Cameo and intaglio surface stability and variability of additively, subtractively, and conventionally manufactured occlusal devices after long-term storage.

STATEMENT OF PROBLEM: Additive and subtractive manufacturing have become alternative technologies for fabricating occlusal devices. However, knowledge of the long-term stability of occlusal devices fabricated using these recent technologies is limited. PURPOSE: The purpose of this in vitro study was to evaluate the cameo and intaglio surface stability and variability of additively, subtractively, and conventionally manufactured occlusal devices after 18 months of storage. MATERIAL AND METHODS: A standard tessellation language (STL) file of a dentate maxillary typodont was used to design a master occlusal device. The STL file of this design was used to fabricate occlusal devices additively either with a digital light processing (AM-1) or a continuous liquid interface production (AM-2) printer, subtractively with 2 different 5-axis milling units (SM-1 and SM-2), and conventionally (TM-HP) (n=10). STL files of each device's cameo and intaglio surfaces were generated using a laboratory scanner after fabrication and after 18 months of storage in a moist environment. These generated files were imported into an analysis software program (Geomagic Control X) to analyze the dimensional stability of tested devices by using the root mean square method. The average deviation values defined the variability of measured changes over time. Cameo and intaglio surface deviations were analyzed using the Kruskal-Wallis and Dunn tests, while the variability of measured deviations was analyzed with 1-way analysis of variance and the Tukey HSD tests (α=.05). RESULTS: Significant differences were observed among tested devices when the intaglio surface deviations and the cameo surface variability were considered (P<.001). SM-2 had significantly higher intaglio surface deviations than AM-1, SM-1, and AM-2 (P≤.036). Among the test groups, AM-1 had the greatest cameo surface variability (P≤.004). CONCLUSIONS: SM-2 resulted in lower intaglio surface stability than the additive and the other subtractive manufacturing technologies, while AM-1 led to the highest cameo surface variability among the test groups.

Effects of dipeptidyl peptidase 4 inhibition on the endothelial control of the vascular tone.

Dipeptidyl peptidase 4 (DPP4) is a serine protease known to cleave incretin hormones, which stimulate insulin secretion after food intake, a fact that supported the development of its inhibitors (DPP4i or gliptins) for the treatment of type 2 diabetes mellitus. In addition to their glucose-lowering effects, DPP4i show benefits for the cardiovascular system that could be related, at least in part, to their protective action on vascular endothelium. DPP4i have been associated with the reversal of endothelial dysfunction, an important predictor of cardiovascular events and a hallmark of diseases such as atherosclerosis, diabetes mellitus, hypertension, and heart failure. In animal models of these diseases, DPP4i increase nitric oxide bioavailability and limits oxidative stress, thereby improving the endothelium-dependent relaxation. Similar effects on flow-mediated dilation and attenuation of endothelial dysfunction have also been noted in human studies, suggesting a value for gliptins in the clinical scenario, despite the variability of the results regarding the DPP4i used, treatment duration, and presence of comorbidities. In this mini-review, we discuss the advances in our comprehension of the DPP4i effects on endothelial regulation of vascular tone. Understanding the role of DPP4 and its involvement in the signaling mechanisms leading to endothelial dysfunction will pave the way for a broader use of DPP4i in conditions that endothelial dysfunction is a pivotal pathophysiological player.

Comparison of 17ß-estradiol, bisphenol-A and caffeine concentration levels before and after the water treatment plant.

This article compares the concentration levels of 17ß-estradiol (E2), bisphenol-A (BPA) and caffeine (CAF) in the Sinos River, Brazil, which is a source of drinking water and the presence of contaminants after the conventional treatment in a municipal water treatment plant (WTP). A total of nine sampling campaigns were carried out, with sample collection in the Sinos River, upstream and downstream of the WTP, in addition to a drinking water sample (DW). The samples were extracted with solid phase extraction (SPE) and the concentration by liquid chromatography coupled to mass spectrometry (LC-MS). The maximum concentration in the Sinos River was 6,127.99 ng·L-1 for E2, 3,294.63 ng·L-1 for BPA and 1,221.95 ng·L-1 for CAF. In drinking water, the concentration range of E2, BPA and CAF was from less than the Detection Limit (DL) up to 437.50 ng·L-1,

Estimating intrinsic growth rates of arthropods from partial life tables using predatory mites as examples.

The intrinsic rate of natural increase of a population (rm) has been in focus as a key parameter in entomology and acarology. It is considered especially important in studies of predators that are potential biological control agents of fast-growing pests such as mites, whiteflies and thrips. Life-table experiments under controlled laboratory conditions are standard procedures to estimate rm. However, such experiments are often time consuming and may critically depend on the precise assessment of the developmental time and the fecundity rate early in the reproductive phase. Using selected studies of predatory mites with suitable life-table data, we investigated whether and how measurements of growth rates can be simplified. We propose a new method for estimating rm from partial life tables, in which the researcher can choose a level of precision based on a stand-in measure of relative error. Based on this choice, the procedure helps the researcher to decide when a life-table experiment can be terminated. Depending on the chosen precision, significant amounts of experimental time can be saved without seriously compromising the reliability of the estimated growth parameter.

Acute copper overload induces vascular dysfunction in aortic rings due to endothelial oxidative stress and increased nitric oxide production.

The mechanisms involved in vascular reactivity alterations promoted by copper (Cu) overload were investigated. Thoracic aorta obtained from male Wistar rats were cut into rings and exposed for 1 h to 10 µg/ml Cu. Exposure to Cu decreased the contractile responses of aortic rings to phenylephrine (PHE). Removal of endothelium and subsequent administration of N-nitro-L arginine methyl ester (L-NAME), tetrahydrobiopterin, aminoguanidine, diethyldithiocarbamic acid, catalase, or tetraethylammonium increased contractile responses. Incubation with apocinyn and tiron enhanced the sensitivity to PHE. Data demonstrated that high concentrations of Cu reduced PHE-mediated vascular reactivity which was associated with elevated production of nitric oxide (NO), which was attributed to activation of inducible NO synthase, and elevated levels of hydrogen peroxide probably related to a rise in superoxide dismutase activity and reactive oxygen species generation.

Tributyltin chloride increases phenylephrine-induced contraction and vascular stiffness in mesenteric resistance arteries from female rats.

Tributyltin chloride (TBT) is an organotin compound that reduces estrogen levels in female rats. We aimed to investigate the effects of TBT exposure on vascular tonus and vascular remodelling in the resistance arteries of female rats. Rats were treated daily with TBT (500 ng/kg) for 15 days. TBT did not change arterial blood pressure but did modify some morpho-physiological parameters of third-order mesenteric resistance arteries in the following ways: (1) decreased lumen and external diameters; (2) increased wall/lm ratio and wall thickness; (3) decreased distensibility and increased stiffness; (4) increased collagen deposition; and (5) increased pulse wave velocity. TBT exposure increased the phenylephrine-induced contractile response in mesenteric resistance arteries. However, vasodilatation responses induced by acetylcholine and sodium nitroprusside were not modified by TBT. It is suggested that TBT exposure reduces vascular nitric oxide (NO) production, because:(1) L-NAME incubation did not cause a leftward shift in the concentration-response curve for phenylephrine; (2) both eNOS protein expression; (3) in situ NO production were reduced. Incubation with L-NAME; and (4) SOD shifted the phenylephrine response curve to the left in TBT rats. Tiron, catalase, ML-171 and VAS2870 decreased vascular reactivity to phenylephrine only in TBT rats. Moreover, increased superoxide anion production was observed in the mesenteric resistance arteries of TBT rats accompanied by an increase in gp91phox, catalase, AT1 receptor and total ERK1/2 protein expression. In conclusion, these findings show that TBT induced alterations are most likely due to a reduction of NO production combined with increased O2(-) production derived from NADPH oxidase and ERK1/2 activation. These findings offer further evidence that TBT is an environmental risk factor for cardiovascular disease.

Distortion assessment of different materials in full-arch dentate impressions in relation to operator experience: a comparative in vivo.

PURPOSE: Evaluating the distortion probability in impressions of completely dentate arches when different impression materials are used in relation to operator experience. MATERIAL AND METHODS: Twenty-eight students (group A) and 7 dentists (group B) performed 3 maxillary impressions on 28 students (participants), each using vinyl siloxane ether (VSE), polyether (PE), and irreversible hydrocolloid (IHC). Gypsum master casts were fabricated and subsequently digitized. Intraoral scans were taken as a control. Differences between master casts and intraoral scans were visualized by heatmaps and planar deviations were investigated. If planar deviations of >120 µm were found, the impression was rated as "distorted." An additional superimposition using the casts from VSE or PE was performed to confirm the presence of distortions. The relative number of surfaces with distortions in each impression was calculated. The procedure was repeated for a distortion threshold of 500 µm. The statistical analyses included measures ANOVA and post-hoc tests (a < 0.05). RESULTS: When 120 µm was considered as the threshold for distortions, IHC impressions showed higher distortion probability than PE impressions in group A (P = 0.003) and group B (P < 0.0001). In group B only, PE showed a lower distortion probability than VSE (P = 0.02). There was no difference between the study groups (P = 0.42). Considering 500 µm as a threshold for distortions, there was no difference between impression materials (P = 0.17) or study groups (P = 0.53). CONCLUSION: There were no statistic significant differences in relation to operator experience. Different impression materials had a significant impact on distortion probability. Polyether impressions showed the lowest distortion probability. Int J Prosthodont. 10.11607/ijp.8555.

Iron overload, oxidative stress and vascular dysfunction: Evidences from clinical studies and animal models.

Although iron is a metal involved in many vital processes due to its redox capacity, body iron overloads lead to tissue damage, including the cardiovascular system. While cardiomyopathy was the focus since the 1960s, the impact on the vasculature was comparatively neglected for about 40 years, when clinical studies correlating iron overload, oxidative stress, endothelial dysfunction, arterial stiffness and atherosclerosis reinforced an "iron hypothesis". Due to controversial results from some epidemiological studies investigating atherosclerotic events and iron levels, well-controlled trials and animal studies provided essential data about the influence of iron, per se, on the vasculature. As a result, the pathophysiology of vascular dysfunction in iron overload have been revisited. This review summarizes the knowledge obtained from epidemiological studies, animal models and "in vitro" cellular systems in recent decades, highlighting a more harmful than innocent role of iron excess for the vascular homeostasis, which supports our proposal to hereafter denominate "iron overload vasculopathy". Additionally, evidence-based potential therapeutic targets are pointed out to be tested in pre-clinical research that may be useful in cardiovascular protection for patients with iron overload syndromes.

Comparison of measured deviations in digital implant scans depending on software and operator.

OBJECTIVES: To investigate the effect of 3-dimensional (3D) analysis software and operator on the measured deviations in implant scans. MATERIAL AND METHODS: A combined healing abutment-scan body (CHA-SB) system was digitized with an industrial scanner (ATOS Core 80) to generate a master standard tessellation language file (MRM-STL) and an intraoral scanner (TRIOS 3) to generate 9 test-scan STL files, which were transferred into metrology-grade (Geomagic Control X, GX and GOM Inspect, GM) and nonmetrology-grade (Medit Link, ML) software for deviation analysis. Test-scan STLs were superimposed over MRM-STL and 2 planes passing through the center of the SB were generated. Distance deviations at 8 points on these planes were analyzed by two different operators with similar level of experience. Data were analyzed with analysis of variance and F tests (α=.05). RESULTS: Only model 1 (P=.049) analyzed by operator 2 showed significant differences among tested software, and the highest deviations were measured with GM (P≤.037). However, the difference in values measured with GX and ML was nonsignificant (P=.91). Operator correlation was high (ICC≥.712, P≤.011), except for models 1 (GM, ICC=-.335, P=.813), 2 (GM, ICC=.025, P=.468 and ML, ICC=-.013, P=.507), 6 (GM, ICC=-.085, P=.583), and 8 (GM, ICC=-.386, P=.85). CONCLUSION: The measured deviations in implant scans in all models, except for one, were similar among the tested software, regardless of the operator. The inter-rater reliability of operators while using tested 3D analysis software was overall high. When observed, low inter-rater reliability was mostly with only one of the metrology grade software. CLINICAL SIGNIFICANCE: Nonmetrology-grade 3D analysis software may be a suitable alternative to metrology-grade software to measure the deviations in digital implant scan body scans. When GOM metrology-software is used, measured deviations in implant scan body scans may vary more across operators.

Effect of Scanned Area and Operator on the Accuracy of Dentate Arch Scans with a Single Implant.

Studies have shown the effect of the operator and scanned areas on the accuracy of single implant scans. However, the knowledge on the scan accuracy of the remaining dental arch during single implant scans, which may affect the occlusion, is limited. The aim of this study was to investigate the effect of scanned areas and the operator on the scan accuracy of a dentate arch while scanning a single implant. A dentate model with an anterior implant was digitized with a laboratory scanner (reference scan). Three operators with similar experience performed 10 complete- and 10 partial-arch scans (left 2nd molar to right canine) with an intraoral scanner (TRIOS 3), and these scans were superimposed over the reference. The accuracy was analyzed at 22 points in complete-arch and at 16 points in partial-arch scans on 2nd molars and incisors. Data were evaluated with 2-way ANOVA and Tukey HSD tests (α = 0.05). The trueness of the total scanned area was higher in partial- than in complete-arch scans (p < 0.001). The trueness and precision of the scans were higher in the anterior site compared with the posterior in complete- (trueness: p ≤ 0.022, precision: p ≤ 0.003) and partial-arch (trueness: p ≤ 0.016, precision: p ≤ 0.016) scans of each operator and when the operator scan data were pooled. The complete-arch scan's precision was not influenced by the operator (p ≥ 0.029), whereas the partial-arch scans of operator 1 and 2 were significantly different (p = 0.036). Trueness was higher in partial- compared with complete-arch scans, but their precision was similar. Accuracy was higher in the anterior site regardless of the scan being a partial- or a complete-arch. The operator's effect on the accuracy of partial- and complete-arch scans was small.

Congruence between the meshes of a combined healing abutment-scan body system acquired with four different intraoral scanners and the corresponding library file: An in vitro analysis.

OBJECTIVES: To investigate the congruence between the meshes of a combined healing abutment-scan body (CHA-SB) system acquired with four different intraoral scanners and the corresponding library file. MATERIAL AND METHODS: A CHA-SB was fixed to an implant at the right first molar position in a dentate mandibular model and digitized by using 4 different intraoral scanners (IOSs) [TRIOS 3 (T3), Omnicam (OC), Primescan (PS), and Virtuo Vivo (VV)] (n = 8) and an industrial grade optical scanner (ATOS Core 80) (n = 1) to generate standard tessellation language (STL) files of the test scans (CHA-SB-STLs) and the master reference model scan (MRM-STL). A reverse engineering software (Studio Geomagic X) was used to superimpose the proprietary library file of the CHA-SB over the generated STL files. Root mean square (RMS) values representing the deviations between the library file and the superimposed STL files were statistically analyzed by using 1-way ANOVA (α=0.05). Qualitative analysis of the deviations was performed by visual inspection. RESULTS: Differences between the congruence of the library file and the CHA-SB scans among different IOSs were nonsignificant (F = 1.619, df= 3, P = .207). The single best result was 29 ± 28.9 µm for OC, 30.8 ± 29.6 µm for VV, 35.6 ± 35.5 µm for T3, and 39.5 ± 39.2 µm for PS, which were all above the deviation value of the scan performed by using the industrial-grade scanner (23.2 ± 23.2 µm). CONCLUSION: The dimensional congruence between the library file and the STL file of the CHA-SB system scans was similar when intraoral scanners with different acquisition technologies were used to scan a model with an implant. CLINICAL SIGNIFICANCE: Scans of the tested intraoral scanners may result in crowns with similar positional accuracy, given the similarities in congruence of their scans with the library file.

Influence of 3D analysis software on measured deviations of CAD-CAM resin crowns from virtual design file: An in-vitro study.

OBJECTIVES: To evaluate a nonmetrology-grade and a metrology-grade 3D analysis software when measuring the deviations of computer-aided-design/ computer-aided-manufacturing (CAD-CAM) fabricated crowns from the virtual design file. MATERIALS AND METHODS: A right first molar on a mandibular dentate model was prepared and scanned with an intraoral scanner, i500 (Medit). A complete coverage crown was designed in standard tessellation language (STL) format and 20 resin crowns were fabricated with CAD-CAM. The crowns were then digitized using the same intraoral scanner (test-scans). Root mean square (RMS) method was used to evaluate the deviations between the test-scans and the design file of the crowns on 3 surfaces (overall, external, and internal) using a metrology-grade, Geomagic Control X (3D Systems) and a nonmetrology-grade, Medit Link (Medit) software. The data were analyzed with Welch two-sample t-tests to compare two software for the non-inferiority of the nonmetrology-grade software with a 50 µm threshold and the potential superiority of the metrology-grade software (α = 0.05). RESULTS: The Welch two-sample t-tests for the non-inferiority analysis showed that the differences between the nonmetrology-grade and the metrology-grade software were below the threshold of 50 µm for each surface tested (p <0.001). The differences between the two-tested software were nonsignificant for each surface analyzed when superiority was considered (p ≥.194). CONCLUSION: The nonmetrology-grade software performed similar to the metrology-grade software when analyzing the deviations of CAD-CAM crowns. Therefore, the nonmetrology-grade 3D analysis software may be considered for the deviation measurements of similar restorations. CLINICAL SIGNIFICANCE: The trueness of crowns after fabrication may affect their fit, and 3D analysis of trueness prior to the delivery appointment with the tested nonmetrology-grade software after fabrication may facilitate potential clinical adjustments and delivery of the crowns.

The accuracy of single implant scans with a healing abutment-scanpeg system compared with the scans of a scanbody and conventional impressions: An in vitro study.

PURPOSE: To compare the accuracy of polyvinylsiloxane (PVS) impressions and intraoral scans when a healing abutment-scanpeg system (HASP) or a conventional scanbody (CSB) was used on a single implant. MATERIALS AND METHODS: A maxillary model with an implant (4.0 × 11 mm) (Neoss) and a CSB or an HASP (Neoss) was scanned by using a laboratory scanner (Ceramill Map 600; Amann Girrbach) (reference scans) and an intraoral scanner (Trios 3) (n = 10). PVS open-tray impressions were also made and stone casts of the model with a CSB were digitized with the laboratory scanner. Intraoral scanner and cast scans were superimposed to their reference scans. On superimposed scans, points were selected on HASP and CSB to calculate distance deviations (at points 1-4) and angular deviations (at points 5 and 6 on CSB and PVS, and 5-8 on HASP) between scans (trueness), and their variation (precision). The deviation data was analyzed with ANOVA and pairwise comparisons (trueness) with Tukey's adjustment, and F-tests (precision). RESULTS: At point 1, PVS had lower trueness than CSB (difference in means (DIMs) = 0.184 mm, p = 0.006) and HASP (DIMs = 0.122 mm, p = 0.042). At point 3, CSB had higher trueness than HASP (DIMs = 0.134 mm, p = 0.001). Angular deviations with PVS were higher than with CSB (DIMs = 0.6°, p = 0.013) and HASP (DIMs = 0.7°, p = 0.005). CSB had higher precision than PVS (p < 0.05). HASP had higher precision than PVS for distance (Point 1)(p < 0.001) and angular deviations (p < 0.05). Deviation differences within the HASP parts were not significant. CONCLUSION: The accuracy of intraoral scans and PVS impressions of an implant was similar. CLINICAL RELEVANCE: The combined healing abutment-scanpeg system and the conventional scanbody can be recommended for scans of anterior single implants with the intraoral scanner used.

The effect of scanned area on the accuracy and time of anterior single implant scans: An in vitro study.

OBJECTIVES: To investigate the effect of scanned area on the accuracy and scan time of intraoral scans of an anterior implant. MATERIALS AND METHODS: Three operators experienced in intraoral scanning (at least 2-year experience) performed partial and complete-arch scans (n = 10) of a dentate resin model with an implant at left central incisor site by using an intraoral scanner (Trios3; 3Shape, Copenhagen, Denmark). Each partial- or complete-arch scan was superimposed to a reference scan from a laboratory scanner (Ceramill Map 600; Amann Girrbach AG). Mean distance (selected 7 points) and angular (mesiodistal and buccolingual) scanbody deviations in test scans (trueness) and their variance (precision) were calculated. Linear-regressions (trueness), two-sided F-tests with a Bonferroni correction (precision), and multiple linear regressions (scan time), with the operator as a covariate were applied (alpha = .05). RESULTS: Interactions were found between the scanned area and the operator for their effect on trueness of all points and angles, except for point 6 at implant-abutment connection in mesiodistal plane (p < .05). No significant difference was found between the precision of partial and complete-arch scans for all operators (p > .05). Partial-arch scan times were significantly shorter, overall, and for each operator (p < .001). No significant effect of scan time was found on the trueness of partial- and complete-arch scans (p > .05). CONCLUSIONS: Partial and complete-arch scans of anterior single implants with an intraoral scanner resulted in similar accuracies, and were not influenced by the operator or the scan time. Scan times of partial-arch scans were significantly shorter. CLINICAL SIGNIFICANCE: Partial-arch scans can be used for the fabrication of monolithic anterior single implant crowns because the scans can be completed in shorter times without compromising the accuracy.

Does refuge spillover affect arthropod food webs associated with Bt maize?

BACKGROUND: A high dose/refuge combination is the main tactic recommended for mitigating resistance selection of target herbivore species in crops expressing insecticidal proteins of the bacterium Bacillus thuringiensis (i.e. Bt proteins). The tactic consists of the simultaneous use of Bt crops expressing high levels of the Bt protein associated with neighboring areas of refuge of the same non-Bt crop species. Nonetheless, the approach faces controversy regarding its effectiveness and scale of adoption, at least in some regions. One concern focuses on its potential impact on the arthropod community, including its short-term and spatially dependent impact considering the likely biota spillover effect between Bt and non-Bt neighboring areas. Thus, the eventual spillover of Bt maize targeted and non-targeted arthropods was surveyed along transects extending from the refuge border to the center of the Bt maize area. RESULTS: Arthropods were collected throughout the maize vegetative and reproductive stages. A total of 85 arthropod species were collected, but their richness and abundance did not vary with distance from the refuge. By contrast, cultivation season played a significant role in distinguishing the arthropod communities. Refuge distance from the sampling point within Bt-fields did not significantly affect the food web metrics, unlike season, which affected the number of nodes integrating each food web. Winter maize cultivation exhibited higher arthropod diversity and combined values of species numeric abundance and biomass at each trophic level. CONCLUSIONS: No arthropod spillover was evident between the refuge edge and Bt maize, adding further controversy to the tactic currently subjected to lower usage in the region with a disputed cost-benefit relationship, because not even the target and its interdependent species were affected. © 2021 Society of Chemical Industry.

Multifunctional potential of endophytic bacteria from Anacardium othonianum Rizzini in promoting in vitro and ex vitro plant growth.

Anacardium othonianum Rizzini, a cashew tree native to the Brazilian Cerrado, is economically important due to its applications in the food, chemical and pharmaceutical industries. However, A. othonianum yields a crop with low productivity due to a number of factors, such as nutritionally poor soils, drought and losses due to pests and diseases. Brazil is one of the nine largest cashew nut producers worldwide, and sustainable technologies are needed to increase the productivity of this crop. In this context, the use of endophytic microorganisms could promote plant growth and provide protection against phytopathogens. In this study, the isolation of the root endophytic community of A. othonianum led to the characterization of 22 distinct bacterial strains with multifunctional traits for plant growth promotion. The results of in vitro assays to assess auxin synthesis, phosphate solubilization, phosphatase and siderophore production and biocontrol against Fusarium oxysporum led to the selection of Acinetobacter lwoffii Bac109 and Pantoea agglomerans Bac131 as the most promising strains. The reinoculation of the Bac109 and Bac131 strains onto A. othonianum seeds showed that the treatment containing a mixture of these strains was the most effective in promoting increases in the biometric parameters of early plant growth. Thus, this study highlights the biotechnological potential of a consortium of A. lwoffii Bac109 and P. agglomerans Bac131 for future applications in sustainable cashew cultivation.

Changes in the renal function after acute mercuric chloride exposure in the rat are associated with renal vascular endothelial dysfunction and proximal tubule NHE3 inhibition.

Mercury is an environmental pollutant and a threat to human health. Mercuric chloride (HgCl2)-induced acute renal failure has been described by several reports, but the mechanisms of renal dysfunction remain elusive. This study tested the hypothesis that HgCl2 directly impairs renal vascular reactivity. Additionally, due to the mercury toxicity on the proximal tubule, we investigated whether the HgCl2-induced natriuresis is accompanied by inhibition of Na+/H+ exchanger isoform-3 (NHE3). We found that 90-min HgCl2 infusion (6.5 µg/kg i.v.) remarkably increased urinary output, reduced GFR and renal blood flow, and increased vascular resistance in rats. "In vitro" experiments of HgCl2 infusion in isolated renal vascular bed demonstrated an elevation of perfusion pressure in a concentration- and time-dependent manner, associated with changes on the endothelium-dependent vasodilatation and the flow-pressure relationship. Moreover, by employing "in vivo" stationary microperfusion of the proximal tubule, we found that HgCl2 inhibits NHE3 activity and increases the phosphorylation of NHE3 at serine 552 in the renal cortex, in line with the HgCl2-induced diuresis. Changes in renal proximal tubular function induced by HgCl2 were parallel to increased urinary markers of proximal tubular injury. Besides, atomic spectrometry showed that mercury accumulated in the renal cortex. We conclude that acute HgCl2 exposure causes renal vasoconstriction that is associated with reduced endothelial vasodilator agonist- and flow-mediated responses and inhibition of NHE3-mediated sodium reabsorption. Thus, our data suggest that HgCl2-induced acute renal failure may be attributable at least in part by its direct effects on renal hemodynamics and NHE3 activity.

Hypercaloric diet models do not develop heart failure, but the excess sucrose promotes contractility dysfunction.

Several diseases are associated with excess of adipose tissue, and obesity is considered an independent risk factor for the development of cardiac remodeling and heart failure. Dietary aspects have been studied to elucidate the mechanisms involved in these processes. Thus, the purpose was the development and characterization of an obesity experimental model from hypercaloric diets, which resulted in cardiac remodeling and predisposition to heart failure. Thirty- day-old male Wistar rats (n = 52) were randomized into four groups: control (C), high sucrose (HS), high-fat (HF) and high-fat and sucrose (HFHS) for 20 weeks. General characteristics, comorbidities, weights of the heart, left (LV) and right ventricles, atrium, and relationships with the tibia length were evaluated. The LV myocyte cross sectional area and fraction of interstitial collagen were assayed. Cardiac function was determined by hemodynamic analysis and the contractility by cardiomyocyte contractile function. Heart failure was analyzed by pulmonary congestion, right ventricular hypertrophy, and hemodynamic parameters. HF and HFHS models led to obesity by increase in adiposity index (C = 8.3 ± 0.2% vs. HF = 10.9 ± 0.5%, HFHS = 10.2 ± 0.3%). There was no change in the morphological parameters and heart failure signals. HF and HFHS caused a reduction in times to 50% relaxation without cardiomyocyte contractile damage. The HS model presented cardiomyocyte contractile dysfunction visualized by lower shortening (C: 8.34 ± 0.32% vs. HS: 6.91 ± 0.28), as well as the Ca2+ transient amplitude was also increased when compared to HFHS. In conclusion, the experimental diets based on high amounts of sugar, lard or a combination of both did not promote cardiac remodeling with predisposition to heart failure under conditions of obesity or excess sucrose. Nevertheless, excess sucrose causes cardiomyocyte contractility dysfunction associated with alterations in the myocyte sensitivity to intracellular Ca2+.

Blockade of angiotensin AT1 receptors prevents arterial remodelling and stiffening in iron-overloaded rats.

BACKGROUND AND PURPOSE: Damage to the vasculature caused by chronic iron-overload in both humans and animal models, is characterized by endothelial dysfunction and reduced compliance. In vitro, blockade of the angiotensin II AT1 receptors reversed functional vascular changes induced by chronic iron-overload. In this study, the effect of chronic AT1 receptor blockade on aorta stiffening was assessed in iron-overloaded rats. EXPERIMENTAL APPROACH: Male Wistar rats were treated for 15 days with saline as control group, iron dextran 200 mg·kg-1 ·day-1 , 5 days a week (iron-overload group), losartan (20 mg·kg-1 ·day-1 in drinking water), and iron dextran plus losartan. Mechanical properties of the aorta were assessed in vivo. In vitro, aortic geometry and biochemical composition were assessed with morphometric and histological methods. KEY RESULTS: Thoracoabdominal aortic pulse wave velocity (PWV) increased significantly, indicating a decrease in aortic compliance. Co-treatment with losartan prevented changes on PWV, ß-index, and elastic modulus in iron-overloaded rats. This iron-related increase in PWV was not related to changes in aortic geometry and wall stress. but to increased elastic modulus/wall stress ratio, suggesting that a change in the composition of the wall was responsible for the stiffness. Losartan treatment also ameliorated the increase in aorta collagen content of the iron-overload group, without affecting circulating iron or vascular deposits. CONCLUSIONS AND IMPLICATIONS: Losartan prevented the structural and functional indices of aortic stiffness in iron-overloaded rats, implying that inhibition of the renin-angiotensin system would limit the vascular remodelling in chronic iron-overload.

Sildenafil reduces aortic endothelial dysfunction and structural damage in spontaneously hypertensive rats: Role of NO, NADPH and COX-1 pathways.

Arterial hypertension is a condition associated with endothelial dysfunction, accompanied by an imbalance in the production of reactive oxygen species (ROS) and NO. The aim of this study was to investigate and elucidate the possible mechanisms of sildenafil, a selective phosphodiesterase-5 inhibitor, actions on endothelial function in aortas from spontaneously hypertensive rats (SHR). SHR treated with sildenafil (40 mg/kg/day, p.o., 3 weeks) were compared to untreated SHR and Wistar-Kyoto (WKY) rats. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography and vascular reactivity was determined in isolated rat aortic rings. Circulating endothelial progenitor cells and systemic ROS were measured by flow cytometry. Plasmatic total antioxidant capacity, NO production and aorta lipid peroxidation were determined by spectrophotometry. Scanning electron microscopy was used for structural analysis of the endothelial surface. Sildenafil reduced high SBP and partially restored the vasodilator response to acetylcholine and sodium nitroprusside in SHR aortic rings. Using selective inhibitors, our experiments revealed an augmented participation of NO, with a simultaneous decrease of oxidative stress and of cyclooxygenase-1 (COX-1)-derived prostanoids contribution in the endothelium-dependent vasodilation in sildenafil-treated SHR compared to non-treated SHR. Also, the relaxant responses to sildenafil and 8-Br-cGMP were normalized in sildenafil-treated SHR and sildenafil restored the pro-oxidant/antioxidant balance and the endothelial architecture. In conclusion, sildenafil reverses endothelial dysfunction in SHR by improving vascular relaxation to acetylcholine with increased NO bioavailability, reducing the oxidative stress and COX-1 prostanoids, and improving cGMP/PKG signaling. Also, sildenafil reduces structural endothelial damage. Thus, sildenafil is a promising novel pharmacologic strategy to treat endothelial dysfunction in hypertensive states reinforcing its potential role as adjuvant in the pharmacotherapy of cardiovascular diseases.