Asymmetric Wigner molecules in nanowire Y-junctions.

The possibility of crystalline states of interacting electrons, known as Wigner crystals, has been intensively studied in each of the three dimensions. One-dimensional (1D) systems, however, can be interconnected forming two-dimensional (2D) lattices, being a three-terminal Y-junction (Y-J) the simplest one. Then, even when electrons in the individual branches of the Y are confined in 1D, as the Y-J is in 2D, one could expect significant differences in the crystalline state of the electron gas in a Y-J. With the recent report of fabrication of defect-free GaAs/AlGaAs Y-Js by epitaxial methods, the study of semiconductor Y-Js acquires a special relevance due to its eventual direct exploration. Here, by considering the collective electron interactions using a Yukawa-like effective potential, we explore a two-electron distribution in nanowire Y-Js by modulating its electron density via a screening parameter. We find that the electrons changes from a quasi-continuous to a Wigner molecule-like distribution when the electron density decreases in the Y-J. In bold contrast to the strict 1D case, where equidistant distributions of equal density are obtained in the Wigner regime, in the Y-J equidistant distributions of asymmetric density are induced. We also explore the effect of an external electric field acting along the Y-axis on the asymmetric distributions.

Tunneling between parallel one-dimensional Wigner crystals.

Vertically aligned arrays are a frequent outcome in the nanowires synthesis by self-assembly techniques or in its subsequent processing. When these nanowires are close enough, quantum electron tunneling is expected between them. Then, because extended or localized electronic states can be established in the wires by tuning its electron density, the tunneling configuration between adjacent wires could be conveniently adjusted by an external gate. In this contribution, by considering the collective nature of electrons using a Yukawa-like effective potential, we explore the electron interaction between closely spaced, parallel nanowires while varying the electron density and geometrical parameters. We find that, at a low-density Wigner crystal regime, the tunneling can take place between adjacent localized states along and transversal to the wires axis, which in turn allows to create two- and three-dimensional electronic distributions with valuable potential applications.

Differential effect of high-fat, high-sucrose and combined high-fat/high-sucrose diets consumption on fat accumulation, serum leptin and cardiac hypertrophy in rats.

The consumption of high calorie-content diets is the first cause of obesity, probably the main health issue worldwide; however, the experimental evidences for evaluating the differential metabolic modifications of high-sucrose or high-fat diets are scare. We evaluated the metabolic outcomes of the obesity induced by the chronic consumption of high-sucrose (HS), high-fat (HF) or combined diets (HSHF), among the effect on the development of cardiac hypertrophy in Wistar rats. Rats from the HS, HF, and HSHS groups developed moderate obesity. Only the HS group showed increased triglycerides levels after four months. Increased leptin levels were observed in HS and HF groups without changes on cardiac hypertrophy; on the opposing, HSHF group presented hypertrophy without the changes in serum leptin. The three experimental groups showed a decreased expression of leptin receptors ObR-b. In our results, the kind of diet for the induction of obesity is relevant for the outcome of the pathological profile.

ACCIONES PARA DESARROLLAR LA INTERDISCIPLINARIEDAD DESDELA ASIGNATURA ANATOMÍA PATOLÓGICA

RESUMEN:El artículo es el resultado de una investigación efectuada con el objetivo de realizar una propuesta de acciones para contribuir al enfoque interdisciplinario en el proceso docente educativo de la asignatura Anatomía Patológica. La población estuvo conformada por el claustro de profesores de esta asignatura de la Universidad de Ciencias Médicas de Sancti Spíritus y un total de 217 estudiantes del segundo año de la carrera de Medicina, con una muestra intencional de 27 de estudiantes. Se aplicaron encuestas a docentes y estudiantes, se analizaron documentos y se propusieron varias acciones que fueron evaluadas por el comité de expertos las que fueron validadas.[AU]

BIOPSIA ASPIRATIVA CON AGUJA FINA Y SU CORRELACIÓN CON LAHISTOLOGÍA EN LAS PATOLOGÍAS TIROIDEAS

Introducción: La biopsia aspirativa con aguja fina (BAF) del tiroides es sugerida en la actualidad para la valoración inicial del nódulo tiroideo y de otras afecciones de la glándula tiroides. Objetivo: Determinar la efectividad de la biopsia aspirativa con aguja fina al relacionarla con el diagnóstico histológico del nódulo tiroideo en el Hospital Provincial Camilo Cienfuegos de Sancti Spíritus en el período enero 2011-diciembre 2014. Métodos: Se realizó un estudio descriptivo bajo un diseño no experimental de tipo transversal donde se revisaron citologías tiroideas. Resultados: Los resultados citológicos fueron comparados con los de las piezas quirúrgicas correspondientes. Se revisaron 164 citologías correspondientes a 164 pacientes. El 79.3porciento eran mujeres. Del total, el 1.2porciento fue informada como no útil, el 76.8porciento, como benigna, el 1.2porciento, como maligna y el 7.3porciento, como sospechosa. Los 164 pacientes fueron tiroidectomizados, confirmándose el diagnóstico de benignidad en el 89.1porciento de los casos y el de sospechoso para malignidad y malignidad en el 77.8porciento, todas las citologías insatisfactorias arrojaron resultados negativos en la pieza quirúrgica. Los falsos positivos fueron un 10.9porciento. Conclusiones: Se demostró que la BAAF es un procedimiento útil, efectivo y confiable en la evaluación preoperatoria de las patologías tiroideas.[AU]

RESULTADOS DEL MANEJO TERAPÉUTICO DE LAS LESIONESTRAUMÁTICAS DE LOS TENDONES FLEXORES DE LA MANO

Introducción: La lesión de los tendones flexores de la mano debe considerarse una verdadera urgencia quirúrgica. Se realizó un estudio observacional descriptivo de corte transversal.Objetivo: Evaluar los resultados y evolución de las lesiones traumáticas de los tendones flexores de la mano a las que se aplicó el manejo terapéutico propuesto por el autor en el Hospital General Provincial Camilo Cienfuegos desde enero 2013 a diciembre 2015.Métodos: La muestra quedó constituida por pacientes mayores de15 años con lesiones traumáticas de los tendones flexores de la mano a los que se aplicó el manejo terapéutico y fueron seguidos por el autor de la investigación durante el período analizado. Se utilizaron variables demográficas, tipo de lesión,localización de la lesión, lesiones asociadas, respuesta al tratamiento y complicaciones postoperatorias. Resultados: Con los datos obtenidos se confeccionó una base de datos lacual se analizó mediante el software estadístico SPSS.Conclusiones: Se concluyó que prevalecieron las heridas nítidas, con afectación de la Zona II, las cuales se asocian a lesiones de más de un dedo, existió una relación directa en cuanto al tipo de reparación según el tiempo y los resultados obtenidos dela misma.[AU]

Upregulation of NKG2D ligands and enhanced natural killer cell cytotoxicity by hydralazine and valproate.

Natural killer cells play a role in the immune antitumor response by recognizing and eliminating tumor cells through the engagement of NKG2D receptors with their ligands on target cells. This work aimed to investigate whether epigenetic drugs are able to increase MICA and MICB expression as well as NK cell cytotoxicity. Prostate, colon, breast and cervical cancer cell lines were analyzed for the expression of MICA and MICB at the mRNA and protein levels by RT-PCR, Western blot, flow cytometry and ELISA. The activating mark H3K4m2 at the MICA and MICB promoters was investigated by ChIP assays. Cytotoxicity of NK cells against the target epithelial cancer cells was investigated with the CD107 cytotoxicity assay. The results show that hydralazine and valproic acid not only increase the expression of MICA and MICB ligands of target cells, but also reduce their shedding to the supernatant. This upregulation occurs at the transcriptional level as revealed by increase of the H3K4 activating mark at the promoter of MICA and MICB genes. These effects are paralleled by increased cytotoxicity of NK cells, which was attenuated at different degrees by using blocking antibodies against the NKG2D receptor and ligands. In conclusion, our results demonstrate the ability of hydralazine and valproate to increase the NK activity against epithelial cancer cell lines and suggest that these drugs could reduce the levels of soluble MICA and MICB helping in avoiding tumor-induced suppression of NK cytotoxicity against the tumor.

Pharmacokinetics of hydralazine, an antihypertensive and DNA-demethylating agent, using controlled-release formulations designed for use in dosing schedules based on the acetylator phenotype.

PURPOSE: The antihypertensive hydralazine has recently been repositioned as DNA demethylating for the epigenetic therapy of cancer. As the acetylator phenotype is the key determinant of its plasma levels, the dose of hydralazine needs to be adjusted for the acetylation status of patients. METHODS: The pharmacokinetics of orally administered hydralazine was evaluated in 26 healthy volunteers (13 slow and 13 fast acetylators) after a single dose of 182 mg administered as a controlled-release tablet. Plasma levels of hydralazine were analyzed in 85 cancer patients treated with this formulation at a dose of 83 mg/day and 182 mg/day for slow and fast acetylators, respectively. RESULTS: The C(max) and t(max) of hydralazine for fast acetylators were 208.4 ± 56.9 SD ng/ml and 2.8 ± 2.5 h, respectively. The corresponding results for slow acetylators were 470.4 ± 162.8 ng/ml, and 4.4 ± 3.1 h. Healthy volunteers who were fast acetylators had no clinically significant changes in blood pressure and heart rate or any other side-effect, however, slow acetylators had transient episodes of headache, tachycardia and faintness. Among 85 cancer patients that received either 182 mg or 83 mg of hydralazine daily, according to their acetylator status, the mean concentrations of hydralazine in plasma were 239.1 ng/ml and 259.2 ng/ml for fast and slow acetylators, respectively. These differences were not significantly different, p = 0.3868. CONCLUSIONS: The administration of dose-adjusted controlled-release hydralazine according to the acetylation status of cancer patients yields similar levels of hydralazine.

Epigenetic therapy and cisplatin chemoradiation in FIGO stage IIIB cervical cancer.

INTRODUCTION: This trial aimed to evaluate the safety and efficacy of epigenetic therapy associated with cisplatin chemoradiation in FIGO Stage IIIB patients. METHODS: Hydralazine containing either 182 mg for rapid-, or 83 mg for slow acetylators and magnesium valproate were administered at 30 mg/kg tid. Both drugs were taken until intracavitary therapy was finished. Pelvic external beam radiation and low-dose rate brachytherapy were administered at a total cumulative dose to point A of at least 85 Gy. Weekly cisplatin at 40 mg/m2 was delivered for six cycles. RESULTS: Twenty-two patients were included and 18 (82%) patients completed treatment. Mean dose to point A was 84.6 + 2.2. Median number of cisplatin cycles was 5.5 (range, 1-6). Brachytherapy was delayed for technical reasons; the mean overall treatment time was 11.8 weeks. Grade 3 anemia, leucopenia, neutropenia, and thrombocytopenia were observed in 9%, 45%, 45%, and 9% of patients, respectively. CONCLUSIONS: Hydralazine and valproate are well-tolerated and safe when administered with cisplatin chemoradiation. Unfortunately, the suboptimal administration of brachytherapy for technical reasons in this study, precluded assessing the efficacy of epigenetic therapy. However, the tolerability of this regimen administered concurrent to radiation needs to be further tested.

Pharmacogenetics and pharmacoepigenetics of gemcitabine.

Gemcitabine (2',2'-difluoro 2'deoxycytidine, dFdC) is an analog of cytosine with distinctive pharmacological properties and a wide antitumor-activity spectrum. The pharmacological characteristics of gemcitabine are unique because two main classes of genes are essential for its antitumor effects: membrane transporter protein-coding genes, whose products are responsible for drug intracellular uptake, as well as enzyme-coding genes, which catalyze its activation and inactivation. The study of the pharmacogenetics and pharmacoepigenetics of these two gene classes is greatly required to optimize the drug's therapeutic use in cancer. This review aims to provide an update of genetic and epigenetic bases that may account for interindividual variation in therapeutic outcome exhibited by gemcitabine.

A phase II study of epigenetic therapy with hydralazine and magnesium valproate to overcome chemotherapy resistance in refractory solid tumors.

BACKGROUND: Epigenetic aberrations lead to chemotherapy resistance; hence, their reversal by inhibitors of DNA methylation and histone deacetylases may overcome it. PATIENTS AND METHODS: Phase II, single-arm study of hydralazine and magnesium valproate added to the same schedule of chemotherapy on which patients were progressing. Schedules comprised cisplatin, carboplatin, paclitaxel, vinorelbine, gemcitabine, pemetrexed, topotecan, doxorubicin, cyclophosphamide, and anastrozole. Patients received hydralazine at 182 mg for rapid, or 83 mg for slow, acetylators, and magnesium valproate at 40 mg/kg, beginning a week before chemotherapy. Response, toxicity, DNA methylation, histone deacetylase activity, plasma valproic acid, and hydralazine levels were evaluated. RESULTS: Seventeen patients were evaluable for toxicity and 15 for response. Primary sites included cervix (3), breast (3), lung (1), testis (1), and ovarian (7) carcinomas. A clinical benefit was observed in 12 (80%) patients: four PR, and eight SD. The most significant toxicity was hematologic. Reduction in global DNA methylation, histone deacetylase activity, and promoter demethylation were observed. CONCLUSIONS: The clinical benefit noted with the epigenetic agents hydralazine and valproate in this selected patient population progressing to chemotherapy' and re-challenged with the same chemotherapy schedule after initiating hydralazine and valproate' lends support to the epigenetic-driven tumor-cell chemoresistance hypothesis (ClinicalTrials.gov Identifier: NCT00404508).