Mouse anti-RANKL antibody delays oral wound healing and increases TRAP-positive mononuclear cells in bone marrow

Objectives: Denosumab, a human monoclonal antibody (mAb) that neutralizes receptor activator for nuclear factor κB ligand (RANKL), is associated with osteonecrosis of the jaw. However, the effect of denosumab on oral wounds is unclear. The aim was to determine the effect of anti-RANKL mAb on oral wounds and bone marrow. Materials and methods: The direct effect of the mAb on fibroblasts, macrophages, and osteoclasts were assessed in vitro. In vivo, mouse anti-RANKL mAb was administered to mice for 9 weeks prior to palatal bone denudation surgery. Mice were euthanized 3 weeks post-surgery, and wound healing was histomorphometrically analyzed. Long bones were assessed using micro-computed tomography, quantitative real-time polymerase chain reaction, and flow cytometry. Results: The mAb had no effect on macrophages and fibroblasts but significantly suppressed osteoclast proliferation in vitro. The mAb treatment significantly increased bone mass by suppressing osteoclasts in vivo. The expression of pro-osteoclastic genes was promoted in the bone marrow of the mAb-administered animals. Consistently, the mAb significantly induced the development of tartrate-resistant acid phosphatase (TRAP)-positive mononuclear cells (MNCs) but not osteoclasts in bone marrow. The mAb treatment had no effect on gross healing of the palatal wounds. However, significant inflammation was retained in the connective tissue facing the once denuded bone surface. Conclusions: Repair of the damaged palate was delayed, and significant inflammation was sustained in the connective tissue by anti-RANKL mAb treatment. Clinical relevance: Denosumab impairs osteoclastic bone repair. Care should be exercised to minimize osseous trauma when invasive procedures are performed on patients taking denosumab

RESULTADOS PRELIMINARES DA DISTRIBUIÇÃO DE FÓSFORO E SUAS FORMAS NOS SEDIMENTOS DA PLATAFORMA CONTINENTAL DO ESTADO DE SANTA CATARINA

Distribuition of phosphorus in marine sediments have been recognized as a useful tool for the knowledgement of its geochemical cicle, that have been undergoing chances by human actions. Marine sediments represents the major reservoir of this constituint, where processes take place and control its disponibility to water column. Differents forms of phosphorus were determined by sequencial extrations in 27 samples of bottom sediment collected in the inner shelf off Santa Catarina. The aim of this study was to investigate the distribuition of phosphorus in the sequencial extrated frations and the relationship with sediment facies. The highest total phosphorus concentrations have been related to fine grained sediments. Although, there were some differences between samples with similar sedimentar patterns. Iron plus aluminium phosphate has been showed high concentrations in the neigborhood of river mounths, declining off shore. Calcium phosphate was the predominant form in most samples.O estudo de fósforo em sedimentos marinhos tem sido utilizado como importante ferramenta para compreensão do ciclo geoquímico deste nutriente, o qual vem sendo alterado pela ação antropogênica. Os sedimentos marinhos representam o depósito final deste constituinte e, dependendo dos processos de interação química que ali ocorrem, podem ser responsáveis por sua maior ou menor disponibilidade para a coluna d’água. Neste estudo foram determinadas as diferentes formas de fósforo, através do método de extração sequencial (modificado de SILVEIRA, 1993), em 27 amostras de sedimentos superficiais coletados na plataforma interna do litoral centro-norte catarinense. O objetivo era verificar a distribuição de fósforo e suas formas de acordo com as fácies sedimentares encontradas na área de estudo. As concentrações de fósforo total variaram entre 1,27 a 18,77 µmol/g, com as mais elevadas estando associadas aos sedimentos finos, embora tenham ocorrido diferenças entre fácies com características granolumétricas similares. O fosfato de ferro + alumínio apresentou concentrações mais altas próximo as desembocaduras dos rios diminuindo com o aumento da distância da linha de costa, indicando o aporte continental. A forma predominante na maioria das amostras foi o fosfato de cálcio que apresentou uma relação direta com a profundidade

VARIABILIDADE NAS TAXAS FISIOLÓGICAS DO MEXILHÃO PERNA PERNA EM DOIS SÍTIOS DE CULTIVO DO LITORAL NORTE DE SANTA CATARINA

With the growing socioeconomic activity of mussel farming on Santa Catarina’s coast, the identification of new cultivation sites became necessary. Among a variety of methods used for the analysis of potential producing areas, studying of the mussel physiological rates may be considered as one of the most appropriated, specially when addressing the monitoring of sites already established and the negative effects of environmental pollution. This report presents a preliminary comparison between two areas of cultivation in the northern coast of the state (municipalities of Penha and Bombinhas). In both locations, environmental data (temperature, salinity and seston) and physiological parameters of the mussels (growth, and filtration, respiration and assimilation rates) were analysed. Our findings suggested a direct relationship between temperature and mussel growth rate and also between salinity and respiration rates for both areas. The seston concentration showed a high environmental variability as a response to the continental drainage. In addition, the filtration and assimilation rates seemed to be influenced by the stages of embryonic follicle maturation. In terms of production, the sites showed larger differences during the colder months as compared to the warmer ones, when the results were quite similar. More conclusive results are dependent of studies conducted along a complete annual cycle.Com a crescente atividade sócio-econômica da mitilicultura na costa do estado de Santa Catarina, problemas relacionados com a identificação de novos sítios de cultivo tornaram-se prioritários. Dentre os mais diferentes métodos utilizados para análise de potenciais regiões produtoras, o estudo das taxas fisiológicas dos mexilhões enquadram-se como uma das mais adequadas, incluindo neste caso, o monitoramento de sítios já estabelecidos e problemas relacionados com a poluição ambiental. Este relatório faz referência a uma preliminar comparação entre duas áreas de cultivo do mexilhão Perna perna no litoral norte do estado (municípios de Penha e Bombinhas). Dados ambientais de temperatura, salinidade, material em suspensão e fisiológicos do mexilhão como crescimento, filtração, respiração e assimilação foram comparados. Os principais resultados deste estudo podem ser resumidos em: relação direta entre a temperatura e a taxa de crescimento e relação entre a salinidade e a taxa de respiração para os dois ambientes. O material em suspensão apresentou uma maior variabilidade ambiental influenciada pelos aportes continentais mas que necessitam de maiores investigações. A importância das taxas de maturação dos folículos embrionários dos mexilhões foi sugerida na relação com as taxas de filtração e assimilação. Em termos de produção, os ambientes mostraram maiores diferenças nos meses frios e similar resultados nos meses quentes. Entretanto, resultados conclusivos estão dependentes de estudos ao longo de um ciclo anual

Early effects of parathyroid hormone on bisphosphonate/steroid-associated compromised osseous wound healing

Summary: Administration of intermittent parathyroid hormone (PTH) promoted healing of tibial osseous defects and tooth extraction wounds and prevented the development of necrotic lesions in rats on a combined bisphosphonate and steroid regimen. Introduction: Osteonecrosis of the jaw (ONJ) has emerged in association with antiresorptive therapies. The pathophysiology of ONJ is unknown and no established cure currently exists. Our objective was to determine the effect of intermittent PTH administration on early osseous healing in the jaw and long bones of rats receiving bisphosphonate and steroid treatment. Methods: Ovariectomized rats received the combination therapy of alendronate and dexamethasone (ALN/DEX) for 12 weeks. Osseous wounds were created in the jaw and tibia. PTH was administered intermittently and healing at 2 weeks post-op was compared between the jaw and tibia by microcomputed tomography and histomorphometric analyses. Results: ALN/DEX treatment was associated with necrotic open wounds in the jaw but had no negative effects on healing and promoted bone fill in tibial defects. PTH therapy prevented the development of necrotic lesions in the jaw and promoted healing of the tibial defects. PTH therapy was associated with the promotion of osteocyte survival in osseous wounds both in the jaw and tibia. Conclusions: Wound healing was impaired in the jaw in rats on a combined bisphosphonate and steroid regimen, and PTH therapy rescued necrotic lesions. These findings suggest that PTH therapy could be utilized to prevent ONJ from occurring in patients on combination antiresorptive and steroid therapy

Human Fibroblast Sheet Promotes Human Pancreatic Islet Survival and Function In Vitro

In previous work, we engineered functional cell sheets using bone marrow-derived mesenchymal stem cells (BM-MSCs) to promote islet graft survival. In the present study, we hypothesized that a cell sheet using dermal fibroblasts could be an alternative to MSCs, and then we aimed to evaluate the effects of this cell sheet on the functional viability of human islets. Fibroblast sheets were fabricated using temperature-responsive culture dishes. Human islets were seeded onto fibroblast sheets. The efficacy of the fibroblast sheets was evaluated by dividing islets into three groups: the islets-alone group, the coculture with fibroblasts group, and the islet culture on fibroblast sheet group. The ultrastructure of the islets cultured on each fibroblast sheet was examined by electron microscopy. The fibroblast sheet expression of fibronectin (as a component of the extracellular matrix) was quantified by Western blotting. After 3 days of culture, islet viabilities were 70.2 ± 9.8%, 87.4 ± 5.8%, and 88.6 ± 4.5%, and survival rates were 60.3 ± 6.8%, 65.3 ± 3.0%, and 75.8 ± 5.6%, respectively. Insulin secretions in response to high-glucose stimulation were 5.1 ± 1.6, 9.4 ± 3.8, and 23.5 ± 12.4 μIU/islet, and interleukin-6 (IL-6) secretions were 3.0 ± 0.7, 5.1 ± 1.2, and 7.3 ± 1.0 ng/day, respectively. Islets were found to incorporate into the fibroblast sheets while maintaining a three-dimensional structure and well-preserved extracellular matrix. The fibroblast sheets exhibited a higher expression of fibronectin compared to fibroblasts alone. In conclusion, human dermal fibroblast sheets fabricated by tissue-engineering techniques could provide an optimal substrate for human islets, as a source of cytokines and extracellular matrix

Dogs avoid people who behave negatively to their owner: third-party affective evaluation

イヌは飼い主に協力しない人物を嫌う. 京都大学プレスリリース. 2015-06-12.Social eavesdropping, or social evaluation of third-party interactions, is a first step to image scoring, which is a key feature of humans' large-scale cooperative society. Here we asked whether domestic dogs evaluate humans interacting with one another over neutral objects. In two experimental conditions, the dog's owner tried to open a container to get a junk object that was inside, then requested help from an actor sitting next to her/him, while the dog watched the interaction. In the Helper condition, the actor held the container stable to help the owner to open it. In the Nonhelper condition, the actor turned away and refused to help. In the Control condition, the actor simply turned away in the absence of any request for help. A neutral person sat at the other side of the owner throughout these interactions. After the interaction the actor and the neutral person each offered a piece of food to the dog. Dogs chose food randomly in the Helper and the Control conditions, but were biased against the actor in the Nonhelper condition. The dogs' avoidance of someone who behaved negatively to the owner suggests that social eavesdropping may be shared with a nonprimate species

Simulation study of the in-situ formation deformation behavior of a shallow formation in the Southern Kanto Natural gas field, Chiba Prefecture, Japan

In 2010, eight companies which are exploiting natural gas and brine water in the Southern Kanto natural gas field, Chiba prefecture, Japan constructed an in-situ formation deformation monitoring well with a depth of approximately 80 m, and in-situ formation deformation was measured on a trial basis. After this field test, by conducting the simulation study, we verified whether the deformation behavior at the monitoring well was perfectly elastic or not. In addition, we compared in-situ rock properties like Young's modulus and Poisson's ratio which were estimated by the simulation study with those determined from a triaxial compression test

Modifying the dissolved-in-water type natural gas field simulation model based on the distribution of estimated Young's modulus for the Kujukuri region, Japan

A simulation model, which covers the part of Southern-Kanto natural gas field in Chiba prefecture, was developed to perform studies and make predictions of land subsidence. However, because large differences between simulated and measured subsidence occurred in the northern modeled area of the gas field, the model was modified with an estimated Young's modulus distribution. This distribution was estimated by the yield value distribution and the correlation of yield value with Young's modulus. Consequently, the simulated subsidence in the north area was improved to some extent