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1.
Water Sci Technol ; 85(12): 3479-3492, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35771059

RESUMO

In Brazil, domestic effluents represent the primary source of pressure on water resources. Water pollution can be controlled by defining, applying, and enforcing the effluent standards for wastewater discharge. Discussions are ongoing in Minas Gerais State regarding the possibility of setting a discharge standard for ammonia nitrogen in municipal wastewater, which is currently not required. However, providing technical support for decision-making is challenging because of the difficulties in accessing monitoring data from sewage treatment plants. This study aimed to analyze the monitoring data from 49 sewage treatment plants operating in Minas Gerais to offer guidance for decision making. High concentrations of ammonia nitrogen in the effluents of the treatment plants were found, reinforcing the need for better control and the adoption of more advanced technologies. Furthermore, it was observed an increase in concentrations downstream of the discharges in the receiving water bodies. Adopting a progressive and adaptable discharge standard can be a solution for better control of treatment systems.


Assuntos
Esgotos , Águas Residuárias , Amônia , Brasil , Nitrogênio/análise
2.
Opt Lett ; 46(11): 2654-2657, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34061080

RESUMO

Soot temperature measurements in laminar flames are often performed through two-color broadband emission pyrometry (BEMI) or modulated absorption/emission (BMAE) techniques, using models to relate the ratio between flame intensities at two different wavelengths with soot temperature. To benefit from wider spectral range and increase the accuracy of experimental estimation of soot temperature, this work proposes a new approach that uses three-color broadband images captured with a basic color camera. The methodology is first validated through simulations using numerically generated flames from the CoFlame code and then used to retrieve soot temperature in an experimental campaign. The experimental results show that using three-color and BEMI provides smoother reconstruction of soot temperature than two-color and BMAE when small disturbances exist in the measured signals due to a reduced experimental noise effect. A sensitivity analysis shows that the retrieved temperature from three-color BEMI is more resilient to variations on the ratio of measured signals than BMAE, which is confirmed by an error propagation analysis based on a Monte Carlo approach.

3.
Inorg Chem ; 60(2): 1062-1079, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33372756

RESUMO

Silver tungstate (Ag2WO4) shows structural polymorphism with different crystalline phases, namely, orthorhombic, hexagonal, and cubic structures that are commonly known as α, ß, and γ, respectively. In this work, these Ag2WO4 polymorphs were selectively and successfully synthesized through a simple precipitation route at ambient temperature. The polymorph-controlled synthesis was conducted by means of the volumetric ratios of the silver nitrate/tungstate sodium dehydrate precursors in solution. The structural and electronic properties of the as-synthesized Ag2WO4 polymorphs were investigated by using a combination of X-ray diffraction and Rietveld refinements, X-ray absorption spectroscopy, X-ray absorption near-edge structure spectroscopy, field-emission scanning electron microscopy images, and photoluminescence. To complement and rationalize the experimental results, first-principles calculations, at the density functional theory level, were carried out, leading to an unprecedented glimpse into the atomic-level properties of the morphology and the exposed surfaces of Ag2WO4 polymorphs. Following the analysis of the local coordination of Ag and W cations (clusters) at each exposed surface of the three polymorphs, the structure-property relationship between the morphology and the photocatalytic and antibacterial activities against amiloride degradation under ultraviolet light irradiation and methicillin-resistant Staphylococcus aureus, respectively, was investigated. A possible mechanism of the photocatalytic and antibacterial activity as well the formation process and growth of the polymorphs is also explored and proposed.


Assuntos
Antibacterianos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Óxidos/farmacologia , Prata/farmacologia , Tungstênio/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Catálise , Teoria da Densidade Funcional , Testes de Sensibilidade Microbiana , Modelos Moleculares , Óxidos/química , Tamanho da Partícula , Processos Fotoquímicos , Prata/química , Relação Estrutura-Atividade , Propriedades de Superfície , Tungstênio/química , Raios Ultravioleta
4.
Reprod Domest Anim ; 55(4): 429-437, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31916315

RESUMO

Although stem cell therapy is a promising alternative for treatment of degenerative diseases, there are just few reports on the use of stem cells therapy in horse's reproductive system. This study aims to evaluate the effect of intratesticular injection of bone marrow mesenchymal stromal/stem cells (MSCs) in healthy stallions, and its outcome on seminal parameters and fertility. In Experiment 1, 24 stallions were divided into treatment group (TG) and control group (CG). In the TG, an intratesticular application of MSC was performed, and in the CG, only PBS was used. Measurements of testicular volume, surface temperature and Doppler ultrasonography were performed 24 and 48 hr after treatments. Fifteen days after application, the testicles were removed and submitted to histological analysis. In Experiment 2, 3 fertile stallions received similarly treatment with MSCs. Physical examination and sperm analysis were performed weekly during 60 days after treatment, and at the end, semen from one of them was used for artificial inseminations of 6 healthy mares. In Experiment 1, clinical examinations showed no signals of acute inflammation on both groups according to the analysed variables (p > .05). Also, no signal of chronic inflammation was observed on histological evaluation. In Experiment 2, stallions presented no physical alterations or changes in sperm parameters, and a satisfactory fertility rate (83%; 5/6) was observed after AI. The results support the hypothesis that intratesticular application of bone marrow MSCs is a safe procedure, and this could be a promising alternative to treat testicular degenerative conditions.


Assuntos
Transplante de Células-Tronco Mesenquimais/veterinária , Células-Tronco Mesenquimais , Testículo , Tolerância ao Transplante , Animais , Feminino , Fertilidade , Cavalos , Inseminação Artificial/veterinária , Masculino , Análise do Sêmen , Testículo/anatomia & histologia , Testículo/fisiologia , Transplante Homólogo/veterinária
5.
Int J Mol Sci ; 21(19)2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33019757

RESUMO

The intermediate filament synemin has been previously identified as novel regulator of cancer cell therapy resistance and DNA double strand break (DSB) repair. c-Abl tyrosine kinase is involved in both of these processes. Using PamGene technology, we performed a broad-spectrum kinase activity profiling in three-dimensionally, extracellular matrix grown head and neck cancer cell cultures. Upon synemin silencing, we identified 86 deactivated tyrosine kinases, including c-Abl, in irradiated HNSCC cells. Upon irradiation and synemin inhibition, c-Abl hyperphosphorylation on tyrosine (Y) 412 and threonine (T) 735 was significantly reduced, prompting us to hypothesize that c-Abl tyrosine kinase is an important signaling component of the synemin-mediated radioresistance pathway. Simultaneous targeting of synemin and c-Abl resulted in similar radiosensitization and DSB repair compared with single synemin depletion, suggesting synemin as an upstream regulator of c-Abl. Immunoprecipitation assays revealed a protein complex formation between synemin and c-Abl pre- and post-irradiation. Upon pharmacological inhibition of ATM, synemin/c-Abl protein-protein interactions were disrupted implying synemin function to depend on ATM kinase activity. Moreover, deletion of the SH2 domain of c-Abl demonstrated a decrease in interaction, indicating the dependency of the protein-protein interaction on this domain. Mechanistically, radiosensitization upon synemin knockdown seems to be associated with an impairment of DNA repair via regulation of non-homologous end joining independent of c-Abl function. Our data generated in more physiological 3D cancer cell culture models suggest c-Abl as further key determinant of radioresistance downstream of synemin.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia/genética , Reparo do DNA , DNA de Neoplasias/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Filamentos Intermediários/genética , Proteínas Proto-Oncogênicas c-abl/genética , Animais , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Proliferação de Células/efeitos da radiação , Quebras de DNA de Cadeia Dupla , DNA de Neoplasias/metabolismo , Embrião não Mamífero , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Proteínas de Filamentos Intermediários/antagonistas & inibidores , Proteínas de Filamentos Intermediários/metabolismo , Fosforilação , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Proteínas Proto-Oncogênicas c-abl/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Tolerância a Radiação/genética , Transdução de Sinais , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Raios X , Peixe-Zebra
6.
Eur J Appl Physiol ; 119(5): 1235-1243, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30848358

RESUMO

PURPOSE: Physical exercise is associated with reduced blood pressure (BP). Moderate-intensity continuous exercise (MCE) promotes post-exercise hypotension (PEH), which is highly recommended to hypertensive patients. However, recent studies with high-intensity interval exercise (HIIE) have shown significant results in cardiovascular disease. Thus, this study aimed to analyze PEH in hypertensive subjects submitted to HIIE and compare it to post MCE hypotension. METHODS: 20 hypertensive adults (51 ± 8 years), treated with antihypertensive medications, were submitted to two different exercise protocols and a control session. The MCE was performed at 60-70% of VO2 reserve, while HIIE was composed of five bouts of 3 min at 85-95% VO2 reserve with 2 min at 50% of VO2 reserve. The following variables were evaluated during exercise, pre- and post-session: clinical BP, heart rate (HR), double product, perception of effort, body mass, height and body mass index. RESULTS: Systolic BP decreased after exercise in both sessions, showing greater decrease after HIIE (- 7 ± 10 and - 11 ± 12 mmHg, after MCE and HIIE, respectively, p ≤ 0.01). Diastolic BP also decreased after both sessions, but there were no significant differences between the two sessions (- 4 ± 8 and - 7 ± 8 mmHg, after MCE and HIIE, respectively). CONCLUSION: Both exercise sessions produced PEH, but HIIE generated a greater magnitude of hypotension. The HIIE protocol performed in this study caused a greater cardiovascular stress during exercise; however, it was safe for the studied population and efficient for reducing BP after exercise.


Assuntos
Treinamento Intervalado de Alta Intensidade/efeitos adversos , Hipotensão Pós-Exercício/etiologia , Adulto , Pressão Sanguínea , Feminino , Frequência Cardíaca , Treinamento Intervalado de Alta Intensidade/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio , Hipotensão Pós-Exercício/fisiopatologia
7.
Int J Toxicol ; 38(5): 415-422, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31470746

RESUMO

Minipigs are an emerging nonrodent alternative for ocular toxicology owing to anatomical similarities in the minipig eyes when compared to humans. Ocular structures and components from Göttingen minipigs were characterized and compared to species commonly used in toxicology. Ocular reference data from Göttingen minipig including intraocular pressure, vitreous electrolyte and thiol concentration, and electroretinography (ERG) data are essential to model characterization and data interpretation during drug safety assessments. Intravitreal positive control agents including gentamicin, indocyanine green, and glycine were used to demonstrate ERG alterations caused by retinal cell toxicity, light transmission obstruction, or neurotransmission interferences, respectively. Electrolyte concentrations of the aqueous and vitreous humors from Göttingen minipigs were similar to other species including humans. The reference data presented herein supports the use of the Göttingen minipig as an alternate nonrodent species in ocular toxicology.


Assuntos
Avaliação Pré-Clínica de Medicamentos/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Olho/efeitos dos fármacos , Modelos Animais , Porco Miniatura , Testes de Toxicidade/métodos , Animais , Cães , Eletrorretinografia , Macaca fascicularis , Coelhos , Ratos Sprague-Dawley , Suínos
8.
Int Braz J Urol ; 44(6): 1182-1193, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30325606

RESUMO

PURPOSE: This study aims to evaluate the link between preoperative parameters and oxidative stress (OS) markers in the bladder wall of men undergoing open prostatectomy. MATERIALS AND METHODS: From July 2014 to August 2016, men aged ≥ 50 years and presenting with LUTS were prospectively enrolled. Preoperative assessment included validated questionnaires (IPSS and OAB - V8), lower urinary tract ultrasound and urodynamics. Bladder biopsies were taken during open prostatectomy for determination of OS markers. Increased OS was defined by increased concentration of malondialdehyde (MDA) and / or decreased concentration of antioxidant enzymes (superoxide dismutase and / or catalase). P<0.05 was regarded as statistically significant. RESULTS: Thirty - eight consecutive patients were included. Mean age was 66.36 ± 6.44 years, mean prostate volume was 77.7 ± 20.63 cm3, and mean IPSS was 11.05 ± 8.72 points. MDA concentration was increased in men with severe bladder outlet obstruction (BOO grade V - VI according to the Schaefer's nomogram) in comparison with BOO grade III - IV (p = 0.022). Patients with severe LUTS also had higher MDA concentration when compared to those with mild LUTS (p = 0.031). There was a statistically significant association between increased post - void residual urine (cut off ≥ 50 mL) and not only higher levels of MDA, but also reduced activity of SOD and catalase (p < 0.05). CONCLUSIONS: This pilot study showed that severity of LUTS and BOO were associated with increased MDA concentration in the bladder wall of men undergoing open prostatectomy. Further studies are still needed to assess the role of non - invasive biomarkers of OS in predicting bladder dysfunction in men with LUTS.


Assuntos
Sintomas do Trato Urinário Inferior/cirurgia , Estresse Oxidativo/fisiologia , Obstrução do Colo da Bexiga Urinária/cirurgia , Idoso , Biomarcadores/sangue , Humanos , Sintomas do Trato Urinário Inferior/sangue , Sintomas do Trato Urinário Inferior/fisiopatologia , Masculino , Projetos Piloto , Estudos Prospectivos , Prostatectomia , Índice de Gravidade de Doença , Obstrução do Colo da Bexiga Urinária/sangue , Obstrução do Colo da Bexiga Urinária/fisiopatologia
9.
Cytotherapy ; 17(11): 1655-61, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26344464

RESUMO

BACKGROUND AIMS: On review of the use of stem cells in the literature, promissory outcomes for functional organ recovery in many subspecialties in medicine underscore its therapeutic potential. The application of stem cells through the use of a needle can result in additional scar formation, which is undesired for delicate organs. The present work describes the use of a needle-less stem cell injector with the Immediate Drop on Demand Technology (I-DOT) for cell injection in vitro. METHODS: Mesenchymal stromal cells from human bone marrow were labeled with ethynyl-deoxyuridine (EdU) for 2 days and then were re-suspended. With the use of I-DOT, the cells were applied to type 1 collagen matrices or pig bladder tissue specimens with or without mucosa at different levels of energy. The collagen matrices were analyzed after 4 h and 5 days; bladder tissue specimens were analyzed 4 h after cell implantation. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test (MTT) assay was performed immediately after cell application to the collagen matrices. Histological analysis with the use of frozen sections and immunofluorescence was used to localize EdU-labeled cells. RESULTS: A considerable number of cells were detected by use of the MTT assay for collagen matrices. In the collagen matrix, the mean measured depth immediately after application ranged between 210 µm and 489 µm, 220 µm and 270 µm for entire bladder specimens, and 230 µm and 370 µm for bladder without mucosa. Cells survived for up to 5 days in the collagen matrix in both bladder specimens. CONCLUSIONS: Cells can survive during I-DOT application, which suggests that the I-DOT device may be a potentially suitable technology for needle-less cell application onto tissues.


Assuntos
Transplante de Células-Tronco Mesenquimais/instrumentação , Transplante de Células-Tronco Mesenquimais/métodos , Animais , Colágeno/metabolismo , Colágeno Tipo I/metabolismo , Desenho de Equipamento , Humanos , Masculino , Células-Tronco Mesenquimais/metabolismo , Agulhas , Suínos , Bexiga Urinária/transplante
10.
Neurosurg Rev ; 38(4): 641-8, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25957055

RESUMO

Vestibular schwannomas (VS) are the most common lesions of cerebellopontine angle (CPA) corresponding to 76-91 % of the cases. Usually, these lesions present typical CT and MRI findings. Non-schwannomatous tumors restricted to the internal auditory meatus (IAM) are rare and their preoperative radiological diagnosis may be difficult. This article describes nine surgically treated intrameatal non-schwannomatous lesions (NSL) and reviews the literature. In the last 16 years, a total of 471 patients with diagnosis of VS were operated on in our department. Preoperatively, 42 patients had diagnosis of intrameatal schwannomas, but surgery revealed in nine cases NSL (3 meningiomas, 3 arachnoiditis/neuritis, 1 cavernoma, 1 vascular loop, and 1 arachnoid cyst). Most frequent symptoms presented by patients with NSL were hearing loss 89 % (8/9) of patients, tinnitus 78 % (7/9), and vertigo 33 % (3/9). Almost all lesions (8/9) presented MRI findings of isointense signal in T1W with contrast enhancement. The only exception was the arachnoid cyst with intracystic bleeding, which was hyperintense in T1W that is not enhanced with contrast. This series shows an occurrence of 21.4 % of non-schwannomatous tumors in 42 cases of lesions restricted to the IAM. Whenever a solely intrameatal enhanced tumor is detected, it is necessary to think about other diagnostic possibilities rather than VS. Therapeutic management may be changed, specially if radiosurgical treatment is considered.


Assuntos
Ângulo Cerebelopontino/cirurgia , Neoplasias Infratentoriais/diagnóstico , Neoplasias Infratentoriais/cirurgia , Neoplasias Cranianas/diagnóstico , Neoplasias Cranianas/cirurgia , Osso Temporal/cirurgia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/métodos , Resultado do Tratamento
11.
Sci Adv ; 10(26): eado4513, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38924394

RESUMO

Coordination of cellular activity through Ca2+ enables ß cells to secrete precise quantities of insulin. To explore how the Ca2+ response is orchestrated in space and time, we implement optogenetic systems to probe the role of individual ß cells in the glucose response. By targeted ß cell activation/inactivation in zebrafish, we reveal a hierarchy of cells, each with a different level of influence over islet-wide Ca2+ dynamics. First-responder ß cells lie at the top of the hierarchy, essential for initiating the first-phase Ca2+ response. Silencing first responders impairs the Ca2+ response to glucose. Conversely, selective activation of first responders demonstrates their increased capability to raise pan-islet Ca2+ levels compared to followers. By photolabeling and transcriptionally profiling ß cells that differ in their thresholds to a glucose-stimulated Ca2+ response, we highlight vitamin B6 production as a signature pathway of first responders. We further define an evolutionarily conserved requirement for vitamin B6 in enabling the Ca2+ response to glucose in mammalian systems.


Assuntos
Cálcio , Glucose , Células Secretoras de Insulina , Optogenética , Peixe-Zebra , Animais , Células Secretoras de Insulina/metabolismo , Glucose/metabolismo , Cálcio/metabolismo , Sinalização do Cálcio
12.
Chemosphere ; 341: 140028, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37660783

RESUMO

The knowledge of the lithological context is necessary to interpret trace elements concentrations in the soil. Soil magnetic signature (χ) and soil X-ray fluorescence (XRF) are promising approaches in the study of the spatial variability of trace elements and the environmental monitoring of soil quality. This research aimed to assess the efficiency of measurements of χ and XRF sensors for spatial characterization of zinc (Zn), manganese (Mn), and copper (Cu) contents in soils of a sandstone-basalt transitional environment, using machine learning modeling. The studied area consisted of the Western Plateau of São Paulo (WPSP), with soils originating from sandstone and basalt. A total of 253 soil samples were collected at a depth of 0.0-0.2 m. The soils were characterized by particle size and chemical analysis: organic matter (OM), cation exchange capacity (CEC), ammonium oxalate-extracted iron (Feo), sodium dithionite-citrate-bicarbonate-extracted iron (Fed), and sulfuric acid-extracted iron (Fet). Hematite (Hm), goethite (Gt), kaolinite (Kt), and gibbsite (Gb) contents were obtained by X-ray diffraction (XRD). Magnetite (Mt) and maghemite (Mh) contents were obtained by soil χ, while trace elements contents were obtained by XRF and predicted by χ. Descriptive analysis, the test of means, and correlation were performed between attributes. Zn, Mn, and Cu contents were predicted using the machine learning algorithm random forest, and the spatial variability was obtained using the ordinary kriging interpolation technique. Landscape dissections influenced iron oxides, which had the highest contents in slightly dissected environments. Trace elements contents were not influenced by landscape dissections, demonstrating that lithological knowledge is necessary to characterize trace elements in soils. The prediction models developed through the machine learning algorithm random forest showed that χ can be used to characterize trace elements. The similar spatial pattern of trace elements obtained by XRF and χ measurements confirm the applicability of these sensors for mapping it under lithological and landscape transition, aiming for sustainable strategic planning of land use and occupation.


Assuntos
Oligoelementos , Raios X , Fluorescência , Brasil , Zinco , Ferro , Manganês
13.
Cien Saude Colet ; 28(10): 2797-2807, 2023 Oct.
Artigo em Português, Inglês | MEDLINE | ID: mdl-37878924

RESUMO

The present article analyzed the process of precarious work relations in the health sector, demonstrating how this situation generated illness and suffering among workers. The text sought to register how the institutional adoption of neoliberal economic conceptions, of the reduction of State social policies, coupled with a history of cultural rejection of labor rights, provided the attraction of mechanisms of precarious work for the public sector, notably, the outsourcing of labor and the provision of services. In a second moment, the text points out the legal improprieties committed, presenting the consequences of the weakening of the legal bond in the working conditions of these workers, mainly regarding working hours and remuneration, also highlighting how much the dissemination of these links represented a factor of a general reduction in wages and labor and social security rights in the sector. Data from Fiocruz surveys on working conditions during the pandemic were also presented. The article concludes by showing the urgency of rescuing the legal labor institutes that were abandoned in the historical path studied in order to guide the public health policies in a new direction.


O artigo analisou o processo de precarização das relações de trabalho no setor da saúde, demonstrando como essa situação gerou sofrimento dos trabalhadores. O texto buscou registrar como a adoção institucional das concepções econômicas neoliberais, de redução das políticas sociais de Estado, acopladas a um histórico de rejeição cultural aos direitos trabalhistas, proporcionou a atração dos mecanismos de precarização do trabalho, notadamente, a terceirização da mão de obra e da prestação de serviços. No segundo momento, o texto aponta as impropriedades jurídicas cometidas, apresentando as consequências da fragilização do vínculo jurídico nas condições de trabalho desses trabalhadores, principalmente no que se refere às jornadas de trabalho e a remuneração, destacando-se, também, o quanto a disseminação desses vínculos representou um fator de rebaixamento geral dos salários e direitos trabalhistas e previdenciários no setor. Foram apresentados, ainda, dados das pesquisas da Fiocruz sobre condições de trabalho durante a pandemia. Conclui mostrando a urgência de se resgatarem os institutos jurídicos trabalhistas que foram abandonados no percurso histórico estudado, para direcionar a novo rumo as políticas públicas na saúde.


Assuntos
COVID-19 , Pandemias , Humanos , Salários e Benefícios , Inquéritos e Questionários , Setor Público
14.
Toxicol Sci ; 192(1): 83-96, 2023 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-36617169

RESUMO

Arsenic exposure is correlated with atherosclerosis in epidemiological studies and in animal models. We have previously shown that arsenic exposure enhanced the atherosclerotic plaque size, increased the plaque lipid content, and decreased the plaque smooth muscle cell and collagen contents in the apolipoprotein E knockout (apoE-/-) mice. However, the percentage of plaque-resident macrophages, the primary drivers of atherosclerosis remained unchanged. Therefore, we hypothesized that although arsenic does not change the quantity of macrophages, it alters the macrophage transcriptome towards a proatherogenic state. To test this hypothesis, we used bone marrow-derived macrophages, polarized them to either interferon-γ (IFN-É£) stimulated, proinflammatory or interleukin-4 (IL-4) stimulated, alternatively activated macrophages in the presence or absence of 0.67 µM (50 ppb) arsenic and performed RNA sequencing. Arsenic exposure altered the gene expression of the macrophages in a subtype-specific manner. Most differentially expressed genes (88%) were altered specifically in either IFN-É£- or IL-4-stimulated macrophages, whereas in the remaining 12% of genes that changed in both cell types, did so in opposite directions. In IL-4-stimulated macrophages, arsenic significantly downregulated the genes involved in cholesterol biosynthesis and the chemokines CCL17/CCL22, whereas in IFN-É£-stimulated macrophages, the genes associated with the liver X receptor (LXR) pathway were downregulated by arsenic. Using a bone marrow transplant experiment, we validated that the deletion of LXRα from the hematopoietic compartment rescued arsenic-enhanced atherosclerosis in the apoE-/- mouse model. Together, these data suggest that arsenic modulates subtype-specific transcriptomic changes in macrophages and further emphasize the need to define macrophage heterogeneity in atherosclerotic plaques in order to evaluate the proatherogenic role of arsenic.


Assuntos
Arsênio , Aterosclerose , Placa Aterosclerótica , Animais , Camundongos , Arsênio/metabolismo , Interferon gama/genética , Interferon gama/metabolismo , Interleucina-4/genética , Interleucina-4/metabolismo , Camundongos Knockout , Aterosclerose/induzido quimicamente , Aterosclerose/genética , Aterosclerose/metabolismo , Placa Aterosclerótica/metabolismo , Macrófagos/metabolismo , Expressão Gênica , Apolipoproteínas E/genética , Camundongos Endogâmicos C57BL
15.
Nat Commun ; 13(1): 6255, 2022 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-36271049

RESUMO

Diabetes is a multifactorial disorder characterized by loss or dysfunction of pancreatic ß-cells. ß-cells are heterogeneous, exhibiting different glucose sensing, insulin secretion and gene expression. They communicate with other endocrine cell types via paracrine signals and between ß-cells via gap junctions. Here, we identify the importance of signaling between ß-cells via the extracellular signal WNT4. We show heterogeneity in Wnt4 expression, most strikingly in the postnatal maturation period, Wnt4-positive cells, being more mature while Wnt4-negative cells are more proliferative. Knock-out in adult ß-cells shows that WNT4 controls the activation of calcium signaling in response to a glucose challenge, as well as metabolic pathways converging to lower ATP/ADP ratios, thereby reducing insulin secretion. These results reveal that paracrine signaling between ß-cells is important in addition to gap junctions in controling insulin secretion. Together with previous reports of WNT4 up-regulation in obesity our observations suggest an adaptive insulin response coordinating ß-cells.


Assuntos
Sinalização do Cálcio , Insulinas , Glucose/metabolismo , Trifosfato de Adenosina/metabolismo , Insulinas/metabolismo , Difosfato de Adenosina/metabolismo
16.
J Vis Exp ; (175)2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34633379

RESUMO

The pancreatic ß-cells sustain systemic glucose homeostasis by producing and secreting insulin according to the blood glucose levels. Defects in ß-cell function are associated with hyperglycemia that can lead to diabetes. During the process of insulin secretion, ß-cells experience an influx of Ca2+. Thus, imaging the glucose-stimulated Ca2+ influx using genetically encoded calcium indicators (GECIs) provides an avenue to studying ß-cell function. Previously, studies showed that isolated zebrafish islets expressing GCaMP6s exhibit significant Ca2+ activity upon stimulation with defined glucose concentrations. However, it is paramount to study how ß-cells respond to glucose not in isolation, but in their native environment, where they are systemically connected, vascularized, and densely innervated. To this end, the study leveraged the optical transparency of the zebrafish larvae at early stages of development to illuminate ß-cell activity in vivo. Here, a detailed protocol for Ca2+ imaging and glucose stimulation to investigate ß-cell function in vivo is presented. This technique allows to monitor the coordinated Ca2+ dynamics in ß-cells with single-cell resolution. Additionally, this method can be applied to work with any injectable solution such as small molecules or peptides. Altogether, the protocol illustrates the potential of the zebrafish model to investigate islet coordination in vivo and to characterize how environmental and genetic components might affect ß-cell function.


Assuntos
Cálcio , Células Secretoras de Insulina , Animais , Cálcio/metabolismo , Glucose/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Peixe-Zebra/metabolismo
17.
Environ Health Perspect ; 129(5): 57008, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34014776

RESUMO

BACKGROUND: Epidemiologic studies indicate that early life arsenic exposures are linked to an increased risk of cardiovascular diseases. Different oxidation and methylation states of arsenic exist in the environment and are formed in vivo via the action of arsenic (+3 oxidation state) methyltransferase (As3MT). Methylated arsenicals are pro-atherogenic postnatally, but pre- and perinatal effects are unclear. This is particularly important because methylated arsenicals are known to cross the placenta. OBJECTIVES: We tested the effects of early life exposure to inorganic and methylated arsenicals on atherosclerotic plaque formation and its composition in apolipoprotein E knock-out (apoE-/-) mice and evaluated whether apoE-/- mice lacking As3MT expression were susceptible to this effect. METHODS: We exposed apoE-/- or apoE-/-/As3MT-/- mice to 200 ppb inorganic or methylated arsenic in the drinking water from conception to weaning and assessed atherosclerotic plaques in the offspring at 18 wk of age. Mixed regression models were used to estimate the mean difference in each outcome relative to controls, adjusting for sex and including a random effects term to account for within-litter clustering. RESULTS: Early life exposure to inorganic arsenic, and more profoundly methylated arsenicals, resulted in significantly larger plaques in the aortic arch and sinus in both sexes. Lipid levels in these plaques were higher without a substantial difference in macrophage numbers. Smooth muscle cell content was not altered, but collagen content was lower. Importantly, there were sex-specific differences in these observations, where males had higher lipids and lower collagen in the plaque, but females did not. In mice lacking As3MT, arsenic did not alter the plaque size, although the size was highly variable. In addition, control apoE-/-/As3MT-/- mice had significantly larger plaque size compared with control apoE-/-. CONCLUSION: This study shows that early life exposure to inorganic and methylated arsenicals is pro-atherogenic with sex-specific differences in plaque composition and a potential role for As3MT in mice. https://doi.org/10.1289/EHP8171.


Assuntos
Arsênio , Placa Aterosclerótica , Efeitos Tardios da Exposição Pré-Natal , Animais , Arsênio/toxicidade , Arsenicais , Feminino , Masculino , Metilação , Metiltransferases/genética , Metiltransferases/metabolismo , Camundongos , Camundongos Knockout , Placa Aterosclerótica/induzido quimicamente , Gravidez , Fatores Sexuais
18.
Environ Res ; 110(3): 237-43, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20144457

RESUMO

The present study aimed to verify the time course of the effects of environmental levels of urban air pollution toxicity on lung arterioles. BALB/c mice (n=56) were continuously exposed to selective chambers equipped with (filtered, F) or without (non-filtered, NF) filter devices for particles and toxic gases for 24h/day, over 14, 21, 30 or 45 days. After exposure, we evaluated the lumen-wall relationship (an estimator of arteriolar narrowing), endothelial nitric oxide synthase (eNOS) and endothelin type A receptor (ETAr) expression in the vascular wall and inflammatory influx of the peribronchiolar area. Concentrations of fine particulate matter (PM

Assuntos
Poluentes Atmosféricos/toxicidade , Pulmão/irrigação sanguínea , Pulmão/efeitos dos fármacos , Receptor de Endotelina A/metabolismo , Vasoconstrição/efeitos dos fármacos , Animais , Arteríolas/efeitos dos fármacos , Arteríolas/metabolismo , Câmaras de Exposição Atmosférica , Cidades , Exposição por Inalação/análise , Pulmão/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Dióxido de Nitrogênio/toxicidade , Material Particulado/toxicidade , Receptor de Endotelina A/efeitos dos fármacos , Fumaça , Tempo , Testes de Toxicidade
19.
Sci Rep ; 10(1): 11364, 2020 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-32647154

RESUMO

Soot emissions from flaming combustion are relevant as a significant source of atmospheric pollution and as a source of nanomaterials. Candles are interesting targets for soot characterization studies since they burn complex fuels with a large number of carbon atoms, and yield stable and repeatable flames. We characterized the soot particle size distributions in a candle flame using the planar two-color time-resolved laser induced incandescence (2D-2C TiRe-LII) technique, which has been successfully applied to different combustion applications, but never before on a candle flame. Soot particles are heated with a planar laser sheet to temperatures above the normal flame temperatures. The incandescent soot particles emit thermal radiation, which decays over time when the particles cool down to the flame temperature. By analyzing the temporal decay of the incandescence signal, soot particle size distributions within the flame are obtained. Our results are consistent with previous works, and show that the outer edges of the flame are characterized by larger particles ([Formula: see text]), whereas smaller particles ([Formula: see text]) are found in the central regions. We also show that our effective temperature estimates have a maximum error of 100 K at early times, which decreases as the particles cool.

20.
Clin Biomech (Bristol, Avon) ; 69: 197-204, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31376810

RESUMO

BACKGROUND: Rigid-rocker shoes may induce gait instability in diabetics, however, this is not clearly investigated. The present study investigates if rigid-rocker shoes influence diabetic gait stability. METHODS: Fourteen non-neuropathic and nine neuropathic diabetics, plus eleven healthy young-adults were recruited. Full-body kinematic data was captured during walking. Experimental conditions included barefoot and three rocker-shoe designs according to the rocker angle, apex angle and apex position (R10: 10°, 80°, 60%; R15: 15°, 95°, 52%; R20: 20°, 95°, 60%). Sagittal and frontal stability margin, plus fear of fall were main outcome measures. FINDINGS: Sagittal stability margin was not affected by health, however, was increased with R10 and R15 in non-neuropathic diabetics and healthy individuals (R2 = 0.16). Variability of sagittal stability margin was not altered in neuropathic diabetics, but was increased with R15 and R20 in healthy participants, with R15 in non-neuropathic diabetics (R2 = 0.12). Frontal stability margin (R2 = 0.46) and its variability (R2 = 0.39) were significantly increased in neuropathic and non-neuropathic diabetics compared to healthy individuals. Frontal stability margin was significantly higher with R15 in neuropathic diabetics, and with R20 in both non-neuropathic and healthy participants. Sagittal and frontal stability margin were strongly correlated with fear of fall in neuropathic diabetics. INTERPRETATIONS: R15 and R20 might challenge gait stability of diabetics cause them restrict centre of mass motion thereby imposing a tighter control over walking. However, neuropathic diabetics generally walk very cautious due to neuropathy and increased fear of fall. Frontal stability margin, highly affected by health and experimental condition, is a more sensitive indicator of gait stability.


Assuntos
Neuropatias Diabéticas/fisiopatologia , Marcha/fisiologia , Sapatos , Caminhada , Acidentes por Quedas , Adulto , Fenômenos Biomecânicos , Diabetes Mellitus/fisiopatologia , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
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