Angiotensin-(1-7) decreases inflammation and lung damage caused by betacoronavirus infection in mice.

OBJECTIVE: Pro-resolving molecules, including the peptide Angiotensin-(1-7) [Ang-(1-7)], have potential adjunctive therapy for infections. Here we evaluate the actions of Ang-(1-7) in betacoronavirus infection in mice. METHODS: C57BL/6J mice were infected intranasally with the murine betacoronavirus MHV-3 and K18-hACE2 mice were infected with SARS-CoV-2. Mice were treated with Ang-(1-7) (30 µg/mouse, i.p.) at 24-, 36-, and 48-hours post-infection (hpi) or at 24, 36, 48, 72, and 96 h. For lethality evaluation, one additional dose of Ang-(1-7) was given at 120 hpi. At 3- and 5-days post- infection (dpi) blood cells, inflammatory mediators, viral loads, and lung histopathology were evaluated. RESULTS: Ang-(1-7) rescued lymphopenia in MHV-infected mice, and decreased airways leukocyte infiltration and lung damage at 3- and 5-dpi. The levels of pro-inflammatory cytokines and virus titers in lung and plasma were decreased by Ang-(1-7) during MHV infection. Ang-(1-7) improved lung function and increased survival rates in MHV-infected mice. Notably, Ang-(1-7) treatment during SARS-CoV-2 infection restored blood lymphocytes to baseline, decreased weight loss, virus titters and levels of inflammatory cytokines, resulting in improvement of pulmonary damage, clinical scores and lethality rates. CONCLUSION: Ang-(1-7) protected mice from lung damage and death during betacoronavirus infections by modulating inflammation, hematological parameters and enhancing viral clearance.

The angiotensin-(1-7)/MasR axis improves pneumonia caused by Pseudomonas aeruginosa: Extending the therapeutic window for antibiotic therapy.

Pseudomonas aeruginosa is a frequent cause of antimicrobial-resistant hospital-acquired pneumonia, especially in critically ill patients. Inflammation triggered by P. aeruginosa infection is necessary for bacterial clearance but must be spatially and temporally regulated to prevent further tissue damage and bacterial dissemination. Emerging data have shed light on the pro-resolving actions of angiotensin-(1-7) [Ang-(1-7)] signaling through the G protein-coupled receptor Mas (MasR) during infections. Herein, we investigated the role of the Ang-(1-7)/Mas axis in pneumonia caused by P. aeruginosa by using genetic and pharmacological approach and found that Mas receptor-deficient animals developed a more severe form of pneumonia showing higher neutrophilic infiltration into the airways, bacterial load, cytokines, and chemokines production and more severe pulmonary damage. Conversely, treatment of pseudomonas-infected mice with Ang-(1-7) was able to decrease neutrophilic infiltration in airways and lungs, local and systemic levels of pro-inflammatory cytokines and chemokines, and increase the efferocytosis rates, mitigating lung damage/dysfunction caused by infection. Notably, the therapeutic association of Ang-(1-7) with antibiotics improved the survival rates of mice subjected to lethal inoculum of P. aeruginosa, extending the therapeutic window for imipenem. Mechanistically, Ang-(1-7) increased phagocytosis of bacteria by neutrophils and macrophages to accelerate pathogen clearance. Altogether, harnessing the Ang-(1-7) pathway during infection is a potential strategy for the development of host-directed therapies to promote mechanisms of resistance and resilience to pneumonia.

Neurogenic Background for Emotional Stress-Associated Hypertension.

PURPOSE OF REVIEW: The response to natural stressors involves both cardiac stimulation and vascular changes, primarily triggered by increases in sympathetic activity. These effects lead to immediate flow redistribution that provides metabolic support to priority target organs combined with other key physiological responses and cognitive strategies, against stressor challenges. This extremely well-orchestrated response that was developed over millions of years of evolution is presently being challenged, over a short period of time. In this short review, we discuss the neurogenic background for the origin of emotional stress-induced hypertension, focusing on sympathetic pathways from related findings in humans and animals. RECENT FINDINGS: The urban environment offers a variety of psychological stressors. Real or anticipatory, emotional stressors may increase baseline sympathetic activity. From routine day-to-day traffic stress to job-related anxiety, chronic or abnormal increases in sympathetic activity caused by emotional stressors can lead to cardiovascular events, including cardiac arrhythmias, increases in blood pressure and even sudden death. Among the various alterations proposed, chronic stress could modify neuroglial circuits or compromise antioxidant systems that may alter the responsiveness of neurons to stressful stimuli. These phenomena lead to increases in sympathetic activity, hypertension and consequent cardiovascular diseases. The link between anxiety, emotional stress, and hypertension may result from an altered neuronal firing rate in central pathways controlling sympathetic activity. The participation of neuroglial and oxidative mechanisms in altered neuronal function is primarily involved in enhanced sympathetic outflow. The significance of the insular cortex-dorsomedial hypothalamic pathway in the evolution of enhanced overall sympathetic outflow is discussed.

Assembly and use of a low-cost paracentesis simulator for the teaching of puncture and drainage of ascites.

OBJECTIVES: to describe the assembly of a low-cost paracentesis simulator and evaluate its effectiveness, acceptance and impact on the learning of medical students. METHODOLOGY: a paracentesis simulator was built using a mannequin and materials such as plastic bottles, Velcro, polyvinyl chloride sheets and silicone were used. A cross-sectional and experimental study was carried out with undergraduate medical students without previous practical experience with paracentesis, which sought to validate the model, evaluating its benefits in learning and obtaining technical skills. RESULTS: after using the simulator there was an increase of 82.4% in the level of confidence in performing paracentesis in a patient, with 98% of respondents considering that the model fulfilled the simulator function with satisfaction, and 100% considering it useful as a teaching tool. CONCLUSION: the built simulator was effective as an educational resource, serving as an alternative to high-cost commercial models, allowing for greater accessibility in the use of this tool in medical education.

Effect of processing methods on the chipping resistance of veneered zirconia.

OBJECTIVES: To evaluate the edge chipping resistance (ReA) and the fracture toughness (KC) of 3Y-TZP bilayers produced with the following materials/processing combinations: fluorapatite glass-ceramic applied on zirconia using the traditional layering and hot-pressing (press-on) techniques; feldspathic porcelain using rapid layer technology (RLT); and lithium disilicate glass-ceramic using CAD-on method. The influence of the cooling rate (slow and fast) was analyzed for layering and hot-pressing. METHODS: Bilayer bars (25x4x2 mm) were made following manufacturers' instructions. The edge chipping test was performed in an universal testing machine, using a coupled Vickers indenter. ReA was calculated dividing the critical load at fracture by the edge distance. Fracture toughness was calculated by a regression fit with a fixed slope of 1.5 correlating the critical chipping load regarding edge distance and also with indentation fracture (IF) method. Data were statistically analyzed using ANOVA and Tukey's test (α = 5%). RESULTS: ReA and KC was significantly higher for the CAD-on bilayers. RLT showed intermediate ReA means, and layering and hot-pressing techniques showed the lowest ReA values. For both processing methods there was no effect of the cooling protocol on the ReA and fracture toughness. CONCLUSIONS: There is a significant effect of the material/processing association on the edge chipping resistance and fracture toughness of the bilayers. There was no effect of the cooling protocol on the edge chipping resistance and fracture toughness for the specimens processed by both the layering and hot-pressing techniques.

Assembly and use of a low-cost paracentesis simulator for the teaching of puncture and drainage of ascites / Montagem e uso de simulador de paracentese de baixo custo - aplicabilidade no ensino de punção e drenagem de ascite

ABSTRACT Objectives: to describe the assembly of a low-cost paracentesis simulator and evaluate its effectiveness, acceptance and impact on the learning of medical students. Methodology: a paracentesis simulator was built using a mannequin and materials such as plastic bottles, Velcro, polyvinyl chloride sheets and silicone were used. A cross-sectional and experimental study was carried out with undergraduate medical students without previous practical experience with paracentesis, which sought to validate the model, evaluating its benefits in learning and obtaining technical skills. Results: after using the simulator there was an increase of 82.4% in the level of confidence in performing paracentesis in a patient, with 98% of respondents considering that the model fulfilled the simulator function with satisfaction, and 100% considering it useful as a teaching tool. Conclusion: the built simulator was effective as an educational resource, serving as an alternative to high-cost commercial models, allowing for greater accessibility in the use of this tool in medical education.

RESUMO Objetivos: descrever a montagem de simulador de paracentese de baixo custo e avaliar eficácia, aceitação e impacto no aprendizado de acadêmicos do curso de medicina. Método: um simulador de paracentese foi construído a partir de manequim e de materiais como garrafas plásticas, velcro, folhas de policloreto de vinila e silicone. Foi feito estudo transversal com estudantes da graduação do curso de medicina sem experiência real prévia com paracentese, que buscou validar o modelo, por meio da análise de benefícios no aprendizado e na obtenção de habilidades técnicas. Resultados: após o uso do simulador, observou-se aumento de 82,4% no nível de segurança na realização da paracentese em paciente, 98% dos pesquisados consideraram que o uso do modelo cumpriu com satisfação a função de simulador e 100% definiram-no útil como ferramenta de ensino. Conclusão: a montagem do simulador mostrou-se factível e eficaz como recurso educacional. Serviu como alternativa aos modelos comerciais de alto custo e permitiu maior acessibilidade do uso dessa ferramenta na educação médica.

Moderate-intensity exercise and renin angiotensin system blockade improve the renovascular hypertension (2K1C)-induced gastric dysmotility in rats.

Actually, arterial hypertension is a major public health concern, which involves the renin angiotensin aldosterone system (RAS), via activation of the angiotensin receptors AT1 and AT2 of the cardiovascular system. Although angiotensin is an important stimulant of the gut permeability to sodium and water, little is known about the effects of arterial hypertension on gut motor behavior. Thus, we evaluated in rats the effect of hypertension induced by two-kidney one-clip (2K1C) model on the gastric motility, as well as the influence of exercise and RAS blockers treatment in such phenomenon. One week after surgery the rats were treated with Aliskiren (50 mg·kg-1, p.o.), Captopril (50 mg·kg-1, p.o.) or Losartan (10 mg·kg-1, p.o). Other group of rats was submitted to swimming with 5% body weight overload. After 4 weeks of physical training or pharmacological treatment, we assessed the gastric retention in all groups (GR) of a liquid test meal, the mean arterial pressure (MAP), the heart rate (HR) and the HR variation (HRV) as well as the in vitro contractility of gastric fundus. Renovascular hypertension increased (p < 0.05) the GR, MAP and HR, a phenomenon prevented by pretreatment with RAS blockers or exercise. The two kidney one-clip Hypertension (2K1C) decreased (p < 0.05) the gastric fundus responsiveness, a phenomenon also prevented by exercise. It conclusion, renovascular hypertension delays the gastric emptying of liquids, a phenomenon involving the activation of RAS, where exercise or blockade with aliskiren, captopril and losartan prevent gastric dysmotility.

Dental ceramics: a review of new materials and processing methods.

The evolution of computerized systems for the production of dental restorations associated to the development of novel microstructures for ceramic materials has caused an important change in the clinical workflow for dentists and technicians, as well as in the treatment options offered to patients. New microstructures have also been developed by the industry in order to offer ceramic and composite materials with optimized properties, i.e., good mechanical properties, appropriate wear behavior and acceptable aesthetic characteristics. The objective of this literature review is to discuss the main advantages and disadvantages of the new ceramic systems and processing methods. The manuscript is divided in five parts: I) monolithic zirconia restorations; II) multilayered dental prostheses; III) new glass-ceramics; IV) polymer infiltrated ceramics; and V) novel processing technologies. Dental ceramics and processing technologies have evolved significantly in the past ten years, with most of the evolution being related to new microstructures and CAD-CAM methods. In addition, a trend towards the use of monolithic restorations has changed the way clinicians produce all-ceramic dental prostheses, since the more aesthetic multilayered restorations unfortunately are more prone to chipping or delamination. Composite materials processed via CAD-CAM have become an interesting option, as they have intermediate properties between ceramics and polymers and are more easily milled and polished.

Dental ceramics: a review of new materials and processing methods

Abstract The evolution of computerized systems for the production of dental restorations associated to the development of novel microstructures for ceramic materials has caused an important change in the clinical workflow for dentists and technicians, as well as in the treatment options offered to patients. New microstructures have also been developed by the industry in order to offer ceramic and composite materials with optimized properties, i.e., good mechanical properties, appropriate wear behavior and acceptable aesthetic characteristics. The objective of this literature review is to discuss the main advantages and disadvantages of the new ceramic systems and processing methods. The manuscript is divided in five parts: I) monolithic zirconia restorations; II) multilayered dental prostheses; III) new glass-ceramics; IV) polymer infiltrated ceramics; and V) novel processing technologies. Dental ceramics and processing technologies have evolved significantly in the past ten years, with most of the evolution being related to new microstructures and CAD-CAM methods. In addition, a trend towards the use of monolithic restorations has changed the way clinicians produce all-ceramic dental prostheses, since the more aesthetic multilayered restorations unfortunately are more prone to chipping or delamination. Composite materials processed via CAD-CAM have become an interesting option, as they have intermediate properties between ceramics and polymers and are more easily milled and polished.

Synthesis and characterization of silver phosphate/calcium phosphate mixed particles capable of silver nanoparticle formation by photoreduction.

Silver phosphate is a semi-conductor sensitive to UV-Vis radiation (<530nm). Exposure to radiation removes electrons from the oxygen valence shell, which are scavenged by silver cations (Ag+), forming metallic silver (Ag0) nanoparticles. The possibility of silver nanoparticle formation in situ by a photoreduction process was the basis for the application of mixed calcium phosphate/silver phosphate particles as remineralizing and antibacterial fillers in resin-based dental materials. Mixed phosphate particles were synthesized, characterized and added to a dimethacrylate resin in 20% or 30% mass fractions to investigate their efficacy as ion-releasing fillers for dental remineralization and antibacterial activity. The formation of metallic silver nanoparticles after exposure to visible radiation from a dental curing unit (peak emission: 470nm) was demonstrated by particle X-ray diffraction and scanning electron microscopy analysis of the composite fractured surface. Calcium and phosphate release from materials containing the mixed particles were similar to those containing pure CaP particles, whereas Streptococcus mutans colonies were reduced by three orders of magnitude in relation to the control, which can be attributed to silver release. As expected, the optical properties of the materials containing mixed phosphate particles were compromised by the presence of silver. Nevertheless, materials containing mixed phosphate particles presented higher fracture strength and elastic modulus than those with pure CaP particles.

Influence of Resin Cements on Color Stability of Different Ceramic Systems.

The purpose of this study was to evaluate color stability of two dental ceramics cemented with two resin cements, assessing the color difference (ΔE00) by the measurement of L*, a*, b*, c* and h* of transmittance. The combination of two ceramic system (feldspathic and lithium disilicate) and two resin cements - color A3 (RelyX ARC and Variolink II) resulted in 4 groups (n=5). Ten disks-shaped specimens were fabricated for each ceramic system (10x1.5 mm), etched with hydrofluoric acid (10%) and silanized prior to cementation. The color analysis was performed 24 h after cementation of the samples and after 6 months of storage in relative humidity by means of spectrophotometry. The ΔE00 values were analyzed statistically by two-way ANOVA followed by the Tukey test (p<0.05). One-way ANOVA were calculated for the means of individual color coordinates (L*, a*, b*, c* and h*). Two-way ANOVA showed that only the ceramic factor was significant (p=0.003), but there was no difference for the cement factor (p=0.275) nor for the ceramic/cement interaction (p=0.161). The feldspathic ceramic showed the highest values of ΔE00. Variations in L*, a*, b*, c* and h* were more significant for feldspathic ceramic. In conclusion, storage alters similarly the optical properties of the resin cements and feldspathic porcelain was more susceptible to cement color change after aging.

Influence of Resin Cements on Color Stability of Different Ceramic Systems

Abstract The purpose of this study was to evaluate color stability of two dental ceramics cemented with two resin cements, assessing the color difference (ΔE00) by the measurement of L*, a*, b*, c* and h* of transmittance. The combination of two ceramic system (feldspathic and lithium disilicate) and two resin cements - color A3 (RelyX ARC and Variolink II) resulted in 4 groups (n=5). Ten disks-shaped specimens were fabricated for each ceramic system (10x1.5 mm), etched with hydrofluoric acid (10%) and silanized prior to cementation. The color analysis was performed 24 h after cementation of the samples and after 6 months of storage in relative humidity by means of spectrophotometry. The ΔE00 values were analyzed statistically by two-way ANOVA followed by the Tukey test (p<0.05). One-way ANOVA were calculated for the means of individual color coordinates (L*, a*, b*, c* and h*). Two-way ANOVA showed that only the ceramic factor was significant (p=0.003), but there was no difference for the cement factor (p=0.275) nor for the ceramic/cement interaction (p=0.161). The feldspathic ceramic showed the highest values of ΔE00. Variations in L*, a*, b*, c* and h* were more significant for feldspathic ceramic. In conclusion, storage alters similarly the optical properties of the resin cements and feldspathic porcelain was more susceptible to cement color change after aging.

Resumo O objetivo deste estudo foi avaliar a estabilidade da cor de dois sistemas cerâmicos em função de dois cimentos resinosos, avaliando a diferença de cor (ΔE00) pela mensuração de L*, a*, b*, c* e h* de transmitância. Formou-se 4 grupos (n=5) de acordo com as duas cerâmicas (reforçada com dissilicato de lítio e feldspática) e dois cimentos resinosos - cor A3 (RelyX ARC e Variolink II). Dez discos foram confeccionados para cada sistema cerâmico (10 x 1,5 mm), tratados com ácido fluorídrico (10%) e silanizados antes da cimentação. A análise de cor foi feita 24 h após a cimentação das amostras e após 6 meses de armazenamento em umidade relativa por meio de espectrofotometria. ANOVA a dois fatores foi utilizada para análise dos dados de ΔE00 seguido pelo teste de Tukey (p<0,05). ANOVA a um fator foi realizada para avaliação das coordenadas individuais de cor (L*, a*, b*, c* e h*). Apenas o fator cerâmica foi significativo (p=0,003),mas não houve diferença para o fator imento (p=0,275) nem para a interação entre cerâmica e cimento (p=0,161). A cerâmica feldspática apresentou os maiores valores de ΔE00. Variações de L*, a*, b*, c* e h* foram mais significativas para cerâmica feldspática. Concluiu-se que o armazenamento alterou as propriedades ópticas dos cimentos resinosos de forma semelhante e a porcelana feldspática foi mais susceptível à mudança de cor do cimento após o envelhecimento.

Influence of resin cement shade on the color and translucency of ceramic veneers.

OBJECTIVE: This in vitro study evaluated the effect of two different shades of resin cement (RC- A1 and A3) layer on color change, translucency parameter (TP), and chroma of low (LT) and high (HT) translucent reinforced lithium disilicate ceramic laminates. MATERIAL AND METHODS: One dual-cured RC (Variolink II, A1- and A3-shade, Ivoclar Vivadent) was applied to 1-mm thick ceramic discs to create thin RC films (100 µm thick) under the ceramics. The RC was exposed to light from a LED curing unit. Color change (ΔE) of ceramic discs was measured according to CIEL*a*b* system with a standard illuminant D65 in reflectance mode in a spectrophotometer, operating in the light range of 360-740 nm, equipped with an integrating sphere. The color difference between black (B) and white (W) background readings was used for TP analysis, while chroma was calculated by the formula C*ab=(a*2+b*2)½. ΔE of 3.3 was set as the threshold of clinically unacceptable. The results were evaluated by two-way ANOVA followed by Tukey's post hoc test. RESULTS: HT ceramics showed higher ΔE and higher TP than LT ceramics. A3-shade RC promoted higher ΔE than A1-shade cement, regardless of the ceramic translucency. No significant difference in TP was noted between ceramic discs with A1- and those with A3-shade cement. Ceramic with underlying RC showed lower TP than discs without RC. HT ceramics showed lower chroma than LT ceramics, regardless of the resin cement shade. The presence of A3-shade RC resulted in higher chroma than the presence of A1-shade RC. CONCLUSIONS: Darker underlying RC layer promoted more pronounced changes in ceramic translucency, chroma, and shade of high translucent ceramic veneers. These differences may not be clinically differentiable.

Influence of resin cement shade on the color and translucency of ceramic veneers

ABSTRACT Objective This in vitro study evaluated the effect of two different shades of resin cement (RC- A1 and A3) layer on color change, translucency parameter (TP), and chroma of low (LT) and high (HT) translucent reinforced lithium disilicate ceramic laminates. Material and Methods One dual-cured RC (Variolink II, A1- and A3-shade, Ivoclar Vivadent) was applied to 1-mm thick ceramic discs to create thin RC films (100 µm thick) under the ceramics. The RC was exposed to light from a LED curing unit. Color change (ΔE) of ceramic discs was measured according to CIEL*a*b* system with a standard illuminant D65 in reflectance mode in a spectrophotometer, operating in the light range of 360-740 nm, equipped with an integrating sphere. The color difference between black (B) and white (W) background readings was used for TP analysis, while chroma was calculated by the formula C*ab=(a*2+b*2)½. ΔE of 3.3 was set as the threshold of clinically unacceptable. The results were evaluated by two-way ANOVA followed by Tukey's post hoc test. Results HT ceramics showed higher ΔE and higher TP than LT ceramics. A3-shade RC promoted higher ΔE than A1-shade cement, regardless of the ceramic translucency. No significant difference in TP was noted between ceramic discs with A1- and those with A3-shade cement. Ceramic with underlying RC showed lower TP than discs without RC. HT ceramics showed lower chroma than LT ceramics, regardless of the resin cement shade. The presence of A3-shade RC resulted in higher chroma than the presence of A1-shade RC. Conclusions Darker underlying RC layer promoted more pronounced changes in ceramic translucency, chroma, and shade of high translucent ceramic veneers. These differences may not be clinically differentiable.

Flexural strength and failure modes of layered ceramic structures.

OBJECTIVE: To evaluate the effect of the specimen design on the flexural strength (σ(f)) and failure mode of ceramic structures, testing the hypothesis that the ceramic material under tension controls the mechanical performance of the structure. METHODS: Three ceramics used as framework materials for fixed partial dentures (YZ--Vita In-Ceram YZ; IZ--Vita In-Ceram Zirconia; AL--Vita In-Ceram AL) and two veneering porcelains (VM7 and VM9) were studied. Bar-shaped specimens were produced in three different designs (n=10): monolithic, two layers (porcelain-framework) and three layers (TRI) (porcelain-framework-porcelain). Specimens were tested for three-point flexural strength at 1MPa/s in 37°C artificial saliva. For bi-layered design, the specimens were tested in both conditions: with porcelain (PT) or framework ceramic (FT) layer under tension. Fracture surfaces were analyzed using stereomicroscope and scanning electron microscopy (SEM). Young's modulus (E) and Poisson's ratio (ν) were determined using ultrasonic pulse-echo method. Results were statistically analyzed by Kruskal-Wallis and Student-Newman-Keuls tests. RESULTS: Except for VM7 and VM9, significant differences were observed for E values among the materials. YZ showed the highest ν value followed by IZ and AL. YZ presented the highest σ(f). There was no statistical difference in the σ(f) value between IZ and IZ-FT and between AL and AL-FT. σ(f) values for YZ-PT, IZ-PT, IZ-TRI, AL-PT, AL-TRI were similar to the results obtained for VM7 and VM9. Two types of fracture mode were identified: total and partial failure. SIGNIFICANCE: The mechanical performance of the specimens was determined by the material under tension during testing, confirming the study hypothesis.