Impact of cholesterol on ABC and SLC transporters expression and function and its role in disposition variability to lipid-lowering drugs

This report focuses on the effects of cholesterol on the expression and function of the ATP-binding cassette (ABCB1, ABCG2 and ABCC2) and solute-linked carrier (SLCO1B1 and SLCO2B1) drug transporters with a particular focus on the potential impact of cholesterol on lipid-lowering drug disposition. Statins are the most active agents in the treatment of hypercholesterolemia. However, considerable interindividual variation exists in the response to statin therapy. Therefore, it would be huge progress if factors were identified that reliably differentiate between responders and nonresponders. Many studies have suggested that plasma lipid concentrations can affect drug disposition of compounds, such as ciclosporin and amphotericin B. Both compounds are able to affect the expression and function of ABC transporters. Although still speculative, these effects might be owing to the regulation of drug transporters by plasma cholesterol levels. Studies with normo- and hyper-cholesterolemic individuals, before and after atorvastatin treatment, have demonstrated that plasma cholesterol levels are correlated with drug transporter expression, as well as being related to atorvastatin`s cholesterol-lowering effect. The mechanism influencing the correlation between cholesterol levels and the expression and function of drug transporters remains unclear. Some studies provide strong evidence that nuclear receptors, such as the pregnane X receptor and the constitutive androstane receptor, mediate this effect. In the near future, pharmacogenomic studies with individuals in a pathological state should be performed in order to identify whether high plasma cholesterol levels might be a factor contributing to interindividual oral drug bioavailability.

Pediatric glioblastoma cell line shows different patterns of expression of transmembrane ABC transporters after in vitro exposure to vinblastine

Resistance to drug is a major cause of treatment failure in pediatric brain cancer. The multidrug resistance (MDR) phenotype can be mediated by the superfamily of adenosine triphosphate-binding cassette (ABC) transporters. The dynamics of expression of the MDR genes after exposure to chemotherapy, especially the comparison between pediatric brain tumors of different histology, is poorly described. To compare the expression profiles of the multidrug resistance genes ABCB1, ABCC1, and ABCG2 in different neuroepithelial pediatric brain tumor cell lines prior and following short-term culture with vinblastine. Immortalized lineages from pilocytic astrocytoma (R286), anaplasic astrocytoma (UW467), glioblastoma (SF188), and medulloblastoma (UW3) were exposed to vinblastine sulphate at different schedules (10 and 60 nM for 24 and 72 h). Relative amounts of mRNA expression were analyzed by real-time quantitative polymerase chain reaction. Protein expression was assessed by immunohistochemistry for ABCB1, ABCC1, and ABCG2. mRNA expression of ABCB1 increased together with augmenting concentration and time of exposure to vinblastine for R286, UW467, and UW3 cell lines. Interestingly, ABCB1 levels of expression diminished in SF188. Following chemotherapy, mRNA expression of ABCC1 decreased in all cell lines other than glioblastoma. ABCG2 expression was influenced by vinblastine only for UW3. The mRNA levels showed consistent association to protein expression in the selected sets of cell lines analyzed. The pediatric glioblastoma cell line SF188 shows different pattern of expression of multidrug resistance genes when exposed to vinblastine. These preliminary findings may be useful in determining novel strategies of treatment for neuroepithelial pediatric brain tumors.

T-wave alternans: desempenho clínico, limitações, metodologias de análise

Reconhecer com precisão indivíduos com maior risco imediato de morte súbita cardíaca (MSC) ainda é uma questão em aberto. A natureza fortuita dos eventos cardiovasculares agudos não parece se adequar ao conhecido modelo de indução de taquicardia/fibrilação ventricular por um gatilho em sincronia a um substrato arritmogênico estático. Quanto ao mecanismo da MSC, uma instabilidade elétrica dinâmica explicaria melhor a raridade da associação simultânea de um gatilho certo a um substrato cardíaco apropriado. Diversos estudos tentaram medir essa instabilidade elétrica cardíaca (ou um equivalente válido) em uma sequência de batimentos cardíacos no ECG. Dentre os mecanismos possíveis podemos citar o prolongamento do QT, dispersão do QT, potenciais tardios, alternância de onda T ou T-wave alternans (TWA), e turbulência da frequência cardíaca. Este artigo se atém em particular ao papel da TWA no panorama atual da estratificação de risco cardíaco. Os achados sobre TWA ainda são heterogêneos, variando de um desempenho prognóstico muito bom até um quase nulo, dependendo da população clínica observada e protocolo clínico usado. Para preencher as atuais lacunas no conhecimento sobre TWA, profissionais médicos e pesquisadores devem explorar melhor as características técnicas das diversas tecnologias disponíveis para a avaliação de TWA e atentar ao fato de que os valores de TWA respondem a diversos outros fatores, além de medicamentos. Informações sobre mecanismos celulares e subcelulares da TWA estão fora do escopo deste artigo, mas são referenciados alguns dos principais trabalhos sobre este tópico, com o intuito de auxiliar no entendimento dos conceitos e fatos cobertos neste artigo.

Impact and fracture resistance of an experimental acrylic polymer with elastomer in different proportions

The purpose of this study was to evaluate the impact and fracture resistance of acrylic resins: a heat-polymerized resin, a high-impact resin and an experimental polymethyl methacrylate with elastomer in different proportions (10, 20, 40 and 60%). 120 specimens were fabricated and submitted to conventional heat-polymerization. For impact test, a Charpy-type impact tester was used. Fracture resistance was assessed with a 3-point bending test by using a mechanical testing machine. Ten specimens were used for each test. Fracture (MPa) and impact resistance values (J.m-1) were submitted to ANOVA - Bonferroni's test - 5% significance level. Materials with higher amount of elastomer had statistically significant differences regarding to impact resistance (p < 0.05). Fracture resistance was superior (p < 0.01) for high-resistance acrylic resin. The increase in elastomer concentration added to polymethyl methacrylate raised the impact resistance and decreased the fracture resistance. Processing the material by injection decreased its resistance to impact and fracture.

Influence of surface sealant on the translucency of composite resin: effect of immersion time and immersion media

This study evaluated the effect of surface sealant on the translucency of composite resin immersed in different solutions. The study involved the following materials: Charisma, Fortify and coffee, Coca-Cola®, tea and artificial saliva as solutions. Sixty-four specimens (n = 8) were manufactured and immersed in artificial saliva at 37 ± 1 °C. Samples were immersed in the solutions for three times a day and re-immersed in artificial saliva until the translucency readings. The measurements were carried out at nine times: T1 - 24 hours after specimen preparation, T2 - 24 hours after immersion in the solutions, T3 - 48 hours and T4 to T9 - 7, 14, 21, 30, 60 and 90 days, respectively, after immersion. The translucency values were measured using a JOUAN device. The results were subjected to ANOVA and Tukey's test at 5%. The surface sealant was not able to protect the composite resin against staining, the coffee showed the strongest staining action, followed by tea and regarding immersion time, a significant alteration was noted in the translucency of composite resin after 21 days.

Influence of light-curing unit systems on shear bond strength and marginal microleakage of composite resin restorations

The aim of the present study was to evaluate the influence of different photopolymerization (halogen, halogen soft-start and LED) systems on shear bond strength (SBS) and marginal microleakage of composite resin restorations. Forty Class V cavities (enamel and dentin margins) were prepared for microleakage assessment, and 160 enamel and dentin fragments were prepared for the SBS test, and divided into 4 groups. Kruskal-Wallis and Wilcoxon tests showed statistically significant difference in microleakage between the margins (p < 0.01) with incisal margins presenting the lowest values. Among the groups, it was observed that, only at the cervical margin, halogen soft-start photo polymerization presented statistically significant higher microleakage values. For SBS test, ANOVA showed no statistical difference (p > 0.05) neither between substrates nor among groups. It was concluded that Soft-Start technique with high intensity end-light influenced negatively the cervical marginal sealing, but the light-curing systems did not influence adhesion.

Doença periodontal em portadoras de valvopatia durante a gravidez: estudo clínico e microbiológico

FUNDAMENTO: A doença periodontal representa risco à gestante portadora de valvopatia reumática, seja para contrair endocardite infecciosa, seja por propiciar complicações obstétricas. OBJETIVO: Estudar a frequência da doença periodontal em portadoras de valvopatia reumática durante a gravidez. MÉTODOS: Foram estudadas 140 gestantes, comparáveis quanto a idade e o nível socioeconômico, divididas em: 70 portadoras de doença valvar reumática e 70 mulheres saudáveis. Todas se submeteram a: 1) avaliação clínica odontológica que incluiu a análise dos seguintes parâmetros: 1.1) profundidade à sondagem, 1.2) distância da linha esmalte-cemento à margem gengival, 1.3) nível clínico de inserção, 1.4) índice de sangramento, 1.5) índice de placa bacteriana, e, 1.6) comprometimento de furca; e, 2) exame microbiológico nas amostras de saliva e do cone que considerou o controle positivo para as cepas das bactérias Porphyromonas gingivalis, Tannerella forsithia e Aggregobacter actinomycetemcomitans. RESULTADOS: A lesão valvar mitral foi prevalente (65 casos = 92,8%) dentre as gestantes cardiopatas. A comparação entre os grupos mostrou não haver diferenças entre idade e a paridade, e embora tenham sido verificadas diferenças entre as medidas da distância da linha esmalte-cemento à margem gengival (p = 0,01) e o índice de placa (p=0,04), a frequência da doença periodontal identificada em 20 (14,3%) gestantes, não foi diferente entre os grupos (p = 0,147). O exame microbiológico mostrou uma proporção maior da bactéria P. gingivalis na saliva de gestantes saudáveis (p = 0,004). CONCLUSÃO: O estudo clínico e microbiológico periodontal durante a gravidez demonstrou igual frequência da doença periodontal em portadoras de valvopatia reumática quando comparada às mulheres saudáveis.

Preparation and characterization of Ti-15Mo alloy used as biomaterial

With the increase in life expectancy, biomaterials have become an increasingly important focus of research because they are used to replace parts and functions of the human body, thus contributing to improved quality of life. In the development of new biomaterials, the Ti-15Mo alloy is particularly significant. In this study, the Ti-15Mo alloy was produced using an arc-melting furnace and then characterized by density, X-ray diffraction, optical microscopy, hardness and dynamic elasticity modulus measurements, and cytotoxicity tests. The microstructure was obtained with β predominance. Microhardness, elasticity modulus, and cytotoxicity testing results showed that this material has great potential for use as biomaterial, mainly in orthopedic applications.

Influence of bioactive materials used on the dentin surface whitened with carbamide peroxide 16%

This study investigated the influence of bioactive materials on the dentin surface whitened. MATERIAL AND METHODS: Three bovine teeth were shaped into three dentin wafers. Each wafer was then sectioned, into six dentin slices. One slice from each tooth was distributed into one of 6 groups: 1.CG = control group (distilled water); 2.WT = whitening treatment; 3.WT + MI Paste Plus, applied once a day; 4.WT + Relief ACP30, applied once a day for 30 mintes; 5.WT + Relief ACP60, applied once a day for 60 minutes; 6.WT + Biosilicate®, applied once a week. All groups were treated over 14 days. RESULTS: CG presented all dentinal tubules occluded by smear layer; WT group was observed all dentinal tubules opened. In the groups 3, 4 and 6, tubules were occluded. Group 5, dentinal tubules were completely occluded by mineral deposits. CONCLUSION: The use of bioactive materials immediately after whitening treatment can reduce or even avoid the demineralization effect of whitening and avoid exposing dentinal tubules.

Influence of specimens' design and manufacturing process on microtensile bond strength to enamel: laboratory and FEA comparison

This study evaluated the effect of specimens' design and manufacturing process on microtensile bond strength, internal stress distributions (Finite Element Analysis - FEA) and specimens' integrity by means of Scanning Electron Microscopy (SEM) and Laser Scanning Confocal Microscopy (LCM). Excite was applied to flat enamel surface and a resin composite build-ups were made incrementally with 1-mm increments of Tetric Ceram. Teeth were cut using a diamond disc or a diamond wire, obtaining 0.8 mm² stick-shaped specimens, or were shaped with a Micro Specimen Former, obtaining dumbbell-shaped specimens (n = 10). Samples were randomly selected for SEM and LCM analysis. Remaining samples underwent microtensile test, and results were analyzed with ANOVA and Tukey test. FEA dumbbell-shaped model resulted in a more homogeneous stress distribution. Nonetheless, they failed under lower bond strengths (21.83 ± 5.44 MPa)c than stick-shaped specimens (sectioned with wire: 42.93 ± 4.77 MPaª; sectioned with disc: 36.62 ± 3.63 MPa b), due to geometric irregularities related to manufacturing process, as noted in microscopic analyzes. It could be concluded that stick-shaped, nontrimmed specimens, sectioned with diamond wire, are preferred for enamel specimens as they can be prepared in a less destructive, easier, and more precise way.

Mechanical properties and porosity of dental glass-ceramics hot-pressed at different temperatures

The objective of this work was to evaluate biaxial-flexural-strength (σf), Vickers hardness (HV), fracture toughness (K Ic), Young's modulus (E), Poisson's ratio (ν) and porosity (P) of two commercial glass-ceramics, Empress (E1) and Empress 2 (E2), as a function of the hot-pressing temperature. Ten disks were hot-pressed at 1065, 1070, 1075 and 1080 °C for E1; and at 910, 915, 920 and 925 °C for E2. The porosity was measured by an image analyzer software and s f was determined using the piston-on-three-balls method. K Ic and HV were determined by an indentation method. Elastic constants were determined by the pulse-echo method. For E1 samples treated at different temperatures, there were no statistical differences among the values of all evaluated properties. For E2 samples treated at different temperatures, there were no statistical differences among the values of σf, E, and ν, however HV and K Ic were significantly higher for 910 and 915 °C, respectively. Regarding P, the mean value obtained for E2 for 925 °C was significantly higher compared to other temperatures.

O extrato de maracujá sobre a morfometria de hepatócitos da tilápia do Nilo

Avaliaram-se os efeitos do extrato de maracujá veiculado na dieta (0, 50, 100 e 200mg kg-1) sobre o consumo de alimento, o ganho em peso e os níveis de glicose e cortisol plasmático de juvenis de tilápias do Nilo (87,0±6,6g). Ao final do experimento (28 dias), os peixes foram eutanasiados para remoção do fígado, visando à avaliação da área citoplasmática, contagem de células e verificação dos estoques de glicogênio hepático. Os dados foram submetidos à ANOVA unidirecional, comparando-se as médias pelo Teste de Tukey (P<0,05), com posterior estudo de regressão, buscando estabelecer as curvas das áreas citoplasmáticas, em função das diferentes doses do extrato. A inclusão do extrato na dieta não afetou o consumo de alimento e o crescimento e todos os peixes apresentaram aumento da glicose e redução do cortisol plasmático, porém sem diferenças entre os tratamentos. As curvas de regressão indicaram aumento quadrático da área citoplasmática com a elevação da doses do extrato, principalmente para 100mg kg-1, resultando em uma curva dose-resposta em forma de "U" invertido. O aumento da área do citoplasma decorreu de um acúmulo de glicogênio hepático, conforme comprovado pela prova da amilase salivar. Concluiu-se que o extrato de maracujá pode ser fornecido na dieta de juvenis de tilápia, sem prejudicar o consumo alimentar e o crescimento dos animais e que o produto altera a morfometria dos hepatócitos, sugerindo a atividade de flavonóides sobre o metabolismo de carboidratos.

Protocols for obtainment and isolation of two mesenchymal stem cell sources in sheep

PURPOSE: To evaluate different protocols to isolate stem cells from ovine umbilical cord blood and adipose tissue. METHODS: There were used 5 samples of umbilical blood and 5 samples of perirenal adipose tissue from 10 female sheep. All the samples were obtained through surgery, to harvest aseptic samples. There were used 3 protocols for obtainment and culture of umbilical cord blood stem cells and 4 protocols for ovine adipose tissue stem cells. RESULTS: It was possible to observe only one successful protocol for the obtainment of umbilical cord blood stem cells. When analyzing the techniques used to obtain adipose tissue stem cells, only one of the methods was effective as well. Through colony forming unit assay, there were obtained 58 colonies of cells after seven days in culture. Flow citometry tests revealed the cells were positive to CD44 and exhibited negative reaction to CD38, CD45, CD41/61. These cells showed a growth curve with very well defined phases LOG, LAG and PLATEAU. This phases are typically seem in mesenchymal stem cells growth curves. CONCLUSIONS: The isolation and culture of mesenchymal stem cells from ovine umbilical cord blood are complex and request more detailed assays. Stem cells from fat tissue sheep showed mesenchymal characteristics, according to their cell growth curve, ability to origin colonies of fibroblastoid cells and positive reactivity with the antibody CD44 by flow citometry.

Sisal organosolv pulp as reinforcement for cement based composites

The present work describes non-conventional sisal (Agave sisalana) chemical (organosolv) pulp from residues of cordage as reinforcement to cement based materials. Sisal organosolv pulp was produced in a 1:1 ethanol/water mixture and post chemically and physically characterized in order to compare its properties with sisal kraft pulp. Cement based composites reinforced with organosolv or kraft pulps and combined with polypropylene (PP) fibres were produced by the slurry de-watering and pressing method as a crude simulation of the Hatschek process. Composites were evaluated at 28 days of age, after exposition to accelerated carbonation and after 100 soak/dry cycles. Composites containing organosolv pulp presented lower mechanical strength, water absorption and apparent porosity than composites reinforced with kraft pulp. The best mechanical performance after ageing was also achieved by samples reinforced with kraft pulp. The addition of PP fibres favoured the maintenance of toughness after ageing. Accelerated carbonation promoted the densification of the composites reinforced with sisal organosolv + PP fibres.

Avaliação audiológica pré-cirurgia otológica de indivíduos com fissura labiopalatina operada

OBJETIVO: descrever as características audiológicas de indivíduos com fissura labiopalatina operada (FLP) e indicação de cirurgia otológica, comparando os grupos quanto ao tipo e grau da perda auditiva, bem como a curva timpanométrica. MÉTODOS: análise de 150 prontuários, ambos os gêneros, idade igual ou superior a 4 anos, FLP e indicação de cirurgia otológica, divididos em 3 grupos: I - Tubo de ventilação (TV), II - Timpanoplastia e III - Timpanomastoidectomia, analisando aspectos quanto a entrevista audiológica, audiometria tonal limiar e imitanciometria. RESULTADOS: o grupo I apresentou porcentagem maior de cirurgia bilateral (86%), o que não ocorreu nos demais grupos. Na entrevista audiológica, 83% apresentou algum tipo de queixa auditiva, sendo a mais frequente a perda auditiva (64%) com p<0,05 entre os grupos I e II; I e III. O tipo de perda auditiva de maior ocorrência foi condutivo bilateral (56%) seguido de unilateral (35%), com p<0,05 entre os grupos I e II; I e III. A perda de grau leve unilateral foi a de maior ocorrência (41%), seguida de grau leve a moderada bilateral (20%), com p<0,05 entre os três grupos. A curva timpanométrica mais frequente foi a do tipo B bilateral (39%) com p<0,05 entre os três grupos. CONCLUSÃO: a maioria dos indivíduos apresentou algum tipo de queixa na entrevista audiológica e alterações na audiometria tonal limiar e imitanciometria. A maioria dessas alterações foi compatível com problemas de orelha média, com perda auditiva do tipo condutiva, de grau leve e bilateral, independentemente da indicação cirúrgica.