Salecan-Clay Based Polymer Nanocomposites for Chemotherapeutic Drug Delivery Systems; Characterization and In Vitro Biocompatibility Studies

Salecan is a microbial polysaccharide suitable to obtain hydrogel for biomedical applications due to the excellent hydrophilicity and biocompatibility properties. In this work, Salecan of different concentrations was introduced into polymethacrylic acid (PMAA) in the presence of clay to form novel semi synthetic hydrogel nanocomposites systems and loaded afterwards with doxorubicin (DOX). The physical–chemical characteristics of the nanocomposites systems and their effect on the viability, and morphology of MDBK (Madin–Darby bovine kidney), HT-29 human colorectal adenocarcinoma and Colo 205 human colon adenocarcinoma cell lines were investigated. DOX release from the nanocomposite systems, cell up-take and subsequent effect on cell proliferation was also analyzed. It was found that Salecan concentration determined the swelling behavior, structural parameters and morphological features of the nanocomposite systems. The hydrogen bonds strongly influenced the formation of PMAA–Salecan–clay systems, each component bringing its own contribution, thus demonstrating the achievement of an advanced crosslinked network and a more compacted hydrogel nanocomposite morphology. All the synthesized nanocomposites had negligible toxicity to normal MDBK cells and chemoresistent HT-29 cell line, whereas in the case of Colo 205 cells a decrease by 40% of the cell viability was obtained for the sample containing the highest amount of Salecan. This effect was correlated with the lowest pore size distribution leading to highest available specific surface area and entrapped amount of DOX which was further released from the nanocomposite sample. Corroborating all the data it can be suggested that the synthesized nanocomposites with Salecan and clay could be good candidates as vehicles for chemotherapeutic agents.     

The role of Doppler ultrasound in rheumatic diseases

The use of Doppler techniques, including power, colour and spectral Doppler, has greatly increased in rheumatology in recent years. This is due to the ability of Doppler US (DUS) to detect pathological vascularization within joints and periarticular soft tissues, thereby demonstrating the presence of active inflammation, which has been reported to be correlated with the local neo-angiogenesis. In synovitis, DUS showed a high correlation with histological and MRI findings, thus it is considered a valid tool to detect pathological synovial vascularization. Moreover, it is more sensitive than clinical examination in detecting active joint inflammation and in the evaluation of response to treatment. In addition, DUS may be considered as a reference imaging modality in the assessment of enthesitis, MRI being not sensitive and histology not feasible. Moreover, it has been demonstrated to be able to detect changes in asymptomatic enthesis. In conclusion, DUS is a useful and sensitive tool in the evaluation and monitoring of active inflammation. Its widespread use in clinical rheumatological practice is recommended. The aim of this article is to review the current literature about the role of DUS in rheumatic diseases, analysing its validity, reliability and feasibility.     

Limited in-depth invasion of Fusobacterium nucleatum into in vitro reconstructed human gingiva

ObjectiveFusobacterium nucleatum is an opportunistic pathogen with a key role in subgingival plaque formation and it is found in increased numbers in periodontally affected sites. This study aimed to investigate the potential of F. nucleatum to penetrate and induce alterations in an in vitro reconstructed human gingival mucosa model.MethodsThree-dimensional (3D) organotypic models of human gingiva were engineered using primary gingival keratinocytes and fibroblasts. The reconstructed tissues were challenged with four different strains of fluorescently labelled F. nucleatum in suspension placed on top of epithelial layers. Confocal laser scanning was used to assess the presence of fusobacteria through the organotypic model. Apoptosis (cleaved caspase-3) and cell proliferation (Ki-67) were evaluated by the use of immunohistochemistry in 3D-tissue models. Quantitative real-time PCR was performed to investigate the mRNA expression for MMP-13 and E-cadherin in both 3D-tissues and monolayers.ResultsF. nucleatum invaded the superficial epithelial layers of gingival 3D-tissue models. Challenged tissues showed accentuated shedding of superficial layers and increased number of cleaved caspase-3 and Ki-67 positive cells than controls, although not statistically significant. Levels of E-cadherin and MMP-13 mRNA were not significantly perturbed in multilayer culture. A variable and disproportionate response of MMP-13 mRNA level resulted in challenged primary keratinocytes in monolayers, compared to multilayer culture.ConclusionThese results indicate that F. nucleatum is able to invade superficially a differentiated, stratified gingival epithelium in vitro and triggers the efficient elimination of bacterial infection through epithelial shredding without causing a permanent damage of the tissue.     

Mapping air pollutants at municipality level in Italy and Spain in support to health impact evaluations

A growing health concern, due to poor air quality, recently led to an increased number of studies regarding air pollution effects on public health. Consequently, close attention is paid to estimation methods of exposure to atmospheric pollutants. This paper aims to meet a specific requirement of epidemiological researchers, that is providing annual air pollution maps at municipality scale for health impact assessment purposes on national basis. Firstly, data fusion through kriging with external drift is implemented, combining pollution data from two different sources, models and measurements, in order to improve the spatial distribution of surface concentrations at grid level. Then, the assimilated data of air pollution are upscaled, so as to obtain concentrations at municipality level. This methodology was applied to Italy and Spain (in Spain, only the second step was carried out since the modeled concentration already included an assimilation procedure). In both countries, for each municipality, an estimate of the concentration value for atmospheric pollutants of major concern for human health (PM₁₀ and NO₂) was provided, offering more relevant information from a surveillance point of view.     

Cultural animation in health research: An innovative methodology for patient and public involvement and engagement

Background

A significant challenge in Patient and Public Involvement and Engagement (PPIE) in health research is to include a wide range of opinions and experiences, including from those who repeatedly find themselves at the margins of society.

Objective

To contribute to the debate around PPIE by introducing a bottom‐up methodology: cultural animation (CA). Cultural Animation is an arts‐based methodology of knowledge co‐production and community engagement which employs a variety of creative and participatory exercises to help build trusting relationships between diverse participants (expert and non‐experts) and democratize the process of research.

Design

Three CA full‐day workshops for the research project “A Picture of Health.”

Participants

Each workshop was attended by 20‐25 participants including 4 academics, 5 retired health professionals who volunteered in the local community and 15 community members. Participants ranged in age from 25 to 75 years, and 80% of the participants were women over the age of 60.

Results

The CA workshops unearthed a diversity of hidden assets, increased human connectivity, led to rethinking of and co‐creating new health indicators and enabled participants to think of community health in a positive way and to consider what can be developed.

Discussion

Cultural animation encourages participants to imagine and create ideal pictures of health by experimenting with new ways of working together.

Conclusion

We conclude by highlighting the main advantages to PPIE as follows: CA provides a route to co‐produce research agendas, empowers the public to engage actively with health professionals and make a positive contribution to their community.     

Synthesis of isotope‐labeled HSP90 inhibitor: [13CD3] and [14C]‐TAK‐459

[¹³CD₃]‐TAK‐459 (1A), an HSP90 inhibitor, was synthesized from [¹³CD₃]‐sodium methoxide in three steps in an overall yield of 29%. The key intermediate [¹³CD₃]‐2‐methoxy‐6‐(4,4,5,5‐tetramethyl‐1,3,2‐dioxaborolan‐2‐yl)pyridine was synthesized in two steps from 2,6‐dibromopyridine and stable isotope‐labeled sodium methoxide. [¹⁴C]‐TAK‐459 (1B) was synthesized from [¹⁴C(U)]‐guanidine hydrochloride in five steps in an overall radiochemical yield of 5.4%. The key intermediate, [¹⁴C]‐(R)‐2‐amino‐7‐(2‐bromo‐4‐fluorophenyl)‐4‐methyl‐7,8‐dihydropyrido[4,3‐d]pyrimidin‐5(6H)‐one, was prepared by microwave‐assisted condensation.     

Molecular Interactions between Saliva and Dental Composites Resins: A Way Forward

Dentin and enamel loss related to trauma or especially caries is one of the most common pathological issues in dentistry that requires restoration of the teeth by using materials with appropriate properties. The composite resins represent dental materials with significant importance in today’s dentistry, presenting important qualities, including their mechanical behavior and excellent aesthetics. This paper focuses on the saliva interactions with these materials and on their biocompatibility, which is continuously improved in the new generations of resin-based composites. Starting from the elements involved on the molecular landscape of the dental caries process, the paper presents certain strategies for obtaining more advanced new dental composite resins, as follows: suppression of oral biofilm acids formation, promotion of remineralization process, counteraction of the proteolytic attack, and avoidance of cytotoxic effects; the relation between dental composite resins and salivary oxidative stress biomarkers is also presented in this context.