RESUMO
In this study, a novel electrochemical assay for determining 17-ß-estradiol (E2) was proposed. The approach involves modifying a glassy carbon electrode (GCE) with a nanocomposite consisting of α-Fe2O3 nanoparticles supported on carbon nanotubes (CNTs)-denoted as α-Fe2O3-CNT/GCE. The synthesis of the α-Fe2O3-CNT nanocomposite was achieved through a simple and cost-effective hydrothermal process. Morphological and chemical characterization were conducted using scanning electron microscopy (SEM), Raman spectroscopy, and energy-dispersive X-ray spectroscopy (EDX). The presence of the α-Fe2O3-CNT film on the GCE surface resulted in an enhanced electrochemical response to E2, preventing electrode surface fouling and mitigating the decrease in peak current intensity during E2 oxidation. These outcomes substantiate the rationale behind the GCE modification. After the optimization of experimental conditions, E2 was determined by the square wave voltammetry technique using 0.1 mol L-1 KCl solution (pH = 7.0) with 20% ethanol as a supporting electrolyte. A linear concentration range of 5.0-100.0 nmol L-1 and a low limit of detection of 4.4 nmol L-1 were obtained. The electroanalytical method using α-Fe2O3-CNT/GCE was applied for E2 determination in pharmaceutical, lake water, and synthetic urine samples. The obtained results were attested by recovery tests and by high-performance liquid chromatography as a comparative technique at a 95% confidence level. Thus, the developed electrochemical sensor is simple and fast to obtain, presents high accuracy, and is viable for determining E2 in routine analysis.
Assuntos
Leucemia Megacarioblástica Aguda , Humanos , Lactente , Proteínas de Fusão bcr-abl/genética , Leucemia Megacarioblástica Aguda/complicações , Leucemia Megacarioblástica Aguda/diagnóstico , Leucemia Megacarioblástica Aguda/genética , Proteínas de Fusão Oncogênica/genética , Proteínas Repressoras , Fatores de TranscriçãoRESUMO
An electrochemical sensor for simultaneous determination of Benserazide (BEZ) and levodopa (L-dopa) was successfully developed using a glassy carbon electrode (GCE) modified with multi-walled carbon nanotube and nitrogen-doped titanium dioxide nanoparticles (GCE/MWCNT/N-TiO2). Cyclic voltammetry and square wave voltammetry were employed to investigate the electrochemical behavior of different working electrodes and analytes. In comparison with unmodified GCE, the modified electrode exhibited better electrocatalytic activity towards BEZ and L-dopa and was efficient in providing a satisfactory separation for oxidation peaks, with a potential difference of 140 mV clearly allows the simultaneous determination of these compounds. Under the optimized conditions, linear ranges of 2.0-20.0 and 2.0-70.0 µmol L-1 were obtained for BEZ and L-dopa, respectively, with a limit of detection of 1.6 µmol L-1 for BEZ and 2.0 µmol L-1 for L-dopa. The method was applied in simultaneous determination of the analytes in pharmaceutical samples, and the accuracy was attested by comparison with HPLC-DAD as the reference method, with a relative error lower than 4.0%.
Assuntos
Nanotubos de Carbono , Nanotubos de Carbono/química , Levodopa , Benserazida , Eletrodos , Oxirredução , Técnicas Eletroquímicas/métodosAssuntos
Regulação Leucêmica da Expressão Gênica , Leucemia Promielocítica Aguda , Mutação , Proteínas de Neoplasias , Brasil , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/metabolismo , Masculino , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genéticaRESUMO
A depressão é atualmente um dos assuntos mais difundidos na sociedade. Trata-se de um quadro clínico que acomete milhões de pessoas no mundo inteiro todos os anos e seu diagnóstico é cada vez mais frequente. Nessa perspectiva, ela é tratada como um problema do campo médico e sua etiologia estaria associada à uma desordem neuroquímica. A psicanálise propõe outra alternativa que vai além da perspectiva biomédica. Nesse sentido, nos amparamos no ensino de Lacan e realizamos uma articulação precisa entre a tristeza e o desejo. Dessa maneira os estados depressivos seriam na verdade uma consequência da desorientação do sujeito em relação ao seu desejo. Essa direção se mostra precisa, pois nos fornece elementos para pensarmos o diagnóstico diferencial de melancolia e os estados depressivos que se apresentam sob esse quadro. Trata-se de uma situação em que ocorre o apagamento do desejo do sujeito em função da sua identificação com o objeto perdido. Essa perspectiva também nos permite pensar a depressão neurótica e situá-la como um recuo do sujeito diante do seu desejo que é suscitado pelo Outro. Por fim, a psicanálise nos mostra que a depressão enquanto entidade clínica não existe. Nessas coordenadas, os estados depressivos traduzem sempre uma posição do sujeito diante do objeto, que deve sempre ser analisada a partir da lógica pulsional.
Depression is currently one of the most widespread issues in society. It is a clinical picture that affects millions of people worldwide every year and its diagnosis is increasingly frequent. In this perspective, it is treated as a medical field problem and its etiology would be associated with a neuro-chemical disorder. Psychoanalysis proposes another alternative that goes beyond the biomedical perspective. In this sense, we rely on the teaching of Lacan and make a precise articulation between sadness and desire. In this way depressive states would in fact be a consequence of the subject disorientation in relation to his desire. This direction is precise, as it provides us with elements to think about the differential diagnosis of melancholia and the depressive states that appear under this condition. It is a situation in which the desire of the subject is erased due to its identification with the lost object. This perspective also allows us to think of neurotic depression and situate it as a retreat from the subject before his desire that is raised by the Other. Finally, psychoanalysis shows us that depression as a clinical entity does not exist. In these coordinates, depressive states always translate a position of the subject before the object, which must always be analyzed from the drive logic.
La depresión actualmente es uno de los temas más difundidos en la sociedad. Es un cuadro clínico que millones de personas sufren en todo el mundo todos los años y su diagnóstico es cada día más frecuente. Bajo esa perspectiva, ella es tratada como un problema del campo médico, y su etiología estaría relacionada a un desorden neuroquímico. El psicoanálisis propone otra opción que va más allá de la perspectiva biomédica. En este sentido, tomamos por base la enseñanza de Lacan y realizamos una articulación precisa entre la tristeza y el deseo. De esa manera los estados depresivos serían, en verdad, una consecuencia de la desorientación del sujeto en relación a su deseo. Ese rumbo se presenta enfocado, dándonos elementos para pensar el diagnóstico deferencial de melancolía y los estados depresivos que se presentan bajo ese cuadro. Es una situación en la que ocurre la supresión del deseo del sujeto en función de su identificación con el objeto perdido. Esa perspectiva también nos permite pensar la depresión neurótica y ubicarla como un retroceso del sujeto ante su deseo que es provocado por el Otro. Por fin, el psicoanálisis nos muestra que la depresión mientras entidad clínica no existe. En estas coordenadas, los estados depresivos siempre traducen una posición del sujeto ante el objeto, que debe ser siempre analizada a partir de la lógica pulsional.
La dépression est actuellement l'un des problèmes les plus diffusés dans la société. C'est un tableau clinique qui touche des millions de personnes dans le monde entier et dont le diagnostic est de plus en plus fréquent à chaque année. Dans cette perspective, elle est traitée comme un problème médical et sa cause pourrait être associée à un trouble neurochimique. La psychanalyse propose une autre alternative qui dépasse la perspective biomédicale. En ce sens, on s'appuie sur l'enseignement de Lacan et on a fait une articulation précise entre la tristesse et le désir. De cette manière, les états dépressifs seraient en réalité une conséquence de la désorientation du sujet par rapport à son désir. Cette direction se montre précise car elle fournit des éléments de réflexion sur le diagnostic différentiel de la mélancolie et des états dépressifs qui apparaissent sous ce tableau clinique. Il s'agit d'une situation dans laquelle il y a l'effacement du désir du sujet à cause de son identification avec l'objet perdu. Cette perspective permet aussi de penser à la dépression névrotique, bien comme de la situer comme un retrait du sujet avant son désir, qui est suscité par l'Autre. Finalement, la psychanalyse montre que la dépression en tant qu'entité clinique n'existe pas. Dans ces coordonnées, les états dépressifs traduisent toujours une position du sujet devant l'objet, qui doit toujours être analysée à partir de la logique instinctif.
RESUMO
BACKGROUND: Myelodysplastic syndrome (MDS) is rare in the pediatric age group and it may be associated with inheritable bone marrow failure (BMF) such as Fanconi anemia (FA). FA is a rare multi-system genetic disorder, characterized by congenital malformations and progressive BMF. Patients with FA usually present chromosomal aberrations when evolving to MDS or acute myeloid leukemia (AML). Thus, the cytogenetic studies in the bone marrow (BM) of these patients have an important role in the therapeutic decision, mainly in the indication for hematopoietic stem cell transplantation (HSCT). The most frequent chromosomal alterations in the BM of FA patients are gains of the chromosomal regions 1q and 3q, and partial or complete loss of chromosome 7. However, the significance and the predictive value of such clonal alterations, with respect to malignant progress, are not fully understood and data from molecular cytogenetic studies are very limited. CASE PRESENTATION: A five-year-old boy presented recurrent infections and persistent anemia. The BM biopsy revealed hypocellularity. G-banding was performed on BM cells and showed a normal karyotype. The physical examination showed to be characteristic of FA, being the diagnosis confirmed by DEB test. Five years later, even with supportive treatment, the patient presented severe hypocellularity and BM evolution revealing megakaryocyte dysplasia, intense dyserythropoiesis, and 11% myeloblasts. G-banded analysis showed an abnormal karyotype involving a der(9)t(9;11)(p24;q?22). The FISH analysis showed the monoallelic loss of ATM and KMT2A genes. At this moment the diagnosis was MDS, refractory anemia with excess of blasts (RAEB). Allogeneic HSCT was indicated early in the diagnosis, but no donor was found. Decitabine treatment was initiated and well tolerated, although progression to AML occurred 3 months later. Chemotherapy induction was initiated, but there was no response. The patient died due to disease progression and infection complications. CONCLUSIONS: Molecular cytogenetic analysis showed a yet unreported der(9)t(9;11)(p24;q?22),der(11)t(9;11)(p24;q?22) during the evolution from FA to MDS/AML. The FISH technique was important allowing the identification at the molecular level of the monoallelic deletion involving the KMT2A and ATM genes. Our results suggest that this chromosomal alteration conferred a poor prognosis, being associated with a rapid leukemic transformation and a poor treatment response.
RESUMO
Myeloid neoplasms are a heterogeneous group of hematologic disorders with divergent patterns of cell differentiation and proliferation, as well as divergent clinical courses. Rare recurrent genetic abnormalities related to this group of cancers are associated with poor outcomes. One such abnormality is the MECOM gene rearrangement that typically occurs in cases with chromosome 7 abnormalities. MECOM encodes a transcription factor that plays an essential role in cell proliferation and maintenance and also in epigenetic regulation. Aberrant expression of this gene is associated with reduced survival. Hence, its detailed characterization provides biological and clinical information relevant to the management of pediatric myeloid neoplasms. In this work, we describe a rare karyotype harboring three copies of MECOM with overexpression of the gene in a child with a very aggressive myeloid neoplasm. Cytogenetic studies defined the karyotype as 46,XX,der(7)t(3;7)(q26.2;q21.2). Array comparative genomic hybridization (aCGH) revealed a gain of 26.04 Mb in the 3q26.2-3qter region and a loss of 66.6 Mb in the 7q21.2-7qter region. RT-qPCR analysis detected elevated expression of the MECOM and CDK6 genes (458.5-fold and 35.2-fold, respectively). Overall, we show the importance of performing detailed molecular cytogenetic analysis of MECOM to enable appropriate management of high-risk pediatric myeloid neoplasms.
Assuntos
Análise Citogenética/métodos , Proteína do Locus do Complexo MDS1 e EVI1/genética , Transtornos Mieloproliferativos/genética , Pré-Escolar , Feminino , HumanosRESUMO
Pediatric acute myeloid leukemia (AML) is a highly heterogeneous disease, presenting cytogenetic and molecular abnormalities which turned out to be critical prognostic factors. Ploidy changes as gain or loss of individual chromosomes are rare in AML, occurring only in about 1-2% of the affected children. Hyperdiploid karyotypes are exceedingly rare in infants less than 12 months of age. In this age group, structural rearrangements involving the KMT2A gene occur in about 58% of the cases. Among them, the translocation t(9;11)(p22;q23), KMT2A-MLLT3, is the most common abnormality accounting for approximately 22% of KMT2A rearrangements in infant AML cases. Here, we describe a 7- month-old girl with a history of fever and severe diarrhea, and a physical examination remarkable for pallor and hepatosplenomegaly. A novel complex hyperdiploid karyotype 53,XX,+X,+6,t(9;11)(p21.3;q23.3),+der(9)t(9;11)(p21.3;q23.3),dup(13)(q31q34),+14,+19,+21,+22 was characterized by high-resolution molecular cytogenetic approaches. Fluorescence in situ hybridization, multiplex-FISH, and multicolor chromosome banding were applied, revealing 2 reverse MLLT3-KMT2A fusions and a duplication of the GAS6 oncogene. Our work suggests that molecular cytogenetic studies are crucial for the planning of a proper strategy for risk therapy in AML infants with hyperdiploid karyotypes.
Assuntos
Duplicação Cromossômica , Análise Citogenética/métodos , Diploide , Peptídeos e Proteínas de Sinalização Intercelular/genética , Cariótipo , Leucemia Mieloide Aguda/genética , Proteínas Nucleares/genética , Oncogenes , Feminino , Rearranjo Gênico , Histona-Lisina N-Metiltransferase/genética , Humanos , Lactente , Proteína de Leucina Linfoide-Mieloide/genética , Translocação GenéticaRESUMO
In pediatric acute leukemias, reciprocal chromosomal translocations frequently cause gene fusions involving the lysine (K)-specific methyltransferase 2A gene (KMT2A, also known as MLL). Specific KMT2A fusion partners are associated with the disease phenotype (lymphoblastic vs. myeloid), and the type of KMT2A rearrangement also has prognostic implications. However, the KMT2A partner gene cannot always be identified by banding karyotyping. We sought to identify such partner genes in 13 cases of childhood leukemia with uninformative karyotypes by combining molecular techniques, including multicolor banding FISH, reverse-transcriptase PCR, and long-distance inverse PCR. Of the KMT2A fusion partner genes, MLLT3 was present in five patients, all with acute lymphoblastic leukemia, MLLT1 in two patients, and MLLT10, MLLT4, MLLT11, and AFF1 in one patient each. Reciprocal reading by long-distance inverse PCR also disclosed KMT2A fusions with PITPNA in one patient, with LOC100132273 in another patient, and with DNA sequences not compatible with any gene in three patients. The most common KMT2A breakpoint region was intron/exon 9 (3/8 patients), followed by intron/exon 11 and 10. Finally, multicolor banding revealed breakpoints in other chromosomes whose biological and prognostic implications remain to be determined. We conclude that the combination of molecular techniques used in this study can efficiently identify KMT2A fusion partners in complex pediatric acute leukemia karyotypes. Copyright © 2016 John Wiley & Sons, Ltd.
Assuntos
Histona-Lisina N-Metiltransferase/genética , Leucemia Mieloide Aguda/genética , Proteína de Leucina Linfoide-Mieloide/genética , Proteínas de Fusão Oncogênica/genética , Criança , Pré-Escolar , Citogenética , Humanos , Lactente , Cariótipo , Leucemia Mieloide Aguda/enzimologia , Leucemia Mieloide Aguda/patologia , MasculinoRESUMO
O presente artigo procura conduzir uma análise e um debate com base nas críticas feitas à psicanálise, as quais se encontram presentes na primeira parte da obra O Livro Negro da Psicanálise - Viver e Pensar melhor sem Freud. Cotejamos essas críticas com a letra do texto freudiano com a finalidade de averiguar se as mesmas são pertinentes. Delimitou-se à primeira seção por ela ter capítulos que compreendem uma dimensão importante para a teoria e para a clínica psicanalítica: a noção de sexualidade, além de melhor apontar quais são os pressupostos clínicos e epistemológicos que sustentam a crítica à psicanálise.(AU)
This article tries to conduct an analysis and discussion from the psychoanalysis criticism which are present in the first part of the book The Black Book of Psychoanalysis - Living and Thinking better without Freud. It was used freudian text to reveal if those criticisms are relevant or not. It was delimited to the first section because those chapters are constituted with an important dimension to the psychoanalytic theory and to psychoanalytic clinic: the notion of sexuality,pointing out what are the best clinical and epistemological assumptions that sustain thepsychoanalysis review.(AU)
Este artículo busca conducir un análisis y una discusión a partir de las críticas hechas al psicoanálisis que están en la primera parte del trabajo El Libro Negro del Psicoanálisis -Vivir, pensar y estar mejor sin Freud. Comparamos estas críticas con la letra del texto freudiano con la finalidad de averiguar si estas críticas son válidas. Fue delimitadala primera sección pues ella contiene capítulos que dicen respeto de una dimensión importante para lateoría y práctica psicoanalítica: la noción de sexualidad,apuntando así cuales son los presupuestos clínicos y epistemológicos que sostien en la crítica al psicoanálisis.(AU)