94 research outputs found

    Immunohistochemical/histochemical double staining method in the study of columnar metaplasia of the oesophagus

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    Intestinal metaplasia in Barrett\u2019s oesopha- gus (BO) represents an important risk factor for oesophageal adenocarcinoma. Instead, few and controversial data are reported about the progression risk of columnar-lined oesophagus without intestinal metaplasia (CLO), posing an issue about its clinical management. The aim was to evaluate if some immunophenotyp- ic changes were present in CLO independently of the presence of the goblet cells. We studied a series of oesophageal biopsies from patients with endoscopic finding of columnar metapla- sia, by performing some immunohistochemical stainings (CK7, p53, AuroraA) combined with histochemistry (Alcian-blue and Alcian/PAS), with the aim of simultaneously assess the his- tochemical features in cells that shows an aber- rant expression of such antigens. We evidenced a cytoplasmic expression of CK7 and a nuclear expression of Aurora A and p53, both in goblet cells of BO and in non-goblet cells of CLO, some of which showing mild dysplasia. These find- ings suggest that some immunophenotypic changes are present in CLO and they can pre- cede the appearance of the goblet cells or can be present independently of them, confirming the conception of BO as the condition charac- terized by any extention of columnar epitheli- um. This is the first study in which a combined immunohistochemical/histochemical method has been applied to Barrett pathology

    Keratin 7 expression as an early marker of reflux-related columnar mucosa without intestinal metaplasia in the esophagus

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    BACKGROUND: The role of Barrett esophagus in carcinogenesis is widely accepted, but the significance of esophageal columnar mucosa without histological intestinal metaplasia, known as columnar-lined esophagus, is debated. MATERIAL/METHODS: We studied 128 patients free of Helicobacter pylori with reflux-related symptoms and columnar mucosa in the esophagus at endoscopy, 106 patients with Barrett esophagus (referred to as the Barrett group) and 22 patients without intestinal metaplasia (columnar group). Samples from 20 subjects free of H. pylori were used as controls. Immunostaining for keratin 7 (KRT7), keratin 20 (KRT20), caudal type homeobox 2 (CDX2), mucin 2, oligomeric mucus/gel-forming (MUC2), and tumor protein p53 (TP53) was assessed. RESULTS: Samples taken 1 cm above the gastroesophageal junction showed KRT7 staining in all cases in the Barrett and columnar groups and none in the control group. Immunostaining for TP53 was absent in the control group, and more frequent in the columnar group (7, 31.8%) compared with the Barrett group (14, 13.2%, P=0.033). In the columnar group, low grade dysplasia and TP53 expression was seen in 7 of 22 biopsy specimens (31.8%) at baseline and in 4 additional specimens after 2 years, for a total of 11 specimens (50.0%). CONCLUSIONS: The expression of KRT7 might help to explain the pathological, reflux-related nature of columnar-lined esophagus, as aberrant expression in a very early stage of the multistep Barrett esophagus progression. Expression of KRT7 may occur in basal glandular cells as a result of their multipotentiality and susceptibility to immunophenotype changes induced by reflux

    Alginate bioconjugate and graphene oxide in multifunctional hydrogels for versatile biomedical applications

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    In this work, we combined electrically-conductive graphene oxide and a sodium alginatecaffeic acid conjugate, acting as a functional element, in an acrylate hydrogel network to obtain multifunctional materials designed to perform multiple tasks in biomedical research. The hybrid material was found to be well tolerated by human fibroblast lung cells (MRC-5) (viability higher than 94%) and able to modify its swelling properties upon application of an external electric field. Release experiments performed using lysozyme as the model drug, showed a pH and electro-responsive behavior, with higher release amounts and rated in physiological vs. acidic pH. Finally, the retainment of the antioxidant properties of caffeic acid upon conjugation and polymerization processes (Trolox equivalent antioxidant capacity values of 1.77 and 1.48, respectively) was used to quench the effect of hydrogen peroxide in a hydrogel-assisted lysozyme crystallization procedure

    Functionalized carbon nanostructures versus drug resistance: Promising scenarios in cancer treatment

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    Carbon nanostructures (CN) are emerging valuable materials for the assembly of highly engineered multifunctional nanovehicles for cancer therapy, in particular for counteracting the insurgence of multi-drug resistance (MDR). In this regard, carbon nanotubes (CNT), graphene oxide (GO), and fullerenes (F) have been proposed as promising materials due to their superior physical, chemical, and biological features. The possibility to easily modify their surface, conferring tailored properties, allows different CN derivatives to be synthesized. Although many studies have explored this topic, a comprehensive review evaluating the beneficial use of functionalized CNT vs G or F is still missing. Within this paper, the most relevant examples of CN-based nanosystems proposed for MDR reversal are reviewed, taking into consideration the functionalization routes, as well as the biological mechanisms involved and the possible toxicity concerns. The main aim is to understand which functional CN represents the most promising strategy to be further investigated for overcoming MDR in cancer

    A new tool for sepsis screening in the Emergency Department

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    In this study, we developed and evaluated the diagnostic accuracy of the Sepsis Index for early sepsis screening in the Emergency Department (ED). Sepsis Index is based on the combination of monocyte distribution width (MDW) and mean monocyte volume (MMV). Sepsis Index≥1 was selected to define sepsis. We tested its diagnostic accuracy in an ED population stratified in four groups: Controls, Systemic Inflammatory Response Syndrome (SIRS), infection, and sepsis, according to Sepsis-2 criteria. Patients with sepsis displayed higher median Sepsis Index value than patients without sepsis. At the receiver operating characterictis (ROC) curve analysis for the prediction of sepsis, the area under the curve (AUC) of MDW and Sepsis Index were similar: 0.966 (95%CI 0.947-0.984), and 0.964 (95%CI 0.942-0.985), respectively. Sepsis Index showed increased specificity than MDW (94.7 vs. 90.6%), without any decrease in sensitivity (92.0%). Additionally, LR+ increased from 9.8 (MDW) to 17.4 (Sepsis Index), without any substantial change in LR-(respectively 0.09 vs. 0.08). Finally, PPV increased from 0.286 (MDW) to 0.420 (Sepsis Index). Sepsis Index improves the diagnostic accuracy of MDW alone for sepsis screening

    p53 mutations in L3-loop zinc-binding domain, DNA-ploidy, and S phase fraction are independent prognostic indicators in colorectal cancer: A prospective study with a five-year follow-up

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    p53 gene alterations are among the most common events observed in colorectal cancer, and are accompanied frequently by DNA aneuploidy and high proliferative activity. The prognostic significance of such mutations remains controversial. We prospectively evaluated the prognostic significance of p53 mutations, DNA-ploidy, and S phase fraction (SPF) in a consecutive series of 160 colorectal cancer patients (median follow-up 71 months). Tumor DNA was screened for p53 mutations by PCR/single-strand conformational polymorphism/sequencing. DNA-ploidy and SPF were assessed by DNA flow cytometry. p53 mutations were detected in 68 of 160 (42.5%) cases. In 56% (38 of 68) of these, p53 mutations were found in conserved areas of the gene and in 44% (30 of 68 cases) outside the conserved regions. Eighteen of the 68 cases (26%) had mutations in the L3 loop, 11 of 68 (16%) in the L1 loop-sheet-\u3b1 helix motif, and 39 of 68 (58%) outside L3 and loop-sheet-\u3b1 helix. Seventy-five percent of the cases (120 of 160) showed DNA aneuploidy, whereas 18% of these (22 of 120) were multiclonal. The major independent predictors for both disease relapse and death were advanced Dukes' stage, p53 mutations affecting L3 loop, DNA-aneuploid tumors, and high SPF (>18.5%). Our results show that mutations in L3 functional domain, more than any mutations, are important biological indicators to predict the outcome of patients indicating that these mutations have biological relevance in terms of colorectal cancer disease course

    Gastrointestinal stromal tumors (GISTs): focus on histopathological diagnosis and biomolecular features

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    Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the gastrointestinal tract that are believed to originate from a neoplastic transformation of the intestinal pacemaker cells (interstitial cells of Cajal) normally found in the bowel wall or their precursors. Although the microscopic features have been known for a long time, the defining characteristic of GIST is the presence of the cell-surface antigen CD117 (KIT), which is demonstrated by immunohistochemistry. KIT, which is a growth factor transmembrane receptor, is the product of the proto-oncogene c-kit (chromosome 4). Surgical removal remains the only curative treatment for patients with GISTs. Tumor size, mitotic index, anatomic location, tumor rupture and disease-free interval are the classic characteristics used to predict the clinical course of patients who undergo complete gross resection. Most GISTs express constitutively activated mutant isoforms of KIT or kinase platelet-derived growth factor receptor alpha (PDGFRA) that are potential therapeutic targets for imatinib mesylate. Imatinib mesylate is a rationally designed, molecularly specific oral anticancer agent that selectively inhibits several protein tyrosine kinases central to the pathogenesis of human cancer and which has demonstrated remarkable clinical efficacy in patients with chronic myeloid leukemia and malignant GISTs. More recently Sunitinib, a new KIT/PDGFRA kinase inhibitor, has been tested in patients with GIST resistant to imatinib, with promising results. Key words: gastrointestinal stromal tumors, histopathological diagnosis, molecular biology, novel therapie

    Muestras de granos de maíz: análisis de micotoxinas

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    El mundo demanda granos sanos e inocuos, las regulaciones de los países compradores impactan en los países productores quienes desean satisfacer las crecientes demandas impuestas para asegurar la protección de la salud y los derechos de los consumidores. La presencia de micotoxinas ocasiona pérdidas, porque la contaminación comienza a campo, se presenta en cosecha y continua en el almacenamiento especialmente, cuando las buenas prácticas están ausentes.La importancia consiste en impulsar la vigilancia a nivel nacional y la implementación de monitoreos para determinar la incidencia de las diferentes micotoxinas en las partidas de maíz. Es por ello, que se requiere de muestras, y determinar el tamaño de muestra, es una decisión importante en cualquier investigación. Se presenta el diseño del muestreo1 (determinación de tamaño de muestra y plan de muestreo) realizado en el monitoreo de las partidas comerciales de granos de maíz para exportación. Las muestras de granos de maíz fueron obtenidas al momento de arribo en las terminales portuarias de los camiones provenientes de zonas de la región pampeana Argentina. La presencia de Fumonisina B total (FBt: B1, B2 y B3) fue predominante en dichas muestras. Sin embargo, según el programa conjunto FAO/OMS y las normas alimentarias Comité del Codex (2014), los niveles máximos en granos de maíz entero y sin elaborar establecidos para un lote indicaron que se considera aceptable, si este contiene menos de 5000 μg/g. Según los resultados de los niveles de concentración de FBt obtenidos en las muestras2, en general, estuvieron por debajo de estos límites, excepto en zonas de Córdoba donde solo 4 muestras presentaron valores superiores al contenido máximo fijado por UE (CE Nº1126/7 y 1881/6). El muestreo presentado podría servir de guía a futuros trabajos de investigación, así como la influencia de otros factores tales como, las variables meteorológicas y sus interacciones

    New insights to assess the consolidation of stone materials used in built heritage: the case study of ancient graffiti (Tituli Picti) in the archaeological site of Pompeii

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    Tituli Picti are an ancient form of urban graffiti very common in the archaeological site of Pompeii (Naples, South—Italy). They are generally made of red pigments applied on walls of Campanian ignimbrite. This paper deals with a scientific investigation aimed to their conservation. This is a challenging task since it requires a multidisciplinary approach that includes restorers, archaeologists and conservation scientists. The study has provided suggestions on the proper way to conserve Tituli Picti over time. In the present work, several specimens of Campanian ignimbrite were painted with red earth pigment; lime and Arabic gum have been used as binders as well. Such painted stones were treated with three consolidants: a suspension of reactive nanoparticles of silica, ethyl silicate and an acrylic microemulsion. Treated and untreated specimens were subjected to thermal aging, artificial solar radiation and induced crystallization decay. It has been assessed the colorimetric variations induced by treatments. Moreover, the micromorphologic features of the consolidated surfaces have been highlighted by means of electron microscope observations. The scotch tape test allowed to compare the superficial cohesion induced by the three used products. According to the results, ethyl silicate seems to represent the most successful product
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