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The aim of this study was to investigate if grape or apple juices are able to protect bone tissue of rats exposed to cadmium. For this purpose, histopathological analysis and immunohistochemistry for RUNX-2 and RANK-L were investigated in this setting. A total of 20 adult Wistar rats were distributed into four groups ( n  = 5), as follows: control group, cadmium group, cadmium and grape juice group, and Cadmium and apple juice group. Control group received a single intraperitoneal (i.p.) water injection. Cadmium group received a single i.p. injection of cadmium chloride (1.2 mg/kg body weight) diluted in water. Cadmium and grape juice and cadmium and apple juice groups received a single i.p. injection of cadmium chloride (1.2 mg/kg body), and after 15 days, the rats were treated with grape or apple juices for 15 days, by gavage. All animals were euthanized 30 days after the beginning of experiment. Histopathological analysis in rat femur revealed extensive bone loss in rats intoxicated with cadmium. Grape or apple juices were able to increase bone formation. Cadmium inhibited RUNX-2 immunoexpression whereas cadmium increased RANK-L immunoexpression in rat bone cells. Grape or apple juices increased RUNX-2 and decreased RANK-L immunoexpression after cadmium intoxication. Taken together, our results demonstrate that grape or apple juices are able to exert therapeutic activity following cadmium intoxication in rat bone tissue as result of stimulatory effect of bone formation by RUNX-2 upregulation and RANK-L downregulation.

The purpose of the present study was to evaluate yellow mombin (Spondias mombin L.) juice as a vehicle for the Lactobacillus acidophilus NRRL B-4495 probiotic. The initial pH and fermentation temperature conditions were optimized by central composite rotational design. The beverage was evaluated for its chemical composition, bioactive properties, microbiological stability, survival in simulated gastrointestinal conditions and sensory analysis. The ideal conditions for probiotic juice production were an initial pH of 6.4 and 16 h of fermentation, with maximum viability of 12.9 ± 0.4 Log CFU/mL. The fermented juice showed a total phenolic concentration of 94.90 ± 7.12 GAE/mL and antioxidant activity, as measured by DPPH (0.31 ± 0.00 [mu]mol TE/mL) and ABTS sequestration (2.59 ± 0.30 [mu]mol TE/mL). Antibacterial activity could also be observed against S. aureus, E. coli and K. pneumoniae. The obtained formulation showed good microbiological stability when stored at 4ºC for 28 days. In addition, there was no significant change in viability after exposure to simulated gastrointestinal conditions. The sensory analysis showed that the probiotic beverage was not well accepted. However, the Just-About-Right (JAR) ideal scale test enabled identifying the specific attributes which need to be improved from the tasters' point of view so that it is possible to improve product acceptance.

The aim of the present study was to evaluate the in vivo response of different wavelengths (red and near-infrared) of light-emitting diode (LED) on full-thickness skin grafts (FTSG) in rats. Thirty rats were randomly allocated into three experimental groups: control group (C); red LED treated group (R); and near-infrared LED group (NIR). Skin grafts were irradiated daily for ten consecutive days, starting immediately after the surgery using a red (630 nm) or near-infrared (850 nm) LED. The results showed that the red wavelength LED significantly enhanced the skin graft score in relation to the NIR group and increased transforming growth factor beta (TGF-β) protein expression and density of collagen fibers compared with the other experimental groups. These results suggest that the red wavelength LED was efficient to improve the dermo-epidermal junction and modulate the expression proteins related to tissue repair.

Relapsing-remitting multiple sclerosis (RRMM) is a chronic, progressive, inflammatory and immune-mediated disease that affects the central nervous system and is characterized by episodes of neurological dysfunction followed by a period of remission. The pharmacological strategy aims to delay the progression of the disease and prevent relapse. Interferon beta and glatiramer are commonly used in the Brazilian public health system and are available to patients who meet the guideline criteria. The scenario of multiple treatments available and in development brings the need for discussion and evaluation of the technologies already available before the incorporation of new drugs. This study analyses the effectiveness of first-line treatment of RRMS measured by real-world evidence data, from the Brazilian National Health System (SUS). We conducted a non-concurrent national cohort between 2000 and 2015. The study population consisted of 22,722 patients with RRMS using one of the following first-line drugs of interest: glatiramer or one of three presentations of interferon beta. Kaplan-Meier analysis was used to estimate the time to treatment failure. A univariate and multivariate Cox proportional hazard model was used to evaluate factors associated with treatment failure. In addition, patients were propensity score-matched (1:1) in six groups of comparative first-line treatments to evaluate the effectiveness among them. The analysis indicated a higher risk of treatment failure in female patients (HR = 1.08; P = 0,01), those with comorbidities at baseline (HR = 1.20; P<0,0001), in patients who developed comorbidities after starting treatment (i.e., rheumatoid arthritis-HR = 1.65; P<0,0001), those exclusive SUS patients (HR = 1.31; P<0,0001) and among patients using intramuscular interferon beta (IM βINF-1a) (28% to 60% compared to the other three treatments; P<0,0001). Lower risk of treatment failure was found among patients treated with glatiramer. This retrospective cohort suggests that glatiramer is associated with greater effectiveness compared to the three presentations of interferon beta. When evaluating beta interferons, the results suggest that the intramuscular presentation is not effective in the treatment of multiple sclerosis.

The aim of this study was to evaluate the effectiveness of an aquatic progressive resistance exercise (APRE) and PBM (associated or not) on morphology of skeletal muscle and biochemical markers using an experimental model of knee osteoarthritis (OA). Fifty male Wistar rats were randomly distributed into 5 groups: control group (CG); OA control (OAC); OA submitted to APRE (OAE); OA submitted to PBM (OAL); OA submitted to APRE and PBM (OAEL). Trained rats performed a water-jumping program carrying a load equivalent to 50–80% of their body mass strapped to their chest. Laser irradiation (808 nm) was performed on 2 points of the knee joint. Treatments (3 days a week, for 8 weeks) started 4 weeks after the OA induction. The results showed that all OA groups presented a significantly increase in the muscle cross-section area (CSA) and a decrease in muscle fiber density compared to CG. Moreover, both trained groups presented a reduced expression of atrogin and an intense myoD immunoexpression in the laser exercised animals. The results demonstrate that APRE was effective in reducing muscle atrophy markers and its association with PBM could be effective in modulating molecules involved in muscle recovery in knee OA.

Chagas disease (CD) is caused by the protozoan parasite . Although endemic mainly in Latin America, CD has become a global public health problem due to migration of infected individuals to non-endemic regions. Despite progress made in drug development, preclinical assays for drug discovery are required to accelerate the development of new drugs with reduced side effects, which are much needed for human treatment. We used a cure model of infected mice treated with Fexinidazole (FZ) to further validate a novel Enzyme Linked Aptamer (ELA) assay that detects parasite biomarkers circulating in the blood of infected animals. The ELA assay showed cure by FZ in ~71% and ~77% of mice infected with the VL-10 and Colombiana strains of , respectively. The ELA assay also revealed superior treatment efficacy of FZ compared to Benznidazole prior to immunosuppression treatment. Our study supports the use of ELA assay as an alternative to traditional serology or blood PCR to assess the efficacy of antichagasic drugs during their preclinical phase of development. Further, the combination of high sensitivity and ease of use make this parasite antigen detection assay an attractive new tool to facilitate the development of much needed new therapies for CD.

In the present study, patients with acute OROV fever were classified as early seroconverters (IgM/IgG positive at baseline) or late seroconverters (IgM/IgG negative at baseline) and the timeline kinetics of the production of chemokines and cytokines were assessed at 1–3, 4–7, 8–10 and ≥11 days after patients have reported the first symptoms. Regardless immunoglobulin profile, all OROV fever patients presented higher levels of CXCL8, and IFN-α and lower levels of TNF and IL-10 at baseline as compared to healthy donors (HD). Lower levels of CCL2, CXCL10, and IFN-γ and higher levels of CCL2, CXCL10, IL-6, and IL-17A were detected in early and late seroconverters, respectively, as compared to HD. While early seroconverters presented the increasing levels of CCL2 along the timeline, late seroconverters displayed decreasing levels of CCL2, CXCL10, and IL-6 following days of disease onset. Noteworthy was that IFN-α was revealed as universal biomarker of human OROV fever, while CXCL8 & IL-5 and CXCL10 & IL-17 were consistently observed in early and late seroconverters, respectively. Thus, our results suggest that the production of IFN-α, CXCL10, and IL-17 precede the seroconversion bringing novel insights on the immunological events triggered by the OROV disease.

The present study aims to characterize and to evaluate the biological effects of a skin dressing manufactured with the organic part of the Chondrilla caribensis marine sponge (called spongin-like collagen (SC)) associated or not to photobiomodulation (PBM) on the skin wound healing of rats. Skin dressings were manufactured with SC and it was characterized using scanning electron microscopy (SEM) and a tensile assay. In order to evaluate its biological effects, an experimental model of cutaneous wounds was surgically performed. Eighteen rats were randomly distributed into three experimental groups: control group (CG): animals with skin wounds but without any treatment; marine collagen dressing group (DG): animals with skin wounds treated with marine collagen dressing; and the marine collagen dressing + PBM group (DPG): animals with skin wounds treated with marine collagen dressing and PBM. Histopathological, histomorphometric, and immunohistochemical evaluations (qualitative and semiquantitative) of COX2, TGFβ, FGF, and VEGF were done. SEM demonstrates that the marine collagen dressing presented pores and interconnected fibers and adequate mechanical strength. Furthermore, in the microscopic analysis, an incomplete reepithelialization and the presence of granulation tissue with inflammatory infiltrate were observed in all experimental groups. In addition, foreign body was identified in the DG and DPG. COX2, TGFβ, FGF, and VEGF immunostaining was observed predominantly in the wound area of all experimental groups, with a statistically significant difference for FGF immunostaining score of DPG in relation to CG. The marine collagen dressing presented adequate physical characteristics and its association with PBM presented favorable biological effects to the skin repair process.

ABSTRACT A healthy 15-year-old boy with anterior open bite, edge-to-edge transverse discrepancy, and Class III skeletal relationship sought a nonsurgical orthodontic treatment. The patient was treated with premolars extraction, a Hyrax expander and intrusion mechanics with vertical elastics. This mechanics allowed for excellent facial and occlusal results. The final occlusion presented Class I molar and canine relationships, ideal overjet and overbite, and straight facial profile. Analysis of the posttreatment and follow-up radiographs showed that the treatment outcomes remained stable seven years after active orthodontic treatment. Thus, although combined orthodontic and surgical treatment should be considered for patients with this skeletal malocclusion, this case report proves that well controlled orthodontic movement with the patient’s cooperation can be a valid alternative treatment, with good and stable outcomes for patients who refuse surgery. RESUMO Paciente saudável, 15 anos de idade, com mordida aberta anterior, discrepância transversa e relação esquelética de Classe III, buscando tratamento ortodôntico não cirúrgico. O paciente foi tratado com extração de pré-molares associada a expansor Hyrax e mecânica de intrusão com elásticos verticais. Essa mecânica permitiu excelentes resultados faciais e oclusais. A oclusão final apresentou relação de molares e caninos em Classe I, sobremordida e sobressaliência ideais e perfil facial reto. A análise das radiografias pós-tratamento e o acompanhamento demonstraram que os resultados alcançados permaneceram estáveis sete anos após o tratamento ortodôntico ativo. Assim, embora o tratamento ortodôntico-cirúrgico combinado deva ser levado em consideração para pacientes com essa má oclusão esquelética, o presente relato de caso demonstrou que a movimentação ortodôntica bem controlada e com a colaboração do paciente se torna uma alternativa boa e estável para pacientes que recusam a cirurgia.

A panoramic analysis of chemokines, pro-inflammatory/regulatory cytokines, and growth factors was performed in serum samples from patients with acute DENV infection (n=317) by a high-throughput microbeads array. Most soluble mediators analyzed were increased in DENV patients regardless of the DENV serotype. The substantial increase (≥10-fold) of CXCL10, IL-6, and IFN-γ, and decreased levels of PDGF (<0.4-fold) was universally identified in all DENV serotypes. Of note, increased levels of CXCL8, CCL4, and IL-12 (≥3-9-fold) were selectively observed in DENV2 as compared to DENV1 and DENV4. Heatmap and biomarker signatures further illustrated the massive release of soluble mediators observed in DENV patients, confirming the marked increase of several soluble mediators in DENV2. Integrative correlation matrices and networks showed that DENV infection exhibited higher connectivity among soluble mediators. Of note, DENV2 displayed a more complex network, with higher connectivity involving a higher number of soluble mediators. The timeline kinetics (Day 0-1, D2, D3, D4-6) analysis additionally demonstrated differences among DENV serotypes. While DENV1 triggers a progressive increase of soluble mediators towards D3 and with a decline at D4-6, DENV2 and DENV4 develop with a progressive increase towards D4-6 with an early plateau observed in DENV4. Overall, our results provided a comprehensive overview of the immune response elicited by DENV infection, revealing that infection with distinct DENV serotypes causes distinct profiles, rhythms, and dynamic network connectivity of soluble mediators. Altogether, these findings may provide novel insights to understand the pathogenesis of acute infection with distinct DENV serotypes.