115 research outputs found

    Infraorbital nerve block for postoperative pain following cleft lip repair in children

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    Background Postoperative pain is a barrier to the quality of paediatric care, the proper management of which is a challenge. Acute postoperative pain often leads to adverse functional and organic consequences that may compromise surgical outcome. Cleft lip is one of the most common craniofacial birth defects and requires surgical correction early in life. As expected after a surgical intervention in such a sensitive and delicate area, the immediate postoperative period of cleft lip repair may be associated with moderate to severe pain. Infraorbital nerve block associated with general anaesthesia has been used to reduce postoperative pain after cleft lip repair. Objectives To assess the effects of infraorbital nerve block for postoperative pain following cleft lip repair in children. Search methods We searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library, Issue 6, 2015), MEDLINE, EMBASE, and Literatura Latino-Americana e do Caribe em Ciencias da Saude (LILACS) from inception to 17 June 2015. There were no language restrictions. We searched for ongoing trials in the following platforms: the metaRegister of Controlled TrialsClinicalTrials.gov (the US National Institutes of Health Ongoing Trials Register), and the World Health Organization International Clinical Trials Registry Platform(on 17 June 2015). We checked reference lists of the included studies to identify any additional studies. We contacted specialists in the field and authors of the included trials for unpublished data. Selection criteria We included randomised controlled clinical trials that tested perioperative infraorbital nerve block for cleft lip repair in children, compared with other types of analgesia procedure, no intervention, or placebo (sham nerve block). We considered the type of drug, dosage, and route of administration used in each study. For the purposes of this review, the term 'perioperative' refers to the three phases of surgery, that is preoperative, intraoperative, and postoperative, and commonly includes ward admission, anaesthesia, surgery, and recovery. Data collection and analysis Two review authors (GF and EH) independently identified, screened, and selected the studies, assessed trial quality, and performed data extraction using the Cochrane Pain, Palliative and Supportive Care Review Group criteria. In case of disagreements, a third review author (EMKS) was consulted. We assessed the evidence using Grading of Recommendations, Assessment, Development and Evaluation (GRADE). Main results We included eight studies involving 353 children in the review. These studies reported different types of interventions (lignocaine or bupivacaine), observation times, and forms of measuring and describing the outcomes, making it difficult to conduct meta-analyses. In the comparison of infraorbital nerve block versus placebo, there was a large effect in mean postoperative pain scores (our first primary outcome) favouring the intervention group (standardised mean difference (SMD) -3.54, 95% confidence interval (CI) -6.13 to -0.95very low-quality evidence3 studies120 children). Only one study reported the duration of analgesia (in hours) (second primary outcome) with a difference favouring the intervention group (mean difference (MD) 8.26 hours, 95% CI 5.41 to 11.11very low-quality evidence) and less supplemental analgesic requirements in the intervention group (risk ratio (RR) 0.05, 95% CI 0.01 to 0.18low-quality evidence). In the comparison of infraorbital nerve block versus intravenous analgesia, there was a difference favouring the intervention group in mean postoperative pain scores (SMD -1.50, 95% CI -2.40 to -0.60very low-quality evidence2 studies107 children) and in the time to feeding (MD -9.45 minutes, 95% CI -17.37 to -1.53moderate-quality evidence2 studies128 children). No significant adverse events (third primary outcome) were associated with the intervention, although three studies did not report this outcome. Five out of eight studies found no unwanted side effects after the nerve blocks. Overall, the included studies were at low or unclear risk of bias. The reasons for downgrading the quality of the evidence using GRADE related to the lack of information about randomisation methods and allocation concealment in the studies, very small sample sizes, and heterogeneity of outcome reporting. Authors' conclusions There is low-to very low-quality evidence that infraorbital nerve block with lignocaine or bupivacaine may reduce postoperative pain more than placebo and intravenous analgesia in children undergoing cleft lip repair. Further studies with larger samples are needed. Future studies should standardise the observation time and the instruments used to measure outcomes, and stratify children by age group.National Institute for Health Research (NIHR)Universidade Federal de São Paulo - UNIFESP, Sao Paulo, BrazilCochrane Brazil, Centro de Estudos de Saúde Baseada em Evidências e Avaliação Tecnológica em Saúde, São Paulo, BrazilEmergency Medicine and Evidence Based Medicine, Universidade Federal de São Paulo, São Paulo, BrazilUniversidade Federal de São Paulo - UNIFESP, Sao Paulo, BrazilCochrane Brazil, Centro de Estudos de Saúde Baseada em Evidências e Avaliação Tecnológica em Saúde, São Paulo, BrazilEmergency Medicine and Evidence Based Medicine, Universidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

    Endothelial Wnt/β-catenin signaling inhibits glioma angiogenesis and normalizes tumor blood vessels by inducing PDGF-B expression

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    Endothelial Wnt/β-catenin signaling is necessary for angiogenesis of the central nervous system and blood–brain barrier (BBB) differentiation, but its relevance for glioma vascularization is unknown. In this study, we show that doxycycline-dependent Wnt1 expression in subcutaneous and intracranial mouse glioma models induced endothelial Wnt/β-catenin signaling and led to diminished tumor growth, reduced vascular density, and normalized vessels with increased mural cell attachment. These findings were corroborated in GL261 glioma cells intracranially transplanted in mice expressing dominant-active β-catenin specifically in the endothelium. Enforced endothelial β-catenin signaling restored BBB characteristics, whereas inhibition by Dkk1 (Dickkopf-1) had opposing effects. By overactivating the Wnt pathway, we induced the Wnt/β-catenin–Dll4/Notch signaling cascade in tumor endothelia, blocking an angiogenic and favoring a quiescent vascular phenotype, indicated by induction of stalk cell genes. We show that β-catenin transcriptional activity directly regulated endothelial expression of platelet-derived growth factor B (PDGF-B), leading to mural cell recruitment thereby contributing to vascular quiescence and barrier function. We propose that reinforced Wnt/β-catenin signaling leads to inhibition of angiogenesis with normalized and less permeable vessels, which might prove to be a valuable therapeutic target for antiangiogenic and edema glioma therapy

    Comparison of TCP and TCP/HA Hybrid Scaffolds for Osteoconductive Activity

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    Two types of porous ceramic scaffolds were prepared, consisting of β-tricalcium phosphate (TCP) or the mixed powder of TCP and hydroxyapatite (HA) at a 2:1 mass ratio. A variety of methods have been used to fabricate bone scaffolds, while the sintering approach was adopted in this work. An extremely high temperature was used on sintering that proposed to consolidate the ceramic particles. As revealed by SEM, a well opened pore structure was developed within the scaffolds. The θ-values were measured to be of 73.3° and 6.5° for the composite scaffold and TCP sample, respectively. According to XRD patterns, the existence of grains coalescence and partial bonding between HA and TCP powders was demonstrated. Scaffold mechanical property in the term of flexural strength was also determined. The result showed decreasing of the strength by HA supplement, suggesting the more brittle characteristic of HA in comparison with TCP. By soaking the composite scaffold in PBS for a period of 2 weeks, transformation from particles to flank-like crystalline was clearly observed. Such change was found to be favorable for cell attachment, migration, and growth. By implanting cell-seeded scaffolds into nude mice, an abundant osseous extracellular matrix was identified for the composite implants. In contrast, the matrix was minimally detected in TCP implanted samples. Thus, the composite scaffold was found superior for hard tissue regeneration

    Bone morphogenetic proteins in tissue engineering: the road from laboratory to clinic, part II (BMP delivery)

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    Bone morphogenetic proteins (BMPs) are cytokines with a strong effect on bone and cartilage growth and with important roles during embryonic patterning and early skeletal formation. BMPs have promising potential for clinical bone and cartilage repair, working as powerful boneinducing components in diverse tissue-engineering products. Synthetic polymers, natural origin polymers, inorganic materials and composites may be used as carriers for the delivery of BMPs. Carriers range from nanoparticles to complex three-dimensional (3D) scaffolds, membranes for tissue-guided regeneration, biomimetic surfaces and smart thermosensitive hydrogels. Current clinical uses include spinal fusion, healing of long bone defects and craniofacial and periodontal applications, amongst others. BMP-2 and BMP-7 have recently received approval by the US Food and Drug Administration (FDA) for specific clinical cases, delivered in absorbable collagen sponges. Considering the expanding number of publications in the field of BMPs, there are prospects of a brilliant future in the field of regenerative medicine of bone and cartilage with the use of BMPs

    Endothelial Differentiation of Human Stem Cells Seeded onto Electrospun Polyhydroxybutyrate/Polyhydroxybutyrate-Co-Hydroxyvalerate Fiber Mesh

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    Tissue engineering is based on the association of cultured cells with structural matrices and the incorporation of signaling molecules for inducing tissue regeneration. Despite its enormous potential, tissue engineering faces a major challenge concerning the maintenance of cell viability after the implantation of the constructs. The lack of a functional vasculature within the implant compromises the delivery of nutrients to and removal of metabolites from the cells, which can lead to implant failure. In this sense, our investigation aims to develop a new strategy for enhancing vascularization in tissue engineering constructs. This study's aim was to establish a culture of human adipose tissue-derived stem cells (hASCs) to evaluate the biocompatibility of electrospun fiber mesh made of polyhydroxybutyrate (PHB) and its copolymer poly-3-hydroxybutyrate-co-3-hydroxyvalerate (PHB-HV) and to promote the differentiation of hASCs into the endothelial lineage. Fiber mesh was produced by blending 30% PHB with 70% PHB-HV and its physical characterization was conducted using scanning electron microscopy analysis (SEM). Using electrospinning, fiber mesh was obtained with diameters ranging 300 nm to 1.3 µm. To assess the biological performance, hASCs were extracted, cultured, characterized by flow cytometry, expanded and seeded onto electrospun PHB/PHB-HV fiber mesh. Various aspects of the cells were analyzed in vitro using SEM, MTT assay and Calcein-AM staining. The in vitro evaluation demonstrated good adhesion and a normal morphology of the hASCs. After 7, 14 and 21 days of seeding hASCs onto electrospun PHB/PHB-HV fiber mesh, the cells remained viable and proliferative. Moreover, when cultured with endothelial differentiation medium (i.e., medium containing VEGF and bFGF), the hASCs expressed endothelial markers such as VE-Cadherin and the vWF factor. Therefore, the electrospun PHB/PHB-HV fiber mesh appears to be a suitable material that can be used in combination with endothelial-differentiated cells to improve vascularization in engineered bone tissues
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