Computational approaches to shed light on molecular mechanisms in biological processes

Computational approaches based on Molecular Dynamics simulations, Quantum Mechanical methods and 3D Quantitative Structure-Activity Relationships were employed by computational chemistry groups at the University of Milano-Bicocca to study biological processes at the molecular level. The paper reports the methodologies adopted and the results obtained on Aryl hydrocarbon Receptor and homologous PAS proteins mechanisms, the properties of prion protein peptides, the reaction pathway of hydrogenase and peroxidase enzymes and the defibrillogenic activity of tetracyclines. © Springer-Verlag 2007

A model eye for fluorescent characterization of retinal cultures and tissues

Many human neural or neurodegenerative diseases strongly affect the ocular and retinal environment showing peculiar alterations which can be employed as specific disease biomarkers. The noninvasive optical accessibility of the retina makes the ocular investigation a potentially competitive strategy for screening, thus the development of retinal biomarkers is rapidly growing. Nevertheless, a tool to study and image biomarkers or biological samples in a human-like eye environment is still missing. Here we report on a modular and versatile eye model designed to host biological samples, such as retinal cultures differentiated from human induced pluripotent stem cells and ex-vivo retinal tissue, but also suited to host any kind of retinal biomarkers. We characterized the imaging performance of this eye model on standard biomarkers such as Alexa Fluor 532 and Alexa Fluor 594

Prevalence and Assessment of Malnutrition Risk among Hospitalized Children in Romania

Malnutrition is a prevalent condition in hospitalized children. Our aims were to evaluate the nutritional state and to validate the STRONGkids risk assessment tool in a hospitalized paediatric population in Romania. This is a prospective single-centre study in a tertiary teaching hospital in Romania (May 2011-January 2012). We calculated the STRONGkids score and measured the children\u2019s height and weight. Standard deviation <-2 for weight-for-height and height-for-age was considered to indicate acute or chronic malnutrition respectively. Two hundred seventy-one children were included, with median age of 5.2 years and median hospital stay of 2.01 days. Prevalence of malnutrition and severe malnutrition was 37% and 15% respectively. Using the STRONGkids screening tool, 58% of the children were found at risk of malnutrition (24% were at high risk). The kappa coefficient of agreement between STRONGkids and WHO malnutrition classification was 0.61. When a low serum protein level was used in upgrading STRONGkids risk category, kappa increased significantly to 0.71 (p=0.001). A modified STRONGkids score, incorporating total serum protein levels, performs well in predicting malnutrition in hospitalized paediatric population in Romania

po 207 ferritin engineered nanoparticles as targeted drug delivery system for cancer treatment

Introduction Cancer remains still one of the major causes of death worldwide, therefore continuous improvements in tumor-fighting strategies are necessary. Targeting drugs directly to the tumour site, to overcome the systemic side effects, represents a great challenge. Nanoparticles have increasingly been used as drug delivery system showing intriguing therapeutic efficacies. Material and methods A genetically engineered nanocarrier based on human ferritin heavy chain (HFt) able to incorporate and deliver drugs was developed. These nanoparticles contain a short motif sequence (MP) cleavable by matrix metalloproteases between the HFt subunit and a masking sequence rich in proline (P), alanine (A) and serine (S): HFt-MP-PASE40. A topoisomerase I inhibitor was loaded into these nanocarriers (HFt-MP-PASE-Topo). Cell viability of different pancreatic cancer cell lines was evaluated in vitro. In vivo the therapeutic efficacy of HFt-MP-PASE-Topo was investigated on both a pancreatic cancer cell-line-derived xenograft and a patient-derived pancreatic cancer xenograft (PDX). Results and discussions In vitro studies showed a potent cytotoxic activity of HFt-MP-PASE-Topo with an IC50 that ranges between 0,005 µM to 0,05 µM. In vivo studies further demonstrated the therapeutic efficacy of HFt-MP-PASE-Topo in pancreatic cancer-bearing mice and in PDX model. In vivo treatments exhibited a robust decrease in tumour growth furthermore the animal overall survival significantly increased in HFt-MP-PASE-Topo treated mice. Conclusion Altogether, our results indicate that HFt-MP-PASE-Topo may constitute a promising tool in anticancer therapeutics

A comparative analysis of molecular electrostatic potentials of chlorinated dibenzo-p-dioxins in relation to their biological activity

Our aim was to find some relationships between the MEP pattern and biological activity of the chlorinated dibenzo-p-dioxins. As an initial step, we calculated the RHF/3-21G MEP of 2,7-dichloro dibenzo-p-dioxin (2,7-DCDD) and of 2,3,7,8-tetrachloro dibenzo-p-dioxin (2,3,7,8-TCDD) in a number of relevant planes.To extend our analysis to higher chlorinated isomers, we also investigated the capability of semiempirical wave functions to produce reliable MEP maps. Results obtained suggest that semiempirical methods must be used with caution

Difficult Biliary Cannulation in Endoscopic Retrograde Cholangiopancreatography: An Overview of Advanced Techniques.

Endoscopic retrograde cholangiopancreatography (ERCP) plays a significant role in the treatment of a vast array of pancreatobiliary diseases. However, despite significant progress in the optimisation of ERCP methods and accessories, the technical and clinical success of ERCP can vary significantly due to a variety of patient and operator factors. Over the past several decades, a number of advanced techniques have been developed to improve cannulation success rates, including the use of double-guidewire, pancreatic duct accessory-assisted, precut, and rendezvous techniques. Here, the authors provide an update and overview of the existing advanced techniques used in cases of difficult biliary cannulation, as well as the approach to their selection