Nanomedicines for Increased Specificity and Therapeutic Efficacy of Rheumatoid Arthritis

Rheumatoid arthritis (RA), the most frequent chronic inflammatory autoimmune disease, can lead to pain, bone and articular destruction, and limb deformity and impairment, with great impact on the activities of daily life. Several drug modifiers of the inflammatory process have been used in the treatment of the disease, all with specific patient targets and indications. However, the side effects are a frequent cause of undertreatment and non-adherence. To promote better compliance with the therapy, drug researchers have been trying to develop a new carrier of the immunomodulated molecules to increase their concentration in the target cell (mostly synovial), avoiding side effects for organs that are not targeted, as well as providing an easier manner of administration. The research results from animal models are promising and the clinical applications will show if these results are similarly impressive. This paper aims to explain the major applications of nanomedicine in RA treatment and diagnosis. The use of nanocarriers able to act as a diagnostic imaging agent and targeted drug delivery system, simultaneously, also known as nanotheranostics, can allow an improved efficacy and safety pharmacological profile, earlier detection, and thither monitoring of the disease.1 Commercial successes of RA active targeting of nanomedicine and products under development will be revised

Characterization of insulin-loaded alginate nanoparticles produced by ionotropic pre-gelation through DSC and FTIR studies

Insulin-loaded nanoparticles were prepared by ionotropic pre-gelation of alginate with calcium chloride followed by complexation between alginate and chitosan. The influence of the pH and stoichiometry relationship between polyelectrolytes providing individual particles with a nano-scale size was assessed by photon correlation spectroscopy (PCS) and scanning electron microscopy (SEM). Insulin-polyelectrolyte interactions at varying pH and polyelectrolytes stoichiometry were assessed by differential scanning calorimetry (DSC) and Fourier-transform infrared (FTIR) studies. Individual and smaller sizing nanoparticles, around 800 nm, were obtained at pH 4.7 with an alginate:chitosan mass ratio of 6:1. Thermograms of insulin-loaded nanoparticles originated shifts on same unloaded nanoparticle peaks and suggested polyelectrolytes-protein interactions at pH around 4.5-5.0. FTIR spectra of insulin-loaded nanoparticles showed amide absorption bands characteristic of protein spectra and revealed the formation of new chemical entities.http://www.sciencedirect.com/science/article/B6TFD-4JKYTNH-1/1/f2878177436b8ca802aa251efe948a9

Uso religioso em salas de cinema preservadas

No presente artigo será analisado o processo da transformação de uso de edifícios históricos localizados na cidade do Rio de Janeiro. Para tanto será utilizado como estudo de caso as salas de cinema preservadas que foram adaptadas para receber novas funções. O artigo tratará dos aspectos materiais e imateriais concernentes à preservação dos edifícios, considerando as teorias contemporâneas de restauração e conservação, além de aspectos relacionados ao simbolismo, à memória e à história inerentes a este tipo de construção. Em particular será analisado o caso das salas de cinema que, após um período de abandono, foram transformadas em templos religiosos. A questão da memória e do simbolismo toma então um vulto de fundamental importância a ser considerada no momento de se propor novas diretrizes para a transmissão destes bens ao futuro, que tão bem guardam o registro de uma época e de uma arquitetura específica voltada para o entretenimento e difusão da cultura cinematográfica. O objetivo no momento não é o de se estabelecer a postura de intervenção que mais se adeque as espaço construído considerando os aspectos materiais e arquitetônicos, mas sim o de iniciar uma análise acerca da dimensão histórica e importância da atividade religiosa como forma de preservação das edificações destinadas originalmente à exibição de filmes

A biophysical insight of Camptothecin biodistribution: towards a molecular understanding of its pharmacokinetic issues

Camptothecin (CPT) is a potent anticancer drug, and its putative oral administration is envisioned although difficult due to physiological barriers that must be overcome. A comprehensive biophysical analysis of CPT interaction with biointerface models can be used to predict some pharmacokinetic issues after oral administration of this or other drugs. To that end, different models were used to mimic the phospholipid composition of normal, cancer, and blood–brain barrier endothelial cell membranes. The logD values obtained indicate that the drug is well distributed across membranes. CPT-membrane interaction studies also confirm the drug’s location at the membrane cooperative and interfacial regions. The drug can also permeate membranes at more ordered phases by altering phospholipid packing. The similar logD values obtained in membrane models mimicking cancer or normal cells imply that CPT has limited selectivity to its target. Furthermore, CPT binds strongly to serum albumin, leaving only 8.05% of free drug available to be distributed to the tissues. The strong interaction with plasma proteins, allied to the large distribution (VDSS = 5.75 ± 0.932 L·Kg−1) and tendency to bioaccumulate in off-target tissues, were predicted to be pharmacokinetic issues of CPT, implying the need to develop drug delivery systems to improve its biodistribution.This work was supported by Fundação para a Ciência e Tecnologia (FCT) in the framework of the Strategic Funding [UID/FIS/04650/2019], and by the project CONCERT [POCI-01- 0145-FEDER-032651 and PTDC/NAN-MAT/326512017], co-financed by the European Regional Development Fund (ERDF), through COMPETE 2020, under Portugal 2020, and FCT I.P. The authors thank Elettra Sincrotone and Sigrid Bernstorff, Trieste, Italy, for beam time and support through the project 20155321. Marlene Lúcio thanks FCT and ERDF for doctoral position [CTTI-150/18-CF (1)] in the ambit of the project CONCERT. Andreia Almeida (SFRH/BD/118721/2016) and Eduarda Fernandes (SFRH/BD/147938/2019) grants are supported by FCT, POPH and FEDER/COMPETE

Coach decision-making in Futsal: from preparation to competition

The purpose of this paper was to analyse expert futsal coaches process of decision-making from preparation to competitive moments. Ten expert and professional coaches’ (M = 46,9 ± 7,93 years old andM= 15,4 ± 7,22 years of coaching experience) from different countries were interviewed using asemi-structured interview (quantitative and qualitative) with two different goals: (1) evaluate the preparation for decision-making moment during the game; (2) classifying the importance of different game related points for decision-making during match moment. The data analysis was processed through combination of deductive and inductive methods through software QSR NVivo 11. The results revealed that coaches’ share similar ideas when preparing their teams. Coaches focus first their attention on their own team identity and frame andsecond on opposition team behaviour and frame. It was also possible to identify clear coaching behavioural signs possible to be structured as cues and guiding lines for their decision-making process and actions before and during competitive moments. Such information can be important for the development of most appropriated coaching education curriculums according to game demands specificities.info:eu-repo/semantics/publishedVersio

Visualizing networks of music artists with RAMA

In this paper we present RAMA (Relational Artist MAps), a simple yet efficient interface to navigate throughnetworks of music artists. RAMA is built upon a dataset of artist similarity and user-defined tags regarding583.000 artists gathered from Last.fm. This third-party, publicly available, data about artists similarity andartists tags is used to produce a visualization of artists relations. RAMA provides two simultaneous layers ofinformation: (i) a graph built from artist similarity data, and (ii) overlaid labels containing user-defined tags.Differing from existing artist network visualization tools, the proposed prototype emphasizes commonalitiesas well as main differences between artist categorizations derived from user-defined tags, hence providingenhanced browsing experiences to users.In this paper we present RAMA (Relational Artist MAps), a simple yet efficient interface to navigate through networks of music artists. RAMA is built upon a dataset of artist similarity and user-defined tags regarding 583.000 artists gathered from Last.fm. This third-party, publicly available, data about artists similarity and artists tags is used to produce a visualization of artists relations. RAMA provides two simultaneous layers of information: (i) a graph built from artist similarity data, and (ii) overlaid labels containing user-defined tags. Differing from existing artist network visualization tools, the proposed prototype emphasizes commonalities as well as main differences between artist categorizations derived from user-defined tags, hence providing enhanced browsing experiences to users

Chitosan nanoparticles for daptomycin delivery in ocular treatment of bacterial endophthalmitis

Context: Chitosan nanoparticles were prepared to encapsulate daptomycin and proposed as a delivery system of this antibiotic to the eye for the treatment of bacterial endophthalmitis. Objective: The aim of this study was to develop daptomycin-loaded nanoparticles to apply directly to the eye, as a possible non-invasive and less painful alternative for the treatment of endophthalmitis, increasing the effectiveness of treatment and reducing toxicity associated with systemic administration.Materials and methods: Nanoparticles were obtained by ionotropic gelation between chitosan and sodium tripolyphosphate (TPP). Physicochemical and morphological characteristics of nanoparticles were evaluated, as well as determination of antimicrobial efficiency of encapsulated daptomycin and stability of the nanoparticles in the presence of lysozyme and mucin.Results: Loaded nanoparticles presented mean particle sizes around 200 nm, low polydispersity index, and positive zeta potential. Morphological examination by scanning electron microscopy (SEM) confirmed their small size and round-shaped structure. Encapsulation efficiency ranged from 80 to 97%. Total in vitro release of daptomycin was obtained within 4 h. Determination of minimum inhibitory concentrations (MICs) showed that bacteria were still susceptible to daptomycin encapsulated into the nanoparticles. Incubation with lysozyme did not significantly affect the integrity of the nanoparticles, although mucin positively affected their mucoadhesive properties. Discussion and conclusion: The obtained nanoparticles have suitable characteristics for ocular applications, arising as a promising solution for the topical administration of daptomycin to the eye.info:eu-repo/semantics/publishedVersio

Screening of the activity of quercetin-biapigenin and their poly(ε-caprolactone)-loaded nanoparticles in HepG2 cells

Hypericum perforatum extracts have been used for their antidepressive effects. A selected fraction (HP) containing quercetin and biapigenin proved to be neuroprotective. Liver is the organ primary responsible for compound metabolization and extremely susceptibility to toxic effects. This study aims to determine the hepatotoxic/protective activity of HP and HP PCL-loaded nanoparticles.info:eu-repo/semantics/publishedVersio

Quercetin-biapigenin nanoparticles are effective to penetrate the blood–brain barrier

Search for efficient therapeutic agents for central nervous system (CNS) disorders has been extensive. Nevertheless, blood-brain barrier (BBB) is an obstacle that prevents the majority of compounds to act in these diseases. It is, thus, of extreme relevance the BBB overcome, in order to deliver a drugs therapeutically active concentration to the action site, with the least losses and interaction with other organs, tissues, or cells. The present study aimed to investigate the potential protective effect of quercetin-biapigenin encapsulated into poly(Ɛ-polycaprolactone) (PCL) nanoparticles against t-BOOH-induced oxidative stress in several brain cell lines, as well as evaluate the permeability of those active molecules through an in vitro BBB model. The three cell lines under study (BV-2, hcmec/D3, and U87) presented different reactions to t-BOOH. In general, quercetin-biapigenin PCL-loaded nanoparticles were able to minimize compound toxicity they convey, regardless the cell line. Quercetin-biapigenin PCL-loaded nanoparticles (Papp of approximately 80 × 10-6 cm/s) revealed to be more permeable than free compounds (Papp of approximately 50 × 10-6 cm/s). As of our knowledge, this is the first report of quercetin-biapigenin PCL-loaded nanoparticle activity in brain cells. It is also the first determining its permeability through BBB, as an effective nanocarrier for brain delivery.info:eu-repo/semantics/publishedVersio