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In human and nonhuman primates, deep brain stimulation applied at or near the internal medullary lamina of the thalamus [a region referred to as "central thalamus," (CT)], but not at nearby thalamic sites, elicits major changes in the level of consciousness, even in some minimally conscious brain-damaged patients. The mechanisms behind these effects remain mysterious, as the connections of CT had not been specifically mapped in primates. In marmoset monkeys (Callithrix jacchus) of both sexes, we labeled the axons originating from each of the various CT neuronal populations and analyzed their arborization patterns in the cerebral cortex and striatum. We report that, together, these CT populations innervate an array of high-level frontal, posterior parietal, and cingulate cortical areas. Some populations simultaneously target the frontal, parietal, and cingulate cortices, while others predominantly target the dorsal striatum. Our data indicate that CT stimulation can simultaneously engage a heterogeneous set of projection systems that, together, target the key nodes of the attention, executive control, and working-memory networks of the brain. Increased functional connectivity in these networks has been previously described as a signature of consciousness.SIGNIFICANCE STATEMENT In human and nonhuman primates, deep brain stimulation at a specific site near the internal medullary lamina of the thalamus ["central thalamus," (CT)] had been shown to restore arousal and awareness in anesthetized animals, as well as in some brain-damaged patients. The mechanisms behind these effects remain mysterious, as CT connections remain poorly defined in primates. In marmoset monkeys, we mapped with sensitive axon-labeling methods the pathways originated from CT. Our data indicate that stimulation applied in CT can simultaneously engage a heterogeneous set of projection systems that, together, target several key nodes of the attention, executive control, and working-memory networks of the brain. Increased functional connectivity in these networks has been previously described as a signature of consciousness.
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Lesões Encefálicas , Callithrix , Masculino , Animais , Feminino , Humanos , Tálamo/fisiologia , Córtex Cerebral/fisiologia , Nível de Alerta/fisiologia , Estado de Consciência/fisiologia , Vias Neurais/fisiologiaRESUMO
Surface functionalized ultrafine CoFe2O4 nanoparticles (NPs), with mean diameter â¼5 nm, were investigated by means of DC magnetization and AC susceptibility over the temperature range of 4-400 K. All NPs present the same CoFe2O4 core, with different molecular surface coatings, increasing gradually the number of carbon atoms in the coating layer: glycine (C2H5NO2), alanine (C3H7NO2), aminobutanoic acid (C4H9NO2), aminohexanoic acid (C6H13NO2), and aminododecanoic acid (C12H25NO2). Samples were intentionally fabricated in order to modulate the core-core magnetic dipolar interaction, as the thickness of the coating layer increases with the number of carbon atoms in the coating molecule. The magnetic data of the uncoated CoFe2O4 NPs were also collected for comparison. All investigated CoFe2O4 NPs (coated and uncoated) are in a magnetically blocked state at room temperature as evidenced by ZFC/FC measurements and the presence of hysteresis with â¼700 Oe coercivity. Low temperature magnetization scans show slightly constricted hysteresis loops with coercivity decreasing systematically with a decreasing number of carbon atoms in the coating molecule, possibly resulting from differences in magnetic dipole coupling between NPs. Large thermomagnetic irreversibility, slow monotonic increase in the FC magnetization and non-saturation of the magnetization give evidence for the cluster glass (CG) nature in the CoFe2O4 NPs. The out of phase part (χ'') of AC susceptibility for all samples shows a clear frequency dependent hump which was analyzed to distinguish superparamagnetic (SPM), cluster glass (CG) and spin glass (SG) behavior by using Néel-Arrhenius, Vogel-Fulcher, and power law fittings. These analyses rule out the SPM state and suggest the presence of significant inter-cluster dipolar interaction, giving rise to CG cooperative freezing in the high-temperature region. In the low-temperature range, however, the disordered spins on the nanoparticle's surface play an important role in the formation of the SG-like state, as evidenced by Arrott plots and temperature dependency of dM/dH in the initial magnetization curves. In summary, the magnetic measurements showed that undercooling the system evolves from a SPM state of weakly interacting spin clusters, through the CG state induced by strong dipolar interaction, to the SG state resulting from the frustration of the disordered surface spins.
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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.
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Neoplasias da Mama/terapia , Hipertermia Induzida , Nanopartículas de Magnetita/uso terapêutico , Nanocápsulas/uso terapêutico , Compostos de Selênio/uso terapêutico , Animais , Neoplasias da Mama/patologia , Carcinoma de Ehrlich/patologia , Carcinoma de Ehrlich/terapia , Ciclo Celular/efeitos dos fármacos , Terapia Combinada , Fragmentação do DNA/efeitos dos fármacos , Feminino , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/ultraestrutura , Camundongos , Nanocápsulas/química , Nanocápsulas/ultraestrutura , Compostos de Selênio/química , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacosRESUMO
To characterize moderate to severe psoriasis (PsO) adult patients treated with secukinumab, estimate drug persistence and assess any reasons for treatment discontinuation. Non-interventional, retrospective, longitudinal record-based study including patients diagnosed with PsO who started secukinumab between January 2018 and January 2020. Baseline characteristics were analyzed by descriptive statistics; drug persistence and predictive factors were assessed through Kaplan-Meier curves and univariate and multivariate analysis, respectively. A total of 302 patients were included in the study: mean age was 48.4 years, 41.7% were female, median time since diagnosis was 12.9 years. 51.3% of patients were bio-naïve while 48.7% had previously been treated with biologics. PsO in difficult-to-treat locations (DTL) was present in 82.1% of patients, with scalp PsO in about half of patients. At 5-years follow-up, 84 patients discontinued secukinumab, 45 of which due to loss of efficacy. At week 104, overall treatment persistence was 71.7%. A higher probability of drug persistence was identified among those patients who initiated secukinumab ≥5 years after diagnosis, were bio-naïve or treated with only one previous biologic, had no PsO on DTL, and had diabetes mellitus. The predictive factors for discontinuation identified in our study were the start of secukinumab <5 years after diagnosis (p = 0.001), the bio-experimented status with ≥2 biologics (p = 0.007), and the presence of PsO on DTL (p = 0.014). A time since diagnosis of ≥5 years, naïve status or previous use of only one biologic are predictors for secukinumab persistence, whereas the presence of PsO on DTL predicts drug discontinuation.
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Produtos Biológicos , Psoríase , Adulto , Anticorpos Monoclonais Humanizados , Produtos Biológicos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Portugal , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
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.
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Banisteriopsis , Alucinógenos , Transtornos Relacionados ao Uso de Substâncias , Brasil/epidemiologia , Estudos Transversais , Humanos , Internet , Qualidade de Vida , Transtornos Relacionados ao Uso de Substâncias/epidemiologiaRESUMO
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.
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Melanoma , Neoplasias Cutâneas , Banho de Sol , Humanos , Pele , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/prevenção & controle , Raios Ultravioleta/efeitos adversosRESUMO
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.
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Portadores de Fármacos/química , Compostos Férricos/química , Nanopartículas Magnéticas de Óxido de Ferro/química , Nanocápsulas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Compostos de Selênio/química , Antineoplásicos/química , Fenômenos Magnéticos , TemperaturaRESUMO
Algal polysaccharides (extracellular polysaccharides) and carbon nanotubes (CNTs) were adsorbed on dioctadecyldimethylammonium bromide Langmuir monolayers to serve as a matrix for the incorporation of urease. The physicochemical properties of the supramolecular system as a monolayer at the air-water interface were investigated by surface pressure-area isotherms, surface potential-area isotherms, interfacial shear rheology, vibrational spectroscopy, and Brewster angle microscopy. The floating monolayers were transferred to hydrophilic solid supports, quartz, mica, or capacitive electrolyte-insulator-semiconductor (EIS) devices, through the Langmuir-Blodgett (LB) technique, forming mixed films, which were investigated by quartz crystal microbalance, fluorescence spectroscopy, and field emission gun scanning electron microscopy. The enzyme activity was studied with UV-vis spectroscopy, and the feasibility of the thin film as a urea sensor was essayed in an EIS sensor device. The presence of CNT in the enzyme-lipid LB film not only tuned the catalytic activity of urease but also helped to conserve its enzyme activity. Viability as a urease sensor was demonstrated with capacitance-voltage and constant capacitance measurements, exhibiting regular and distinctive output signals over all concentrations used in this work. These results are related to the synergism between the compounds on the active layer, leading to a surface morphology that allowed fast analyte diffusion owing to an adequate molecular accommodation, which also preserved the urease activity. This work demonstrates the feasibility of employing LB films composed of lipids, CNT, algal polysaccharides, and enzymes as EIS devices for biosensing applications.
Assuntos
Técnicas Biossensoriais/métodos , Enzimas Imobilizadas/metabolismo , Nanotubos de Carbono/química , Polissacarídeos/química , Urease/metabolismo , Brometos/química , Enzimas Imobilizadas/química , Lipídeos/química , Compostos de Amônio Quaternário/química , Espectrometria de Fluorescência , Propriedades de Superfície , Urease/químicaRESUMO
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.
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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.
Assuntos
Nanocápsulas , Neoplasias , Compostos de Selênio , Animais , Linhagem Celular Tumoral , Ácido Fólico , Células HeLa , Humanos , Maleatos , Camundongos , Neoplasias/tratamento farmacológico , PolietilenosRESUMO
We study the effect of Co co-doping on the optical properties of Mn-doped ZnTe nanocrystals (NCs) embedded in a glass matrix. Optical absorption (OA) and crystal field theory strongly indicated the substitutional incorporation of Co2+ ions into these semiconducting NCs as well as the characteristic transitions of these ions in the visible and near infrared spectral region. Transmission electron microscopy (TEM) images revealed an invariant NC lattice parameter with the incorporation of Mn2+ and Co2+ ions. The same was confirmed by X-ray diffraction (XRD). The photoluminescence (PL) spectra showed that the characteristic emission bands of Co2+ ions (E1Co2+ and E2Co2+) are intense and evident at low temperatures. Indeed, Raman spectra showed that the dependence of luminescence intensity on temperature is due to the electron-phonon interaction that arises from multiphonon relaxation processes. The redshifts in the PL spectra from green to orange with the incorporation of Mn2+ ions into ZnTe NCs, and in the near infrared with increasing Co-concentration, result from sp-d exchange interactions associated with the increase in Mn2+ and Co2+ ions in tetrahedral sites of ZnTe NCs, which may be very interesting for applications in luminescent devices. These observations provide strong evidence that higher Co-concentrations inhibit the incorporation of Mn2+ into ZnTe NCs, suggesting that there may be competition between Co2+ and Mn2+ ions substituting Zn2+ ions and, furthermore, that these ions replace zinc vacancies (VZn) in these NCs.
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Selol is a semi-synthetic compound containing selenite that is effective against cancerous cells and safer for clinical applications in comparison with other inorganic forms of selenite. Recently, we have developed a formulation of poly(methyl vinyl ether-co-maleic anhydride)-shelled selol nanocapsules (SPN), which reduced the proliferative activity of lung adenocarcinoma cells and presented little deleterious effects on normal cells in in vitro studies. In this study, we report on the antitumor activity and systemic effects induced by this formulation in chemically induced lung adenocarcinoma-bearing mice. The in vivo antitumor activity of the SPN was verified by macroscopic quantification, immunohistochemistry and morphological analyses. Toxicity analyses were performed by evaluations of the kidney, liver, and spleen; analyses of hemogram and plasma levels of alanine aminotransferase, aspartate transaminase, urea, and creatinine; and DNA fragmentation and cell cycle activity of the bone marrow cells. Furthermore, we investigated the potential of the SPN formulation to cause hemolysis, activate the complement system, provoke an inflammatory response and change the conformation of the plasma proteins. Our results showed that the SPN reduced the area of the surface tumor nodules but not the total number of tumor nodules. The biochemical and hematological findings were suggestive of the low systemic toxicity of the SPN formulation. The surface properties of the selol nanocapsules point to characteristics that are consistent with the treatment of the tumors in vivo: low hemolytic activity, weak inflammatory reaction with no activation of the complement system, and mild or absent conformational changes of the plasma proteins. In conclusion, this report suggests that the SPN formulation investigated herein exhibits anti-tumoral effects against lung adenocarcinoma in vivo and is associated with low systemic toxicity and high biocompatibility.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Maleatos/administração & dosagem , Nanocápsulas/administração & dosagem , Polietilenos/administração & dosagem , Compostos de Selênio/administração & dosagem , Adenocarcinoma/ultraestrutura , Adenocarcinoma de Pulmão , Animais , Antineoplásicos/química , Antineoplásicos/toxicidade , Peso Corporal/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proteínas do Sistema Complemento/metabolismo , Fragmentação do DNA/efeitos dos fármacos , Feminino , Inflamação/induzido quimicamente , Neoplasias Pulmonares/ultraestrutura , Maleatos/química , Maleatos/toxicidade , Camundongos , Nanocápsulas/química , Nanocápsulas/toxicidade , Tamanho do Órgão/efeitos dos fármacos , Polietilenos/química , Polietilenos/toxicidade , Compostos de Selênio/química , Compostos de Selênio/toxicidadeRESUMO
The micellar extraction (ME) of chlorophenols (CPs) from solid samples is rapid and avoids the use of organic solvents. The cationic surfactant cetyltrimethylammonium bromide (CTAB) is a powerful agent for ME of CPs. However, CTAB will be an important interference when the extracts are subsequently analyzed by direct solid phase microextraction (SPME) without a previous derivatization step. Therefore, CTAB is usually replaced by the nonionic surfactant polyoxyethylene-10-lauryl ether (POLE), which causes less interference but is less efficient in extracting CPs. In order to assess to what extent the derivatization of CPs with headspace (HS) sampling would be able to reduce surfactant interferences, CPs were measured in the presence of CTAB or POLE using acetylation and HS-SPME coupled to GC with an electron capture detector. Experiments were carried out both in water and in a 0.1 g/mL solution of NaCl (salting out agent). Acetylation and HS-SPME strongly decreased the interference of CTAB for CP determination. Therefore, the application of CTAB followed by SPME determination for an efficient ME of CPs from solid samples should be reconsidered since using CTAB with HS-SPME after acetylation proved to be a potential tool for CP determination in those matrixes after method optimization.
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Clorofenóis/química , Cromatografia Gasosa/métodos , Microextração em Fase Sólida/métodos , Tensoativos/química , Poluentes Ambientais/químicaRESUMO
Population genetic data of 12 X chromosomal short tandem repeats markers (DXS10074, DXS10079, DXS10101, DXS10103, DXS10134, DXS10135, DXS10146, DXS10148, DXS7132, DXS7423, DXS8378 and HPRTB) were analysed in 54 females and 95 males of an immigrant population from Cabo Verde living in Lisboa. The obtained results for forensic statistical parameters such as observed heterozigosity, polymorphism information content, power of discrimination and mean exclusion chance, based on single allele frequencies, reveal that this multiplex system is highly informative and can represent an important tool for genetic identification purposes in the immigrant population of Cabo Verde. Since the studied short tandem repeats genetic markers are distributed on four linkage groups, that can provide independent genotype information, we studied those groups as haploytes. The forensic efficiency parameters for the linked groups were all higher than 0.97, with linkage group I being the most polymorphic and linkage group III the less informative.
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Cromossomos Humanos X , Emigrantes e Imigrantes , Genética Populacional , Repetições de Microssatélites , Alelos , Feminino , Genética Forense , Frequência do Gene , Genótipo , Haplótipos , Voluntários Saudáveis , Humanos , Masculino , Polimorfismo Genético , Portugal , Locos de Características QuantitativasRESUMO
BACKGROUND: Selol is an oily mixture of selenitetriacylglycerides that was obtained as a semi-synthetic compound containing selenite. Selol is effective against cancerous cells and less toxic to normal cells compared with inorganic forms of selenite. However, Selol's hydrophobicity hinders its administration in vivo. Therefore, the present study aimed to produce a formulation of Selol nanocapsules (SPN) and to test its effectiveness against pulmonary adenocarcinoma cells (A549). RESULTS: Nanocapsules were produced through an interfacial nanoprecipitation method. The polymer shell was composed of poly(methyl vinyl ether-co-maleic anhydride) (PVM/MA) copolymer. The obtained nanocapsules were monodisperse and stable. Both free Selol (S) and SPN reduced the viability of A549 cells, whereas S induced a greater reduction in non-tumor cell viability than SPN. The suppressor effect of SPN was primarily associated to the G2/M arrest of the cell cycle, as was corroborated by the down-regulations of the CCNB1 and CDC25C genes. Apoptosis and necrosis were induced by Selol in a discrete percentage of A549 cells. SPN also increased the production of reactive oxygen species, leading to oxidative cellular damage and to the overexpression of the GPX1, CYP1A1, BAX and BCL2 genes. CONCLUSIONS: This study presents a stable formulation of PVM/MA-shelled Selol nanocapsules and provides the first demonstration that Selol promotes G2/M arrest in cancerous cells.
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Adenocarcinoma/tratamento farmacológico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Maleatos/química , Nanocápsulas/química , Polietilenos/química , Compostos de Selênio/farmacologia , Adenocarcinoma/patologia , Adenocarcinoma/ultraestrutura , Adenocarcinoma de Pulmão , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral/ultraestrutura , Ciclina B1/genética , Relação Dose-Resposta a Droga , Glutationa Peroxidase/genética , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/ultraestrutura , Nanoconchas/química , Espécies Reativas de Oxigênio/metabolismo , Compostos de Selênio/administração & dosagem , Compostos de Selênio/química , Termodinâmica , Fosfatases cdc25/genética , Glutationa Peroxidase GPX1RESUMO
The determination of chlorophenols (CPs) in water samples is a subject of increasing interest. Reduction of sample storage space and the stability of CPs when present at very low levels are still problems that deserve research. The stability of CPs at ng/L levels at different temperatures and in the presence or absence of sodium carbonate and acetic anhydride was studied for up to 39 days. Stable and reproducible CP concentrations for about a month of storage in both river and wastewater were achieved in two storage conditions as follows: at -18 degrees C with addition of 10% sodium chloride; and at 4 degrees C with addition of both 10% sodium chloride and 10 mglmL sodium carbonate. These sample treatments are good alternatives to the immobilization of CPs on SPE cartridges in terms of both analyte stability and saving of storage space.
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Clorofenóis/química , Água/química , Carbonatos/química , Técnicas de Química Analítica , Fatores de Tempo , Poluentes Químicos da Água/químicaRESUMO
A case study A previously healthy woman, aged 37 years, presented with a 4-week history of pruritic periungual rash and subungual pain. Physical examination revealed scaly, fissured, erythematous plaques around her fingernails (Figure 1). Underneath the acrylic artificial nails that she had been wearing for 6 weeks, onycholysis and nail bed hyperkeratosis were evident. Oral terbinafine and amorolfine nail polish were prescribed by the general practitioner but had no clinical benefit.
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Acrilatos/efeitos adversos , Dermatite Alérgica de Contato/diagnóstico , Exantema/etiologia , Unhas , Adulto , Anti-Inflamatórios/uso terapêutico , Betametasona/análogos & derivados , Betametasona/uso terapêutico , Cosméticos/efeitos adversos , Dermatite Alérgica de Contato/tratamento farmacológico , Dermatite Alérgica de Contato/etiologia , Diagnóstico Diferencial , Feminino , Humanos , Onicomicose/diagnóstico , Testes do Emplastro , Psoríase/diagnósticoRESUMO
Over time, the body undergoes a natural, multifactorial, and ongoing process named senescence, which induces changes at the molecular, cellular, and micro-anatomical levels in many body systems. The brain, being a highly complex organ, is particularly affected by this process, potentially impairing its numerous functions. The brain relies on chemical messengers known as neurotransmitters to function properly, with dopamine being one of the most crucial. This catecholamine is responsible for a broad range of critical roles in the central nervous system, including movement, learning, cognition, motivation, emotion, reward, hormonal release, memory consolidation, visual performance, sexual drive, modulation of circadian rhythms, and brain development. In the present review, we thoroughly examine the impact of senescence on the dopaminergic system, with a primary focus on the classic delimitations of the dopaminergic nuclei from A8 to A17. We provide in-depth information about their anatomy and function, particularly addressing how senescence affects each of these nuclei.
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Envelhecimento , Dopamina , Neurônios Dopaminérgicos , Humanos , Animais , Envelhecimento/metabolismo , Envelhecimento/fisiologia , Dopamina/metabolismo , Neurônios Dopaminérgicos/metabolismo , Encéfalo/metabolismoRESUMO
The physiological aging process is well known for functional decline in visual abilities. Among the components of the visual system, the dorsal lateral geniculate nucleus (DLG) and superior colliculus (SC) provide a good model for aging investigations, as these structures constitute the main visual pathways for retinal inputs reaching the visual cortex. However, there are limited data available on quantitative morphological and neurochemical aspects in DLG and SC across lifespan. Here, we used optical density to determine immunoexpression of glial fibrillary acidic protein (GFAP) and design-based stereological probes to estimate the neuronal number, total volume, and layer volume of the DLG and SC in marmosets (Callithrix jacchus), ranging from 36 to 143 months of age. Our results revealed an age-related increase in total volume and layer volume of the DLG, with an overall stability in SC volume. Furthermore, a stable neuronal number was demonstrated in DLG and superficial layers of SC (SCv). A decrease in GFAP immunoexpression was observed in both visual centers. The results indicate region-specific variability in volumetric parameter, possibly attributed to structural plastic events in response to inflammation and compensatory mechanisms at the cellular and subcellular level. Additionally, the DLG and SCv seem to be less vulnerable to aging effects in terms of neuronal number. The neuropeptidergic data suggest that reduced GFAP expression may reflect morphological atrophy in the astroglial cells. This study contributes to updating the current understanding of aging effects in the visual system and stablishes a crucial foundation for future research on visual perception throughout the aging process.