Magnetic field responsive drug release from magnetoliposomes in biological fluids

The magnetically triggered drug release properties of magnetoliposomes are strongly affected by the presence of serum proteins.</p

Inorganic nanoparticles as potential regulators of immune response in dendritic cells

Aim: The spontaneous adsorption of proteins on nanoparticles (NPs) in biological media is exploited to prepare complexes of NPs and proteins from cancer cells’ lysates for application in cancer immunotherapy. Materials &amp; methods: Gold (Au) and silica NPs were synthesized, incubated with cancer cells’ lysates and characterized. Dendritic cells (DCs) were challenged with protein-coated NPs, their maturation, viability and morphology were evaluated and lymphocytes T proliferation was determined. Results: Silica and Au NPs bound different pools of biomolecules from lysates, and are therefore promising selective carriers for antigens. When incubated with immature DCs, NPs were efficiently endocytosed without cytotoxicity. Finally, protein-coated AuNPs promoted DC maturation and DC-mediated lymphocyte proliferation, at variance with lysate alone and protein-coated silica NPs, that did not promote DCs maturation. Conclusion: These results demonstrate that the spontaneous formation of protein coronas on NPs represents a possible approach to fast, easy, cost-effective DCs stimulation. </jats:p

Inorganic nanoparticles interactions with dendritic cells

Stimulation of the immune system may be of help for several diseases including cancer, for which the proposed vaccination strategies include the use of nanomaterials and dendritic cells (DCs) as adjuvants. Silica and gold nanoparticles (SiO2NPs and AuNPs) are easy to produce and are endowed with high biocompatibility, tunable physicochemical properties and high adsorption power, which can lead to the formation of a protein corona. We have evaluated the interactions between human DCs and these types of NPs either alone or covered with a corona from cancer cell lysates. AuNPs and SiO2NPs were prepared [1-2] and exposed to lysates from two different cancer cell lines. Some SiO2NPs were made fluorescent with rhodamine. The NPs and the protein corona were characterized by physico-chemical methods. DCs were generated in vitro from human monocytes [3], incubated up to 48 h with NPs at different concentrations and analyzed by phase contrast, fluorescence and electron microscopy, flow cytometry and mixed lymphocyte reaction. When incubated with immature DCs, pure NPs were internalized and localized within vesicles and lysosomes. They did not cause cytotoxic nor stimulatory effects. The amount absorbed depended on NP concentration and did not increase appreciably between 4 and 24 h of incubation. Silica and gold NPs bound different pools of biomolecules from the same lysates. All lysate coated NPs promoted DC-mediated CD4+ cell proliferation. Lysate coated AuNPs also promoted DC maturation and DC-mediated CD8+ cell proliferation. The results indicate that NPs are well tolerated by DCs and can represent a simple, cost-effective and versatile method to deliver antigens to DCs in view of cancer immunotherapy

In vitro evaluation of the effect of dental bleaching prior to cementation of indirect restorations

O presente trabalho experimental, tem como objetivo avaliar \"in vitro\" possíveis falhas na cimentação de fragmentos cerâmicos sobre substrato de esmalte dentário previamente submetido ao clareamento dental e analisados pelo sistema de tomografia por coerência ótica. O ensaio experimental foi realizado in vitro, fazendo uso de trinta pré-molares superiores humanos. Cada elemento dental teve sua porção de esmalte vestibular aplainada por meio de disco de sílica na granulação 120, foram cimentados fragmentos cerâmicos retangulares de 1.5mm de espessura. Os dentes foram distribuídos aleatoriamente em 3 grupos de 10 dentes cada (n=10), Grupo 1: Fragmentos cimentados sem serem submetidos ao tratamento clareador; Grupo 2: Fragmentos cimentados 24 hrs. Após serem submetidos ao clareamento dental; Grupo 3: Fragmentos cimentados 7 dias após serem submetidos ao clareamento dental. Os espécimes foram transferidos para o sistema de tomografia por coerência óptica para seus respectivos monitoramentos após exposição ao agente clareador e cimentação da restauração indireta e ao final dos ensaios de envelhecimento artificial por termociclagem. A variável de resposta, falhas na interface esmalte e cimento resinoso, foi avaliada por escores (0,1 e 2) que representam em ordem crescente as falhas entre o substrato dental e a restauração indireta. Os valores obtidos foram analisados por meio de testes não paramétricos (Kruskal-Wallis e Wilcoxon). Os resultados constituíram de 60 escores de fendas referentes aos 3 grupos (G1;G2;G3) analisados imediatamente após a cimentação e após a termociclagem. A comparação entre os 3 grupos após termociclagem demonstrou haver diferença estatisticamente significante (p<0,0001) pela comparação dois a dois pelo teste complementar de Dunn e detectou-se que o G2 cimentado após 24 horas do clareamento apresentou mais fendas que G1 e G3. Com base nestes resultados e na metodologia utilizada pode-se concluir que, dentes submetidos ao tratamento clareador, o protocolo clinico de cimentação de restaurações cerâmicas indiretas, quando realizado 7 dias após o clareamento gerou menor quantidade de fendas na interface, propondo assim melhor qualidade na adaptação dente/restauração.The present experimental study has the objective of evaluating in vitro possible failures in the cementation of ceramic fragments over dental enamel substrate previously submitted to dental bleaching and analyzed by optical coherence tomography system. The experimental trial was performed in vitro using thirty human maxillary premolars. Each dental element had have it\'s portion of vestibular enamel planed by a silic disk in granulation 120, ceramic fragments with a diameter of 1.5mm thickness were cemented. The teeth were randomly distributed in 3 groups of 10 teeth each (n = 10), Group 1: Bonded Veneer without being subjected to bleaching treatment Group 2: Bonded Veneer 24 hours after being submitted to dental bleaching Group 3: Bonded Veneer 7 days after being submitted to dental bleaching. The specimens were transferred to the optical coherence tomography system for their respective monitoring after being exposured to the whitening agent and cementation of the indirect restoration and at the end of the artificial aging tests by thermocycling. The variable of response, at faults in the interface enamel and resin cement, was evaluated by scores (0,1 and 2) that represent in increasing order the failures between dental substrate and indirect restoration. The values obtained were analyzed by non-parametric tests (Kruskal-Wallis and Wilcoxon). The results consisted of 60 gaps scores for the three groups (G1, G2, G3) analyzed immediately after bonding and after thermocycling. The comparison between the 3 groups after thermocycling, showed a statistically significant difference (p <0.0001) by the two-to-two comparison by Dunn\'s complementary test and it was detected that G2 after 24 hours of bleaching, showed more gaps than G1 and G3. Based on these results and the methodology used, it was concluded that, when teeth were submitted to the bleaching treatment, the clinical cementation protocol of indirect ceramic restorations, when performed 7 days after bleaching, generated fewer gaps at the interface, thus proposing a better quality in the relation Tooth / restoration

Surface Modification of Ultra - Thin Zirconia Veneer For Cementation: A Scoping Review of Surface Treatment and Bond Strength

O objetivo deste estudo foi realizar uma revisão da literatura sobre a modificação de superficie interna em facetas ultra finas em zirconia para aumentar a resistência de união aos cimentos resinosos. Foi realizada uma busca eletrônica no banco de dados de literatura médica e científica on-line, usando os seguintes termos de pesquisa: zircônia ultrafina, superfície, rugosidade, resistência da união e adesão. A busca identificou 643 estudos, dos quais 79 foram considerados relevantes para este estudo. Dos 79 estudos relevantes, 17 foram selecionados para o presente estudo. A maioria dos estudos relatou o jateamento abrasivo como o principal método de modificação para superfícies à base de zircônia, embora possam ocorrer falhas do tipo rachadura devido as diferenças na pressão e no tipo de partículas abrasivas. A rugosidade das superfícies modificadas por jateamento variou de 0,25 µm a 1,3 µm. O aumento da rugosidade resultou em altos valores médios de resistência da união de superfícies de zircônia a cimentos com matriz de resina. Assim, métodos alternativos, como irradiação a laser e aplicação de camada de revestimento a base de vidro, foram descritos como métodos potenciais para modificação da superfície à base de zircônia. Os valores médios mais altos de resistência de união foram registrados em 27 MPa para superfícies modificadas por infiltração adesiva seletiva quando comparados aos valores médios em 7 MPa para superfícies com jateamento abrasivo. Assim, a combinação de métodos para modificação de superfície, infiltração seletiva adesiva após jateamento abrasivo, aumentou a resistência de união de superfícies à base de zircônia com cimentos de matriz resinosa, uma vez que os aspectos morfológicos e a rugosidade da superfície promoveram o interconexão do cimento resinoso contendo MDP

Temperature-Sensitive Auditory Neuropathy: Report of a Novel Variant of OTOF Gene and Review of Current Literature

Background and objectives: Otoferlin is a multi-C2 domain protein implicated in neurotransmitter-containing vesicle release and replenishment of the cochlear inner hair cell (IHC) synapses. Mutations in the OTOF gene have been associated with two different clinical phenotypes: a prelingual severe-to-profound sensorineural hearing loss (ANSD-DFNB9); and the peculiar temperature-sensitive auditory neuropathy (TS-ANSD), characterized by a baseline mild-to-moderate hearing threshold that worsens to severe-to-profound when the body temperature rises that returns to a baseline a few hours after the temperature has fallen again. The latter clinical phenotype has been described only with a few OTOF variants with an autosomal recessive biallelic pattern of inheritance. Case report: A 7-year-old boy presented a picture compatible with TS-ANSD exacerbated by febrile states or physical exercise with mild-to-moderate hearing loss at low and medium frequencies and a decrease in speech discrimination that worsened with an unfavorable speech-to-noise ratio. Otoacoustic emissions (OAEs) were present whereas auditory brainstem responses (ABRs) evoked by a click or tone-burst were generally absent. No inner ear malformations were described from the CT scan or MRI. Next-generation sequencing (NGS) of the known deafness genes and multi-phasic bioinformatic analyses of the data detected in OTOF a c.2521G>A missense variant and the deletion of 7.4 Kb, which was confirmed by array-comparative genomic hybridization (array-CGH). The proband’s parents, who were asymptomatic, were tested by Sanger sequencing and the father presented the c.2521G>A missense variant. Conclusions: The picture presented by the patient was compatible with OTOF-induced TS-ANSD. OTOF has been generally associated with an autosomal recessive biallelic pattern of inheritance; in this clinical report, two pathogenic variants never previously associated with TS-ANSD were described

A flexible SNP genotyping system to study allelic determinants of brain function

We developed a system for SNP-genotyping consisting of two ‘‘microchips’’, one investigating 40 SNPs in genes involved in the hepatic metabolism of antidepressant drugs, the other 100 SNPs in genes involved in brain response to antidepressants. Candidate genes were chosen by literature screening. SNPs were selected on HapMap data, using the pairwise algorithm combinedwith the ‘‘BestN’’ method; a few SNPs, reported as associated with treatment outcome, were added to the set. The main advantages of our experimental design are: a) simultaneous analysis of several genes (22) involved in distinct aspects of antidepressant response; b) a comprehensive search for common variability in candidate genes by HapMap ‘‘tag-SNPs’’. DNA samples are genotyped by ‘‘padlock probes’’, which specifically recognise the two variants of each SNP; padlock probes are amplified with universal primers, and contain unique tags for hybridisation to known positions on ad hoc designed micro-arrays, where the two alleles are distinguished by distinct fluorophores. Since reactions carried out on multiplex and signal intensities on microarrays are homogeneous, as they are not affected bySNPflanking sequences, tens of SNPsfrom tens of individuals can be analysed simultaneously on a single slide, with high accuracy and reproducibility. Considering that 100 SNPs from manygenes related to neural transmission, plasticity and neurogenesis are included in the secondmicrochip and that each of them can easily be substituted withothers if needed, our system represents a powerful tool for investigating genetic influence on normal and pathological brain function