Photofunctionalization of titanium: an alternative explanation of its chemical-physical mechanism

Objectives To demonstrate that titanium implant surfaces as little as 4 weeks from production are contaminated by atmospheric hydrocarbons. This phenomenon, also known as biological ageing can be reversed by UVC irradiation technically known as photofunctionalization. To propose a new model from our experimental evidence to explain how the changes in chemical structure of the surface will affect the adsorption of amino acids on the titanium surface enhancing osteointegration. Methods In our study XPS and AES were used to analyze the effects of UVC irradiation (photofunctionalization) in reversing biological ageing of titanium. SEM was used to analyze any possible effects on the topography of the surface. Results UVC irradiation was able to reverse biological ageing of titanium by greatly reducing the amount of carbon contamination present on the implant surface by up to 4 times, while the topography of the surface was not affected. UVC photon energy reduces surface H2 O and increases TiOH with many -OH groups being produced. These groups explain the superhydrophilic effect from photofunctionalization when these groups come into contact with water. Significance Photofunctionalization has proven to be a valid method to reduce the amount of hydrocarbon contamination on titanium dental implants and improve biological results. The chemisorption mechanisms of amino acids, in our study, are dictated by the chemical structure and electric state present on the surface, but only in the presence of an also favourable geometrical composition at the atomical level

A kinetic study of gamma-glutamyltransferase (GGT)-mediated S-nitrosoglutathione catabolism.

S-Nitrosoglutathione (GSNO) is a nitric oxide (NO) donor compound which has been postulated to be involved in transport of NO in vivo. It is known that c-glutamyl transpeptidase (GGT) is one of the enzymes involved in the enzyme-mediated decomposition of GSNO, but no kinetics studies of the reaction GSNO-GGT are reported in literature. In this study we directly investigated the kinetics of GGT with respect to GSNO as a substrate and glycyl- glycine (GG) as acceptor co-substrate by spectrophotometry at 334 nm. GGT hydrolyses the c-glutamyl moiety of GSNO to give S-nitroso-cysteinylglycine (CGNO) and c-glutamyl-GG. However, as both the substrate GSNO and the first product CGNO absorb at 334 nm, we optimized an ancillary reaction coupled to the enzymatic reaction, based on the copper-mediated decomposition of CGNO yielding oxidized cysteinyl-glycine and NO. The ancillary reaction allowed us to study directly the GSNO/GGT kinetics by following the decrease of the characteristic absorbance of nitrosothiols at 334 nm. A Km of GGT for GSNO of 0.398 ± 31 mM was thus found, comparable with Km values reported for other c-glutamyl substrates of GGT

in memoriam mario comporti 1935 2014 co editor in chief since 2009

Mario Comporti was born in Siena and earned a high school diploma (Classical studies) at the local Liceo Classico Enea Silvio Piccolomini. He was proud of this title, and always firmly considered classical studies an essential aspect in the education of young generations. Mario attended as a student at the University of Siena the Institute of Medical Pathology managed by Cesare Bartorelli, and was positively impressed by the ability of many physicians of the Institute to connect the scientific research with the medical-care activity. That was the time period when research first captivated him, to follow him for the rest of his subsequent life. Comporti graduated with honours in 1960, and then worked as Assistant professor at the Institutes of General Pathology of Siena and Turin.[...]</p

Adjuvant Treatment in Pancreatic Cancer: Shaping the Future of the Curative Setting

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease even in the early stages, despite progresses in surgical and pharmacological treatment in recent years. High potential for metastases is the main cause of therapeutic failure in localized disease, highlighting the current limited knowledge of underlying pathological processes. However, nowadays research is focusing on the search for personalized approaches also in the adjuvant setting for PDAC, by implementing the use of biomarkers and investigating new therapeutic targets. In this context, the aim of this narrative review is to summarize the current treatment scenario and new potential therapeutic approaches in early stage PDAC, from both a preclinical and clinical point of view. Additionally, the review examines the role of target therapies in localized PDAC and the influence of neoadjuvant treatments on survival outcomes

Pancreatic cancer molecular classifications: From bulk genomics to single cell analysis

Pancreatic cancer represents one of the most lethal disease worldwide but still orphan of a molecularly driven therapeutic approach, although many genomic and transcriptomic classifications have been proposed over the years. Clinical heterogeneity is a hallmark of this disease, as different patients show different responses to the same therapeutic regimens. However, genomic analyses revealed quite a homogeneous disease picture, with very common mutations in four genes only (KRAS, TP53, CDKN2A, and SMAD4) and a long tail of other mutated genes, with doubtful pathogenic meaning. Even bulk transcriptomic classifications could not resolve this great heterogeneity, as many informations related to small cell populations within cancer tissue could be lost. At the same time, single cell analysis has emerged as a powerful tool to dissect intratumoral heterogeneity like never before, with possibility of generating a new disease taxonomy at unprecedented molecular resolution. In this review, we summarize the most relevant genomic, bulk and single-cell transcriptomic classifications of pancreatic cancer, and try to understand how novel technologies, like single cell analysis, could lead to novel therapeutic strategies for this highly lethal disease

Antioxidant capacity and protein oxidation in cerebrospinal fluid of amyotrophic lateral sclerosis.

Background The causes of Amyotrophic Lateral Sclerosis (ALS) are unknown. A bulk of evidence supports the hypothesis that oxidative stress and mitochondrial dysfunction can be implicated in ALS pathogenesis. Methods We assessed, in cerebrospinal fluid (CSF) and in plasma of 49 ALS patients and 8 controls, the amount of oxidized proteins (AOPP, advanced oxidation protein products), the total antioxidant capacity (FRA, the ferric reducing ability), and, in CSF, two oxidation products, the 4-hydroxynonenal and the sum of nitrites plus nitrates. Results The FRA was decreased (p = 0.003) in CSF, and AOPP were increased in both CSF (p = 0.0039) and plasma (p = 0.001) of ALS patients. The content of AOPP was differently represented in CSF of ALS clinical subsets, resulting in increase in the common and pseudopolyneuropathic forms (p < 0.001) and nearly undetectable in the bulbar form, as in controls. The sum of nitrites plus nitrates and 4-hydroxynonenal were unchanged in ALS patients compared with controls. Conclusion Our results, while confirming the occurrence of oxidative stress in ALS, indicate how its effects can be stratified and therefore implicated differently in the pathogenesis of different clinical forms of ALS

Serum gamma-glutamyltransferase fractions in Myotonic Dystrophy type I: Differences with healthy subjects and patients with liver disease.

Objectives: Elevation of serum gamma-glutamyltransferase (GGT), in absence of a clinically significant liver damage, is often found in Myotonic Dystrophy type-1 (DM1). In this study we investigated if a specific GGT fraction pattern is present in DM1. Designs and methods: We compared total and fractional GGT values (b-, m-, s-, f-GGT) among patients with DM1 or liver disease (LD) and healthy subjects (HS). Results: The increase of GGT in DM1 and LD, vs HS, was mainly due to s-GGT (median: 32.7; 66.7; and 7.9 U/L, respectively), and b-GGT (8.5; 18.9; and 2.1 U/L). The subset of DM1 patients matched with HS with corresponding serum GGT showed higher b-GGT (6.0 vs 4.2 U/L). Conclusions: DM1 patients with normal total GGT values showed an alteration of the production and release in the blood of GGT fractions. Since increased s-GGT is also found in LD, a sub-clinical liver damage likely occurs in DM1 subjects apparently free of liver disease