Prevalencia, severidad de caries dental y necesidad de tratamiento restaurador en escolares de 6 a 12 Años de la Provincia de Santiago, Región Metropolitana / Prevalence, severity of dental caries, and treatments needs, among 6 to 12 years old school children, in Santiago-Metropolitan Region

RESUMEN: Objetivo: el objetivo de este estudio epidemiológico, fue determinar la prevalencia y severidad de caries dental, expresados en el índice de dientes definitivos con caries, obturados y perdidos (COPD), índice de dientes primarios con caries, extraídos y obturados (ceod) e Índice Significante de Caries (ISC) además establecer la necesidad de tratamiento restaurador y recursos humanos necesarios para ello, en una población escolar de 6 a 12 años de la Provincia de Santiago, Región Metropolitana. Metodología: Este estudio de corte transversal se realizó en 7 colegios entre públicos y privados que se encontraban debidamente registrados en la base de datos de la Secretaría Regional Ministerial de Educación pertenecientes a Provincia de Santiago, Región Metropolitana. Se seleccionó mediante un muestreo aleatorio estratificado por nivel socioeconómico, sexo y edad, una muestra de 1333 escolares de entre 6 a 12 años los cuales fueron evaluados previo asentimiento y con el consentimiento de sus tutores legales, por dos dentistas calibrados (Kappa 0.94). Para el diagnóstico de caries se utilizaron los criterios OMS. Los datos fueron recolectados en una ficha diseñada especialmente para ello y analizados utilizando el programa estadístico SPSS realizando pruebas no paramétricas de Kruskal-Wallis y U Mann-Whitney con un valor de significancia estadística del 95% (p<0,05). Resultados La prevalencia de caries encontrada en esta población, en dentición permanente fue de 24,5%, mientras que para dentición primaria 47,8%, los valores obtenidos del Índice COPD 0,48; ceod 1,67; ISC para COPD 1,45 y ISC para ceod 4,52. Las horas profesionales de odontólogos/as con sus respectivos/as asistentes, necesarias destinadas sólo a tratamiento restaurador para dar solución al daño encontrado en la muestra de estudio al momento del examen, corresponden a 167 horas para dentición permanente y 689 horas para dentición primaria. Conclusiones: La prevalencia y distribución de caries dental en escolares de 6 a 12 años de la Provincia de Santiago correspondió a cifras menores a las consignadas en el Diagnóstico de Salud Oral del Ministerio de Salud del año 2007, y menores a los índices propuestos por las organizaciones internacionales. Para resolver la necesidad de tratamiento restaurador en esta muestra se necesitarán 856 horas odontológicas.

ABSTRACT: Objective: The aim of the study was to determine prevalence and severity of dental caries, treatment needs and human resources required, in a school population aged 6 to 12 years in province of Santiago. Methodology: This cross-sectional study was conducted in seven schools. A stratified random sample was selected by socioeconomic level, sex and age. 1333 school children were evaluated by two calibrated dentists (Kappa 0.94). WHO criteria were used for caries diagnosis. Data were statistically analyzed by nonparametric tests of Kruskal-Wallis and U Mann-Whitney, statistical significance value of 95% (p <0.05). Results: 1333 patients fit the inclusion criteria. Caries prevalence was 24.5% for permanent teeth and 47.8% for primary teeth. DMFT index was 0.48, dmft index was 1.67. SiC was 1.45 for DMFT and 4.52 for dmft. A total of 167 and 689 hours of restorative treatment were required for permanent dentition and primary dentition, respectively. Conclusions: The prevalence and severity distribution of dental caries in school children aged 6 to 12 years in the Province of Santiago were lower than those recorded in the past, and lower than the rates proposed by the international organizations. To restore damaged founded in this sample 856 hours will be needed.

Histopathological Analysis of Sealant Infiltration in White Spot Enamel Lesions (WSEL) / Análisis Histopatológico de Infiltración de Sellante en Lesiones de Mancha Blanca en Esmalte (LMBE)

ABSTRACT: The use of resin sealants has shown partial infiltration of White-Spot Enamel Lesions in vitro (WSEL). The aim of the present study was to perform a morphological evaluation of natural WSEL when infiltrated using a commercially available sealant (Concise, 3M- ESPE). 20 bicuspids extracted for orthodontic reasons from patients ranging 18 to 30 years old, which had WSEL, were used in this study. The patients agreed to donate their teeth by signing a written consent. Every WSEL was assessed microscopically (Stereo Zeiss Axiscop) and then photographed (ProScope HR microscope). Prior to applying the sealant the lesion was etched using phosphoric acid at 37 % (3M-ESPE, St Paul, MN, USA.) for 30 seconds, washed for 40 seconds and then air-dried. The sealant was marked with rhodamine B (1mg/ml) and was applied according to the manufacturer directions. A specimen of approximately 100 mm was obtained for every WSEL by cutting perpendicularly through the lesion (Isomet 1000, Buehler Co.) and grinding (600 grit). The specimens were evaluated using: clear camp, polarized light, and epifluorescence microscopy. Images were taken of each specimen for every microscopic evaluation using a slide film (Kodak Ektachrome film 400 ASA). The images were digitalized by scanning at 1200 dpi resolution (Epson Filmscan 200) and then saved as JPEG and TIFF files. The sealant infiltration into The WSEL was assessed by means of analysis, processing and digital superimposing using Adobe Photoshop 7.0 and Matrox Inspector 1.07. It was concluded that the sealant infiltrated the whole body zone of the lesion. The depth of penetration of sealants into White Spot Enamel Lesion plays an important role in the control of caries lesion progression.

RESUMEN: El uso de sellantes de resina ha demostrado lograr la infiltración parcial de lesiones de mancha blanca en esmalte in vitro (LMBE). El objetivo del presente estudio fue realizar una evaluación morfológica de la infiltración a LMBE naturales utilizando un sellante disponible comercialmente (Concise, 3M-ESPE). Se utilizaron en este estudio, 30 bicúspides extraídos por razones de ortodoncia en pacientes que tenían entre 18 a 30 años de edad, y presentaban LMBE. Los pacientes aceptaron donar sus dientes firmando un consentimiento informado. Cada LMBE se evaluó microscópicamente (Stereo Zeiss Axiscop) y luego se fotografió (microscopio ProScope HR). Antes de aplicar el sellante, la lesión se grabó usando ácido fosfórico al 37 % (3M-ESPE, St Paul, MN, EE. UU.) durante 20 segundos, luego se lavó durante 40 segundos y finalmente se secó con aire de jeringa triple. El sellante se marcó con rodamina B (1 mg / ml) y se aplicó siguiendo las instrucciones del fabricante. Se obtuvo una muestra de aproximadamente 100 mm para cada LMBE cortando perpendicularmente a través de la lesión (Isomet 1000, Buehler Co.) y trituración (grano 600). Las muestras se evaluaron usando: campo claro, luz polarizada y microscopía de epifluorescencia. Se tomaron imágenes de cada espécimen para la evaluación microscópica usando una película deslizante (Kodak Ektachrome film 400 ASA). Las imágenes se digitalizaron escaneando a una resolución de 1200 ppp (Epson Filmscan 200) y luego se guardaron como archivos JPEG y TIFF. La infiltración del sellante en las LMBE se evaluaron mediante análisis, procesamiento y superposición digital utilizando Adobe Photoshop 7.0 y Matrox Inspector 1.07. Se concluyó que el sellante infiltró toda la zona del cuerpo de la lesión. La capacidad de penetración en profundidad de los sellantes en Lesiones de Mancha Blanca del Esmalte desempeñan un rol importante en el control de la progresión de las lesiones de caries.

Intravenous immunoglobulin therapy for refractory recurrent pericarditis.

Recurrent pericarditis is a troublesome complication of idiopathic acute pericarditis and occurs more frequently in pediatric patients after cardiac surgery (postpericardiotomy syndrome). Conventional treatment with nonsteroidal antiinflammatory drugs, corticosteroids, and colchicine is not always effective or may cause serious adverse effects. There is no consensus, however, on how to proceed in those patients whose disease is refractory to conventional therapy. In such cases, human intravenous immunoglobulin, immunosuppressive drugs, and biological agents have been used. In this report we describe 2 patients with refractory recurrent pericarditis after cardiac surgery who were successfully treated with 3 and 5 monthly high-dose (2 g/kg) intravenous immunoglobulin until resolution of the effusion. Our experience supports the effectiveness and safety of this therapy.

Automatic rectum limit detection by anatomical markers correlation.

Several diseases take place at the end of the digestive system. Many of them can be diagnosed by means of different medical imaging modalities together with computer aided detection (CAD) systems. These CAD systems mainly focus on the complete segmentation of the digestive tube. However, the detection of limits between different sections could provide important information to these systems. In this paper we present an automatic method for detecting the rectum and sigmoid colon limit using a novel global curvature analysis over the centerline of the segmented digestive tube in different imaging modalities. The results are compared with the gold standard rectum upper limit through a validation scheme comprising two different anatomical markers: the third sacral vertebra and the average rectum length. Experimental results in both magnetic resonance imaging (MRI) and computed tomography colonography (CTC) acquisitions show the efficacy of the proposed strategy in automatic detection of rectum limits. The method is intended for application to the rectum segmentation in MRI for geometrical modeling and as contextual information source in virtual colonoscopies and CAD systems.

EGFR signaling upregulates expression of microsomal prostaglandin E synthase-1 in cancer cells leading to enhanced tumorigenicity.

In this report we describe the contribution of prostaglandin E(2) (PGE(2)) derived from the inducible microsomal PGE-synthase type-1 (mPGES-1) to the epidermal growth factor receptor (EGFR) oncogenic drive in tumor epithelial cells and in tumor-bearing mice. EGFR stimulation upregulated expression of mPGES-1 in HT-29, A431 and A549 cancer cells. Egr-1, a transcription factor induced by EGF, mediated this response. The Egr-1 rise provoked the overexpression of mPGES-1 messenger and protein, and enhanced PGE(2) formation. These changes were suppressed either by silencing Egr-1, or by upstream blockade of EGFR or ERK1/2 signals. Further, in a clonogenic assay on tumor cells, EGF induced a florid tumorigenic phenotype, which regressed when mPGES-1 was silenced or knocked down. EGF-induced mPGES-1 overexpression in epithelial cell reduced E-cadherin expression, whereas enhancing that of vimentin, suggesting an incipient mesenchymal phenotype. Additionally, inhibiting the EGFR in mice bearing the A431 tumor, the mPGES-1 expression and the tumor growth, exhibited a parallel decline. In conclusion, these findings provide novel evidence that a tight cooperation between the EGF/EGFR and mPGES-1 leads to a significant tumorigenic gain in epithelial cells, and provide clues for controlling the vicious association.

Después de cien años de uso: ¿las férulas oclusales tienen algún efecto terapéutico? / After a century of use: do the occlusal appliances have any therapeutic effects?

Las férulas o planos oclusales han sido utilizadas desde hace más de un siglo, generando controversia acerca de su verdadero valor terapéutico. Esto motivó una revisión histórica y actualizada que permitiera evaluar sus efectos de acuerdo a la evidencia científica. Se discuten múltiples aspectos como el concepto de relación céntrica y su determinación como punto de inicio de tratamiento en la rehabilitación oral; el uso de las férulas para deprogramar; su efecto sobre la conducta motora oral que conocemos como bruxismo; su efecto en la actividad electromiográfica tónica, durante la deglución y el máximo apriete en los músculos masticatorios y cervicales; su influencia en la eficiencia muscular; su efecto en la carga articular y las evidencias experimentales del uso de distintas férulas sobre signos y síntomas especíicos como dolor y ruido articular. Se plantean desafíos para la investigación sobre cambios degenerativos en las articulaciones, en la relación craneovertebral y en la curvatura e inclinación de la columna cervical. Se concluye que es necesario utilizar una férula diseñada para el trastorno específico del paciente y que su verdadero valor terapéutico queda demostrado al mejorar algunos signos y síntomas, en músculos masticatorios y cervicales. El conocimiento parcial del mecanismo de acción de las férulas contribuye a que persista la controversia de su utilización en el tratamiento de ruidos articulares y para revertir cambios degenerativos en las articulaciones. Persiste el desafío de nuevas investigaciones, que sustenten el uso de estos dispositivos como un método eficaz para tratar a nuestros pacientes, utilizando protocolos de manejo y controles periódicos.

Occlusal appliances or splints have been used for over a century, generating controversy about their real therapeutic value. This led to an updated review to assess their effects according to scientific evidence. The concept of centric relation and its determination as a starting point of treatment; the use of splints to deprogram; their effect on the oral motor behaviour known as bruxism are discussed. Their effect on EMG activity during resting, swallowing and maximal clenching in the masticatory and neck muscles; their effect on muscular eficiency; their effect decreasing the joint overload; and experimental evidence of the use of several appliances on speciic symptoms such as pain and joint noise, are also treated. The true challenge is to generate new knowledge about joint degenerative changes, the craniocervical relationships, tilt and curvature of the cervical spine. In conclusion, it's necessary to use an occlusal appliance designed for the specific condition of the patient, and its real therapeutic value is demonstrated by the improvement of some signs and symptoms in masticatory and cervical muscles. However, the action mechanisms of occlusal appliances are not fully understood. The lack of scientiic support contributes to the persistent controversy of the use of these appliances in the treatment of temporomandibular joint sounds and reversing degenerative changes. It is still a challenge to carry out new researches supporting the use of these appliances as an effective method to treat our patients using management protocols and periodic evaluations.

Contamination of cheese by polycyclic aromatic hydrocarbons in traditional smoking. Influence of the position in the smokehouse on the contamination level of smoked cheese.

This paper sets out to determine the polycyclic aromatic hydrocarbon (PAH) contamination degree of a traditionally smoked cheese: Herreño cheese, which comes from one of the Canary Islands. Its PAH profile is thoroughly studied by means of gas chromatography-mass spectrometry in SIM mode, and compared with that of an unsmoked cheese. Furthermore, a parameter not previously studied is evaluated, namely the influence of the position of the individual cheeses in the smokehouse on their PAH contamination level. Heavy PAH, among which are included most of the carcinogens, are very scarce and their concentrations low. In fact, benz[a]anthracene, together with chrysene+triphenylene, are the only heavy PAH detected in all of the smoked samples studied. The concentration of benzo[a]pyrene, detected only in 1 of the samples, is below the limit established in Spain for the rind of smoked cheese. In contrast, high concentrations of light PAH have been found, especially of naphthalene and its alkyl derivatives, whose effect on human health is not yet well established. The results derived from the analysis of the PAH profile suggest the potential usefulness of certain ratios between some pairs of PAH (phenanthrene/anthracene, naphthalene/acenaphthylene) to provide information on the PAH contamination source. Furthermore, differences have been found, depending on the position of the cheeses in the smokehouse, those placed in the path followed by the smoke being more contaminated. Therefore, the findings of this study could help in improving the design of smokehouses, to decrease the PAH contamination degree of smoked cheese.

In vivo behavior of complete human oral mucosa equivalents: characterization in athymic mice.

BACKGROUND AND OBJECTIVE: The interest in tissue engineering as a way to achieve repair of damaged body tissues has led to the carrying out of many studies whose results point to the potential effectiveness of these methods. In a previous study, we reported the obtaining of complete autologous oral mucosa equivalents (CAOMEs), characterized by oral immature keratinocytes and stem cells on an autologous plasma and fibroblast scaffold. The purpose of this study is to show their behavior in vivo, by using them as free grafts in experimental animals, and to demonstrate their potential capacity to regenerate oral mucosa. MATERIAL AND METHODS: We engineered CAOMEs, as previously described. All CAOMEs thus obtained were used as free grafts in nu/nu mice. To assess their evolution in vivo, we studied their histological and immunohistochemical features by using AE1/AE3 pancytokeratin, the 5/6 cytokeratin pair, cytokeratin 13, laminin 5, collagen IV, vimentin, p-63 and Ki-67, at 7, 14 and 21 d. RESULTS: The structure became progressively closer to that of oral mucosa samples. Cytokeratin 5/6 staining became increasingly intense in the basal and suprabasal layers, and cytokeratin 13 was exclusively positive in the superficial layers. The basal membrane was completed in 21 d. Vimentin showed a correct formation of the chorion. The increasingly positive staining of p-63 and Ki-67 indicated that the regeneration process was taking place. CONCLUSION: The present study shows the potential regenerative capacity of the CAOMEs by their ability to reach maturity similar to that seen in oral mucosa.

[MALT B cell lymphoma with kidney damage and monoclonal gammopathy: a case study and literature review]. / Linfoma de células B tipo MALT con afectación renal y gammapatía monoclonal: presentación de un caso y revisión de la literatura.

We report a case of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) involving the left kidney and simultaneous onset of a monoclonal gammopathy IgM kappa. No predisposing local inflammatory condition was identified. Following left nephrectomy, the renal specimen showed the centrocyte like cells and lymphoid cells in the lymphoepithelial lesions were positive for CD20 and CD79α. The neoplastic cells expressed monotypic cytoplasmic IgM kappa. The demonstration of bone marrow cells of B-lineage expressing the same monoclonal protein as the tumor suggested bone marrow involvement, even in the absence of identical morphology. Despite chemotherapy and rituximab treatment, clinical follow-up showed right kidney extension with high-grade transformation, and finally systemic dissemination. This case illustrates that the kidney is among the sites that may be involved by MALT B-cell lymphomas in a primary or secondary fashion, and the need for expanded investigation of the possible dissemination. We review the literature on this unusual extranodal lymphoma.

Prevalencia de caries, pérdida de dientes y necesidad de tratamiento en población adulta Mapuche-Huilliche de Isla Huapi / Prevalence of caries, teeth loss and treatment needs in adult Mapuche-Huilliche population in Isla Huapi

Objetivo: El objetivo de este estudio transversal fue evaluar el estado de salud oral y cuantificar la prevalencia de caries dental, pérdida de dientes y necesidad de tratamiento en la población adulta de etnia Mapuche-Huilliche que habita la Isla Huapi. Método: Se examinó una muestra representativa de 64 habitantes adultos de la Isla Huapi, constituida por 31 hombres y 33 mujeres de entre 25 a 82 años de edad, que tenían a lo menos un apellido de origen Mapuche-Huilliche. Todos los individuos, previa firma de un consentimiento informado, fueron examinados por un solo dentista calibrado durante el mes de agosto 2009. Los datos fueron registrados en una ficha diseñada especialmente y analizados estadísticamente usando los test T de Student y ANOVA. Resultados: El promedio del índice COPD de la muestra fue 14.59. Todos los individuos tenían historia de caries. De los que conservaban dientes, el 71.43 por ciento tenían caries sin tratar, con un promedio de 1.25. El 98.43 por ciento de los individuos de la muestra presentaban algún grado de desdentamiento, el 12.5 por ciento eran edéntulos. El 100 por ciento de la población necesitaba atención odontológica, ya fuera para operatoria o prótesis. Conclusiones: Esta población presenta un gran daño en cuanto a su salud oral, especialmente debido a pérdida de dientes. La magnitud del daño e importancia del entorno social como determinante en la generación de éste, obliga a enfrentar el problema y buscar soluciones desarrollando y aplicando programas gubernamentales de promoción y atención en salud oral a toda la población.

Objectives: The aim of this cross- sectional study was to assess oral health status and quantify prevalence of dental caries, teeth loss and treatment needs in an ethnic group of Mapuche-Huilliche adult population in Isla Huapi. Method: A representative sample of 64 adult inhabitants of Isla Huapi was selected. 31 men and 33 women aged 25 to 82 years of age who had at least one Mapuche-Huilliche surname, after signing an informed consent, individuals were examined by a calibrated examiner during August 2009. Data were recorded and analyzed statistically using T Student and ANOVA tests. Results: The DMFT index average of the sample was 14.59. All individuals had caries experience. Untreated caries were found in a 71.43 percent of individuals retaining teeth, with an average of 1.25 each. 98.43 percent of the individuals had some degree of edentulism, 12.5 percent were edentulous. 100 percent of the population needed either restorative or prosthetic dental care. Conclusions: This population has a high degree of damage in their oral health, especially due to teeth loss, which could be explained by their limited access to preventive and restorative dental care. The extent of the damage and the importance of the social environment as a determiner in the generation of it, will mean addressing the problem and seeking solutions by developing and implementing government programs for the promotion and oral health care to the entire population.

Intraosseous mandibular schwannoma mimicking an odontogenic keratocyst, with a postsurgical pathological fracture.

OBJECTIVE: Schwannomas are slowly growing tumours derived from Schwann cells. We present a clinical case of schwannoma in the mandibular angle. METHOD: Case report and a review of the world literature concerning intraosseous schwannoma of the maxillofacial region. RESULTS: Schwannomas or neurilemmomas are slow-growing, benign neoplasms derived from Schwann cells. Intraoral lesions are unusual and intraosseous schwannomas are even rarer, representing less than 1 per cent of benign primary tumours of the bones. We present a clinical case of schwannoma in the mandibular angle mimicking a keratocystic odontogenic tumour, with a complicated posterior evolution. CONCLUSION: Clinically, neurilemmomas are slow-growing tumours which may be present for years before becoming symptomatic. Radiographically, the image may be suggestive of a benign process such as an odontogenic keratocyst. Histological analysis of the specimens obtained is extremely important in order to establish the final diagnosis.

Distinctive clinicopathological associations of amplification of the cortactin gene at 11q13 in head and neck squamous cell carcinomas.

Amplification of the 11q13 region is a prevalent genetic alteration in head and neck squamous cell carcinoma (HNSCC). We investigated the clinical significance of cortactin (CTTN) and cyclin D1 (CCND1) amplification in both malignant transformation and tumour progression. CTTN and CCND1 amplification was analysed by differential and real-time PCR in a prospective series of laryngeal/pharyngeal carcinomas and archival premalignant tissues. CTTN mRNA and protein expression were respectively determined by real-time RT-PCR and immunohistochemistry, and correlated with gene status. Molecular alterations were associated with clinicopathological parameters and disease outcome. CTTN and CCND1 amplifications were respectively found in 75 (37%) and 90 (45%) tumours. Both correlated with advanced disease; however, only CTTN amplification was associated with recurrence and reduced disease-specific survival (p = 0.0022). Strikingly, CTTN amplification differentially influenced survival depending on tumour site (p = 0.0001 larynx versus p = 0.68 pharynx) and was an independent predictor of reduced survival in the larynx (p = 0.04). CCND1 amplification was detected in early tumourigenesis and increased with the severity of dysplasia. Importantly, CTTN amplification was only found in high-grade dysplasias that progressed to invasive carcinoma. CTTN gene status strongly correlated with mRNA and protein expression. Furthermore, CTTN overexpression correlated significantly with reduced disease-specific survival (p = 0.018). Taken together, these data indicate that CTTN may serve as a valuable biomarker to identify patients with laryngeal tumours at high risk of recurrence and poor outcome.

[Folliculotropic mycosis fungoides. Study of four cases]. / Micosis fungoide folicular. Estudio de cuatro casos.

Folliculotropic mycosis fungoides is a variant of mycosis fungoides characterized by the presence of folliculotropic infiltrates, often with sparing of the epidermis, and preferential involvement of the head and neck. We report our experience with four cases of folliculotropic mycosis fungoides followed in our department in the last years. There are four patients (three men and one woman) aged 45 to 68 years. Clinically the lesions presented as cysts, comedones, follicular papules and plaques with follicular plugging. The histopathological study showed a peri and intrafollicular infiltrate with partial or total sparing of the epidermis. This infiltrate was mainly composed of atypical lymphocytes. Some cystic formations were also observed. Three cases showed mucin deposits and one showed syringotropism. The immunohistochemical analysis was positive for CD3, CD5 and CD4. All patients received different treatments based on the stage of their disease. One of them died of septic shock and the rest showed partial responses and frequent relapses.

Expression of MMP-7 and MT1-MMP in oral squamous cell carcinoma as predictive indicator for tumor invasion and prognosis.

BACKGROUND: Squamous cell carcinoma of the oral cavity is a highly invasive neoplasm that spreads locally and metastasizes to regional lymph nodes. This process involves multiple proteolytic enzymes including matrilysin (MMP-7) and membrane type I-matrix metalloproteinase (MT1-MMP). This study was designed to explore the association between MMP-7 and MT1-MMP in the invasiveness and prognosis of oral squamous cell carcinoma (OSCC). METHODS: About 4-microM, formalin-fixed, paraffin-embedded tissue sections from 69 patients with OSCC were immunohistochemically studied using specific antibodies against MMP-7 and MT1-MMP proteins. Immunostaining was semiquantitatively scored, and results were correlated with histologic and clinical variables including clinical behavior and survival. RESULTS: MMP-7 was observed only in cancer cells, and MT1-MMP in both tumoral tissue and stroma. MMP-7 expression was significantly correlated with lymph node metastasis (P = 0.03; RR = 3.2). MT1-MMP showed a significant association with TIMP-2 (in N+ cases) and p53 expression (P = 0.01). MMP-7 and MT1-MMP displayed a survival relevance, and in multivariate analysis they were independent prognostic indicators, particularly in neck node-positive cases.

Bombesin induces cyclooxygenase-2 expression through the activation of the nuclear factor of activated T cells and enhances cell migration in Caco-2 colon carcinoma cells.

Cyclooxygenase-2 (Cox-2), the gastrin-release peptide (GRP) and its cognate receptor (GRP-R) are overexpressed in a significant percentage of colorectal carcinomas and are associated with cell growth, invasiveness and tumor progression. However, a molecular link between all of them in adenocarcinomas has not been established. Here, we show that bombesin (BBS), a GRP homolog, stimulates the expression of Cox-2 mRNA and protein in human colon adenocarcinoma Caco-2 cells, resulting in enhanced release of prostaglandin E(2). These effects were markedly inhibited by the specific BBS antagonist RC-3940-II. BBS promotes the activation of the nuclear factor of activated T cells (NFAT) through a Ca(2+)/calcineurin (Cn)-linked pathway. Upon BBS stimulation, the NFATc1 isoform translocates into the nucleus with a concomitant increase in NFATc1 binding to two specific recognition sites in the promoter region of the Cox-2 gene. Furthermore, inhibition of Cn activity by the immunosuppressive drug cyclosporin A impaired NFAT activation and diminished Cox-2 expression in BBS-stimulated cells. Interestingly, BBS pretreatment strongly enhances the invasive capacity of carcinoma cells, effect which was inhibited by a Cox-2-specific inhibitor. These findings provide the first evidence for the involvement of the Ca(2+)/Cn/NFAT pathway in BBS-mediated induction of genes involved in colon carcinoma invasiveness such as Cox-2.

The efficacy of photochemical treatment with methylene blue and light for the reduction of Trypanosoma cruzi in infected plasma.

BACKGROUND AND OBJECTIVES: Chagas disease is a transfusion-transmitted infection. This study evaluates the efficacy of a methylene blue (MB) and light system for reducing the viability of Trypanosoma cruzi in plasma. MATERIALS AND METHODS Trypanosoma cruzi strains were spiked in plasma pools. Treatment arms included combined filtration, MB, light and freezing. Post-treatment parasite viability was assayed through in vitro cultures and in vivo inoculation in inducible nitric oxide synthase- and interferon-gamma-receptor-deficient mice. RESULTS: The filtration, MB and light combined treatment showed a log reduction of > 3.4 in in vitro cultures, and log reductions that ranged from > 4.9 to > 5.8 in deficient mice inoculated with different T. cruzi strains. CONCLUSION: The treatment of plasma units with the MB and light system reduces the T. cruzi burden and could be useful in preventing transfusion-transmitted Chagas disease.

Encephalitozoon microsporidia modulates p53-mediated apoptosis in infected cells.

Microsporidia are intracellular obligate parasites which have recently been found to be related to fungi. They have a unique extrusion apparatus that is able to inject the sporoplasm directly into the target cell without using receptors. Encephalitozoon microsporidia are a source of morbidity and mortality in humans. It has been suggested that microsporidia may modulate the host cell cycle and apoptosis. We report here that caspase-3 cleavage is inhibited at different times of Vero cell infection by Encephalitozoon microsporidia and that the phosphorylation and translocation of p53 to the nucleus, previous steps for the activation of this protein, do not occur after infection of Vero cells. Consequently, the transcriptional function of p53 is impaired during the infection cycle as demonstrated by luciferase reporter assays. Thus, to our knowledge, for the first time it is shown that an intracellular parasite may be able to multiply in the host cell without activating the p53 apoptotic pathway of that cell. However, changes in the expression of Bcl-2 or Bax levels were not observed.

Trypanosoma cruzi-induced molecular mimicry and Chagas' disease.

Chagas' disease, caused by Trypanosoma cruzi, has been considered a paradigm of infection-induced autoimmune disease. Thus, the scarcity of parasites in the chronic phase of the disease contrasts with the severe cardiac pathology observed in approximately 30% of chronic patients and suggested a role for autoimmunity as the origin of the pathology. Antigen-specific and antigen-non-specific mechanisms have been described by which T. cruzi infection might activate T and B cells, leading to autoimmunity. Among the first mechanisms, molecular mimicry has been claimed as the most important mechanism leading to autoimmunity and pathology in the chronic phase of this disease. In this regard, various T. cruzi antigens, such as B13, cruzipain and Cha, cross-react with host antigens at the B or T cell level and their role in pathogenesis has been widely studied. Immunization with those antigens and/or passive transfer of autoreactive T lymphocytes in mice lead to clinical disturbances similar to those found in Chagas' disease patients. On the other hand, the parasite is becoming increasingly detected in chronically infected hosts and may also be the cause of pathology either directly or through parasite-specific mediated inflammatory responses. Thus, the issue of autoimmunity versus parasite persistence as the cause of Chagas' disease pathology is hotly debated among many researchers in the field. We critically review here the evidence in favor of and against autoimmunity through molecular mimicry as responsible for Chagas' disease pathology from clinical, pathological and immunological perspectives.

Mismatch repair protein MSH2 expression and prognosis of colorectal cancer patients.

INTRODUCTION AND AIMS: The role of genetic factors in the etiology and prognosis of patients with sporadic colorectal cancer is controversial. We have therefore investigated the biological and clinicopathological influence of immunohistochemical MSH2 expression in colorectal cancer. PATIENTS AND METHODS: A total of 49 consecutive patients with unselected colorectal cancer operated on in our unit were included in the study. All tumors were resected and tumor specimens were evaluated for MSH2 expression. Clinicopathological data and patient survival were correlated with MSH2 staining. Uni- and multivariate analyses were performed. The minimum follow-up period was five years. RESULTS: Curative resection was performed in 34 patients (64.9%), 14 of whom subsequently relapsed. At the end of the overall follow-up 25 (51%) patients had died, 21 of cancer-related causes. Twenty-eight patients (57.1%) were negative for MSH2 staining. Only vascular invasion was significantly correlated with MSH2 expression (lower median values; p=0.04). The overall median survival was 47.9 months (95% CI=27-86.6%). Multivariate analysis of variables in relation to survival showed that T stage (p=0.001), N stage (p<0.001) and MSH2 expression (p=0.01) were independent factors for survival. CONCLUSIONS: Reduced MSH2 expression is frequent in unselected colorectal cancer patients. Only vascular invasion was correlated with MSH2 expression in this study. Survival was related to TN stage and MSH2 staining.

Components detected by means of solid-phase microextraction and gas chromatography/mass spectrometry in the headspace of artisan fresh goat cheese smoked by traditional methods.

The study of the headspace components of fresh smoked goat cheese, was carried out by means of solid-phase microextraction using a polyacrylate fiber followed by gas chromatography/mass spectrometry. The samples studied were six artisan Palmero cheeses manufactured following traditional methods and smoked using pine needles. The cheese regions studied were exterior, interior, and a cross section. In total, more than 320 components were detected, the exterior region being the richest in components, among which were acids, alcohols, esters, hydrocarbons, aldehydes, ketones, furan and pyran derivatives, terpenes and sesquiterpenes, nitrogen derivatives, phenol, guaiacol and syringol derivatives, ethers, and others. In addition to typical cheese components, typical smoke components were also detected; these latter were present especially in the headspace of the exterior region and only those in significant concentrations in the exterior region were also detected in the interior. The main components were acids and phenolic derivatives. These latter compounds play an important role in the flavor of this cheese, and their relative proportions together with the presence of specific smoke components derived from pine leaves may be considered of interest in order to distinguish this cheese from others smoked with different vegetable matter.