liver, the TNF-α (56% and 104%) and IL-10 (52% and 73%) contents were increased in the CF group relative to the C and TF groups. CONCLUSIONS: Supplementation of the diet of the dams with 10% of oligofructose during pregnancy and lactation, independent of supplementation with hydrogenated vegetable fat, adversely affected the development of the offspring and contributed to development of a pro-inflammatory status in the pups on postnatal day 21.
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Suplementos Nutricionais , Inflamação/dietoterapia , Oligossacarídeos/administração & dosagem , Ácidos Graxos trans/metabolismo , Animais , Glicemia , Feminino , Humanos , Inflamação/metabolismo , Lactação/efeitos dos fármacos , Gravidez , RatosRESUMO
This study analyzed the effect of diet enriched with 30% lipids on cytokines content in different tissues. Swiss male mice were distributed into four groups treated for 8 weeks with control (C, normolipidic diet); soybean oil (S); lard (L); and hydrogenated vegetable fat (H). We observed an increase in carcass fat in groups S and L, and the total amount of fatty deposits was only higher in group L compared with C group. The serum levels of free fatty acids were lower in the L group, and insulin, adiponectin, lipid profile, and glucose levels were similar among the groups. IL-10 was lower in group L in mesenteric and retroperitoneal adipose tissues. H reduced IL-10 only in retroperitoneal adipose tissue. There was an increase in IL-6 in the gastrocnemius muscle of the L group, and a positive correlation between TNF-α and IL-10 was observed in the livers of groups C, L, and H and in the muscles of all groups studied. The results suggested relationships between the quantity and quality of lipids ingested with adiposity, the concentration of free fatty acids, and cytokine production in white adipose tissue, gastrocnemius muscle, and liver.
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Tecido Adiposo/metabolismo , Citocinas/metabolismo , Dieta , Ácidos Graxos Insaturados/química , Fígado/metabolismo , Músculo Esquelético/metabolismo , Ácidos Graxos trans/química , Animais , Peso Corporal , Ensaio de Imunoadsorção Enzimática , Insulina/metabolismo , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Masculino , Camundongos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The diagnostic methods in an emergency scenario must be simple, fast, and efficient to provide an effectiveness and efficient treatment, thus reducing the consequences of exposure. Considering the sample analysis, the protein precipitation combined with LC-MS/MS has been shown to be a good strategy for the simultaneous determination of compounds of toxicological interest, such as medicines and drugs of abuse. In this study, a rapid and simple multi-analyte method was developed and validated for the quantification of 57 pharmaceuticals and illicit drugs in plasma samples. Sample pre-treatment consists of protein precipitation of 50 µL of the sample with 240 µL of organic solvent mixture (MeOH:ACN, 3:1, v/v), centrifugation, and injection into the LC-MS/MS, with a chromatographic run time of 7 min. The method was validated considering lower limit of quantification (LLOQ), interferences, linearity, precision, accuracy, dilution integrity, carryover, and matrix effect. The LLOQs ranged from 5 to 20 ng/mL and all analytes were linear (r2>0.99) in the tested concentration ranges. The method proved to be precise and accurate, presenting QC concentrations for all analytes within acceptable limits by the guideline used (CV % ≤20 % and bias ± 20 %). The developed method was successfully applied in 470 plasma samples of real cases of poisoning. A total of 80 % of the samples were positive for at least one substance, with acetaminophen (32.1 %), diazepam (25.1 %), and lidocaine (18.9 %) being the most detected. The most prevalent exposure circumstance among the cases was suicide attempt. The most frequent age groups were young adults between 20 and 29 years old and children under 5 years old. The methodology developed proved to be efficient in the simultaneous determination of 57 substances of toxicological interest, contributing to a correct diagnosis and, consequently, to the most appropriate management and treatment of the intoxicated patient. Furthermore, it is possible to observe the most commonly involved toxic agents in the Rio Grande do Sul, southern Brazil, helping to trace a profile of the poisoning patient, important in toxicovigilance actions.
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Drogas Ilícitas , Humanos , Criança , Pré-Escolar , Adulto Jovem , Adulto , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Plasma , Brasil , Reprodutibilidade dos Testes , Limite de DetecçãoRESUMO
PURPOSE: To demonstrate the importance of optical coherence tomography (OCT) in identifying macular changes not detected at clinical examination preceding cataract surgery in patients older than 60 years. SETTING: Hospital Oftalmológico Visão Laser, Santos, São Paulo, Brazil. DESING: Prospective case series. METHODS: Patients older than 60 years were selected for this cross-sectional prospective study conducted during preoperative examination for cataract surgery. Eyes with a previous diagnosis or clinical evidence of macular disease or with media opacity preventing OCT from being performed were excluded from the study. All the study participants underwent OCT and were then divided into 2 groups: patients with macular changes and patients without macular changes found on OCT. RESULTS: Of 364 eyes screened (212 patients), 300 eyes (180 patients) were included in the study. OCT identified macular changes in 40 eyes (13.3%), with age-related macular degeneration being found in 13 eyes (4.3%), epiretinal membrane in 12 eyes (4%), intraretinal fluid in 12 eyes (4%), and macular hole in 3 eyes (1%). In the group with macular changes, the mean age was 74.4 ± 6.3 years compared with 70.4 ± 6.7 years for those without changes ( P < .001). CONCLUSIONS: OCT proved an effective method for identifying macular diseases not detected at clinical evaluation before cataract surgery. Therefore, the relevance of performing OCT in these cases was confirmed and should be taken into consideration, particularly when evaluating patients older than 60 years.
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Catarata , Doenças Retinianas , Humanos , Idoso , Idoso de 80 Anos ou mais , Tomografia de Coerência Óptica/métodos , Estudos Prospectivos , Estudos Transversais , Brasil , Catarata/diagnósticoRESUMO
Background: The increasing prevalence of poisoning cases related to antidepressants and antipsychotics has raised concerns. Methods: To address this issue, a new adaptation of the dried plasma spot technique was developed using a 24-well plate and fast gas chromatography-mass spectrometry. The method involves the optimization of extraction variables and sample preparation, and was successfully validated. Results: The limits of quantitation ranged from 20 to 60 ng/ml, and accuracy ranged from 87.8% to 112.2%. The technique was applied to 102 human plasma samples from suspected poisoning cases, with positivity of 90.2%. Conclusion: This method provides a cheap, easy to implement and fast approach, making it ideal for toxicological emergency laboratories and promoting valuable support for healthcare professionals managing poisoning cases involving antidepressants and antipsychotics.
Assuntos
Antipsicóticos , Humanos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Espectrometria de Massas em Tandem/métodos , Antidepressivos , Plasma , Teste em Amostras de Sangue Seco/métodos , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: The aim of this study was to evaluate the influence of the sandblasting treatment on the microstructure, optical and mechanical properties of multi-layered translucent zirconia. METHODS: Samples of yttria-stabilized zirconia were prepared by stratifying four layers (L1, L2, L3 and L4) of ML-type KATANA multi-layered monolithic discs, whose surfaces were then sandblasted with alumina particles (110 µm and 0.2 MPa) in order to evaluate its effect on the presence of different crystalline phases as well as on the optical and mechanical properties of each of the four layers. The optical characterization was carried out by measuring the reflectance spectrum and colorimetric parameters by UV-Vis spectrophotometric analysis and the transmittance curves were indirectly obtained using the Kubelka-Munk model (KM). Microstructural, structural, mechanical and roughness characterizations were also performed using SEM, XRD, biaxial flexural strength B3B, and light interferometry, respectively RESULTS: According to the KM model there are different degrees of translucency between the upper and lower layers of the monolithic discs, but there was no influence of the Al2O3-sandblasting treatment on this optical property. The disk pigmentation causes greater absorption of light below 600 nm, decreasing the transmittance rate to values below 25% in this region of the spectrum. The yellowing index presented higher values for inner disk layers L3 and L4, in agreement with the highest values of the light absorption coefficient K observed for these layers. The roughness of the samples did not change significantly with the surface treatment performed and the sandblasting did not result in new crystalline phases. SEM analysis showed the presence of different grain sizes in all layers analyzed, being related to the co-occurring presence of cubic (c-ZrO2) and tetragonal (t-ZrO2) phases in similar contents (â¼ 50 wt%). The Weibull statistical analysis, in turn, showed an increase in the Weibull characteristic stress value (σ0) for most layers subjected to sandblasting, except for the second layer (central region of the disk). It was also verified an increase in the value of the structural reliability of the material (m), referring to the samples of the central region of the disc (L2 and L3 layers) after sandblasting. SIGNIFICANCE: The pigmentation in the disk causes a decrease of the transmittance rate to values well below 25% in the region of the spectrum 400-600 nm and the inner layers (L3 and L4) have even lower transmittance than the outer layers in this spectrum range. Although the CR index indicates variation related to the Al2O3-sandblasting treatment, the transmittance spectra of KM model show that the sandblasting did not cause a significant change in the transmittance rate of the four analyzed layers. Also, there is no significant difference in the light scattering of the different layers of the disc, either before or after Al2O3-sandblasting treatment.