The bacterial lipopolysaccharide (LPS) is a highly toxic molecule derived from the outer membrane of gram‐negative bacteria. LPS endotoxin affects the lungs and is used as a model of acute pulmonary ...inflammation affecting the cellular morphology of the organ. Previously, gold nanoparticles (GNPs) have been shown to demonstrate anti‐inflammatory and antioxidative activity in muscle and epithelial injury models. The objective of this study was to investigate the effect of the intraperitoneal treatment using GNPs on the inflammatory response and pulmonary oxidative stress induced by LPS. Wistar rats were divided into four groups (N = 10): Sham; Sham + GNPs 2.5 mg/kg; LPS; and LPS + GNPs 2.5 mg/kg. Treatment with LPS upregulated the levels of markers of cellular and hepatic damage (CK, LDH, AST, and alanine aminotransferase); however, the group treated with only GNPs exhibited no toxicity. Treatment with GNPs reversed LPS‐induced changes with respect to total peritoneal leukocyte count and the pulmonary levels of pro‐inflammatory cytokines (IFN‐γ and IL‐6). Histological analysis revealed that treatment with GNPs reversed the increase in alveolar septum thickness due to LPS‐induced fibrosis. In addition, treatment with GNPs decreased production of oxidants (nitrite and DCFH), reduced oxidative damage (carbonyl and sulfhydryl), and downregulated activities of superoxide dismutase and catalase. Treatment with GNPs did not showed toxicity; however, it exhibited anti‐inflammatory and antioxidative activity that reversed morphological alterations induced by LPS.
Abstract It is generally believed that NMDA receptor antagonism accounts for most of the anesthetic and analgesic effects of ketamine, however, it interacts at multiple sites in the central nervous ...system, including NMDA and non-NMDA glutamate receptors, nicotinic and muscarinic cholinergic receptors, and adrenergic and opioid receptors. Interestingly, it was shown that at supraspinal sites, ketamine interacts with the μ-opioid system and causes supraspinal antinociception. In this study, we investigated the involvement of endogenous opioids in ketamine-induced central antinociception. The nociceptive threshold for thermal stimulation was measured in Swiss mice using the tail-flick test. The drugs were administered via the intracerebroventricular route. Our results demonstrated that the opioid receptor antagonist naloxone, the μ-opioid receptor antagonist clocinnamox and the δ-opioid receptor antagonist naltrindole, but not the κ-opioid receptor antagonist nor - binaltorphimine, antagonized ketamine-induced central antinociception in a dose-dependent manner. Additionally, the administration of the aminopeptidase inhibitor bestatin significantly enhanced low-dose ketamine-induced central antinociception. These data provide evidence for the involvement of endogenous opioids and μ- and δ-opioid receptors in ketamine-induced central antinociception. In contrast, κ-opioid receptors not appear to be involved in this effect.
Mucociliary clearance is a crucial mechanism that supports the elimination of inhaled particles, bacteria, pollution, and hazardous agents from the human airways, and it also limits the diffusion of ...aerosolized drugs into the airway epithelium. In spite of its relevance, few in vitro models sufficiently address the cumulative effect of the steric and interactive barrier function of mucus on the one hand, and the dynamic mucus transport imposed by ciliary mucus propulsion on the other hand. Here, ad hoc mucus models of physiological and pathological mucus are combined with magnetic artificial cilia to model mucociliary transport in both physiological and pathological states. The modular concept adopted in this study enables the development of mucociliary clearance models with high versatility since these can be easily modified to reproduce phenomena characteristic of healthy and diseased human airways while allowing to determine the effect of each parameter and/or structure separately on the overall mucociliary transport. These modular airway models can be available off‐the‐shelf because they are exclusively made of readily available materials, thus ensuring reproducibility across different laboratories.
Material‐based in vitro models of mucociliary clearance were developed by combining both steric and interactive barrier functions of the human mucus with the dynamic mucus transport generated by ciliary beating. By using a modular approach, ad hoc models of physiological and pathological mucus are combined with magnetic artificial cilia actuated externally to reproduce mucociliary clearance of physiological and cystic fibrosis airways. These versatile models enable the study of the individual contribution of each parameter and/or structure on the overall mucociliary transport.
Inhalation of harmful particles appears as a primary factor for the onset and establishment of chronic obstructive pulmonary disease (COPD). Cigarette smoke acutely promotes an exacerbated ...inflammatory response with oxidative stress induction with DNA damage. Administration of Gold Nanoparticles (GNPs) with 20 nm in different concentrations can revert damages caused by external aggravations. The effects of GNPs in a COPD process have not been observed until now. The objective of this work was to evaluate the therapeutic effects of intranasal administration of different doses of GNPs after acute exposure to industrial cigarette smoke. Thirty male Swiss mice were randomly divided into five groups: Sham; cigarette smoke (CS); CS + GNPs 2.5 mg/L; CS + GNPs 7.5 mg/L and CS + GNPs 22.5 mg/L. The animals were exposed to the commercial cigarette with filter in an acrylic inhalation chamber and treated with intranasal GNPs for five consecutive days. The results demonstrate that exposure to CS causes an increase in inflammatory cytokines, histological changes, oxidative and nitrosive damage in the lung, as well as increased damage to the DNA of liver cells, blood plasma and lung. Among the three doses of GNPs (2.5, 7.5, and 22.5 mg/L) used, the highest dose had better anti‐inflammatory effects. However, GNPs at a dose of 7.5 mg/L showed better efficacies in reducing ROS formation, alveolar diameter, and the number of inflammatory cells in histology, in addition to significantly reduced rate of DNA damage in lung cells without additional systemic genotoxicity already caused by cigarette smoke.
Engineered models have emerged as relevant in vitro tools to foresee the translational potential of new therapies from the bench to the bedside in a fast and cost-effective fashion. The principles ...applied to the development of tissue-engineered constructs bring the foundation concepts to engineer relevant in vitro models. Engineered models often face scepticism, because regularly these do not include the extreme complexity of nature, but rather a simplification of a phenomenon. While engineering in vitro models, a hypothesis is imposed towards which defined parameters are included to assess the degree of similarity between the in vitro model and the native phenomenon, keeping in mind their intrinsic limitations. The development of in vitro models has been highly supported and disseminated by different regulatory agencies. This review aims at defining and exploring the multifaceted potential of tangible, not theoretical, models within the biomedical field to represent physiological tissues and organ-related phenomena.
The intrinsic heterogeneity of bacterial niches should be retained in in vitro cultures to represent the complex microbial ecology. As a case study, mucin‐containing hydrogels ‐CF‐Mu3Gel ‐ are ...generated by diffusion‐induced gelation, bioinspired on cystic fibrosis (CF) mucus, and a microbial niche challenging current therapeutic strategies. At breathing frequency, CF‐Mu3Gel exhibits a G′ and G″ equal to 24 and 3.2 Pa, respectively. Notably, CF‐Mu3Gel exhibits structural gradients with a gradual reduction of oxygen tension across its thickness (280–194 µmol L−1). Over the culture period, a steep decline in oxygen concentration occurs just a few millimeters below the air–mucus interface in CF‐Mu3Gel, similar to those of CF airway mucus. Importantly, the distinctive features of CF‐Mu3Gel significantly influence bacterial organization and antimicrobial tolerance in mono‐ and co‐cultures of Staphylococcus aureus and Pseudomonas aeruginosa that standard cultures are unable to emulate. The antimicrobial susceptibility determined in CF‐Mu3Gel corroborates the mismatch on the efficacy of antimicrobial treatment between planktonically cultured bacteria and those in patients. With this example‐based research, new light is shed on the understanding of how the substrate influences microbial behavior, paving the way for improved fundamental microbiology studies and more effective drug testing and development.
The inherent heterogeneity is a feature of multi‐bacterial habitats. With a mucin‐based 3D hydrogel, the influence of structural properties on the organization and antimicrobial tolerance of co‐cultured bacteria is demonstrated. This platform provides valuable insights to study microbial behavior and drug testing in complex environments that reproduce the microbial environment of different body districts.
Despite being a key concept in rehabilitation, controlling weight-bearing load while walking, following lower limb injury is very hard to achieve. Walking in water provides an opportunity to ...prescribe load for people who have pain, weakness or weight bearing restrictions related to stages of healing. The aim of this experimental study was to evaluate and validate regression models for predicting ground reaction forces while walking in water. One hundred and thirty seven individuals (24±5 years, 1.71±0.08 m and 68.7±12.5 kg) were randomly assigned to a regression group (n = 113) and a validation group (n = 24). Trials were performed at a randomly assigned water depth (0.75 to 1.35 m), and at a self-selected speed. Independent variables were: immersion ratio, velocity, body mass, and waist, thigh and leg circumferences. Stepwise regression was used for the prediction of ground reaction forces and validation included agreement and consistency statistical analyses. Data from a force plate were compared with predicted data from the created model in the validation group. Body mass, immersion ratio, and velocity independently predicted 95% of the vertical and resultant ground reaction force variability, while, together, velocity and thigh circumference explained 81% of antero-posterior ground reaction force variability. When tested against the data measured in validation samples, the models output resulted in statistically similar values, intraclass correlation coefficients ranging from 0.88 to 0.90 and standard errors of measurement, 11.8 to 42.3 N. The models introduced in this study showed good predictive performance in our evaluation procedures and may be considered valid in the prediction of vertical, antero-posterior and resultant ground reaction forces while walking in water. All predictive variables can be easily determined in clinical practice. Future studies should focus on the validation of these models in specific populations.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Tissue-engineered constructs made of biotechnology-derived materials have been preferred due to their chemical and physical composition, which offers both high versatility and a support to enclose/ ...incorporate relevant signaling molecules and/or genes known to therapeutically induce tissue repair. Herein, a critical overview of the impact of different biotechnology-derived materials, scaffolds, and recombinant signaling molecules over the behavior of cells, another element of tissue engineered constructs, as well its regulatory role in tissue regeneration and disease progression is given. Additionally, these tissue-engineered constructs evolved to three-dimensional (3D) tissue-like models that, as an advancement of two-dimensional standard culture methods, are expected to be a valuable tool in the field of drug discovery and pharmaceutical research. Despite the improved design and conception of current proposed 3D tissue-like models, advanced control systems to enable and accelerate streamlining and automation of the numerous labor-intensive steps intrinsic to the development of tissue-engineered constructs are still to be achieved. In this sense, this review intends to present the biotechnology- derived materials that are being explored in the field of tissue engineering to generate 3D tissue-analogues and briefly highlight their foremost breakthroughs in tissue regeneration and drug discovery. It also aims to reinforce that the crosstalk between tissue engineering and pharmaceutical biotechnology has been fostering the outcomes of tissue engineering approaches through the use of biotechnology-derived signaling molecules. Gene delivery/therapy is also discussed as a forefront area that represents another cross point between tissue engineering and pharmaceutical biotechnology, in which nucleic acids can be considered a "super pharmaceutical" to drive biological responses, including tissue regeneration.
Cryotherapy is an affordable and popular treatment of soft tissue injuries, which can reduce inflammation and pain. Studies have specifically addressed young adults and athletes, and these findings ...have been extended to older adults in clinical practice. Aging is associated with changes in the skin, including collagen degradation, decreased fat layer thickness, and reduced blood flow, which can alter the skin response to stress. Because of age-related changes, there are concerns about the direct use of ice on the skin of older individuals. Skin injuries were also observed after cryotherapy. This study aimed to assess the most effective and safe cryotherapy for superficial skin cooling among older women.
Eighteen older women were enrolled in this blinded, randomized, crossover, clinical trial. The mean values (SD) of their age, height, and weight were 70.0 years (6.0), 156.0 cm (9.1), and 72.8 kg (19.5), respectively. The participants underwent cryotherapy using bagged ice, bagged ice plus a wet towel, or gel pack for 20 minutes. The surface temperature of the skin was measured at the end of a 20-minute cryotherapy session using an infrared thermometer. Repeated-measures analysis of variance was conducted to analyze the effect of cryotherapy modalities and time, as well as the interaction between these 2 factors. The secondary outcome was the presence of cryotherapy-induced lesions.
Cryotherapy modalities had significant effects on superficial skin temperature (P = .001). Time points after application also had an effect (P = .0001), and no interaction was observed between cryotherapy modalities and time points (P = .051). Bonferroni post hoc evaluation showed that bagged ice (P = .008) and gel (P = .007) were more effective in decreasing the superficial skin temperature than bagged ice plus wet towel. No difference was observed between bagged ice and gel (P = .32). Three of the 18 patients experienced adverse effects with the gel pack.
This study of older women found that ice and gel cooled the skin more effectively than ice wrapped in towels. However, the gel pack had some adverse effects. Therefore, bagged ice is recommended for cryotherapy in older women.
O objetivo deste artigo é analisar o uso das mídias sociais digitais pelos vereadores da Câmara Municipal de Belo Horizonte da 19ª Legislatura (2021-2024). Para tanto, aplicou-se, presencialmente, ...aos assessores dos gabinetes dos vereadores um questionário que permitiu identificar a estrutura da comunicação nos gabinetes; a presença e o objetivo do uso das mídias sociais, focando nas estratégias pensadas para o Facebook e o WhatsApp. Do total de 41 gabinetes, 39 participaram da pesquisa. As conclusões indicam que a maioria dos gabinetes apresenta assessores com competências específicas na comunicação, sugerindo uma profissionalização dos gabinetes na área e uma preocupação com a manutenção de uma imagem pública positiva do vereador. Sobre os objetivos do uso das redes, destaca-se a divulgação das ações do mandato, especialmente as que reforçam a conexão entre parlamentar e sua base eleitoral. Importante mencionar que as redes sociais são empregadas para receber demandas dos cidadãos.
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