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Tetracyclines (TCs) are a class of broad-spectrum antibacterial agents recognized for their multifaceted properties, including anti-inflammatory, angiogenic and osteogenic effects. This versatility positions them as suitable candidates for drug repurposing, benefitting from well-characterized safety and pharmacological profiles. In the attempt to explore both their antibacterial and pleiotropic effects locally, innovative therapeutic strategies were set on engineering tetracycline-loaded micro and nanoparticles to tackle a vast number of clinical applications. Moreover, the conjoined drug carrier can function as an active component of the therapeutic approach, reducing off-target effects and accumulation, synergizing to an improvement of the therapeutic efficacy. In this comprehensive review we will critically evaluate recent advances involving the use of tetracyclines loaded onto micro- or nanoparticles, intended for biomedical applications, and discuss emerging approaches and current limitations associated with these drug carriers. Owing to their distinctive physical, chemical, and biological properties, these novel carriers have the potential to become a platform technology in personalized regenerative medicine and other therapeutic applications.
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Nanopartículas , Tetraciclinas , Tetraciclinas/farmacologia , Sistemas de Liberação de Medicamentos , Portadores de Fármacos/química , Antibacterianos , Nanopartículas/químicaRESUMO
The mass production of screen-printed electrochemical devices with integrated electrodes has facilitated the widespread adoption of electroanalytical methods. The SPEs (screen-printed electrodes) overcome some obstacles associated with the use of conventional electrochemical cells, making them accessible to untrained operators. Despite their advantages, SPEs require activation/modification of the working electrode (WE) to enhance sensitivity. Nanomaterials, with metal nanoparticles (NPs) dispersed in polymers and/or carbon NPs has gaining popularity for this purpose. In this study, we describe a modification of carbon SPEs (SPCEs) using Pt NPs and reduced graphene oxide (ERGO). The Pt-ERGO@SPCE is prepared by galvanostatic reduction of drop-casted precursors directly onto the WE surface, eliminating complex synthetic steps and high temperatures. After optimizing Pt amount and reduction extent, the modified SPCEs were tested for detecting hydroquinone (HQ) and bisphenol A (BPA). DPV results show significantly increased sensitivity for the quantification of both compounds. The modified SPCEs demonstrates promising performance: precision (5 % HQ, 8 % BPA), detection limits (1.4 µM HQ, 4.6 µM BPA), sensitivity (1688 µA mM-1 HQ, 441 µA mM-1 BPA), and recoveries (98-113 % HQ, 98-104 % BPA). This simple electrode modification holds great potential, allowing the preparation of the sensor by personnel who may lack access to well-equipped laboratories, particularly in developing countries.
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Tetracyclines (TCs) are a class of broad-spectrum antibiotics with diverse pharmacotherapeutic properties due to their various functional groups being attached to a common core structure. Beyond their antibacterial activity, TCs trigger pleiotropic effects on eukaryotic cells, including anti-inflammatory and potentially osteogenic capabilities. Consequently, TCs hold promise for repurposing in various clinical applications, including bone-related conditions. This study presents the first comprehensive comparison of the in vitro osteogenic potential of four TCs-tetracycline, doxycycline, minocycline, and sarecycline, within human mesenchymal stem cells. Cultures were characterized for metabolic activity, cell morphology and cytoskeleton organization, osteogenic gene expression, alkaline phosphatase (ALP) activity, and the activation of relevant signaling pathways. TCs stimulated actin remodeling processes, inducing morphological shifts consistent with osteogenic differentiation. Osteogenic gene expression and ALP activity supported the osteoinduction by TCs, demonstrating significant increases in ALP levels and the upregulation of RUNX2, SP7, and SPARC genes. Minocycline and sarecycline exhibited the most potent osteogenic induction, comparable to conventional osteogenic inducers. Signaling pathway analysis revealed that tetracycline and doxycycline activate the Wnt pathway, while minocycline and sarecycline upregulated Hedgehog signaling. Overall, the present findings suggest that TCs promote osteogenic differentiation through distinct pathways, making them promising candidates for targeted therapy in specific bone-related disorders.
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Doenças Ósseas , Compostos Heterocíclicos , Células-Tronco Mesenquimais , Humanos , Proteínas Hedgehog , Minociclina , Doxiciclina/farmacologia , Tetraciclina , Osteogênese , Antibacterianos/farmacologia , Fatores ImunológicosRESUMO
Infections associated with the surfaces of medical devices represent a critical problem due to biofilm formation and the growing resistance towards antibacterial drugs. This is particularly relevant in commonly used invasive devices such as silicone-based ones where a demand for alternative antibiofilm surfaces is increasing. In this work, an antimicrobial chitosan-biosurfactant hydrogel mesh was produced by 3D-printing. The 3D structure was designed to coat polydimethylsiloxane-based medical devices for infection prevention. Additionally, the porous 3D structure allows the incorporation of customized bioactive components. For this purpose, two biosurfactants (surfactin and sophorolipids) were biosynthesized and tested for their antimicrobial activity. In addition, the printing of surfactant-chitosan-based coatings was optimized, and the resulting 3D structures were characterized (i.e., wettability, FTIR-ATR, antimicrobial activity, and biocompatibility). Compared with surfactin, the results showed a better yield and higher antibacterial activity against Gram-positive bacteria for sophorolipids (SLs). Thus, SLs were used to produce chitosan-based 3D-printed coatings. Overall, the SLs-impregnated coatings showed the best antibacterial activity against Staphylococcus aureus planktonic bacteria (61 % of growth inhibition) and antibiofilm activity (2 log units reduction) when compared to control. Furthermore, concerning biocompatibility, the coatings were cytocompatible towards human dermal fibroblasts. Finally, the coating presented a mesh suitable to be filled with a model bioactive compound (i.e., hyaluronic acid), paving the way to be used for customized therapeutics.
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Anti-Infecciosos , Quitosana , Humanos , Silicones/química , Quitosana/farmacologia , Quitosana/química , Antibacterianos/farmacologia , Antibacterianos/química , Staphylococcus aureus , Impressão Tridimensional , Materiais Revestidos Biocompatíveis/química , BiofilmesRESUMO
Changes in the properties of resin-based polymers exposed to the oral environment can emerge when chlorhexidine (CHX) is incorporated to develop bioactive systems for treating denture stomatitis. Three reline resins loaded with CHX were prepared: 2.5 wt% in Kooliner (K), 5 wt% in Ufi Gel Hard (UFI), and Probase Cold (PC). A total of 60 specimens were submitted to physical aging (1000 cycles of thermal fluctuations, 5-55 °C) or chemical aging (28 days of pH fluctuations in artificial saliva, 6 h at pH = 3, 18 h at pH = 7). Knoop microhardness (30 s, 98 mN), 3-point flexural strength (5 mm/min), and surface energy were tested. Color changes (ΔE) were determined using the CIELab system. Data were submitted to non-parametric tests (α = 0.05). After aging, bioactive K and UFI specimens were not different from the controls (resins without CHX) in mechanical and surface properties. Thermally aged CHX-loaded PC specimens showed decreased microhardness and flexural strength but not under adequate levels for function. The color change was observed in all CHX-loaded specimens that underwent chemical aging. The long-term use of CHX bioactive systems based on reline resins generally does not impair removable dentures' proper mechanical and aesthetic functions.
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Chitosan is an interesting polymer to produce hydrogels suitable for the 3D printing of customized drug delivery systems. This study aimed at the achievement of chitosan-based scaffolds suitable for the incorporation of active components in the matrix or loaded into the pores. Several scaffolds were printed using different chitosan-based hydrogels. To understand which parameters would have a greater impact on printability, an optimization study was conducted. The scaffolds with the highest printability were obtained with a chitosan hydrogel at 2.5 wt%, a flow speed of 0.15 mm/s and a layer height of 0.41 mm. To improve the chitosan hydrogel printability, starch was added, and a design of experiments with three factors and two responses was carried out to find out the optimal starch supplementation. It was possible to conclude that the addition of starch (13 wt%) to the chitosan hydrogel improved the structural characteristics of the chitosan-based scaffolds. These scaffolds showed potential to be tested in the future as drug-delivery systems.
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Quitosana , Drogas Desenhadas , Alicerces Teciduais/química , Quitosana/química , Hidrogéis/química , Sistemas de Liberação de Medicamentos , Impressão Tridimensional , Engenharia TecidualRESUMO
The bone tissue can regenerate itself completely and continuously; however, large-scale bone defects may overpower this self-regenerative process. Furthermore, the aging population, the increment in obesity incidence, and the sedentary lifestyles are serious risk factors for bone diseases' development which are associated with the self-regenerative process's failure, high morbidity, and mortality rates. Thus, there is an ever-growing need for strategic approaches targeting bone replacement, its remodelling, and its regeneration. Bone scaffolds have successfully been used as synthetic bone grafts for many years, yet recent bone tissue engineering strategies attempt to explore their multifunctionality by investigating them as drug delivery systems. Bone diseases' treatments can be substantially difficult due to the avascular nature of the surrounding cartilage; thus, targeted drug delivery to the bone can be advantageous: it provides local high drug concentrations and minimizes adverse effects while securing a space for new, healthy tissue growth. Despite the promising scientific progress, studies underlining bone scaffolds' use as local drug delivery systems are not abundant. Hence, this work reviews bone scaffolds' therapeutic interest for local drug delivery in five distinct bone disorders-osteomyelitis, osteoporosis, osteoarthritis, osteosarcoma, and cancer bone metastasis. Additionally, it presents the challenges of this possible therapeutic approach and its future perspectives. Albeit bone scaffolds present therapeutic benefits by acting as drug delivery systems, further pre-clinical and clinical assessments are needed to strengthen their understanding and enable research evidence translation into clinical practice. The mismatch between scientific evolution and regulatory frameworks remains one of the major future challenges.
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Doenças Ósseas , Humanos , Idoso , Doenças Ósseas/tratamento farmacológico , Sistemas de Liberação de MedicamentosRESUMO
The high recurrence rate of common denture stomatitis after antifungal treatment is still concerning. This condition is caused by low patient compliance and incomplete local elimination of the main etiological factor - Candida albicans, often associated with other microorganisms, such as Streptococcus species. Impregnating denture materials with antimicrobials for local delivery is a strategy that can overcome the side effects and improve the efficacy of conventional treatments (topical and/or systemic). In this work, we describe the development of three hard autopolymerizing reline acrylic resins (Kooliner, Ufi Gel Hard, and Probase Cold) loaded with different percentages of chlorhexidine (CHX). The novel formulations were characterized based on their antimicrobial activity, mechanical, morphological and surface properties, in-vitro drug release profiles, and cytotoxicity. The addition of CHX in all resins did not change their chemical and mechanical structure. Among all the tested formulations, Probase Cold loaded with 5 wt% CHX showed the most promising results in terms of antimicrobial activity and lack of serious detrimental mechanical, morphological, surface, and biological properties.
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Anti-Infecciosos , Clorexidina , Humanos , Teste de Materiais , Resinas Acrílicas/químicaRESUMO
Packaging plays an important role in food quality and safety, especially regarding waste and spoilage reduction. The main drawback is that the packaging industry is among the ones that is highly dependent on plastic usage. New alternatives to conventional plastic packaging such as biopolymers-based type are mandatory. Examples are cellulose films and its derivatives. These are among the most used options in the food packaging due to their unique characteristics, such as biocompatibility, environmental sustainability, low price, mechanical properties, and biodegradability. Emerging concepts such as active and intelligent packaging provides new solutions for an extending shelf-life, and it fights some limitations of cellulose films and improves the properties of the packaging. This article reviews the available cellulose polymers and derivatives that are used as sustainable alternatives for food packaging regarding their properties, characteristics, and functionalization towards active properties enhancement. In this way, several types of films that are prepared with cellulose and their derivatives, incorporating antimicrobial and antioxidant compounds, are herein described, and discussed.
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Titanium dioxide nanoparticles (TiO2-NPs) are widely used, and humans are exposed through food (E171), cosmetics (e.g., toothpaste), and pharmaceuticals. The oral and gastrointestinal (GIT) tract are the first contact sites, but it may be systemically distributed. However, a robust adverse outcome pathway (AOP) has not been developed upon GIT exposure to TiO2-NPs. The aim of this review was to provide an integrative analysis of the published data on cellular and molecular mechanisms triggered after the ingestion of TiO2-NPs, proposing plausible AOPs that may drive policy decisions. A systematic review according to Prisma Methodology was performed in three databases of peer-reviewed literature: Pubmed, Scopus, and Web of Science. A total of 787 records were identified, screened in title/abstract, being 185 used for data extraction. The main endpoints identified were oxidative stress, cytotoxicity/apoptosis/cell death, inflammation, cellular and systemic uptake, genotoxicity, and carcinogenicity. From the results, AOPs were proposed where colorectal cancer, liver injury, reproductive toxicity, cardiac and kidney damage, as well as hematological effects stand out as possible adverse outcomes. The recent transgenerational studies also point to concerns with regard to population effects. Overall, the findings further support a limitation of the use of TiO2-NPs in food, announced by the European Food Safety Authority (EFSA).
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Silicone-based medical devices composed of polydimethylsiloxane (PDMS) are widely used all over the human body (e.g., urinary stents and catheters, central venous catheters stents) with extreme clinical success. Nevertheless, their abiotic surfaces, being prone to microorganism colonization, are often involved in infection occurrence. Improving PDMS antimicrobial properties by surface functionalization with biosurfactants to prevent related infections has been the goal of different works, but studies that mimic the clinical use of these novel surfaces are missing. This work aims at the biofunctional assessment of PDMS functionalized with rhamnolipids (RLs), using translational tests that more closely mimic the clinical microenvironment. Rhamnolipids were covalently bonded to PDMS, and the obtained surfaces were characterized by contact angle modification assessment, ATR-FTIR analysis and atomic force microscopy imaging. Moreover, a parallel flow chamber was used to assess the Staphylococcus aureus antibiofilm activity of the obtained surfaces under dynamic conditions, and an in vitro characterization with human dermal fibroblast cells in both direct and indirect characterization assays, along with an in vivo subcutaneous implantation assay in the translational rabbit model, was performed. A 1.2 log reduction in S. aureus biofilm was observed after 24 h under flow dynamic conditions. Additionally, functionalized PDMS lessened cell adhesion upon direct contact, while supporting a cytocompatible profile, within an indirect assay. The adequacy of the biological response was further validated upon in vivo subcutaneous tissue implantation. An important step was taken towards biofunctional assessment of RLs-functionalized PDMS, reinforcing their suitability for medical device usage and infection prevention.
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Background/aims: Combination products are therapeutic and/or diagnostic products that can combine drugs and medical devices and which increasing complexity has raised new regulatory framework challenges. To reach the market, a combination product must be classified based on the principal mode of action (PMOA). However, research and technological progress has been leading to the development of novel combination products with no clearly defined PMOA, emphasizing the lack of a systematization process, thus challenging the correct classification of these products. To illustrate the regulatory challenge, two case studies are discussed: innovative combination products with PMOA that can change due to an external stimulus, specifically custom-made 3D-printed scaffolds with incorporated medicinal substances. Methods: Data was collected through computational search engines, regulatory agencies and equally relevant associations. The analysis of the data resulted on this state-of-the-art review, a description of the decision-making process by the regulatory authorities, and case studies analysis that culminated in the proposal of a decision-tree scheme. Findings: Current regulations do not fully address complex combination products namely personalized 3D-printed scaffolds. Two merged regulatory approaches are suggested along with the schematization of the rational assisted by a decision-tree tool. Conclusion: Combination products have become increasingly sophisticated, which has furthered the need to develop multidisciplinary collaborations within the health sector to adapt to these innovative healthcare solutions as well as with regulators to overcome the challenges posed for their classification.
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Implant-related infections, mainly caused by Staphylococcus aureus, are a major health concern. Treatment is challenging due to multi-resistant strains and the ability of S. aureus to adhere and form biofilms on bone and implant surfaces. The present work involved the preparation and evaluation of a novel dual polymeric film coating on stainless steel. Chitosan and polycaprolactone (PCL) multilayers, loaded with poly(methyl methacrylate) (PMMA) microspheres encapsulating vancomycin or daptomycin, produced by the dip-coating technique, allowed local antibiotic-controlled delivery for the treatment of implant-related infections. Enhanced adhesion of the film to the metal substrate surface was achieved by mechanical abrasion of its surface. Studies have shown that for both drugs the release occurs by diffusion, but the release profile depends on the type of drug (daptomycin or vancomycin), the pH of the solution, and whether the drug is freestanding (directly incorporated into the films) or encapsulated in PMMA microspheres. Daptomycin freestanding films reached 90% release after 1 day at pH 7.4 and 4 days at pH 5.5. In comparison, films with daptomycin encapsulated microspheres reached 90% release after 2 h at pH 5.5 and 2 days at pH 7.4. Vancomycin encapsulated and freestanding films showed a similar behavior reaching 90% release after 20 h of release at pH 5.5 and 2 and 3 days, respectively, at pH 7.4. Furthermore, daptomycin-loaded films showed activity (assessed by agar diffusion assays) against sensitive (ATCC 25923) and clinically isolated (MRSA) S. aureus strains.
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In clinic there is a demand to solve the drawback of medical devices multispecies related infections. Consequently, different biomaterial surfaces, such as vascular catheters, urgently need improvement regarding their antifouling/antimicrobial properties. In this work, we covalently functionalized medical grade polydimethylsiloxane (PDMS) with antimicrobial rhamnolipids to investigate the biomaterial surface activity towards mono and dual species biofilms. Preparation of surfaces with "piranha" oxidation, followed by APTES bonding and carbodiimide reaction with rhamnolipids effectively bonded these compounds to PDMS surface as confirmed by FTIR-ATR and XPS analysis. Generated surfaces were active towards S. aureus biofilm formation showing a 4.2 log reduction while with S. epidermidis and C. albicans biofilms a reduction of 1.2 and 1.0 log reduction, respectively, was observed. Regarding dual-species testing the higher biofilm log reduction observed was 1.9. Additionally, biocompatibility was assessed by cytocompatibility towards human fibroblastic cells, low platelet activation and absence of vascular irritation. Our work not only sheds light on using covalently bonded rhamnolipids towards dual species biofilms but also highlights the biocompatibility of the obtained PDMS surfaces.
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Anti-Infecciosos , Infecções Relacionadas a Cateter , Antibacterianos , Materiais Biocompatíveis/farmacologia , Biofilmes , Candida albicans , Infecções Relacionadas a Cateter/tratamento farmacológico , Infecções Relacionadas a Cateter/prevenção & controle , Dimetilpolisiloxanos/farmacologia , Glicolipídeos , Humanos , Staphylococcus aureus/fisiologia , Staphylococcus epidermidisRESUMO
Different types of natural and synthetic polymeric nanocarriers are being tested for diverse biomedical applications ranging from drug/gene delivery vehicles to imaging probes. The development of such innovative nanoparticulate systems (NPs) should include in the very beginning of their conception a comprehensive evaluation of the nano-bio interactions. Specifically, intrinsic physicochemical properties as size, surface charge and shape may have an impact on cellular uptake, intracellular trafficking, exocytosis and cyto- or genocompatibility. Those properties can be tuned for effectiveness purposes such as targeting intracellular organelles, but at the same time inducing unforeseen adverse nanotoxicological effects. Further, those properties may change due to the adsorption of biological components (e.g. proteins) with a tremendous impact on the cellular response. The evaluation of these NPs is highly challenging and has produced some controversial results. Future research work should focus on the standardization of analytical or computational methodologies, aiming the identification of toxicity trends and the generation of a useful meta-analysis database on polymeric nanocarriers.This chapter covers all the aforementioned aspects, emphasizing the importance of the in vitro cellular studies in the first stages of polymeric nanocarriers development.
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Nanopartículas , Nanoestruturas , Transporte Biológico , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Nanoestruturas/química , Nanoestruturas/toxicidade , Organelas/metabolismo , Polímeros/química , Proteínas/metabolismoRESUMO
Controlling bacterial biofilm formation on silicone-based bloodstream catheters is of great concern to prevent related-infections. In this study, rhamnolipids (RLs), glycolipid biosurfactants, specifically a RLs mixture and the purified di-RL (RhaRhaC10:0C10:0) were covalently bonded to silicone with the intention of reaching long-lasting antibiofilm surfaces. RLs mixture and di-RL were identified by an UHPLC-MS method that also allowed the confirmation of compound isolation by automated flash chromatography. Silicone surfaces underwent air-plasma treatment, inducing reactive oxygen radicals able to promote the RLs grafting that was confirmed by contact angle, FTIR-ATR and AFM measurements. The antibiofilm activity towards different Gram positive strains was evaluated by colony forming units (CFU) count and confocal laser microscopy. In addition, protein adsorption and biocompatibility were also investigated. RLs were successfully grafted onto silicone and RLs mixture and RhaRhaC10C10:0 functionalized specimens reduced the biofilm formation over 2.3 log units against methicillin sensitive Staphylococcus aureus. Additionally, a decrease of 1 log unit was observed against methicillin resistant S. aureus and S. epidermidis. Functionalized samples showed cytocompatibility towards human dermal fibroblasts, hemocompatibility and no vascular irritation potential. The results mentioned above revealed a synergy between the antimicrobial and the anti-adhesive properties of RLs, making these compounds good candidates for the improvement of the medical devices antibiofilm properties.
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Anti-Infecciosos , Staphylococcus aureus Resistente à Meticilina , Antibacterianos/farmacologia , Biofilmes , Catéteres/microbiologia , Dimetilpolisiloxanos , Glicolipídeos/farmacologia , Humanos , Staphylococcus epidermidisRESUMO
Cellulose micro/nanomaterials (CMNM), comprising cellulose microfibrils (CMF), nanofibrils (CNF), and nanocrystals (CNC), are being recognized as promising bio-nanomaterials due to their natural and renewable source, attractive properties, and potential for applications with industrial and economical value. Thus, it is crucial to investigate their potential toxicity before starting their production at a larger scale. The present study aimed at evaluating the cell internalization and in vitro cytotoxicity and genotoxicity of CMNM as compared to two multi-walled carbon nanotubes (MWCNT), NM-401 and NM-402, in A549 cells. The exposure to all studied NM, with the exception of CNC, resulted in evident cellular uptake, as analyzed by transmission electron microscopy. However, none of the CMNM induced cytotoxic effects, in contrast to the cytotoxicity observed for the MWCNT. Furthermore, no genotoxicity was observed for CNF, CNC, and NM-402 (cytokinesis-block micronucleus assay), while CMF and NM-401 were able to significantly raise micronucleus frequency. Only NM-402 was able to induce ROS formation, although it did not induce micronuclei. Thus, it is unlikely that the observed CMF and NM-401 genotoxicity is mediated by oxidative DNA damage. More studies targeting other genotoxicity endpoints and cellular and molecular events are underway to allow for a more comprehensive safety assessment of these nanocelluloses.
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Paraganglioma is a catecholamine-secreting tumor (CST) in extra-adrenal autonomic ganglia and a rare cause of hypertension during pregnancy. If not properly treated, it can lead to disastrous outcomes for both the mother and fetus. This report describes the successful anesthetic management of a paraganglioma diagnosed during pregnancy. A pregnant woman, with 32 weeks of gestational age, presented with severe paroxysmal hypertension, refractory to methyldopa and nifedipine at maximum dosages, headache, sweating, and palpitations. Diagnostic work-up was positive for elevated serum and urinary normetanephrines, and magnetic resonance showed a solid nodule above the hilum of the right kidney, suggestive of paraganglioma. Optimal alpha-blockade was achieved with doxazosin, and given the advanced gestational age, tumor resection was postponed until after delivery. Cesarean delivery was scheduled at 34 weeks, under combined spinal-epidural anesthesia and continuous blood pressure monitoring. Antihypertensive drugs were prepared for immediate administration as needed. Intraoperative and postoperative periods went uneventfully for both the mother and newborn, both under intensive care observation for 24 h.
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The widespread use of titanium dioxide nanomaterials (TiO2 NMs) in food and consumer products such as toothpaste or food contact materials, suggests the relevance of human oral exposure to these nanomaterials (NMs) and raises the possibility of adverse effects in the gastrointestinal tract (GIT). We previously showed that the in vitro digestion of TiO2 NMs may increase their toxicity in intestinal cells. In this work, we analyzed the genotoxicity and the intracellular reactive oxygen species induction by physiologically relevant concentrations of three different TiO2 NMs (NM-102, NM-103 and NM-105) in Caco-2 and HT29-MTX-E12 intestinal cells, while considering the potential influence of the digestion process in the NMs' physiochemical characteristics. The results evidenced a DNA-damaging effect dependent on the NM, more relevant for the rutile/anatase NM-105, possibly due to its lower hydrodynamic size in the cells medium. In addition, the results of the micronucleus assay suggest effects on chromosomal integrity, an indicator of cancer risk, in the HT29-MTX-E12 cells, for all the tested TiO2 NMs, especially after the in vitro digestion. This work supports the evidence for concerns on the use of TiO2 NMs as a food additive, recently reported by EFSA, and for their use in applications in consumer products that may drive human exposure through ingestion.
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Intestinos/citologia , Nanoestruturas/efeitos adversos , Titânio/efeitos adversos , Células CACO-2 , Neoplasias do Colo , Dano ao DNA/efeitos dos fármacos , Células HT29 , Humanos , Peróxido de Hidrogênio , Testes para Micronúcleos , Nanoestruturas/química , Espécies Reativas de Oxigênio , Titânio/químicaRESUMO
Food packaging is the best way to protect food while it moves along the entire supply chain to the consumer. However, conventional food packaging poses some problems related to food wastage and excessive plastic production. Considering this, the aim of this work was to examine recent findings related to bio-based alternative food packaging films by means of conventional methodologies and additive manufacturing technologies, such as 3D printing (3D-P), with potential to replace conventional petroleum-based food packaging. Based on the findings, progress in the development of bio-based packaging films, biopolymer-based feedstocks for 3D-P, and innovative food packaging materials produced by this technology was identified. However, the lack of studies suggests that 3D-P has not been well-explored in this field. Nonetheless, it is probable that in the future this technology will be more widely employed in the food packaging field, which could lead to a reduction in plastic production as well as safer food consumption.