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1.
Int J Mol Sci ; 24(17)2023 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-37686114

RESUMO

Gold nanorods are the most commonly used nanoparticles in photothermal therapy for cancer treatment due to their high efficiency in converting light into heat. This study aimed to investigate the efficacy of gold nanorods of different sizes (large and small) in eliminating two types of cancer cell: melanoma and glioblastoma cells. After establishing the optimal concentration of nanoparticles and determining the appropriate time and power of laser irradiation, photothermal therapy was applied to melanoma and glioblastoma cells, resulting in the highly efficient elimination of both cell types. The efficiency of the PTT was evaluated using several methods, including biochemical analysis, fluorescence microscopy, and flow cytometry. The dehydrogenase activity, as well as calcein-propidium iodide and Annexin V staining, were employed to determine the cell viability and the type of cell death triggered by the PTT. The melanoma cells exhibited greater resistance to photothermal therapy, but this resistance was overcome by irradiating cells at physiological temperatures. Our findings revealed that the predominant cell-death pathway activated by the photothermal therapy mediated by gold nanorods was apoptosis. This is advantageous as the presence of apoptotic cells can stimulate antitumoral immunity in vivo. Considering the high efficacy of these gold nanorods in photothermal therapy, large nanoparticles could be useful for biofunctionalization purposes. Large nanorods offer a greater surface area for attaching biomolecules, thereby promoting high sensitivity and specificity in recognizing target cancer cells. Additionally, large nanoparticles could also be beneficial for theranostic applications, involving both therapy and diagnosis, due to their superior detection sensitivity.


Assuntos
Glioblastoma , Melanoma , Humanos , Glioblastoma/terapia , Terapia Fototérmica , Morte Celular , Ouro
2.
J Nanobiotechnology ; 13: 20, 2015 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-25890124

RESUMO

BACKGROUND: Magnetic resonance imaging is the ideal modality for non-invasive in vivo cell tracking allowing for longitudinal studies over time. Cells labeled with superparamagnetic iron oxide nanoparticles have been shown to induce sufficient contrast for in vivo magnetic resonance imaging enabling the in vivo analysis of the final location of the transplanted cells. For magnetic nanoparticles to be useful, a high internalization efficiency of the particles is required without compromising cell function, as well as validation of the magnetic nanoparticles behaviour inside the cells. RESULTS: In this work, we report the development, optimization and validation of an efficient procedure to label human neural stem cells with commercial nanoparticles in the absence of transfection agents. Magnetic nanoparticles used here do not affect cell viability, cell morphology, cell differentiation or cell cycle dynamics. Moreover, human neural stem cells progeny labeled with magnetic nanoparticles are easily and non-invasively detected long time after transplantation in a rat model of Parkinson's disease (up to 5 months post-grafting) by magnetic resonance imaging. CONCLUSIONS: These findings support the use of commercial MNPs to track cells for short- and mid-term periods after transplantation for studies of brain cell replacement therapy. Nevertheless, long-term MR images should be interpreted with caution due to the possibility that some MNPs may be expelled from the transplanted cells and internalized by host microglial cells.


Assuntos
Encéfalo/patologia , Imageamento por Ressonância Magnética/métodos , Nanopartículas de Magnetita/química , Células-Tronco Neurais/química , Doença de Parkinson/patologia , Animais , Sobrevivência Celular , Rastreamento de Células/métodos , Transplante de Células/métodos , Células Cultivadas , Dextranos/química , Feminino , Humanos , Células-Tronco Neurais/citologia , Células-Tronco Neurais/transplante , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Transfecção/métodos
3.
Int J Pharm ; 655: 124023, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38513815

RESUMO

This study delves into the biomolecular mechanisms underlying the antitumoral efficacy of a hybrid nanosystem, comprised of a silver core@shell (Ag@MSNs) functionalized with transferrin (Tf). Employing a SILAC proteomics strategy, we identified over 150 de-regulated proteins following exposure to the nanosystem. These proteins play pivotal roles in diverse cellular processes, including mitochondrial fission, calcium homeostasis, endoplasmic reticulum (ER) stress, oxidative stress response, migration, invasion, protein synthesis, RNA maturation, chemoresistance, and cellular proliferation. Rigorous validation of key findings substantiates that the nanosystem elicits its antitumoral effects by activating mitochondrial fission, leading to disruptions in calcium homeostasis, as corroborated by RT-qPCR and flow cytometry analyses. Additionally, induction of ER stress was validated through western blotting of ER stress markers. The cytotoxic action of the nanosystem was further affirmed through the generation of cytosolic and mitochondrial reactive oxygen species (ROS). Finally, in vivo experiments using a chicken embryo model not only confirmed the antitumoral capacity of the nanosystem, but also demonstrated its efficacy in reducing cellular proliferation. These comprehensive findings endorse the potential of the designed Ag@MSNs-Tf nanosystem as a groundbreaking chemotherapeutic agent, shedding light on its multifaceted mechanisms and in vivo applicability.


Assuntos
Antineoplásicos , Prata , Embrião de Galinha , Animais , Prata/farmacologia , Prata/metabolismo , Cálcio/metabolismo , Apoptose , Antineoplásicos/farmacologia , Estresse do Retículo Endoplasmático , Espécies Reativas de Oxigênio/metabolismo , Transferrina
4.
Exp Cell Res ; 318(19): 2446-59, 2012 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-22884477

RESUMO

Understanding the molecular programs of the generation of human dopaminergic neurons (DAn) from their ventral mesencephalic (VM) precursors is of key importance for basic studies, progress in cell therapy, drug screening and pharmacology in the context of Parkinson's disease. The nature of human DAn precursors in vitro is poorly understood, their properties unstable, and their availability highly limited. Here we present positive evidence that human VM precursors retaining their genuine properties and long-term capacity to generate A9 type Substantia nigra human DAn (hVM1 model cell line) can be propagated in culture. During a one month differentiation, these cells activate all key genes needed to progress from pro-neural and pro-dopaminergic precursors to mature and functional DAn. For the first time, we demonstrate that gene cascades are correctly activated during differentiation, resulting in the generation of mature DAn. These DAn have morphological and functional properties undistinguishable from those generated by VM primary neuronal cultures. In addition, we have found that the forced expression of Bcl-X(L) induces an increase in the expression of key developmental genes (MSX1, NGN2), maintenance of PITX3 expression temporal profile, and also enhances genes involved in DAn long-term function, maintenance and survival (EN1, LMX1B, NURR1 and PITX3). As a result, Bcl-X(L) anticipates and enhances DAn generation.


Assuntos
Diferenciação Celular/genética , Neurônios Dopaminérgicos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Mesencéfalo/metabolismo , Proteína bcl-X/genética , Proteína bcl-X/metabolismo , Linhagem Celular , Dopamina/genética , Dopamina/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Mesencéfalo/citologia , Prosencéfalo/metabolismo , Substância Negra/citologia , Substância Negra/crescimento & desenvolvimento , Substância Negra/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
5.
Eur J Psychotraumatol ; 14(2): 2282003, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38039055

RESUMO

Background: Women are more likely to develop post-traumatic stress disorder (PTSD) than men. Recent research suggests an impact of oral contraceptive (OC) intake on PTSD and intrusive memories, a hallmark symptom of PTSD. Although a majority of women use OCs at some point in their lives, the effects on PTSD pathogenesis are only poorly understood.Objective: In the current paper, we aimed to investigate the impact of OC intake on the acquisition and consolidation of intrusive memories in healthy women after watching a trauma film paradigm.Methods: We performed a secondary analysis of a pooled dataset (N = 437) of two previously conducted and published studies investigating the effect of oxytocin on the development of intrusive memories.Results: Women taking OCs showed an attenuated decline of intrusive memories over time after having watched the trauma film compared to naturally cycling women (F(2.75, 1167) = 3.79, p = .03, ηp2 = .01).Conclusion: These findings indicate that the intake of OCs is associated with the development of intrusive memories after a trauma film paradigm. This indication emphasizes the need to further investigate the complex impact of OCs and gonadal hormones on fear learning processes and PTSD.


The objective of the current study was to analyze the effect of oral contraceptives on the development of intrusive memories after a trauma film paradigm by conducting a secondary analysis of previously published data.Women taking oral contraceptives show an attenuated decline of intrusive memories after watching a trauma film paradigm compared to naturally cycling women in the luteal phase.Women using oral contraceptives show higher basal saliva cortisol levels.


Assuntos
Memória , Transtornos de Estresse Pós-Traumáticos , Masculino , Humanos , Feminino , Anticoncepcionais Orais/farmacologia , Medo , Filmes Cinematográficos
6.
Artigo em Espanhol | MEDLINE | ID: mdl-37408602

RESUMO

Objective: To determine the clinical characteristics, therapeutic and in-hospital mortality of patients with mechanical complications post myocardial infarction. Materials and methods: Observational, descriptive and retrospective study. We included patients >18 years old with a diagnosis of mechanical complication post myocardial infarction hospitalized at the Instituto Nacional Cardiovascular- INCOR in Lima -Peru, from January 1, 2017 to December 31, 2021. Variables like clinical characteristics, treatments, complications, and in-hospital mortality were studied. Results: We found 37 cases, with a predominance of males (73.0%) and a median age of 73 years old. The location of the myocardial infarction was 51.4% in the anterior wall and 43.2% in the inferior wall. The patients received reperfusion therapy with fibrinolysis in 5 cases (13.5%), coronary angioplasty in 5 (13.5%), and 73% received only medical management prior to the diagnosis of mechanical complications. Of the 37 patients, 13 (35.1%) presented isolated ventricular free wall rupture, 12 (32.4%) isolated interventricular septum rupture, 10 (27.0%) the combination of ventricular free wall rupture and interventricular septum, and 2 (5.4%) papillary muscle rupture. In-hospital mortality was 51.4%. Conclusions: The ventricular free wall rupture was the most frequent complication, patients with mechanical complications after myocardial infarction still maintain high intra-hospital mortality rates, mainly in those who did not have adequate surgical treatment.

7.
Arch Peru Cardiol Cir Cardiovasc ; 2(4): 268-273, 2021.
Artigo em Espanhol | MEDLINE | ID: mdl-37727663

RESUMO

Homozygous familial hypercholesterolemia (HFH) is a rare and life-threatening disease that can manifest as coronary artery disease or severe aortic stenosis before twenties. We present the case of a male adolescent who was hospitalized with a clinical diagnosis of HFH and severe aortic stenosis. He underwent aortic valve replacement with mechanical prosthesis and aortic annulus enlargement, and two aortocoronary bypasses were implanted due to an intraoperative complication. The patient evolved favourably and was discharged with combination therapy with high-intensity statins and ezetimibe.

8.
Mater Sci Eng C Mater Biol Appl ; 126: 112140, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34082951

RESUMO

Multiscale 3D carbon architectures are of particular interest in tissue engineering applications, as these structures may allow for three-dimensional cell colonization essential for tissue growth. In this work, carbon fiber/microlattice hybrid architectures are introduced as innovative multi-scale scaffolds for tissue engineering. The microlattice provides the design freedom and structural integrity, whereas the fibrous component creates a cellular microenvironment for cell colonization. The hybrid structures are fabricated by carbonization of stereolithographically 3D printed epoxy microlattice architectures which are pre-filled with cotton fibers within the empty space of the architectures. The cotton filling result in less shrinkage of the architecture during carbonization, as the tight confinement of the fibrous material prevents the free-shrinkage of the microlattices. The hybrid architecture exhibits a compressive strength of 156.9±25.6 kPa, which is significantly higher than an empty carbon microlattice architecture. Furthermore, the hybrid architecture exhibits a flexible behavior up to 30% compressive strain, which is also promising towards soft-tissue regeneration. Osteoblast-like murine MC3T3-E1 cells are cultured within the 3D hybrid structures. Results show that the cells are able to not only proliferate on the carbon microlattice elements as well as along the carbon fibers, but also make connections with each other across the inner pores created by the fibers, leading to a three-dimensional cell colonization. These carbon fiber/microlattice hybrid structures are promising for future fabrication of functionally graded scaffolds for tissue repair applications.


Assuntos
Engenharia Tecidual , Alicerces Teciduais , Animais , Fibra de Carbono , Força Compressiva , Camundongos , Osteoblastos , Impressão Tridimensional
9.
Acta Gastroenterol Latinoam ; 40(4): 332-8, 2010 Dec.
Artigo em Espanhol | MEDLINE | ID: mdl-21381408

RESUMO

INTRODUCTION: It has been demonstrated that scintigraphy with somatostatin analogues is useful for the diagnosis, staging and follow up of patients with neuroendocrine tumors from the gastrointestinal tract (NET-GIT). Some studies suggest that the use of 99mTc-Hydrazinonicotinyl-Tyr3-octreotide (99mTc-HYNIC-TOC) yields similar diagnostic results than the use of 111In-DTPA-octreotide. OBJECTIVE: To determine the clinical value of scintigraphy using 99mTc-HYNIC-TOC for the detection of primary and secondary lesions in patients with NET-GIT. METHODS: From September 2004 to May 2009, 32 patients (17 women, age range 18 to 82 years old) with histologically proven or clinically suspected NET-GIT underwent scintigraphy using 99mTc-HYNIC-TOC Patients underwent a whole body scan, with additional static images of abdomen and pelvis, followed by SPECT at 4-hrs post injection of 925 MBq of the tracer. Patients underwent clinical, imaging and histopathology follow-up during 3 to 18 months. RESULTS: Histopathology demonstrated carcinoid tumor in 20 patients, insulinoma in 2, gastrinoma in 2 and non-specific NET-GIT in 6. Total sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 87%, 100%, 100%, 89% and 94%, respectively. To detect the primary lesion, the values were 94%, 100% 100%, 94% and 97%, respectively and to detect secondary lesions, 79%, 100%, 100%, 86% and 91%, respectively. CONCLUSIONS: 99mTc-HYNIC-TOC is a specific somatostatin analog, with high affinity to receptor subtype SST-2, widely available and affordable by Latin American countries. It has a good performance to be used for diagnosis, staging and follow-up of patients with NET-GIT.


Assuntos
Neoplasias Gastrointestinais/diagnóstico por imagem , Tumores Neuroendócrinos/diagnóstico por imagem , Octreotida/análogos & derivados , Compostos de Organotecnécio , Neoplasias Pancreáticas/diagnóstico por imagem , Compostos Radiofarmacêuticos , Adolescente , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Tomografia Computadorizada de Emissão de Fóton Único , Adulto Jovem
10.
Int Urol Nephrol ; 52(5): 977-980, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32297181

RESUMO

Among the different hemodialysis (HD) strategies, the short daily hemodialysis performed at home (SDHHD) provides clinical benefits to the patient. Expanded hemodialysis (HDx) employs cutoff medium membranes that exhibit greater clearance capacity of uremic toxins of medium-high molecular weight. This case series study reported the results of seven patients who were transferred to expanded hemodialysis at home (HHDx), from December 2017 to March 2019, over a 12-month follow-up period. The AK-98 monitor and Theranova 400 membrane (Baxter International Inc., Deerfield, IL, USA) were used. The main outcome measures were blood analytical values and drug consumption. The blood levels of ß2-microglobulin were significantly reduced (p = 0.0082), while maintaining albumin levels with less use of phosphorus binders. Regarding the safety profile, technique-related adverse events were not reported. According to the results of the current study, HHDx was a safe technique, which additionally had the ability to provide benefits to patients due to its greater purification capacity. Further studies, especially multicenter ones, with a greater number of patients are needed to confirm these results.


Assuntos
Hemodiálise no Domicílio/métodos , Insuficiência Renal Crônica/terapia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/sangue
11.
ACS Biomater Sci Eng ; 6(12): 6842-6852, 2020 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-33320622

RESUMO

The recovery of injured nervous tissue, one of the main goals for regenerative therapeutic approaches, is often hindered by the limited axonal regeneration ability of the central nervous system (CNS). In this regard, the identification of scaffolds that support the reconstruction of functional neuronal tissues and guide the alignment of regenerating neurons is a major challenge in tissue engineering. Ideally, the usage of such scaffolds would promote and guide the axonal growth, a crucial phase for the restoration of neuronal connections and, consequently, the nerve function. Among the materials proposed as scaffolds for CNS regeneration, silk has been used to exploit its outstanding features as a biomaterial to promote axonal regeneration. In this study, we explore, for the first time, the possibility of using high-performance regenerated silk fibers obtained by straining flow spinning (SFS) to serve as scaffolds for inducing and guiding the axonal growth. It is shown that SFS fibers promote the spontaneous organization of dissociated cortical primary cells into highly interconnected cellular spheroid-like tissue formations. Neuronal projections (i.e., axons) from these cellular spheroids span hundreds of microns along the SFS fibers that act as guides and allow the connection of distant spheroids. In addition, it is also shown that SFS fibers serve as scaffolds for neuronal migration covering short and long distances. As a consequence, the usage of high-performance SFS fibers appears as a promising basis for the development of novel therapies, leading to directed axonal regeneration.


Assuntos
Axônios , Seda , Regeneração Nervosa , Neurônios , Engenharia Tecidual
12.
Sci Rep ; 9(1): 14886, 2019 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-31624307

RESUMO

Several computational models, both continuum and discrete, allow for the simulation of collective cell behaviors in connection with challenges linked to disease modeling and understanding. Normally, discrete cell modelling employs quasi-infinite or boundary-less 2D lattices, hence modeling collective cell behaviors in Petri dish-like environments. The advent of lab- and organ-on-a-chip devices proves that the information obtained from 2D cell cultures, upon Petri dishes, differs importantly from the results obtained in more biomimetic micro-fluidic environments, made of interconnected chambers and channels. However, discrete cell modelling within lab- and organ-on-a-chip devices, to our knowledge, is not yet found in the literature, although it may prove useful for designing and optimizing these types of systems. Consequently, in this study we focus on the establishment of a direct connection between the computer-aided designs (CAD) of microfluidic systems, especially labs- and organs-on-chips (and their multi-chamber and multi-channel structures), and the lattices for discrete cell modeling approaches aimed at the simulation of collective cell interactions, whose boundaries are defined directly from the CAD models. We illustrate the proposal using a quite straightforward cellular automata model, apply it to simulating cells with different growth rates, within a selected set of microsystem designs, and validate it by tuning the growth rates with the support of cell culture experiments and by checking the results with a real microfluidic system.


Assuntos
Comunicação Celular , Dispositivos Lab-On-A-Chip , Modelos Biológicos , Células 3T3 , Animais , Técnicas de Cultura de Células , Linhagem Celular , Simulação por Computador , Desenho Assistido por Computador , Desenho de Equipamento , Humanos , Camundongos , Técnicas Analíticas Microfluídicas , Microfluídica
13.
Nanoscale Res Lett ; 14(1): 36, 2019 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-30684043

RESUMO

BACKGROUND: Considering the high incidence of Alzheimer's disease among the world population over the years, and the costs that the disease poses in sanitary and social terms to countries, it is necessary to develop non-invasive diagnostic tests that allow to detect early biomarkers of the disease. Within the early diagnosis methods, the development of contrast agents for magnetic resonance imaging becomes especially useful. Accumulating evidence suggests that cholesterol may play a role in the pathogenesis of Alzheimer's disease since abnormal deposits of cholesterol surrounding senile plaques have been described in animal transgenic models and patients with Alzheimer's disease. In vivo experiments have also shown that diet-induced hypercholesterolemia enhances intraneuronal accumulation of ß-amyloid protein accompanied by microgliosis and accelerates ß-amyloid deposition in brains. PRESENTATION OF THE HYPOTHESIS: In the present study, we propose for the first time the synthesis of a new nanoconjugate composed of magnetic nanoparticles bound to an anti-cholesterol antibody, to detect the abnormal deposits of cholesterol observed in senile plaques in Alzheimer's disease by magnetic resonance imaging. The nanoplatform could also reveal the decrease of cholesterol observed in neuronal plasmatic membranes associated with this pathology. TESTING THE HYPOTHESIS: Experimental design to test the hypothesis will be done first in vitro and then in ex vivo and in vivo studies in a second stage. IMPLICATIONS OF THE HYPOTHESIS: The designed nanoplatform could therefore detect cholesterol deposits at the cerebral level. The detection of this biomarker in areas coinciding with senile plaque accumulations could provide early information on the onset and progression of Alzheimer's disease.

14.
ACS Chem Neurosci ; 9(5): 912-924, 2018 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-29298040

RESUMO

Early diagnosis in Alzheimer's disease (AD), prior to the appearance of marked clinical symptoms, is critical to prevent irreversible neuronal damage and neural malfunction that lead to dementia and death. Therefore, there is an urgent need to generate new contrast agents which reveal by a noninvasive method the presence of some of the pathological signs of AD. In the present study, we demonstrate for the first time a new nanoconjugate composed of magnetic nanoparticles bound to an antiferritin antibody, which has been developed based on the existence of iron deposits and high levels of the ferritin protein present in areas with a high accumulation of amyloid plaques (particularly the subiculum in the hippocampal area) in the brain of a transgenic mouse model with five familial AD mutations. Both in vitro and after intravenous injection, functionalized magnetic nanoparticles were able to recognize and bind specifically to the ferritin protein accumulated in the subiculum area of the AD transgenic mice.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Ferritinas/farmacologia , Nanopartículas de Magnetita/uso terapêutico , Neurônios/efeitos dos fármacos , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Meios de Contraste/metabolismo , Modelos Animais de Doenças , Camundongos , Neurônios/metabolismo
15.
Biochim Biophys Acta ; 1743(3): 269-79, 2005 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-15843040

RESUMO

It has been reported that inhibition of extracellular signal-regulated protein kinases (ERKs) attenuates the toxicity cisplatin (cis-platinum (II)-diammine dichloride) in some cell types. This response was here investigated using human myeloid leukemia cells. Cisplatin stimulated ERK1/2 phosphorylation and caused apoptosis in U-937 promonocytic cells, an effect which was attenuated by the MEK/ERK inhibitors PD98059 and U0126. While ERK1/2 activation was a general phenomenon, irrespective of the used cell type or antitumour drug, the MEK/ERK inhibitors only reduced cisplatin toxicity in human myeloid cells (THP-1, HL-60 and NB-4), but not in RAW 264.7 mouse macrophages and NRK-52E rat renal tubular cells; and failed to reduce the toxicity etoposide, camptothecin, melphalan and arsenic trioxide, in U-937 cells. U0126 attenuated cisplatin-DNA binding and intracellular peroxide accumulation, which are important regulators of cisplatin toxicity. Although cisplatin decreased the intracellular glutathione (GSH) content, which was restored by U0126, treatments with GSH-ethyl ester and dl-buthionine-(S,R)-sulfoximine revealed that GSH does not regulate cisplatin toxicity in the present experimental conditions. In spite of it, PD98059 and U0126 reduced the intracellular accumulation of cisplatin. These results suggest that GSH-independent modulation of drug transport is a major mechanism explaining the anti-apoptotic action of MEK/ERK inhibitors in cisplatin-treated myeloid cells.


Assuntos
Apoptose , Cisplatino , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Hidroxianisol Butilado/farmacologia , Linhagem Celular Tumoral , Cisplatino/antagonistas & inibidores , Cisplatino/metabolismo , DNA/metabolismo , Inibidores Enzimáticos/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Glutationa/metabolismo , Humanos , Leucemia Mieloide , Camundongos , Necrose , Oxirredução , Fosforilação , Fatores de Tempo
16.
Neural Regen Res ; 11(1): 49-52, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26981077

RESUMO

Human neural stem cells (hNSCs) derived from the ventral mesencephalon are powerful research tools and candidates for cell therapies in Parkinson's disease. However, their clinical translation has not been fully realized due, in part, to the limited ability to track stem cell regional localization and survival over long periods of time after in vivo transplantation. Magnetic resonance imaging provides an excellent non-invasive method to study the fate of transplanted cells in vivo. For magnetic resonance imaging cell tracking, cells need to be labeled with a contrast agent, such as magnetic nanoparticles, at a concentration high enough to be easily detected by magnetic resonance imaging. Grafting of human neural stem cells labeled with magnetic nanoparticles allows cell tracking by magnetic resonance imaging without impairment of cell survival, proliferation, self-renewal, and multipotency. However, the results reviewed here suggest that in long term grafting, activated microglia and macrophages could contribute to magnetic resonance imaging signal by engulfing dead labeled cells or iron nanoparticles dispersed freely in the brain parenchyma over time.

17.
Sci Total Environ ; 565: 557-563, 2016 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-27196992

RESUMO

Consumption of vegetables grown in arsenic (As)-contaminated soils is an important exposure route to the element for humans. The present study is focused on locally-grown, frequently-consumed vegetables, such as carrots (Daucus carota), beets (Beta vulgaris) and quinoa (Chenopodium) from the As-polluted Chiu Chiu area in Northern Chile. The latter region is affected both by As discharge from copper mining activity and natural As contamination, leading to a high As content in local food and water. For the selected vegetables, the following aspects were investigated: i) Their total As, Cu, Pb, Cr, Cd and Mn content; ii) Arsenic speciation in the edible part of the vegetables by liquid chromatography inductively-coupled plasma mass spectrometry (LC-ICPMS) analysis; iii) Arsenic bioaccessibility in the vegetables during in vitro gastrointestinal digestion; iv) Arsenic species present in the extracts obtained from in vitro gastrointestinal digestion; and v) Arsenic dietary exposure estimates for the assessment of the risk posed by the vegetables consumption. A significant degree of As contamination was found in the vegetables under study, their metal content having been compared with that of similar Spanish uncontaminated products. In vitro gastrointestinal digestion of the studied vegetables led to quantitative extraction of As from carrots and beets, whereas efficiency was about 40% for quinoa. For carrots, only As(III) and As(V) species were found, being their concentration levels similar. In the case of quinoa, around 85% of the element was present as As(V). For beets, inorganic As(V) and unknown overlapped As species (probably arsenosugars) were found. No significant transformation of the original As species was observed during in vitro gastrointestinal digestion. Arsenic dietary exposure values obtained for the three vegetables (0.017-0.021µg As person(-1)day(-1)) were much lower than the JFCFA's safety limit of 50µg As person(-1)day(-1). Therefore, no toxicological risk would be expected from the intake of these vegetables.


Assuntos
Arsênio/análise , Contaminação de Alimentos/análise , Poluentes do Solo/análise , Arsênio/química , Beta vulgaris/metabolismo , Chenopodium quinoa/metabolismo , Chile , Cromatografia Líquida , Daucus carota/metabolismo , Espectrometria de Massas , Poluentes do Solo/química
18.
Neuroreport ; 13(11): 1403-5, 2002 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-12167762

RESUMO

Alzheimer disease (AD) risk is significantly influenced by the APOE2 and APOE4 alleles. In turn, the -491AT and TH1/E47cs polymorphisms alter APOE gene expression levels. To determine whether these two alleles exert any significant effect on AD development we have analysed the genotypes of the APOE promoter -491AT and Th1/E47cs polymorphisms in 163 AD patients and 155 controls divided into three age at onset/age dependent subgroups. Our study has detected a Th1/E47cs-T allele accumulation in healthy individuals over 75 years of age, which suggests it plays a protective role against AD. The Th1/E47cs-T allele may provide greater protection against AD than APOE2, although this awaits proof of Th1/E47cs-T allele overrepresentation in healthy individuals of other populations.


Assuntos
Alelos , Doença de Alzheimer/genética , Doença de Alzheimer/prevenção & controle , Apolipoproteínas E/genética , Predisposição Genética para Doença/genética , Polimorfismo Genético/genética , Regiões Promotoras Genéticas/genética , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Feminino , Frequência do Gene/genética , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances
19.
Neurosci Lett ; 326(3): 187-90, 2002 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-12095653

RESUMO

Several polymorphisms in the apolipoprotein E (APOE) promoter region have been recently described. Of interest, APOE gene expression is increased in association with the -491AT polymorphism T-allele and decreased in relation to the Th1/E47cs polymorphism G-allele. In the present study we have investigated both polymorphisms in a series of 183 Alzheimer disease (AD) patients and 169 controls divided into age at onset/age dependent subgroups and the data obtained have been corrected for the presence of both expression-changing alleles in APOE homozygous individuals. Subsequently, the associations among APOE promoter polymorphisms, APOE4, and AD were assessed by chi-square and logistic regression analyses. Significantly, patients whose age at onset of AD was 80 years or more showed an association between the Th1/E47cs-G allele and AD that was independent of the APOE4 allele.


Assuntos
Doença de Alzheimer/genética , Apolipoproteínas E/genética , Polimorfismo Genético , Regiões Promotoras Genéticas , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
20.
Rev. colomb. nefrol. (En línea) ; 5(2): 127-136, jul.-dic. 2018. graf
Artigo em Espanhol | LILACS, COLNAL | ID: biblio-1093014

RESUMO

Resumen Antecedentes: existe actualmente un interés creciente, a nivel mundial, por las posibilidades que ofrece la hemodiálisis domiciliaria, la cual se encuentra más extendida en países del norte de Europa, Canadá, Reino Unido, Estados Unidos, Australia y Nueva Zelanda. En España, ha crecido de manera muy lenta, excepto en determinadas regiones como la provincia de Castellón, donde hemos puesto especial interés en la expansión de las técnicas dialíticas domiciliarias. Objetivo: describir la experiencia en el programa de hemodiálisis domiciliaria del Hospital General de Castellón. Metodología: estudio descriptivo de los pacientes incluidos en el programa de hemodiálisis domiciliaria del Hospital General de Castellón, desde su inicio en enero del 2008 hasta diciembre del 2017. Resultados: en su conjunto, entrenamos a 41 pacientes, de los que 36 llegaron a hemodializarse en casa (régimen corto-diario). La edad de los pacientes era 58,3±13,4 años; y el índice de Charlson, 4,1±1,6. 62 % de los pacientes eran hombres, 25,6 % padecían diabetes mellitus; 15,4 % tenían diagnóstico de insuficiencia cardíaca y 32 % eran portadores de fístula de hemodiálisis. El 38,5 % de los pacientes en edad laboral estaba activo. Obtuvimos una supervivencia técnica considerando el evento muerte+fallo técnico, censurando el trasplante, del 79,4 % al año, 75,2 % a los 2 años y 42,1 % a los 5 años. En el análisis univariante, resultaron determinantes la edad, la presencia de diabetes mellitus y la presencia de insuficiencia cardíaca. En el análisis multivariante, solo se mantuvo la insuficiencia cardíaca. Las reducciones semanales de fósforo y beta-2-microglobulina fueron significativamente mayores con hemodiálisis corta diaria, en comparación con la hemodiafiltración on-line. La hemodiafiltración on-line fue superior en la reducción semanal a partir de los 17 800 daltons para la mioglobina. Conclusiones: la hemodiálisis domiciliaria es una técnica posible que ofrece al paciente una adecuada reinserción sociolaboral, buenos niveles de reducción semanal de toxinas urémicas y una aceptable supervivencia técnica en el tiempo.


Abstract Background: There is currently a growing interest, worldwide, for the possibilities offered by home hemodialysis, which is more widespread in northern European countries, Canada, the United Kingdom, the United States, Australia and New Zealand. In Spain, it has grown very slowly, except in certain regions such as the province of Castellón, where we have placed special interest in the expansion of home dialysis techniques. Objective: To describe the experience in the Home Hemodialysis program of the Hospital General de Castellón. Methodology: Descriptive study of the patients included in the home hemodialysis program of the Hospital General de Castellón, from its beginning in January 2008 to December 2017. Results: As a whole, we trained 41 patients, of whom 36 came to hemodialysis at home (short-day regimen). Age 58,3±13,4 years, Charlson index 4,1±1,6, 62 % men, 25,6 % with diabetes mellitus, 15,4 % with diagnosis of heart failure, 32 % with hemodialysis fistula, 38,5 % of working-age patients were active. We obtained a technical survival considering the event death+technical failure, censoring transplant of 79,4 % a year, 75,2 % at 2 years and 42,1 % at 5 years, resulting determinants of the event in the univariate analysis: age, presence of diabetes mellitus and presence of heart failure, and only heart failure in the multivariate. The weekly reductions of phosphorus and beta-2-microglobulin were significantly greater with daily short hemodialysis with respect to on-line haemodiafiltration. Being the on-line hemodiafiltration superior in the weekly reduction from the 17800 daltons of myoglobin. Conclusions: Home hemodialysis is a possible technique that offers the patient an adequate social-labor reintegration with good levels of weekly reduction of uraemic toxins and an acceptable technical survival over time.


Assuntos
Humanos , Masculino , Feminino , Hemodiálise no Domicílio , Avaliação Momentânea Ecológica , Espanha , Uremia
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