Resinas acrílicas utilizadas em placas estabilizadoras: resistência a fraturas e ensaio microbiológico / Acrylic resins used in stabilizer plates: resistance to fractures and microbiological testing

O aprimoramento da tecnologia CAD/CAM permitiu a confecção de placas estabilizadoras digitais, no entanto, há lacunas acerca do comportamento desses dispositivos frente a variáveis mecânicas e biológicas ainda desconhecidas. Dessa forma, o objetivo desse trabalho foi verificar se as resinas utilizadas na tecnologia digital das placas fresadas e impressas são capazes de influenciar na resistência à fratura e na adesão de micro-organismos em detrimento das resinas empregadas na confecção das placas termopolimerizáveis convencionais e se as propriedades testadas se relacionam com a variação da espessura desses dispositivos. Para tanto, foi realizado um estudo in vitro que contou com as fases mecânica e microbiológica, sendo cada uma composta pelos grupos Convencional (GC) (n=30), Fresado (GF) (n=30) e Impresso (GI) (n=30), de acordo com o método de confecção, possuindo cada um três subgrupos (n=10) que variaram a espessura dos espécimes de 1 a 3 mm. Na fase mecânica, as amostras, com formato de barras de 65 mm, foram testadas quanto à resistência à fratura na máquina de ensaios universal, com célula de carga de 500 kgf e velocidade de 1 mm/min; na microbiológica, a forma foi de discos com 15 mm de diâmetro, submetidos à adesão de micro-organismos à superfície com a exposição a Streptococcus mutans e mantidos por 24h a 35 °C em estufa para sucessiva contagem de UFC, com controle positivo. Os testes foram feitos em triplicata e os dados foram armazenados no SPSS 22.0 e a análise estatística contou com a ANOVA e o pósteste de Tukey. Nos resultados da fase mecânica, o ANOVA identificou diferenças estatisticamente significativas entre os grupos (p≤0,005), mostrando que GC e GF apresentaram melhores resultados. O pós-teste de Tukey considerou diferença estatisticamente significativa entre GF e GI (p=0,031), elencando GF como superior. Para a fase microbiológica, não foram verificadas diferenças estatísticas entre os grupos (p>0,005) em nenhuma das análises. Observou-se que para a resistência a fraturas, as resinas do modo fresado descreveram resultados superiores e/ou próximos aos da técnica convencional; e que as resinas da técnica digital e convencional, quanto à adesão superficial de micro-organismos, não diferiram entre si (AU).

CAD/CAM technology allowed the stabilizing splints manufacture, however there are gaps about these devices' behavior in face of mechanical and biological variables that are still unknown. Thus, the objective of this project was to verify if the resins used in digital technology of milled and printed stabilizer splints can influence fracture resistance and microorganism adhesion, in detriment of the resin applied in manufacture of conventional thermopolymerizable splints and if the tested properties are related to thickness variation of these devices. The method included mechanical and microbiological steps, each one composed by Conventional (CG) (n=30), Milled (MG) (n=30) and Printed (PG) (n=30) groups, according to the method of preparation, each one having three subgroups (n=10) that varied the specimen thickness from 1 to 3 mm. In the mechanical step, the samples, in the form of 65 mm bars, were tested for fracture resistance in a universal testing machine, with load cell of 500 kgf and speed of 1 mm/min; in the microbiological step, the shape was in form of 15 mm diameter discs, subjected to microorganism adhesion to the surface with exposure to Streptococcus mutans and kept for 24 hours at 35 °C in oven for successive CFU counting, with positive control. The tests were performed in triplicate and data were stored in SPSS 22.0 and statistical analysis used ANOVA and Tukey's post hoc. In the results of mechanical step ANOVA had identified statistically significant differences between the groups (p≤0,005), showing CG and MG had presented better results. Tukey´s post hoc had considered statistically significant difference between MG and PG (p=0,031), listing MG as superior. For the microbiological step, they did not show statistical differences between the groups (p>0.005) in any analysis. It was observed milled resins described superior results and/or close to the conventional technique one, for fracture resistance; and resins of digital and conventional technique, regarding the microorganism adhesion to the surface, did not differ from each other (AU).

Integrin activation, focal adhesion maturation and tumor metastasis / 生理学报

Integrins are a large family of heterodimeric cell adhesion molecules composed of α and β subunits. Through interaction with their specific ligands, integrins mediate cell-cell and cell-extracellular matrix interactions. Via outside-in signaling, integrins can recruit cytoplasmic proteins to their intracellular domains and then cluster into supramolecular structures and trigger downstream signaling. Integrin activation is associated with a global conformation rearrangement from bent to extended in ectodomains and the separation of α and β subunit cytoplasmic domains. During cell migration, integrins regulate the focal adhesion dynamics and transmit forces between the extracellular matrix and the cell cytoskeleton. In tumor microenvironment, integrins on multiple kinds of cells could be activated, which modulates cell migration into tumor and contributes to angiogenesis and tumor metastasis. Here, we review the mechanism of integrin activation, dynamics of focal adhesions during cell migration and tumor metastasis.

Anastrozole promotes implantation by altering the expression of paxillin and fak in rat luminal uterine epithelium / El anastrozol promueve la implantación alterando la expresión de paxilina y fak en el epitelio uterino luminal de rata

An alternative hyper-ovulator inducer to replace clomiphene citrate (CC) is needed as it is unsuitable for women with polycystic ovarian syndrome and is associated with low pregnancy rates. Anastrozole is an effective hyper-ovulator inducer, but has not been well researched. In order to determine the effectiveness of anastrozole as a hyper-ovulator inducer and to an extent compare it with CC in similar situations, this study ascertained the effects of these drugs on the expression of the focal adhesion proteins, paxillin and FAK, which are uterine receptivity markers in the surface luminal uterine epithelial cells of day 1 and day 6 pregnant Wistar rats. The results show that paxillin is localized in focal adhesions at the base of the uterine epithelial cells at day 1 of pregnancy whereas at day 6, paxillin disassembles from the basal focal adhesions and localizes and increases its expression apically. FAK is faintly expressed at the basal aspect of the uterine epithelial cells while moderately expressed at the cell-to-cell contact at day 1 in all groups from where it disassembles and relocates apically and becomes more intensely expressed at day 6 of pregnancy in untreated and anastrozole treated rats. Although paxillin is localized apically at day 6, its expression is significantly down-regulated with CC treatment suggesting its interference with the implantation process. These findings seem to suggest that anastrozole could favor implantation.

Para reemplazar el citrato de clomifeno (CC) es necesario un inductor de hiperovulación alternativo, ya que no es adecuado para mujeres con síndrome de ovario poliquístico y está asociado con tasas bajas de embarazo. El anastrozol es un inductor eficaz del hiper-ovulador, pero no se ha investigado adecuadamente. Con el fin de determinar la efectividad del anastrozol como inductor del hiper-ovulador y, en cierta medida, compararlo con CC en situaciones similares, este estudio determinó los efectos de estos fármacos en la expresión de las proteínas de adhesión focal, paxillin y FAK, uterinas marcadores de receptividad en la superficie luminal de células uterinas epiteliales, del día 1 y día 6 en ratas Wistar preñadas. Los resultados muestran que la paxilina se localiza en adherencias focales en la base de las células epiteliales uterinas en el día 1 del embarazo, mientras que en el día 6, la paxilina se desmonta de las adherencias focales basales y localiza y aumenta su expresión apicalmente. FAK se expresa débilmente en el aspecto basal de las células epiteliales uterinas, mientras que se expresa moderadamente en el contacto de célula a célula en el día 1 en todos los grupos, donde se separa y se reubica apicalmente y se expresa con mayor intensidad el día 6 de la preñez, en pacientes no tratados y tratados. ratas tratadas con anastrozol. Aunque la paxillina se localiza apicalmente en el día 6, su expresión está significativamente disminuida con el tratamiento con CC, lo que sugiere su interferencia con el proceso de implantación. Estos hallazgos sugieren que el anastrozol podría favorecer el proceso de implantación.

Compliant substratum modulates vinculin expression in focal adhesion plaques in skeletal cells / 国际口腔科学杂志·英文版

The biophysical properties of the extracellular matrix (ECM) dictate tissue-specific cell behaviour. In the skeleton system, bone shows the potential to adapt its architecture and contexture to environmental rigidity via the bone remodelling process, which involves chondrocytes, osteoblasts, osteoclasts, osteocytes and even peripheral bone marrow-derived stem/stromal cells (BMSCs). In the current study, we generated stiff (~1 014 ± 56) kPa, Young's modulus) and soft (~46 ± 11) kPa silicon-based elastomer polydimethylsiloxane (PDMS) substrates by mixing curing agent into oligomeric base at 1:5 and 1:45 ratios, respectively, and investigated the influence of substrate stiffness on the cell behaviours by characterizing cell spreading area, cell cytoskeleton and cell adhesion capacity. The results showed that the cell spreading areas of chondrocytes, osteoblasts, osteoclasts, osteocytes and BMSCs were all reduced in the soft substrate relative to those in the stiff substrate. F-actin staining confirmed that the cytoskeleton was also changed in the soft group compared to that in the stiff group. Vinculin in focal adhesion plaques was significantly decreased in response to soft substrate compared to stiff substrate. This study establishes the potential correlation between microenvironmental mechanics and the skeletal system, and the results regarding changes in cell spreading area, cytoskeleton and cell adhesion further indicate the important role of biomechanics in the cell-matrix interaction.

Induction of Melanoma Cell-Selective Apoptosis Using Anti-HER2 Antibody-Conjugated Gold Nanoparticles

PURPOSE: This study was conducted to verify the induction and mechanism of selective apoptosis in G361 melanoma cells using anti-HER2 antibody-conjugated gold nanoparticles (GNP-HER2). MATERIALS AND METHODS: Following GNP-HER2 treatment of G361 cells, cell cycle arrest and apoptosis were measured by WST-1 assay, Hemacolor staining, Hoechst staining, immunofluorescence staining, fluorescence-activated cell sorting analysis, and Western blotting.

Far-infrared radiation stimulates platelet-derived growth factor mediated skeletal muscle cell migration through extracellular matrix-integrin signaling

Despite increased evidence of bio-activity following far-infrared (FIR) radiation, susceptibility of cell signaling to FIR radiation-induced homeostasis is poorly understood. To observe the effects of FIR radiation, FIR-radiated materials-coated fabric was put on experimental rats or applied to L6 cells, and microarray analysis, quantitative real-time polymerase chain reaction, and wound healing assays were performed. Microarray analysis revealed that messenger RNA expressions of rat muscle were stimulated by FIR radiation in a dose-dependent manner in amount of 10% and 30% materials-coated. In 30% group, 1,473 differentially expressed genes were identified (fold change [FC] > 1.5), and 218 genes were significantly regulated (FC > 1.5 and p < 0.05). Microarray analysis showed that extracellular matrix (ECM)-receptor interaction, focal adhesion, and cell migration-related pathways were significantly stimulated in rat muscle. ECM and platelet-derived growth factor (PDGF)-mediated cell migration-related genes were increased. And, results showed that the relative gene expression of actin beta was increased. FIR radiation also stimulated actin subunit and actin-related genes. We observed that wound healing was certainly promoted by FIR radiation over 48 h in L6 cells. Therefore, we suggest that FIR radiation can penetrate the body and stimulate PDGF-mediated cell migration through ECM-integrin signaling in rats.

Focal adhesion proteins, vinculin and integrin ß5, during early pregnancy in rat uterine epithelial cells: anastrozole favors their normal distribution / Proteínas de adhesión focales, vinculina e integrina ß5, durante el embarazo temprano en células epiteliales uterinas de rata: anastrozol favorece su distribución normal

SUMMARY: An alternative superovulator to replace clomiphene citrate is needed as clomiphene citrate is associated with low pregnancy rates. Anastrozole is an effective superovulator, but it has not been well researched. In order to determine the effectiveness of anastrozole as a superovulator and to compare it with clomiphene citrate in similar situations, this study ascertained the effects of these drugs on the expression of the focal adhesion proteins, vinculin and integrin β5, which are uterine receptivity markers, in the uterine epithelial cells of day 1 and day 6 pregnant Wistar rats. The results show that vinculin and integrin β5 are co-localized at the base of the uterine epithelium at day 1 of pregnancy whereas at day 6, they disassemble from the basal focal adhesions and co-localize and significantly increase their expression apically (p≤0.0001). Moreover, there is a significant difference in the protein expression levels of vinculin and integrin b5 in uterine luminal epithelial cells between untreated (control) and chlomiphene citrate treated rats (p≤0.0001), anastrozole and chlomiphene citrate treated rats at day 6 (p≤0.0001) suggesting the interpretation that anastrozole seems to enhance their expression in order to perhaps assist in the implantation process of the blastocyst. The immunofluorescence experiments agree with the vinculin and integrin β5 gene expression findings in which at day 6 of pregnancy, vinculin and integrin β5 gene expression are significantly upregulated in uterine luminal epithelial cells in the anastrozole treated group relative to the calibrator sample (p≤0.0001). These findings suggest that anastrozole is implantation friendly.

RESUMEN: Es necesario un superovulador alternativo para reemplazar el citrato de clomifeno, debido a que está asociado con bajas tasas de preñez. El anastrozol es un superovulador eficaz, sin embargo es poca su investigación. Con el fin de determinar la efectividad del anastrozol como superovulador y compararlo con citrato de clomifeno en situaciones similares, se determinaron los efectos de estos fármacos sobre la expresión de las proteínas de adhesión focal, vinculina e integrina β5, en marcadores de receptividad uterina en días 1 y 6, en las células epiteliales uterinas de ratas Wistar preñadas. Los resultados muestran que la vinculina y la integrina β5 se co-localizan en la base del epitelio uterino al día 1 de la gravidez mientras que al día 6 se desmontan de las adherencias focales basales, co-localizan y aumentan significativamente su expresión apicalmente (p≤0.0001). Además, existe una diferencia significativa en los niveles de expresión de proteína de vinculina e integrina β5 en células epiteliales luminales uterinas entre ratas no tratadas (control) y tratadas con citrato declomifeno (p≤0.0001), ratas tratadas con anastrozol y citrato declomifeno al día 6 (p≤0,0001) sugiriendo la interpretación de que el anastrozol parece mejorar su expresión con el fin de ayudar en el proceso de implantación del blastocisto. Los experimentos de inmunofluorescencia coinciden con los resultados de la expresión de los genes vinculina e integrina β5 en los cuales al día 6 de la preñez, la vinculina y la integrina β5 están significativamente reguladas en células epiteliales luminales uterinas en el grupo tratado con anastrozol con respecto a la muestra del calibrador (p<0,0001). Estos hallazgos sugieren que el anastrozol es favorable para la implantación.

Gene Expression Patterns of Cutaneous Squamous Cell Carcinoma and Actinic Keratosis: Biomarkers Screening for Skin Disease Diagnosis

BACKGROUND: Actinic keratosis (AK) was an intraepidermal tumor which caused by ultraviolet irradiation-induced skin damage. OBJECTIVE: The aim was to screen biomarkers for development of skin disease by comparing the gene expression profiles between cutaneous squamous cell carcinoma (CSCC) and AK. METHODS: GSE45216 with 30 cutaneous squamous cell carcinoma patients and 10 actinic keratosis patients were downloaded and significance analysis of microarrays was processed to screen differently expressed genes (DEGs). Fisher's exact test was processed for DEGs enrichment. Pathway relationship network systematically reflected the signal conduction and synergism between enriched pathways based on Kyoto Encyclopedia of Genes and Genomes database. Gene co-expression network was constructed according to gene expression data. Quantitative real-time-PCR was used to verify screened biomarkers. RESULTS: Total 410 DEGs were screened and enriched into various functions, such as signal transduction and negative regulation of apoptotic process. They also participated into cytokine-cytokine receptor interaction and focal adhesion. The pathway relationship network was constructed with 27 nodes. Hub nodes with higher degree of this network were mitogen-activated protein kinase signaling pathway and apoptosis. The gene co-expression network was constructed with 39 nodes. Thereinto, hub node was ELOVL fatty acid elongase. The expression levels of ELOVL4 and HPGD were significantly higher in CSCC samples than that in AK samples, while the expression levels of INHBA and LAMC2 in CSCC samples were significantly lower than that in AK samples. CONCLUSION: These screened genes, including ELOVL4, HPGD, INHBA and LAMC2, played important roles in transformation from AK to CSCC.

Fundus Autofluorescence, Fluorescein Angiography and Spectral Domain Optical Coherence Tomography Findings of Retinal Astrocytic Hamartomas in Tuberous Sclerosis

PURPOSE: To analyze the structural and morphological characteristics of retinal astrocytic hamartomas in tuberous sclerosis patients using fundus autofluorescence, fluorescein angiography and spectral-domain optical coherence tomography. CASE SUMMARY: Fundus examination, fundus autofluorescence, fluorescein angiography and spectral-domain optical coherence tomography were performed in three patients with tuberous sclerosis and the morphological and structural characteristics of retinal astrocytic hamartomas were analyzed. In the fundus autofluorescence, type 1 retinal astrocytic hamartoma showed hypofluorescence and type 3 showed central hyperfluorescence and surrounding hypofluorescence. Spectral domain optical coherence tomography showed dome-shaped hyper-reflectivity within the nerve fiber layer and focal adhesion of the vitreous cortex in the type 1 retinal astrocytic hamartoma. No abnormalities were observed in the outer retinal layer and retinal pigment epithelium. In the type 3 retinal astrocytic hamartoma, optical coherence tomography showed disorganization of retinal tissue and posterior shadowing. Intratumoral cavitation and moth-eaten appearance caused by intratumoral calcification were observed and the vitreous cortex adhered to the top of the tumor and showed traction. Retinal arterial sheathing was observed in all cases and hyper- reflectivity of the arterial wall was noted on optical coherence tomography. CONCLUSIONS: Fundus autofluorescence, fluorescein angiography and spectral-domain optical coherence tomography are helpful for the classification and diagnosis of retinal astrocytic hamartomas found in tuberous sclerosis patients as well as for differentiation from other lesions.

The Outcome of Multiple Slit on Plaque with Plication Technique for the Treatment of Peyronie's Disease

PURPOSE: To evaluate the postoperative outcome of the multiple slit on plaque plication technique for the treatment of Peyronie's disease. MATERIALS AND METHODS: We retrospectively evaluated 22 patients who underwent plaque incision with penile plication for the surgical treatment of Peyronie's disease, who had failed medical treatment between 2009 and 2014. Patients were grouped by preoperative degree of penile curvature into Group I: mild (n=5, 22.7%), Group II: moderate (n=11, 50.0%), and Group III: severe (n=6, 27.3%). After a thorough review of the medical records, we evaluated (a) the correction of the curvature; (b) sexual function; and (c) any penile shortening or other complications. RESULTS: The mean postoperative follow-up period was 39 months. Complete correction of the curvature was attained in 21 patients (95.5%). As an inevitable complication, minimal penile shortening (21). The most frequent complication was subcutaneous penile edema in three patients (13.6%), which was resolved within about 3 months following surgery. CONCLUSIONS: As a modified technique, multiple slit on plaque with plication is a simple, minimally-invasive and effective technique for correcting penile curvature regardless of curvature severity. The degree of penile curvature does not significantly predict the amount of penile length loss.

Concepções de idosos sobre vulnerabilidade ao HIV/Aids para construção de diagnósticos de enfermagem / Las concepciones de ancianos sobre vulnerabilidad al VIH/Sida para la construcción de diagnósticos de enfermeira / Beliefs of older adults about their vulnerability to HIV/Aids, for the construction of nursing diagnoses

RESUMOObjetivo:conhecer concepções de idosos sobre vulnerabilidade ao HIV/Aids e identificar diagnósticos de enfermagem.Método:pesquisa de campo desenvolvida em Unidades de Saúde da Família, João Pessoa. A amostra compreendeu 250 idosos de ambos os sexos com coleta de dados de abril a julho, 2011. Aplicou-se um Teste da Associação Livre de Palavras utilizando o termo: HIV/Aids. Realizou-se análise de conteúdo e mapeamento cruzado dos termos mais frequentes com os da Classificação Internacional para a Prática de Enfermagem, 2011.Resultados:identificaram-se 202 termos, numa frequência total de 1156. Dos 202 termos, 16 foram mais frequentes e utilizados para a construção de diagnósticos de enfermagem. Identificaram-se os diagnósticos conhecimento sobre comportamento sexual adequado, capacidade para proteção parcial, medo da morte e desesperança.Conclusão:compreender essas concepções trouxe conhecimentos acerca de fatores de vulnerabilidades ao HIV/Aids tendo em vista o planejamento de ações de saúde para esse segmento populacional.

RESUMENObjetivo:conocer concepciones de ancianos sobre vulnerabilidad a HIV/Sida y identificar de diagnósticos de enfermería.Método:investigación de campo desarrollado en Unidades de Salud de Familia, João Pessoa. La muestra incluyó 250 ancianos de ambos sexos con recogida de datos de abril a julio, 2011. Se aplicó prueba de asociación de palabras el uso del término: HIV/Sida. Tenido análisis de contenido de proceder cruzar términos más frecuentes con la Clasificación Internacional para la Práctica de Enfermería, 2011.Resultados:202 términos fueron identificados en frecuencia 1156. De los 202 términos, 16 fueron más frecuentes y utilizados para construcción de diagnósticos de enfermería. Se identificaron conocimiento sobre comportamiento sexual apropiado, capacidad de protección parcial, miedo a la muerte y desesperanza.Conclusión:La comprensión de conceptos trajo reflexiones sobre factores de vulnerabilidad ante el HIV/Sida en vista de planificación de acciones la salud para este segmento de población.

ABSTRACTObjective:to know the beliefs of older adults about their vulnerability to HIV/Aids, and to identify nursing diagnoses.Method:a field research implemented in Family Health Units, in João Pessoa, Brazil. The sample included 250 older adults of both genders with data collected from April to July of 2011. A Test of Free Word Association was applied using the term HIV/Aids. A content analysis and cross-mapping of the most frequent terms with the International Classification for Nursing Practice, 2011 were performed.Results:202 terms were identified in terms, with an overall frequency of 1156. Of the 202 terms, 16 were more frequent and were used to construct the nursing diagnoses. The diagnoses identified were knowledge about appropriate sexual behavior, ability for partial protection, fear of death and hopelessness.Conclusion:understanding these beliefs drew from knowledge about factors related to, vulnerability to HIV/Aids aimed at planning health care actions for this population segment.

Modo de contacto: efecto sobre la adquisición y transferencia de una discriminación condicional de segundo orden y la emergencia de reglas / Contact mode: effect on conditional discrimination acquisition, transfer and rule emergence / Modo de contato: efeito sobre a aquisição e transferência de uma discriminação condicional de segunda ordem e a emergência de regras

Se evaluó el efecto de cuatro modos de contacto (directo, morfología lingüística, observacional y directo más descripción) sobre la adquisición y transferencia de una discriminación condicional y la generación de descripciones tipo regla. Participaron dieciséis universitarios experimentalmente ingenuos, con edades entre 18 y 21 años. Se utilizó un diseño intragrupo con prueba inicial, entrenamiento, tarea de generación de regla y pruebas de transferencia (extrainstancia, extramodal y extrarrelacional), con igualación a la muestra de segundo orden como tarea experimental base. Los resultados sugieren que: a) tanto el modo observacional -sin componentes instrumentales- como el de morfología lingüística -sin contacto perceptual directo con los arreglos- permiten la adquisición y transferencia de la discriminación condicional, así como la emergencia de reglas; y b) no hay una relación consistente entre la emergencia de reglas y la transferencia extrarrelacional efectiva. Los resultados se discuten en torno a la necesidad de: a) contacto directo con las contingencias para la transferencia y la emergencia de reglas, b) participación de un segmento lingüístico (i.e. regla) para la transferencia extrarrelacional efectiva.

This study examined the effect of four contact modes (direct, morphology, linguistic, observational, and direct plus description) on the acquisition and transfer of conditional discrimination and the emergence of rules. Sixteen experimentally naive university students, aged between 18 and 21 years, participated in the study. A within-subject design that involved initial test, training, rule generation, and testing transfer (extra instance test, extra modal test, extra relational test) was used. A second order matching to sample task was used. The results suggest that: a) both the observational mode without instrumental components and the linguistic morphology without direct perceptual contact allow the acquisition and transfer of conditional discrimination and the emergence of rules; b) there is no consistent relationship between the rules and the effective extrarelational transfer. Results are discussed in terms of the need for: i) direct contact with contingencies for the transfer and emergence of rules, ii) participation of a linguistic segment (rule) for the effective extrarelational transfer.

Avaliou-se o efeito de quatro modos de contato (direto, morfologia linguística, observacional e direto mais descrição) sobre a aquisição e transferência de uma discriminação condicional e a geração de descrições tipo regra. Participaram dezesseis universitários experimentalmente ingênuos, com idades entre 18 e 21 anos. Utilizou-se um desenho intragrupo com teste inicial, treinamento, tarefa de geração de regra e testes de transferência (extra instância, extra modal e extra relacional), com igualação à mostra de segunda ordem como tarefa experimental base. Os resultados sugerem que: a) tanto o modo observacional -sem componentes instrumentais- como o de morfologia linguística -sem contato perceptual direto com os arranjos- permitem a aquisição e transferência da discriminação condicional, bem como a emergência de regras; e b) não há uma relação consistente entre a emergência de regras e a transferência extra relacional efetiva. Os resultados discutem-se ao redor da necessidade de: i) contato direto com as contingências para a transferência e a emergência de regras, ii) participação de um segmento linguístico (ex. regra) para a transferência extra relacional efetiva.

Syntenin Is Expressed in Human Follicular Dendritic Cells and Involved in the Activation of Focal Adhesion Kinase

Syntenin is an adaptor molecule containing 2 PDZ domains which mediate molecular interactions with diverse integral or cytoplasmic proteins. Most of the results on the biological function of syntenin were obtained from studies with malignant cells, necessitating exploration into the role of syntenin in normal cells. To understand its role in normal cells, we investigated expression and function of syntenin in human lymphoid tissue and cells in situ and in vitro. Syntenin expression was denser in the germinal center than in the extrafollicular area. Inside the germinal center, syntenin expression was obvious in follicular dendritic cells (FDCs). Flow cytometric analysis with isolated cells confirmed a weak expression of syntenin in T and B cells and a strong expression in FDCs. In FDC-like cells, HK cells, most syntenin proteins were found in the cytoplasm compared to weak expression in the nucleus. To study the function of syntenin in FDC, we examined its role in the focal adhesion of HK cells by depleting syntenin by siRNA technology. Knockdown of syntenin markedly impaired focal adhesion kinase phosphorylation in HK cells. These results suggest that syntenin may play an important role in normal physiology as well as in cancer pathology.

Study on FAK regulation of migration of vascular endothelial cells depending upon focal adhesion proteins / 生物医学工程学杂志

Tumor angiogenesis induced by vascular endothelial cells (VECs) migration is a necessary condition for tumor growth and metastasis. The purpose of this study is to investigate the effect of focal adhesion kinase (FAK) inhibitor (50nmol/mL) on the adhesion and migration of endothelial cells(ECs) and the expression of focal adhesion proteins vinculin, talin and paxillin. Scratch wound migration assay was performed to examine the effect of FAK inhibitor with 50nmol/mL on ECs migration at 0, 5, 10, 30, 60 and 120min, respectively. And immunofluorescence analysis was performed to detect the expression of F-actin in ECs treated with FAK inhibitor within 2h. Western blot was carried out to determine the effect of FAK inhibitor on expression of vinculin, talin and paxillin proteins. The results showed that the migration distance and the expression of F-actin in ECs treated with FAK inhibitor decreased significantly compared with that of the controls, and the level of vinculin showed no significant difference with increasing of treated time of FAK inhibitor. However, the talin and paxillin showed an identical decreasing tendency in 5-10min, but slowly going up in 30min and then after subsequently decreasing. The results of this study proved that blocking phosphorylation of FAK could inhibit VECs adhesion and migration by downregulating focal adhesion proteins so that it may inhibit tumor angiogenesis. This may provide a new approach for tumor therapy.

Focal adhesion linker proteins expression of fibroblast related to adhesion in response to different transmucosal abutment surfaces

PURPOSE: To evaluate adherence of human gingival fibroblasts (HGFs) to transmucosal abutment of dental implant with different surface conditions with time and to investigate the roles of focal adhesion linker proteins (FALPs) involved in HGFs adhesion to abutment surfaces. MATERIALS AND METHODS: Morphologies of cultured HGFs on titanium and ceramic discs with different surface were observed by scanning electron microscopy. Biocompatibility and focal adhesion were evaluated by ultrasonic wave application and cell viability assay. FALPs expression levels were assessed by RT-PCR and western blot. RESULTS: There seemed to be little difference in biocompatibility and adhesion strength of HGFs depending on the surface conditions and materials. In all experimental groups, the number of cells remaining on the disc surface after ultrasonic wave application increased more than 2 times at 3 days after seeding compared to 1-day cultured cells and this continued until 7 days of culture. FALPs expression levels, especially of vinculin and paxillin, also increased in 5-day cultured cells compared to 1-day cultured fibroblasts on the disc surface. CONCLUSION: These results might suggest that the strength of adhesion of fibroblasts to transmucosal abutment surfaces increases with time and it seemed to be related to expressions of FALPs.

Preferential Cytotoxic Effect of Genistein on G361 Melanoma Cells Via Inhibition of the Expression of Focal Adhesion Kinase

Resistance to the induction of apoptosis is a possible mechanism by which tumor cells can survive anti-neoplastic treatments. Melanoma is notoriously resistant to anti-neoplastic therapy. Previous studies have demonstrated focal adhesion kinase (FAK) overexpression in melanoma cell lines. Given its probable role in mediating resistance to apoptosis, many researchers have sought to determine whether the downregulation of FAK in melanoma cells would confer a greater sensitivity to anti-neoplastic agents. Genistein is a known inhibitor of protein-tyrosine kinase (PTK), which may attenuate the growth of cancer cells by inhibiting the PTK-mediated signaling pathway. This present study was undertaken to investigate the effect of genistein on the expression of FAK and cell cycle related proteins in the G361 melanoma cell line. Genistein was found to have a preferential cytotoxic effect on G361 melanoma cells over HaCaT normal keratinocytes. Genistein decreased the expression of 125 kDa phosphotyrosine kinase and the FAK protein in particular. Genistein treatment did not affect the expression of p53 in G361 cells in which p21 is upregulated. The expression of cyclin B and cdc2 was downregulated by genistein treatment. Taken together, our data indicate that genistein induces the decreased proliferation of G361 melanoma cells via the inhibition of FAK expression and regulation of cell cycle genes. This suggests that the use of genistein may be a viable approach to future melanoma treatments.

Expression of Cortactin and Focal Adhesion Kinase in Colorectal Adenocarcinoma: Correlation with Clinicopathologic Parameters and Their Prognostic Implication

BACKGROUND: Cortactin and focal adhesion kinase (FAK) are two important components among actin cross-linking proteins that play a central role in cell migration. METHODS: The aims of this study were to evaluate the expression of cortactin and FAK in normal colorectal mucosa and colorectal adenocarcinoma (CRC) using tissue microarray of 2 mm cores to correlate their expression with other clinicopathological factors and, investigate their prognostic significance. RESULTS: Twenty (9%) and 24 cases (11%) of normal colorectal mucosa were immunoreactive for cortactin and FAK. In addition, 184 (84%) and 133 cases (61%) of CRCs were immunoreactive for cortactin and FAK, respectively. Cortactin expression was associated with histologic differentiation and FAK expression. Cortactin, but not FAK expression was also correlated with poor overall and relapse-free survival and served well as an independent prognostic factor for poor survival. CONCLUSIONS: Cortactin expression, in association with FAK expression, may plays an important role in tumor progression. Furthermore, it may also be a satisfactory biomarker to predict tumor progression and survival in CRC patients.

Respuesta de la terapia antirretroviral en niños con infección por VIH-1. Corte Transversal / Response of antiretroviral therapy in children with HIV-1 infection. Cross-cutting

En el 2003 se inició el Tratamiento Antirretrov iral de Gran Act ividad (TARGA) por parte de la Secretaria de Salud de nuestro país. El seguimiento de estos pacientes se hac ía clí nicamente y con exámenes de laboratorio como hemograma y quím ica Sanginea, del conteo de CD4 se inicio en el 2005 al igual que la carga viral (CV), esta ultima de modo muy irregular. Neuroestudio, inicia en el 2009 con la disponibilidad permanebte de exámenes de CD4 y CV. Nuestro objetivo fueron identificar las respuestas terapeutica de los niños(a) con infección del VIH-1 tratado en el Centro de atención integral del Hospital Nacional del Dr. Mario Catarino Rivas entre el 2009 y el 2011; realizando un análisis descriptivo de la situación clínica, inmunológica y virológica de los niños(as) en tratamiento antirretroviral. utilizamos la Clasificación de CDC para la valoración clínica e inmunológica. Consideramos no detectable la CV que es menor de 50 copias/mi a los 6 meses de iniciado el tratatamiento antirretroviral por el método aplificación por RT-PCR (Abbott Real Time m2000rt). Se analizaron 338 expedientes, encontrando una eficacia terapéutica total del 80.2%. El esquema terapeutico de segunda línea sin falla terapéutica. La causa mas frecuente de falla fue la mala adherencia en un 73.9% y por resistenci a en un 10.1%. En conclusión la adherenci a es un factor importante para mantener la eficac ia terapéutica, aunque en nuestr o estudio no resultó estadísticamente significativo...(AU)

The Interface between Cytoskeletal Aberrations and Mitochondrial Dysfunction in Alzheimer's Disease and Related Disorders

The major defining pathological hallmarks of Alzheimer's disease (AD) are the accumulations of Abeta in senile plaques and hyperphosphorylated tau in neurofibrillary tangles and neuropil threads. Recent studies indicate that rather than these insoluble lesions, the soluble Abeta oligomers and hyperphosphorylated tau are the toxic agents of AD pathology. Such pathological protein species are accompanied by cytoskeletal changes, mitochondrial dysfunction, Ca2+ dysregulation, and oxidative stress. In this review, we discuss how the binding of Abeta to various integrins, defects in downstream focal adhesion signaling, and activation of cofilin can impact mitochondrial dysfunction, cytoskeletal changes, and tau pathology induced by Abeta oligomers. Such pathological consequences can also feedback to further activate cofilin to promote cofilin pathology. We also suggest that the mechanism of Abeta generation by the endocytosis of APP is mechanistically linked with perturbations in integrin-based focal adhesion signaling, as APP, LRP, and beta-integrins are physically associated with each other.

Transcriptome Analysis of the Effects of Gomisin A on the Recovery of Carbon Tetrachloride-Induced Damage in Rat Liver / 한국실험동물학회지

Gomisin A possesses a hepatic function-facilitating property in liver-injured rats. Its preventive action on carbon tetrachloride-induced cholestasis is due to maintenance of the function of the bile acids-independent fraction. To investigate alterations in gene expression after gomisin A treatment on injured rat liver, DNA microarray analyses were performed on a Rat 44K 4-Plex Gene Expression platform with duplicated reactions after gomisin A treatment. We identified 255 up-regulated and 230 down-regulated genes due to the effects of gomisin A on recovery of carbon tetrachloride-induced rat liver damage. For functional characterization of these genes, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes biochemical pathways analyses were performed. Many up-regulated or down-regulated genes were related to cell cycle or focal adhesion and cell death genes, respectively. Our microarray experiment indicated that the liver repair mechanism induced by gomisin A was strongly associated with increased gene expressions related to cell cycle and suppression of the gene expression related in cell death.