Comparison of biological behavior between early-stage adenocarcinoma and squamous cell carcinoma of the uterine cervix

Objectives: (1) To compare the anatomopathological variables and recurrence rates in patients with early-stage adenocarcinoma (AC) and squamous cell carcinoma (SCC) of the uterine cervix; (2) to identify the independent risk factors for recurrence. Study design: This historical cohort study assessed 238 patients with carcinoma of the uterine cervix (113 and IIA), who underwent radical hysterectomy with pelvic lymph node dissection between 1980 and 1999. Comparison of category variables between the two histological types was carried out using the Pearson`s X-2 test or Fisher exact test. Disease-free survival rates for AC and SCC were calculated using the Kaplan-Meier method and the curves were compared using the log-rank test. The Cox proportional hazards model was used to identify the independent risk factors for recurrence. Results: There were 35 cases of AC (14.7%) and 203 of SCC (85.3%). AC presented lower histological grade than did SCC (grade 1: 68.6% versus 9.4%; p < 0.001), lower rate of lymphovascular space involvement (25.7% versus 53.7%; p = 0.002), lower rate of invasion into the middle or deep thirds of the uterine cervix (40.0% versus 80.8%; p < 0.001) and lower rate of lymph node metastasis (2.9% versus 16.3%; p = 0.036). Although the recurrence rate was lower for AC than for SCC (11.4% versus 15.8%), this difference was not statistically significant (p = 0.509). Multivariate analysis identified three independent risk factors for recurrence: presence of metastases in the pelvic lymph nodes, invasion of the deep third of the uterine cervix and absence of or slight inflammatory reaction in the cervix. When these variables were adjusted for the histological type and radiotherapy status, they remained in the model as independent risk factors. Conclusion: The AC group showed less aggressive histological behavior than did the SCC group, but no difference in the disease-free survival rates was noted. (C) 2006 Elsevier Ireland Ltd. All rights reserved.

Large Unicystic Ameloblastoma of the Mandible: Management Guided by Biological Behavior

Ameloblastoma is a true neoplasm of odontogenic epithelial origin. It is a slow-growing benign tumor of the jaw, and patients usually present late after the tumor achieves considerable size to cause facial disfigurement. Diagnosis mainly from tissue biopsy and radiograph findings does assist in differentiating between types of ameloblastoma. Unicystic ameloblastoma is a tumor with a strong propensity for recurrence. There is a difference in biological behavior between mural unicystic ameloblastoma and those which are simply cystic or show intraluminal proliferation. The challenges in the management of this tumor are to provide complete excision in addition to reconstructing the bony defect, to provide the patient with reasonable cosmetic and functional outcome. The authors report a case of a mural unicystic ameloblastoma in a 23-year-old man who was treated by partial resection of the mandible. Biomedical prototypes were used because they provide acceptable precision and are useful for treatment planning.

Biological behavior of the gerbil ventral prostate in three phases of postnatal development

In this study, we characterized the gerbil's ventral prostate histology ultrastructurally and quantitatively throughout three phases of postnatal development (young, adult, and old) in order to comprehend its biological behavior and propensity to developing spontaneous lesions with aging. The gerbil prostate is composed of alveoli and ducts immersed in a stroma composed of smooth muscle, fibroblasts, collagen and elastic fibers and vessels. The prostate tissue components present morphological and quantitative aspects that vary according to age. Young animals have an immature gland with modest secretory activity. Synthetic activity remained stable in adult and old gerbil. However, prostatic morphology was altered in the aging, showing an increased epithelium and stromal fibrosis. The nuclei of the secretory cells increased with aging, whereas nucleoli presented few alterations during postnatal development. The epithelial proliferation and stromal remodeling noted in this study indicate that the gerbil prostate may respond to the androgen declines typical of senescence through epithelial proliferation and stromal remodeling.

Comparison of the biological behavior of wollastonite bioceramics prepared from synthetic and natural precursors

Wollastonite bioceramics prepared from synthetic and natural precursors were implanted in rats in bone and subcutaneous tissues. The implant sites were excised after 7, 30 and 120 days, fixed, dehydrated, embedded in paraffin wax for serial cutting and examined under transmitted light microscope. It was found a very similar behavior for both wollastonite bioceramics. They were biocompatible, bioactive and biodegradable when implanted in rat bone. The synthetic ceramic was more reabsorbable than the one from natural powder. When implanted in subcutaneous rat tissue, both materials elicited a mild initial inflammatory reaction that practically disappeared after 120 days. Both materials were encapsulated with a very thin fibrous capsule and slightly reabsorbed at their surfaces. None of the materials induced ectopic osteogenesis. According to the results, the studied materials seem to be able for manufacturing reabsorbable bone implants.

In vivo biological behavior of calcium phosphate cements with different Ca/P ratio

Bioceramics with different Ca/P ratio were prepared from a mechanical mixture of NaPO3, CaCO3, Ca(OH)2 and phosphate buffer solution and implanted in rats subcutaneous tissues. The cements were characterized by Thermo gravimetric analysis (TG-TDA), X-ray diffraction and 31P-NMR. The implant sites were excised after 1, 4 and 16 weeks, fixed, dehydrated, included in paraffin wax for serial cutting and examined under the light transmitted microscope. They were biocompatible and biodegradable when implanted in rat subcutaneous. None of the materials induced ectopic osteogenesis. According to the results, the studied materials seem to be able for manufacturing reabsorbable bone implants.

In vitro and in vivo biological behavior of CDHA/OCP/β-TCP scaffold

The biological behavior of a new bioactive material composed of calcium-deficient hydroxyapatite, octacalcium phosphate, and beta-tricalcium phosphate was investigated by in vitro indirect and direct cytotoxicity, cell adhesion and proliferation tests, and by in vivo subcutaneous and bone implantation in rats. The results of the in vitro studies showed that the material is biocompatible and no cytotoxic. Slightly poorer initial cell adhesion and lower cell proliferation than in control was observed, which were attributed to the reactivity and roughness of the material surface, In vivo results showed that the material is biodegradable and bioactive in bone tissue, but only biocompatible and partially biodegradable in soft tissue.

Effects of alloying elements on the corrosion behavior and biocompatibility of biodegradable magnesium alloys: a review

Magnesium (Mg) based alloys have been extensively considered for their use as biodegradable implant materials. However, controlling their corrosion rate in the physiological environment of the human body is still a significant challenge. One of the most effective approaches to address this challenge is to carefully select alloying compositions with enhanced corrosion resistance and mechanical properties when designing the Mg alloys. This paper comprehensively reviews research progress on the development of Mg alloys as biodegradable implant materials, highlighting the effects of alloying elements including aluminum (Al), calcium (Ca), lithium (Li), manganese (Mn), zinc (Zn), zirconium (Zr), strontium (Sr) and rare earth elements (REEs) on the corrosion resistance and biocompatibility of Mg alloys, from the viewpoint of the design and utilization of Mg biomaterials. The REEs covered in this review include cerium (Ce), erbium (Er), lanthanum (La), gadolinium (Gd), neodymium (Nd) and yttrium (Y). The effects of alloying elements on the microstructure, corrosion behavior and biocompatibility of Mg alloys have been critically summarized based on specific aspects of the physiological environment, namely the electrochemical effect and the biological behavior. This journal is © the Partner Organisations 2014.

Effectiveness and biological compatibility of different generations of dentin adhesives

Besides possessing good mechanical properties, dental materials should present a good biological behavior and should not injure the involved tissues. Bond strength and biocompatibility are both highly significant properties of dentin adhesives. For that matter, these properties of four generations of adhesive systems (Multi-Purpose/Single Bond/SE Plus/Easy Bond) were evaluated.Eighty bovine teeth had their dentin exposed (500- and 200-mu m thickness). Adhesive was applied on the dentin layer of each specimen. Following that, the microshearing test was performed for all samples. A dentin barrier test was used for the cytotoxicity evaluation. Cell cultures (SV3NeoB) were collected from testing materials by means of 200- or 500-mu m-thick dentin slices and placed in a cell culture perfusion chamber. Cell viability was measured 24 h post-exposition by means of a photometrical test (MTT test).The best bonding performance was shown by the single-step adhesive Easy Bond (21 MPa, 200 mu m; 27 MPa, 500 mu m) followed by Single Bond (15.6 MPa, 200 mu m; 23.4 MPa, 500 mu m), SE Plus (18.2 MPa, 200 mu m; 20 MPa, 500 mu m), and Multi-Purpose (15.2 MPa, 200 mu m; 17.9 MPa, 500 mu m). Regarding the cytotoxicity, Multi-Purpose slightly reduced the cell viability to 92 % (200 mu m)/93 % (500 mu m). Single Bond was reasonably cytotoxic, reducing cell viability to 71 % (200 mu m)/64 % (500 mu m). The self-etching adhesive Scotchbond SE decreased cell viability to 85 % (200 mu m)/71 % (500 mu m). Conversely, Easy Bond did not reduce cell viability in this test, regardless of the dentin thickness.Results showed that the one-step system had the best bond strength performance and was the least toxic to pulp cells. In multiple-step systems, a correct bonding technique must be done, and a pulp capping strategy is necessary for achieving good performance in both properties.The study showed a promising system (one-step self-etching), referring to it as a good alternative for specific cases, mainly due to its technical simplicity and good biological responses.

Influence of the Freeze-Drying Process on the Physicochemical and Biological Properties of Pre-heated Amphotericin B Micellar Systems

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Nanoparticular iron complex drugs for parenteral administration - physicochemical characterization, biological distribution and pharmacological safety

Iron deficiency is the most common deficiency disease worldwide with many patients who require intravenous iron. Within the last years new kind of parenteral iron complexes as well as generic preparations entered the market. There is a high demand for methods clarifying benefit to risk profiles of old and new iron complexes. It is also necessary to disclose interchangeability between originator and intended copies to avoid severe anaphylactic and anaphylactoid side reaction and assure equivalence of therapeutic effect.rnrnThe investigations presented in this work include physicochemical characterization of nine different parenteral iron containing non-biological complex drugs. rnWe developed an in-vitro assay, which allows the quantification of labile iron in the different complexes and thus it is a useful tool to estimate the pharmaclogical safety regarding iron related adverse drug events. This assay additionally allowed the estimation of complex stability by evaluation of degradation kinetics at the applied conditions.rnrnAn in-ovo study was performed to additionally compare different complexes in respect to body distribution. This in combination with complex stability information allowed the risk estimation of potential local acute and chronic reactions to iron overload.rnrnInformation obtained by the combination of the methods within this work are helpful to estimate the safety and efficacy profile of different iron containing non-biological complex drugs. rnrnPhysicochemical differences between the complexes were demonstrated in respect to size of the inorganic fraction, size and size distribution of the complete particles, structure of the inorganic iron fraction, morphology of the complexes and charge of the complexes. And furthermore significant differences in the biological behavior of different complexes were demonstrated. rnrnThe combination of complex stability and biodistribution as well as the combination of structure, size and stability represent helpful tools for the physicochemical characterization of iron containing non-biological complex drugs and for the estimation of pharmacological safety. This work thus represents an up to date summary of some relevant methods for the characterization of intravenous iron complex drugs in respect to pharmaceutical quality, pharmacological safety and aspects of efficacy. rnrnProspectively, it is worthwhile that the methods within this work will contribute to the development and/or characterization of iron containing nanoparticular formulations with beneficial efficacy and safety profiles.rn

Determinants of biological activity of nanomaterials in innate immunity cells: the role of aspect ratio, environmental contaminants and protein corona

As defined by the European Union, “ ’Nanomaterial’ (NM) means a natural, incidental or manufactured material containing particles, in an unbound state or as an aggregate or agglomerate, where, for 50 % or more of the particles in the number size distribution, one or more external dimensions is in the size range 1 nm-100 nm ” (2011/696/UE). Given their peculiar physico-chemical features, nanostructured materials are largely used in many industrial fields (e.g. cosmetics, electronics, agriculture, biomedical) and their applications have astonishingly increased in the last fifteen years. Nanostructured materials are endowed with very large specific surface area that, besides making them very useful in many industrial processes, renders them very reactive towards the biological systems and, hence, potentially endowed with significant hazard for human health. For these reasons, in recent years, many studies have been focused on the identification of toxic properties of nanostructured materials, investigating, in particular, the mechanisms behind their toxic effects as well as their determinants of toxicity. This thesis investigates two types of nanostructured TiO2 materials, TiO2 nanoparticles (NP), which are yearly produced in tonnage quantities, and TiO2 nanofibres (NF), a relatively novel nanomaterial. Moreover, several preparations of MultiWalled Carbon Nanotubes (MWCNT), another nanomaterial widely present in many products, are also investigated.- Although many in vitro and in vivo studies have characterized the toxic properties of these materials, the identification of their determinants of toxicity is still incomplete. The aim of this thesis is to identify the structural determinants of toxicity, using several in vitro models. Specific fields of investigation have been a) the role of shape and the aspect ratio in the determination of biological effects of TiO2 nanofibres of different length; b) the synergistic effect of LPS and TiO2 NP on the expression of inflammatory markers and the role played therein by TLR-4; c) the role of functionalization and agglomeration in the biological effects of MWCNT. As far as biological effects elicited by TiO2 NF are concerned, the first part of the thesis demonstrates that long TiO2 nanofibres caused frustrated phagocytosis, cytotoxicity, hemolysis, oxidative stress and epithelial barrier perturbation. All these effects were mitigated by fibre shortening through ball-milling. However, short TiO2 NF exhibited enhanced ability to activate acute pro-inflammatory effects in macrophages, an effect dependent on phagocytosis. Therefore, aspect ratio reduction mitigated toxic effects, while enhanced macrophage activation, likely rendering the NF more prone to phagocytosis. These results suggest that, under in vivo conditions, short NF will be associated with acute inflammatory reaction, but will undergo a relatively rapid clearance, while long NF, although associated with a relatively smaller acute activation of innate immunity cells, are not expected to be removed efficiently and, therefore, may be associated to chronic inflammatory responses. As far as the relationship between the effects of TiO2 NP and LPS, investigated in the second part of the thesis, are concerned, TiO2 NP markedly enhanced macrophage activation by LPS through a TLR-4-dependent intracellular pathway. The adsorption of LPS onto the surface of TiO2 NP led to the formation of a specific bio-corona, suggesting that, when bound to TiO2 NP, LPS exerts a much more powerful pro-inflammatory effect. These data suggest that the inflammatory changes observed upon exposure to TiO2 NP may be due, at least in part, to their capability to bind LPS and, possibly, other TLR agonists, thus enhancing their biological activities. Finally, the last part of the thesis demonstrates that surface functionalization of MWCNT with amino or carboxylic groups mitigates the toxic effects of MWCNT in terms of macrophage activation and capability to perturb epithelial barriers. Interestingly, surface chemistry (in particular surface charge) influenced the protein adsorption onto the MWCNT surface, allowing to the formation of different protein coronae and the tendency to form agglomerates of different size. In particular functionalization a) changed the amount and the type of proteins adsorbed to MWCNT and b) enhanced the tendency of MWCNT to form large agglomerates. These data suggest that the different biological behavior of functionalized and pristine MWCNT may be due, at least in part, to the different tendency to form large agglomerates, which is significantly influenced by their different capability to interact with proteins contained in biological fluids. All together, these data demonstrate that the interaction between physico-chemical properties of nanostructured materials and the environment (cells + biological fluids) in which these materials are present is of pivotal importance for the understanding of the biological effects of NM. In particular, bio-persistence and the capability to elicit an effective inflammatory response are attributable to the interaction between NM and macrophages. However, the interaction NM-cells is heavily influenced by the formation at the nano-bio interface of specific bio-coronae that confer a novel biological identity to the nanostructured materials, setting the basis for their specific biological activities.

Bacterial adherence and biofilm formation on medical implants : a review

Biofilms are a complex group of microbial cells that adhere to the exopolysaccharide matrix present on the surface of medical devices. Biofilm-associated infections in the medical devices pose a serious problem to the public health and adversely affect the function of the device. Medical implants used in oral and orthopedic surgery are fabricated using alloys such as stainless steel and titanium. The biological behavior, such as osseointegration and its antibacterial activity, essentially depends on both the chemical composition and the morphology of the surface of the device. Surface treatment of medical implants by various physical and chemical techniques are attempted in order to improve their surface properties so as to facilitate bio-integration and prevent bacterial adhesion. The potential source of infection of the surrounding tissue and antimicrobial strategies are from bacteria adherent to or in a biofilm on the implant which should prevent both biofilm formation and tissue colonization. This article provides an overview of bacterial biofilm formation and methods adopted for the inhibition of bacterial adhesion on medical implants

Tipagem das células do infiltrado inflamatório peritumoral em carcinoma de células escamosas da mucosa bucal: correlação com expressão de Ki67

O emprego de técnicas imunoistoquímicas, utilizando marcadores biológicos como o Ki67, que permite a avaliação do índice de proliferação celular em neoplasias malignas, vem sendo preconizado como um importante caminho de investigação do comportamento biológico das neoplasias malignas, tendo como consequências contribuições para o estabelecimento do prognóstico e desenvolvimento de novos protocolos terapêuticos. Neste trabalho, utiliza-se o método imunoistoquímico da avidina-biotina-peroxidase avaliada a expressão de Ki67 no parênquima de amostras de carcinomas de células escamosas da mucosa bucal com diferentes graus de diferenciação histológica. Além disso, a quantificação da área de infiltrado inflamatório foi avaliada. Os resultados demonstraram que a resposta imunológica celular é o principal mecanismo de defesa no carcinoma de células escamosas da mucosa bucal, expressada pelo grande número de linfócitos T e macrófagos e a expressão de Ki67 está relacionado ao índice mitótico e, consequentemente, à proliferação celular e, também, à diferenciação da neoplasia.

Nanocompósitos de PMMA/HA/grafeno para aplicações biomédicas

Os cimentos ósseos à base de PMMA para aplicações em artroplastia da anca apresentam como grande limitação o facto do seu constituinte principal ser um elemento bioinerte o que leva à falta de integração entre as interfaces cimento ósseo/tecido ósseo, comprometendo assim o desempenho mecânico da prótese ortopédica ao longo do tempo. Esta dissertação tem como objetivo principal a preparação de novas formulações de cimentos ósseos com a capacidade de estabelecer interações com os tecidos vivos circundantes. De modo a melhorar a bioatividade do sistema e facilitar a sua osseointegração, os cimentos ósseos comerciais foram reforçados com cargas significativas de HA. No entanto o recurso a elevadas cargas de HA (~60% m/m) no cimento ósseo promove debilidades do ponto de vista estrutural, levando a uma baixa resistência mecânica do material final. No sentido de ultrapassar esta limitação, foram inseridas nanoestruturas de carbono (GO ou CNTs) em baixas percentagens na matriz polimérica por forma a maximizar a sua performance mecânica através da perfeita integração de todos os componentes. A primeira fase deste trabalho consistiu no desenvolvimento de metodologias que permitissem a síntese de GO através da exfoliação química da grafite em solução aquosa. Os resultados obtidos demonstraram a obtenção de folhas de GO em larga escala e com número de camadas uniforme. A funcionalização orgânica superficial via ATRP do GO obtido, com cadeias de PMMA possibilitou o desenvolvimento de novos materiais nanocompósitos, no entanto alguns fatores de natureza tecnológica inviabilizaram o seu uso como agente de reforço na matriz idealizada. O desenvolvimento de novas formulações de cimentos ósseos consistiu numa matriz de PMMA/HA (1:2 (m/m)) reforçada com pequenas percentagens de GO ou CNTs (0,01, 0,1, 0,5 e 1,0% m/m). A síntese destes materiais nanocompósitos resultou da combinação de diversas técnicas: ultrassons, granulação por congelamento e liofilização. A análise estrutural dos nanocompósitos obtidos demonstrou a eficácia da metodologia desenvolvida na homogeneização de todos os elementos do sistema. Os estudos desenvolvidos após a conformação e caracterização estrutural dos novos materiais nanocompósitos permitiram verificar que as nanoestruturas de carbono apresentavam efeitos adversos na polimerização via radicalar do PMMA. A análise da fração orgânica permitiu verificar a presença de espécies oligoméricas o que reduziu significativamente o comportamento mecânico dos nanocompósitos. Através do estudo do aumento da concentração das espécies radicalares iniciais foi possível suplantar este problema e tirar o máximo rendimento dos agentes de reforço, tendo-se destacado os nanocompósitos reforçados com GO. A validação do ponto de vista mecânico das novas formulações de cimentos ósseos recaiu sobre o procedimento descrito na norma europeia ISO 5833 de 2002 – Implantes para cirurgia – cimentos acrílicos, tendo sido realizados os testes de compressão e de flexão. A avaliação biológica do comportamento dos cimentos ósseos assentou em duas abordagens complementares: estudos de mineralização em SBF e estudos de biocompatibilidade em meios celulares. Após a incubação das amostras em SBF ficou demonstrada a excelente capacidade para promoverem a integração de uma camada apatítica. Através de estudos celulares com Fibroblastos L929 e Osteoblastos Saos-2, nos quais foram avaliados a proliferação celular, viabilidade celular, espécies reativas de oxigénio, apoptose e morfologia celular, foi possível verificar bons níveis de biocompatibilidade para os materiais devolvidos.