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1.
Circ Res ; 134(9): 1061-1082, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38662865

RESUMO

Wildfire smoke (WFS) is a mixture of respirable particulate matter, environmental gases, and other hazardous pollutants that originate from the unplanned burning of arid vegetation during wildfires. The increasing size and frequency of recent wildfires has escalated public and occupational health concerns regarding WFS inhalation, by either individuals living nearby and downstream an active fire or wildland firefighters and other workers that face unavoidable exposure because of their profession. In this review, we first synthesize current evidence from environmental, controlled, and interventional human exposure studies, to highlight positive associations between WFS inhalation and cardiovascular morbidity and mortality. Motivated by these findings, we discuss preventative measures and suggest interventions to mitigate the cardiovascular impact of wildfires. We then review animal and cell exposure studies to call attention on the pathophysiological processes that support the deterioration of cardiovascular tissues and organs in response to WFS inhalation. Acknowledging the challenges of integrating evidence across independent sources, we contextualize laboratory-scale exposure approaches according to the biological processes that they model and offer suggestions for ensuring relevance to the human condition. Noting that wildfires are significant contributors to ambient air pollution, we compare the biological responses triggered by WFS to those of other harmful pollutants. We also review evidence for how WFS inhalation may trigger mechanisms that have been proposed as mediators of adverse cardiovascular effects upon exposure to air pollution. We finally conclude by highlighting research areas that demand further consideration. Overall, we aspire for this work to serve as a catalyst for regulatory initiatives to mitigate the adverse cardiovascular effects of WFS inhalation in the community and alleviate the occupational risk in wildland firefighters.


Assuntos
Doenças Cardiovasculares , Fumaça , Incêndios Florestais , Humanos , Animais , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Fumaça/efeitos adversos , Exposição por Inalação/efeitos adversos , Poluentes Atmosféricos/efeitos adversos , Material Particulado/efeitos adversos , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/prevenção & controle , Exposição Ambiental/efeitos adversos
2.
Cell Biochem Funct ; 42(5): e4086, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38956862

RESUMO

Wounds represent a growing global issue demanding increased attention. To expedite wound healing, technologies are under development, and light emitting diode (LED) devices of varying wavelengths are being explored for their stimulating influence on the healing process. This article presents a systematic literature review aiming to compile, organize, and analyze the impacts of LED devices on wound healing. This review is registered on the PROSPERO platform [CRD42023403870]. Two blinded authors conducted searches in the Pubmed, Web of Science, Scopus, Embase, and ScienceDirect databases. In vitro and in vivo experimental studies assessing LED utilization in the wound healing process were included. The search yielded 1010 studies, of which 27 were included in the review. It was identified that LED stimulates different healing pathways, promoting enhanced cell proliferation and migration, angiogenesis stimulation, increased collagen deposition, and modulation of the inflammatory response. Thus, it can be concluded that the LED stimulates cellular and molecular processes contingent on the utilized parameters. The effects depend on the standards used. Cell migration and proliferation were better influenced by green and red LED. The extracellular matrix components and angiogenesis were regulated by all wavelengths and the modulation of inflammation was mediated by green, red, and infrared LEDs.


Assuntos
Proliferação de Células , Cicatrização , Animais , Humanos , Movimento Celular , Luz , Fototerapia
3.
Clin Oral Implants Res ; 35(10): 1286-1298, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38884385

RESUMO

OBJECTIVE: To compare the implant-abutment connection microgap between computer-aided design and computer-aided manufacturing (CAD/CAM) milled or laser-sintered cobalt-chrome custom abutments with or without ceramic veneering and titanium stock abutments with or without crown cementation. MATERIAL AND METHODS: Six groups of six abutments each were prepared: (1) CAD/CAM cobalt-chrome custom abutments: milled, milled with ceramic veneering, laser-sintered, and laser-sintered with ceramic veneering (four groups: MIL, MIL-C, SIN, and SIN-C, respectively) and (2) titanium stock abutments with or without zirconia crown cementation (two groups: STK and STK-Z, respectively). Abutments were screwed to the implants by applying 30 Ncm torque. All 36 samples were sectioned along their long axes. The implant-abutment connection microgap was measured using scanning electron microscopy on the right and left sides of the connection at the upper, middle, and lower levels. Data were analyzed using the Kruskal-Wallis test (p < .05). RESULTS: Mean values (µm) of the microgap were 0.54 ± 0.44 (STK), 0.55 ± 0.48 (STK-Z), 1.53 ± 1.30 (MIL), 2.30 ± 2.2 (MIL-C), 1.53 ± 1.37 (SIN), and 1.87 ± 1.8 (SIN-C). Although significant differences were observed between the STK and STK-Z groups and the other groups (p < .05), none were observed between the milled and laser-sintered groups before or after ceramic veneering. The largest microgap was observed at the upper level in all groups. CONCLUSIONS: Titanium stock abutments provided a closer fit than cobalt-chrome custom abutments. Neither crown cementation nor ceramic veneering resulted in significant changes in the implant-abutment connection microgap.


Assuntos
Cerâmica , Ligas de Cromo , Desenho Assistido por Computador , Coroas , Dente Suporte , Facetas Dentárias , Titânio , Titânio/química , Cerâmica/química , Ligas de Cromo/química , Técnicas In Vitro , Microscopia Eletrônica de Varredura , Projeto do Implante Dentário-Pivô/métodos , Cimentação/métodos , Humanos , Zircônio/química , Adaptação Marginal Dentária , Propriedades de Superfície
4.
J Med Ethics ; 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38851293

RESUMO

Donor conceived persons are likely to have a lower quality of life than persons who are genetically related to both parents. Empirical evidence is presented to corroborate this point. The evidence is subdivided into three sections: (1) negative experience of the donor conception itself, (2) negative effects of secrecy and openness and (3) negative effects of donor anonymity and donor identifiability. The principle of procreative beneficence requires parents to select the child with the best possible life. Given the difference in quality of life, intended parents should try to have a genetically related child. This finding is also a strong reason for society to invest public resources in the development of techniques that enable people to create genetically related children.

5.
J Med Ethics ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38697769

RESUMO

Within feminist literature from the early 1970s to this day, assisted reproductive technologies have been largely known to divide, replace or eliminate biological motherhood. For example, while in the past biological motherhood was considered a continuous experience, in vitro fertilisation (IVF) and IVF using egg donation allowed a split between two biological mothers, one providing eggs (genetic mother) and the other one gestation (gestational mother). This split was considered irreparable: the genetic mother could not be also gestational, and vice versa. On the contrary, this paper aims to show that assisted reproductive technologies may also have a constructive potential towards biological motherhood(s). To explain how it could be possible, two existing techniques are explored: the first is maternal spindle transfer, which allows a double genetic motherhood; the second is reciprocal effortless IVF, which supposedly enables a double gestational motherhood. While in the first part, these techniques are examined singularly, in the second part a feasible combination of them is speculated. The idea is that assisted reproductive technologies could 'recombine' genetic and gestational motherhood in two figures that include both, namely in two 'complete' biological mothers, both genetic and gestational.

6.
BMC Musculoskelet Disord ; 25(1): 769, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39354427

RESUMO

BACKGROUND: Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by chronic inflammation and progressive cartilage degradation, ultimately leading to joint dysfunction and disability. Oleocanthal (OC), a bioactive phenolic compound derived from extra virgin olive oil, has garnered significant attention due to its potent anti-inflammatory properties, which are comparable to those of non-steroidal anti-inflammatory drugs (NSAIDs). This study pioneers the investigation into the effects of OC on the Protease-Activated Receptor-2 (PAR-2) mediated inflammatory pathway in OA, aiming to validate its efficacy as a functional food-based therapeutic intervention. METHODS: To simulate cartilage tissue in vitro, human bone marrow-derived mesenchymal stem cells (BMSCs) were differentiated into chondrocytes. An inflammatory OA-like environment was induced in these chondrocytes using lipopolysaccharide (LPS) to mimic the pathological conditions of OA. The therapeutic effects of OC were evaluated by treating these inflamed chondrocytes with various concentrations of OC. The study focused on assessing key inflammatory markers, catabolic enzymes, and mitochondrial function to elucidate the protective mechanisms of OC. Mitochondrial function, specifically mitochondrial membrane potential (ΔΨm), was assessed using Rhodamine 123 staining, a fluorescent dye that selectively accumulates in active mitochondria. The integrity of ΔΨm serves as an indicator of mitochondrial and bioenergetic function. Additionally, Western blotting was employed to analyze protein expression levels, while real-time polymerase chain reaction (RT-PCR) was used to quantify gene expression of inflammatory cytokines and catabolic enzymes. Flow cytometry was utilized to measure cell viability and apoptosis, providing a comprehensive evaluation of OC's therapeutic effects on chondrocytes. RESULTS: The results demonstrated that OC significantly downregulated PAR-2 expression in a dose-dependent manner, leading to a substantial reduction in pro-inflammatory cytokines, including TNF-α, IL-1ß, and MCP-1. Furthermore, OC attenuated the expression of catabolic markers such as SOX4 and ADAMTS5, which are critically involved in cartilage matrix degradation. Importantly, OC was found to preserve mitochondrial membrane potential (ΔΨm) in chondrocytes subjected to inflammatory stress, as evidenced by Rhodamine 123 staining, indicating a protective effect on cellular bioenergetics. Additionally, OC modulated the Receptor Activator of Nuclear Factor Kappa-Β Ligand (RANKL)/Receptor Activator of Nuclear Factor Kappa-Β (RANK) pathway, suggesting a broader therapeutic action against the multifactorial pathogenesis of OA. CONCLUSIONS: This study is the first to elucidate the modulatory effects of OC on the PAR-2 mediated inflammatory pathway in OA, revealing its potential as a multifaceted therapeutic agent that not only mitigates inflammation but also protects cartilage integrity. The preservation of mitochondrial function and modulation of the RANKL/RANK pathway further underscores OC's comprehensive therapeutic potential in counteracting the complex pathogenesis of OA. These findings position OC as a promising candidate for integration into nutritional interventions aimed at managing OA. However, further research is warranted to fully explore OC's therapeutic potential across different stages of OA and its long-term effects in musculoskeletal disorders.


Assuntos
Anti-Inflamatórios , Condrócitos , Monoterpenos Ciclopentânicos , Células-Tronco Mesenquimais , Osteoartrite , Receptor PAR-2 , Humanos , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Osteoartrite/metabolismo , Osteoartrite/tratamento farmacológico , Receptor PAR-2/metabolismo , Anti-Inflamatórios/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Monoterpenos Ciclopentânicos/farmacologia , Células Cultivadas , Alimento Funcional , Inflamação/metabolismo , Inflamação/tratamento farmacológico , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Lipopolissacarídeos/farmacologia , Aldeídos , Fenóis
7.
Odontology ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769194

RESUMO

This research aims to evaluate the efficiency of cavitary varnishes containing experimental bioglasses in the occlusion of dentinal tubules. One hundred and sixty-eight cervical buccal dentin samples were obtained from bovine teeth. Samples were randomized into the following groups: I. Distilled Water (DW); II. Cavity Varnish (CV); III. Colgate® Sensitive Pro-Relief™ (CS); IV. 45S5 Bioglass (45S5); V. KSr Bioglass strontium potassium (KSr); VI. P Bioglass phosphorus (P); and VII. PSi Bioglass phosphorus silica (PSi). The treatments were applied to the surfaces of the samples, which were then subjected to simulated brushing. The samples were analyzed for a) characterization of bioactive glasses; b) surface roughness; c) descriptive analysis of the dentin surface; d) total versus occluded number of dentinal tubules; e) diameter of the dentinal tubules; f) chemical composition of the dentin surfaces, and g) dentin permeability. All groups treated with biomaterials without the brushing challenge showed an increase in roughness and (total or partial) occlusion of the dentinal tubules. The PSi group had the best values for occlusion, while the KSr group had the highest calcium and phosphorus concentrations. After the brushing challenge the roughness was controlled by the presence of biomaterials; 45S5, KSr, and PSi showed occlusion of the dentin tubules. All bioactive glasses showed reduced tooth permeability compared to distilled water. The PSi group had the smallest tubule diameter and highest phosphorus concentration. KSr and PSi bioglasses are promising materials for dentin occlusion and remineralization and are promising new biomaterials for the treatment of dentin hypersensitivity.

8.
J Esthet Restor Dent ; 36(2): 402-409, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37681984

RESUMO

OBJECTIVE: To evaluate the penetration of hydrogen peroxide (HP) into the pulp chamber and the color change of different bleaching varnishes in low concentrations used for at-home bleaching. MATERIALS AND METHODS: Ninety healthy premolars were used, randomly distributed into nine groups (n = 10) according to bleaching varnish (PL, PolaLuminate; VS, VivaStyle Paint On Plus; CA, Cavex Bite&White whitening pen and; AW AlignerWhite) and time (10 and 30 min), and a control group (no bleaching). The penetration of HP was evaluated by UV-Vis spectroscopy. To evaluate the color change (ΔEab , ΔE00 , ΔWID ) a digital spectrophotometer was used (α = 0.05). RESULTS: The AW group in 10 min and the control group showed similar and lower HP penetration in the pulp chamber when compared to the other groups (p = 0.003). Increasing the application time to 30 minutes elevated the amount of HP inside the pulp chamber for all groups (p = 0.003), except for PL (p > 0.05). When applied for 30 min all bleaching varnishes showed higher color change (ΔWID ) when compared to 10 min (p = 0.04). CONCLUSIONS: For all bleaching varnishes evaluated, PolaLuminate applied for 30 min showed lower penetration into the pulp chamber and higher bleaching effects. CLINICAL SIGNIFICANCE: The use of bleaching varnishes seems promising for teeth bleaching, but it varies according to user product and protocol.


Assuntos
Clareadores Dentários , Clareamento Dental , Peróxido de Hidrogênio/farmacologia , Cavidade Pulpar , Clareamento Dental/métodos , Clareadores Dentários/farmacologia , Espectrofotometria , Cor
9.
J Neuroradiol ; 51(4): 101194, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38637231

RESUMO

BACKGROUND: Thrombectomy with a stent retriever (SR) may lead to intracranial hemorrhage due to vessel displacement. We aimed to explore factors related to vessel displacement using an in vitro vessel model. METHODS: A vessel model mimicking two-dimensional left internal carotid angiography findings was used in this study. Six SR types (Solitaire 3 × 40, 4 × 40, and 6 × 40; Embotrap 5 × 37; Trevo 4 × 41; and Tron 4 × 40) were fully deployed in the M2 ascending, M2 bend, or M1 horizontal portion. Subsequently, the SR was retracted, and the vessel displacement, maximum SR retraction force, and angle of the M2 bend portion were measured. A total of 180 SR retraction experiments were conducted using 6 SR types at 3 deployment positions with 10 repetitions each. RESULTS: The mean maximum distance of vessel displacement for Embotrap Ⅲ 5 × 37 (6.4 ± 3.5 mm, n = 30) was significantly longer than that for the other five SR types (p = 0.029 for Solitaire 6 × 40 and p < 0.001 for the others, respectively). Vessel displacement was significantly longer in the M2 ascending portion group (5.4 ± 3.0 mm, n = 60) than in the M2 bend portion group (3.3 ± 1.6 mm, n = 60) (p < 0.001) and it was significantly longer in the M2 bend portion group than in the M1 horizontal portion group (1.1 ± 0.7 mm, n = 60) (p < 0.001). A positive correlation existed between the mean maximum SR retraction force or mean angle of the M2 bend portion due to SR retraction (i.e., vessel straightening) and the mean maximum distance of vessel displacement (r = 0.90, p < 0.001; r = 0.90, p < 0.001, respectively). CONCLUSIONS: Vessel displacement varied with the SR type, size, and deployment position. Moreover, vessel displacement correlated with the SR retraction force or vessel straightening of the M2 bend portion.


Assuntos
Artéria Carótida Interna , Stents , Humanos , Artéria Carótida Interna/diagnóstico por imagem , Trombectomia/métodos , Trombectomia/instrumentação , Técnicas In Vitro , Hemorragias Intracranianas/etiologia , Hemorragias Intracranianas/diagnóstico por imagem
10.
BMC Oral Health ; 24(1): 1090, 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39277707

RESUMO

The present study aimed to compare the effect of photobiomodulation with different energy densities on the angiogenic differentiation of human periodontal ligament stem cells (hPDLSCs) and stem cells from human exfoliated deciduous teeth (SHED). Photobiomodulation therapy with a 660 nm diode laser (2.4 J/cm2 and 3.9 J/cm2) on two consecutive days post-culture was applied to two types of stem cells (hPDLSCs and SHED). The Quantitative Real-time Polymerase Chain Reaction (RT-qPCR) test was undertaken to investigate Vascular Endothelial Growth Factor-A (VEGF-A) and Angiopoietin I (ANG-I) genes on days 1, 3, 5, 7, and 10 after the first session of laser application. The 4',6-diamidino-2-phenylindole (DAPI) staining and Methyl Thiazolyl Tetrazolium (MTT) test were conducted on days 1, 3, and 5 after the first session of laser application, to assess the cell viability. The Two-way ANOVA with Tukey post hoc test was used to analyze the outcomes of the MTT and RT-qPCR tests. The results of the MTT and DAPI convergently illustrated that the groups receiving photobiomodulation with 2.4 J/cm2 had higher cell viability compared to 3.9 J/cm2. All experimental groups showed an upregulation of VEGF-A and ANG-I gene expression from day 1 to 5, followed by a downregulation from day 5 to 10. The groups with cultured hPDLSCs and SHED receiving photobiomodulation using 2.4 J/cm2 had the most amounts of VEGF-A and ANG-I gene expression on day 5, respectively. In conclusion, the 660 nm mediated photobiomodulation therapy of cultured SHED and hPDLSCs with 2.4 J/cm2 energy density may be associated with higher angiogenic differentiation (the expression of VEGF-A and ANG-I) as well as higher cell viability compared to the photobiomodulation therapy with 3.9 J/cm2.


Assuntos
Diferenciação Celular , Terapia com Luz de Baixa Intensidade , Ligamento Periodontal , Células-Tronco , Dente Decíduo , Fator A de Crescimento do Endotélio Vascular , Humanos , Diferenciação Celular/efeitos da radiação , Terapia com Luz de Baixa Intensidade/métodos , Ligamento Periodontal/citologia , Ligamento Periodontal/efeitos da radiação , Fator A de Crescimento do Endotélio Vascular/metabolismo , Células-Tronco/efeitos da radiação , Dente Decíduo/citologia , Neovascularização Fisiológica/efeitos da radiação , Reação em Cadeia da Polimerase em Tempo Real , Angiopoietina-1 , Sobrevivência Celular/efeitos da radiação , Lasers Semicondutores/uso terapêutico , Técnicas In Vitro , Células Cultivadas
11.
Int J Dent Hyg ; 22(2): 458-464, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37661658

RESUMO

OBJECTIVES: To simulate the abrasive potential of an interdental brush when applied with toothpastes and prophylactic gels/solutions in a novel laboratory brushing simulation set-up. METHODS: A brushing device was customized to treat dentin samples mimicking a simplified interdental space with an interdental brush (ISO 2). The brushing, that is, 7200 strokes for 1 h, was performed with artificial saliva (control), a povidone-iodine solution, and slurries of chlorhexidine and fluoride gels as well as three toothpastes with different RDA values ranging from 29 to 100, respectively. The loss of dentin was profilometrically assessed and compared with ANOVA and Fishers LSD. RESULTS: While artificial saliva as control, the solution and the gel slurries showed no measurable dentin loss, toothpastes resulted in a measurable linear surface damage with respect to the actual intrinsic RDA values and ranged from 12.6 to 26.5 µm (p < 0.001). CONCLUSIONS: Any interdental cleaning product should be tailored and carefully instructed. Any over- and misuse should be avoided, which applies especially to the use of interdental brushes in combination with abrasive toothpastes.


Assuntos
Abrasão Dentária , Erosão Dentária , Humanos , Cremes Dentais/uso terapêutico , Abrasão Dentária/etiologia , Abrasão Dentária/prevenção & controle , Saliva Artificial , Dentina , Escovação Dentária , Géis
12.
Polim Med ; 54(1): 7-14, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38545926

RESUMO

BACKGROUND: There is a lack of studies evaluating the toxicity of nitric oxide (NO) precursors in chitosan/L-arginine hydrogels and their topical administration. However, clarifying the characteristics of these elements is essential for their possible use in non-surgical techniques of tooth movement acceleration. Such characteristics include interaction with different cell types, metabolism and drug safety. OBJECTIVES: This in vitro study aimed to assess the cytotoxicity of chitosan hydrogels on human HeLa cells using different concentrations of L-arginine. MATERIAL AND METHODS: The hydrogels were synthesized in a materials engineering laboratory, with a controlled environment, using 4 different L-arginine concentrations of 0%, 10%, 15%, and 20%. Once the hydrogels were prepared, their physical and chemical properties were characterized, and viability analysis was performed using 2 different methods, including a 48-h assay with Artemia salina nauplii and a 24-h cell culture with human HeLa cells followed by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) proliferation assay. Data analysis was performed using a Mann-Whitney U test to evaluate positive and negative controls in the cell culture, with a significance level of 0.01. A Wilcoxon paired test contrasted the 24-h compared to 48-h Artemia salina assays, with a Kruskal-Wallis and post hoc Dunn test used to compare groups using a significance level of 0.05. RESULTS: In the more viscous hydrogels, Artemia salina nauplii decreased drastically in 24 h, while the 15% and 20% hydrogels had no statistical differences from the negative control. The 10% and 20% hydrogels were statistically different from the negative control when comparing cell culture data. CONCLUSIONS: Our findings suggest that chitosan/L-arginine hydrogels could be used in humans without toxic effects. However, more trials and tests are needed to evaluate tooth movement rate during orthodontic treatment.


Assuntos
Arginina , Sobrevivência Celular , Quitosana , Hidrogéis , Quitosana/química , Hidrogéis/química , Humanos , Células HeLa , Arginina/química , Arginina/farmacologia , Sobrevivência Celular/efeitos dos fármacos
13.
J Med Ethics ; 2023 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-37130754

RESUMO

Mitochondrial replacement techniques (MRTs) are a new group of biotechnologies that aim to aid women whose eggs have disease-causing deleteriously mutated mitochondria to have genetically related healthy children. These techniques have also been used to aid women with poor oocyte quality and poor embryonic development, to have genetically related children. Remarkably, MRTs create humans with DNA from three sources: nuclear DNA from the intending mother and father, and mitochondrial DNA from the egg donor. In a recent publication Françoise Baylis argued that MRTs are detrimental for genealogical research via mitochondrial DNA because they would obscure the lines of individual descent. In this paper, I argue that MRTs do not obscure genealogical research, but rather that MRT-conceived children can have two mitochondrial lineages. I argue for this position by showing that MRTs are reproductive in nature and, thus, they create genealogy.

14.
Drug Metab Rev ; 54(1): 46-62, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35188018

RESUMO

The pharmacokinetic and safety assessment of drug candidates is becoming increasingly dependent upon in vitro models of hepatic metabolism and toxicity. Predominant among these is the HepG2 cell line, although HepaRG is becoming increasingly popular because of its perceived closer resemblance to human hepatocytes. We review the functionality of these cell lines in terms of Phase I protein expression, basal cytochrome P450-dependent activity, and utility in P450 induction studies. Our analysis indicates that HepG2 cells are severely compromised: proteomic studies show that they express few key proteins in common with hepatocytes and they lack drug-metabolizing capacity. Differentiated HepaRGs are more hepatocyte-like than HepG2s, but they also have limitations, and it is difficult to assess their utility because of the enormous variability in data reported, possibly arising from the complex differentiation protocols required to obtain hepatocyte-like cells. This is exacerbated by the use of DMSO in the induction protocol, together with proprietary supplements whose composition is a commercial secret. We conclude that, while currently available data on the utility of HepaRG generates a confusing picture, this line does have potential utility in drug metabolism studies. However, to allow studies to be compared directly a standardized, reproducible differentiation protocol is essential and the cell line's functionality in terms of known mechanisms of P450 regulation must be demonstrated. We, therefore, support the development of regulatory guidelines for the use of HepaRGs in induction studies as a first step in generating a database of consistent, reliable data.


Assuntos
Hepatócitos , Proteômica , Linhagem Celular , Citocromo P-450 CYP3A/metabolismo , Células Hep G2 , Hepatócitos/metabolismo , Humanos , Taxa de Depuração Metabólica
15.
Inflamm Res ; 71(7-8): 741-758, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35612604

RESUMO

INTRODUCTION: Several experimental models have been designed to promote the development of new anti-inflammatory drugs. The in vitro model using RAW 264.7 cells has been widely used. However, there is still no consensus on which inflammatory mediators should initially be measured to screen for possible anti-inflammatory effects. To determine the rationality of measuring inflammatory mediators together with NO, such as the levels of tumor necrosis factor (TNF)-α, and interleukins (IL) 1ß and 6, we carried out this systematic review (SR) and meta-analysis (MA). METHODOLOGY: We conducted this SR and MA in accordance with the Preferred Reporting of Systematic Reviews and Meta-Analysis and the Cochrane Handbook for Systematic Reviews of Intervention. This review was registered in the Open Science Framework ( https://doi.org/10.17605/OSF.IO/8C3HT ). RESULTS: LPS-induced cells produced high NO levels compared to non-LPS induced, and this production was not related to cell density. TNF-α, IL-1ß, and IL-6, also showed high levels after cells had been stimulated with LPS. Though with some restrictions, all studies were reliable, as the risk of bias was detected in the test compounds and systems. CONCLUSION: Measurement of NO levels may be sufficient to screen for possible anti-inflammatory action in the context of LPS-induced RAW 264.7 cells.


Assuntos
Lipopolissacarídeos , Macrófagos , Animais , Anti-Inflamatórios/farmacologia , Biomarcadores , Mediadores da Inflamação , Interleucina-1beta/farmacologia , Lipopolissacarídeos/farmacologia , Camundongos , NF-kappa B , Óxido Nítrico , Células RAW 264.7 , Fator de Necrose Tumoral alfa/farmacologia
16.
Eur J Vasc Endovasc Surg ; 63(1): 119-137, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34674936

RESUMO

OBJECTIVE: Vascular graft infection (VGI) is a feared complication. Prevention is of the utmost importance and vascular graft coatings (VGCs) could offer a potential to do this, with in vitro research a first crucial step. The aim of this study was to summarise key features of in vitro models investigating coating strategies to prevent VGI in order to provide guidance for the setup of future translational research. DATA SOURCES: A comprehensive search was performed in MEDLINE, Embase, and Web of Science. METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. For each database, a specific search strategy was developed. Quality was assessed with the Toxicological data Reliability Assessment Tool (ToxRTool). In vitro models using a VGC and inoculation of the graft with a pathogen were included. The type of graft, coating, and pathogen were summarised. The outcome assessment in each study was evaluated. RESULTS: In total, 4 667 studies were identified, of which 45 papers met the inclusion criteria. The majority used polyester grafts (68.2%). Thirty-one studies (68.9%) included antibiotics, and nine studies (20%) used a commercial silver graft in their protocol. New antibacterial strategies (e.g., proteolytic enzymes) were investigated. A variety of testing methods was found and focused mainly on bacterial adherence, coating adherence and dilution, biofilm formation, and cytotoxicity. Ninety-three per cent of the studies (n = 41) were considered unreliable. CONCLUSION: Polyester is the preferred type of graft to coat on. The majority of coating studies are based on antibiotics; however, new coating strategies (e.g., antibiofilm coating) are coming. Many in vitro setups are available. In vitro studies have great potential, they can limit the use, but cannot replace in vivo studies completely. This paper can be used as a guidance document for future in vitro research.


Assuntos
Prótese Vascular , Desenho de Prótese , Infecções Relacionadas à Prótese/prevenção & controle , Antibacterianos/administração & dosagem , Humanos , Técnicas In Vitro , Poliésteres , Infecções Relacionadas à Prótese/microbiologia , Prata/administração & dosagem
17.
Eur J Oral Sci ; 130(5): e12890, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35959863

RESUMO

Glass ionomer (GI) cements and self-etch (SE) or universal adhesives after etching (ER) adapt variably with dentine. Dentine characteristics vary with depth (deep/shallow), location (central/peripheral), and microscopic site (intertubular/peritubular). To directly compare adhesion to dentine, non-destructive imaging and testing are required. Here, GI, ER, and SE adapted at different dentine depths, locations, and sites were investigated using micro-CT, xenon plasma focused ion beam scanning electron microscopy (Xe PFIB-SEM), and energy dispersive X-ray spectroscopy (EDS). Extracted molars were prepared to deep or shallow slices and treated with the three adhesives. Micro-CT was used to compare changes to air volume gaps, following thermocycling, and statistically analysed using a quantile regression model and Fisher's exact test. The three adhesives performed similarly across dentine depths and locations, yet no change or overall increases and decreases in gaps at all dentine depths and locations were measured. The Xe PFIB-SEM-milled dentine-adhesive interfaces facilitated high-resolution characterization, and element profiling revealed variations across the tooth-material interfaces. Dentine depth and location had no impact on adhesive durability, although microscopic differences were observed. Here we demonstrate how micro-CT and Xe PFIB-SEM can be used to compare variable dental materials without complex multi-stage specimen preparation to minimize artefacts.


Assuntos
Colagem Dentária , Adesivos Dentinários , Colagem Dentária/métodos , Cimentos Dentários , Materiais Dentários/química , Dentina/química , Adesivos Dentinários/química , Cimentos de Ionômeros de Vidro , Teste de Materiais , Microscopia Eletrônica , Microscopia Eletrônica de Varredura , Cimentos de Resina/química , Propriedades de Superfície , Raios X , Xenônio/análise
18.
J Med Ethics ; 48(7): 439-446, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35277466

RESUMO

A large body of literature considers the ethico-legal and regulatory issues surrounding assisted conception. Surrogacy, however, within this body of literature is an odd-fit. It involves a unique demand of another person-a form of reproductive labour-that many other aspects of assisted conception, such as gamete donation do not involve. Surrogacy is a form of assisted gestation. The potential alternatives for individuals who want a genetically related child but who do not have the capacity to gestate are ever increasing: with the advent of uterus transplantation (UTx), and the anticipated development of artificial placentas.In this paper, I highlight the pertinent conceptual differences between technologies assisting conception and those assisting gestation to demonstrate that distinct issues arise when assisted gestative technologies (AGTs) are used. I argue that there is utility in considering AGTs as a genus of technologies. These technologies perform the same function from the perspective of putative parents and might exist on a spectrum of alternatives when they become more available. Moreover, since many of the same or very similar ethical, social and legal issues are raised by surrogacy, UTx and ectogestation, analysis of these issues will be better contextualised by considering these technologies together. Many of the matters currently being highlighted for reform in the context of surrogacy will inevitably impact on how other forms of assisted gestation are governed. The conversation should be broadened; we should consider how far other emerging technologies might be accommodated in revised regulatory schemes.


Assuntos
Técnicas de Reprodução Assistida , Feminino , Células Germinativas , Humanos , Pais , Gravidez , Mães Substitutas , Tecnologia , Útero
19.
Biofouling ; 38(3): 250-259, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35332825

RESUMO

This study sought to evaluate the physical and antimicrobial properties of a thermopolymerizable acrylic resin (PMMA) modified with metallic methacrylate monomers -zirconia (ZM), tin (TM), and di-n-butyl (DNTMB) methacrylates. Color stability was evaluated before and after immersion of samples in a staining solution by a digital spectrophotometer. The mechanical brushing test was evaluated by the roughness test. The flexural strength test used a mechanical testing machine. Human keratinocytes were used to assess cell viability and the biofilm formation assay was carried out for 5 days, in a microcosms model after one year of specimen storage. For statistical analysis, the method chosen was based on adherence to the normal distribution model and equality of variances (p < 0.05). The addition of DNTMB to PMMA promoted great antimicrobial action, acceptable cytocompatibility, without hampering the physical-mechanical properties of the commercial material. Therefore, the modified PMMA proved to be a promisor alternative to conventional resins.This study sought to evaluate the physical and antimicrobial properties of a thermopolymerizable acrylic resin (PMMA) modified with metallic methacrylate monomers -zirconia (ZM), tin (TM), and di-n-butyldimethacrylate-tin (DNTMB) methacrylates. Color stability was evaluated before and after immersion of samples in a staining solution using a digital spectrophotometer. The mechanical brushing test was evaluated by the roughness test. The flexural strength test used a mechanical testing machine. Human keratinocytes were used to assess cell viability and the biofilm formation assay was carried out for 5 days in a microcosm model after one year of specimen storage. For statistical analysis, the method chosen was based on adherence to the normal distribution model and equality of variances (p < 0.05). The addition of DNTMB to PMMA promoted great antimicrobial action, acceptable cytocompatibility, without hampering the physical-mechanical properties of the commercial material. Therefore, the modified PMMA proved to be a promising alternative to conventional denture base resins for dental use.


Assuntos
Anti-Infecciosos , Polimetil Metacrilato , Resinas Acrílicas/farmacologia , Biofilmes , Humanos , Teste de Materiais , Metacrilatos/farmacologia , Propriedades de Superfície , Estanho
20.
Ceska Gynekol ; 87(2): 137-143, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35667866

RESUMO

Cross-border reproductive care is undoubtedly a current phenomenon. The number of people interested in receiving reproductive care abroad is increasing every year. This new context needs a political solution that would respond to the definition of standard care within the circumstances of providing healthcare to the citizens of another country. Patients that undergo reproductive treatment abroad very often face complications such as language problems, insufficient information, separation from family members, cultural differences and customs, potential unrealistic expectations, and also restrictions by law. This work is descriptive in nature and aims to illustrate the variables that come into play when choosing the Czech Republic over other destinations as a country to receive infertility treatment. We analyze the phenomenon by selecting documents used as sources of data. In our research, we focused on infertility treatment and justified the reasons why foreign citizens choose the Czech Republic over other destinations for infertility treatment. The variables that lead to the selection of cross-border infertility treatment in the Czech Republic include no waiting time, anonymous donations, international departments in various languages, and affordable prices compared to other destinations.


Assuntos
Infertilidade , Turismo Médico , República Tcheca , Humanos , Infertilidade/terapia , Motivação , Reprodução , Técnicas de Reprodução Assistida
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