Dimorfismo sexual em adultos brasileiros por meio de medidas cranianas / Sexual dimorphism in Brazilian adults through cranial measurements

O presente estudo buscou validar a metodologia desenvolvida por Galvão in Vanrell (2016) para determinação de dimorfismo sexual e criar um modelo de regressão logística para a estimativa do sexo. Foram estudadas onze medidas a saber: (Meato acústico externo (MAE) ao gnátio, Meato acústico externo ao próstio, Meato acústico externo à espinha nasal anterior, Meato acústico externo à glabela, Meato acústico externo ao bregma, Meato acústico externo ao vértex, Meato acústico externo ao lâmbda, Meato acústico externo ao opistocrânio, Meato acústico externo ao ínio, Meato acústico externo ao mastoideo esquerdo, Meato acústico externo ao gônio) em 200 crânios, sendo 109 masculinos e 91 femininos, com idades compreendidas entre 23 e 100 anos, com sexo, idade, ancestralidade e causa da morte conhecidas, devidamente catalogadas junto ao Biobanco Osteológico e Tomográfico Prof. Eduardo Daruge da FOP/UNICAMP. Para a análise estatística utilizou-se o programa IBM® SPSS® 25 Statistics (Nova Iorque/Estados Unidos). Foram aplicados os testes de Kolmogorov-Smirnov e Teste t para análise dos dados e regressão logística Stepwise-Forward (Wald). Por meio deste estudo foi possível concluir que dentre as 11 medidas analisadas, quatro não foram dimórficas (MAE-BREGMA, MAE-VÉRTEX, MAE-OPISTOCRÂNIO, MAE-ÍNIO) tendo em vista os testes estatísticos aplicados, o que significa que estas medidas lineares não fornecem segurança para a determinação do dimorfismo sexual, considerando a amostra estudada.

[60]Fullerene for Medicinal Purposes, A Purity Criterion towards Regulatory Considerations.

Since the early nineties countless publications have reported promising medicinal applications for [60]fullerene (C60) related to its unparalleled affinity towards free radicals. Yet, until now no officially approved C60-based drug has reached the market, notably because of the alleged dangers of C60. Nevertheless, since the publication of the effects of C60 on the lifespan of rodents, a myriad of companies started selling C60 worldwide for human consumption without any approved clinical trial. Nowadays, several independent teams have confirmed the safety of pure C60 while demonstrating that previously observed toxicity was due to impurities present in the used samples. However, a purity criterion for C60 samples is still lacking and there are no regulatory recommendations on this subject. In order to avoid a public health issue and for regulatory considerations, a quality-testing strategy is urgently needed. Here we have evaluated several analytical tools to verify the purity of commercially available C60 samples. Our data clearly show that differential scanning calorimetry is the best candidate to establish a purity criterion based on the sc-fcc transition of a C60 sample (Tonset ≥ 258 K, ∆sc-fccH ≥ 8 J g-1).

Brazilian's dental anthropometry: Human identification.

BACKGROUND: Human stature and sex determination are significant data that can and should be used in criminal profiling in the human identification processes. Teeth are widely used in investigations because of their properties of resistance and uniqueness. AIMS: The present study aimed to verify, by means of dental anthropometry, the correlation of these with the stature and sex. MATERIALS AND METHODS: Measurements of linear (mid distal and incisor cervical) dental measurements were performed on the upper right teeth of Brazilians, aged between 18 and 30 years, being 100 male and 100 female participants. Linear dental measurements were measured with a digital caliper and stature was measured with a stadiometer. For the statistical analysis, the IBM® SPSS® 25 Statistics program was used. Kolmogorov-Smirnov, Pearson correlation, and Stepwise-Forward (Wald) logistic regression analyses were applied to sex determination and stature estimation. RESULTS: The results indicated that all measures performed are dimorphic, but that lateral incisor and canine tooth measurements are statistically significant with a P ≤ 0.001. The obtained model allows for sexing with 70.5% accuracy, being able to be used in anthropological studies in Brazilians. CONCLUSION: It can be concluded that dental measurements are useful tools to identify gender and the canine measurements also showed a strong and proportional correlation with stature, but it was not possible to establish a mathematical model for this.

Biodistribution of polyacrylic acid-coated iron oxide nanoparticles is associated with proinflammatory activation and liver toxicity.

Iron oxide nanoparticles (IONs) have physical and chemical properties that render them useful for several new biomedical applications. Still, so far, in vivo safety studies of IONs with coatings of biomedical interest are still scarce. The aim of this study, therefore, was to clarify the acute biological effects of polyacrylic acid (PAA)-coated IONs, by determining their biodistribution and their potential proinflammatory and toxic effects in CD-1 mice. The biodistribution of PAA-coated IONs in several organs (liver, spleen, kidneys, brain, heart, testes and lungs), the plasma cytokines, chemokine and aminotransferases levels, white blood cell count, oxidative stress parameters, adenosine triphosphate and histologic features of liver, spleen and kidneys were evaluated 24 h after a single acute (8, 20 or 50 mg kg(-1) ) intravenous administration of PAA-coated IONs in magnetite form. The obtained results showed that these IONs accumulate mainly in the liver and spleen and, to a lesser extent, in the lungs. Although our data showed that PAA-coated IONs do not cause severe organ damage, an inflammatory process was triggered in vivo, as evidenced by as evidenced by increased neutrophils and large lymphocytes in the differential blood count. Moreover, an accumulation of iron in macrophages of the liver and spleen was observed and hepatic lipid peroxidation was elicited, showing that the IONs are able to induce oxidative stress. The effects of these nanoparticles need to be further investigated regarding the mechanisms involved and the long-term consequences of intravenous administration of PAA-coated IONs. Copyright © 2016 John Wiley & Sons, Ltd.

Iron Oxide Nanoparticles: An Insight into their Biomedical Applications

Iron oxide nanoparticles (IONs) are among the most common types of nanoparticles (NPs) used in biomedical applications. IONs can be presented in different forms [e.g. magnetite (Fe3O4), hematite (α-Fe2O3) and maghemite (γ- Fe2O3)], and are usually coated with substances and/or polymers according to the purpose for which they are intended to be used. In recent years, IONs use has been increasing exponentially in many fields of biomedicine, namely in magnetic resonance imaging, cell sorting, tissue repair, induction of hyperthermia and drug delivery, among others. This review aims to provide an update on the different IONs and the substances and/or polymers that can be used to coat the IONs core as well as their applications and biological properties, namely their biodistribution in the human body and their cellular internalization pathways.

Polyacrylic acid coated and non-coated iron oxide nanoparticles are not genotoxic to human T lymphocytes.

The use of iron oxide nanoparticles (ION) for diagnostic and therapeutic purposes requires a clear favorable risk-benefit ratio. This work was performed with the aim of studying the ability of polyacrylic acid (PAA)-coated and non-coated ION to induce genotoxicity in human T lymphocytes. For that purpose, their influence on cell cycle progression and on the induction of chromosome aberrations was evaluated. Blood samples collected from healthy human donors were exposed to PAA-coated and non-coated ION, at different concentrations, for 48h. The obtained results showed that, for all culture conditions, the tested ION are not genotoxic and do not influence the cell cycle arrest. Their possible cumulative effect with the iron-dependent genotoxic agent BLM was also evaluated. Blood samples collected from healthy human donors were exposed to ION, at different concentrations, for 48h, in the presence of a pre-determined toxic concentration of BLM. The obtained results showed that, for all culture conditions, the tested ION do not potentiate the clastogenic effects of BLM.

Polyacrylic acid-coated and non-coated iron oxide nanoparticles induce cytokine activation in human blood cells through TAK1, p38 MAPK and JNK pro-inflammatory pathways.

Iron oxide nanoparticles (ION) can have a wide scope of applications in biomedicine, namely in magnetic resonance imaging, tissue repair, drug delivery, hyperthermia, transfection, tissue soldering, and as antimicrobial agents. The safety of these nanoparticles, however, is not completely established, namely concerning their effect on immune system and inflammatory pathways. The aim of this study was to evaluate the in vitro effect of polyacrylic acid (PAA)-coated ION and non-coated ION on the production of six cytokines [interleukin 1 beta (IL-1ß), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 8 (IL-8), interferon gamma (IFN-γ) and interleukin 10 (IL-10)] by human peripheral blood cells, and to determine the inflammatory pathways involved in this production. The obtained results showed that PAA-coated and non-coated ION were able to induce all the tested cytokines and that activation of transforming growth factor beta (TGF-ß)-activated kinase (TAK1), p38 mitogen-activated protein kinases (p38 MAPK) and c-Jun N-terminal kinases (JNK) were involved in this effect.

Interaction of polyacrylic acid coated and non-coated iron oxide nanoparticles with human neutrophils.

Iron oxide nanoparticles (ION), with different coatings and sizes, have attracted extensive interest in the last years to be applied in drug delivery, cancer therapy and as contrast agents in imagiologic techniques such as magnetic resonance imaging. However, the safety of these nanoparticles is still not completely established, particularly to host defense systems that are usually recruited for their clearance from the body. In this paper, given the importance of neutrophils in the immune response of the organism to nanoparticles, the effect of polyacrylic acid (PAA)-coated and non-coated ION on human neutrophils was evaluated in vitro, namely their capacity to activate the oxidative burst and to modify their lifespan. The obtained results showed that the studied PAA-coated and non-coated ION triggered neutrophils' oxidative burst in a NADPH oxidase dependent manner, and that PAA-coated ION increased - while non-coated ION prevented - apoptotic signaling and apoptosis. These effects may have important clinical implications in biomedical applications of ION.

Acetaminophen prevents oxidative burst and delays apoptosis in human neutrophils.

Acetaminophen is a frequently prescribed over-the-counter drug to reduce fever and pain in the event of inflammatory process. As neutrophils are relevant cells in inflammatory processes, the putative interaction of acetaminophen with these cells, if present, would be of paramount importance. The present study was undertaken to evaluate the effect of acetaminophen in human neutrophils' oxidative burst and lifespan in vitro. The obtained results demonstrate that acetaminophen efficiently modulates neutrophils' oxidative burst in phorbol myristate acetate-activated neutrophils, in a concentration-dependent manner, at in vivo relevant concentrations. It was clearly demonstrated that acetaminophen is a strong scavenger of HOCl and H2O2, which probably contributed to the effect observed in neutrophils. Acetaminophen also induced the depletion of glutathione in stimulated neutrophils, suggesting its transformation into a reactive intermediate. Obtained results further revealed that acetaminophen affects programmed cell death of human neutrophils, resulting in a delay of previously stimulated neutrophils-mediated apoptosis. Overall, our data suggested that acetaminophen has considerable potential to be included in anti-inflammatory therapeutic strategies, by preventing biological damage induced by an excessive production of reactive species generated in activated neutrophils and by extending the lifespan of neutrophils, favoring the elimination of pathogens, thus contributing to tissue healing and resolution of inflammation.

Trihydroxyflavones with antioxidant and anti-inflammatory efficacy.

The classical anti-inflammatory therapies are frequently ineffective and present numerous and severe side effects, especially in long term use, which requires the development of anti-inflammatory drugs with different scaffolds and mechanisms of action. Owing to the high antioxidant potential and anti-inflammatory activities already inferred for hydroxyflavones, we found it would be relevant to evaluate the anti-inflammatory potential of a series of trihydroxyflavones by testing their ability to scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS) in cells and cell-free systems and to inhibit the proinflammatory pathways mediated by the enzymes cyclooxygenase (COX) and 5-lipoxygenase (5-LOX), in which reactive species have a proven involvement. The tested trihydroxyflavones proved to be effective inhibitors of neutrophils' oxidative burst and were shown to scavenge different ROS and RNS in cell-free systems. The most active compound in the majority of the assays was 3,3',4'-trihydroxyflavone, which was somehow expected due to the presence of the ortho-dihydroxy in the B-ring, an important structural feature in terms of free radical scavenging activity. Additionally, the studied compounds were able to inhibit the production of leukotriene B(4) by 5-LOX in activated neutrophils. 3,5,7-Trihydroxyflavone was able to inhibit both COX-1 and COX-2, which makes it a dual inhibitor of COX and 5-LOX pathways and, therefore, a promising candidate for a new therapeutic option in the treatment of inflammatory processes.

Antioxidant activity of unexplored indole derivatives: synthesis and screening.

The present study envisaged the development of novel antioxidant candidates using the indole scaffold. Several tryptophan and tryptamine derivatives were synthesized, in particular prenylated indole compounds, and their scavenging activity for reactive oxygen species (ROS) and reactive nitrogen species (RNS) was investigated. The library substitution pattern included several alkyl chains at positions N-1, C-2 of the indole nucleus, including prenyl and isopentyl chain, as well as different groups at the side chain (C-3) that allowed the investigation of a possible radical stabilization. The results obtained showed that tryptophan (8), tryptamine (9), N-phthaloyl tryptamine (5) and N-prenyl tryptophan (13) were the most active against peroxyl radical (ROO(•)) with activities higher than Trolox, which was used as control. The scavenging of hypochlorous acid (HOCl) was also evaluated and tryptophan (8) and tryptamine (9) showed IC(50) of 3.50 ± 0.4 and 6.00 ± 0.60 µM, respectively. Significant activity was also found for the N-prenyl tryptophan (13) with an IC(50) of 4.13 ± 0.17 µM and C-2 prenylated derivative (14), with 4.56 ± 0.48 µM. The studies were extended to RNS and best results were obtained against peroxynitrite anion (ONOO(-)) in the presence of NaHCO(3). N-alkylated tryptophan (18) showed a high activity with an IC(50) of 14.0 ± 6.8 µM. The results show that the tested compounds are effective scavengers of ROS and RNS, and suggest that the radical stabilization is strongly dependent on the type of substituents on the indolic moiety and on their relative positions. In addition, the radical dissipation inside the indolic system is mandatory for the observed antioxidant activity.

Scavenging of reactive oxygen and nitrogen species by the prodrug sulfasalazine and its metabolites 5-aminosalicylic acid and sulfapyridine.

Sulfasalazine is a prodrug composed by a molecule of 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP), linked by an azo bond, which has been shown to be effective in the therapy of inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease, as well as of rheumatic diseases, such as rheumatoid arthritis and ankylosing spondylitis. The precise mechanism of action of sulfasalazine and/or its metabolites has not been completely elucidated, though its antioxidant effects are well established and are probably due to its scavenging effects against reactive oxygen and nitrogen species (ROS and RNS), as well as metal chelating properties, in association to its inhibitory effects over neutrophil oxidative burst. The present work was focused on screening and comparing the potential scavenging activity for an array of ROS (O(2)(•-), H(2)O(2), (1)O(2), ROO(•) and HOCl) and RNS ((•)NO and ONOO(-)), mediated by sulfasalazine and its metabolites 5-ASA and SP, using validated in vitro screening systems. The results showed that both 5-ASA and sulfasalazine were able to scavenge all the tested ROS while SP was practically ineffective in all the assays. For HOCl, (1)O(2), and ROO(•), 5-ASA showed the best scavenging effects. A new and important finding of the present study was the strong scavenging effect of 5-ASA against (1)O(2). 5-ASA was shown to be a strong scavenger of (•)NO and ONOO(-). Sulfasalazine was also able to scavenge these RNS, although with a much lower potency than 5-ASA. SP was unable to scavenge (•)NO in the tested concentrations but was shown to scavenge ONOO(-), with a higher strength when the assay was performed in the presence of 25 mM bicarbonate, suggesting further scavenging of oxidizing carbonate radical. In conclusion, the ROS- and RNS-scavenging effects of sulfasalazine and its metabolites shown in this study may contribute to the anti-inflammatory effects mediated by sulfasalazine through the prevention of the oxidative/nitrative/nitrosative damages caused by these species.

Synthesis and antioxidant properties of new chromone derivatives.

Nowadays, the recognition of the benefits of antioxidants is eliciting an increasingly interest in the search for new molecules with improved activity. The aim of the present work was to search for improved reactive oxygen species (ROS) and reactive nitrogen species (RNS) scavengers by testing new structures of 2-styrylchromones (2-SC) and 3-substituted flavones, which were synthesised by the Baker-Venkataraman approach. The new compounds were also tested for their metal chelating capacity and reducing activity. The obtained results showed that the methylation of hydroxyl groups decreases the scavenging of ROS and RNS by 2-SC. The decrease in the scavenging activities was, generally, more evident when the methylation occurred in B-ring, except for O2*- and (1)O(2). On the other hand, the introduction of a substituent, either hydroxyl or methoxyl, in position 8 was sometimes favourable and others unfavourable to the scavenging activities, depending on the reactive species. In conclusion, the study of the antioxidant properties of the new 2-SC and flavones allowed establishing new structure-activity relationships and brought out, in some cases, pharmacophores with improved activity.