Radiofrequency driving antitumor effect of graphene oxide-based nanocomposites: a Hill model analysis.

Aim: This report proposes using the Hill model to assess the benchmark dose, the 50% lethal dose, the cooperativity and the dissociation constant while analyzing cell viability data using nanomaterials to evaluate the antitumor potential while combined with radiofrequency therapy. Materials & methods: A nanocomposite was synthesized (graphene oxide-polyethyleneimine-gold) and the viability was evaluated using two tumor cell lines, namely LLC-WRC-256 and B16-F10. Results: Our findings demonstrated that while the nanocomposite is biocompatible against the LLC-WRC-256 and B16-F10 cancer cell lines in the absence of radiofrequency, the application of radiofrequency enhances the cell toxicity by orders of magnitude. Conclusion: This result points to prospective studies with the tested cell lines using tumor animal models.

S100 proteins and their implication in the thalamus: an integrative review / Las proteínas S100 y su implicación en el tálamo: una revisión integradora

SUMMARY: S100 proteins belong group of calcium-binding proteins and are present in physiological intracellular and extracellular regulatory activities, such as cell differentiation, and act in inflammatory and neoplastic pathological processes. Recently, its expressions in the nervous system have been extensively studied, seeking to elucidate its action at the level of the thalamus: A structure of the central nervous system that is part of important circuits, such as somatosensory, behavioral, memory and cognitive, as well as being responsible for the transmission and regulation of information to the cerebral cortex. This article is an integrative review of scientific literature, which analyzed 12 studies present in Pubmed. The analysis showed that the relationship of S100 proteins and the thalamus has been described in neoplastic processes, mental disorders, hypoxia, trauma, stress, infection, Parkinson's disease and epilepsy. In summary, it is possible to conclude that this protein family is relevant as a marker in processes of thalamic injury, requiring further studies to better understand its clinical, preclinical meanings and its prognostic value.

Las proteínas S100 pertenecen al grupo de proteínas fijadoras de calcio y están presentes en actividades reguladoras fisiológicas intracelulares y extracelulares, como la diferenciación celular, y actúan en procesos patológicos inflamatorios y neoplásicos. Recientemente, sus expresiones en el sistema nervioso han sido ampliamente estudiadas, buscando dilucidar su acción a nivel del tálamo: una estructura del sistema nervioso central que forma parte de importantes circuitos, como el somatosensorial, conductual, de memoria y cognitivo, así como además de ser responsable de la transmisión y regulación de la información a la corteza cerebral. Este artículo es una revisión integradora de la literatura científica, que analizó 12 estudios presentes en Pubmed. El análisis mostró que la relación de las proteínas S100 y el tálamo ha sido descrita en procesos neoplásicos, trastornos mentales, hipoxia, trauma, estrés, infección, enfermedad de Parkinson y epilepsia. En resumen, es posible concluir que esta familia de proteínas es relevante como marcador en procesos de lesión talámica, requiriendo más estudios para comprender mejor su significado clínico, preclínico y su valor pronóstico.

Psychosocial and Drug Use Assessment of Regular vs. Non-Regular Ayahuasca Users in a Brazilian Sample: a Web-Based Survey.

Background: Preliminary evidence suggests that long-term ayahuasca use is associated with better psychosocial outcomes and less drug use; however, available data on the association between ayahuasca intake frequency and psychosocial outcomes is limited. Objectives: We sought to characterize and investigate the association of regular ayahuasca use, as compared to non-regular use, on licit (alcohol and tobacco) and illicit (cannabis, psychostimulants, psychedelics, and non-medical opioids) drug use and psychosocial outcomes. Methods: An online-based cross-sectional survey was taken among people who use ayahuasca in Brazil assessing sociodemographic, drug and ayahuasca use, anxiety and depression (HAD-S), intrinsic religiosity (IRI), negative and positive affects (PANAS), satisfaction with life (SWLS), and five quality of life domains (WHOQOL-Brief). Multivariate regressions for each psychosocial outcome and drug use were performed comparing regular to non-regular ayahuasca users while correcting for sociodemographic variables. Results: A total of 286 valid answers were retrieved, divided into people with regular (n = 101) and non-regular (n = 185) ayahuasca use. Groups had similar sociodemographic profiles and lifetime use of drugs. In the multivariate analysis, regular use of ayahuasca was associated with lower anxiety (B: -0.97), negative affect (B: -2.62), general (B: 0.22) and physical (B: 0.17) quality of life, higher intrinsic religiosity scores (B: 4.16), and less past-month licit (OR = 0.30) and illicit (OR = 0.49) use of substances. Conclusions: Our results show that ceremonial regular ayahuasca compared to non-regular use is associated with better psychosocial and mental health outcomes and less drug use. Studies with repeated ayahuasca administration and extended follow-ups are essential to clarify the nature of ayahuasca's therapeutic effects and to guide future clinical research.

Effects of repeated ayahuasca administration on behaviour and c-Fos expression in male rats exposed to the open field.

Considering the long-lasting effects of ayahuasca on the brain and emotional processing, the objective of this study was to evaluate the behavioural and neurobiological effects of repeated ayahuasca administration in an animal model of exploratory behaviour related to novel-environment anxiety. Male Wistar rats received water, 120, 240, 480 or 3600 mg/kg of resuspended freeze-dried ayahuasca by gavage once a day for 30 days; there was also a non-manipulated homecage group. One hour after the last administration, animals were placed individually in the open field for 20 min. We analysed the weight gain, the behavioural response through a stochastic analysis, and c-Fos immunoreactive levels in the hippocampus, amygdala, pre-frontal and barrel field cortex. Ayahuasca at 120 mg/kg increased ambulation, and at 3600 mg/kg decreased vertical exploration and reduced weight gain. Aya3600 had higher c-Fos expression in regions of the hippocampus and infralimbic cortex than homecage, water or aya120 groups. Water-receiving animals had less c-Fos expression in the anterior basolateral amygdala than others groups. Our results show different behavioural effects of ayahuasca: a stimulant-like effect in small doses, and decreased activity in extreme high-dose, probably due to adverse effects. Higher activation of areas involved in emotional processing and the serotonergic pathway adds to the neurobiological literature on repeated/chronic ingestion of ayahuasca. Our data do not support an anxiolytic effect of repeated ayahuasca related to exploring new anxiogenic-environment but suggest that low ayahuasca doses should be further studied. The absence of severe impairment and behavioural syntax alteration reinforce ayahuasca safety.

Artificial tanning devices (Sunbeds): where do we stand?

Exposure to ultraviolet radiation emitted by indoor tanning devices (sunbeds) has well-documented negative effects on human health, but no clear benefit beyond cosmetic outcomes. Sunbed use is responsible for a significant proportion of both melanoma and non-melanoma skin cancers, especially in patients exposed to this practice in early life, premature skin ageing, immunosuppression, skin burns, and eye damage. Artificial tanning is now seen as a public health issue. In this review we discuss the potential additive effect of indoor tanning, misleading facts regarding sunbed benefit, safety concerns and negative effects on human health, indoor tanning legislation and current position of several international organisations, and the impact of some policies adopted in order to mitigate the effects of this dangerous practice.

Combination of selol nanocapsules and magnetic hyperthermia hinders breast tumor growth in aged mice after a short-time treatment.

Short time treatment with reduced dosages of selol-loaded PLGA nanocapsules (NcSel) combined with magnetic hyperthermia (MHT) is evaluated in aged Erhlich tumor-bearing mice. Clinical, hematological, biochemical, genotoxic and histopathological parameters are assessed during 7 d treatment with NcSel and MHT, separately or combined. The time evolution of the tumor volume is successfully modeled using the logistic mathematical model. The combined therapy comprising NcSel and MHT is able to hinder primary tumor growth and a case of complete tumor remission is recorded. Moreover, no metastasis was diagnosed and the adverse effects are negligible. NcSel plus MHT may represent an effective and safe alternative to cancer control in aged patients. Future clinical trials are encouraged.

Tumor vascular heterogeneity and the impact of subtumoral nanoemulsion biodistribution.

Aim: Investigate the heterogeneous tumor tissue organization and examine how this condition can interfere with the passive delivery of a lipid nanoemulsion in two breast cancer preclinical models (4T1 and Ehrlich). Materials & methods: The authors used in vivo image techniques to follow the nanoemulsion biodistribution and microtomography, as well as traditional histopathology and electron microscopy to evaluate the tumor structural characteristics. Results & conclusion: Lipid nanoemulsion was delivered to the tumor, vascular organization depends upon the subtumoral localization and this heterogeneous organization promotes a nanoemulsion biodistribution to the highly vascular peripherical region. Also, the results are presented with a comprehensive mathematical model, describing the differential biodistribution in two different breast cancer models, the 4T1 and Ehrlich models.

Physical exercise and flaxseed oil supplementation influence the glial plasticity in the rat hippocampus.

Brain benefits from physical exercise associated with antioxidant supplements such as flaxseed oil. This low cost and simple association may improve hippocampal plasticity, which may work as a preventive and effective therapy in neuroprotection and neuroplasticity processes. This work evaluated the effects of physical exercise with flaxseed oil supplementation (Linum usitatissimum L.) in the hippocampus of Wistar rats. We separated male Wistar rats into four experimental groups: control group (sedentary), a sedentary group with a supplemental diet of flaxseed oil, a group under exercise program with flaxseed oil supplementation, and a group exclusively under exercise program. The swimming exercise consisted of a progressive 28­day protocol followed by behavioral assessment, brain perfusion, microtomy, immunohistochemistry for glial fibrillary acidic protein (GFAP), cellular morphology, and optical density analysis. We used the ANOVA test with Tukey's post­test for behavioral analysis. The exercise program with flaxseed oil supplementation was able to alter the GFAP expression in astrocytes in the CA1, CA3 and dentate gyrus regions of the hippocampus and modulate the behavioral aspects of memory and anxiety.

Single-Atom Gadolinium Anchored on Graphene Quantum Dots as a Magnetic Resonance Signal Amplifier.

A single-atom metal doped on carbonaceous nanomaterials has attracted increasing attention due to its potential applications as high-performance catalysts. However, few studies focus on the applications of such nanomaterials as nanotheranostics for simultaneous bioimaging and cancer therapy. Herein, it is pioneeringly demonstrated that the single-atom Gd anchored onto graphene quantum dots (SAGd-GQDs), with dendrite-like morphology, was successfully prepared. More importantly, the as-fabricated SAGd-GQDs exhibits a robustly enhanced longitudinal relaxivity (r1 = 86.08 mM-1 s-1) at a low Gd3+ concentration of 2 µmol kg-1, which is 25 times higher than the commercial Gd-DTPA (r1 = 3.44 mM-1 s-1). In vitro and in vivo studies suggest that the obtained SAGd-GQDs is a highly potent and contrast agent to obtain high-definition MRI, thereby opening up more opportunities for future precise clinical theranostics.

Magnetic studies of polylactic-co-glicolic acid nanocapsules loaded with selol and γ-Fe2O3 nanoparticles.

The as-prepared (MSE-NCs sample) and lyophilized (LMSE-NCs sample) polylactic-co-glicolic acid (PLGA) nanocapsules loaded with maghemite (γ-Fe2O3) nanoparticles and selol (Se-based anticancer drug) were investigated by means of dc magnetization, ac susceptibility and electron spin resonance (ESR) measurements over the temperature range of 4-300 K. The magnetic data of the as-synthesized nanocapsules containing only maghemite nanoparticles (M-NCs sample) or selol (SE-NCs sample) were also collected for comparison. The magnetic nanocapsules reveal perfect superparamagnetic (SPM) behavior only around room temperature; at temperatures lower than 200 K the SPM scaling is not observed and all samples behave as interacting superparamagnetic (ISPM) materials. The evolution from the ISPM to the SPM regime is marked by a steady decrease in the hysteretic properties of all samples, with the temperature dependence of the coercivity decreasing slower than the T1/2 behavior predicted for non-interacting SPM particles. The SPM character of the samples is also confirmed by the occurrence of a maximum in the temperature dependence of both real χ'(T) and imaginary χ''(T) components of the ac magnetic susceptibility, which shifts towards higher temperatures with increasing frequency. Moreover, upon decreasing the temperature the ESR signal shifts to lower fields and gradually broadens, following closely the predictions for the ESR of SPM particles. Additionally, an unusual giant diamagnetic response is observed at low temperatures. The ZFC magnetization is found to reverse its direction and becomes diamagnetic, whereas the FC branch remains positive. Even when compared with usual superconductors, the order of the diamagnetic susceptibility for the lyophilized sample (-10-2 emu g-1 Oe-1) is quite considerable. The nanocapsules herein reported and the presented analysis of their magnetic properties we envisage can support the engineering of magnetic nanocapsules for applications in magnetic drug delivery systems and as magnetic hyperthermia inductors in antitumor therapy.

Fluorine-containing graphene quantum dots with a high singlet oxygen generation applied for photodynamic therapy.

Recently, graphene quantum dots (GQDs) have been extensively studied in biomedical areas such as bio-imaging, bio-sensing and photothermal therapy due to their superior optical and physiochemical properties compared to traditional organic biomarkers. Application of GQDs in photodynamic therapy (PDT) has been explored since 2014, but currently the main challenges are inadequate singlet oxygen (1O2) quantum yield (QY), poor solubility and biocompatibility. Herein, we report on the synthesis of a new class of fluorine-containing GQDs (F-GQDs) by an oxidative cutting method using fluorinated graphite as the raw material. The as-synthesized F-GQD sample demonstrates an average particle size of 2.1 nm with a fluorine doping content of 1.43%. The F-GQDs have a better water solubility and biocompatibility than the GQDs, and emit strong green fluorescence at 365 nm excitation with a relative fluorescence QY of 13.72%. Moreover, the fluorescence imaging effect as well as photodynamic activity was successfully tested in both an in vitro HepG2 cell line model and a 3D multicellular spheroid model, the latter of which mimics the tumour microenvironment. Further studies using UV-visible spectroscopy to monitor the degradation of water-soluble 9,10-anthracenediyl-bis(methylene)dimalonic acid (ABDA) demonstrate that the F-GQD sample generates 1O2 efficiently (QY = 0.49) under visible light irradiation. Compared to non-fluorinated GQDs, the as-reported F-GQDs appear to be a more promising photosensitizer for image-guided PDT.

Community-based approaches for malaria case management in remote communities in the Brazilian Amazon

Abstract INTRODUCTION Malaria case management is a pivotal intervention in malaria elimination. However, many remote areas in Brazil still lack access to basic health services. This study describes a community-based approach (CBA) for malaria case management in the large remote area of the Jaú National Park (JNP), Amazonas, Brazil. METHODS In 2001, a general health CBA was initiated with a motor group (MG); a participative community health diagnosis (PCHD) was subsequently implemented between 2001 and 2005. In 2006, a CBA for malaria case management started with an expanded MG including all sectors with a stake in malaria control, from the local residents to the federal government. In 2008, community microscopists were selected and trained to diagnose hemoparasites. A full malaria strategy was implemented in 2009 with subsequent quality control follow-up. RESULTS Two educational materials were co-created with local communities. The MG identified malaria as a major health problem and the malaria MG planned the control activities. Ten communities selected a resident to become malaria microscopists, and ten solar-operated health centers were built. The number of slide readings increased from 923 in 2006 to 1,900 in 2009, while malaria infections decreased from 354 cases in 2005 to 20 cases in 2015. The excess time (≥ 48 hours) between first symptoms and diagnosis/treatment decreased from 68.9% of cases in 2005 to 14.3% in 2010. CONCLUSIONS While many factors were likely involved in the reduction of malaria transmission in the JNP, the CBA played an important role in the sustained success of the initiative.

Fluorine and Nitrogen Co-Doped Carbon Dot Complexation with Fe(III) as a T1 Contrast Agent for Magnetic Resonance Imaging.

Commercial gadolinium-based materials have been widely used as contrast agents for magnetic resonance imaging (MRI), but the high toxicity of leaking free Gd3+ ions still raises biosafety concerns. Here, we develop a novel, safe, and efficient MRI contrast agent based on a stable Fe(III) complex of fluorine and nitrogen co-doped carbon dots (F,N-CDs) that was prepared from glucose and levofloxacin by a simple microwave-assisted thermal decomposition method. The obtained Fe3+@F,N-CD complex exhibits higher longitudinal relaxivity ( r1 = 5.79 mM-1·s-1) than that of the control samples of the Fe3+@CD complex ( r1 = 4.23 mM-1 s-1) and free Fe3+ ( r1 = 1.59 mM-1 s-1) in aqueous solution, as assessed by a 1.5 T NMR analyzer. More importantly, the Fe3+@F,N-CD complex is very stable with a large coordination constant of 1.06 × 107 in aqueous medium. While incubated with HeLa cells, the Fe3+@F,N-CD complex shows clear MR images, demonstrating that it has potential to be an excellent MRI contrast agent. Furthermore, in vivo MRI experiments indicate that the Fe3+@F,N-CD complex provides high-resolution MRI pictures of 4T1 tumor bearing BALB/c mice 15 min after injection and can be completely excreted 2 h after administration. No cytotoxicity was observed with F,N-CDs and Fe concentration up to 0.2 mg/mL and 0.3 mM in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell proliferation assay, respectively. The possible mechanism of the enhanced MRI effect of the Fe3+@F,N-CD complex is therefore proposed. The extremely low toxicity, high r1 relaxivity, strong photoluminescence, and low synthetic cost enable the Fe3+@F,N-CD complex to be a safe and promising T1-weighted MRI contrast agent for clinical applications.

Estratégias de enfrentamento do craving em dependentes de crack em tratamento em Comunidades Terapêuticas* / Estrategias de afrontamiento en craving de dependiente de crack em tratamiento en Comunidades Terapéuticas / Coping strategies of craving in crack-cocaine dependents in treatment in Therapeutic Communities

OBJETIVOS: identificar e descrever as estratégias de enfrentamento utilizadas perante o craving por usuários de crack que estavam em tratamento internados em Comunidades Terapêuticas. MÉTODO: a amostra foi composta por 133 homens. Os instrumentos utilizados foram: Questionário sociodemográfico e rastreio do uso de drogas, Mini-Exame do Estado Mental e uma Escala de Perguntas sobre craving. A análise utilizada foi a estatística descritiva e de frequências para análise exploratória com nível de significância de 5%. RESULTADOS: os participantes relataram um predomínio da categoria Força de Vontade e de comportamento de Esquiva em resposta ao craving. CONCLUSÃO: esses resultados são importantes contribuições na compreensão do enfrentamento do craving, sinalizando a importância do trabalho da prevenção de recaídas, da família e tratamentos eficazes.

OBJECTIVES: to identify and describe the coping strategies used in the face of craving by crack-cocaine users who were under treatment in the Therapeutic Communities. METHOD: the sample consisted of 133 men. The instruments were a socio-demographic questionnaire and on drug use screening, the Mini-Mental State Examination and the scale of questions on craving. The analysis used was descriptive and frequency statistics for exploratory analysis with significance level of 5%. RESULTS: the results demonstrate a predominance of the Willpower category and Dodge in response to craving. CONCLUSION: these results are important contributions in understanding the coping of craving, signaling the importance of relapse prevention work, of the family and of effective treatments.

OBJETIVOS: el objetivo del estudio fue identificar y describir las estratégias de afrontamiento utilizadas frente al craving por consumidores de crack que estaban em tratamiento internados en Comunidades Terapéuticas. MÉTODO: la muestra consistió en 133 hombres. Los instrumentos fueron: cuestionario sociodemográfico y la detección del consumo de drogas; Mini Examen del Estado Mental y Craving Cuestionario. El análisis utilizada fue descriptiva y las estadísticas de frecuencia para el análisis exploratorio con un nivel de significación del 5%. RESULTADOS: los resultados muestran el predominio de la categoría de fuerza de voluntad y el comportamiento de Esquivar en respuesta a las ansias. CONCLUSIÓN: estos resultados son importantes contribuciones en la comprensión de la cofia antojo, lo que indica la importancia de la labor de prevención de recaídas, la familia y los tratamientos eficaces.

Magnetic studies of layer-by-layer assembled polyvinyl alcohol/iron oxide nanofilms.

This study reports on investigation of the magnetic properties of layer-by-layer (LbL) assembled nanofilms comprising polyvinyl alcohol (PVA) and citrate-coated magnetite (cit-MAG) nanoparticles deposited onto silicon (SF sample) and glass (GF sample) substrates. DC magnetization measurements were performed over the temperature range of 4 K to 300 K, in the applied magnetic field range of ±60 kOe. The magnetic data of the as-synthesized cit-MAG nanoparticles (F sample) are also collected for comparison. The three as-fabricated samples reveal perfect superparamagnetic (SPM) behavior only around room temperature; at temperatures lower than 200 K the SPM scaling is not observed and all samples behave as interacting superparamagnetic (ISPM) materials. The evolution from the ISPM to the SPM regime is marked by a steady decrease in the hysteretic properties of all samples, with the temperature-dependence of the coercivity decreasing slower than the T1/2 behavior predicted for non-interacting superparamagnetic particles. The modified Bloch's law used to assess information on nanoparticles' surface spins gives the Bloch's exponent close to 2 (for the F and SF samples) and close to 1 (for the GF sample). Interestingly, the surface spin freezing temperature (Tf) is 8 ± 1 K for all samples. The magnetic behavior of all three samples can be described within the model picture of a core-shell structure for the cit-MAG nanoparticles; the core comprising magnetically-ordered spins whereas the shell behaving as a spin-glass-like system. However, the contribution of the shell magnetism to the effective magnetic properties is much more evident in the GF sample in which magnetic dipole-dipole interaction is three-times weaker than in the SF sample and two times weaker than in the F sample. In contrast, the strong magnetic dipole-dipole interaction in the SF sample affects the surface spins, hindering the onset of magnetically-ordered regions in the nanoparticle's shell, making the surface magnetism contribution negligible. The LbL-fabricated nanofilms herein reported and the presented analysis of their magnetic properties we envisage can support the engineering of magnetic nanofilms for multiple applications.

Magneto low-density nanoemulsion (MLDE): A potential vehicle for combined hyperthermia and photodynamic therapy to treat cancer selectively.

In this paper, we introduce a new drug delivery system (DDS) called magneto low-density nanoemulsion (MLDE), which can carry maghemite nanoparticles and Chlorin e6 as an active photosensitizer drug. This design can enhance tumor damage after minor heat dissipation and/or minimum visible light photosensitization doses by classical magnetic hyperthermia (MHT) and photodynamic therapy (PDT), respectively. We establish protocols to prepare the MLDE and to load the drug combination onto it. The MLDE prepared herein is nanometric (<200 nm), has high encapsulation efficiency, and is stable for at least 12 months in water dispersions. Flow cytometry results demonstrated that MLDE presents targeted selectivity toward the MCF-7 breast cancer cell line but not in NHI-3T3 mouse fibroblast cell lines, because the MCF-7 cancer cell surface contains overexpressed low density lipoprotein (LDL) receptors. Despite this targeted effect, MHT or PDT alone does not prompt significant antiproliferative outcomes. On the other hand, MHT and PDT in combination induce a strong and synergic action on MCF-7 cells and reduce the cell viability. In conclusion, the developed MLDE deserves further investigation because it is biocompatible, displays good encapsulation efficiency, and is highly stable. Moreover, it is selectively taken up by cancer cell surfaces with receptor recognition based on LDL receptor overexpression, which potentiates the action of combined MHT and PDT.

The Suprachiasmatic Nucleus and the Intergeniculate Leaflet of the Flat-Faced Fruit-Eating Bat (Artibeus planirostris): Retinal Projections and Neurochemical Anatomy.

In mammals, the suprachiasmatic nucleus (SCN) and the intergeniculate leaflet (IGL) are the main components of the circadian timing system. The SCN, classically known as the master circadian clock, generates rhythms and synchronizes them to environmental cues. The IGL is a key structure that modulates SCN activity. Strategies on the use of time by animals can provide important clues about how some species are adapted to competitive process in nature. Few studies have provided information about temporal niche in bats with special attention on the neural substrate underlies circadian rhythms. The aim of this study was to investigate these circadian centers with respect to their cytoarchitecture, chemical content and retinal projections in the flat-faced fruit-eating bat (Artibeus planirostris), a chiropteran endemic to South America. Unlike other species of phyllostomid bats, the flat-faced fruit-eating bat's peak of activity occurs 5 h after sunset. This raises several questions about the structure and function of the SCN and IGL in this species. We carried out a mapping of the retinal projections and cytoarchitectural study of the nuclei using qualitative and quantitative approaches. Based on relative optical density findings, the SCN and IGL of the flat-faced fruit-eating bat receive bilaterally symmetric retinal innervation. The SCN contains vasopressin (VP) and vasoactive intestinal polypeptide (VIP) neurons with neuropeptide Y (NPY), serotonin (5-HT) and glutamic acid decarboxylase (GAD) immunopositive fibers/terminals and is marked by intense glial fibrillary acidic protein (GFAP) immunoreactivity. The IGL contains NPY perikarya as well as GAD and 5-HT immunopositive terminals and is characterized by dense GFAP immunostaining. In addition, stereological tools were combined with Nissl stained sections to estimate the volumes of the circadian centers. Taken together, the present results in the flat-faced fruit-eating bat reveal some differences compared to other bat species which might explain the divergence in the hourly activity among bats in order to reduce the competitive potential and resource partitioning in nature.

Selol nanocapsules with a poly(methyl vinyl ether-co-maleic anhydride) shell conjugated to doxorubicin for combinatorial chemotherapy against murine breast adenocarcinoma in vivo.

Nanocapsules containing selol and doxorubicin (NCS-DOX) with an oily core of selol and a shell of poly(methyl vinyl ether-co-maleic anhydride) covalently conjugated to doxorubicin were developed in a previous work. In this study, these nanocapsules showed a similar antitumour effect in comparison to the free doxorubicin (DOX) treatment, but showed no evident DOX-related cardiotoxicity, as evidenced by serum creatine kinase-MB (CK-MB) activity. The histopathological analysis showed that the free DOX treatment induced more intense morphological damage to myocardial tissues in comparison to NCS-DOX treatment. Animals treated with free DOX presented important muscle fibre degradation and animals treated with NCS-DOX, heart tissue did not present signals of muscle fibre degeneration. These results indicate that the cardiotoxicity related to DOX is reduced when this drug is carried by the NCS-DOX. Noteworthy, biodistribution analyses showed that NCS-DOX accumulated more intensely in tumours than the free DOX. Thus, this study reinforces the importance of the development of nanocapsules as drug carriers for the treatment of cancer.

Decoration of a Poly(methyl vinyl ether-co-maleic anhydride)-Shelled Selol Nanocapsule with Folic Acid Increases Its Activity Against Different Cancer Cell Lines In Vitro.

Due to the low therapeutic index of different chemotherapeutic drugs used for cancer treatment, the development of new anticancer drugs remains an intense field of research. A recently developed mixture of selenitetriacylglycerides, selol, was shown to be active against different cancer cells in vitro. As this compound is highly hydrophobic, it was encapsulated, in a previous study, into poly(methyl vinyl ether-co-maleic anhydride)-shelled nanocapsules in order to improve its dispersibility in aqueous media. Following this line of research, the present report aimed at enhancing the In Vitro activity of the selol nanocapsules against cancerous cells by decorating their surface with folic acid. It is known that several cancer cells overexpress folate receptors. Stable folic acid-decorated selol nanocapsules (SNP-FA) were obtained, which showed to be spherical, with a hydro-dynamic diameter of 364 nm, and zeta potential of -24 mV. In comparison to non-decorated selol nanocapsules, SNP-FA presented higher activity against 4T1, MCF-7 and HeLa cells. Moreover, the decoration of the nanocapsules did not alter their toxicity towards fibroblasts, NIH-3T3 cells. These results show that the decoration with folic acid increased the toxicity of selol nanocapsules to cancer cells. These nanocapsules, besides enabling to disperse selol in an aqueous medium, increased the toxicity of this drug In Vitro, and may be useful to treat cancer in vivo, potentially increasing the specificity of selol towards cancer cells.