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1.
Chimia (Aarau) ; 75(10): 882-885, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34728016

RESUMO

The study of plastic particles, particularly those in the micro-, sub-micro-, and nano-size ranges, within food and beverages has gained increasing interest within recent years. However, many analytical techniques have limits of detection which hinder their use for the study of these particles in these sample matrices. In addition, remaining contaminants from the matrices can interfere with the signals from plastic particles. Thus, great care must be given to sample preparation and data interpretation to ensure accurate results. This study proposes the use of sample purification through chemical digestion protocols to facilitate the study of plastic particles present in tea samples, and serves to highlight technical limitations which must be overcome in future studies.


Assuntos
Nanopartículas , Plásticos , Bebidas , Chá
2.
Nanomaterials (Basel) ; 11(10)2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34685208

RESUMO

Research in nanoscience continues to bring forward a steady stream of new nanomaterials and processes that are being developed and marketed. While scientific committees and expert groups deal with the harmonization of terminology and legal challenges, risk assessors in research labs continue to have to deal with the gap between regulations and rapidly developing information. The risk assessment of nanomaterial processes is currently slow and tedious because it is performed on a material-by-material basis. Safety data sheets are rarely available for (new) nanomaterials, and even when they are, they often lack nano-specific information. Exposure estimations or measurements are difficult to perform and require sophisticated and expensive equipment and personal expertise. The use of banding-based risk assessment tools for laboratory environments is an efficient way to evaluate the occupational risks associated with nanomaterials. Herein, we present an updated version of our risk assessment tool for working with nanomaterials based on a three-step control banding approach and the precautionary principle. The first step is to determine the hazard band of the nanomaterial. A decision tree allows the assignment of the material to one of three bands based on known or expected effects on human health. In the second step, the work exposure is evaluated and the processes are classified into three "nano" levels for each specific hazard band. The work exposure is estimated using a laboratory exposure model. The result of this calculation in combination with recommended occupational exposure limits (rOEL) for nanomaterials and an additional safety factor gives the final "nano" level. Finally, we update the technical, organizational, and personal protective measures to allow nanomaterial processes to be established in research environments.

3.
J Vis Exp ; (171)2021 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-34125092

RESUMO

A three-dimensional human epidermis model reconstructed from neonatal primary keratinocytes is presented. Herein, a protocol for the cultivation process and the characterization of the model is described. Neonatal primary keratinocytes are grown submerged on permeable polycarbonate inserts and lifted to the air-liquid interface three days after seeding. After fourteen days of stimulation with defined growth factors and ascorbic acid in high calcium culture medium, the model is fully differentiated. Histological analysis revealed a completely stratified epidermis, mimicking the morphology of native human skin. To characterize the model and its barrier functions, protein levels and localization specific for early-stage keratinocyte differentiation (i.e., keratin 10), late-stage differentiation (i.e., involucrin, loricrin, and filaggrin) and tissue adhesion (i.e., desmoglein 1), were assessed by immunofluorescence. The tissue barrier integrity was further evaluated by measuring transepithelial electrical resistance. Reconstructed human epidermis was responsive to proinflammatory stimuli (i.e., lipopolysaccharide and tumor necrosis factor alpha), leading to increased cytokine release (i.e., interleukin 1 alpha and interleukin 8). This protocol represents a straightforward and reproducible in vitro method to cultivate reconstructed human epidermis as a tool to assess environmental effects and a broad range of skin-related studies.


Assuntos
Técnicas de Cocultura , Células Epidérmicas , Epiderme , Pele , Diferenciação Celular , Células Cultivadas , Humanos , Queratinócitos
4.
J Mater Chem B ; 9(26): 5365-5373, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34161405

RESUMO

Cancer cells generally exhibit higher metabolic demands relative to that of normal tissue cells. This offers great possibilities to exploit metabolic glycoengineering in combination with bio-orthogonal chemistry reactions to achieve tumour site-targeted therapeutic delivery. This work addresses the selectivity of metabolic glycan labelling in diseased (i.e., cancer) versus normal cells grown in a multicellular environment. Dibenzocylooctyne (DBCO)-bearing acetylated-d-mannosamine (Ac4ManNDBCO) was synthesised to metabolically label three different types of cell lines originating from the human lung tissues: A549 adenocarcinomic alveolar basal epithelial cells, MeT5A non-cancerous mesothelial cells, and MRC5 non-cancerous fibroblasts. These cell lines displayed different labelling sensitivity, which trended with their doubling time in the following order: A549 ≈ MeT5A > MRC5. The higher metabolic labelling efficiency inherently led to a higher extent of specific binding and accumulation of the clickable N3-conjugated gold nanoparticles (N3-AuNps, core diameter = 30 nm) in the DBCO-glycan modified A549 and MeT5A cells, but to a less prominent effect in MRC5 cells. These findings demonstrate that relative rates of cell metabolism can be exploited using metabolic labelling to recruit nanotherapeutics whilst minimising non-specific targeting of surrounding tissues.

5.
Toxicol In Vitro ; 75: 105178, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33905840

RESUMO

In vitro cell models offer a unique opportunity for conducting toxicology research, and the human lung adenocarcinoma cell line A549 is commonly used for toxicology testing strategies. It is essential to determine whether the response of these cells grown in different laboratories is consistent. In this study, A549 cells were grown under both submerged and air-liquid interface (ALI) conditions following an identical cell seeding protocol in two independent laboratories. The cells were switched to the ALI after four days of submerged growth, and their behaviour was compared to submerged conditions. The membrane integrity, cell viability, morphology, and (pro-)inflammatory response upon positive control stimuli were assessed at days 3, 5, and 7 under submerged conditions and at days 5, 7, and 10 at the ALI. Due to the high variability of the results between the two laboratories, the experiment was subsequently repeated using identical reagents at one specific time point and condition (day 5 at the ALI). Despite some variability, the results were more comparable, proving that the original protocol necessitated improvements. In conclusion, the use of detailed protocols and consumables from the same providers, special training of personnel for cell handling, and endpoint analysis are critical to obtain reproducible results across independent laboratories.

6.
Nanomaterials (Basel) ; 11(5)2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33925012

RESUMO

Small plastic particles such as micro- (<5 mm), sub-micro- (1 µm-100 nm) and nanoplastics (<100 nm) are known to be ubiquitous within our surrounding environment. However, to date relatively few methods exist for the reliable detection of nanoplastic particles in relevant sample matrices such as foods or environmental samples. This lack of relevant data is likely a result of key limitations (e.g., resolution and/or scattering efficiency) for common analytical techniques such as Fourier transform infrared or Raman spectroscopy. This study aims to address this knowledge gap in the field through the creation of surface-enhanced Raman scattering spectroscopy substrates utilizing spherical gold nanoparticles with 14 nm and 46 nm diameters to improve the scattering signal obtained during Raman spectroscopy measurements. The substrates are then used to analyze polystyrene particles with sizes of 161 nm or 33 nm and poly(ethylene terephthalate) particles with an average size of 62 nm. Through this technique, plastic particles could be detected at concentrations as low as 10 µg/mL, and analytical enhancement factors of up to 446 were achieved.

7.
Chem Soc Rev ; 50(9): 5397-5434, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33666625

RESUMO

Nanoparticles (NPs) have attracted considerable attention in various fields, such as cosmetics, the food industry, material design, and nanomedicine. In particular, the fast-moving field of nanomedicine takes advantage of features of NPs for the detection and treatment of different types of cancer, fibrosis, inflammation, arthritis as well as neurodegenerative and gastrointestinal diseases. To this end, a detailed understanding of the NP uptake mechanisms by cells and intracellular localization is essential for safe and efficient therapeutic applications. In the first part of this review, we describe the several endocytic pathways involved in the internalization of NPs and we discuss the impact of the physicochemical properties of NPs on this process. In addition, the potential challenges of using various inhibitors, endocytic markers and genetic approaches to study endocytosis are addressed along with the principal (semi) quantification methods of NP uptake. The second part focuses on synthetic and bio-inspired substances, which can stimulate or decrease the cellular uptake of NPs. This approach could be interesting in nanomedicine where a high accumulation of drugs in the target cells is desirable and clearance by immune cells is to be avoided. This review contributes to an improved understanding of NP endocytic pathways and reveals potential substances, which can be used in nanomedicine to improve NP delivery.


Assuntos
Nanomedicina , Nanopartículas/metabolismo , Animais , Endocitose , Humanos , Nanopartículas/química
8.
Small ; 17(15): e2007628, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33559363

RESUMO

Faster, cheaper, sensitive, and mechanisms-based animal alternatives are needed to address the safety assessment needs of the growing number of nanomaterials (NM) and their sophisticated property variants. Specifically, strategies that help identify and prioritize alternative schemes involving individual test models, toxicity endpoints, and assays for the assessment of adverse outcomes, as well as strategies that enable validation and refinement of these schemes for the regulatory acceptance are needed. In this review, two strategies 1) the current nanotoxicology literature review and 2) the adverse outcome pathways (AOPs) framework, a systematic process that allows the assembly of available mechanistic information concerning a toxicological response in a simple modular format, are presented. The review highlights 1) the most frequently assessed and reported ad hoc in vivo and in vitro toxicity measurements in the literature, 2) various AOPs of relevance to inhalation toxicity of NM that are presently under development, and 3) their applicability in identifying key events of toxicity for targeted in vitro assay development. Finally, using an existing AOP for lung fibrosis, the specific combinations of cell types, exposure and test systems, and assays that are experimentally supported and thus, can be used for assessing NM-induced lung fibrosis, are proposed.


Assuntos
Rotas de Resultados Adversos , Nanoestruturas , Fibrose Pulmonar , Alternativas aos Testes com Animais , Animais , Nanoestruturas/toxicidade , Medição de Risco
9.
Macromol Biosci ; 21(4): e2100016, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33624920

RESUMO

Tissue models mimic the complex 3D structure of human tissues, which allows the study of pathologies and the development of new therapeutic strategies. The introduction of perfusion overcomes the diffusion limitation and enables the formation of larger tissue constructs. Furthermore, it provides the possibility to investigate the effects of hematogenously administered medications. In this study, the applicability of hydrophilic polytetrafluoroethylene (PTFE) membranes as vessel-like constructs for further use in perfused tissue models is evaluated. The presented approach allows the formation of stable and leakproof tubes with a mean diameter of 654.7 µm and a wall thickness of 84.2 µm. A polydimethylsiloxane (PDMS) chip acts as a perfusion bioreactor and provides sterile conditions. As proof of concept, endothelial cells adhere to the tube's wall, express vascular endothelial cadherin (VE-cadherin) between neighboring cells, and resist perfusion at a shear rate of 0.036 N m-2 for 48 h. Furthermore, the endothelial cell layer delays significantly the diffusion of fluorescently labeled molecules into the surrounding collagen matrix and leads to a twofold reduced diffusion velocity. This approach represents a cost-effective alternative to introduce stable vessel-like constructs into tissue models, which allows adapting the surrounding matrix to the tissue properties in vivo.

10.
Small ; 17(15): e2006027, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33480475

RESUMO

Due to economic, practical, ethical, and scientific reasons, researchers, among others, are pushing for alternative in vitro test methods to replace or reduce existing animal experiments. In order for these tests to be more broadly used by the industrial sector and regulatory bodies, orchestrated efforts are required to show the robustness and reliability of in vitro methods, which can accelerate the use for early screening testing. Another way of increasing the use of alternatives is to coordinate validation studies, that is, multi-laboratory trials, and to gain regulatory approval and instatement as test guidelines or standard method. However, awareness of the exact standardization, validation, and approval process has been a major obstacle for many researchers. Herein, the process has been broken down into three main phases: i) test method development; ii) intra- and inter-laboratory validation; and iii) regulatory acceptance. This general process applies to all alternative methods seeking validation and approval, although the intricacies of different toxicological endpoints and/or chemical sectors may lead to additional work, particularly in the validation stage. The authors' aim is to provide insight in the development process of alternative methods with a focus on in vitro cell culture methods over validation to regulatory acceptance.


Assuntos
Alternativas aos Testes com Animais , Animais , Técnicas In Vitro , Padrões de Referência , Reprodutibilidade dos Testes
11.
Adv Healthc Mater ; 10(6): e2001667, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33434386

RESUMO

Cellular surface recognition and behavior are driven by a host of physical and chemical features which have been exploited to influence particle-cell interactions. Mechanical and topographical cues define the physical milieu which plays an important role in defining a range of cellular activities such as material recognition, adhesion, and migration through cytoskeletal organization and signaling. In order to elucidate the effect of local mechanical and topographical features generated by the adsorption of particles to an underlying surface on primary human monocyte-derived macrophages (MDM), a series of poly(N-isopropylacrylamide) (pNIPAM) particles with differing rigidity are self-assembled to form a defined particle-decorated surface. Assembly of particle-decorated surfaces is facilitated by modification of the underlying glass to possess a positive charge through functionalization using 3-aminopropyltriethoxysilane (APTES) or coating with poly(L-lysine) (PLL). MDMs are noted to preferentially remove particles with higher degrees of crosslinking (stiffer) than those with lower degrees of crosslinking (softer). Alterations to the surface density of particles enabled a greater area of the particle-decorated surface to be cleared. Uniquely, the impact of particle adsorption is evinced to have a direct impact on topographical recognition of the surface, suggesting a novel approach for controllably affecting cell-surface recognition and response.


Assuntos
Vidro , Macrófagos , Adsorção , Humanos , Tamanho da Partícula , Propriedades de Superfície
12.
J Expo Sci Environ Epidemiol ; 31(1): 137-148, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33127990

RESUMO

Being exposed to ground-level ozone (O3), as it is often the case in polluted cities, is known to have a detrimental impact on skin. O3 induces antioxidant depletion and lipid peroxidation in the upper skin layers and this effect has repercussions on deeper cellular layers, triggering a cascade of cellular stress and inflammatory responses. Repetitive exposure to high levels of O3 may lead to chronic damages of the cutaneous tissue, cause premature skin aging and aggravate skin diseases such as contact dermatitis and urticaria. This review paper debates about the most relevant experimental approaches that must be considered to gather deeper insights about the complex biological processes that are activated when the skin is exposed to O3. Having a better understanding of O3 effects on skin barrier properties and stress responses could help the whole dermato-cosmetic industry to design innovative protective solutions and develop specific cosmetic regime to protect the skin of every citizen, especially those living in areas where exposure to high levels of O3 is of concern to human health.


Assuntos
Poluentes Atmosféricos , Ozônio , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Cidades , Humanos , Peroxidação de Lipídeos , Estresse Oxidativo , Ozônio/efeitos adversos , Ozônio/análise , Pele/metabolismo
13.
Nat Nanotechnol ; 16(3): 344-353, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33318639

RESUMO

In plants, pathogen attack can induce an immune response known as systemic acquired resistance that protects against a broad spectrum of pathogens. In the search for safer agrochemicals, silica nanoparticles (SiO2 NPs; food additive E551) have recently been proposed as a new tool. However, initial results are controversial, and the molecular mechanisms of SiO2 NP-induced disease resistance are unknown. Here we show that SiO2 NPs, as well as soluble Si(OH)4, can induce systemic acquired resistance in a dose-dependent manner, which involves the defence hormone salicylic acid. Nanoparticle uptake and action occurred exclusively through the stomata (leaf pores facilitating gas exchange) and involved extracellular adsorption in the air spaces in the spongy mesophyll of the leaf. In contrast to the treatment with SiO2 NPs, the induction of systemic acquired resistance by Si(OH)4 was problematic since high Si(OH)4 concentrations caused stress. We conclude that SiO2 NPs have the potential to serve as an inexpensive, highly efficient, safe and sustainable alternative for plant disease protection.


Assuntos
Arabidopsis/efeitos dos fármacos , Resistência à Doença/genética , Nanopartículas/química , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Doenças das Plantas/genética , Doenças das Plantas/prevenção & controle , Espécies Reativas de Oxigênio/química , Ácido Salicílico/química , Dióxido de Silício/química , Dióxido de Silício/farmacologia
14.
PLoS One ; 15(12): e0241500, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33270665

RESUMO

The presence of ascites in the peritoneal cavity leads to morphological and functional changes of the peritoneal mesothelial cell layer. Cells loose cell-cell interactions, rearrange their cytoskeleton, activate the production of fibronectin, and change their cell surface morphology in a proinflammatory environment. Moreover, ovarian cancer cell adhesion has been shown to be facilitated by these changes due to increased integrin- and CD44-mediated binding sites. In this study, the biological responsiveness of the human pleural mesothelial cell line MeT-5A to patient-derived and artificial ascites was studied in vitro and adhesion of ovarian cancer cells, i.e. SKOV-3 cells, investigated. Changes were mainly observed in cells exposed to artificial ascites containing higher cytokine concentrations than patient-derived ascites. Interestingly, reduced cell-cell interactions were already observed in untreated MeT-5A cells and effects on tight junction protein expression and permeability upon exposure to ascites were minor. Ascites induced upregulation of CDC42 effector protein 2 expression, which affects stress fiber formation, however significant F-actin reorganization was not observed. Moreover, fibronectin production remained unchanged. Analysis of mesothelial cell surface characteristics showed upregulated expression of intercellular adhesion molecule 1, slightly increased hyaluronic acid secretion and decreased microvillus expression upon exposure to ascites. Nevertheless, the observed changes were not sufficient to facilitate adhesion of SKOV-3 cells on MeT-5A cell layer. This study revealed that MeT-5A cells show a reduced biological responsiveness to the presence of ascites, in contrast to published studies on primary human peritoneal mesothelial cells.


Assuntos
Adesão Celular/efeitos dos fármacos , Citocinas/farmacologia , Neoplasias Mesoteliais/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Ascite/metabolismo , Ascite/patologia , Linhagem Celular Tumoral , Citocinas/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Receptores de Hialuronatos/genética , Integrina beta1/genética , Molécula 1 de Adesão Intercelular/genética , Neoplasias Mesoteliais/genética , Neoplasias Mesoteliais/metabolismo , Neoplasias Mesoteliais/patologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Pacientes , Peritônio/química , Peritônio/metabolismo , Transdução de Sinais/genética , Proteína cdc42 de Ligação ao GTP/genética
16.
Elife ; 92020 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-33026975

RESUMO

The extracellular matrix (ECM) plays critical roles in tumor progression and metastasis. However, the contribution of ECM proteins to early metastatic onset in the peritoneal cavity remains unexplored. Here, we suggest a new route of metastasis through the interaction of integrin alpha 2 (ITGA2) with collagens enriched in the tumor coinciding with poor outcome in patients with ovarian cancer. Using multiple gene-edited cell lines and patient-derived samples, we demonstrate that ITGA2 triggers cancer cell adhesion to collagen, promotes cell migration, anoikis resistance, mesothelial clearance, and peritoneal metastasis in vitro and in vivo. Mechanistically, phosphoproteomics identify an ITGA2-dependent phosphorylation of focal adhesion kinase and mitogen-activated protein kinase pathway leading to enhanced oncogenic properties. Consequently, specific inhibition of ITGA2-mediated cancer cell-collagen interaction or targeting focal adhesion signaling may present an opportunity for therapeutic intervention of metastatic spread in ovarian cancer.


Assuntos
Colágeno/metabolismo , Integrina alfa2/metabolismo , Metástase Neoplásica/fisiopatologia , Omento/fisiopatologia , Peritônio/fisiopatologia , Animais , Carcinoma Epitelial do Ovário/metabolismo , Linhagem Celular Tumoral , Feminino , Camundongos , Peixe-Zebra
17.
18.
Cells ; 9(9)2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32942641

RESUMO

Silica nanoparticles (NPs) are widely used in various industrial and biomedical applications. Little is known about the cellular uptake of co-exposed silica particles, as can be expected in our daily life. In addition, an inflamed microenvironment might affect a NP's uptake and a cell's physiological response. Herein, prestimulated mouse J774A.1 macrophages with bacterial lipopolysaccharide were post-exposed to micron- and nanosized silica particles, either alone or together, i.e., simultaneously or sequentially, for different time points. The results indicated a morphological change and increased expression of tumor necrosis factor alpha in lipopolysaccharide prestimulated cells, suggesting a M1-polarization phenotype. Confocal laser scanning microscopy revealed the intracellular accumulation and uptake of both particle types for all exposure conditions. A flow cytometry analysis showed an increased particle uptake in lipopolysaccharide prestimulated macrophages. However, no differences were observed in particle uptakes between single- and co-exposure conditions. We did not observe any colocalization between the two silica (SiO2) particles. However, there was a positive colocalization between lysosomes and nanosized silica but only a few colocalized events with micro-sized silica particles. This suggests differential intracellular localizations of silica particles in macrophages and a possible activation of distinct endocytic pathways. The results demonstrate that the cellular uptake of NPs is modulated in inflamed macrophages but not in the presence of micron-sized particles.


Assuntos
Macrófagos/imunologia , Macrófagos/metabolismo , Nanopartículas/química , Nanopartículas/metabolismo , Tamanho da Partícula , Dióxido de Silício/metabolismo , Animais , Transporte Biológico , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citometria de Fluxo , Inflamação/induzido quimicamente , Inflamação/imunologia , Lipopolissacarídeos/farmacologia , Lisossomos/metabolismo , Macrófagos/efeitos dos fármacos , Camundongos , Microscopia Confocal
19.
Artigo em Inglês | MEDLINE | ID: mdl-32974315

RESUMO

A large number of prevalent lung diseases is associated with tissue inflammation. Clinically, corticosteroid therapies are applied systemically or via inhalation for the treatment of lung inflammation, and a number of novel therapies are being developed that require preclinical testing. In alveoli, macrophages and dendritic cells play a key role in initiating and diminishing pro-inflammatory reactions and, in particular, macrophage plasticity (M1 and M2 phenotypes shifts) has been reported to play a significant role in these reactions. Thus far, no studies with in vitro lung epithelial models have tested the comparison between systemic and direct pulmonary drug delivery. Therefore, the aim of this study was to develop an inflamed human alveolar epithelium model and to test the resolution of LPS-induced inflammation in vitro with a corticosteroid, methylprednisolone (MP). A specific focus of the study was the macrophage phenotype shifts in response to these stimuli. First, human monocyte-derived macrophages were examined for phenotype shifts upon exposure to lipopolysaccharide (LPS), followed by treatment with MP. A multicellular human alveolar model, composed of macrophages, dendritic cells, and epithelial cells, was then employed for the development of inflamed models. The models were used to test the anti-inflammatory potency of MP by monitoring the secretion of pro-inflammatory mediators (interleukin [IL]-8, tumor necrosis factor-α [TNF-α], and IL-1ß) through four different approaches, mimicking clinical scenarios of inflammation and treatment. In macrophage monocultures, LPS stimulation shifted the phenotype towards M1, as demonstrated by increased release of IL-8 and TNF-α and altered expression of phenotype-associated surface markers (CD86, CD206). MP treatment of inflamed macrophages reversed the phenotype towards M2. In multicellular models, increased pro-inflammatory reactions after LPS exposure were observed, as demonstrated by protein secretion and gene expression measurements. In all scenarios, among the tested mediators the most pronounced anti-inflammatory effect of MP was observed for IL-8. Our findings demonstrate that our inflamed multicellular human lung model is a promising tool for the evaluation of anti-inflammatory potency of drug candidates in vitro. With the presented setup, our model allows a meaningful comparison of the systemic vs. inhalation administration routes for the evaluation of the efficacy of a drug in vitro.

20.
J Aerosol Med Pulm Drug Deliv ; 33(6): 300-304, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32783675

RESUMO

National and international guidelines recommend droplet/airborne transmission and contact precautions for those caring for coronavirus disease 2019 (COVID-19) patients in ambulatory and acute care settings. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, an acute respiratory infectious agent, is primarily transmitted between people through respiratory droplets and contact routes. A recognized key to transmission of COVID-19, and droplet infections generally, is the dispersion of bioaerosols from the patient. Increased risk of transmission has been associated with aerosol generating procedures that include endotracheal intubation, bronchoscopy, open suctioning, administration of nebulized treatment, manual ventilation before intubation, turning the patient to the prone position, disconnecting the patient from the ventilator, noninvasive positive-pressure ventilation, tracheostomy, and cardiopulmonary resuscitation. The knowledge that COVID-19 subjects can be asymptomatic and still shed virus, producing infectious droplets during breathing, suggests that health care workers (HCWs) should assume every patient is potentially infectious during this pandemic. Taking actions to reduce risk of transmission to HCWs is, therefore, a vital consideration for safe delivery of all medical aerosols. Guidelines for use of personal protective equipment (glove, gowns, masks, shield, and/or powered air purifying respiratory) during high-risk procedures are essential and should be considered for use with lower risk procedures such as administration of uncontaminated medical aerosols. Bioaerosols generated by infected patients are a major source of transmission for SARS CoV-2, and other infectious agents. In contrast, therapeutic aerosols do not add to the risk of disease transmission unless contaminated by patients or HCWs.


Assuntos
COVID-19/prevenção & controle , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Exposição por Inalação/prevenção & controle , Exposição Ocupacional/prevenção & controle , Aerossóis , COVID-19/transmissão , Humanos , Exposição por Inalação/efeitos adversos , Exposição Ocupacional/efeitos adversos , Saúde do Trabalhador , Medição de Risco , Fatores de Risco
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