Maria Quarto

Photodynamic therapy with topical δ-aminolaevulinic acid for the treatment of plantar warts

Treatments currently employed for plantar warts are often painful (electrosurgery, cryotherapy) and not always effective (keratolytic agents). In this paper we investigate the effect of photodynamic therapy (PDT) with topical delta-aminolaevulinic acid (ALA) on plantar warts. In order to remove the superficial hyperkeratotic layer of the warts an ointment containing 10% urea and 10% salicylic acid was applied for 7 days. After gentle curettage, a cream containing 20% ALA was applied under an occlusive dressing for 5 h on 64 warts, while 57 warts (controls) received only the vehicle. Both the ALA-treated warts and the controls were irradiated using a visible light lamp (with a range of 400-700 nm, peaking at 630 nm). The light dose was 50 J/cm(2). Patients were followed-up for 22 months. Two months after the last irradiation session 48 (75.0%) out of 64 ALA-PDT treated warts had resolved. By contrast only 13 (22.8%) of the 57 control warts had done so. During the treatment a few patients complained of a mild burning sensation. The absorption of ALA by the verrucous tissue was demonstrated by in vivo fluorescence spectroscopy. This study shows that topical ALA-PDT can be an alternative treatment for plantar warts. Further studies will be necessary in order to optimize the concentration of ALA and duration of treatment.

Proteomic characterization of donkey milk “caseome”

At present, compared with bovine milk, the characterization of donkey milk caseins is at a relatively early stage progress, and only limited data are related to its genetic polymorphism. In this work, the heterogeneity of donkey caseome was investigated using a proteomic approach, based on one- (PAGE, UTLIEF) and two-dimensional (PAGE-->UTLIEF) electrophoresis, stained with either Coomassie Brilliant Blue or specific polyclonal antibodies, and structural MS analysis. These combined methodologies allowed the contemporary identification of donkey alpha(s1), alpha(s2), beta and kappa-CN with their related heterogeneity due to phosphorylation (alpha(s1), alpha(s2) and beta-CN), glycosylation (kappa-CN) and incorrect splicing of RNA in mRNA (deleted forms of alpha(s1)-CN and beta-CN). The results achieved showed 11 components for kappa-CN, six phosphorylated components for beta and alpha(s1)-CN and three main phosphorylated components for alpha(s2)-CN, each accounting for 10, 11 and 12 P/mole. At this regard, for the first time, the primary structure of the expressed protein corresponding to the only available donkey alpha(s2)-CN cDNA sequence was determined. Furthermore beta-CN was found in homozygous and heterozygous state for the occurrence of a genetic beta-CN variant having a MW value 28 mass units higher than the common beta-CN phenotype.

Hypericin photosensitization of tumor and metastatic cell lines of human prostate

We have investigated the photoactivating effect of hypericin on two cancer cell lines: PC-3, a prostatic adenocarcinoma non-responsive to androgen therapy and LNCaP, a lymphonodal metastasis of prostate carcinoma responsive to androgen therapy. The two cell lines are incubated for 24 h with hypericin at concentrations ranging from 0.001 to 0.3 microg/ml in cell culture medium. The cells are irradiated at 599 nm (fluence = 11 J/cm2) using a dye laser pumped by an argon laser. Hypericin exerts phototoxic effects on both cell lines, while it does not produce toxic effects in the absence of irradiation. These results suggest that photodynamic therapy (PDT) with hypericin could be an alternative approach to the treatment of prostatic tumors, and could be beneficial in tumors that are non-responsive to androgen therapy.

Protective effect of yogurt extract on dental enamel demineralization in vitro

BACKGROUND Casein phosphopeptides (CPPs) are phosphorylated casein-derived peptides produced synthetically by proteolytic digestion of alpha(s1)-, alpha(s2)- and beta-casein. The anticariogenic activity of CPPs is due to their ability to stabilize high levels of amorphous calcium phosphate (ACP) on tooth surface, preventing demineralization and enhancing remineralization of enamel caries. The aim of this study was to test the in vitro ability of natural CPPs (contained in yogurt) to prevent demineralization and promote remineralization of dental enamel. METHODS Eighty human molars were used. After standardizing an in vitro demineralization procedure for producing artificial caries (Group 1: pH 4.8; Group 2: pH 3.97), this procedure was used on teeth, but with the addition of natural CPPs (Group 3: pH 4.8; Group 4: pH 3.97). The effects of these procedures were evaluated by quantitative analysis (change in weight and calcium titration) and qualitative analysis (SEM). Statistical analysis of the results was performed using ANOVA. RESULTS Statistical analysis showed significant differences in weight changes between the groups with and without natural CPPs. The SEM observation showed the protective effects of natural CPPs. CONCLUSIONS The results demonstrated that CPPs contained in yogurt have an inhibitory effect on demineralization and promote the remineralization of dental enamel.

PTPD1 supports receptor stability and mitogenic signaling in bladder cancer cells

PTPD1, a cytosolic non-receptor protein-tyrosine phosphatase, stimulates the Src-EGF transduction pathway. Localization of PTPD1 at actin cytoskeleton and adhesion sites is required for cell scattering and migration. Here, we show that during EGF stimulation, PTPD1 is rapidly recruited to endocytic vesicles containing the EGF receptor. Endosomal localization of PTPD1 is mediated by interaction with KIF16B, an endosomal kinesin that modulates receptor recycling at the plasma membrane. Silencing of PTPD1 promotes degradation of EGF receptor and inhibits downstream ERK signaling. We also found that PTPD1 is markedly increased in bladder cancer tissue samples. PTPD1 levels positively correlated with the grading and invasiveness potential of these tumors. Transgenic expression of an inactive PTPD1 mutant or genetic knockdown of the endogenous PTPD1 severely inhibited both growth and motility of human bladder cancer cells. These findings identify PTPD1 as a novel component of the endocytic machinery that impacts on EGF receptor stability and on growth and motility of bladder cancer cells.

Elevated expression of the tyrosine phosphatase SHP-1 defines a subset of high-grade breast tumors

Objectives: Protein tyrosine phosphatases are key regulators of intracellular signaling that contribute to determining cancer cell growth, which thus makes them attractive targets for therapeutic and diagnostic agents. SHP-1 phosphotyrosine phosphatase is rarely expressed in epithelial tumor cells, but expression has been found in several breast cancer cell lines and tumors. To determine the potential significance of SHP-1 as a prognostic marker in the clinical setting, we examined SHP-1 protein expression in breast tumors. Methods: We analyzed SHP-1 expression by immunohistochemistry in a breast tissue microarray composed of 2,081 cores, either alone or in combination with known prognostic markers. Results: Our data showed that SHP-1 expression was confined to a well-defined subset of high-grade tumors characterized by unique biological parameters. SHP-1 expression correlated directly with expression of the tyrosine kinase receptor HER-2 and inversely with expression of the estrogen receptor, while it was weakly associated with Bcl-2 expression. Conclusions: Levels of SHP-1 were correlated with conventional pathologic parameters of tumor aggressiveness and were associated with reduced patient survival, suggesting that elevated expression of SHP-1 is a common molecular abnormality in a defined subset of breast tumors and might be used in routine diagnosis to identify patients with high-risk tumors.

A Simple Noninvasive Score Predicts Gastroesophageal Varices in Patients With Chronic Viral Hepatitis

Background Guidelines recommend upper endoscopic screening of cirrhotic patients for gastroesophageal varices. Cirrhosis is not always distinguishable from chronic hepatitis. Goals To identify low-risk patients who can be spared upper endoscopy irrespective of a diagnosis of cirrhosis. Study We evaluated 13 nonendoscopic variables as predictors of esophagogastric varices in 254 patients with hepatitis B or hepatitis C-related chronic liver disease who underwent upper endoscopy. Results Any size varices occurred in 30.3% (77/254), and large varices in 12.2% of patients (31/254). Age >50 years [odds ratio (OR): 11.29; 95% confidence interval (CI): 2.33-54.67], platelet count <150,000/mmc (OR: 4.40; 95% CI: 1.85-10.45), albumin <3.6 g/dL (OR: 2.99; 95% CI: 1.31-6.79), and aspartate aminotransferase/alanine aminotransferase ratio >1 (OR: 2.83; 95% CI: 1.26-6.34) independently predicted varices by logistic regression. Using a score based on age >50 years, platelets <150,000/mmc, and aspartate aminotransferase/alanine aminotransferase ratio >1 (1 point/predictor), only 3.2% of patients with a score <2 had varices, all small. Conclusions Patients with chronic viral hepatitis and a score <2 need not undergo upper endoscopy, as they are unlikely to have large varices. Because about 50% of our patients had this score, 50% of upper endoscopies may be safely avoided.

Multiple processor version of a Monte Carlo code for photon transport in turbid media

Abstract Although Monte Carlo (MC) simulations represent an accurate and flexible tool to study the photon transport in strongly scattering media with complex geometrical topologies, they are very often infeasible because of their very high computation times. Parallel computing, in principle very suitable for MC approach because it consists in the repeated application of the same calculations to unrelated and superposing events, offers a possible approach to overcome this problem. It was developed an MC multiple processor code for optical and IR photon transport which was run on the parallel processor computer CRAY-T3E (128 DEC Alpha EV5 nodes, 600 Mflops) at CINECA (Bologna, Italy). The comparison between single processor and multiple processor runs for the same tissue models shows that the parallelization reduces the computation time by a factor of about N , where N is the number of used processors. This means a computation time reduction by a factor ranging from about 10 2 (as in our case where 128 processors are available) up to about 10 3 (with the most powerful parallel computers with 1024 processors). This reduction could make feasible MC simulations till now impracticable. The scaling of the execution time of the parallel code, as a function of the values of the main input parameters, is also evaluated.

MS‐2 fibrosarcoma characterization by laser induced autofluorescence

MS‐2 fibrosarcoma implanted in BALB‐CDF1 mice was investigated by frequency and time domain measurements of the autofluorescence (AF) radiation emitted upon excitation by a N2 laser beam (337.1 nm).

Molecular aspects of photodynamic therapy: low energy pre-sensitization of hypericin-loaded human endometrial carcinoma cells enhances photo-tolerance, alters gene expression and affects the cell cycle

Photosensitization of HEC1‐B cells with a low concentration of hypericin and doses of light below 10 J/cm2 caused cell death (apoptosis occurred mainly at doses between 2 and 5 J/cm2, whereas necrosis prevailed above 6 J/cm2). However, pre‐exposure of cells to innocuous irradiation (2 J/cm2) and successive challenge with a light dose that normally induced apoptosis (5 J/cm2) altered the expression of the proteins involved in the regulation of apoptosis, stress response and cell cycle. This change resulted in a significant increase in cell photo‐tolerance.