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1.
Rev. int. androl. (Internet) ; 21(1): 1-6, ene.-mar. 2023. tab, graf
Artículo en Inglés | IBECS | ID: ibc-216602

RESUMEN

Introduction: Depression is not uncommon among infertile couples. The objective of the study is to analyze factors that predict depression in these couples, when they are in Assisted Reproduction Techniques programs. Materials and method: We analyze the level of depression in couples referred from the Human Reproduction Unit to study the male factor using the Beck Depression Inventory and the clinical information contained in the SARAplus program. Results: Depressive ranges appear in approximately half of the participants. The degree of depression correlates in a statistically significant way between both members of the couple. Among the analyzed clinical factors, we observed relational tendency between depression and obesity and depression and smoking. Conclusions: Depression in infertile couples is a fact. ART specialists should be on the lookout for symptoms of depression in order to provide patients psychological and psychiatric care and treatments, as part of the overall therapeutic framework for infertility. (AU)


Asunto(s)
Humanos , Masculino , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , Depresión/diagnóstico , Infertilidad/terapia , Encuestas y Cuestionarios , Técnicas Reproductivas Asistidas/psicología , Escalas de Valoración Psiquiátrica , Psicoterapia
2.
Rev Int Androl ; 21(1): 100324, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36273995

RESUMEN

INTRODUCTION: Depression is not uncommon among infertile couples. The objective of the study is to analyze factors that predict depression in these couples, when they are in Assisted Reproduction Techniques programs. MATERIALS AND METHOD: We analyze the level of depression in couples referred from the Human Reproduction Unit to study the male factor using the Beck Depression Inventory and the clinical information contained in the SARAplus program. RESULTS: Depressive ranges appear in approximately half of the participants. The degree of depression correlates in a statistically significant way between both members of the couple. Among the analyzed clinical factors, we observed relational tendency between depression and obesity and depression and smoking. CONCLUSIONS: Depression in infertile couples is a fact. ART specialists should be on the lookout for symptoms of depression in order to provide patients psychological and psychiatric care and treatments, as part of the overall therapeutic framework for infertility.


Asunto(s)
Depresión , Infertilidad , Humanos , Masculino , Depresión/diagnóstico , Infertilidad/terapia , Escalas de Valoración Psiquiátrica , Técnicas Reproductivas Asistidas/psicología , Psicoterapia
3.
Curr Bladder Dysfunct Rep ; 18(1): 10-15, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36466948

RESUMEN

Purpose of Review: No specific guidelines have been developed for acute cystitis management during the COVID-19 pandemic. This review aims to provide up-to-date information about treatment and follow-up in patients with symptoms suggesting lower urinary tract infection. Recent Findings: Uncomplicated cystitis does not need microbiological confirmation; thus, clinical diagnosis via telephone interview or questionnaires may be done. When complicated infections are suspected, in-person evaluation or close follow-up is mandatory. Antibiotic treatment is still the gold standard for treatment, although non-pharmacological strategies have also been suggested and further investigations are warranted. Summary: Urinary tract infections are still a frequent reason for consultation that needs to be addressed in both primary care and specialized levels. Their management during the pandemic is similar than in precedent years, but telehealth options have emerged which can facilitate diagnosis and treatment.

4.
Front Med (Lausanne) ; 8: 654847, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33829030

RESUMEN

Objective: We tested the hypothesis that an enhanced bowel preparation strategy (EBS) improves colonic cleansing in patients at high risk for inadequate bowel cleansing (HRI). Methods: This prospective randomized clinical trial included consecutive HRI patients referred for outpatient colonoscopy between February and October 2019. HRI was considered if patients scored >1.225 according to a previously validated bowel-cleansing predictive score. HRI patients were randomized (1:1) to a low-volume conventional bowel cleansing strategy (CBS) (1-day low residue diet (LRD) plus 2 L of polyethylene glycol (PEG) plus ascorbic acid) or to an EBS (3-day LRD plus 10 mg oral bisacodyl plus 4 L PEG). The Boston Bowel Preparation Scale (BBPS) was used to assess the quality of cleanliness. Intention-to-treat (ITT) and per protocol (PP) analyses were performed. A sample size of 130 patients per group was estimated to reach a 15% difference in favor of EBP. Results: A total of 253 HRI patients were included (mean age 69.8 ± 9.5 years, 51.8% women). No statistically significant differences were found in the BBPS scale between the two groups in the ITT analysis (CBS 76.8% vs. EBS 79.7%, P = 0.58) or PP analysis (CBS 78% vs. EBS 84.3%, P = 0.21), risk difference 2.9% (95% CI-7.26 to 39.16) in the ITT analysis, or risk difference 6.3% (95% CI-3.48 to 16.08) in PP analysis. No differences in preparation tolerance, compliance, adverse effects, or colonoscopy findings were found. Conclusion: EBS is not superior to CBS in hard-to-prepare patients. (EUDRACT: 2017-000787-15, NCT03830489). Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03830489.

5.
Gastroenterol Hepatol ; 44(3): 183-190, 2021 Mar.
Artículo en Inglés, Español | MEDLINE | ID: mdl-32948359

RESUMEN

BACKGROUND: Recent evidence suggests that the number of low residue diet (LRD) days does not influence the bowel cleansing quality in non-selected patients. However, there are not data in the subgroup of patients with risk factors of inadequate bowel cleansing. OBJECTIVE: The aim of this study was to assess whether a 3-day LRD improved the bowel cleansing quality in patients with risk factors of poor bowel cleansing. PATIENTS AND METHODS: Post hoc analysis of a randomized controlled trial carried out between December 2017 and March 2018 in a tertiary care hospital. Patients with high risk of poor bowel cleansing were selected following a validated score. The patients were randomized to the 1-day LRD or 3-day LRD groups. All patients received a 2-L split-dose of polyethylene glycol plus ascorbic acid. Intention-to-treat (ITT) and per-protocol (PP) analyses were conducted for the main outcome. RESULTS: 135 patients (1-day LRD group=67, 3-day LRD=68) were included. The rate of adequate cleansing quality was not significantly different between the groups in the ITT analysis: 76.1%, 95% CI: [64.6-84.8] vs. 79.4%, 95% CI: [68.2-87.4]; odds ratio (OR) 1.2, 95% CI [0.54-2.73]) or in the PP analysis: 77.3%, 95% CI: [65.7-85.8] vs. 80.3%, 95% CI: [69.0-88.3]; OR 1.2, 95% CI [0.52-2.77]). Compliance with the diet or cleansing solution, satisfaction or difficulties with the LRD and the polyp/adenoma detection rates were not significantly different. CONCLUSION: Our results suggest that 1-day LRD is not inferior to 3-day LRD in patients with risk factors of inadequate bowel cleansing.


Asunto(s)
Ácido Ascórbico/administración & dosificación , Catárticos/administración & dosificación , Colonoscopía , Dieta/métodos , Fibras de la Dieta , Polietilenglicoles/administración & dosificación , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cooperación del Paciente/estadística & datos numéricos , Periodo Preoperatorio , Estudios Prospectivos , Método Simple Ciego , Factores de Tiempo
6.
PLoS One ; 15(6): e0233967, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32497067

RESUMEN

Radiation-induced heart disease presents a significant challenge in the event of an accidental radiation exposure as well as to cancer patients who receive acute doses of irradiation as part of radiation therapy. We utilized the spontaneously hypertensive Wistar-Kyoto rat model, previously shown to demonstrate drug-induced cardiomyopathy, to evaluate the acute and long-term effects of sub-lethal total body gamma irradiation at two, four, and fifty-two weeks. We further examined irreversible oxidative protein carbonylation in the heart immediately following irradiation in the normotensive Wistar-Kyoto rat. Both males and females sustained weight loss and anemic conditions compared to untreated controls over a one-year period as reflected by reduced body weight and low red blood cell count. Increased inflammation was detected by elevated IL-6 serum levels selectively in males at four weeks. Serum cardiac troponin T and I analyses revealed signs of cardiomyopathy at earlier timepoints, but high variability was observed, especially at one year. Echocardiography at two weeks following 5.0Gy treatment revealed a significant decrease in cardiac output in females and a significant decrease in both diastolic and systolic volumes in males. Following 10.0Gy irradiation in the normotensive Wistar-Kyoto rat, the heart tissue showed an increase in total protein oxidative carbonylation accompanied by DNA damage indicated by an increase in γ-H2AX. Using proteomic analyses, we identified several novel proteins which showed a marked difference in carbonylation including those of mitochondrial origin and most notably, cardiac troponin T, one of the key proteins involved in cardiomyocyte contractility. Overall, we present findings of acute oxidative protein damage, DNA damage, cardiac troponin T carbonylation, and long-term cardiomyopathy in the irradiated animals.


Asunto(s)
Rayos gamma/efectos adversos , Corazón/efectos de la radiación , Oxidación-Reducción/efectos de la radiación , Carbonilación Proteica/efectos de la radiación , Proteínas/química , Animales , Femenino , Masculino , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Irradiación Corporal Total/efectos adversos
7.
Endoscopy ; 51(7): 628-636, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30943553

RESUMEN

BACKGROUND: The aim of this study was to assess whether a 3-day low-residue diet (LRD) improved bowel cleansing quality compared with a 1-day LRD regimen. METHODS: Consecutive patients scheduled for outpatient colonoscopy were randomized to the 1-day LRD or 3-day LRD groups. All patients received a 2-L split-dose of polyethylene glycol plus ascorbic acid. The primary outcome was bowel cleansing quality as evaluated using the Boston Bowel Preparation Scale (BBPS) (adequate cleansing ≥ 2 points per segment). Secondary outcomes were adherence to and level of satisfaction with the LRD, difficulty following the dietary recommendations, and willingness to repeat the same LRD in the future. Intention-to-treat (ITT) and per-protocol (PP) analyses were conducted for the primary outcome. A superiority analysis was performed to demonstrate that a 3-day LRD regimen was superior to a 1-day LRD regimen with a margin of 10 %. RESULTS: 390 patients (1-day LRD group = 196, 3-day LRD = 194) were included. The cleansing quality was not significantly different between the groups: ITT analysis 82.7 % (95 % confidence interval [CI] 77.4 to 88.0) vs. 85.6 % (95 %CI 80.7 to 90.5), with odds ratio (OR) 1.2 (95 %CI 0.72 to 2.15); PP analysis 85.0 % (95 %CI 79.9 to 90.1) vs. 88.6 % (95 %CI 84.0 to 93.2), with OR 1.4 (95 %CI 0.88 to 2.52). No differences were found regarding adherence to the diet or cleansing solution, satisfaction or difficulty with the LRD, and the polyp/adenoma detection rates. CONCLUSION: 3-day LRD did not offer advantages over 1-day LRD in preparation for colonoscopy.


Asunto(s)
Catárticos/farmacología , Colonoscopía/métodos , Neoplasias Colorrectales/diagnóstico , Dieta/métodos , Cooperación del Paciente , Polietilenglicoles/farmacología , Cuidados Preoperatorios/métodos , Colon , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Estudios Prospectivos , Tensoactivos/farmacología
8.
Endoscopy ; 49(6): 536-543, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28282690

RESUMEN

Background and study aim Inadequate bowel cleansing negatively affects the efficiency of colonoscopy in routine clinical practice. The aim of this study was to design and validate a predictive model for inadequate bowel cleanliness. Patients and methods The model was built from 667 consecutive outpatients (development cohort) who were prospectively scheduled for colonoscopy between June and September 2014. The validation cohort included 409 outpatients who underwent colonoscopy between October and December 2014. Cleansing was evaluated using the Boston Bowel Preparation Scale (BBPS). Bowel preparation was administered on the same day as the examination. Results In the development cohort, BBPS was adequate in 541 patients (81.1 %). At multivariate analysis, antidepressants (odds ratio [OR] 4.25, 95 % confidence interval [CI] 1.91 - 9.47), co-morbidity (OR 3.35, 95 %CI 2.16 - 5.18), constipation (OR 2.09, 95 %CI 1.29 - 3.40), and abdominal/pelvic surgery (OR 1.60, 95 %CI 1.03 - 2.47) were independent predictors for inadequate cleansing. The model built with these variables showed an area under the curve of 0.72 in the development cohort and 0.70 in the validation cohort. A cutoff of 1.225 predicted inadequate bowel preparation with a sensitivity, specificity, positive predictive value, and negative predictive value of 60.3 % (95 %CI 51.6 - 68.4), 75.4 % (95 %CI 71.6 - 78.9), 36.4 % (95 %CI 30.1 - 43.1), and 89.1 % (95 %CI 85.9 - 91.6) in the development cohort, and 50.0 % (95 %CI 38.1 - 61.9), 80.0 % (95 %CI 75.3 - 84.2), 35.7 % (95 %CI 26.4 - 45.6), and 87.9 % (95 %CI 83.7 - 91.3) in the validation cohort. Conclusion A simple score may assist the clinician in predicting which patients are at high risk of inadequate bowel cleanliness. This may guide changes in bowel preparation strategy accordingly.


Asunto(s)
Colonoscopía/normas , Neoplasias Colorrectales/diagnóstico por imagen , Abdomen/cirugía , Adulto , Anciano , Antidepresivos/uso terapéutico , Catárticos/uso terapéutico , Comorbilidad , Estreñimiento/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pelvis/cirugía , Valor Predictivo de las Pruebas , Curva ROC , Factores de Riesgo
9.
Am J Gastroenterol ; 112(6): 951-958, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28291237

RESUMEN

OBJECTIVES: Inadequate bowel cleansing is a major burden for endoscopy units. The aim of this study was to compare two intensive bowel cleansing regimens in patients with previous colonoscopy with inadequate bowel preparation. METHODS: Patients with inadequate cleansing at index colonoscopy were randomized to 4-L split-dose polyethylene-glycol (PEG) regimen vs. 2-L split-dose PEG plus ascorbic acid (PEG+Asc) regimen. All individuals underwent a 3-day low-residue diet and received 10 mg of bisacodyl, the day before colonoscopy. Cleansing was considered to be adequate if the Boston Bowel Preparation Scale scored ≥2 at each colonic segment. A non-inferiority analysis was performed to demonstrate that colonic cleansing with 2-L PEG+Asc was not inferior to 4-l PEG, considering a non-inferiority margin of 10%. RESULTS: Adequate bowel cleansing was significantly higher in patients assigned to 4-L PEG regimen (n=127) vs. those randomized to 2-L PEG+Asc regimen (n=129) by intention-to-treat analysis (81.1 vs. 67.4%, odds ratio (OR) 2.07, 95% confidence interval (CI) (1.163-3.689)) and by per-protocol analysis (86.6 vs. 71.7%, OR: 2.55, 95% CI: (1.316-4.922)). The study was terminated for futility after the interim analysis, because the 95% CI of the difference of proportions was 3.13-24.27% in the intention-to-treat analysis and 3.33-26.47% in the per-protocol analysis, confirming the superiority of 4-L PEG preparation. CONCLUSIONS: After 3-day low-residue diet and oral bisacodyl before colonoscopy, colon cleansing with 4-L split-dose PEG was superior to 2-L split-dose PEG+Asc in patients with previous inadequate cleansing. (EUDRACT: 2013-002506-31, NCT02073552).


Asunto(s)
Adenoma/diagnóstico , Catárticos/administración & dosificación , Pólipos del Colon/diagnóstico , Colonoscopía/métodos , Neoplasias Colorrectales/diagnóstico , Polietilenglicoles/administración & dosificación , Anciano , Ácido Ascórbico/administración & dosificación , Bisacodilo/administración & dosificación , Catárticos/efectos adversos , Ciego , Fibras de la Dieta/administración & dosificación , Terminación Anticipada de los Ensayos Clínicos , Femenino , Humanos , Análisis de Intención de Tratar , Intubación Gastrointestinal , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Polietilenglicoles/efectos adversos , Vitaminas/administración & dosificación
10.
Bol Asoc Med P R ; 107(2): 34-9, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26434081

RESUMEN

Sepsis is the combination of infection and physiological changes known as the systemic inflammatory response syndrome. There have been improvements in mortality rates and outcomes of septic patients based on "Surviving Sepsis Campaign" guidelines. Current management of sepsis at our Institution follows no specific mandatory protocols. This study aimed to verify the incidence and outcome of sepsis in Manati Medical Center, Puerto Rico. An observational retrospective study was conducted. All the Emergency Department admissions from May 1/ to October 31/ 2013 were screened for sepsis per ICD-9 code. For all included patients, demographic and clinical data at ED admission were collected. During this period 8931 patients were admitted and 148 met criteria for sepsis and related conditions. The overall mortality rate was 43.91%. Mortality increased with age, from 10.52% among ≤ 44 years old to 68.75% in those ≥ 85 years old. The main infection sources were respiratory (32.66%) and urinary tract (24.62%). Mean age among non-survivors was 10.8 years higher than the survivor group (95% Cl 5.2-1 6.5, p < 0.05). Multivariate analysis showed an increased fatality rate associated to severity of sepsis (HR 1.33; 95% Cl; 1.03-1.72, p = 0.02) and the APACHE2 score (HR 1.05; 95% Cl, 1.01-1.09 p = 0.03). Our data suggests that sepsis is an important problem to consider. We strongly encourage an institutional standardized protocol to diminish the mortality impact. Our results will allow adequate preventive strategies to improve early diagnosis, mortality rates and outcomes of septic patients.


Asunto(s)
Paquetes de Atención al Paciente , Sepsis/terapia , APACHE , Adulto , Anciano , Anciano de 80 o más Años , Comorbilidad , Manejo de la Enfermedad , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Adhesión a Directriz , Mortalidad Hospitalaria , Hospitales de Enseñanza/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/epidemiología , Insuficiencia Multiorgánica/etiología , Modelos de Riesgos Proporcionales , Puerto Rico/epidemiología , Estudios Retrospectivos , Sepsis/epidemiología , Choque Séptico/epidemiología , Choque Séptico/etiología , Factores Socioeconómicos , Adulto Joven
11.
Cancer Chemother Pharmacol ; 76(3): 447-59, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26108538

RESUMEN

PURPOSE: Chemotherapy with doxorubicin (Dox) causes dose-limiting cardiotoxicity. We investigated the role that gender has on cardiosensitivity to Dox treatment by evaluating reproductive hormone levels in male, castrated male (c-male), female and ovariectomized female (o-female) adult spontaneously hypertensive rats (SHRs) and expression of mitochondria-related genes in male and female adult SHRs. METHODS: SST-2 breast tumor-bearing SHRs were treated with saline, Dox, dexrazoxane (Drz) or both Dox and Drz and monitored for 14 days. Tumor size was used to monitor anticancer activity. Heart weight, cardiac lesion score and serum levels of cardiac troponin T (cTnT) were used to determine cardiotoxicity. Serum estradiol (E2) and testosterone were evaluated using electrochemiluminescence immunoassays. Expression of mitochondria-related genes was profiled in heart by MitoChip array analyses. RESULTS: Dox significantly reduced tumor volume (±Drz) and increased heart weight in all genders (13-30% vs. control). Higher heart lesion scores were observed in reproductively normal animals (male 2.9, female 2.2) than in hormone-deficient animals (c-male 1.7, o-female 1.9). Lesion score and cTnT inversely correlated with hormone levels. Reduced levels of both sex hormones were observed after Dox treatment. Gene expression analyses of Dox-treated hearts showed significant differential expression of oxidative stress genes in male hearts and apoptotic genes in both male and female hearts. CONCLUSIONS: Our results demonstrate that adult tumor-bearing male SHRs are more cardiosensitive to Dox than female or hormone-deficient animals. We provide evidence to suggest that reproductive hormones negatively regulate or are inhibited by Dox-induced cardiotoxicity and the selective cytotoxic mechanism likely functions through the greater activation of oxidative stress and apoptosis in male SHRs.


Asunto(s)
Doxorrubicina/farmacología , Hormonas Esteroides Gonadales/metabolismo , Cardiopatías/metabolismo , Hipertensión/metabolismo , Mitocondrias/genética , Animales , Apoptosis/fisiología , Doxorrubicina/toxicidad , Femenino , Expresión Génica/efectos de los fármacos , Cardiopatías/inducido químicamente , Hipertensión/inducido químicamente , Masculino , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Neoplasias Mamarias Experimentales/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Modelos Animales , Estrés Oxidativo/genética , Ratas , Ratas Endogámicas SHR , Factores Sexuales
12.
Oncotarget ; 5(6): 1526-37, 2014 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-24681637

RESUMEN

The interplay between oxidative stress and autophagy is critical for determining the fate of cancer cells exposed to redox-active and cytotoxic chemotherapeutic agents. Mitoquinone (MitoQ), a mitochondrially-targeted redox-active ubiquinone conjugate, selectively kills breast cancer cells over healthy mammary epithelial cells. We reported previously that MitoQ, although a derivative of the antioxidant ubiquinone, can generate excess ROS and trigger the Keap1-Nrf2 antioxidant response in the MDA-MB-231 cell line. Following MitoQ treatment, a greater number of cells underwent autophagy than apoptosis. However, the relationship between MitoQ-induced oxidative stress and autophagy as a primary cellular response was unclear. In this report, we demonstrate that MitoQ induces autophagy related gene 7 (Atg7)-dependent, yet Beclin-1-independent, autophagy marked by an increase in LC3-II. Both the ATG7-deficient human MDA-MB-231 cells and Atg7-knockout mouse embryonic fibroblasts exhibited lower levels of autophagy following MitoQ treatment than their respective wild-type counterparts. Increased apoptosis was confirmed in these autophagy-deficient isogenic cell line pairs, indicating that autophagy was attempted for survival in wild type cell lines. Furthermore, we observed higher levels of ROS in Atg7-deficient cells, as measured by hydroethidine oxidation. In Atg7-deficient cells, redox-sensitive Keap1 degradation was decreased, suggesting autophagy- and Atg7-dependent degradation of Keap1. Conversely, downregulation of Keap1 decreased autophagy levels, increased Nrf2 activation, upregulated cytoprotective antioxidant gene expression, and caused accumulation of p62, suggesting a feedback loop between ROS-regulated Keap1-Nrf2 and Atg7-regulated autophagy. Our data indicate that excessive ROS causes the upregulation of autophagy, and autophagy acts as an antioxidant feedback response triggered by cytotoxic levels of MitoQ.


Asunto(s)
Autofagia/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Compuestos Organofosforados/farmacología , Estrés Oxidativo/efectos de los fármacos , Ubiquinona/análogos & derivados , Enzimas Activadoras de Ubiquitina/metabolismo , Animales , Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis/antagonistas & inhibidores , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteína 7 Relacionada con la Autofagia , Beclina-1 , Western Blotting , Neoplasias de la Mama/metabolismo , Proliferación Celular/efectos de los fármacos , Femenino , Humanos , Técnicas para Inmunoenzimas , Péptidos y Proteínas de Señalización Intracelular/antagonistas & inhibidores , Péptidos y Proteínas de Señalización Intracelular/genética , Proteína 1 Asociada A ECH Tipo Kelch , Proteínas de la Membrana/antagonistas & inhibidores , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales Cultivadas , Ubiquinona/farmacología , Enzimas Activadoras de Ubiquitina/antagonistas & inhibidores , Enzimas Activadoras de Ubiquitina/genética
13.
PLoS One ; 8(8): e70575, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23940596

RESUMEN

Several front-line chemotherapeutics cause mitochondria-derived, oxidative stress-mediated cardiotoxicity. Iron chelators and other antioxidants have not completely succeeded in mitigating this effect. One hindrance to the development of cardioprotectants is the lack of physiologically-relevant animal models to simultaneously study antitumor activity and cardioprotection. Therefore, we optimized a syngeneic rat model and examined the mechanisms by which oxidative stress affects outcome. Immune-competent spontaneously hypertensive rats (SHRs) were implanted with passaged, SHR-derived, breast tumor cell line, SST-2. Tumor growth and cytokine responses (IL-1A, MCP-1, TNF-α) were observed for two weeks post-implantation. To demonstrate the utility of the SHR/SST-2 model for monitoring both anticancer efficacy and cardiotoxicity, we tested cardiotoxic doxorubicin alone and in combination with an established cardioprotectant, dexrazoxane, or a nitroxide conjugated to a triphenylphosphonium cation, Mito-Tempol (4) [Mito-T (4)]. As predicted, tumor reduction and cardiomyopathy were demonstrated by doxorubicin. We confirmed mitochondrial accumulation of Mito-T (4) in tumor and cardiac tissue. Dexrazoxane and Mito-T (4) ameliorated doxorubicin-induced cardiomyopathy without altering the antitumor activity. Both agents increased the pro-survival autophagy marker LC3-II and decreased the apoptosis marker caspase-3 in the heart, independently and in combination with doxorubicin. Histopathology and transmission electron microscopy demonstrated apoptosis, autophagy, and necrosis corresponding to cytotoxicity in the tumor and cardioprotection in the heart. Changes in serum levels of 8-oxo-dG-modified DNA and total protein carbonylation corresponded to cardioprotective activity. Finally, 2D-electrophoresis/mass spectrometry identified specific serum proteins oxidized under cardiotoxic conditions. Our results demonstrate the utility of the SHR/SST-2 model and the potential of mitochondrially-directed agents to mitigate oxidative stress-induced cardiotoxicity. Our findings also emphasize the novel role of specific protein oxidation markers and autophagic mechanisms for cardioprotection.


Asunto(s)
Autofagia/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Dexrazoxano/uso terapéutico , Compuestos Organofosforados/uso terapéutico , Piperidinas/uso terapéutico , Animales , Antioxidantes/uso terapéutico , Línea Celular Tumoral , Modelos Animales de Enfermedad , Femenino , Proteínas Asociadas a Microtúbulos/metabolismo , Mitocondrias Cardíacas/efectos de los fármacos , Mitocondrias Cardíacas/metabolismo , Oxidación-Reducción/efectos de los fármacos , Carbonilación Proteica/efectos de los fármacos , Ratas , Ratas Endogámicas SHR
14.
Nucleus ; 3(1): 60-76, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22540024

RESUMEN

In animal cells the nuclear lamina, which consists of lamins and lamin-associated proteins, serves several functions: it provides a structural scaffold for the nuclear envelope and tethers proteins and heterochromatin to the nuclear periphery. In yeast, proteins and large heterochromatic domains including telomeres are also peripherally localized, but there is no evidence that yeast have lamins or a fibrous nuclear envelope scaffold. Nonetheless, we found that the Lem2 and Man1 proteins of the fission yeast Schizosaccharomyces pombe, evolutionarily distant relatives of the Lap2/Emerin/Man1 (LEM) sub-family of animal cell lamin-associated proteins, perform fundamental functions of the animal cell lamina. These integral inner nuclear membrane localized proteins, with nuclear localized DNA binding Helix-Extension-Helix (HEH) domains, impact nuclear envelope structure and integrity, are essential for the enrichment of telomeres at the nuclear periphery and by means of their HEH domains anchor chromatin, most likely transcriptionally repressed heterochromatin, to the nuclear periphery. These data indicate that the core functions of the nuclear lamina are conserved between fungi and animal cells and can be performed in fission yeast, without lamins or other intermediate filament proteins.


Asunto(s)
Lámina Nuclear/metabolismo , Proteínas de Schizosaccharomyces pombe/metabolismo , Schizosaccharomyces/metabolismo , Animales , Microtúbulos/metabolismo , Membrana Nuclear/metabolismo , Transporte de Proteínas , Schizosaccharomyces/citología
15.
Gastroenterol. hepatol. (Ed. impr.) ; 33(4): 303-306, Abr. 2010. tab, ilus
Artículo en Español | IBECS | ID: ibc-84019

RESUMEN

El tumor fibroso solitario es un tumor raro de origen mesenquimal, de localización preferentemente en la pleura y las meninges, y menos frecuentemente se diagnostica como masa asintomática peritoneal hepática, en el páncreas o renal. Los hallazgos clínicos y radiológicos no son específicos, aunque nos permiten sospechar una evolución maligna por invasión o metástasis. Sin embargo, la citología preoperatoria suele ser de resultado dudoso o equívoco. Por tanto, el diagnóstico definitivo se logra tras la resección quirúrgica y el estudio mediante inmunohistoquímica con marcadores tales como CD34, vimentina y desmina. Presentamos un caso de tumor fibroso solitario de difícil diagnóstico, incluso tras una extensa serie de pruebas de imagen (AU)


Solitary fibrous tumor (SFT) is a rare neoplasm of mesenchymal origin. The most commonly reported locations are the pleura and meninges. Less frequently, SFT manifests as an asymptomatic mass in the pancreas, liver, peritoneum or kidney. Clinical and radiological findings have failed to provide any specific diagnostic pattern but allow malignant development to be suspected due to infiltration or metastasis. In addition, preoperative cytology often yields inconclusive or misleading results. Therefore the definitive diagnosis is achieved after both surgical resection and immunohistochemical analysis, with markers such as CD34, vimentin and desmin. We present a case of SFT, which was difficult to diagnose, even after an extensive battery of tests based on imaging techniques (AU)


Asunto(s)
Humanos , Masculino , Persona de Mediana Edad , Neoplasias Peritoneales/diagnóstico , Tumores Fibrosos Solitarios/diagnóstico , Antígenos CD34/análisis , Diagnóstico Diferencial , Hallazgos Incidentales , Laparoscopía , Tomografía Computarizada por Rayos X , Biomarcadores de Tumor/análisis , Endosonografía , Vimentina/análisis
16.
Gastroenterol Hepatol ; 33(4): 303-6, 2010 Apr.
Artículo en Español | MEDLINE | ID: mdl-20206414

RESUMEN

Solitary fibrous tumor (SFT) is a rare neoplasm of mesenchymal origin. The most commonly reported locations are the pleura and meninges. Less frequently, SFT manifests as an asymptomatic mass in the pancreas, liver, peritoneum or kidney. Clinical and radiological findings have failed to provide any specific diagnostic pattern but allow malignant development to be suspected due to infiltration or metastasis. In addition, preoperative cytology often yields inconclusive or misleading results. Therefore the definitive diagnosis is achieved after both surgical resection and immunohistochemical analysis, with markers such as CD34, vimentin and desmin. We present a case of SFT, which was difficult to diagnose, even after an extensive battery of tests based on imaging techniques.


Asunto(s)
Neoplasias Peritoneales/diagnóstico , Tumores Fibrosos Solitarios/diagnóstico , Antígenos CD34/análisis , Biomarcadores de Tumor/análisis , Diagnóstico Diferencial , Endosonografía , Humanos , Hallazgos Incidentales , Laparoscopía , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/análisis , Neoplasias Peritoneales/química , Neoplasias Peritoneales/diagnóstico por imagen , Neoplasias Peritoneales/cirugía , Tumores Fibrosos Solitarios/química , Tumores Fibrosos Solitarios/diagnóstico por imagen , Tumores Fibrosos Solitarios/cirugía , Tomografía Computarizada por Rayos X , Vimentina/análisis
17.
J Cell Sci ; 122(Pt 14): 2464-72, 2009 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-19571115

RESUMEN

The double lipid bilayer of the nuclear envelope (NE) remains intact during closed mitosis. In the fission yeast Schizosaccharomyces pombe, the intranuclear mitotic spindle has envelope-embedded spindle pole bodies (SPB) at its ends. As the spindle elongates and the nucleus divides symmetrically, nuclear volume remains constant but nuclear area rapidly increases by 26%. When Ran-GTPase function is compromised in S. pombe, nuclear division is strikingly asymmetrical and the newly synthesized SPB is preferentially associated with the smaller nucleus, indicative of a Ran-dependent SPB defect that interferes with symmetrical nuclear division. A second defect, which specifically influences the NE, results in breakage of the NE upon spindle elongation. This defect, but not asymmetric nuclear division, is partially rescued by slowing spindle elongation, stimulating endoplasmic reticulum (ER) proliferation or changing conformation of the ER membrane. We propose that redistribution of lipid within the ER-NE network is crucial for mitosis-specific NE changes in both open and closed mitosis.


Asunto(s)
Forma del Núcleo Celular , Retículo Endoplásmico/enzimología , Mitosis/fisiología , Membrana Nuclear/enzimología , Proteínas de Schizosaccharomyces pombe/metabolismo , Schizosaccharomyces/enzimología , Huso Acromático/enzimología , Proteína de Unión al GTP ran/metabolismo , Proteasas ATP-Dependientes/metabolismo , Membranas Intracelulares/enzimología , Lípidos de la Membrana/metabolismo , Proteínas Mitocondriales/metabolismo , Mutación , Proteínas Recombinantes de Fusión/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Schizosaccharomyces/genética , Schizosaccharomyces/crecimiento & desarrollo , Proteínas de Schizosaccharomyces pombe/genética , Serina Endopeptidasas/metabolismo , Temperatura , Factores de Tiempo , Proteína de Unión al GTP ran/genética
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