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1.
Pulmonology ; 2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38182470

ABSTRACT

RATIONALE: The baseline value of eosinophils in peripheral blood (BEC) has been associated with different degrees of severity, prognosis and response to treatment in patients with bronchiectasis. It is not known, however, if this basal value remains constant over time. OBJECTIVES: The aim of this study was to assess whether the BEC remains stable in the long term in patients with bronchiectasis. METHODS AND MEASUREMENTS: Patients from the RIBRON registry of bronchiectasis diagnosed by computed tomography with at least 2 BEC measurements one year apart were included in the study. Patients with asthma and those taking anti-eosinophilic drugs were excluded. Reliability was assessed using the intra-class correlation coefficient (ICC). A patient with a BEC of at least 300 cells/uL or less than 100 cells/uL was considered eosinophilic or eosinopenic, respectively. Group changes over time were also calculated. MAIN RESULTS: Seven hundred and thirteen patients were finally included, with a mean age of 66.5 (13.2) years (65.8 % women). A total of 2701 BEC measurements were performed, with a median number of measurements per patient of 4 (IQR: 2-5) separated by a median of 12.1 (IQR: 10.5-14.3) months between two consecutive measurements. The ICC was good (>0.75) when calculated between two consecutive measurements (approximately one year apart) but had dropped significantly by the time of the next annual measurements. Similarly, the change from an eosinophilic or eosinopenic patient to a non-eosinophilic or non-eosinopenic patient, respectively, was less than 30 % during the first year with respect to the baseline value but was close to 50 % in later measurements. CONCLUSIONS: Given the significant changes observed in the baseline value of the BEC over time, its monitoring is necessary in patients with bronchiectasis in order to more reliably assess its usefulness.

2.
Nanotechnology ; 32(40)2021 Jul 14.
Article in English | MEDLINE | ID: mdl-34186516

ABSTRACT

The present study was aimed to develop nitrogen-doped nanostructured ZnO thin films. These films were produced in a sequential procedure involving the atomic layer deposition technique, and a hydrothermal process supported by microwave heating. Employing the atomic layer deposition technique, through self-limited reactions of diethylzinc (DEZn) and H2O, carried out at 3.29 × 10-4atm and 190 °C, a high-quality ZnO seed was grown on a Si (100) substrate, producing a textured film. In a second stage, columnar ZnO nanostructures were grown perpendicularly oriented to the silicon substrate on those films, using a solvothermal process in a microwave heating facility, employing Zn(NO3)2as zinc precursor, while hexamethylenetetramine (HMTA) was used to produce the bridging of Zn2+ions. The consequence of N-doping concentration on the physicochemical properties of ZnO thin films was studied. The manufactured films were structurally analyzed by scanning electron microscopy and x-ray diffraction. Also, x-ray photoelectron spectroscopy, Raman, and UV-vis spectroscopies were used to provide further insight on the effect of nitrogen doping. The N-doped films displayed textured wurtzite-like structures that changes their preferential growth from the (002) to the (100) crystallographic plane, apparently promoted by the increase of nitrogen precursor. It is also shown that nitrogen-doped films undergo a reduction in their bandgap, compared to ZnO. The methodology presented here provides a viable way to perform high-quality N-ZnO nanostructured thin films.

4.
Clin Oncol (R Coll Radiol) ; 33(8): e323-e330, 2021 08.
Article in English | MEDLINE | ID: mdl-33888381

ABSTRACT

AIMS: To retrospectively analyse the impact of prophylactic cranial irradiation (PCI) on survival and intracranial progression in patients with limited stage small cell lung cancer (LS-SCLC) in the modern era of widespread magnetic resonance imaging brain screening. MATERIALS AND METHODS: Patients with LS-SCLC treated within our network between 2009 and 2020 who responded to initial therapy were stratified by receipt of PCI and stage of disease. A propensity score match analysis was carried out for stage II-III patients. Overall and neurological survival were defined as time to death and presumed death due to uncontrolled intracranial disease, respectively. Brain metastasis-free survival and symptomatic brain metastasis-free survival were defined as freedom from intracranial progression and symptomatic intracranial progression, respectively. The effect of PCI on these outcomes was assessed using Kaplan-Meier and Cox proportional hazards models. RESULTS: In total, 243 (69.6%) of 349 patients received PCI. On multivariate analysis in the propensity matched stage II-III cohort, PCI was a significant predictor of improved neurological survival (hazard ratio 0.23, 95% confidence interval 0.08-0.65; P = 0.01), brain metastasis-free survival (hazard ratio 0.25, 95% confidence interval 0.12-0.51; P < 0.01) and symptomatic brain metastasis-free survival (hazard ratio 0.21, 95% confidence interval 0.08-0.55; P < 0.01), but not improved overall survival. Two-year neurological survival estimates within the propensity matched cohort were 96.8% (95% confidence interval 87.6-99.2%) with PCI and 77.2% (95% confidence interval 63.0-86.4%) without PCI and 1- and 2-year estimates of incidence of brain metastases were 3.9% (95% confidence interval 1.3-11.7%) and 11.7% (95% confidence interval 5.6-23.5%) in the PCI group and 31.6% (95% confidence interval 22.1-43.9%) and 40.4% (95% confidence interval 29.2-54.0%) in the no PCI group, respectively. CONCLUSIONS: In the modern era of magnetic resonance imaging screening, PCI was associated with reduced incidence of intracranial progression in patients with stage II-III LS-SCLC who respond to initial therapy. This, importantly, translated to a decreased risk of neurological death within our propensity matched cohort, without significant improvement in overall survival.


Subject(s)
Brain Neoplasms , Lung Neoplasms , Small Cell Lung Carcinoma , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/radiotherapy , Cranial Irradiation , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/radiotherapy , Magnetic Resonance Imaging , Retrospective Studies , Small Cell Lung Carcinoma/diagnostic imaging , Small Cell Lung Carcinoma/radiotherapy
5.
Brachytherapy ; 20(1): 104-111, 2021.
Article in English | MEDLINE | ID: mdl-32952053

ABSTRACT

PURPOSE: The Vienna and Venezia (Elekta) are hybrid intracavitary/interstitial brachytherapy (BT) applicators for cervical cancers unsuitable for intracavitary BT alone to improve target coverage or reduce critical organ dose. There is limited outcome data with the use of these applicators outside published experience of the EMBRACE group. We report feasibility and early outcomes with the use of these hybrid applicators at our institution. METHODS AND MATERIALS: Hybrid applicators were used to treat 61 patients with cervical cancer from November 2011 to December 2019. Indications for hybrid applicator use were involvement of the vagina in 10 patients (16%), residual central or parametrial disease in 46 patients (75%), and a narrow introitus in 5 patients (9%). Toxicities were graded using the CTCAE v4.0. Outcomes were assessed with the Kaplan-Meier method. RESULTS: Median follow-up was 16 months (IQR 9-32 mos). Median HRCTV volume was 31.6 cm3 (IQR 25-48 cm3). Median HRCTV D90 was 86.1 Gy (IQR 84.3-88.0 Gy). In 54 patients with follow-up PET/CT at 3 months, complete initial imaging response locally was seen in 46 patients.Estimated 12-month Kaplan-Meier overall survival, locoregional control, distant control, and recurrence-free survival estimates were 86.9%, 80.6%, 73.8%, and 65.9%, respectively. The 12-month incidence of Grade 3+ GI/GU chronic toxicities was 5.7%, consisting of vesicovaginal fistula, rectovaginal fistula, and ureterovesical fistula. CONCLUSIONS: Our single-institution data support the use of the hybrid applicators, as an alternative to traditional BT applicators when clinically warranted. Use of hybrid applicators is feasible with adequate coverage of disease in the vagina and parametrium.


Subject(s)
Brachytherapy , Uterine Cervical Neoplasms , Brachytherapy/methods , Chemoradiotherapy , Female , Humans , Positron Emission Tomography Computed Tomography , Radiotherapy Dosage , Uterine Cervical Neoplasms/radiotherapy
6.
Ann. intern. med ; 173(12): 989-1001, Dec. 15, 2020.
Article in English | BIGG - GRADE guidelines | ID: biblio-1146660

ABSTRACT

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease with an estimated prevalence of 1 in 5000 that is characterized by the presence of vascular malformations (VMs). These result in chronic bleeding, acute hemorrhage, and complications from shunting through VMs. The goal of the Second International HHT Guidelines process was to develop evidence-based consensus guidelines for the management and prevention of HHT-related symptoms and complications. The guidelines were developed using the AGREE II (Appraisal of Guidelines for Research and Evaluation II) framework and GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. The guidelines expert panel included expert physicians (clinical and genetic) in HHT from 15 countries, guidelines methodologists, health care workers, health care administrators, patient advocacy representatives, and persons with HHT. During the preconference process, the expert panel generated clinically relevant questions in 6 priority topic areas. A systematic literature search was done in June 2019, and articles meeting a priori criteria were included to generate evidence tables, which were used as the basis for recommendation development. The expert panel subsequently convened during a guidelines conference to conduct a structured consensus process, during which recommendations reaching at least 80% consensus were discussed and approved. The expert panel generated and approved 6 new recommendations for each of the following 6 priority topic areas: epistaxis, gastrointestinal bleeding, anemia and iron deficiency, liver VMs, pediatric care, and pregnancy and delivery (36 total). The recommendations highlight new evidence in existing topics from the first International HHT Guidelines and provide guidance in 3 new areas: anemia, pediatrics, and pregnancy and delivery. These recommendations should facilitate implementation of key components of HHT care into clinical practice.


Subject(s)
Humans , Telangiectasia, Hereditary Hemorrhagic/genetics , Telangiectasia, Hereditary Hemorrhagic/prevention & control , Vascular Malformations/genetics , Epistaxis/prevention & control , Gastrointestinal Hemorrhage/prevention & control , Nasal Mucosa
7.
Clin Transl Oncol ; 21(10): 1348-1356, 2019 Oct.
Article in English | MEDLINE | ID: mdl-30783917

ABSTRACT

BACKGROUND: Recently, the quantification of mitoses in cutaneous melanoma has been discharged from the main prognostic variables of the TNM classification. OBJECTIVE: To investigate the prognostic value of the presence of mitoses in primary cutaneous melanoma and to establish the number of mitoses per mm2 that may have prognostic significance. METHODS: A retrospective observational study was performed on 141 patients treated for cutaneous melanoma, who were assessed by the same pathologist, and who had a minimum follow-up of 2 years. Clinical, epidemiological, histopathological and follow-up variables were gathered and compared with the number of mitoses to distinguish the significance of differences by means of univariate, multivariate, and survival analyses. RESULTS: The cut-off level related to a better sensitivity and specificity was 1.50 mitoses per mm2. The presence of two or more mitoses/mm2 showed a better relationship with prognostic variables and both the overall and disease-free survival than the presence of 1 or more mitoses/mm2. This happens especially in melanomas thicker than 0.8 mm and it could affect the staging in cases with Breslow between 1 and 2 mm. CONCLUSIONS: A mitotic rate of two or more mitoses per mm2 in cutaneous melanoma should be considered as a more accurate prognostic factor than one or more mitoses per mm2, particularly in tumors equal or greater than 0.8 mm in thickness.


Subject(s)
Melanoma/mortality , Melanoma/pathology , Mitotic Index , Skin Neoplasms/mortality , Skin Neoplasms/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Analysis of Variance , Child , Disease-Free Survival , Female , Humans , Male , Middle Aged , Neoplasm Staging/standards , Prognosis , ROC Curve , Reference Values , Retrospective Studies , Sensitivity and Specificity , Sentinel Lymph Node Biopsy , Survival Analysis , Young Adult , Melanoma, Cutaneous Malignant
8.
J Intern Med ; 285(2): 223-231, 2019 02.
Article in English | MEDLINE | ID: mdl-30191646

ABSTRACT

BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is a rare hereditary multisystem vascular disorder causing visceral arteriovenous malformations and mucocutaneous bleeding. Chronic gastrointestinal bleeding and epistaxis often produce profound anaemia refractory to conventional treatment. Bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody, may be effective in treatment of bleeding in HHT. METHODS: All HHT patients treated with systemic bevacizumab for chronic bleeding were selected for retrospective analysis. Data collected included demographics, baseline HHT characteristics, epistaxis grade, surgical interventions, bevacizumab dosing, adverse events, haemoglobin, red cell transfusions, intravenous iron infusions, and other anaemia and/or bleeding-directed therapies. RESULTS: Thirteen HHT patients were treated with bevacizumab for a median of 13.9 (range 4.9-30.1) months. Compared with pretreatment values, bevacizumab treatment increased the mean haemoglobin by 4.0 g dL-1 (95% CI, 2.6-5.3 g dL-1 ) [mean (95% CI) haemoglobin 8.5 (7.8, 9.9) g dL-1 vs. 12.5 (11.2, 13.7) g dL-1 , P < 0.001)], reduced red cell units transfused by 92% [median of 6 (range 0-59) units vs. 0 (range 0-15) units, P = 0.004] and reduced quantity of iron infused by 73% [mean (95% CI) 462 (257, 668) mg month-1 vs. 126 (75, 178) mg month-1 , P = 0.002]. Epistaxis control was achieved in 85% with bevacizumab versus 0% before treatment (P < 0.001). No patient required nasal or GI procedures during the maintenance period. Two patients (15%) developed grade 3 hypertension requiring medical management. CONCLUSION: Systemic bevacizumab was highly effective to treat chronic bleeding in HHT. Further study is needed to confirm the magnitude of benefit and further define optimal dosing, treatment duration and long-term safety.


Subject(s)
Bevacizumab/administration & dosage , Hemorrhage/drug therapy , Telangiectasia, Hereditary Hemorrhagic/drug therapy , Aged , Angiogenesis Inhibitors/administration & dosage , Chronic Disease , Dose-Response Relationship, Drug , Female , Follow-Up Studies , Hemoglobins/metabolism , Hemorrhage/blood , Hemorrhage/etiology , Humans , Infusions, Intravenous , Male , Middle Aged , Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors , Retrospective Studies , Telangiectasia, Hereditary Hemorrhagic/blood , Telangiectasia, Hereditary Hemorrhagic/complications , Treatment Outcome
9.
Rev. int. med. cienc. act. fis. deporte ; 16(62): 257-275, jun. 2016.
Article in Spanish | IBECS | ID: ibc-153356

ABSTRACT

En este artículo estudiamos la disputa epistemológica y pedagógica sobre la kinesiología/educación física que ha tenido lugar en las universidades de Estados Unidos desde 1990 hasta la actualidad. Hemos recogido el pensamiento de una muestra amplia de autores involucrados, con el propósito de obtener una visión de conjunto de un proceso que, de acuerdo con Morrow (2006), trata de esclarecer ¿de dónde venimos?, ¿qué somos?, ¿a dónde vamos? Tras el cotejo y análisis de la documentación más relevante concluimos que el periodo 1990-2013, caracterizado por una enconada pugna de paradigmas -en la que han estado implicados humanistas, positivistas, crosdisciplinaristas y subdisciplinaristas-, ha dado como resultado el dominio del paradigma integrador de Kretchmar (2007, 2008) (AU)


In this article we review the epistemological and pedagogical debate on Kinesiology and Physical Education that has been going on in the universities of the US from 1990 to the present. We have compiled the opinions of a wide sample of authors, with the intention of getting the most complete picture of a process that, according to Morrow (2006), seeks to answer the questions "where we come from, who we are, and where we are going". After comparing and analysing the most relevant documents, we conclude that the period 1990-2013, characterized by a bitter struggle between paradigms fought by humanists, positivists, cross-disciplinarists, and sub-disciplinarists, has revealed the eventual predominance of the integrative paradigm of Kretchmar (2007, 2008) (AU)


Subject(s)
Humans , Male , Female , Sports/education , Sports/physiology , Sports/history , Physical Education and Training/ethics , Physical Education and Training/methods , Teaching/methods , United States , Muscle Development/genetics , Sports/classification , Sports/standards , Physical Education and Training , Physical Education and Training/standards , Teaching/standards , United States/ethnology , Faculty/standards , Muscle Development/physiology
10.
Oncogene ; 35(47): 6143-6152, 2016 11 24.
Article in English | MEDLINE | ID: mdl-27132511

ABSTRACT

During the course of cancer progression, neoplastic cells undergo dynamic and reversible transitions between multiple phenotypic states, and this plasticity is enabled by underlying shifts in epigenetic regulation. Our results identified a negative feedback loop in which SET9 controls DNA methyltransferase-1 protein stability, which represses the transcriptional activity of the SET9 promoter in coordination with Snail. The modulation of SET9 expression in breast cancer cells revealed a connection with E2F1 and the silencing of SET9 was sufficient to complete an epigenetic program that favored epithelial-mesenchymal transition and the generation of cancer stem cells, indicating that SET9 plays a role in modulating breast cancer metastasis. SET9 expression levels were significantly higher in samples from patients with pathological complete remission than in samples from patients with disease recurrence, which indicates that SET9 acts as a tumor suppressor in breast cancer and that its expression may serve as a prognostic marker for malignancy.


Subject(s)
Biomarkers, Tumor , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Epigenesis, Genetic , Gene Expression Regulation, Neoplastic , Genes, Tumor Suppressor , Histone-Lysine N-Methyltransferase/genetics , Animals , Breast Neoplasms/mortality , Breast Neoplasms/therapy , Cell Line, Tumor , Cluster Analysis , DNA (Cytosine-5-)-Methyltransferase 1 , DNA (Cytosine-5-)-Methyltransferases/genetics , DNA (Cytosine-5-)-Methyltransferases/metabolism , Disease Models, Animal , Epithelial-Mesenchymal Transition/genetics , Female , Follow-Up Studies , Gene Expression Profiling , Humans , Kaplan-Meier Estimate , Models, Biological , Neoplasm Metastasis , Neoplasm Staging , Phenotype , Prognosis , Protein Binding , ROC Curve , Snail Family Transcription Factors/metabolism
11.
Cell Death Dis ; 7: e2180, 2016 Apr 07.
Article in English | MEDLINE | ID: mdl-27054335

ABSTRACT

Cancer is as much an epigenetic disease as it is a genetic disease, and epigenetic alterations in cancer often serve as potent surrogates for genetic mutations. Because the epigenetic factors involved in the DNA damage response are regulated by multiple elements, therapies to target specific components of the epigenetic machinery can be inefficient. In contrast, therapies aimed at inhibiting the methionine cycle can indirectly inhibit both DNA and protein methylation, and the wide variety of genes and pathways that are affected by these methylations make this global strategy very attractive. In the present study, we propose an adjuvant therapy that targets the epigenetics of the DNA damage response in breast cancer cells and that results in efficient apoptosis and a reduction in distant metastases in vivo. We observed that a combined therapy designed to uncouple adenosine metabolism using dipyridamole in the presence of a new synthetic antifolate, 3-O-(3,4,5-trimethoxybenzoyl)-(-)-catechin, simultaneously and efficiently blocked both the folic cycle and the methionine cycle in breast cancer cells and sensitized these cells to radiotherapy. The treatment impeded the recruitment of 53BP1 and BRCA1 to the chromatin regions flanking DNA double-strand breaks and thereby avoided the DNA damage responses in breast cancer cells that were exposed to ionizing radiation. In addition, this hypomethylating therapy was also efficient in reducing the self-renewal capability of breast cancer-initiating cells and induced reversion of mesenchymal phenotypes in breast cancer cells.


Subject(s)
DNA Repair , Epigenesis, Genetic , Animals , Apoptosis/drug effects , Apoptosis/radiation effects , BRCA1 Protein/metabolism , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Breast Neoplasms/radiotherapy , Cell Cycle Checkpoints/drug effects , Cell Cycle Checkpoints/radiation effects , Cell Line, Tumor , Chromatin/metabolism , DNA Breaks, Double-Stranded/drug effects , DNA Breaks, Double-Stranded/radiation effects , DNA Repair/drug effects , DNA Repair/radiation effects , Dipyridamole/metabolism , Female , Folic Acid Antagonists/pharmacology , Histones/metabolism , Humans , MCF-7 Cells , Methylation/drug effects , Methylation/radiation effects , Mice , Mice, Inbred BALB C , Protein-Arginine N-Methyltransferases/antagonists & inhibitors , Protein-Arginine N-Methyltransferases/genetics , Protein-Arginine N-Methyltransferases/metabolism , Repressor Proteins/antagonists & inhibitors , Repressor Proteins/genetics , Repressor Proteins/metabolism , Tumor Suppressor p53-Binding Protein 1/metabolism
12.
Rev. int. med. cienc. act. fis. deporte ; 16(61): 69-83, mar. 2016.
Article in Spanish | IBECS | ID: ibc-149748

ABSTRACT

Se realiza una revisión sobre el origen del juego de pelota mesoamericano en el preclásico temprano (ca.1.700-1.000 a.C.). Por la antigüedad propuesta para sus vestigios sobre el juego de pelota, son candidatos a ser los ‘creadores del juego’ las culturas de Paso de la Amada, los pre-olmecas de San Lorenzo y El Opeño. Los vestigios referidos son fundamentalmente, la cancha de Paso de la Amada, las pelotas de hule de Manatí y las figurillas de El Opeño. Se concluye que la gran cancha de Paso de la Amada, la mayor construcción de Mesoamérica de su tiempo, aparece como el vestigio más antiguo del juego, y se le relaciona con la aparición de la primera sociedad no igualitaria en Mesoamérica. Se sugiere que los pobladores de Paso de la Amada, hacia 1650 a.C., fueron los creadores del juego y no los olmecas como generalmente se ha defendido (AU)


We study here the origin of the Mesoamerican ballgame during the early formative period (ca. 1700 B.C.). We select as candidates for the creators of the Mesoamerican ballgame the cultures of Paso de la Amada, pre-Olmec at San Lorenzo, and El Opeño, as they have the oldest vestiges of the ballgame. These vestiges are, to be exact, a ball court at Paso de la Amada, some rubber balls at Manati, and ceramic figurines at El Opeño. We conclude that the great ball court at Paso de la Amada, the biggest building of Mesoamerica at that time, appears as the oldest vestige of the game and it is in relation with the emergence of ranked societies in Mesoamerica. We suggest that the people of Paso de la Amada, around 1650 BC, were the creators of the game, and not the Olmecs, as generally defended (AU)


Subject(s)
Humans , Sports/history , Competitive Behavior , Spain , Play and Playthings , Fitness Centers/history
13.
Child Abuse Negl ; 51: 379-89, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26318780

ABSTRACT

Different studies have related sexual and physical abuse during childhood and adolescence to the development of substance abuse disorders. Nevertheless, we are not aware of the role that other more common maltreatment types, such as neglect, will play among the most risky pattern of consumption: the polydrug use. A clinical sample of 655 adolescents, divided into two groups: polydrug users and non-polydrug users, were assessed on their pattern of drug consumption, history of childhood maltreatment, current psychopathology and their family history of alcoholism. Polydrug users had a greater prevalence of all types of maltreatment, although the most associated to this group were sexual abuse and emotional neglect. Other relevant variables to adolescent consumption were: the diagnosis of depressive disorder, the presence of anxiety traits and the family history of alcohol dependence. Polydrug users have higher risks of having had problems during infancy and adolescence, such as maltreatment and other psychopathological conditions, with the addition of family history of alcoholism. Accordingly, practitioners should take into account that those variables may influence polydrug abuse because it is the most risky pattern for subsequent dependence of substances, and they should always be considered during treatment.


Subject(s)
Child Abuse/psychology , Substance-Related Disorders/etiology , Adolescent , Adult Survivors of Child Abuse/psychology , Female , Humans , Male , Psychiatric Status Rating Scales , Spain
16.
Oncogene ; 34(2): 135-43, 2015 Jan 08.
Article in English | MEDLINE | ID: mdl-24469033

ABSTRACT

Cancer is characterized by uncontrolled cell growth and the acquisition of metastatic properties. In most cases, the activation of oncogenes and/or deactivation of tumour suppressor genes lead to uncontrolled cell cycle progression and inactivation of apoptotic mechanisms. Although the underlying mechanisms of carcinogenesis remain unknown, increasing evidence links aberrant regulation of methylation to tumourigenesis. In addition to the methylation of DNA and histones, methylation of nonhistone proteins, such as transcription factors, is also implicated in the biology and development of cancer. Because the metabolic cycling of methionine is a key pathway for many of these methylating reactions, strategies to target the epigenetic machinery of cancer cells could result in novel and efficient anticancer therapies. The application of these new epigenetic therapies could be of utility in the promotion of E2F1-dependent apoptosis in cancer cells, in avoiding metastatic pathways and/or in sensitizing tumour cells to radiotherapy.


Subject(s)
Genetic Therapy/methods , Neoplasms/genetics , Neoplasms/therapy , Animals , DNA Methylation , Epigenomics , Humans
17.
An. pediatr. (2003, Ed. impr.) ; 81(3): 155-160, sept. 2014. tab, graf
Article in Spanish | IBECS | ID: ibc-128042

ABSTRACT

INTRODUCCIÓN: Los beneficios de la leche donada frente a la fórmula artificial están demostrados, sin embargo no se conoce la influencia de la apertura de un banco de leche en la práctica clínica habitual. El objetivo de este estudio fue medir el impacto en la práctica clínica de la disponibilidad de leche donada para la nutrición de los prematuros ≤32 semanas de edad gestacional. MÉTODOS: Estudio antes-después de la apertura de un banco de leche. Se incluyeron los ≤32 semanas nacidos en el Hospital 12 de Octubre de julio-diciembre de 2005 y de enero-junio de 2008 (6 primeros meses tras la apertura del banco de leche). RESULTADOS: La apertura del banco de leche permitió empezar 31h antes (p < 0,001) la alimentación enteral, se alcanzaron 59,5h antes los 100ml/kg/día (p < 0,001) y 52h antes los 150ml/kg/día (p = 0,002), permitiendo retirar 72h antes la nutrición parenteral. En ningún prematuro se inició la alimentación enteral con fórmula artificial, la exposición a la misma en los primeros 15días de vida bajó del 50 al 16,6% y su consumo durante los primeros 28 días fue significativamente menor. La cantidad consumida de leche de la propia madre fue mayor, al igual que la tasa de lactancia materna exclusiva al alta (54 vs. 40%). CONCLUSIONES: Disponer de leche donada ha permitido avanzar más rápidamente con la nutrición enteral y retirar antes la nutrición parenteral. La exposición a fórmula artificial ha sido menor y mayor el consumo de leche de madre propia y la lactancia materna al alta


INTRODUCTION: The benefits of donor human milk compared with artificial formulas have been well demonstrated; nevertheless the impact in the clinical practice of opening a human milk bank within a neonatal unit has not yet been studied. The main aim of this study was to analyze the impact on the clinical practice of opening a human milk bank in a neonatal unit to provide donor human milk for preterm infants ≤32 weeks of gestational age. METHODS: A before and after study was designed, with the intervention being the opening a human milk bank. Preterm infants ≤32 weeks of gestational age born in the Hospital 12 Octubre from July to December 2005 and January to June 2008 (firsts 6 months after opening the human milk bank) were included. RESULTS: After opening the human milk bank, enteral feedings were started 31h before (P<0.001), 100ml/kg/day were achieved 59.5h before (P<0.001) and 150ml/kg/day 52h before (P=0.002). Enteral feedings were never started LM with artificial formula, the exposure to formula in the first 15 days of life was reduced from 50% to 16.6%, and it's consumption during the first 28 days of life was significantly reduced. There was a higher consumption of own mother's milk during the hospital stay, and a higher rate of exclusive breastfeeding at hospital discharge (54% vs 40%). CONCLUSIONS: The availability of donor human milk has led to quicker progression with enteral feedings and earlier withdrawal of parenteral nutrition. It has reduced the exposure to artificial formulas, and has also increased the intake of own mother's milk during the hospital stay and the rate of exclusive breastfeeding at hospital discharge


Subject(s)
Humans , Male , Female , Infant, Newborn , Milk Banks/organization & administration , Milk Banks/statistics & numerical data , Milk Banks/trends , Milk, Human/physiology , Antifungal Agents/therapeutic use , Milk Banks/standards , Milk Banks , Child Health Services/methods , Prospective Studies , Enteral Nutrition/methods , Breast Feeding/methods
18.
Animal ; 8(11): 1873-80, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25023391

ABSTRACT

There are important differences in terms of metabolic activity, energy utilization and capacity of protein and fat deposition when Iberian and modern pigs are compared. Primary culture of hepatocytes was used to evaluate hepatic function and sensitivity to hormones between breeds without the interference of circulating blood factors. Hepatocytes were isolated from pure Iberian (n=10) and Landrace (n=8) pigs of similar BW (24.5±12.1 and 32.9±6.1 kg BW, respectively), by collagenase perfusion. Monolayers were established in medium containing fetal bovine serum for 1 day and switched to serum-free medium for the remainder of the culture period. Hepatocytes were maintained in William's E supplemented with ß-mercaptoethanol (0.1 mM), glutamine (2 mM), antibiotics (gentamicin, penicillin, streptomycin and amphotericin B), dimethyl sulfoxide (1 µg/ml), dexamethasone (10-8 M), insulin (0.173 and 17.3 nM) and glucagon (0.287, 2.87 and 28.7 nM) for 24 to 48 h. Gluconeogenesis (GNG), glycogen degradation, triglycerides (TG) content and esterification, ß-hydroxybutyrate (BHB) synthesis, IGF-1 synthesis, albumin and urea synthesis were determined. Iberian pigs had greater capacity of GNG than Landrace (24%, P<0.05), although no difference in glycogen degradation was found (P>0.10). TG content and esterification tended to be lower in hepatocytes from Iberian compared with Landrace pigs (12% and 31%, respectively; 0.100.10). IGF-1 synthesis was diminished in hepatocytes from Iberian compared with Landrace pigs (16%, P<0.05). On the contrary, rate of albumin synthesis was greater in Iberian compared with Landrace pigs (58%, P<0.05). Finally, the capacity of urea synthesis was lower in hepatocytes of Iberian compared with Landrace pigs (37%, P<0.05). When ammonia was added to the media, urea concentration increased (648%, 1108% and 2791% when 0 mM was compared with 2.5, 5 and 10 mM, respectively). Urea synthesis increased on increasing ammonia content (55% and 325% when 0 mM was compared with 5 and 10 mM, respectively; P<0.0001). In conclusion, the genetic background accounts for important differences in protein and energy metabolism pathways found in primary culture of hepatocytes from lean and obese pigs.


Subject(s)
Adiposity , Body Weight , Hepatocytes/metabolism , Sus scrofa/metabolism , Animals , Breeding , Sus scrofa/genetics
19.
J Dairy Sci ; 97(8): 5151-66, 2014.
Article in English | MEDLINE | ID: mdl-24931534

ABSTRACT

Five mid-lactation multicatheterized Jersey cows were used in a 4×4 Latin square design to investigate whether the increase in milk N yield associated with diets rich in starch versus fiber could originate from changes in the splanchnic AA metabolism and if these changes depended upon the dietary crude protein (CP) content. Four isoenergetic diets were formulated to provide 2 different carbohydrate compositions [diets rich in starch (350g of starch and 310g of neutral detergent fiber/kg of dry matter) versus rich in fiber (45g of starch and 460g of neutral detergent fiber/kg of dry matter)] crossed by 2 different CP contents (12.0 vs. 16.5% CP). At the end of each treatment period, 6 hourly blood samples were collected from the portal and hepatic veins as well as the mesenteric artery to determine net nutrient fluxes across the portal-drained viscera (PDV), liver, and total splanchnic tissues. Dry matter and calculated energy intake as well as total absorbed energy were similar across treatments. However, the net portal appearance (NPA) of acetate, total volatile fatty acids, and ß-hydroxybutyrate were higher with diets rich in fiber versus starch, whereas that of oxygen, glucose, butyrate, and insulin were lower. Concomitant to these changes, the percentage of N intake recovered as total AA (TAA) in the portal vein was lower for diets rich in fiber versus starch (42.3 vs. 51.4%, respectively), without, however, any difference observed in the NPA of the main AA used as energy fuels by the PDV (Glu, Gln, and Asp). Despite a higher NPA of TAA with starch versus fiber diets, no differences in the net hepatic flux of TAA, essential and nonessential AA were observed, resulting in a higher (+22%) net splanchnic release of AA and, hence, a greater (+7%) milk N yield. The net hepatic flux and hepatic fractional removal of none of the individual AA was affected as the main carbohydrate changed from fiber to starch, except for Gly and Lys, which were higher for the latter. After correcting for differences in NPA of TAA, the net hepatic uptake of TAA tended to be lower with starch versus fiber diets. The higher transfer of N from feed to milk with diets rich in starch is not the consequence of a direct sparing AA effect of glucogenic diets but rather the result of lower energy requirements by the PDV along with a higher microbial N flow to the duodenum. A better AA use by peripheral tissues with starch versus fiber diets was also hypothesized but more studies are warranted to clarify this issue.


Subject(s)
Amino Acids/metabolism , Cattle/physiology , Diet/veterinary , Dietary Carbohydrates/administration & dosage , Dietary Proteins/administration & dosage , Starch/pharmacology , 3-Hydroxybutyric Acid/blood , Animals , Dietary Carbohydrates/pharmacology , Dietary Proteins/metabolism , Energy Intake , Fatty Acids, Volatile/blood , Female , Insulin/blood , Lactation , Liver/metabolism , Milk/chemistry , Portal Vein/metabolism , Splanchnic Circulation , Starch/administration & dosage , Starch/metabolism
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