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Introduction: Irinotecan (CPT-11) is an inhibitor of DNA topoisomerase I and is clinically effective against several cancers. A major toxic effect of CPT-11 is delayed diarrhea; however, the exact mechanism by which the drug induces diarrhea has not been established.Purpose: Elucidate the mechanisms of induction of delayed diarrhea and determine the effects of the cytokine production inhibitor pentoxifylline (PTX) and thalidomide (TLD) in the experimental model of intestinal mucositis, induced by CPT-11.Materials and Methods: Intestinal mucositis was induced in male Swiss mice by intraperitoneal administration of CPT-11 (75 mg/kg) daily for 4 days. Animals received subcutaneous PTX (1.7, 5 and 15 mg/kg) or TLD (15, 30, 60 mg/kg) or 0.5 ml of saline daily for 5 and 7 days, starting 1 day before the first CPT-11 injection. The incidence of delayed diarrhea was monitored by scores and the animals were sacrificed on the 5th and 7th experimental day for histological analysis, immunohistochemistry for TNF-alpha and assay of myeloperoxidase (MPO) activity, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and KC ELISA.Results: CPT-11 caused significant diarrhea, histopathological alterations (inflammatory cell infiltration, loss of crypt architecture and villus shortening) and increased intestinal tissue MPO activity, TNF-alpha, IL-1beta and KC level and TNF-alpha immuno-staining. PTX inhibited delayed diarrhea of mice submitted to intestinal mucositis and reduced histopathological damage, intestinal MPO activity, tissue level of TNF-alpha, IL-1beta and KC and TNF-alpha immuno-staining. TLD significantly reduced the lesions induced by CPT-11 in intestinal mucosa, decreased MPO activity, TNF-alpha tissue level and TNF-alpha immuno-staining, but did not reduce the severity of diarrhea.Conclusion: These results suggest an important role of TNF-alpha, IL-1beta and KC in the pathogenesis of intestinal mucositis induced by CPT-11. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to evaluate the influence of multidirectional brushing on the surface roughness, morphology, and bonding interface of resin-repaired CAD-CAM ceramic and composite restorations., Materials and Methods: Twelve (N = 12) blocks (4 mm × 4 mm × 2 mm for parallel axis; 5 mm × 4 mm × 2 mm for perpendicular axis) of lithium disilicate glass-ceramic (IPS e.max CAD, Ivoclar AG) and CAD-CAM resin composite (Tetric CAD, Ivoclar AG) were obtained and repaired with direct resin composite (Clearfil AP-X, Kuraray). An abrasive slurry was prepared and the brushing was performed according to each restorative material and axis of brushing (n = 6; perpendicular to repair interface and parallel to repair interface) during 3,650 cycles (240 strokes per minute) to simulate 3 years of brushing. The surface roughness (Ra) and the profile variation for each material (restoration and direct repair resin composite) were measured at the baseline condition and after brushing, and the mean roughness and presence of steps at the repair interface were evaluated through factorial analysis of Variance (ANOVA). Scanning Electron Microscopy (SEM) images were taken to evaluate the surface topography of the repaired materials after brushing., Results: The mean roughness of the repaired CAD-CAM restorations was affected by the brushing (P < .05), mainly when evaluating the repair material and the interface (P < .05), while the restorative CAD-CAM materials presented more stable values. The profile evaluation showed higher steps at the interface when repairing lithium disilicate than for CAD-CAM resin composite., Conclusion: Repaired CAD-CAM restorations were susceptible to wear after brushing simulation. The surface roughness of the direct resin composite was the most affected leading to step development at the interface, particularly in the repaired lithium disilicate samples. Cinical maintenance recalls and polishing protocols must be considered to enhance the longevity of such restorations., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This study aimed to evaluate the masking ability of different resin composite (RC) layering techniques over discolored substrates. Layering strategies were tested (n=10), using different RCs: flowable opaque, white dentin, A1 dentin, A1 body, and A1 enamel (Filtek Z350XT; 3M ESPE). Bilayer and trilayer RC combinations resulted in final thicknesses of 1 mm, 1.5 mm, and 2 mm. Substrates tested were: A1 (reference), A3, A4, B3, C2, and C4 (Filtek Z350XT Dentin; 3M ESPE). Color differences (∆E00) were measured for the RC layers over discolored substrates with the CIEDE2000 formula. The results were compared statistically (One-way ANOVA) and descriptively (acceptability=1.77 and perceptibility=0.81 thresholds). The layering strategy influenced the ∆E00 of RCs over all substrates (P<0.001). The 1 mm bilayer group combining 0.5 mm of dentin and 0.5 mm of enamel led to ∆E00 below AT for substrates A3 and B3; the 1.5 mm bilayer group combining A1 dentin (1 mm) and enamel (0.5 mm) provided ∆E00 below AT for substrates A3, A4, and C2 and ∆E00 below PT for B3; for substrate C4, the 2 mm trilayer group combining flowable opaque (0.2 mm), A1 dentin (1.3 mm) and enamel (0.5 mm) provided ∆E00 below PT, and the 1.5 mm trilayer groups (flowable opaque + 0.8 mm dentin or body + enamel) led to ∆E00 below AT. Resin Composites were effective in masking discolored substrates. The most adequate layering strategy depended on substrate shade.

Statement of the Problem: Biological complications of implant-supported prostheses remain a concern. Therefore, standardizing hygiene protocols to promote their maintenance is important., Purpose: The purpose of this scoping review was to identify available hygiene guidance for home care procedures, as well as periodicity and protocols for the professional maintenance of implant-supported prostheses., Material and Methods: This study was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the study protocol was made available at: https://osf.io/5jdeh/. The search was last performed in the PubMed database on March 15, 2022 and was undertaken by 2 independent researchers. Clinical studies and reviews that evaluated home care and maintenance protocols for dental implant-supported prostheses (fixed or removable), without language restriction or year of publication, were included. A descriptive analysis was performed considering study characteristics (study design, restorative assembly, maintenance strategies, eligibility criteria, number of included studies, quality/level of evidence, and main findings)., Results: The initial search yielded 3138 studies, of which 18 were included for descriptive analysis (6 critical reviews, 4 clinical trials, 3 systematic reviews, 2 guideline reports, 2 retrospective studies, and 1 transversal study). The main instrument recommended for home care was the use of a conventional toothbrush associated with triclosan-containing toothpaste in addition to interproximal aids (brushes or floss) for all types of restorations. The use of irrigation instruments was also frequently considered. For professional maintenance, almost all studies reported a positive effect of regular recalls every 3 months during the first year, followed by less regular recalls according to the motivation of the patient and home care efficacy. At each recall, the professional should evaluate the patient history, oral tissues, implant, abutments, and restorations, as well as perform professional cleaning of the prostheses with appropriate instruments so that the implants and abutments may be preserved., Conclusions: Establishing an adequate hygiene protocol is indispensable for implant-supported restorations. To do so, the professional must guide and support the patient's home care by taking into account the patient's motivation and efficacy during the hygiene procedures. Also, for professional maintenance, the periodicity of recalls should be constant and include an evaluation of the condition of the restoration and adjacent tissues, followed by professional cleaning of prostheses, implants, and abutments, in addition to new instructions to improve patient home care., (Copyright © 2022 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Introduction: This study aimed to investigate the effect of radiotherapy and taper of root canal preparation on the biomechanical behavior of mesial roots of mandibular molars., Methods: Eighty mandibular molars with 2 canals in the mesial root were randomly allocated into 2 groups (n = 40): one group underwent irradiation (60 Gy), while the other did not. Subsequently, the mesial roots were sectioned and each group was subdivided into 5 subgroups (n = 8), according to the preparation taper: no preparation (control); 25.03; 25.04; 25.06; and 25.08. All groups were considered homogeneous regarding their dimensions, weight, and morphology. The prepared specimens were embedded in cylindrical plastic molds and subjected to a cyclic fatigue test. A failure analysis was performed according to the extension and course of the fractures. Two-way ANOVA, Tukey's post-hoc, Fisher's exact, and Kaplan-Meier tests were conducted to evaluate the obtained data (α = 5%)., Results: Fatigue resistance decreased as the taper of the preparation increased (P < .05). Preparation 25.03 presented significantly higher values only than 25.08 (P < .05), while 25.04, 25.06, and 25.08 were considered similar (P > .05). Irradiation significantly reduced the biomechanical performance (P < .05). Survival analysis corroborated these findings. There were no differences in the distribution of fracture types among the groups (P > .05)., Conclusion: The biomechanical behavior of the mesial roots of the mandibular molars decreased significantly in the face of irradiation and as the taper of the preparation increased., (Copyright © 2024 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Investigating the reactivity of small nucleophilic scaffolds is a strategic approach for the design of new catalysts aiming at effective detoxification processes of organophosphorus compounds. The drug methimazole (MMZ) is an interesting candidate featuring two non-equivalent nucleophilic centers. Herein, phosphoryl transfer reactions mediated by MMZ were assessed by means of spectrophotometric kinetic studies, mass spectrometry (MS) analyses, and density functional theory (DFT) calculations using the multi-electrophilic compound O,O-diethyl 2,4-dinitrophenyl phosphate (DEDNPP). MMZ anion acts primarily as an S-nucleophile, exhibiting a nucleophilic activity comparable to that of certain oximes featuring alpha-effect. Selective nucleophilic aromatic substitution was observed, consistent with the DFT prediction of a low energy barrier. Overall, the results bring important advances regarding the mechanistic understanding of nucleophilic dephosphorylation reactions, which comprises a strategic tool for neutralizing toxic organophosphates, hence promoting chemical security., (© 2024 Wiley-VCH GmbH.)

Despite the advancements in indirect monolithic restorations, technical complications may occur during function. To overcome this issues, intraoral repair using resin composite is a practical and low-cost procedure, being able to increase the restoration's longevity. This review aimed to evaluate the need for repair and suggest a standardized repair protocol to the main indirect restorative materials. For this, studies were surveyed from PubMed with no language or date restriction, to investigate the scientific evidence of indirect monolithic restoration repair with direct resin composite. A classification to guide clinical decisions was made based on the FDI World Dental Federation criteria about defective indirect restorations considering esthetic and functional standards, along with the patient's view, to decide when polishing, repairing or replacing a defective restoration. Based on 38 surveyed studies, different resin composite intraoral repair protocols, that included mechanical and chemical aspects, were defined depending on the substrate considering resin-based, glass-ceramic or zirconia restorations. The presented criteria and protocols were developed to guide the clinician's decision-making process regarding defective indirect monolithic restorations, prolonging longevity and increasing clinical success., Competing Interests: João Paulo Mendes Tribst is an Academic Editor for PeerJ., (©2024 da Rosa et al.)

Objective: The study aims to evaluate the shear bond and flexural strength fatigue behavior of yttrium-stabilized zirconia (4YSZ) repaired using different resin composites., Materials and Methods: Cylindric specimens of 4YSZ were obtained for the bond strength (Ø = 6 mm, 1.5 mm of thickness) and biaxial flexural strength (Ø = 15 mm, 1 mm of thickness) fatigue tests and divided into 3 groups according to the repair resin composite: EVO (nanohybrid), BULK (bulk-fill), and FLOW (flowable). The zirconia surface was air-abraded with alumina particles, a 10-methacryloyloxydecyl dihydrogen phosphate (10-MDP) primer was applied, and the resin composite was build-up over the zirconia. Fatigue shear bond strength and flexural fatigue strength tests were performed (n = 15). One-way ANOVA and Tukey post hoc tests were carried out for both outcomes, besides scanning electron microscopy and finite element analysis., Results: The repair material affected the fatigue shear bond strength of zirconia ceramic. The BULK group (18.9 MPa) depicted higher bond strength values than FLOW (14.8 MPa) (p = 0.04), while EVO (18.0 MPa) showed similar results to both groups. No effect was observed for the mechanical behavior (p = 0.53). The stress distribution was similar for all groups., Conclusion: The repair of yttrium-stabilized zirconia (4YSZ) ceramics with bulk-fill resin composites was the best option for high fatigue bond strength. However, the fatigue mechanical performance was similar regardless of the applied repair material., Clinical Relevance: The repair of yttrium-stabilized zirconia (4YSZ) monolithic restorations may be performed with nanohybrid and bulk-fill resin composites in order to promote longevity in the treatment., (© 2024. The Author(s).)

The present study aimed to evaluate the impact of the existence of an abutment screw-access hole and the filling effects on the fatigue mechanical behavior of a luted lithium-disilicate glass-ceramic. Seventy-two discs (Ø = 10 mm, 1.0 mm in thickness) of lithium disilicate (IPS e.max CAD, Ivoclar AG) were obtained from prefabricated blocks. Thirty-six abutment specimens of an opaque zirconia (Yz - IPS e.max ZirCAD, Ivoclar AG) and titanium (Ti - Luminesse Ti-Cam discs, Talladium Inc.) were confectioned, and allocated according to 6 groups: Yz and Ti rigid (without screw access hole); Yz unfilled, Yz filled, Ti unfilled and Ti filled (with the screw access (Ø = 2.5 mm) in the center). For the unfilled groups, only a polytetrafluoroethylene tape was used. Resin composite (Tetric N-Ceram, Ivoclar AG) was applied to the screw access hole for the filled groups (Yz and Ti). A cyclic fatigue test was carried out (load of 200 N, 10,000 cycles each; 20 Hz of frequency, step size of 100 N until failure detection (radial/cone crack). The fatigue failure load (FFL) and number of cycles until failure (CFF) were recorded for statistical purposes. The stress distribution (MPa) was evaluated by finite element analysis. A statistically positive effect of the abutment material and the presence of the screw access hole was observed (p ≤ 0.05). The rigid groups (without screw access holes) depicted almost 100% of survival after the fatigue tests. Among the other groups, the Yz-filled group showed the best performance (p ≤ 0.05), followed by the Yz unfilled group. The Ti groups depicted lower values of FFL and CFF, with the Ti unfilled group showing the most unfavorable fatigue behavior (p ≤ 0.05). The lowest tensile stress concentration in the restorative material was observed with the use of rigid abutments, the filled groups depicted intermediate values, while unfilled groups showed the highest stress concentration (Yz rigid = 306.3 MPa; Ti rigid = 310.4 MPa < Yz filled = 490.7 MPa; Ti filled = 498.9 MPa < Yz unfilled = 707.6 MPa; Ti unfilled = 719.7 MPa). Therefore, the presence of a screw-access hole decreases the mechanical performance of a lithium disilicate ceramic regardless of the abutment material. In the presence of a screw-access hole, zirconia abutments depicted a higher fatigue failure load when compared with titanium. The filling of the abutment screw-access hole with resin composite increased the mechanical performance of the simulated restoration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To evaluate the effect of different surface treatments on the morphology, shear bond, and flexural fatigue strength of a repaired translucent zirconia., Methods: Monolithic disc-shaped specimens of translucent zirconia were prepared and ground to simulate repair areas. Four groups underwent different treatments: Air-MDP (air-abrasion with alumina particles and 10-MDP primer), Si -Sil (silica-coated alumina particles with MDP-containing silane), Si -MDP (silica coating with 10-MDP primer), and Uni adhe (universal adhesive). After roughness measurements and treatments, repairs were done using resin composite. Shear bond and flexural (n = 15) fatigue tests were performed. Surface topography, interfacial analysis, fractographic, and finite element analysis were conducted., Results: The zirconia roughness was similar between the groups, however, the surface topography was modified according to the surface treatments. Si -Sil generated higher and more stable bond strength values (20.69 MPa) between translucent zirconia and resin composite when compared to Uni adhe (15.75 MPa) considering the fatigue bond strength scenario, while it was similar to Si -MDP (17.70 MPa) and Air-MDP (18.97 MPa). Regarding the mechanical behavior, Si -Sil (680.83 MPa) also showed higher and significantly different fatigue strength when compared to Uni adhe (584.55 MPa), while both were similar to Si -MDP (634.22 MPa) and Air-MDP (641.86 MPa)., Conclusion: The association of mechanical and chemical approaches is essential for long-term bond strength and optimized mechanical behavior, being air-abrasion protocols and the use of silane and/or MDP-based primers suitable for zirconia repair protocols. It was found that relying solely on a universal adhesive was not as effective as other options available., Clinical Significance: The surface treatment of repair protocols affects translucent zirconia's morphology. To enhance fatigue behavior in repaired monolithic zirconia, air abrasion is crucial. Exclusive use of a universal adhesive is less effective than other choices. A primer containing silane/MDP holds the potential for stable bond strength and optimized mechanical performance., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

This study aimed to evaluate the effect of low and high viscosities of dual-cured resin cement on the mechanical fatigue behavior of yttria tetragonal zirconia polycrystals (3Y-TZP) and yttria-stabilized zirconia (4YSZ) adhesively luted to a dentin analogue (glass fiber-reinforced epoxy resin). Ceramic discs were randomly divided into four groups (n = 20) based on the following study factors: dual-cured resin cement viscosities (low and high) and zirconia microstructure (3Y-TZP and 4YSZ). The discs were treated by air abrasion with aluminum oxide particles (50 μm), followed by the application of primer, and then luted with high or low viscosity resin cement to the dentin analogue. Subsequently, the luted sets underwent a step-stress fatigue test, which involved an initial load of 200 N, step increments of 100 N, 10,000 cycles per step, and a frequency of 20 Hz. Data on fatigue failure load (FFL) and the number of cycles for failure (CFF) were collected and analyzed using survival tests, including Kaplan-Meier and Mantel-Cox analyses, as well as Weibull analysis. Additionally, topography analysis, fractographic features, bonding interface analysis, and Raman spectroscopy were performed. The results revealed that 3Y-TZP exhibited superior fatigue behavior compared to 4YSZ, regardless of the viscosity of the resin cement used for luting. Among all groups, 3Y-Low exhibited the best fatigue performance, while 4YSZ luted with low or high viscosity resin cements yielded the lowest fatigue behavior (FFL). There were no significant differences in Weibull modulus among the groups. After air abrasion, both ceramics showed similar topography. Raman analysis indicated that the surface of 3Y-TZP ceramics prior to sintering had a monoclinic phase, which transitioned predominantly to tetragonal phase peaks after sintering. A similar transition was observed in 4YSZ ceramics. In summary, 3Y-TZP exhibited superior mechanical fatigue behavior compared to 4YSZ. The influence of resin cement viscosity on fatigue behavior was more pronounced in 3Y-TZP, with low-viscosity resin cement enhancing its performance. However, the mechanical fatigue behavior of 4YSZ was less affected by the viscosity of the dual-cured resin cement, showing similar results with both low and high viscosities. In conclusion, 3Y-TZP demonstrated superior mechanical fatigue behavior compared to 4YSZ. The impact of resin cement viscosity on fatigue behavior was more pronounced in 3Y-TZP, with low-viscosity resin cement enhancing its performance. Conversely, the mechanical fatigue behavior of 4YSZ was less sensitive to the viscosity of the dual-cured resin cement, resulting in similar outcomes with both low and high viscosities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The COVID-19 disease, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), emerged in late 2019 and rapidly spread worldwide, becoming a pandemic that infected millions of people and caused significant deaths. COVID-19 continues to be a major threat, and there is a need to deepen our understanding of the virus and its mechanisms of infection. To study the cellular responses to SARS-CoV-2 infection, we performed an RNA sequencing of infected vs. uninfected Calu-3 cells. Total RNA was extracted from infected (0.5 MOI) and control Calu-3 cells and converted to cDNA. Sequencing was performed, and the obtained reads were quality-analyzed and pre-processed. Differential expression was assessed with the EdgeR package, and functional enrichment was performed in EnrichR for Gene Ontology, KEGG pathways, and WikiPathways. A total of 1040 differentially expressed genes were found in infected vs. uninfected Calu-3 cells, of which 695 were up-regulated and 345 were down-regulated. Functional enrichment analyses revealed the predominant up-regulation of genes related to innate immune response, response to virus, inflammation, cell proliferation, and apoptosis. These transcriptional changes following SARS-CoV-2 infection may reflect a cellular response to the infection and help to elucidate COVID-19 pathogenesis, in addition to revealing potential biomarkers and drug targets.

This study evaluated the mechanical behavior and risk of failure of three CAD-CAM crowns repaired with different resin composites through a three-dimensional (3D) finite element analysis. Three-dimensional models of different cusp-repaired (conventional nanohybrid, bulk-fill, and flowable resin composites) crowns made of zirconia, lithium disilicate, and CAD-CAM resin composite were designed, fixed at the cervical level, and loaded in 100 N at the working cusps, including the repaired one. The models were analyzed to determine the Maximum Principal and Maximum Shear stresses (MPa). Complementary, an in vitro shear bond strength test ( n = 10) was performed to calculate the risk of failure for each experimental group. The stress distribution among the models was similar when considering the same restorative material. The crown material affected the stress concentration, which was higher for the ceramic models (±9 MPa for shear stress; ±3 MPa for tensile stress) than for the CAD-CAM composite (±7 MPa for shear stress; ±2 MPa for tensile stress). The shear bond strength was higher for the repaired CAD-CAM resin composite (±17 MPa) when compared to the ceramics (below 12 MPa for all groups), while the repair materials showed similar behavior for each substrate. The stress distribution is more homogenous for repaired resin composite crowns, and a flowable direct resin composite seems suitable to repair ceramic crowns with less risk of failure.

Statement of Problem: The color of monolithic zirconia restorations is obtained by presintering or postsintering coloring techniques. However, studies on the differences in surface characteristics and their influence on color stability are lacking., Purpose: The purpose of this in vitro study was to evaluate the influence of shading and staining techniques for a zirconia ceramic on the surface characteristics and colorimetric parameters (color difference, translucency, and whiteness index) after exposure to coffee or red wine and then polishing., Material and Methods: Ceramic disks (N=30; Ø10×1mm) were allocated into 3 groups: preshaded-shaded by the manufacturer (IPS e.max ZirCAD MT, shade A2); manually shaded-unshaded zirconia (IPS e.max ZirCAD MT, bleaching shade-BL) colored by the brushing technique, before sintering; stained-unshaded zirconia (IPS e.max ZirCAD MT BL) colored by the staining technique, after sintering. Spectrophotometric color assessments ensured the same initial perceived color (Vita Classical A2) for specimens included in the study (∆E 00 <1.77 acceptability threshold). Surface characteristics were assessed by scanning electron microscopy and atomic force microscopy. The specimens were immersed in coffee (n=5) or red wine (n=5) for 12 and 24 days and subsequently polished. The data were statistically and descriptively analyzed for color differences (∆E 00 ), translucency parameters (TP 00 ), and whiteness indexes for dentistry (WI D ), considering acceptability and perceptibility thresholds., Results: The shaded groups found an irregular ceramic surface with uniformly sized zirconia crystals. The stained group found a glass-covered smoother surface. Significant alterations in color parameters (∆E 00 , TP 00 , WI D ) were observed with immersion in pigmenting beverages (P<.001) both after 12 days, and after 24 days. The shaded specimens had greater color alterations after immersion but benefited from the polishing procedure, which reduced color differences below an acceptable threshold in comparison with the baseline. Stained specimens had lower color alterations after immersion, but the polishing protocol was detrimental as it whitened the ceramic by subsurface exposure., Conclusions: The coloring technique influences the surface characteristics of zirconia ceramic and also the color parameters after exposure to colored beverages and polishing., (Copyright © 2023 Editorial Council for The Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Objective: the aim of this study was to evaluate the effect of resin composite layering on discolored substrates to obtain masking ability with monolithic ceramics., Materials and Methods: Four groups (n = 8) of computer-aided design/computer aided manufacturing (CAD/CAM) monolithic ceramics, shade A1, with thicknesses of 1.0 and 1.5 mm, were tested: feldspathic (FC), leucite-reinforced (LC), lithium disilicate-reinforced (LD), and translucent zirconia (5YSZ). Five substrates were used: A1 (used as reference), A3.5, C4, and coppery and silvery metals. The substrates were separated as non-layered or layered (with flowable opaque resin composite (FL), white opaque restorative resin composite (WD), and A1-shaded opaque restorative resin composite (A1D)). Resin composite layers of 0.5 and 1.0 mm were tested. The try-in paste, shade A1, was used as a luting agent. Translucency parameter (TP 00 ) was assessed for the ceramics. Color differences (∆E 00 ) were assessed for the restorative ceramics and resin composite layers over discolored substrates with the CIEDE2000 formula. The results were compared statistically, and descriptively with acceptability (AT, 1.77) and perceptibility (PT, 0.81) thresholds., Results: Feldspathic showed the highest TP 00 (for both ceramic thicknesses) and LD the lowest (for 1.5 mm of ceramic thickness) (P < 0.001). For substrate A3.5, layering with 1.0 mm of A1D or WD ensured ∆E 00 below PT for all ceramics tested (P < 0.001). The use of 0.5 mm of FL or 1.0 mm of A1D associated with ceramics LC, LD, and 5YSZ ensured ∆E 00 below AT for substrates C4 and coppery metal (P < 0.001). Silvery background layered with 0.5 mm of FL presented ∆E 00 below AT for all ceramics and ∆E 00 below PT for lithium disilicate of 1.0 mm of thickness (∆E 00  = 0.72)., Conclusions: Layering severely discolored substrates with selected opaque resin composites ensures masking ability for restoration with CAD/CAM monolithic ceramics., Clinical Significance: Severely discolored substrates are predictably restored with monolithic CAD/CAM ceramics by performing a previous layering of the substrate with opaque resin composite., (© 2023 Wiley Periodicals LLC.)

The purpose of the present study was to characterize the elastic modulus and Poisson's ratio of a resin cement with distinct viscosities, and to evaluate their impact on the static and fatigue strength of a translucent zirconia (4Y-PSZ) after air-abrasion surface treatment. Bar-shaped specimens of two different viscosities of resin cement (high and low) were obtained (25 × 10 × 3 mm). Sonelastic and Maxwell principles tests were performed to determine the elastic modulus and Poisson's ratio of each resin cement. Disc-shaped specimens of 4Y-PSZ were made (Ø = 15 mm, 1.2 mm in thickness) for the mechanical tests and allocated into groups according to two factors: surface treatment (presence or absence of air-abrasion with alumina particles; 45 μm grain-size); cement (absence, low or high viscosity). The static (n = 10) and cyclical (n = 15) biaxial flexural strength tests were performed by piston-on-three-balls geometry. A fatigue strength test was executed (20 Hz, initial stress of 60 MPa [12% of the mean static biaxial flexural strength], followed by increments of 25 MPa [5% of the mean static biaxial flexural strength] at each step of 10,000 cycles until the failure). The obtained data were analyzed by Weibull analysis. Survival rates were tabulated by the Kaplan-Meier test. Complementary analyses of surface roughness, topography, cross-sectional interfacial zone, fractography, and zirconia crystalline content (X-ray diffraction) were also performed. The evaluated resin cements with high and low viscosity presented similar elastic modulus (13.63 GPa; 12.74 GPa) and Poisson's ratio (0.32; 0.30), respectively. The air-abraded groups depicted higher mechanical strength of the zirconia ceramics than non-abraded groups (p˂ 0.05), regardless of the resin cement. 4Y-PSZ adhesively bonded to a high or low viscosity resin cement have statistically similar behavior (p˃ 0.05). The mechanical structural reliability of the 4Y-PSZ was not affected by the factors. Therefore, resin cement with high and low viscosity presented similar properties and potential to fill the zirconia surface, and did not affect the mechanical behavior of 4Y-PSZ. However, the air-abrasion surface treatment increased the static and fatigue flexural strength of the translucent zirconia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

This study aims to characterize the effect of pre- and/or post-sintering pigmentation techniques on the fatigue behavior of a 4YSZ ceramic (4 mol% yttrium stabilized zirconia). First, 4YSZ ceramic discs (IPS e.max ZirCAD, 15 mm diameter, and 1.2 mm thickness) were obtained and allocated according to the 'pigmentation technique' factor into 5 groups: Ctrl - unshaded ceramic disc (IPS e.max ZirCAD BL); Manuf - ceramic discs shaded by the manufacturer at block formation (IPS e.max ZirCAD MT A2); Brush - unshaded ceramic disc pigmented in the pre-sintered stage using a brush; Stain - unshaded ceramic disc pigmented in the post-sintering stage using a stain glaze (shade A2); Brush + Stain - combination of Brush and Stain techniques. The specimens were sintered and analyzed by a spectrophotometer (VITA Easyshade) for color differences (ΔE 00 calculated according to CIEDE, 2000) to ensure that they present the same perceived color (ΔE 00  ≤ 1.77, acceptability threshold). The specimens (n = 15) were submitted to biaxial flexural fatigue testing using a cyclic fatigue method (frequency of 20 Hz; 10,000 cycles per step; initial stress of 200 MPa; and step-size of 25 MPa) until specimen fracture. Fatigue strength (FS) and number of cycles until failure (CFF) were recorded with statistical purposes. Fractographic, complementary topography, elemental and roughness analyses were performed. The Ctrl shown the highest FS, CFF, and survival rates compared to the other conditions (p < 0.05), being only statistically similar to Brush. Stain showed the lowest FS, CFF and survival rates (p < 0.05). The Manuf and Brush + Stain shown intermediary performance. In regards of Weibull moduli, Brush shown the lowest values (lowest structural reliability), for both FS and CFF, being only statistically similar to Manuf. Topography analysis shown a uniform size of zirconia crystals in Ctrl, Manuf and Brush. In addition, a smooth glassy surface with some spots of impregnated pigment was observed in the groups where glaze was applied (Stain and Brush + Stain). This finding was corroborated by elemental analysis. Despite that, Stain and Brush + Stain presented the roughest surface (p < 0.05). In summary, the pigmentation techniques used to provide a Vita classical A2 color shade have a detrimental effect on the mechanical fatigue properties of a 4YSZ ceramic, except for the technique performed with the brush in the block pre-sintering stage. Despite this, the brush technique presents great variability in mechanical performance, resulting in lower structural reliability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Statement of Problem: Information regarding the masking ability of ceramic crowns over different implant abutment materials is scarce., Purpose: The purpose of this in vitro study was to evaluate the masking ability of different monolithic or bilayer ceramic materials with different thicknesses over substrates indicated for implant restorations by using opaque and translucent evaluation pastes., Material and Methods: Disk-shaped specimens, shade A1 (VITA Classic; Ø10×1.5 to 2.5 mm), of different ceramics (a bilayer system [yttria-stabilized zirconia infrastructure+porcelain veneer: Zir+Pc] and monolithic systems [lithium disilicate under low, medium, or high translucency: LtLD, MtLD, or HtLD, respectively, and a high-translucent yttria-stabilized zirconia: HtZir]) were made (n=4). The color difference (ΔE 00 ) was assessed by using the CIEDE2000 formula and considering the different ceramic systems over 5 implant abutment materials (A1 shade Zir [Zir A1]; white Zir [White Zir]; A1 low-translucency lithium disilicate [LD]; polyetheretherketone [PEEK]; and titanium [Ti]) when using 2 different evaluation pastes (translucent or opaque). The control comparison was the restorative material positioned over the Zir A1 substrate with a translucent evaluation paste. Statistical analysis was made by using a 2-way ANOVA and Tukey post hoc tests (α=.05) for ΔE 00 data considering the restorative material and luting agent factors as their association. Additionally, ΔE 00 data were qualitatively analyzed considering the acceptability and perceptibility thresholds. The translucency parameter (TP 00 ) of each restorative material was evaluated, and data were submitted to 1-way ANOVA and Tukey post hoc tests (α=.05)., Results: The most predictable masking ability was seen with Zir+Pc regardless of the evaluation paste used. Nevertheless, under 1.5-mm thickness, Zir+Pc did not adequately mask Ti (ΔE 00 >1.77). Most monolithic ceramics did not mask discolored substrates (PEEK or Ti, ΔE 00 >1.77). The exception was HtZir, which presented acceptable masking ability over PEEK at 2.5-mm thickness with both evaluation pastes (ΔE 00 <1.77). Regardless of the restorative material thickness, Zir+Pc showed the lowest (P<.05) TP 00 values (TP 00 =3.45 at 1.5-mm thickness; TP 00 =2.00 at 2.5-mm thickness), and HtLD presented the highest (P<.05, TP 00 =23.50 at 1.5-mm thickness; TP 00 =13.36 at 2.5-mm thickness). HtZir showed similar TP 00 to MtLD at 1.5-mm thickness and similar TP 00 to Zir+Pc when used at 2.5-mm thickness (P>.05)., Conclusions: Monolithic ceramics should be used with caution over discolored implant abutments. Bilayer systems (Zir+Pc) were the most predictable approach to adequately masking discolored substrates such as PEEK or Ti. An increased restoration thickness provided higher masking ability for all restorative materials tested., (Copyright © 2022 Editorial Council for The Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

microRNAs (miRNAs) are recognized as diabetes mellitus type 2 (T2DM) biomarkers useful for disease metabolism comprehension and have great potential as therapeutics targets. BDNF and IGF1 increased expression are highly involved in the benefits of insulin and glucose paths, however, they are down-regulated in insulin resistance conditions, while their expression increase is correlated to the improvement of glucose and insulin metabolism. Studies suggest the microRNA regulation of these genes in several different contexts, providing a novel investigation approach for comprehending T2DM metabolism and revealing potential therapeutic targets. In the present study, we investigate in different animal models (human, rat, and mouse) miRNAs that target BDNF and IGF1 in skeletal muscle tissue with T2DM physiological conditions. Bioinformatics tools and databases were used to miRNA prediction, molecular homology, experimental validation of interactions, expression in the studied physiological condition, and network interaction. The findings showed three miRNAs candidates for IGF1(miR-29a, miR-29b, and miR-29c) and one for BDNF (miR-206). The experimental evaluations and the search for the expression in skeletal muscle from T2DM subjects confirmed the predicted interaction between miRNA-mRNA for miR-29b and miR-206 through human, rat, and mouse models. This interaction was reaffirmed in multiple network analyses. In conclusion, our results show the regulation relationship between miR-29b and miR-206 with the investigated genes, in several tissues, suggesting an inhibition pattern. Nevertheless, these data show a large number of possible interaction physiological processes, for future biotechnological prospects.

Background: Alzheimer's disease is the most common neurodegenerative disease in the world, characterized by the progressive loss of neuronal structure and function, whose main histopathological landmark is the accumulation of β-amyloid in the brain., Objective: It is well known that exercise is a neuroprotective factor and that muscles produce and release myokines that exert endocrine effects in inflammation and metabolic dysfunction. Thus, this work intends to establish the relationship between the benefits of exercise through the chronic training of HIIT on cognitive damage induced by the Alzheimer's model by the injection of β amyloid 1-42 ., Methods: For this purpose, forty-eight male Wistar rats were divided into four groups: Sedentary Sham (SS), Trained Sham (ST), Sedentary Alzheimer's (AS), and Trained Alzheimer's (AT). Animals were submitted to stereotactic surgery and received a hippocampal injection of Aβ 1-42 or a saline solution. Seven days after surgery, twelve days of treadmill adaptation followed by five maximal running tests (MRT) and fifty-five days of HIIT, rats underwent the Morris water maze test. The animals were then euthanized, and their gastrocnemius muscle tissue was extracted to analyze the Fibronectin type III domain containing 5 (FNDC5), PPARG Coactivator 1 Alpha (PPARGC1A), and Integrin subunit beta 5 (ITGB5-R) expression by qRT-PCR in addition to cross-sectional areas., Results: The HIIT prevents the cognitive deficit induced by the infusion of amyloid β 1-42 (p < 0.0001), causes adaptation of muscle fibers (p < 0.0001), modulates the gene expression of FNDC5 (p < 0.01), ITGB5 (p < 0.01) and PPARGC1A (p < 0.01), and induces an increase in peripheral protein expression of FNDC5 (p < 0.005)., Conclusion: Thus, we conclude that HIIT can prevent cognitive damage induced by the infusion of Aβ 1-42 , constituting a non-pharmacological tool that modulates important genetic and protein pathways., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The fatigue behavior and FEA analysis of different ceramic materials cemented over distinct substrates for implant-supported crowns were evaluated in this study. Discs of 10 mm in diameter of both restorative and substrate materials were made and randomly allocated into pairs (n = 15) considering the two study factors: 'restorative ceramic material' (1 mm thickness) - polymer-infiltrated ceramic network (PICN), lithium disilicate (LD), zirconia-reinforced lithium silicate (ZLS), or translucent zirconia (TZ); and 'foundation substrate' (2 mm thickness) - polyetheretherketone (Peek) or yttrium-stabilized zirconia (YZ). Adhesive cementation was made with a dual cure resin cement. Fatigue testing was run using the step-stress methodology: initial load of 200 N for 5000 cycles, followed by steps of 10,000 cycles starting at 400 N up to 2800 N or until failure, step size of 200 N, frequency of 20 Hz. Data were analyzed by the Kaplan Meier and log-rank post-hoc tests. Fractography analysis (stereomicroscope and SEM) and FEA were also performed. Both factors under study and their interaction statistically influenced the fatigue failure load (FFL), cycles for failure (CFF) and survival rates (p < 0.001). The restorative materials bonded to YZ had higher FFL and CFF than when adhering to Peek, while restorative materials with more crystalline content (TZ and ZLS) showed higher FFL and CFF than LD and PICN. The fractography analysis showed that all materials bonded to YZ resulted in failures starting at the occlusal surface (Hertzian cone cracks), while materials bonded to Peek had radial cracks from the ceramic-cement intaglio surface. FEA analysis showed that tensile stress concentration decreased in the intaglio surface when testing the restorative material over a stiffer (YZ) foundation substrate. In addition, the higher the restorative material's crystalline content, the more the stress is concentrated within the material (TZ > ZLS ≥ LD > PICN) when bonded to the same foundation substrate. Thus, it concluded that a stiffer foundation substrate (YZ) enhances the load-bearing capacity under fatigue of the restorative set; that restorative materials with higher crystalline content results in higher fatigue performance of the set, regardless of the foundation used; and that the foundation material influences the failure pattern of the restorative set., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The excessive deposition of β-amyloid proteins (Aβ) is directly correlated with the establishment and development of Alzheimer's Disease (AD). Current treatments for AD only reduce symptoms instead of acting on Aβ, the primary etiological agent. Hence, the anti-amyloid effect of regular exercise has been widely investigated as an alternative therapy. This systematic review and meta-analysis examined the anti-amyloid effect of regular physical exercise in animal models of AD. The search was conducted on the electronic databases Pubmed, Embase, Scopus and Web of Science without data limitation and using the following describers: "amyloid beta" (OR senile plaque OR amyloid plaque) and "exercise" (OR physical activity OR training). The risk of bias was evaluated using the SYRCLE's tool. Meta-analyses were conducted using models of random continuous effects. A total of 36 studies were selected and most used: transgenic mice (n = 29), treadmill training, duration of 12 weeks (interval of 4 to 28 weeks), rate of 60 min/day (interval of 30 min and up until free access) and speed of 12 m/min (interval of 3.2 to 32 m/min). The hippocampus and cortex were the most frequently investigated regions. Meta-analysis demonstrated a decrease in Aβ with greater effect in unspecified isoforms Meta-analysis demonstrated a decrease in Aβ with greater effect in unspecified isoforms (N = 4; SMD = -2.71, IC 95%: -3.59, -1.84, p < 0.00001, Q2 = 3.38, I2 = 11%) and Aβ 1-42 (N = 21; SMD = -1.94, IC 95%: -2.37, -1.51, p < 0.00001, Q2 = 33,37, I2 = 40%). Concerning training, greater effect was found with: 1) swimming (N = 4; SMD = -1.98, IC 95%: -3,28 - -0,68, p = 0.003, Q2 = 9.74, I2 = 69%), 2) moderate intensity (N = 4; SMD = -2.03, IC 95%: -3.31 - -0.75, p < 0.005, Q 2  = 12.68, I 2  = 76%); 3) duration up to six weeks (N = 6; N = 6; SMD = -2.35, IC 95%: -3.15 - -1.55, p < 0.00001, Q 2  = 8.38, I 2  = 40%); 4) young animals (SMD = -2.00, IC 95%: -2.59 - -1.42, p < 0.00001, Q 2  = 24.90, I 2  = 52%); 5) in the amygdala region (N = 1; SMD = -8.56, IC 95%: -12.88 - -4.23, p = 0.0001) and females (N = 4; SMD = -2.14, IC 95%: -3.48 - -0.79, p = 0.002, Q 2  = 10.31, I 2  = 71%). However, the reduction of Aβ was associated with decrease of amyloidogenic pathway and increase of non-amyloidogenic. Hence, regular physical exercise demonstrated anti-amyloid effect in experimental models of AD through positive alterations in APP processing through different signaling pathways., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: Alzheimer's disease (AD) is the most common irreversible chronic neurodegenerative disease. It is characterized by the abnormal accumulation of β-amyloid protein (Aβ), which triggers homeostatic breakage in several physiological systems. However, the effect of chronic exercise on the formation of Aβ as an alternative therapy has been investigated. This systematic review examines the antiamyloid effect of different types and intensities of exercise, seeking to elucidate its neuroprotective mechanisms., Main Methods: The research was conducted in the electronic databases Pubmed, Embase, Scopus and Web of Science, using the following descriptors: "amyloid beta" (OR senile plaque OR amyloid plaque) and "exercise" (OR physical activity OR training). The risk of bias was evaluated through SYRCLE's Risk of Bias for experimental studies., Key Findings: 2268 articles were found, being 36 included in the study. A higher frequency of use of mice with genetic alterations was identified for the Alzheimer's disease (AD) model (n = 29). It was used as chronic training: treadmill running (n = 24), voluntary running wheel (n = 7), swimming (n = 4) and climbing (n = 2). The hippocampus and the cortex were the most investigated regions. However, physiological changes accompanied by the reduction of Aβ and associated with AD progression were verified. It is concluded that exercise reduces the production of Aβ in models of animals with AD., Significance: Nevertheless, this effect contributes to the improvement of several physiological aspects related to Aβ and that contribute to neurological impairment in AD., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Physical exercise is a health promotion factor regulating gene expression and causing changes in phenotype, varying according to exercise type and intensity. Acute strenuous exercise in sedentary individuals appears to induce different transcriptional networks in response to stress caused by exercise. The objective of this research was to investigate the transcriptional profile of strenuous experimental exercise., Methodology: RNA-Seq was performed with Rattus norvegicus soleus muscle, submitted to strenuous physical exercise on a treadmill with an initial velocity of 0.5 km/h and increments of 0.2 km/h at every 3 min until animal exhaustion. Twenty four hours post-physical exercise, RNA-seq protocols were performed with coverage of 30 million reads per sample, 100 pb read length, paired-end, with a list of counts totaling 12816 genes., Results: Eighty differentially expressed genes (61 down-regulated and 19 up-regulated) were obtained. Reactome and KEGG database searches revealed the most significant pathways, for down-regulated gene set, were: PI3K-Akt signaling pathway, RAF-MAP kinase, P2Y receptors and Signaling by Erbb2. Results suggest PI3K-AKT pathway inactivation by Hbegf, Fgf1 and Fgr3 receptor regulation, leading to inhibition of cell proliferation and increased apoptosis. Cell signaling transcription networks were found in transcriptome. Results suggest some metabolic pathways which indicate the conditioning situation of strenuous exercise induced genes encoding apoptotic and autophagy factors, indicating cellular stress., Conclusion: Down-regulated networks showed cell transduction and signaling pathways, with possible inhibition of cellular proliferation and cell degeneration. These findings reveal transitory and dynamic process in cell signaling transcription networks in skeletal muscle after acute strenuous exercise., Competing Interests: The authors declare there are no competing interests., (©2021 Felipe et al.)

Aim and Objective: This study aims to evaluate the effect of different resin cements on the bond strength (BS) of custom-made glass fiber posts (GFPs) using the push-out test., Materials and Methods: Twenty-four uniradicular bovine teeth were selected. The crowns were sectioned at the cementoenamel junction, and the root canals were treated. The post spaces of the teeth were prepared to a length of 12 mm to receive a GFP. The specimens were randomly assigned to three experimental groups ( n = 8), according to the resin cement used to fix the GFPs: RelyX U200 (U200), Allcem Core (ACC), and Allcem Dual (ACD). Each specimen was sectioned into six slices per root third (cervical, middle, and apical), which were subjected to the push-out test. BS values were calculated and compared using the Kruskal-Wallis and Friedman tests., Results: There were significant differences in the middle third, according to the resin cement type used ( p < 0.05). ACD showed lower BS values ( p < 0.05). Significant differences were observed for ACD among the thirds of the slices, with the lowest values also observed for the middle third ( p < 0.05)., Conclusion: The present study shows that ACC and U200 showed higher BS values compared with ACD, and were also less influenced by the depth of the root dentin., Clinical Significance: The restoration of endodontically treated teeth is a challenge in dentistry, and, in most cases, will require installation of fiberglass pins. In this respect, several types of resin cements are indicated for cementation of these pins; for this reason, their adhesiveness must be adequately investigated. Conventional cements and self-adhesive cements have shown satisfactory performance in cementing the custom-made GFPs, thereby making these cements satisfactory clinical choices. The present study suggests that ACD had lower performance than the other two cements evaluated.

Background: Alzheimer's disease (AD) is the most common and irreversible neurodegenerative disorder, and amyloid peptide plays a central role in its pathogenesis. Physical training contributes as a beneficial adaptation to AD. However, these effects may be underestimated because much of the literature used fixed training prescription variables (intensity and volume) throughout the protocol. Moreover, researchers poorly understand whether chronic high-intensity interval training (HIIT) exerts similar effects on the brain tissue of individuals with AD., Objective: This study evaluated the effect of 8 minutes of HIIT with incremental overload in an AD model., Methods: Forty male Wistar rats were divided into four groups: an untrained Sham group, Sham trained group, Aβ 1-42 (Alzheimer's) untrained group, and Aβ 1-42 (Alzheimer's) trained group (n=10 rats per group). Animals underwent stereotactic surgery and received a hippocampal injection of Aβ 1-42 or a saline solution. Seven days after surgery, two weeks of treadmill adaptation followed by a maximal running test (MRT) was performed. Then, animals were subjected to eight weeks of HIIT. Rats were sacrificed 24 h after the behavioral tests (open field and Morris water maze), hippocampal tissue was extracted to analyze the redox balance and BDNF/TrkB pathway, and neuritic plaques (NP) were detected by evaluating silver impregnation., Results: The AD trained group presented a physical capacity amelioration every two weeks and locomotor, learning, and memory improvements (p<0.05). These effects were accompanied by increased CAT and SOD levels, followed by decreased lipid peroxidation (p<0.05). Furthermore, increased activation of the BDNF/TrkB (p<0.05) pathway and decreased NP was observed., Conclusion: Based on these results, MRT was essential for an excellent chronic training protocol prescription and overload adjustment. Therefore, 8 minutes of HIIT daily for 8 weeks may reduce behavioral deficits by promoting a positive redox balance and increased activity of the BDNF/TrkB pathway that may contribute to NP attenuation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Leptospirosis is a zoonotic disease caused by a bacterium of the genus Leptospira that affects domestic animals, including cattle. Despite of this importance in livestock, little is known about the epidemiology of leptospirosis in cattle in Brazil and other tropical countries. In this context, the objective of this study was to perform the culture of urine and kidney (n = 372 animals) of slaughtered bovines of Minas Gerais state (Brazil), in order to obtain pure cultures of Leptospira strains and carry out its characterization by serological (microscopic agglutination test) and molecular techniques (rrs, secY sequencing and variable-number tandem-repeat genotyping). One strain, named UFU 02, was obtained from a male bovine without apparent alterations in ante-mortem examination. The strain was characterized belonging to species Leptospira kirschneri and serogroup Grippotyphosa. The serogroup Grippotyphosa is most often described in wild species, suggesting a link between domestic and wild cycles/environments. Considering the importance of the country in livestock breeding, the knowledge about leptospiral strains could help to control the disease in the herds., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

LASSBio-596 (2-[4-(1,4-thiazinan-4-ylsulfonyl) phenylcarbamoyl] benzoic acid) is a molecular hybrid of anti-tumor necrosis factor α (TNF-α) and phosphodiesterase 5 inhibitors, and its anti-inflammatory effects have been demonstrated in experimental models of inflammation. The aim of this study was to evaluate the gastroprotective effect of LASSBio-596 in an ethanol-induced acute gastritis model. Before induction of gastric damage, mice were pretreated with LASSBio-596 (20 mg per os (p.o.), N ω -Nitro-L-arginine methyl ester hydrochloride (L-NAME; 3 mg/kg, intraperitoneally [i.p.]) or with 1400W (10 mg/kg, i.p.) given alone or in their combinations. Thirty minutes later, gastric damage was induced by intragastric instillation of 50% ethanol (0.5 ml/25 g, by gavage). After 1 h, gastric damage (hemorrhagic or ulcerative lesions) was measured by planimetry. Samples of the stomach were also taken for histopathological assessment and for assays of tissue myeloperoxidase (MPO), glutathione (GSH), malondialdehyde (MDA), and inflammatory cytokines. Ethanol administration induced the development of gastric lesions in mice. LASSBio-596 reduced gastric damage, epithelial cell loss and hemorrhage, and restored the antioxidant defense system by decreasing the levels of MDA and the consumption of GSH in gastric mucosa. LASSBio-596 also decreased gastric TNF-α and interleukin-1β (IL-1β) protein levels, MPO enzymatic activity, and hemoglobin levels. Treatment with the nitric oxide synthase inhibitors L-NAME and 1400W reversed the effects of LASSBio-596 on ethanol-induced gastric lesions. LASSBio-596 did not alter mucus content and pH of gastric secretions. In summary, LASSBio-596 exerts protective effects against ethanol-induced gastric injury. The gastroprotective effects of LASSBio seem to be NO-dependent., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Regular exercise is an exogenous factor of gene regulation with numerous health benefits. The study aimed to evaluate human genes linked to physical exercise in an 'omic scale, addressing biological questions to the generated database. Three literature databases were searched with the terms 'exercise', 'fitness', 'physical activity', 'genetics' and 'gene expression'. For additional references, papers were scrutinized and a text-mining tool was used. Papers linking genes to exercise in humans through microarray, RNA-Seq, RT-PCR and genotyping studies were included. Genes were extracted from the collected literature, together with information on exercise protocol, experimental design, gender, age, number of individuals, analytical method, fold change and statistical data. The 'omic scale dataset was characterized and evaluated with bioinformatics tools searching for gene expression patterns, functional meaning and gene clusters. As a result, a physical exercise-related human gene compendium was created, with data from 58 scientific papers and 5.147 genes functionally correlated with 17 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. While 50.9% of the gene set was up-regulated, 41.9% was down-regulated. 743 up- and 530 down-regulated clusters were found, some connected by regulatory networks. To summarize, up- and down-regulation was encountered, with a wide genomic distribution of the gene set and up- and down-regulated clusters possibly assembled by functional gene evolution. Physical exercise elicits a widespread response in gene expression., Competing Interests: The authors declared no conflict of interests regarding the publication of this manuscript.

Objective:  To evaluate the impact of sexual function (SF) in the quality of life (QoL) of women with premature ovarian insufficiency (POI)., Methods:  Case-control study in which 80 women with POI were evaluated using estrogen plus progestogen therapy, compared with 80 women matched by age (±2 years) and presenting preserved gonadal function. Sexual function was evaluated using the Female Sexual Function Index (FSFI), and the QoL was evaluated using the World Health Organization's (WHO) QoL assessment instrument (WHOQoL-BREF)., Results:  The mean age of the women with POI and of the control group was 38.4 ± 7.3 years and 38.1 ± 7.3 years respectively. The QoL, was worse among the POI group, and there were significant differences in the physical (63.4 ± 17.4 and 72.7 ± 15.2 respectively, p  = 0.0004) and psychological (63.2 ± 14.6 and 69.3 ± 13.9 respectively, p  = 0.0075) domains among this group when compared with the control group. Women with POI presented significantly lower arousal, lubrication, orgasm and satisfaction, more dyspareunia and a worse FSFI scores when compared with the control group. All aspects of SF correlate directly with the worsening of the QoL regarding social relationships., Conclusion:  Women with POI showed worse QoL and SF than the control group. The psychological aspects (desire, excitement, orgasm and sexual satisfaction) of SF had greater influence on the parameters of the QoL, while the physical aspects (pain and lubrication) had a low impact on the QoL. The poor SF in women with POI is directly correlated with a worsening across multiple domains of the QoL; however, the negative impact is particularly important in the social domain. These results suggest that the improvement in sexuality can improve the social interactions of women with POI., Competing Interests: The authors have no conflicts of interest to declare., (Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.)

Aim: The objective was to evaluate the effects of nitric oxide (NO) and hydrogen sulfide (H 2 S) donors and possible interactions between these two systems in modulating gastric function., Methods: Mice received saline, sodium nitroprusside (SNP), or sodium hydrosulfite (NaHS), and after 1 h, the animals were killed for immunofluorescence analysis of CSE or eNOS expressions, respectively. Other groups received saline, SNP, NaHS, Lawesson's reagent (H 2 S donor), PAG + SNP, L-NAME, L-NAME + NaHS, or L-NAME + Lawesson's reagent. Then, the gastric secretions (mucous and acid), gastric blood flow, gastric defense against ethanol, and gastric motility (gastric emptying and gastric contractility) were evaluated., Results: SNP and NaHS increased the expression of CSE or eNOS, respectively. SNP or Lawesson's reagent did not alter gastric acid secretion but increased mucus production, and these effects reverted with PAG and L-NAME treatment, respectively. SNP or NaHS increased gastric blood flow and protected the gastric mucosa against ethanol injury, and these effects reverted with PAG and L-NAME treatments, respectively. SNP delayed gastric emptying when compared with saline, and PAG partially reversed this effect. NaHS accelerate gastric emptying, and L-NAME partially reversed this effect. SNP and NaHS alone induced gastric fundus and pylorus relaxation. However, pretreatment with PAG or L-NAME reversed these relaxant effects only in the pylorus but not in the gastric fundus., Conclusion: NO and H 2 S interact in gastric physiological functions, and this "cross-talk" is important in the control of mucus secretion, gastric blood flow, gastric mucosal defense, and gastric motility, but not in the control of basal gastric acid secretion.

Objective:: To evaluate the effects of passive inhalation of cigarette smoke on the respiratory system of guinea pigs., Methods:: Male guinea pigs were divided into two groups: control and passive smoking, the latter being exposed to the smoke of ten cigarettes for 20 min in the morning, afternoon and evening (30 cigarettes/day) for five days. After that period, inflammatory parameters were studied by quantifying mesenteric mast cell degranulation, as well as oxidative stress, in BAL fluid. In addition, we determined MIP, MEP, and mucociliary transport (in vivo), as well as tracheal contractility response (in vitro)., Results:: In comparison with the control group, the passive smoking group showed a significant increase in mast cell degranulation (19.75 ± 3.77% vs. 42.53 ± 0.42%; p < 0.001) and in the levels of reduced glutathione (293.9 ± 19.21 vs. 723.7 ± 67.43 nM/g of tissue; p < 0.05); as well as a significant reduction in mucociliary clearance (p < 0.05), which caused significant changes in pulmonary function (in MIP and MEP; p < 0.05 for both) and airway hyperreactivity., Conclusions:: Passive inhalation of cigarette smoke caused significant increases in mast cell degranulation and oxidative stress. This inflammatory process seems to influence the decrease in mucociliary transport and to cause changes in pulmonary function, leading to tracheal hyperreactivity., Objetivo:: Avaliar os efeitos da inalação passiva da fumaça de cigarro no sistema respiratório de cobaias., Métodos:: Foram utilizadas cobaias machos, divididas em dois grupos: controle e tabagismo passivo, esse último exposto à fumaça de dez cigarros por 20 min pela manhã, tarde e noite (30 cigarros/dia) por 5 dias. Após esse período, parâmetros inflamatórios foram estudados através da contagem de degranulação de mastócitos no mesentério e de estresse oxidativo a partir do LBA. Adicionalmente, foram verificadas PImáx, PEmáx, transporte mucociliar (in vivo) e contratilidade traqueal (in vitro)., Resultados:: Na comparação com o grupo controle, o grupo tabagismo passivo apresentou um aumento significativo na degranulação de mastócitos (19,75 ± 3,77% vs. 42,53 ± 0,42%; p < 0,001), nos níveis de glutationa reduzida (293,9 ± 19,21 vs. 723,7 ± 67,43 nM/g de tecido; p < 0,05) e uma redução significativa no transporte mucociliar (p < 0,05), provocando alterações significativas na função pulmonar, tanto na PImáx como na PEmáx (p < 0,05 para ambas), e hiper-reatividade nas vias aéreas., Conclusões:: A inalação passiva da fumaça de cigarro ocasionou aumentos significativos na degranulação de mastócitos e no estresse oxidativo. Esse processo inflamatório parece ter influenciado a diminuição do transporte mucociliar e causado alterações na função pulmonar, proporcionando um quadro de hiper-reatividade traqueal.

Western Iberia has recently shown increasing frequency of drought conditions coupled with heatwave events, leading to exacerbated limiting climatic conditions for plant growth. It is not clear to what extent wood growth and density of agroforestry species have suffered from such changes or recent extreme climate events. To address this question, tree-ring width and density chronologies were built for a Pinus pinaster stand in southern Portugal and correlated with climate variables, including the minimum, mean and maximum temperatures and the number of cold days. Monthly and maximum daily precipitations were also analyzed as well as dry spells. The drought effect was assessed using the standardized precipitation-evapotranspiration (SPEI) multi-scalar drought index, between 1 to 24-months. The climate-growth/density relationships were evaluated for the period 1958-2011. We show that both wood radial growth and density highly benefit from the strong decay of cold days and the increase of minimum temperature. Yet the benefits are hindered by long-term water deficit, which results in different levels of impact on wood radial growth and density. Despite of the intensification of long-term water deficit, tree-ring width appears to benefit from the minimum temperature increase, whereas the effects of long-term droughts significantly prevail on tree-ring density. Our results further highlight the dependency of the species on deep water sources after the juvenile stage. The impact of climate changes on long-term droughts and their repercussion on the shallow groundwater table and P. pinaster's vulnerability are also discussed. This work provides relevant information for forest management in the semi-arid area of the Alentejo region of Portugal. It should ease the elaboration of mitigation strategies to assure P. pinaster's production capacity and quality in response to more arid conditions in the near future in the region.

Background: An approach to predict fire growth in an operational setting, with the potential to be used as a decision-support tool for fire management, is described and evaluated. The operational use of fire behaviour models has mostly followed a deterministic approach, however, the uncertainty associated with model predictions needs to be quantified and included in wildfire planning and decision-making process during fire suppression activities. We use FARSITE to simulate the growth of a large wildfire. Probabilistic simulations of fire spread are performed, accounting for the uncertainty of some model inputs and parameters. Deterministic simulations were performed for comparison. We also assess the degree to which fire spread modelling and satellite active fire data can be combined, to forecast fire spread during large wildfires events., Results: Uncertainty was propagated through the FARSITE fire spread modelling system by randomly defining 100 different combinations of the independent input variables and parameters, and running the correspondent fire spread simulations in order to produce fire spread probability maps. Simulations were initialized with the reported ignition location and with satellite active fires. The probabilistic fire spread predictions show great potential to be used as a fire management tool in an operational setting, providing valuable information regarding the spatial-temporal distribution of burn probabilities. The advantage of probabilistic over deterministic simulations is clear when both are compared. Re-initializing simulations with satellite active fires did not improve simulations as expected., Conclusion: This information can be useful to anticipate the growth of wildfires through the landscape with an associated probability of occurrence. The additional information regarding when, where and with what probability the fire might be in the next few hours can ultimately help minimize the negative environmental, social and economic impacts of these fires.

Background: Diabetes mellitus is a chronic degenerative disease responsible for hyperglycemic episodes through insulin secretion deficiency or cellular resistance. Clinical diagnosis in diabetic patients established that this disease affects the CNS, damaging the brain and impairing cognition, and thus establishing a clinical diabetic condition named diabetic encephalopathy. Despite the physiological mechanisms responsible for the development diabetic encephalopathy are still unclear, an excessive formation of reactive oxygen species, an alteration of acetylcholinesterase activity, and a reduction of growth factor levels, may be related with the pathogenesis of this condition. Pharmacological treatments with natural compounds have been proven useful to treat and cure a wide variety of diseases through their antioxidant actions., Methods: This study built a compendium of chemical compounds used for the treatment of diabetic encephalopathy demonstrating the most important physiological targets that future drugs should aim for, reviewing them., Results: As previously suspected, antioxidants and acetylcholinesterase inhibitors were useful to prevent memory loss in streptozotocin-induced animals. In addition, growth factors showed an improvement of memory in diabetic rodents. Most studies focused on antioxidant compounds despite cross studies researched both antioxidants and acetylcholinesterase activities., Conclusion: Therefore, it could be suggested that future studies regarding treatments for diabetic encephalopathy should focus on the antioxidant profile and acetylcholinesterase, since they seem to play pivotal roles in cognitive impairment in diabetes. No less important, studies with growth factors are also important physiological targets for treating the diabetic encephalopathy.

Background: It has been reported that simvastatin, a statin commonly prescribed for its anti-inflammatory and antioxidant effects, has gastroprotective effects in indomethacin and ethanol-induced gastric ulcers. However, the effects of simvastatin on alendronate-induced gastric mucosal injury remain unexplored., Aim: This study investigated the use of simvastatin for the treatment of alendronate-induced gastric ulcers in rats., Methods: Female rats were pretreated with vehicle or simvastatin (20 and 60 mg/kg p.o.). After 1 h, the rats received alendronate (50 mg/kg p.o.). Simvastatin was administered once daily for 7 days, and from the fourth day of simvastatin treatment, alendronate was administered once daily for 4 days. On the final day of treatment, 4 h after alendronate administration, animals were euthanized, their stomachs were removed, and gastric damage was measured. Samples of the stomach were fixed in 10 % formalin immediately after their removal for subsequent histopathological assessment. Unfixed samples were weighed, frozen at -80 °C until assayed for glutathione (GSH), malondialdehyde (MDA), and cytokine levels and myeloperoxidase (MPO) activity. A third group was used to measure mucus and gastric secretion., Results: Pretreatment with simvastatin prevented alendronate-induced macroscopic gastric damage and reduced the levels of MDA and GSH, TNF-α and IL-1β, MPO activity, and mucus levels, in the stomach., Conclusions: This study demonstrates the protective effects of simvastatin against alendronate-induced gastric ulceration. Maintenance of mucosal integrity, inhibition of neutrophil activity, and reduced oxidative stress associated with decreased gastric acidity may explain the gastroprotective effects of simvastatin.

Objective and Design: This study had investigated the anti-inflammatory activity of a seed lectin (LAL) isolated from Lonchocarpus araripensis., Material/methods: LAL was purified by affinity chromatography (chitin column) and ion exchange chromatography (DEAE-Sephacel). In vitro LAL was tested for hemagglutinating activity against rabbit erythrocytes. In vivo LAL was assessed for the anti-inflammatory activity via intravenous injection (i.v.) in Swiss mice (25-30 g; n = 6/group) in models of paw edema and peritonitis., Statistical Analysis: ANOVA (p < 0.05)., Results: LAL revealed two bands of 30 and 60 kDa (SDS-PAGE) and exhibited hemagglutinating activity. LAL (10 mg/kg) inhibited the paw edema (77%) and vascular permeability (26%) induced by carrageenan, and the paw edema induced by serotonin (80%), bradykinin (49%), sodium nitroprusside (83%), TNF-α (75%) and PGE2 (64%). LAL also inhibited the neutrophil migration induced by fMLP (70%) or carrageenan (69%). The intravital microscopy showed that LAL inhibited rolling (83%) and adhesion (70%) of leukocytes. LAL anti-inflammatory effect was reversed by its association with N-acetyl-glucosamine. The nine-daily treatment with LAL (10 mg/kg; i.v.) showed no toxicity., Conclusion: The novel N-acetyl-D-glucosamine-binding lectin isolated from L. araripensis seeds presents anti-inflammatory effect involving the lectin domain and the inhibition of 5-HT, BK, PGE2, NO, TNF-α and leukocyte rolling and adhesion.

Aims: This study analyzed the sensorial, structural and functional response of rats subjected to paw immobilization., Main Methods: Animal pelvis, hip, knee and ankle were immobilized using waterproof tape during two weeks for assessment of sensorial response to thermal (hot plate test) and mechanical stimuli (Von Frey test), motor system structure (histology and radiography) and muscle function (soleus contractility)., Key Findings: Disuse animals became more responsive to thermal stimuli (49%), although less responsive to mechanical challenge (58%). Disuse animals showed local injuries such as reduction in muscle fiber diameter (16.7% in gastrocnemius, 5.7% in soleus), contractile activity (55% of the control maximal tonic contraction) and tibia cortical thickness (9.3%), besides increased nitrite:protein ratio, suggestive of protein degradation. Disuse also evoked systemic adaptations that include increase in serum lactate dehydrogenase (36.1%) and alkaline phosphatase (400%), but reduction in calcium (8.4%) and total serum protein (5.5%), especially albumin (34.2%)., Significance: Two weeks of functional paw disuse leads to local and systemic harmful adaptive changes in sensorial and structural systems. This study brings new insights into nervous and motor system mechanism associated with therapeutic limb immobilization in muscle and skeletal pathological conditions., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: Acute kidney injury (AKI) remains a great problem in clinical practice. Renal ischemia/reperfusion (I/R) injury is a complex pathophysiological process. Propolis is a natural polyphenol-rich resinous substance collected by honeybees from a variety of plant sources that has anti-inflammatory and anti-oxidative properties. Red propolis (RP) protection in renal I/R injury was investigated., Methods: Male Wistar rats underwent unilateral nephrectomy and contralateral renal I/R (60 min). Rats were divided into four groups: (1) sham group, (2) RP group (sham-operated rats treated with RP), 3) IR group (rats submitted to ischemia) and (4) IR-RP (rats treated with RP before ischemia). At 48 h after reperfusion, renal function was assessed and kidneys were removed for analysis., Results: I/R increased plasma levels of creatinine and reduced creatinine clearance (CrCl), and RP provided protection against this renal injury. Red propolis significantly improves oxidative stress parameters when compared with the IR group. Semiquantitative assessment of the histological lesions showed marked structural damage in I/R rats compared with the IR-RP rats. RP attenuates I/R-induced endothelial nitric oxide-synthase down regulation and increased heme-oxygenase expression in renal tissue., Conclusion: Red propolis protects kidney against acute ischemic renal failure and this protection is associated with reduced oxidative stress and eNOS and heme-oxygenase up regulation., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

Purpose: To evaluate some microbiological aspects of the vaginal flora and the vaginal trophism of women with premature ovarian failure (POF) in use of oral hormone therapy., Methods: A cross-sectional study with 36 women with POF under the age of 40 years using oral hormonal therapy. They were age matched with 36 women with normal gonadal function (control group). The characteristics of the vaginal epithelium were assessed through the hormonal vaginal cytology, vaginal pH measurement and vaginal health index to identify vaginal disturbances. Vaginal microflora was evaluated by the amine test, bacterioscopy (Nugent score) and culture for fungi to identify vaginal abnormal microflora and fungi infections., Results: Despite the fact that there were no statistical significant differences related to the cytological aspects and pH measurements, it was found that the vaginal health index was highly superior in the control group than in the POF group (23.4 ± 1.8 vs 20.8 ± 3.5), p < 0.0001 despite both groups had trophic scores. There were no statistical significance differences regarding to vaginal microflora types and fungi infection., Conclusion: Oral hormone therapy for young women with POF seems to be good enough to reestablish the epithelium cells, vaginal pH and microflora.

In this study, the amino acid sequence and anti-inflammatory effect of Bauhinia bauhinioides (BBL) lectin were evaluated. Tandem mass spectrometry revealed that BBL possesses 86 amino acid residues. BBL (1 mg/kg) intravenously injected in rats 30 min prior to inflammatory stimuli inhibited the cellular edema induced by carrageenan in only the second phase (21% - 3 h, 19% - 4 h) and did not alter the osmotic edema induced by dextran. BBL also inhibited carrageenan peritoneal neutrophil migration (51%), leukocyte rolling (58%) and adhesion (68%) and the neutrophil migration induced by TNF-α (64%). These effects were reversed by the association of BBL with galactose, demonstrating that the carbohydrate-binding domain is essential for lectin activity. In addition, BBL reduced myeloperoxidase activity (84%) and TNF-α (68%) and IL1-β (47%) levels. In conclusion, the present investigation demonstrated that BBL contains highly homologous isolectins, resulting in a total of 86 amino acid residues, and exhibits anti-inflammatory activity by inhibiting neutrophil migration by reducing TNF-α and IL1-β levels via the lectin domain., (Copyright © 2015 John Wiley & Sons, Ltd.)

Preclinical and clinical studies show that gastrointestinal (GI) inflammation can evoke sensory changes occasionally far from the original inflammatory site. Animal models of colitis with either trinitrobenzenesulphonic acid (TNBS) or mustard oil (MO) produce distinct patterns of somatic and visceral sensory changes. We evaluated the effects of four doses of i.v. vincristine 150 μg kg(-1) (total of 600 μg kg(-1) ) treatment on the somatic (thermal nociceptive threshold) and colonic (morphological) changes induced by TNBS or MO in rats. TNBS and MO groups were further submitted to vincristine or saline pretreatments. TNBS induced somatic hypersensitivity, while MO induced somatic hyposensitivity (P < 0.05) when compared to the saline and ethanol control groups. Vincristine per se induced somatic hypersensitivity (P < 0.05). This effect was enhanced by TNBS and reversed by MO treatments. Although vincristine increased the colitis area (colonic weight length(-1) ratio) and the Morris' score in TNBS-treated rats, it did not alter the colitis area and even lowered the Morris' score in MO-treated rats. Compared to the saline (control) group, vincristine did not alter the colonic microscopic pattern. However, such lesions scores are higher (P < 0.05) in colitis groups induced by TNBS and MO, pretreated or not with vincristine. In conclusion, the somatic changes induced by different models of experimental colitis are diverse and modulated differently by vincristine., (© 2015 John Wiley & Sons Ltd.)

Introduction: Women with premature ovarian failure (POF) often manifest complaints involving different aspects of sexual function (SF), regardless of using hormone therapy. SF involves a complex interaction between physical, psychological, and sociocultural aspects. There are doubts about the impact of different complaints on the global context of SF of women with POF., Aim: To evaluate the percentage of influence of each of the sexuality domains on the SF in women with POF., Methods: Cross-sectional study with 80 women with POF, matched by age to 80 women with normal gonadal function. We evaluated SF through the "Female Sexual Function Index" (FSFI), a comparison between the POF and control groups using the Mann-Whitney test. Component exploratory factor analysis was used to assess the proportional influence of each domain on the composition of the overall SF for women in the POF group., Main Outcome Measures: SF was evaluated using FSFI. Exploratory Factor Analysis for components was used to evaluate the role of each domain on the SF of women with POF., Results: The FSFI score was significantly worse for women with POF, with a decrease in arousal, lubrication, orgasm, satisfaction, and dyspareunia. Exploratory factor analysis of SF showed that the domain with greater influence in the SF was arousal, followed by desire, together accounting for 41% of the FSFI. The domains with less influence were dyspareunia and lubrication, which together accounted for 25% of the FSFI., Conclusion: Women with POF have impaired SF, determined mainly by changes in arousal and desire. Aspects related to lubrication and dyspareunia complaints have lower determination coefficient in SF. These results are important in adapting the approach of sexual disorders in this group of women., (© 2014 International Society for Sexual Medicine.)

Purpose: Lactobacillus acidophilus is widely used for gastrointestinal disorders, but its role in inflammatory conditions like in chemotherapy-induced mucositis is unclear. Here, we report the effect of L. acidophilus on 5-fluorouracil-induced (5-FU) intestinal mucositis in mice., Methods: Mice weighing 25-30 g (n = 8) were separated into three groups, saline, 5-FU, and 5-FU + L. acidophilus (5-FU-La) (16 × 10(9) CFU/kg). In the 5-FU-La group, L. acidophilus was administered concomitantly with 5-FU on the first day and alone for two additional days. Three days after the last administration of L. acidophilus, the animals were euthanized and the jejunum and ileum were removed for histopathological assessment and for evaluation of levels of myeloperoxidase activity, sulfhydryl groups, nitrite, and cytokines (TNF-α, IL-1β, CXCL-1, and IL-10). In addition, we investigated gastric emptying using spectrophotometry after feeding a 1.5-ml test meal by gavage and euthanasia. Data were submitted to ANOVA and Bonferroni's test, with the level of significance at p < 0.05., Results: Intestinal mucositis induced by 5-FU significantly (p < 0.05) reduced the villus height-crypt depth ratio and GSH concentration and increased myeloperoxidase activity and the nitrite concentrations compared with the control group. Furthermore, 5-FU significantly (p < 0.05) increased cytokine (TNF-α, IL-1β, and CXCL-1) concentrations and decreased IL-10 concentrations compared with the control group. 5-FU also significantly (p < 0.05) delayed gastric emptying and gastrointestinal transit compared with the control group. All of these changes were significantly (p < 0.05) reversed by treatment with L. acidophilus., Conclusions: Lactobacillus acidophilus improves the inflammatory and functional aspects of intestinal mucositis induced by 5-FU.

Here, we have evaluated the protective effect of the NO donor cis-[Ru(bpy)2(SO3)NO](PF6) (FOR0810) in experimental models of gastric damage induced by naproxen or ethanol in mice, and the involvement of soluble guanylate cyclase (sGC) and ATP-sensitive K(+) channels (KATP) in these events. Swiss mice were pre-treated with saline, ODQ (a soluble guanylate cyclase inhibitor; 10 mg kg(-1)) or glibenclamide (a KATP channels blocker; 10 mg kg(-1)). After either 30 min or 1 h, FOR0810 (3 mg kg(-1)) was administered. At the end of 30 min, the animals received naproxen (300 mg kg(-1)) by gavage. After 6 h, the animals were sacrificed and gastric damage, myeloperoxidase (MPO) activity, and TNF-α and IL-1β gastric concentrations were evaluated. In addition, the effects of FOR0810 on naproxen-induced mesenteric leukocyte adherence were determined by intravital microscopy. Other groups, were pre-treated with saline, ODQ or glibenclamide. After either 30 min or 1 h, FOR0810 was administered. At the end of 30 min, the animals received 50% ethanol by gavage. After 1 h, the animals were sacrificed, and gastric damage, gastric reduced glutathione (GSH) concentration and malondialdehyde (MDA) levels were determined. In naproxen-induced gastric damage, FOR0810 prevented gastric injury, decreased gastric MPO activity and leukocyte adherence, associated with a decrease in TNFα and IL-1β gastric concentrations. FOR0810 also prevented ethanol-induced gastric damage by increase in GSH levels and decrease in MDA levels. ODQ and glibenclamide completely reversed FOR0810's ability to prevent gastric damage by either naproxen or ethanol. We infer that FOR0810 prevented gastric damage through the activation of both sGC and KATP channels, which triggered a decrease in both free radical and cytokine production via the blocking of neutrophil adhesion and infiltration., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective and Design: The aim of this study was to investigate the possible involvement of the NO/cGMP/PKG/KATP+ pathway, cannabinoids and opioids in remote antinociception associated with 2,4,6-trinitrobenzene sulph onic acid (TNBS)-induced colitis., Methods: TNBS-induced colitis was induced by intracolonic administration of 20 mg of TNBS in 50% ethanol. After induction, carrageenan (500 μg/paw) or prostaglandin (PG) E2 (100 ng/paw) was injected in the rat's plantar surface and hypersensitivity was evaluated by the electronic von Frey test. Rats were pre-treated with L-Noarg one hour before carrageenan injection. L-Arginine was given 10 min before L-Noarg injections. ODQ, KT 5823, glibenclamide (Glib), naloxone and AM 251 or AM 630 were administered 30 min prior to carrageenan or PGE2 treatments., Results: Colitis induction by TNBS reduced PGE2 or carrageenan-induced hypersensitivity. Antinociception produced by TNBS-induced colitis was reversed significantly (P<0.05) by L-Noarg, ODQ, KT 5823, glibenclamide, naloxone, AM251 and AM630 treatments., Conclusions: TNBS-induced colitis causes antinociception in the rat paw. This disorder appears to be mediated by activation of the NO/cGMP/PKG/KATP pathway, endocannabinoids and endogenous opioids. This information may contribute to a better understanding of peripheral neurological dysfunctions occurring in Crohn's disease.

The Iberian viticultural regions are convened according to the Denomination of Origin (DO) and present different climates, soils, topography and management practices. All these elements influence the vegetative growth of different varieties throughout the peninsula, and are tied to grape quality and wine type. In the current study, an integrated analysis of climate, soil, topography and vegetative growth was performed for the Iberian DO regions, using state-of-the-art datasets. For climatic assessment, a categorized index, accounting for phenological/thermal development, water availability and grape ripening conditions was computed. Soil textural classes were established to distinguish soil types. Elevation and aspect (orientation) were also taken into account, as the leading topographic elements. A spectral vegetation index was used to assess grapevine vegetative growth and an integrated analysis of all variables was performed. The results showed that the integrated climate-soil-topography influence on vine performance is evident. Most Iberian vineyards are grown in temperate dry climates with loamy soils, presenting low vegetative growth. Vineyards in temperate humid conditions tend to show higher vegetative growth. Conversely, in cooler/warmer climates, lower vigour vineyards prevail and other factors, such as soil type and precipitation acquire more important roles in driving vigour. Vines in prevailing loamy soils are grown over a wide climatic diversity, suggesting that precipitation is the primary factor influencing vigour. The present assessment of terroir characteristics allows direct comparison among wine regions and may have great value to viticulturists, particularly under a changing climate.

Chronic use of alendronate has been linked to gastrointestinal tract problems. Our objective was to evaluate the role of the NO/cGMP/KATP signaling pathway and nitric oxide synthase expression in alendronate-induced gastric damage. Rats were either treated with the NO donor, sodium nitroprusside (SNP; 1, 3, and 10 mg/kg), or the NO synthase (NOS) substrate, L-arginine (L-Arg; 50, 100, and 200 mg/kg). Some rats were pretreated with either ODQ (a guanylate cyclase inhibitor; 10 mg/kg) or glibenclamide (KATP channels blocker; 10 mg/kg). In other experiments, rats were pretreated with L-NAME (non-selective NOS inhibitor; 10 mg/kg), 1400 W (selective inducible NOS [iNOS] inhibitor; 10 mg/kg), or L-NIO (a selective endothelial NOS [eNOS] inhibitor; 30 mg/kg). After 1 h, the rats were treated with alendronate (30 mg/kg) by gavage for 4 days. SNP and L-Arg prevented alendronate-induced gastric damage in a dose-dependent manner. Alendronate reduced nitrite/nitrate levels, an effect that was reversed with SNP or L-Arg treatment. Pretreatment with ODQ or glibenclamide reversed the protective effects of SNP and L-Arg. L-NAME, 1400 W, or L-NIO aggravated the severity of alendronate-induced lesions. In addition, alendronate reduced the expression of iNOS and eNOS in the gastric mucosa. Gastric ulcerogenic responses induced by alendronate were mediated by a decrease in NO derived from both eNOS and iNOS. In addition, our findings support the hypothesis that activation of the NO/cGMP/KATP pathway is of primary importance for protection against alendronate-induced gastric damage., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to evaluate the protective effect of the sulfated-polysaccharide (PLS) fraction extracted from the seaweed Gracilaria birdiae in rats with trinitrobenzenesulfonic acid (TNBS)-induced colitis., Methods: In the experiments involving TNBS-induced colitis, rats were pretreated with polysaccharide extracted from G. birdiae (PLS: 30, 60 and 90 mg/kg, 500 μL p.o.) or dexamethasone (control group: 1 mg/kg) once daily for 3 days starting before TNBS instillation (day 1). The rats were killed on the third day, the portion of distal colon was excised and washed with 0.9% saline and pinned onto a wax block for the evaluation of macroscopic scores. Samples of the intestinal tissue were used for histological evaluation and assays for glutathione (GSH) levels, malonyldialdehyde (MDA) concentration, myeloperoxidase (MPO) activity, nitrate and nitrite (NO3 /NO2 ) concentration and cytokines levels., Key Findings: PLS treatment reduced the macroscopic and microscopic TNBS-induced intestinal damage. Additionally, it avoided the consumption of GSH, decreased pro-inflammatory cytokine levels, MDA and NO3 /NO2 concentrations and diminished the MPO activity., Conclusions: Our results suggest that the PLS fraction has a protective effect against intestinal damage through mechanisms that involve the inhibition of inflammatory cell infiltration, cytokine releasing and lipid peroxidation., (© 2014 Royal Pharmaceutical Society.)

Intestinal mucositis is an important toxic side effect of 5-fluorouracil (5-FU) treatment. Saccharomyces boulardii is known to protect from intestinal injury via an effect on the gastrointestinal microbiota. The objective of the present study was to evaluate the effect of S. boulardii on intestinal mucositis induced by 5-FU in a murine model. Mice were divided into saline, saline (control)+5-FU or 5-FU+S. boulardii (16 × 10⁹ colony-forming units/kg) treatment groups, and the jejunum and ileum were removed after killing of mice for the evaluation of histopathology, myeloperoxidase (MPO) activity, and non-protein sulfhydryl group (mainly reduced glutathione; GSH), nitrite and cytokine concentrations. To determine gastric emptying, phenol red was administered orally, mice were killed 20 min after administration, and the absorbance of samples collected from the mice was measured by spectrophotometry. Intestinal permeability was measured by the urinary excretion rate of lactulose and mannitol following oral administration. S. boulardii significantly reversed the histopathological changes in intestinal mucositis induced by 5-FU and reduced the inflammatory parameters: neutrophil infiltration (control 1·73 (SEM 0·37) ultrastructural MPO (UMPO)/mg, 5-FU 7·37 (SEM 1·77) UMPO/mg and 5-FU+S. boulardii 4·15 (SEM 0·73) UMPO/mg); nitrite concentration (control 37·00 (SEM 2·39) μm, 5-FU 59·04 (SEM 11·41) μm and 5-FU+S. boulardii 37·90 (SEM 5·78) μm); GSH concentration (control 477·60 (SEM 25·25) μg/mg, 5-FU 270·90 (SEM 38·50) μg/mg and 5-FU+S. boulardii 514·00 (SEM 38·64) μg/mg). Treatment with S. Boulardii significantly reduced the concentrations of TNF-α and IL-1β by 48·92 and 32·21 % in the jejunum and 38·92 and 61·79 % in the ileum. In addition, S. boulardii decreased the concentrations of chemokine (C-X-C motif) ligand 1 by 5-fold in the jejunum and 3-fold in the ileum. Interestingly, S. boulardii reduced the delay in gastric emptying (control 25·21 (SEM 2·55) %, 5-FU 54·91 (SEM 3·43) % and 5-FU+S. boulardii 31·38 (SEM 2·80) %) and induced the recovery of intestinal permeability (lactulose:mannitol ratio: control 0·52 (SEM 0·03), 5-FU 1·38 (SEM 0·24) and 5-FU+S. boulardii 0·62 (SEM 0·03)). In conclusion, S. boulardii reduces the inflammation and dysfunction of the gastrointestinal tract in intestinal mucositis induced by 5-FU.