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1.
J Clin Ultrasound ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38872611

RESUMO

OBJECTIVE: The aim of this study was to evaluate the maternal and ultrasonographic characteristics of pregnant women who underwent cervical length (CL) measurement by transvaginal ultrasound between 11 and 13 + 6 weeks of gestation and who delivered at term or preterm. METHODS: A retrospective cohort study was carried out between March 2013 and December 2018 by analyzing ultrasound data of singleton pregnant women who underwent CL measurement by transvaginal ultrasound during the first trimester scan. CL was compared between the two groups (full-term and preterm birth [PB]) using Student's t-test. RESULTS: A total of 5097 pregnant women were enrolled, of whom 5061 (99.3%) had term and 36 (0.7%) had PB < 34 weeks. CL measurements did not differ between the term and preterm groups (36.62 vs. 37.83 mm, p = 0.08). Maternal age showed a significant and linear association with CL (r = 0.034, p = 0.012) and CRL (r = 0.086, p < 0.001). Smoking status was associated with shorter CL (36.64 vs. 35.09 mm, p = 0.003). When we analyzed the CL of the pregnant women in the term and preterm groups, according to the gestational age cut-offs for prematurity (28, 30, 32, and 34 weeks), we found that there was no significant difference between the measurements in all groups (p > 0.05). CONCLUSION: We observed no significant differences between CL measurements between 11 and 13 + 6 weeks in pregnant women who had preterm and term deliveries. Gestational age and CRL showed a significant and linear association with CL measurement.

2.
J Clin Ultrasound ; 52(6): 680-686, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38587238

RESUMO

OBJECTIVE: To evaluate the association between Doppler patterns in fetuses with Down syndrome (DS) and their placental histopathologic findings. METHODS: A retrospective cross-sectional study was performed by collecting data from medical records of singleton pregnancies between January 2014 and January 2022, whose fetuses had a confirmed diagnosis of DS either prenatally or postnatally. Placental histopathology, maternal characteristics, and prenatal ultrasound (biometric parameters and umbilical artery [UA] Doppler) were evaluated. RESULTS: Of 69 eligible pregnant women, 61 met the inclusion and exclusion criteria. In the sample, 15 fetuses had an estimated fetal weight < 10th percentile for gestational age (GA) and were considered small for gestational age (SGA). Thirty-eight fetuses had increased resistance on the UA Doppler. Histologic changes were detected in 100% of the placentas, the most common being delayed villous maturation, alterations associated with poor fetal vascular perfusion, and villous dysmorphism. More than 50% of the placentas showed alterations related to placental insufficiency. We did not observe a statistically significant association between UA Doppler examination and placental alterations. All placentas analyzed in the SGA subgroup showed findings compatible with placental insufficiency. CONCLUSION: We found no statistically significant association between placental histopathologic findings and UA Doppler abnormalities in fetuses with DS. The placental alterations identified were delayed villous maturation, alterations associated with poor fetal vascular perfusion, and villous dysmorphism.


Assuntos
Síndrome de Down , Placenta , Ultrassonografia Pré-Natal , Humanos , Feminino , Síndrome de Down/diagnóstico por imagem , Síndrome de Down/complicações , Síndrome de Down/fisiopatologia , Gravidez , Estudos Transversais , Estudos Retrospectivos , Ultrassonografia Pré-Natal/métodos , Adulto , Placenta/diagnóstico por imagem , Placenta/patologia , Placenta/irrigação sanguínea , Hemodinâmica/fisiologia , Ultrassonografia Doppler/métodos , Artérias Umbilicais/diagnóstico por imagem , Artérias Umbilicais/fisiopatologia , Feto/diagnóstico por imagem
3.
Twin Res Hum Genet ; 24(1): 37-41, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33745489

RESUMO

Selective intrauterine growth restriction (sIUGR) in monochorionic twin pregnancies is associated with greater morbidity and mortality for both fetuses when compared to singleton and dichorionic pregnancies. This retrospective cohort study aimed to assess the perinatal outcomes of monochorionic twin pregnancies affected by this disorder and conducted expectantly, by analyzing the results according to the end-diastolic flow in the umbilical artery Doppler of the smaller twin (type I: persistently forward/type II: persistently absent or reversed/type III: intermittently absent or reversed). Seventy-five monochorionic diamniotic twin pregnancies with sIUGR were included in this study. sIUGR was defined by estimated fetal weight below the 3rd centile for gestational age, or below the 10th centile, when associated with at least one of the following three criteria: abdominal circumference below the 10th percentile, umbilical artery pulsatility index of the smaller twin above the 95th percentile, or estimated fetal weight discordance of 25% or more. Perinatal outcomes were analyzed from the prenatal period to hospital discharge and included perinatal death, neurological injury, retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), and sepsis. The mortality rate was 1.33% in this cohort. The overall morbidity rate was lower in type I twin pregnancies. In conclusion, this study shows that sIUGR type I has lower morbidity than types II and III in expectant management.


Assuntos
Países em Desenvolvimento , Retardo do Crescimento Fetal , Estudos de Coortes , Feminino , Retardo do Crescimento Fetal/diagnóstico por imagem , Retardo do Crescimento Fetal/epidemiologia , Humanos , Recém-Nascido , Gravidez , Resultado da Gravidez , Gravidez de Gêmeos , Estudos Retrospectivos , Gêmeos Monozigóticos , Ultrassonografia Pré-Natal , Artérias Umbilicais/diagnóstico por imagem
4.
Prenat Diagn ; 40(3): 373-379, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31674030

RESUMO

OBJECTIVE: To identify antenatal predictors of adverse perinatal outcomes in a population of preterm fetuses with early placental insufficiency diagnosed by Doppler abnormalities. METHOD: In this cross-sectional study of a cohort of singleton pregnant women diagnosed with early placental insufficiency, relationships between perinatal variables (arterial and venous Doppler, gestational age, birth weight, oligohydramnios, estimated fetal weight, and fetal weight z-scores) and major neonatal complications were analyzed by logistic regression. RESULTS: Two hundred sixty-five women were delivered, between 24 and 33 weeks gestation. The overall frequency of intact survival was 57.9% (n = 154). Gestational age thresholds for best prediction of survival was 27 + 6 weeks and for intact survival was 29 + 0 weeks gestation. Fetal weight and absent/reversed ductus venosus a-wave were the main predictors of survival in the regression model. When fetal weight was substituted for fetal weight z-score, ductus venosus abnormal Doppler predicted mortality and absent or reversed umbilical artery diastolic velocities predicted intact survival. CONCLUSIONS: This study illustrates the impact of gestational age and fetal weight on perinatal outcomes in early placental insufficiency, with well-defined thresholds. Gestational age and fetal weight, or a combination of fetal weight z-scores and fetal Doppler parameters, were the best predictors of intact survival in our sample.


Assuntos
Retardo do Crescimento Fetal/diagnóstico por imagem , Peso Fetal , Idade Gestacional , Recém-Nascido Prematuro/fisiologia , Resultado da Gravidez , Ultrassonografia Pré-Natal , Adulto , Peso ao Nascer , Brasil , Estudos de Coortes , Estudos Transversais , Feminino , Retardo do Crescimento Fetal/mortalidade , Retardo do Crescimento Fetal/fisiopatologia , Peso Fetal/fisiologia , Humanos , Recém-Nascido , Insuficiência Placentária/diagnóstico por imagem , Insuficiência Placentária/fisiopatologia , Gravidez , Nascimento Prematuro/mortalidade , Nascimento Prematuro/fisiopatologia , Ultrassonografia Doppler , Artérias Umbilicais/diagnóstico por imagem
5.
N Engl J Med ; 375(24): 2321-2334, 2016 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-26943629

RESUMO

BACKGROUND: Zika virus (ZIKV) has been linked to central nervous system malformations in fetuses. To characterize the spectrum of ZIKV disease in pregnant women and infants, we followed patients in Rio de Janeiro to describe clinical manifestations in mothers and repercussions of acute ZIKV infection in infants. METHODS: We enrolled pregnant women in whom a rash had developed within the previous 5 days and tested blood and urine specimens for ZIKV by reverse-transcriptase-polymerase-chain-reaction assays. We followed women prospectively to obtain data on pregnancy and infant outcomes. RESULTS: A total of 345 women were enrolled from September 2015 through May 2016; of these, 182 women (53%) tested positive for ZIKV in blood, urine, or both. The timing of acute ZIKV infection ranged from 6 to 39 weeks of gestation. Predominant maternal clinical features included a pruritic descending macular or maculopapular rash, arthralgias, conjunctival injection, and headache; 27% had fever (short-term and low-grade). By July 2016, a total of 134 ZIKV-affected pregnancies and 73 ZIKV-unaffected pregnancies had reached completion, with outcomes known for 125 ZIKV-affected and 61 ZIKV-unaffected pregnancies. Infection with chikungunya virus was identified in 42% of women without ZIKV infection versus 3% of women with ZIKV infection (P<0.001). Rates of fetal death were 7% in both groups; overall adverse outcomes were 46% among offspring of ZIKV-positive women versus 11.5% among offspring of ZIKV-negative women (P<0.001). Among 117 live infants born to 116 ZIKV-positive women, 42% were found to have grossly abnormal clinical or brain imaging findings or both, including 4 infants with microcephaly. Adverse outcomes were noted regardless of the trimester during which the women were infected with ZIKV (55% of pregnancies had adverse outcomes after maternal infection in the first trimester, 52% after infection in the second trimester, and 29% after infection in the third trimester). CONCLUSIONS: Despite mild clinical symptoms in the mother, ZIKV infection during pregnancy is deleterious to the fetus and is associated with fetal death, fetal growth restriction, and a spectrum of central nervous system abnormalities. (Funded by Ministério da Saúde do Brasil and others.).


Assuntos
Sistema Nervoso Central/anormalidades , Morte Fetal , Retardo do Crescimento Fetal/virologia , Microcefalia/virologia , Complicações Infecciosas na Gravidez , Infecção por Zika virus/complicações , Zika virus/isolamento & purificação , Adolescente , Adulto , Encéfalo/anormalidades , Brasil/epidemiologia , Sistema Nervoso Central/embriologia , Feminino , Morte Fetal/etiologia , Retardo do Crescimento Fetal/epidemiologia , Feto/anormalidades , Idade Gestacional , Humanos , Pessoa de Meia-Idade , Gravidez , Nascimento Prematuro/epidemiologia , Ultrassonografia Pré-Natal , Adulto Jovem
6.
Twin Res Hum Genet ; 19(4): 389-92, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27321141

RESUMO

A dramatic increase in twin pregnancies has been observed in the past few decades, primarily related to assisted reproductive techniques (ART) and increased average maternal age during pregnancy. Multiple pregnancies, compared to singleton pregnancies, are associated with greater perinatal morbidity and mortality. The present study evaluated the perinatal outcomes of pregnancies with discordant anomalous twins in a tertiary maternity ward in a developing country. Data were retrospectively collected from the Instituto Fernandes Figueira/FIOCRUZ, Brazil between January 2002 and December 2014. We identified 74 twin pregnancies with discordant anomalous twins. Final data analysis was based on 40 pregnancies. Congenital defects were classified according to the International Classification of Diseases: ICD-10: the digestive system was responsible in 27 (34%) cases; the central nervous system was responsible in 18 (22%) cases; the urinary tract was responsible in 14 (17%) cases; and the circulatory system was responsible in 14 (17%) cases. A total of 19 deaths occurred during the study period, and delivery before 30.4 weeks was a significant prediction of fetal death (p = .01). The presence of hydrops in the affected fetus was related to a higher number of deaths in healthy fetuses and contributed to a worse prognosis. The presence of this condition was the cause of 12 (55.6%) deaths in healthy fetuses. A 10 times higher risk of death of a normal co-twin was observed in cases of death of the anomalous twin (p = .002, OR 10.55, 95% CI: 1.9-58.52).


Assuntos
Anormalidades Congênitas/etiologia , Gravidez de Gêmeos , Adolescente , Adulto , Brasil , Países em Desenvolvimento , Doenças em Gêmeos/epidemiologia , Doenças em Gêmeos/etiologia , Feminino , Morte Fetal , Humanos , Lactente , Morte do Lactente , Recém-Nascido , Idade Materna , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Adulto Jovem
7.
Adv Drug Deliv Rev ; 194: 114724, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36746307

RESUMO

The use of systemic anticancer chemotherapy is intrinsically limited by its toxicity. Whether dealing with small molecules or biopharmaceuticals, after systemic administration, small doses fail to reach effective intratumoral concentrations, while high doses with significant tumor inhibition effects may also drive the death of healthy cells, endangering the patients. Therefore, strategies based on drug delivery systems (DDSs) for avoiding the systemic toxicity have been designed. Due to their ability to protect drugs from early elimination and control drug release, DDSs can foster tumor exposure to anticancer therapeutics by extending their circulation time or steadily releasing drugs into the tumor sites. However, approval of tailored DDSs systems for clinical use is minimal as the safety and the in vivo activity still need to be ameliorated by manipulating their physicochemical characteristics. During the last few years, several strategies have been described to improve their safety, stability, and fine-tune pharmaceuticals release kinetics. Herein, we reviewed the main DDSs, namely polymeric conjugates, nano or microparticles, hydrogels, and microneedles, explored for long-acting anticancer treatments, highlighting recently proposed modifications and their potential advantages for different anticancer therapies. Additionally, important limitations of long-acting anticancer therapies and future technology directions were also covered.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológico , Polímeros/uso terapêutico
8.
Nurs Rep ; 13(2): 612-621, 2023 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-37092482

RESUMO

(1) Background: Sleep is considered to be a complex condition for human beings, with the aim of ensuring physical and psychological recovery. Technology, including the cell phone, is a tool for teenagers that ensures they are always available to interact, even at night. This study aims to understand the influence of the use of smartphones on adolescent sleep quality. (2) Methods: The guidelines proposed by the Joanna Briggs Institute were followed. The search was conducted in October 2022 through the EBSCOhost platform, with access to the CINAHL Complete and Medline databases and through the b-On database. (3) Results: The use of electronic equipment plays an important role in adolescents' lives. There is a negative relationship between the use of electronic equipment, such as smartphones, and sleep, for reducing both the quality and quantity of sleep. There is also a relationship between nighttime smartphone use, insufficient sleep, and mental health problems. (4) Conclusions: The use of new technologies at night causes a change in the behavior of adolescents with repercussions in terms of the quality of sleep and sleep duration and consequent well-being and performance during the day.

9.
Expert Opin Drug Discov ; 17(6): 569-580, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35343351

RESUMO

INTRODUCTION: Colorectal cancer (CRC) is one of the most common and deadly tumors worldwide. CRC in vitro and in vivo models that recapitulate key features of human disease are essential to the development of novel and effective therapeutics. However, two-dimensional (2D) in vitro culture systems are considered too simple and do not represent the complex nature of the human tumor. However, three-dimensional (3D) models have emerged in recent years as more advanced and complex cell culture systems, able to closely resemble key features of human cancer tissues. AREAS COVERED: The authors' review the currently established in vitro cell culture models and describe the advances in the development of 3D scaffold-free models to study CRC. The authors also discuss intestinal spheroids and organoids. As well as in vitro models for drug screening and metastatic CRC (mCRC). EXPERT OPINION: The ideal CRC in vitro model is not yet established. Spheroid-based 3D models represent one of the most used approaches to recapitulate the tumor environment, overcoming some limitations of 2D models. Mouse and patient-derived organoids are more advanced models that can mimic more closely the characteristics and properties of CRC, with the possibility of including cells derived from patients with metastatic CRC.


Assuntos
Neoplasias Colorretais , Organoides , Animais , Técnicas de Cultura de Células/métodos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Descoberta de Drogas/métodos , Avaliação Pré-Clínica de Medicamentos , Humanos , Camundongos , Esferoides Celulares
10.
Pharmaceutics ; 14(10)2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36297455

RESUMO

Antiglycolytic agents inhibit cell metabolism and modify the tumor's microenvironment, affecting chemotherapy resistance mechanisms. In this work, we studied the effect of the glycolytic inhibitors 3-bromopyruvate (3BP), dichloroacetate (DCA) and 2-deoxyglucose (2DG) on cancer cell properties and on the multidrug resistance phenotype, using lung cancer cells as a model. All compounds led to the loss of cell viability, with different effects on the cell metabolism, migration and proliferation, depending on the drug and cell line assayed. DCA was the most promising compound, presenting the highest inhibitory effect on cell metabolism and proliferation. DCA treatment led to decreased glucose consumption and ATP and lactate production in both A549 and NCI-H460 cell lines. Furthermore, the DCA pretreatment sensitized the cancer cells to Paclitaxel (PTX), a conventional chemotherapeutic drug, with a 2.7-fold and a 10-fold decrease in PTX IC50 values in A549 and NCI-H460 cell lines, respectively. To increase the intracellular concentration of DCA, thereby potentiating its effect, DCA-loaded poly(lactic-co-glycolic acid) nanoparticles were produced. At higher DCA concentrations, encapsulation was found to increase its toxicity. These results may help find a new treatment strategy through combined therapy, which could open doors to new treatment approaches.

11.
Int J Biol Macromol ; 221: 1618-1630, 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-35970371

RESUMO

Atherosclerosis represents one of the main causes of death in the Western world. It is a multifactorial pathology characterized by lesions that reduce the lumen of the vessels causing serious clinical events. The extra-domain B of fibronectin is overexpressed during angiogenesis and in tissues undergoing growth and extensive remodeling, i.e., atherosclerotic plaque. Bevacizumab is a recombinant humanized monoclonal antibody that can play a central role against angiogenesis reducing the risk associated with this process in atherosclerosis. In this work, an innovative nanosystem for the targeted delivery of bevacizumab to the atherosclerotic lesion is proposed. A production protocol for poly(lactic-co-glycolic acid)-polyethylene glycol nanoparticles loaded with bevacizumab and functionalized with immunouteroglobin-1 was designed. Once functionalized nanoparticles with immunouteroglobin-1 were produced, they were characterized in terms of morphology, mean diameter, ζ-potential, association and conjugation efficiencies, bevacizumab release profile, both in phosphate buffered saline and in serum, bevacizumab stability after release, cytocompatibility, and hemocompatibility. Nanoparticle mean diameter was in the range of 217-265 nm, their surface charge was between -22 and -8 mV, and the association and conjugation efficiencies of about 76 and 59 %, respectively. Fourier transform infrared spectroscopy analysis confirmed the functionalization of their surface with immunouteroglobin-1. In vitro assays showed that the studied nanoparticles were cytocompatible, once in contact with human endothelial and murine macrophage cell lines up to 72 h, and hemocompatible, once in contact with red blood cells, at different concentrations of encapsulated bevacizumab (0.1, 1, 10, and 100 µg/mL).


Assuntos
Aterosclerose , Nanopartículas , Humanos , Camundongos , Animais , Bevacizumab/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Nanopartículas/química , Polietilenoglicóis , Neovascularização Patológica , Tamanho da Partícula
12.
Adv Drug Deliv Rev ; 178: 113993, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34619286

RESUMO

In vitro cell-based models have been used for a long time since they are normally easily obtained and have an advantageous cost-benefit. Besides, they can serve a variety of ends, from studying drug absorption and metabolism to disease modeling. However, some in vitro models are too simplistic, not accurately representing the living tissues. It has been shown, mainly in the last years, that fully mimicking a tissue composition and architecture can be paramount for cellular behavior and, consequently, for the outcomes of the studies using such models. Because of this, 3D in vitro cell models have been gaining much attention, since they are able to better replicate the in vivo environment. In this review we focus on 3D models that contain mucus-producing cells, as mucus can play a pivotal role in drug absorption. Being frequently overlooked, this viscous fluid can have an impact on drug delivery. Thus, the aim of this review is to understand to which extent can mucus affect mucosal drug delivery and to provide a state-of-the-art report on the existing 3D cell-based mucus models.


Assuntos
Técnicas de Cultura de Células em Três Dimensões , Modelos Biológicos , Muco/citologia , Humanos , Muco/metabolismo
13.
Drug Deliv Transl Res ; 10(3): 826-837, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32207071

RESUMO

The clinical translation of the multiple pharmacological effects of resveratrol (RSV) found in preclinical studies has been impaired by its poor bioavailability, due to poor solubility and rapid metabolism and elimination. The inclusion of this molecule in medicines or functional food products will be ineffective unless suitable systems are developed. Zein protein may constitute an inexpensive, safe, and effective choice to produce nanoparticles (NPs) to incorporate hydrophobic molecules and overcome the bioavailability issues of RSV. In this work, we loaded RSV into zein NPs by using a nanoprecipitation method. Unloaded and RSV-loaded NPs presented average diameter values in the range of 120-180 nm, narrow size distribution (polydispersity index < 0.150), and zeta potential of around + 20 mV. The association efficiency of the drug was equal to or greater than 77% for different initial drug loads. Scanning electron microscopy imaging revealed that zein NPs were round-shaped and presented a smooth surface. Aqueous suspensions of zein NPs were stable for at least 1 month when stored at 4 °C. The freeze-drying of zein NPs using sucrose as cryoprotectant allowed an easy re-suspension of NPs in water without significantly changing the initial colloidal properties. RSV-loaded NPs presented low cytotoxicity to the human colorectal Caco-2 and HT29-MTX cell lines. Finally, permeability studies of RSV across Caco-2 and Caco-2/HT29-MTX evidenced some ability of zein NPs to protect RSV from metabolism events. However, further investigation is needed in order to confirm the possible role of zein NPs in the metabolic stability of RSV. Overall, zein NPs may present the potential to circumvent bioavailability issues of RSV. Graphical abstract.


Assuntos
Resveratrol/farmacologia , Zeína/química , Administração Oral , Disponibilidade Biológica , Células CACO-2 , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células HT29 , Humanos , Microscopia Eletrônica de Varredura , Nanopartículas , Tamanho da Partícula , Resveratrol/química , Resveratrol/farmacocinética
14.
Biomater Sci ; 8(13): 3720-3729, 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32500879

RESUMO

Colorectal cancer (CRC) is one of the most common and deadly cancers in the world, mainly due to its metastatic and metabolic ability. The CD44 receptor isoform containing exon 6 (CD44v6) is a transmembrane protein that plays an important role in the establishment of tumors and metastasis, which make this molecule a potential target for therapy and diagnosis of tumors. Aiming at a targeted therapy, the anti-VEGF monoclonal antibody (mAb) bevacizumab was loaded into poly(lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG) nanoparticles (NPs) functionalized with an antibody fragment (Fab) specific for CD44v6-expressing human cancer cells. The sizes of NPs were in the range of 150-250 nm and they had a negative charge between -5 and -10 mV, with an association efficiency (AE) of bevacizumab of 86%. v6 Fab-PLGA-PEG NPs containing bevacizumab specifically bonded to the CD44v6 cell surface receptor and exhibited higher internalization into CD44v6+ epithelial cells than bare and (-) Fab-PLGA-PEG NPs. To understand the biological effect of NP targeting, the intracellular levels of bevacizumab and VEGF were evaluated after the incubation of targeted and untargeted NPs. The intracellular levels of bevacizumab were significantly higher in cells incubated with v6 Fab-PLGA-PEG NPs and these NPs resulted in a significant decrease in the intracellular VEGF compared to untargeted NPs and free bevacizumab. PLGA-PEG NPs, surface-functionalized with a v6-specific Fab, have the potential to intracellularly deliver bevacizumab into CD44v6 expressing cancer cells.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Bevacizumab/farmacologia , Neoplasias do Colo/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Receptores de Hialuronatos/antagonistas & inibidores , Antineoplásicos Imunológicos/química , Bevacizumab/química , Materiais Biocompatíveis/química , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Portadores de Fármacos/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Receptores de Hialuronatos/metabolismo , Nanopartículas/química , Polietilenoglicóis/química , Células Tumorais Cultivadas
15.
Diagn Interv Radiol ; 24(2): 63-71, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29467113

RESUMO

PURPOSE: We aimed to evaluate the ADNEX MR scoring system for the prediction of adnexal mass malignancy, using a simplified magnetic resonance imaging (MRI) protocol. METHODS: In this prospective study, 200 patients with 237 adnexal masses underwent MRI between February 2014 and February 2016 and were followed until February 2017. Two radiologists calculated ADNEX MR scores using an MRI protocol with a simplified dynamic study, not a high temporal resolution study, as originally proposed. Sensitivity, specificity, positive and negative predictive values, likelihood ratios, and the area under the receiver operating characteristic curve were calculated (cutoff for malignancy, score ≥ 4). The reference standard was histopathologic diagnosis or imaging findings during >12 months of follow-up. RESULTS: Of 237 lesions, 79 (33.3%) were malignant. The ADNEX MR scoring system, using a simplified MRI protocol, showed 94.9% (95% confidence interval [CI], 87.5%-98.6%) sensitivity and 97.5% (95% CI, 93.6%-99.3%) specificity in malignancy prediction; it was thus highly accurate, like the original system. The level of interobserver agreement on simplified scoring was high (κ = 0.91). CONCLUSION: In a tertiary cancer center, the ADNEX MR scoring system, even based on a simplified MRI protocol, performed well in the prediction of malignant adnexal masses. This scoring system may enable the standardization of MRI reporting on adnexal masses, thereby improving communication between radiologists and gynecologists.


Assuntos
Anexos Uterinos/diagnóstico por imagem , Doenças dos Anexos/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Neoplasias Ovarianas/diagnóstico por imagem , Anexos Uterinos/anatomia & histologia , Anexos Uterinos/patologia , Doenças dos Anexos/patologia , Doenças dos Anexos/cirurgia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/normas , Variações Dependentes do Observador , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Valor Preditivo dos Testes , Estudos Prospectivos , Centros de Atenção Terciária
16.
Autoimmun Rev ; 5(5): 319-23, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16782556

RESUMO

Systemic lupus erythematosus (SLE) is a prototype of autoimmune disease which arises from interactions between susceptibility genes and environmental factors. Despite the heterogeneous manifestations in this disease, all SLE patients present plasma autoantibodies recognizing nuclear components. Thus, auto reactive B cells represent key effectors to be investigated. Human linkage analysis is providing the localization of susceptibility loci distributed in chromosomes contributing to elucidate the manner in which interactions between these loci mediate SLE pathogenesis. We associate the cDNA microarray technology to investigate the differential gene expression of CD19(+) B cells with genetic linkage data. Bioinformatics programs served to evidentiate the differentially expressed sequences and the design of the microarray allowed hierarchical clustering of patients and controls. Sequencing allowed the identification of 8 new gene products differentially expressed (ESTs) that were co-localized in SLE or other autoimmune diseases susceptibility loci on chromosome 1p21, 2q21, 13q33, 16p12.1 and 16q12.1. These findings strongly suggest that chromosomal regions previously identified as SLE susceptibility loci are in fact transcribed in CD19(+) B cells of patients. In this review, we delineate a new possibility for the use of cDNA microarrays in studies focusing the control of gene expression of disease susceptibility loci identified by genetic linkage.


Assuntos
Antígenos CD19/genética , Lúpus Eritematoso Sistêmico/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Antígenos CD19/imunologia , Expressão Gênica , Ligação Genética , Predisposição Genética para Doença , Humanos , Lúpus Eritematoso Sistêmico/imunologia
17.
BMC Microbiol ; 2: 14, 2002 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-12079503

RESUMO

BACKGROUND: Methods for the extraction of DNA from filamentous fungi are frequently laborious and time consuming because most of the available protocols include maceration in liquid nitrogen after the mycelium has been grown in a liquid culture. This paper describes a new method to replace those steps, which involves the growth of the mycelium on cellophane disks overlaid on solid medium and the use of glass beads for cell wall disruption. RESULTS: Extractions carried out by this method provided approximately 2 microg of total DNA per cellophane disk for the filamentous fungus Trichoderma reesei. To assess the DNA's quality, we made a PCR (Polymerase Chain Reaction) amplification of a gene introduced by a transformation in this fungus's genome (hph gene), with successful results. We also confirmed the quality of the DNA by the use of Southern blotting to analyze the presence of the same gene, which was easily detected, resulting in a sharply defined and strong band. CONCLUSIONS: The use of this method enabled us to obtain pure DNA from Trichoderma reesei, dispensing with the laborious and time-consuming steps involved in most protocols. The DNA obtained was found to be suitable for PCR and Southern blot analyses. Another advantage of this method is the fact that several samples can be processed simultaneously, growing the fungus on multiple well cell culture plates. In addition, the absence of maceration also reduces sample handling, minimizing the risks of contamination, a particularly important factor in work involving PCR.


Assuntos
Celofane , DNA Fúngico/isolamento & purificação , Micologia/métodos , Trichoderma/genética , Parede Celular/metabolismo , Criopreservação , Meios de Cultura/metabolismo , Vidro , Microesferas , Micologia/instrumentação , Nitrogênio/metabolismo , Trichoderma/crescimento & desenvolvimento , Trichoderma/metabolismo
18.
Cien Saude Colet ; 16(5): 2361-7, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21655706

RESUMO

Communicating an unfavorable diagnosis during prenatal care is a growing challenge in clinical practice, as more and more tests are being performed to screen for the main conditions affecting the pregnant woman and her fetus. The way patients receive and subsequently deal with bad news is directly influenced by how the news is communicated by the attending physician. Unfortunately, physicians receive little or no training in communicating bad news, and they generally feel quite uncomfortable about doing so. Although many physicians consider the saying that "there's no good way to break bad news" to be the truth, the maxim does not reflect the true picture. The scope of this article is to discuss, in light of the scientific literature and the experience of fetal medicine services, some recommendations that can help to deal with these difficult moments and improve patient care for the remainder of the pregnancy.


Assuntos
Cuidado Pré-Natal , Revelação da Verdade , Atitude do Pessoal de Saúde , Feminino , Humanos , Relações Médico-Paciente , Gravidez , Diagnóstico Pré-Natal
19.
Ann N Y Acad Sci ; 1173: 493-500, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19758191

RESUMO

Patients presenting with active systemic lupus erythematosus (SLE) manifestations may exhibit distinct pathogenetic features in relation to inactive SLE. Also, cDNA microarrays may potentially discriminate the gene expression profile of a disease or disease variant. Therefore, we evaluated the expression profile of 4500 genes in peripheral blood lymphocytes (PBL) of SLE patients. We studied 11 patients with SLE (seven with active SLE and four with inactive SLE) and eight healthy controls. Total RNA was isolated from PBL, reverse transcribed into cDNA, and postlabeled with Cy3 fluorochrome. These probes were then hybridized to a glass slide cDNA microarray containing 4500 human IMAGE cDNA target sequences. An equimolar amount of total RNA from human cell lines served as reference. The microarray images were quantified, normalized, and analyzed using the R environment (ANOVA, significant analysis of microarrays, and cluster-tree view algorithms). Disease activity was assessed by the SLE disease activity index. Compared to the healthy controls, 104 genes in active SLE patients (80 repressed and 24 induced) and 52 genes in nonactive SLE patients (31 induced and 21 repressed) were differentially expressed. The modulation of 12 genes, either induced or repressed, was found in both disease variants; however, each disease variant had differential expression of different genes. Taken together, these results indicate that the two lupus variants studied have common and unique differentially expressed genes. Although the biological significance of the differentially expressed genes discussed above has not been completely understood, they may serve as a platform to further explore the molecular basis of immune deregulation in SLE.


Assuntos
Perfilação da Expressão Gênica , Lúpus Eritematoso Sistêmico/genética , Linfócitos/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Adulto , Análise por Conglomerados , Feminino , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/patologia , Linfócitos/citologia , Pessoa de Meia-Idade , Adulto Jovem
20.
Lisboa; s.n; 2018.
Tese em Português | BDENF - Enfermagem | ID: biblio-1527434

RESUMO

A demência é classificada pela Organização Mundial de Saúde como uma prioridade de saúde pública, sendo, atualmente, uma das áreas que mais debate suscita a nível Europeu, atendendo ao envelhecimento populacional e ao impacto desta doença nas famílias. As dificuldades sentidas pelos cuidadores informais da pessoa com demência são uma realidade já reconhecida e estudada, porém frequentemente subavaliada. A ansiedade é apontada como um dos problemas que afeta esta população, atingindo um quarto destes cuidadores. No entando, as respostas para este problema são ainda escassas. Deste modo, esta é uma pertinente área de intervenção do enfermeiro especialista em saúde mental e psiquiatria. Neste sentido, este projeto de estágio teve como finalidade desenvolver competências enquanto enfermeira especialista em saúde mental e psiquiatria, particularmente, na gestão da ansiedade do cuidador informal da pessoa com demência. Assim, este relatório reflete o meu percurso de aprendizagem, salientando as intervenções de enfermagem na gestão da ansiedade do cuidador informal da pessoa com demência, particularmente, as intervenções de âmbito psicoeducativo. A metodologia utilizada é descritiva e critico-reflexiva, partindo das atividades desenvolvidas em contexto de estágio e dos resultados da evidência, em articulação com aprendizagens efetuadas e o desenvolvimento das competências do enfermeiro especialista em saúde mental e psiquiatria. Analisando os resultados obtidos, verifica-se que os programas de psicoeducação implementados em contexto de estágio contribuíram para a minimização dos níveis de ansiedade apresentados pelos clientes. Ao olhar para o cuidador como um parceiro nos cuidados à pessoa com demência, mas também como alvo dos cuidados de enfermagem, torna-se evidente a necessidade de investir na identificação dos fatores geradores de ansiedade e de ampliar a implementação de intervenções dirigidas ao cuidador.


Dementia is classified by the World Health Organization as a public health priority and is currently one of the most controversial areas at the European level, giving the aging population and the impact of this disease on families. The difficulties experienced by the informal caregivers of the person with dementia are a recognized and studied reality, but often underestimated. Anxiety is pointed out as one of the problems affecting this population, reaching a quarter of these caregivers. However, the answers to this problem are still sparse. Therefore, this is a pertinent intervention area of the mental health and psychiatry nurse specialist. For that matter, this internship project aimed to develop skills as mental health and psychiatry nurse specialist, particularly in managing the anxiety of the person with dementia's informal caregiver. Thus, this report reflects my learning pathway, highlighting the nursing interventions in management of anxiety in the person with dementia's informal caregiver, particularly, psychoeducational interventions. The used methodology is descriptive and critical-reflexive, starting from the developed activities in the internship context and the evidence results, in articulation with the learned lessons and the development of the mental health and psychiatry specialist nurse competences. Analysing the obtained results, it is verified that the psychoeducation programs implemented in internship context contributed to the minimization of the anxiety levels presented by the clients. When looking at the caregiver as a partner in the care of the person with dementia, but also as a target of nursing care, it becomes evident the need to invest in the identification of the factors that generate anxiety and to extend the implementation of caregiver directed interventions.


Assuntos
Ansiedade , Cuidadores , Demência , Enfermagem Psiquiátrica , Educação de Pacientes como Assunto
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