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1.
Cytotherapy ; 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38739074

RESUMO

BACKGROUND: In recent years, dental pulp stromal cells (DPSCs) have emerged as a promising therapeutic approach for Parkinson's disease (PD), owing to their inherent neurogenic potential and the lack of neuroprotective treatments for this condition. However, uncertainties persist regarding the efficacy of these cells in an undifferentiated state versus a neuronally-induced state. This study aims to delineate the distinct therapeutic potential of uninduced and neuronally-induced DPSCs in a rodent model of PD induced by 6-Hydroxydopamine (6-OHDA). METHODS: DPSCs were isolated from human teeth, characterized as mesenchymal stromal cells, and induced to neuronal differentiation. Neuronal markers were assessed before and after induction. DPSCs were transplanted into the substantia nigra pars compacta (SNpc) of rats 7 days following the 6-OHDA lesion. In vivo tracking of the cells, evaluation of locomotor behavior, dopaminergic neuron survival, and the expression of essential proteins within the dopaminergic system were conducted 7 days postgrafting. RESULTS: Isolated DPSCs exhibited typical characteristics of mesenchymal stromal cells and maintained a normal karyotype. DPSCs consistently expressed neuronal markers, exhibiting elevated expression of ßIII-tubulin following neuronal induction. Results from the animal model showed that both DPSC types promoted substantial recovery in dopaminergic neurons, correlating with enhanced locomotion. Additionally, neuronally-induced DPSCs prevented GFAP elevation, while altering DARPP-32 phosphorylation states. Conversely, uninduced DPSCs reduced JUN levels. Both DPSC types mitigated the elevation of glycosylated DAT. CONCLUSIONS: Our results suggested that uninduced DPSCs and neuronally-induced DPSCs exhibit potential in reducing dopaminergic neuron loss and improving locomotor behavior, but their underlying mechanisms differ.

2.
Dement Neuropsychol ; 17: e20220105, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37577181

RESUMO

The development of the human nervous system makes up a series of fundamental and interdependent events involving birth, growth, and neuronal maturation, in addition to the positive or negative selection of synapses of these neurons that will participate in the composition of neural circuits essential to the activity of the nervous system. In this context, where environment and social relationships seem to be relevant markers for neurodevelopment, advanced neuroimaging techniques and behavioral assessment tools have demonstrated alterations in brain regions and cognitive functions among children developing in low or high socioeconomic status environments. Considering the aspects mentioned, this review aimed to identify the importance of socioeconomic status in children's brain development, seeking to identify what are the impacts of these factors on the morphological and physiological formation of the nervous system, allowing a greater understanding of the importance of environmental factors in neurodevelopmental processes.


O desenvolvimento do sistema nervoso humano compõe uma série de eventos fundamentais e interdependentes envolvendo o nascimento, crescimento e maturação neuronal, além da seleção positiva ou negativa de sinapses desses neurônios que participarão da composição de circuitos neurais essenciais à atividade do sistema nervoso. Nesse contexto, em que o ambiente e as relações sociais parecem ser marcadores relevantes para o neurodesenvolvimento, técnicas avançadas de neuroimagem e ferramentas de avaliação comportamental têm demonstrado alterações em regiões cerebrais e funções cognitivas em crianças que se desenvolvem em ambientes de baixo ou alto nível socioeconômico. Considerando os aspectos mencionados, esta revisão teve como objetivo identificar a importância do status socioeconômico no desenvolvimento cerebral infantil, buscando identificar quais são os impactos desses fatores na formação morfológica e fisiológica do sistema nervoso, permitindo maior compreensão da importância dos fatores ambientais nos processos de neurodesenvolvimento.

3.
AAPS PharmSciTech ; 24(6): 156, 2023 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-37468721

RESUMO

This study sought to develop polymer-lipid hybrid solid dispersions containing the poorly soluble drug lopinavir (LPV) by hot-melt extrusion (HME). Hence, the lipid and polymeric adjuvants were selected based on miscibility and compatibility studies. Film casting was used to assess the miscibility, whereas thermal, spectroscopic, and chromatographic analyses were employed to evaluate drug-excipient compatibility. Extrudates were obtained and characterized by physicochemical tests, including in vitro LPV dissolution. Preformulation studies led to select the most appropriate materials, i.e., the polymers PVPVA and Soluplus®, the plasticizers polyethylene glycol 400 and Kolliphor® HS15, phosphatidylcholine, and sodium taurodeoxycholate. HME processing did not result in LPV degradation and significantly increased entrapment efficiency (93.8% ± 2.8 for Soluplus® extrudate against 19.8% ± 0.5 of the respective physical mixture). LPV dissolution was also increased from the extrudates compared to the corresponding physical mixtures (p < 0.05). The dissolution improvement was considerably greater for the Soluplus®-based formulation (24.3 and 2.8-fold higher than pure LPV and PVPVA-based extrudate after 120 min, respectively), which can be attributed to the more pronounced effects of HME processing on the average size and LPV solid-state properties in the Soluplus® extrudates. Transmission electron microscopy and chemical microanalysis suggested that the polymer-lipid interactions in Soluplus®-based formulation depended on thermal processing.


Assuntos
Polietilenoglicóis , Polímeros , Polímeros/química , Composição de Medicamentos/métodos , Solubilidade , Polietilenoglicóis/química , Sistemas de Liberação de Medicamentos , Lipídeos , Temperatura Alta
4.
Dement. neuropsychol ; 17: e20220105, 2023. graf
Artigo em Inglês | LILACS | ID: biblio-1448111

RESUMO

ABSTRACT The development of the human nervous system makes up a series of fundamental and interdependent events involving birth, growth, and neuronal maturation, in addition to the positive or negative selection of synapses of these neurons that will participate in the composition of neural circuits essential to the activity of the nervous system. In this context, where environment and social relationships seem to be relevant markers for neurodevelopment, advanced neuroimaging techniques and behavioral assessment tools have demonstrated alterations in brain regions and cognitive functions among children developing in low or high socioeconomic status environments. Considering the aspects mentioned, this review aimed to identify the importance of socioeconomic status in children's brain development, seeking to identify what are the impacts of these factors on the morphological and physiological formation of the nervous system, allowing a greater understanding of the importance of environmental factors in neurodevelopmental processes.


RESUMO O desenvolvimento do sistema nervoso humano compõe uma série de eventos fundamentais e interdependentes envolvendo o nascimento, crescimento e maturação neuronal, além da seleção positiva ou negativa de sinapses desses neurônios que participarão da composição de circuitos neurais essenciais à atividade do sistema nervoso. Nesse contexto, em que o ambiente e as relações sociais parecem ser marcadores relevantes para o neurodesenvolvimento, técnicas avançadas de neuroimagem e ferramentas de avaliação comportamental têm demonstrado alterações em regiões cerebrais e funções cognitivas em crianças que se desenvolvem em ambientes de baixo ou alto nível socioeconômico. Considerando os aspectos mencionados, esta revisão teve como objetivo identificar a importância do status socioeconômico no desenvolvimento cerebral infantil, buscando identificar quais são os impactos desses fatores na formação morfológica e fisiológica do sistema nervoso, permitindo maior compreensão da importância dos fatores ambientais nos processos de neurodesenvolvimento.


Assuntos
Humanos , Deficiências do Desenvolvimento , Desenvolvimento Infantil , Disfunção Cognitiva
5.
Genes (Basel) ; 13(12)2022 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-36553663

RESUMO

Parkinson's disease (PD) is characterized by a range of motor signs, but cognitive dysfunction is also observed. Supplementation with folic acid and vitamin B12 is expected to prevent cognitive impairment. To test this in PD, we promoted a lesion within the substantia nigra pars compacta of rats using the neurotoxin rotenone. In the sequence, the animals were supplemented with folic acid and vitamin B12 for 14 consecutive days and subjected to the object recognition test. We observed an impairment in object recognition memory after rotenone administration, which was prevented by supplementation (p < 0.01). Supplementation may adjust gene expression through efficient DNA methylation. To verify this, we measured the expression and methylation of the kynureninase gene (Kynu), whose product metabolizes neurotoxic metabolites often accumulated in PD as kynurenine. Supplementation prevented the decrease in Kynu expression induced by rotenone in the substantia nigra (p < 0.05), corroborating the behavioral data. No differences were observed concerning the methylation analysis of two CpG sites in the Kynu promoter. Instead, we suggest that folic acid and vitamin B12 increased global DNA methylation, reduced the expression of Kynu inhibitors, maintained Kynu-dependent pathway homeostasis, and prevented the memory impairment induced by rotenone. Our study raises the possibility of adjuvant therapy for PD with folic acid and vitamin B12.


Assuntos
Doença de Parkinson , Ratos , Animais , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/genética , Rotenona/toxicidade , Ácido Fólico/farmacologia , Vitamina B 12/farmacologia , Modelos Animais de Doenças
6.
Nat Prod Res ; 36(24): 6304-6311, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35156453

RESUMO

Bioassay-guided fractionation of dichloromethane extract from Athenaea velutina leaves led to the isolation of three withanolides, all being reported for the first time in this species. They were identified as withacnistin (1), withacnistin acetate (2) and a new withanolide, designated as withalutin (3). The structures were established by spectral data analysis, including MS, 1D and 2D NMR. In addition, in silico ADMET studies were employed to understand the pharmacokinetic properties of these withanolides. The withanolides isolated from A. velutina reduced cancer cell viability with IC50 values ranging from 1.52 to 5.39 µM. In silico prediction revealed that withanolides have good gastrointestinal absorption or oral bioavailability properties; and are not likely to be mutagenic or hepatotoxic. These findings revealed that A. velutina is an important source of cytotoxic withanolides.


Assuntos
Antineoplásicos , Solanaceae , Vitanolídeos , Vitanolídeos/química , Solanaceae/química , Lactonas/análise , Folhas de Planta/química , Antineoplásicos/análise
7.
J Toxicol Environ Health A ; 85(12): 481-493, 2022 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-35189772

RESUMO

Resistance to glyphosate herbicide has initiated usage of combined application of herbicides as a weed control measure. Imazethapyr-based herbicides associated with glyphosate herbicide seem to be an alternative to suppress weed resistance. The aim of this study was to examine the adverse effects of Glyphosate Atanor 48® (ATN) and Imazethapyr Plus Nortox® (IMZT) formulations in both single forms and mixtures using HepG2 cells and zebrafish early-life stages models. Data demonstrated cytotoxicity due to exposure to ATN, IMZT for both models, as follows: (1) ATN (0.5 mg/L), IMZT (5 mg/L), and M3 (0.05 mg/L ATN + 5 mg/L IMZT) increased cytotoxicity by disturbing the mitochondrial activity of HepG2 cells 24 hr after exposure; (2) ATN and IMZT (5 mg/L), and M3 (0.05 mg/L ATN + 5 mg/L IMZT) also decreased the integrity of the membrane of HepG2 cells after 24 hr incubation; (3) only ATN and IMZT (5 mg/L) in their single forms diminished the mitochondrial potential of zebrafish; (4) ATN (single form) at 0.5 mg/L induced apoptosis in zebrafish larvae. In conclusion, these herbicides in their single forms appeared to produce greater cytotoxicity to HepG2 cells and zebrafish compared to the herbicide mixtures.


Assuntos
Herbicidas , Ácidos Nicotínicos , Animais , Glicina/análogos & derivados , Herbicidas/toxicidade , Ácidos Nicotínicos/toxicidade , Peixe-Zebra , Glifosato
8.
J Biomed Mater Res A ; 110(3): 696-707, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34672417

RESUMO

Endosseous implant surface topography directly affects adherent cell responses following implantation. The aim of this study was to examine the impact of nanoscale topographic modification of titanium implants on Osterix gene expression since this gene has been reported as key factor for bone formation. Titanium implants with smooth and nanoscale topographies were implanted in the femurs of Osterix-Cherry mice for 1-21 days. Implant integration was evaluated using scanning electron microscopy (SEM) to evaluate cell adhesion on implant surfaces, histology, and nanotomography (NanoCT) to observe and quantify the formed bone-to-implant interface, flow cytometry to quantify of Osterix expressing cells in adjacent tissues, and real-time PCR (qPCR) to quantify the osteoinductive and osteogenic gene expression of the implant-adherent cells. SEM revealed topography-dependent adhesion of cells at early timepoints. NanoCT demonstrated greater bone formation at nanoscale implants and interfacial osteogenesis was confirmed histologically at 7 and 14 days for both smooth and nanosurface implants. Flow cytometry revealed greater numbers of Osterix positive cells in femurs implanted with nanoscale versus smooth implants. Compared to smooth surface implants, nanoscale surface adherent cells expressed higher levels of Osterix (Osx), Alkaline phosphatase (Alp), Paired related homeobox (Prx1), Dentin matrix protein 1 (Dmp1), Bone sialoprotein (Bsp), and Osteocalcin (Ocn). In conclusion, nanoscale surface implants demonstrated greater bone formation associated with higher levels of Osterix expression over the 21-day healing period with direct evidence of surface-associated gene regulation involving a nanoscale-mediated osteoinductive pathway that utilizes Osterix to direct adherent cell osteoinduction.


Assuntos
Implantes Dentários , Osseointegração , Animais , Camundongos , Osteogênese , Próteses e Implantes , Propriedades de Superfície , Titânio/farmacologia
9.
Planta Med ; 88(6): 429-439, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-33853120

RESUMO

Athenaea velutina is a promising Brazilian shrub with cytotoxic and antimigratory properties against cancer cells. However, the mechanism of induction of cancer cell death and the compounds involved remain unknown. To ascertain these bioactive compounds, bioassay-guided fractionation was performed, alongside the appropriate in vitro tests. A withanolide-rich fraction (FAv_5) from the dichloromethane extract increased cytotoxic activity by 1.5-fold (IC50 = 2.1 µg/mL). Fourteen withanolide steroids were tentatively identified for the first time for this species by mass spectrometry coupled to liquid chromatography (LC MS/MS), including withanolide A, aurelianolide A, and aurelianolide B. FAv_5 significantly decreased cell proliferation, migration, and invasion with a selectivity index greater than 8 for B16F10 cells. Furthermore, flow cytometry with annexin V fluorescein isothiocyanate/propidium iodide (V-FITC/PI) staining showed FAv_5 to promote cell cycle arrest at the G0/G1-phase as well as apoptotic cell death. Overall, these findings highlight A. velutina as a source of withanolide-steroids that inhibit cancer cell proliferation through apoptosis and cell cycle blockade mechanisms. Details on the geographic distribution of A. velutina and species conservation strategies have also been highlighted.


Assuntos
Melanoma , Vitanolídeos , Apoptose , Ciclo Celular , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Espectrometria de Massas em Tandem , Vitanolídeos/farmacologia
10.
Cad. saúde colet., (Rio J.) ; 29(4): 463-473, out.-dez. 2021. tab
Artigo em Português | LILACS-Express | LILACS | ID: biblio-1360328

RESUMO

Resumo Introdução O metilfenidato, utilizado especialmente para tratar o Transtorno do Déficit de Atenção e Hiperatividade tem conquistado universitários que buscam melhorar o desempenho cognitivo. Objetivo Investigar conhecimentos, motivações, percepções e perfil de uso não prescrito desse medicamento por estudantes de uma Universidade Federal de Minas Gerais. Método Aplicação de questionário estruturado a 696 estudantes de Bioquímica, Enfermagem, Farmácia e Medicina, e análise descritiva e dos fatores associados ao uso, por meio de modelos de regressão logística. Resultados: Dos participantes, 96,7% afirmaram conhecer o medicamento e desses, 4,3% o utilizam/utilizavam por motivos não prescritos. O principal motivo de uso era o melhoramento cognitivo, e a universidade foi o principal local de início de uso. A maior parte dos usuários percebeu aumento na concentração e 50% relatou ocorrência de efeitos indesejados. Houve maior chance de uso não prescrito entre homens, maiores de 21 anos, envolvidos em atividades extracurriculares e menor chance de uso entre estudantes de Enfermagem. Conclusão A análise de diferentes aspectos relacionados com o uso não prescrito do metilfenidato propicia um melhor entendimento das situações vivenciadas entre universitários e aponta os riscos à saúde relacionados à busca por melhores desempenhos acadêmicos e estratégias para lidar com sobrecarga de atividades.


Abstract Background Methylphenidate, especially used to treat Attention Deficit Hyperactivity Disorder, has conquered over university students who seek to improve cognitive performance. Objective To investigate knowledge, motivations, perceptions, and profile of non-prescribed use of this drug by students of a Federal University of Minas Gerais. Method A structured questionnaire was applied to 696 students of Biochemistry, Nursing, Pharmacy, and Medicine, and descriptive analysis and associated factors, using logistic regression models. Results Of the participants, 96.7% said they knew the medicine and of these, 4.3% use it/used it for reasons not prescribed. The main reason for using it was the cognitive improvement and the university was the main place of use. Most users noticed an increased concentration and 50% reported the occurrence of unwanted effects. There was a greater chance of non-prescribed use among men, over 21 years old, involved in extracurricular activities, and less chance of use among nursing students. Conclusion Analysis of different aspects related to the non-prescribed use of Methylphenidate provides a better understanding of the situations experienced by university students and points to health risks related to the search for better academic performance and strategies for dealing with activity overload.

11.
Sci Rep ; 11(1): 16780, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34408211

RESUMO

There are no clinical interventions to prevent post-injury epilepsy, a common and devastating outcome after brain insults. Epileptogenic events that run from brain injury to epilepsy are poorly understood. Previous studies in our laboratory suggested Proechimys, an exotic Amazonian rodent, as resistant to acquired epilepsy development in post-status epilepticus models. The present comparative study was conducted to assess (1) stroke-related brain responses 24-h and 30 days after cortical photothrombosis and (2) post-stroke epilepsy between Proechimys rodents and Wistar rats, a traditional animal used for laboratory research. Proechimys group showed smaller volume of ischemic infarction and lesser glial activation than Wistar group. In contrast to Wistar rats, post-stroke decreased levels of pro-inflammatory cytokines and increased levels of anti-inflammatory mediators and growth factors were found in Proechimys. Electrophysiological signaling changes assessed by cortical spreading depression, in vitro and in vivo, showed that Wistar's brain is most severely affected by stroke. Chronic electrocorticographic recordings showed that injury did not lead to epilepsy in Proechimys whereas 88% of the Wistar rats developed post-stroke epilepsy. Science gains insights from comparative studies on diverse species. Proechimys rodents proved to be a useful animal model to study antiepileptogenic mechanisms after brain insults and complement conventional animal models.


Assuntos
Epilepsia/metabolismo , Floresta Úmida , Estado Epiléptico/metabolismo , Acidente Vascular Cerebral/metabolismo , Animais , Ratos , Ratos Wistar
12.
Dement Neuropsychol ; 15(2): 164-172, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34345357

RESUMO

Considering the variety of mechanisms of Herpes simplex virus (HSV-1) contamination and its broad invasive potential of the nervous system, a life-long latent infection is established. Infected adult individuals may be susceptible to viral reactivation when under the influence of multiple stressors, especially regarding immunocompromised patients. This guides a series of neuroinflammatory events on the cerebral cortex, culminating, rarely, in encephalitis and cytotoxic / vasogenic brain edema. A sum of studies of such processes provides an explanation, even though not yet completely clarified, on how the clinical evolution to cognitive impairment and dementia might be enabled. In addition, it is of extreme importance to recognize the current dementia and cognitive deficit worldwide panorama. The aim of this literature review is to elucidate the available data upon the pathophysiology of HSV-1 infection as well as to describe the clinical panorama of the referred afflictions.


Considerando a variedade de mecanismos de contaminação pelo vírus Herpes simplex (HSV-1) e seu amplo potencial invasivo do sistema nervoso, uma infecção latente por toda a vida é estabelecida. Indivíduos adultos infectados podem ser suscetíveis à reativação viral quando estão sob a influência de múltiplos estressores, principalmente em pacientes imunocomprometidos. Esse fator orienta uma série de eventos neuroinflamatórios no córtex cerebral, culminando, raramente, em encefalite e edema cerebral citotóxico/vasogênico. Um somatório de estudos desses processos fornece uma explanação, embora ainda não totalmente esclarecida, de como a evolução clínica para déficit cognitivo e demência pode ser possibilitada. Além disso, é de extrema importância reconhecer o panorama mundial atual da demência e do déficit cognitivo. O objetivo da presente revisão de literatura é elucidar os dados disponíveis sobre a fisiopatologia da infecção pelo HSV-1, assim como descrever o panorama clínico das referidas afecções.

14.
Nat Prod Res ; 35(24): 5904-5908, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32746634

RESUMO

Antibiotic resistance is a serious global threat to public health. This has promoted the research for new drug targets, and the use of other approaches, such as antimicrobial combined therapy. The present study evaluated the antibacterial activity of 88 extracts from Brazilian Atlantic Forest trees. The organic extract from leaves of Miconia latecrenata (EMl) was the most promising for inhibiting the growth of Staphylococcus aureus (0.3 mg/mL) and Pseudomonas aeruginosa (2.5 mg/mL). After the bioguided fractionation of EMl and metabolite profiling performed by UPLC-DAD-MS/MS, the ethyl acetate (AFMl) and aqueous (WFMl) fractions showed a mixture of phenolic compounds derived from ellagic acid and quercetin. The MIC value of AFMl was two-times lower than EMl for P. aeruginosa, suggesting that these phenolic compounds can perform bioactivity. Furthermore, EMI and AFMl showed synergism with ampicillin and tetracycline for S. aureus and P. aeruginosa, respectively. These findings suggest that extract and fractions of the Miconia latecrenata leaves can be used as therapeutic antibacterial agents.


Assuntos
Melastomataceae , Antibacterianos/farmacologia , Florestas , Testes de Sensibilidade Microbiana , Extratos Vegetais/farmacologia , Staphylococcus aureus , Espectrometria de Massas em Tandem
15.
J Sleep Res ; 30(3): e13170, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32865294

RESUMO

Parkinson's disease motor dysfunctions are associated with improperly organised neural oscillatory activity. The presence of such disruption at the early stages of the disease in which altered sleep is one of the main features could be a relevant predictive feature. Based on this, we aimed to investigate the neocortical synchronisation dynamics during slow-wave sleep (SWS) in the rotenone model of Parkinson's disease. After rotenone administration within the substantia nigra pars compacta, one group of male Wistar rats underwent sleep-wake recording. Considering the association between SWS oscillatory activity and memory consolidation, another group of rats underwent a memory test. The fine temporal structure of synchronisation dynamics was evaluated by a recently developed technique called first return map. We observed that rotenone administration decreased the time spent in SWS and altered the power spectrum within different frequency bands, whilst it increased the transition rate from a synchronised to desynchronised state. This neurotoxin also increased the probability of longer and decreased the probability of shorter desynchronisation events. At the same time, we observed impairment in object recognition memory. These findings depict an electrophysiological fingerprint represented by a disruption in the typical oscillatory activity within the neocortex at the early stages of Parkinson's disease, concomitant with a decrease in the time spent in SWS and impairment in recognition memory.


Assuntos
Eletroencefalografia/métodos , Inseticidas/uso terapêutico , Neocórtex/fisiopatologia , Doença de Parkinson/tratamento farmacológico , Rotenona/uso terapêutico , Sono de Ondas Lentas/fisiologia , Animais , Humanos , Inseticidas/farmacologia , Masculino , Doença de Parkinson/patologia , Ratos , Ratos Wistar , Rotenona/farmacologia
16.
Environ Toxicol Chem ; 40(2): 333-341, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33210755

RESUMO

Thymol, a monoterpene phenol, is used as a natural biocide. To circumvent its chemical instability, we propose use of thymol-loaded biogenic silica nanoparticles (BSiO2 #THY NPs); however, the toxicity of this system for aquatic organisms is unknown. Thus, the present study aimed to evaluate the toxicogenetic effects induced by thymol, BSiO2 NP, and BSiO2 #THY on Artemia salina and zebrafish (Danio rerio) early life stages. We also investigated the impact of BSiO2 aggregation in different exposure media (saline and freshwater). Based on the median lethal concentration at 48 h (LC5048h ), BSiO2 #THY (LC5048h = 1.06 mg/L) presented similar toxic potential as thymol (LC5048h = 1.03 mg/L) for A. salina, showing that BSiO2 had no influence on BSiO2 #THY toxicity. Because BSiO2 aggregated and sedimented faster in A. salina aqueous medium than in the other medium, this NP had lower interaction with this microcrustacean. Thus, BSiO2 #THY toxicity for A. salina is probably due to the intrinsic toxicity of thymol. For zebrafish early life stages, BSiO2 #THY (LC5096h = 13.13 mg/L) was more toxic than free thymol (LC5096h = 25.60 mg/L); however, BSiO2 NP has no toxicity for zebrafish early life stages. The lower aggregation of BSiO2 in the freshwater medium compared to the saline medium may have enhanced thymol's availability for this aquatic organism. Also, BSiO2 #THY significantly induced sublethal effects as thymol, and both were genotoxic for zebrafish. In conclusion, although BSiO2 #THY still needs improvements to ensure its safety for freshwater ecosystems, BSiO2 NP seems to be a safe nanocarrier for agriculture. Environ Toxicol Chem 2021;40:333-341. © 2020 SETAC.


Assuntos
Nanopartículas , Poluentes Químicos da Água , Animais , Ecossistema , Nanopartículas/toxicidade , Dióxido de Silício/toxicidade , Timol/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra
17.
Eur J Pharmacol ; 891: 173722, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33159932

RESUMO

Melatonin MT1 and MT2 receptors are expressed in the glomerular layer of the olfactory bulb (OB); however, the role of these receptors has not been evaluated until now. Considering the association of the OB with olfactory and depressive disorders in Parkinson's disease (PD), we sought to investigate the involvement of melatonin receptors in these non-motor disturbances in an intranigral 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD. We demonstrate the presence of functional melatonin receptors in dopaminergic neurons of the glomerular layer. Local administration of melatonin (MLT, 1 µg/µl), luzindole (LUZ, 5 µg/µl) or the MT2-selective receptor drug 4-P-PDOT (5 µg/µl) reversed the depressive-like behavior elicited by 6-OHDA. Sequential administration of 4-P-PDOT and MLT (5 µg/µl, 1 µg/µl) promoted additive antidepressant-like effects. In the evaluation of olfactory discrimination, LUZ induced an olfactory impairment when associated with the nigral lesion-induced impairment. Thus, our results suggest that melatonin MT2 receptors expressed in the glomerular layer are involved in depressive-like behaviors and in olfactory function associated with PD.


Assuntos
Anosmia/metabolismo , Comportamento Animal , Transtorno Depressivo/metabolismo , Neurônios Dopaminérgicos/metabolismo , Bulbo Olfatório/metabolismo , Transtornos Parkinsonianos/metabolismo , Receptor MT2 de Melatonina/metabolismo , Animais , Anosmia/etiologia , Anosmia/fisiopatologia , Anosmia/psicologia , Comportamento Animal/efeitos dos fármacos , Transtorno Depressivo/etiologia , Transtorno Depressivo/fisiopatologia , Transtorno Depressivo/psicologia , Modelos Animais de Doenças , Neurônios Dopaminérgicos/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Masculino , Melatonina/farmacologia , Bulbo Olfatório/efeitos dos fármacos , Bulbo Olfatório/fisiopatologia , Percepção Olfatória/efeitos dos fármacos , Oxidopamina , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/fisiopatologia , Transtornos Parkinsonianos/psicologia , Ratos Wistar , Receptor MT2 de Melatonina/efeitos dos fármacos , Transdução de Sinais , Olfato/efeitos dos fármacos , Natação , Tetra-Hidronaftalenos/farmacologia , Triptaminas/farmacologia
19.
Int J Implant Dent ; 6(1): 65, 2020 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-33099690

RESUMO

BACKGROUND: An effective biomaterial for bone replacement should have properties to avoid bacterial contamination and promote bone formation while inducing rapid cell differentiation simultaneously. Bone marrow stem cells are currently being investigated because of their known potential for differentiation in osteoblast lineage. This makes these cells a good option for stem cell-based therapy. We have aimed to analyze, in vitro, the potential of pure titanium (Ti), Ti-35Nb-7Zr alloy (A), niobium (Nb), and zirconia (Zr) to avoid the microorganisms S. aureus (S.a) and P. aeruginosa (P.a). Furthermore, our objective was to evaluate if the basic elements of Ti-35Nb-7Zr alloy have any influence on bone marrow stromal cells, the source of stem cells, and observe if these metals have properties to induce cell differentiation into osteoblasts. METHODS: Bone marrow stromal cells (BMSC) were obtained from mice femurs and cultured in osteogenic media without dexamethasone as an external source of cell differentiation. The samples were divided into Ti-35Nb-7Zr alloy (A), pure titanium (Ti), Nb (niobium), and Zr (zirconia) and were characterized by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS). After predetermined periods, cell interaction, cytotoxicity, proliferation, and cell differentiation tests were performed. For monotypic biofilm formation, standardized suspensions (106 cells/ml) with the microorganisms S. aureus (S.a) and P. aeruginosa (P.a) were cultured for 24 h on the samples and submitted to an MTT test. RESULTS: All samples presented cell proliferation, growth, and spreading. All groups presented cell viability above 70%, but the alloy (A) showed better results, with statistical differences from Nb and Zr samples. Zr expressed higher ALP activity and was statistically different from the other groups (p < 0.05). In contrast, no statistical difference was observed between the samples as regards mineralization nodules. Lower biofilm formation of S.a and P.a. was observed on the Nb samples, with statistical differences from the other samples. CONCLUSION: Our results suggest that the basic elements present in the alloy have osteoinductive characteristics, and Zr has a good influence on bone marrow stromal cell differentiation. We also believe that Nb has the best potential for reducing the formation of microbial biofilms.

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