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

RESUMO

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)


Assuntos
Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Depressão/diagnóstico , Infertilidade/terapia , Inquéritos e Questionários , Técnicas de Reprodução Assistida/psicologia , Escalas de Graduação Psiquiátrica , Psicoterapia
2.
Rev Int Androl ; 21(1): 100324, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36273995

RESUMO

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.


Assuntos
Depressão , Infertilidade , Humanos , Masculino , Depressão/diagnóstico , Infertilidade/terapia , Escalas de Graduação Psiquiátrica , Técnicas de Reprodução Assistida/psicologia , Psicoterapia
3.
Curr Bladder Dysfunct Rep ; 18(1): 10-15, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36466948

RESUMO

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.
Artigo em Inglês | MEDLINE | ID: mdl-33829030

RESUMO

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.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32948359

RESUMO

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.


Assuntos
Ácido Ascórbico/administração & dosagem , Catárticos/administração & dosagem , Colonoscopia , Dieta/métodos , Fibras na Dieta , Polietilenoglicóis/administração & dosagem , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente/estatística & dados numéricos , Período Pré-Operatório , Estudos Prospectivos , Método Simples-Cego , Fatores de Tempo
6.
PLoS One ; 15(6): e0233967, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32497067

RESUMO

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.


Assuntos
Raios gama/efeitos adversos , Coração/efeitos da radiação , Oxirredução/efeitos da radiação , Carbonilação Proteica/efeitos da radiação , Proteínas/química , Animais , Feminino , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Irradiação Corporal Total/efeitos adversos
7.
Endoscopy ; 51(7): 628-636, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30943553

RESUMO

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.


Assuntos
Catárticos/farmacologia , Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico , Dieta/métodos , Cooperação do Paciente , Polietilenoglicóis/farmacologia , Cuidados Pré-Operatórios/métodos , Colo , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Prospectivos , Tensoativos/farmacologia
8.
Endoscopy ; 49(6): 536-543, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28282690

RESUMO

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.


Assuntos
Colonoscopia/normas , Neoplasias Colorretais/diagnóstico por imagem , Abdome/cirurgia , Adulto , Idoso , Antidepressivos/uso terapêutico , Catárticos/uso terapêutico , Comorbidade , Constipação Intestinal/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pelve/cirurgia , Valor Preditivo dos Testes , Curva ROC , Fatores de Risco
9.
Am J Gastroenterol ; 112(6): 951-958, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28291237

RESUMO

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).


Assuntos
Adenoma/diagnóstico , Catárticos/administração & dosagem , Pólipos do Colo/diagnóstico , Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico , Polietilenoglicóis/administração & dosagem , Idoso , Ácido Ascórbico/administração & dosagem , Bisacodil/administração & dosagem , Catárticos/efeitos adversos , Ceco , Fibras na Dieta/administração & dosagem , Término Precoce de Ensaios Clínicos , Feminino , Humanos , Análise de Intenção de Tratamento , Intubação Gastrointestinal , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Polietilenoglicóis/efeitos adversos , Vitaminas/administração & dosagem
10.
Bol Asoc Med P R ; 107(2): 34-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26434081

RESUMO

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.


Assuntos
Pacotes de Assistência ao Paciente , Sepse/terapia , APACHE , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Gerenciamento Clínico , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Fidelidade a Diretrizes , Mortalidade Hospitalar , Hospitais de Ensino/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/epidemiologia , Insuficiência de Múltiplos Órgãos/etiologia , Modelos de Riscos Proporcionais , Porto Rico/epidemiologia , Estudos Retrospectivos , Sepse/epidemiologia , Choque Séptico/epidemiologia , Choque Séptico/etiologia , Fatores Socioeconômicos , Adulto Jovem
11.
Cancer Chemother Pharmacol ; 76(3): 447-59, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26108538

RESUMO

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.


Assuntos
Doxorrubicina/farmacologia , Hormônios Esteroides Gonadais/metabolismo , Cardiopatias/metabolismo , Hipertensão/metabolismo , Mitocôndrias/genética , Animais , Apoptose/fisiologia , Doxorrubicina/toxicidade , Feminino , Expressão Gênica/efeitos dos fármacos , Cardiopatias/induzido quimicamente , Hipertensão/induzido quimicamente , Masculino , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Modelos Animais , Estresse Oxidativo/genética , Ratos , Ratos Endogâmicos SHR , Fatores Sexuais
12.
Oncotarget ; 5(6): 1526-37, 2014 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-24681637

RESUMO

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.


Assuntos
Autofagia/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Compostos Organofosforados/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Ubiquinona/análogos & derivados , Enzimas Ativadoras de Ubiquitina/metabolismo , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/antagonistas & inibidores , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Proteína 7 Relacionada à Autofagia , Proteína Beclina-1 , Western Blotting , Neoplasias da Mama/metabolismo , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Técnicas Imunoenzimáticas , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteína 1 Associada a ECH Semelhante a Kelch , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas , Ubiquinona/farmacologia , Enzimas Ativadoras de Ubiquitina/antagonistas & inibidores , Enzimas Ativadoras de Ubiquitina/genética
13.
PLoS One ; 8(8): e70575, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23940596

RESUMO

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.


Assuntos
Autofagia/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Dexrazoxano/uso terapêutico , Compostos Organofosforados/uso terapêutico , Piperidinas/uso terapêutico , Animais , Antioxidantes/uso terapêutico , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Proteínas Associadas aos Microtúbulos/metabolismo , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/metabolismo , Oxirredução/efeitos dos fármacos , Carbonilação Proteica/efeitos dos fármacos , Ratos , Ratos Endogâmicos SHR
14.
Nucleus ; 3(1): 60-76, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22540024

RESUMO

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.


Assuntos
Lâmina Nuclear/metabolismo , Proteínas de Schizosaccharomyces pombe/metabolismo , Schizosaccharomyces/metabolismo , Animais , Microtúbulos/metabolismo , Membrana Nuclear/metabolismo , Transporte Proteico , Schizosaccharomyces/citologia
15.
Gastroenterol. hepatol. (Ed. impr.) ; 33(4): 303-306, Abr. 2010. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-84019

RESUMO

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)


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/diagnóstico , Tumores Fibrosos Solitários/diagnóstico , Antígenos CD34/análise , Diagnóstico Diferencial , Achados Incidentais , Laparoscopia , Tomografia Computadorizada por Raios X , Biomarcadores Tumorais/análise , Endossonografia , Vimentina/análise
16.
Gastroenterol Hepatol ; 33(4): 303-6, 2010 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-20206414

RESUMO

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.


Assuntos
Neoplasias Peritoneais/diagnóstico , Tumores Fibrosos Solitários/diagnóstico , Antígenos CD34/análise , Biomarcadores Tumorais/análise , Diagnóstico Diferencial , Endossonografia , Humanos , Achados Incidentais , Laparoscopia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/análise , Neoplasias Peritoneais/química , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Peritoneais/cirurgia , Tumores Fibrosos Solitários/química , Tumores Fibrosos Solitários/diagnóstico por imagem , Tumores Fibrosos Solitários/cirurgia , Tomografia Computadorizada por Raios X , Vimentina/análise
17.
J Cell Sci ; 122(Pt 14): 2464-72, 2009 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-19571115

RESUMO

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.


Assuntos
Forma do Núcleo Celular , Retículo Endoplasmático/enzimologia , Mitose/fisiologia , Membrana Nuclear/enzimologia , Proteínas de Schizosaccharomyces pombe/metabolismo , Schizosaccharomyces/enzimologia , Fuso Acromático/enzimologia , Proteína ran de Ligação ao GTP/metabolismo , Proteases Dependentes de ATP/metabolismo , Membranas Intracelulares/enzimologia , Lipídeos de Membrana/metabolismo , Proteínas Mitocondriais/metabolismo , Mutação , Proteínas Recombinantes de Fusão/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Schizosaccharomyces/genética , Schizosaccharomyces/crescimento & desenvolvimento , Proteínas de Schizosaccharomyces pombe/genética , Serina Endopeptidases/metabolismo , Temperatura , Fatores de Tempo , Proteína ran de Ligação ao GTP/genética
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