RESUMO
BACKGROUND: The objective of this paper is to describe the clinical and epidemiological profile and the early outcomes of patients with omphalocele born in a fetal medicine, pediatric surgery, and genetics reference hospital in Rio de Janeiro - Brazil. To determine its prevalence, describe the presence of genetic syndromes, and congenital malformations, emphasizing the characteristics of congenital heart diseases and their most common types. METHODS: Using Latin-American Collaborative Study of Congenital Malformations (ECLAMC) database and records review, a retrospective cross-sectional study was performed, including all patients born with omphalocele between January 1st, 2016, and December 31st, 2019. RESULTS: During the period of the study, our unity registered 4,260 births, 4,064 were live births and 196 stillbirths. There were 737 diagnoses of any congenital malformation, among them 38 cases of omphalocele, 27 were live born, but one was excluded for missing data. 62.2% were male, 62.2% of the women were multiparous and 51.3% of the babies were preterm. There was an associated malformation in 89.1% of the cases. Heart disease was the most common (45.9%) of which tetralogy of Fallot was the most frequent (23.5%). Mortality rate was 61.5%. CONCLUSIONS: Our data showed a good correspondence with the existing literature. Most patients with omphalocele had other malformations, especially congenital heart disease. No pregnancy was interrupted. The presence of concurrent defects showed a huge impact on prognosis, since, even if most survived birth, few remained alive and received hospital discharge. Based on these data, fetal medicine and neonatal teams must be able to adjust parents counseling about fetal and neonatal risks, especially when other congenital diseases are present.
Assuntos
Anormalidades Congênitas , Cardiopatias Congênitas , Hérnia Umbilical , Recém-Nascido , Criança , Gravidez , Humanos , Masculino , Feminino , Hérnia Umbilical/epidemiologia , Centros de Atenção Terciária , Estudos Retrospectivos , Estudos Transversais , Brasil/epidemiologia , Cardiopatias Congênitas/epidemiologia , Anormalidades Congênitas/epidemiologia , PrevalênciaRESUMO
Polymer-drug conjugation is an attractive approach for target delivering insoluble and highly toxic drugs to tumor sites to overcome the side-effects caused by cancer chemotherapy. In this study we designed and synthesized novel polymer-drug-peptide conjugates for improved specificity on targeting cancer cells. Chemically modified polysaccharide, carboxymethylcellulose (CMC), was conjugated with doxorubicin (DOX) anticancer drug by amide bonds and dually biofunctionalized with integrin-target receptor tripeptide (RGD) and l-arginine (R) as cell-penetrating amino acid for synergistic targeting and enhancing internalization by cancer cells. These bioconjugates were tested as prodrugs against bone, breast, and brain cancer cell lines (SAOS, MCF7, and U87) and a normal cell line (HEK 293T, reference). The physicochemical characterization showed the formation of amide bonds between carboxylates (-RCOO-) from CMC biopolymer and amino groups (-NH2) from DOX and peptides (RGD or R). Moreover, these polymer-drug-peptide bioconjugates formed nanoparticulate colloidal structures and behaved as "smart" drug delivery systems (DDS) promoting remarkable reduction of the cytotoxicity toward normal cells (HEK 293T) while retaining high killing activity against cancer cells. Based on cell viability bioassays, DNA-staining, and confocal laser microscopy, this effect was assigned to the association of physicochemical aspects with the difference of the endocytic pathways and the drug release rates in live cells caused by the biofunctionalization of the macromolecule-drug systems with RGD and l-arginine. In addition, chick chorioallantoic membrane (CAM) assay was performed as an in vivo xenograft model test, which endorsed the in vitro results of anticancer activities of these polymer-drug systems. Thus, prodrug nanocarriers based on CMC-DOX-peptide bioconjugates were developed for simultaneously integrin-targeting and high killing efficacy against cancer cells, while preserving healthy cells with promising perspectives in cancer chemotherapy.
Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Arginina/metabolismo , Carboximetilcelulose Sódica/metabolismo , Doxorrubicina/administração & dosagem , Portadores de Fármacos/metabolismo , Integrinas/metabolismo , Oligopeptídeos/metabolismo , Animais , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacologia , Arginina/análogos & derivados , Carboximetilcelulose Sódica/análogos & derivados , Linhagem Celular Tumoral , Peptídeos Penetradores de Células/química , Peptídeos Penetradores de Células/metabolismo , Galinhas , Doxorrubicina/química , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Células HEK293 , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Oligopeptídeos/químicaRESUMO
UNLABELLED: Subcellular Ca(2+) signals control a variety of responses in the liver. For example, mitochondrial Ca(2+) (Ca(mit)(2+)) regulates apoptosis, whereas Ca(2+) in the nucleus regulates cell proliferation. Because apoptosis and cell growth can be related, we investigated whether Ca(mit)(2+) also affects liver regeneration. The Ca(2+)-buffering protein parvalbumin, which was targeted to the mitochondrial matrix and fused to green fluorescent protein, was expressed in the SKHep1 liver cell line; the vector was called parvalbumin-mitochondrial targeting sequence-green fluorescent protein (PV-MITO-GFP). This construct properly localized to and effectively buffered Ca(2+) signals in the mitochondrial matrix. Additionally, the expression of PV-MITO-GFP reduced apoptosis induced by both intrinsic and extrinsic pathways. The reduction in cell death correlated with the increased expression of antiapoptotic genes [B cell lymphoma 2 (bcl-2), myeloid cell leukemia 1, and B cell lymphoma extra large] and with the decreased expression of proapoptotic genes [p53, B cell lymphoma 2-associated X protein (bax), apoptotic peptidase activating factor 1, and caspase-6]. PV-MITO-GFP was also expressed in hepatocytes in vivo with an adenoviral delivery system. Ca(mit)(2+) buffering in hepatocytes accelerated liver regeneration after partial hepatectomy, and this effect was associated with the increased expression of bcl-2 and the decreased expression of bax. CONCLUSION: Together, these results reveal an essential role for Ca(mit)(2+) in hepatocyte proliferation and liver regeneration, which may be mediated by the regulation of apoptosis.
Assuntos
Apoptose/fisiologia , Cálcio/metabolismo , Regeneração Hepática/fisiologia , Mitocôndrias Hepáticas/metabolismo , Animais , Sinalização do Cálcio/fisiologia , Proliferação de Células , Masculino , Modelos Animais , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Proteína X Associada a bcl-2/metabolismoRESUMO
BACKGROUND: Multiple opinion-based communications have highlighted the actions of the Brazilian government during the pandemic. Nevertheless, none have appraised public data to identify factors associated with worsening of the healthcare system. OBJECTIVE: To analyze and collate data from public health and treasury information systems in order to understand the escalating process of weakening of Brazilian healthcare and welfare since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. DESIGN AND SETTING: Secondary data study conducted using multiple public databases administered by the Brazilian federal government. METHODS: We processed information from multiple national databases and appraised health and economic-related data. RESULTS: Based on our analyses, there were substantial reductions in inpatient hospital admissions and in the numbers of patients seeking primary care services, along with a decrease in immunization coverage. Moreover, we observed a considerable decline in government transfers to hospital services (reduction of 82.0%) and a diminution of public outlays in several healthcare-related subfunctions ("hospital and outpatient care", "primary care", "prophylactic and therapeutic support" and "epidemiological surveillance"). We observed an increase in the overall mortality rate over the period analyzed, especially regarding all group-based diseases. Notably, there were remarkable differences among geographic, racial, gender and other parameters, thus revealing the impact of vulnerabilities on COVID-19 outcomes. CONCLUSION: This assessment of documentation of public expenditure and the shrinkage of investment in sensitive areas of the healthcare system in Brazil emphasized areas that still require collective attention in order to guarantee national welfare.
Assuntos
COVID-19 , Brasil/epidemiologia , Gastos em Saúde , Hospitalização , Humanos , SARS-CoV-2RESUMO
OBJECTIVE: Because fetal respiratory movements increase left ventricular compliance, we hypothesized that the left atrial shortening fraction increases during fetal respiratory motions. METHODS: A group of 26 normal fetuses with gestational ages between 28 and 38 weeks were assessed in a prospective cross-sectional study. Left atrial telesystolic and presystolic diameters were measured during apnea and after five consecutive respiratory movements. Left atrial shortening fraction was obtained by the ratio: [maximal left atrium diameter (telesystolic) - minimal left atrium diameter (presystolic)]/maximal left atrium diameter (telesystolic). The mean of three measurements were considered. Two-tailed Student's t-test was used. RESULTS: Mean gestational age was (mean ± SD) 30.7 ± 2.8 weeks. Mean left atrial telesystolic diameter in apnea was 10.6 ± 0.7 mm and during respiratory movements it was 10.5 ± 1.1 mm (p = 0.98). Presystolic left atrial diameter was 5.2 ± 0.1 mm in apnea and 4.4 ± 1.3 mm during respiratory movements (p < 0.001). Left atrial shortening fraction was 0.50 ± 0.05 in apnea and 0.58 ± 0.13 during respiratory movements (p < 0.001). CONCLUSION: Left atrial shortening fraction is higher during respiratory movements as a result of increased left ventricular compliance and consequent optimization of left atrial functional status.
Assuntos
Função do Átrio Esquerdo , Feto/fisiologia , Respiração , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Gravidez , Estudos Prospectivos , Adulto JovemRESUMO
This report describes a case of multisystem inflammatory syndrome in a child that evolved with a pattern of toxic shock syndrome with coronary artery ectasia and neurological involvement, documented by magnetic resonance imaging, with changes in the corpus callosum and myopathy in the pelvic girdle and paravertebral musculature.
Assuntos
COVID-19 , Doenças Musculares , Criança , Humanos , Imageamento por Ressonância Magnética , Doenças Musculares/diagnóstico , SARS-CoV-2 , Síndrome , Síndrome de Resposta Inflamatória SistêmicaRESUMO
The palladium(II) complexes [Pd(2Bz4oT)Cl], [Pd(2Bz4mT)Cl], and [Pd(2Bz4pT)Cl] were prepared with N(4)-ortho- (H2Bz4oT) N(4)-meta- (H2Bz4mT) and N(4)-para- (H2Bz4pT) tolyl-thiosemicarbazones derived from 2-benzoylpyridine. The free thiosemicarbazones proved to be highly cytotoxic against Jurkat, HL60 and the resistant HL60.Bcl-X(L) leukemia cell lines at nanomolar concentrations, but were much less cytotoxic to HepG2human hepatoma cells. Upon coordination to palladium(II) the cytotoxic activity against all studied cell lines decreases. However, the high cytotoxicity of the free thiosemicarbazones against leukemia, together with their hepatotoxic profile similar to that of cisplatin suggest that N(4)-tolyl thiosemicarbazones have potential as chemotherapeutic drug candidates.
Assuntos
Antineoplásicos/farmacologia , Leucemia/patologia , Paládio/química , Tiossemicarbazonas/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Tiossemicarbazonas/químicaRESUMO
The study aimed to investigate the short-term association between air pollution and emergency treatments for respiratory diseases in children 0 to 6 years of age. This was an ecological space-time study in Greater Metropolitan Vitória, Espírito Santo State, Brazil. A Poisson regression general additive model (GAM) used the number of daily treatments for respiratory diseases as the dependent variable, and the independent variables were daily concentrations of air pollutants (PM10, SO2, NO2, O3, and CO), temperature, humidity, and precipitation. Average daily concentrations were used to make estimates for the entire metropolitan area and in loco analyses considering children residing in a 2km radius around 8 air quality monitoring stations. An increase of 10µg/m3 in the concentration of air pollutants increased the risk of emergency treatment for respiratory disease. In the overall area, for PM10, the increase was 2.43%, 2.73%, and 3.29% in the cumulative values at 5, 6, and 7 days, respectively. For SO2, the increase was 4.47% on the day of exposure, 5.26% two days later, and 6.47%, 8.8%, 8.76%, and 7.09% for the cumulative values at days 2, 3, 4, and 5 days, respectively. CO showed a significant association for residents around two stations, and O3 for only one. Even within the limits set by the World Health Organization, the pollutants PM10, SO2, NO2, and O3 are associated with increased risk of treatment for respiratory diseases in children 0 to 6 years of age, and some effects were only identified when disaggregating by neighborhood, i.e., in loco, which allows capturing greater variation in the data.
O objetivo foi investigar a associação de curto prazo entre a poluição do ar e atendimentos em emergências por doenças respiratórias, em crianças de 0 a 6 anos. Estudo ecológico, espacial e temporal realizado na Região Metropolitana da Grande Vitoria, Espírito Santo, Brasil. Utilizou-se o modelo aditivo generalizado (MAG) de regressão de Poisson, com a variável dependente o número diário de atendimentos por doenças respiratórias, e as variáveis independentes, concentrações diárias dos poluentes atmosféricos (MP10, SO2, NO2, O3 e CO), temperatura, umidade e precipitação pluviométrica. Por meio das médias diárias das concentrações, foram feitas estimativas para toda a região e análises in loco com a consideração de crianças residentes no entorno de 2km de oito estações de monitoramento da qualidade do ar. O incremento de 10µg/m3 nos níveis de concentração dos poluentes atmosféricos aumentou o risco de atendimento em emergência por doença respiratória. Na região geral, para o MP10, o aumento foi de 2,43%, 2,73% e 3,29% nos acumulados de 5, 6 e 7 dias, respectivamente. Para o SO2, o acréscimo foi de 4,47% no dia da exposição, 5,26% dois dias após, 6,47%, 8,8%, 8,76% e 7,09% nos acumulados de 2, 3, 4 e 5 dias, respectivamente. O CO apresentou associação significativa para residentes no entorno de duas estações, e o O3 somente em uma. Mesmo dentro dos limites estabelecidos pela Organização Mundial da Saúde, os poluentes MP10, SO2, NO2 e O3 estão associados ao maior risco para atendimento por doenças respiratórias em crianças de 0 a 6 anos, e alguns efeitos só foram identificados nas localidades desagregadas por região, isto é, in loco, o que possibilita captar maior variabilidade dos dados.
El objetivo fue investigar la asociación de corto plazo entre la contaminación del aire y la atención en urgencias por enfermedades respiratorias, en niños de 0 a 6 años. Estudio ecológico, espacial y temporal realizado en la Región Metropolitana de la Grande Vitória, Espírito Santo, Brasil. Se utilizó el modelo aditivo generalizado (MAG) de regresión de Poisson, con la variable dependiente que es el número diario de consultas por enfermedades respiratorias, y las variables independientes: concentraciones diarias de los contaminantes atmosféricos (MP10, SO2, NO2, O3 y CO), temperatura, humedad y precipitación pluviométrica. Mediante las medias diarias de las concentraciones, se realizaron estimativas para toda la región y análisis in loco, considerando a niños residentes en un entorno de 2km con 8 estaciones de monitoreo de la calidad del aire. El incremento de 10µg/m3 en los niveles de concentración de los contaminantes atmosféricos aumentó el riesgo de atención en urgencias por enfermedad respiratoria. En la región como un todo, en el caso del MP10, el aumento fue de 2,43%, 2,73% y 3,29% en los acumulados de 5, 6 y 7 días, respectivamente. En el SO2, el incremento fue de 4,47% durante el día de la exposición, 5,26% dos días después, 6,47%, 8,8%, 8,76% y 7,09% en los acumulados de 2, 3, 4 y 5 días, respectivamente. El CO presentó asociación significativa para residentes alrededor de dos estaciones, y el O3 solamente en una. Incluso dentro de los límites establecidos por la Organización Mundial de la Salud, los contaminantes MP10, SO2, NO2 y O3 están asociados a un mayor riesgo en relación con la atención por enfermedades respiratorias en niños de 0 a 6 años, y algunos efectos sólo se identificaron en las localidades desagregadas por región, esto es, in loco, lo que posibilita captar una mayor variabilidad de los datos.
Assuntos
Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , Assistência Ambulatorial/estatística & dados numéricos , Transtornos Respiratórios/induzido quimicamente , Doenças Respiratórias/induzido quimicamente , Poluentes Atmosféricos/análise , Brasil , Criança , Saúde da Criança , Pré-Escolar , Exposição Ambiental/efeitos adversos , Humanos , Lactente , Recém-Nascido , Risco , Análise Espaço-Temporal , População UrbanaRESUMO
Many human diseases, including metabolic, immune, and central nervous system disorders, as well as several types of cancers, are the consequence of an important alteration in lipid-related metabolic biomolecules. Although recognized that one of the most important metabolic hallmarks of cancer cells is deregulation of lipid metabolism, the multiple complex signaling pathways are poorly understood yet. Thus, in this research, novel nanoconjugates made of ZnS quantum dots (QDs) were directly synthesized in aqueous media using phosphoethanolamine (PEA) as the capping ligand, which is an important biomolecule naturally present in cells for de novo biosynthesis of fatty acids and phospholipids involved in the cell structure (e.g., membrane), differentiation, and cancer growth. These QD-PEA bio-nanoconjugates were characterized by spectroscopical and morphological techniques. The results demonstrated that fluorescent ZnS nanocrystalline QDs were produced with uniform spherical morphology and estimated sizes of 3.3 ± 0.6 nm. These nanoconjugates indicated core-shell colloidal nanostructures (ZnS QD-PEA) with the hydrodynamic diameter (H D) of 26.0 ± 3.5 nm and ζ-potential centered at -30.0 ± 4.5 mV. The cell viability response using mitochondrial activity assay in vitroconfirmed no cytotoxicity at several concentrations of PEA (biomolecule) and the ZnS-PEA nanoconjugates. Moreover, these nanoconjugates effectively behaved as fluorescent nanomarkers for tracking the endocytic pathways of cancer cells using confocal laser scanning microscopy bioimaging. Hence, these results proved that biofunctionalized ZnS-PEA nanoprobes offer prospective tools for cellular bioimaging with encouraging forecast for future applications as active fluorescent biomarker conjugates in metabolic-related cancer research.
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BACKGROUND: Antenatal exposure to Zika virus (ZIKV) is related to severe neurological manifestations. A previous study in Brazil reported an increased incidence of non-severe congenital heart defects in infants with diagnosis of congenital Zika syndrome but without laboratory confirmation of ZIKV infection in the mother or infant. The objective of this study is to report echocardiographic (ECHO) findings in infants with laboratory confirmed antenatal exposure to ZIKV. METHODOLOGY: Cross sectional study of cardiologic assessments of infants born between November 2015 and January 2017 with confirmed vertical exposure to ZIKV in Rio de Janeiro, Brazil. RESULTS: The study enrolled 120 children with a median age of 97 days (1 to 376 days). In utero exposure to ZIKV was confirmed in 97 children (80,8%) through positive maternal polymerase chain reaction (PCR) results during pregnancy or a positive PCR result at birth; 23 additional children (19.2%) had maternal positive PCR results during pregnancy and postnatally. Forty- eight infants (40%) had cardiac defects noted on ECHO. Thirteen infants (10.8%) had major cardiac defects (atrial septal defect, ventricular septal defect, patent ductus arteriosus). None of the defects were severe. The frequency of major defects was higher in infants whose mothers had a rash in the 2nd trimester of pregnancy, or who had altered Central Nervous System (CNS) imaging postnatally or were preterm. CONCLUSIONS: Infants with in utero ZIKV exposure have a higher prevalence of major cardiac defects, however none were severe enough to require immediate intervention. For this reason, guidelines for performance of postnatal ECHO in this population should follow general newborn screening guidelines, which significantly reduces the burden of performing emergent fetal or neonatal ECHOs in a setting where resources are not available, such as most Brazilian municipalities.
Assuntos
Cardiopatias Congênitas/diagnóstico por imagem , Complicações Infecciosas na Gravidez , Infecção por Zika virus/congênito , Líquido Amniótico/virologia , Brasil/epidemiologia , Sistema Nervoso Central/diagnóstico por imagem , Sistema Nervoso Central/virologia , Estudos Transversais , Ecocardiografia , Feminino , Feto/virologia , Humanos , Lactente , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Masculino , Mães , Reação em Cadeia da Polimerase , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/virologia , Zika virus/genética , Zika virus/patogenicidade , Infecção por Zika virus/complicações , Infecção por Zika virus/transmissão , Infecção por Zika virus/virologiaRESUMO
ABSTRACT BACKGROUND: Multiple opinion-based communications have highlighted the actions of the Brazilian government during the pandemic. Nevertheless, none have appraised public data to identify factors associated with worsening of the healthcare system. OBJECTIVE: To analyze and collate data from public health and treasury information systems in order to understand the escalating process of weakening of Brazilian healthcare and welfare since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. DESIGN AND SETTING: Secondary data study conducted using multiple public databases administered by the Brazilian federal government. METHODS: We processed information from multiple national databases and appraised health and economic-related data. RESULTS: Based on our analyses, there were substantial reductions in inpatient hospital admissions and in the numbers of patients seeking primary care services, along with a decrease in immunization coverage. Moreover, we observed a considerable decline in government transfers to hospital services (reduction of 82.0%) and a diminution of public outlays in several healthcare-related subfunctions ("hospital and outpatient care", "primary care", "prophylactic and therapeutic support" and "epidemiological surveillance"). We observed an increase in the overall mortality rate over the period analyzed, especially regarding all group-based diseases. Notably, there were remarkable differences among geographic, racial, gender and other parameters, thus revealing the impact of vulnerabilities on COVID-19 outcomes. CONCLUSION: This assessment of documentation of public expenditure and the shrinkage of investment in sensitive areas of the healthcare system in Brazil emphasized areas that still require collective attention in order to guarantee national welfare.
Assuntos
COVID-19 , Brasil/epidemiologia , Gastos em Saúde , SARS-CoV-2 , HospitalizaçãoRESUMO
Abstract Background Juvenile systemic lupus erythematosus (JSLE) is a chronic inflammatory disease that affects the heart in 50% of cases. The behavior of diastolic function in adolescents and the predictors of its occurrence by conventional echocardiography are poorly established. Objectives This study aimed to evaluate diastolic function in adolescents with JSLE and to identify possible predictors of its occurrence by conventional echocardiography. Methods Cross-sectional, observational, control group study in a tertiary hospital of 49 adolescents with JSLE and 49 controls, using the EACVI 2016 guideline classification. Statistical methods used were Fisher and Mann-Whitney tests. Multivariate logistic regression models were constructed. A significance level of 5% was adopted. Results Among 98 patients, the JSLE group had higher indexed left atrial volume (p <0.001), lower lateral E' value (p<0.001) and lower E/A ratio value (p<0.001). The diagnosis of JSLE was associated with a higher chance of increased left atrial index volume (OR 3.3; p value 0.03). Conclusions Based on the 2016 guideline, no diastolic dysfunction was found in JSLE. However, differences in the analyzed echocardiographic parameters were found in these adolescents.
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BACKGROUND: The angiotensin-I converting enzyme (ACE) plays a central role in the renin-angiotensin system, acting by converting the hormone angiotensin-I to the active peptide angiotensin-II (Ang-II). More recently, ACE was shown to act as a receptor for Ang-II, and its expression level was demonstrated to be higher in melanoma cells compared to their normal counterparts. However, the function that ACE plays as an Ang-II receptor in melanoma cells has not been defined yet. AIM: Therefore, our aim was to examine the role of ACE in tumor cell proliferation and migration. RESULTS: We found that upon binding to ACE, Ang-II internalizes with a faster onset compared to the binding of Ang-II to its classical AT1 receptor. We also found that the complex Ang-II/ACE translocates to the nucleus, through a clathrin-mediated process, triggering a transient nuclear Ca2+ signal. In silico studies revealed a possible interaction site between ACE and phospholipase C (PLC), and experimental results in CHO cells, demonstrated that the ß3 isoform of PLC is the one involved in the Ca2+ signals induced by Ang-II/ACE interaction. Further studies in melanoma cells (TM-5) showed that Ang-II induced cell proliferation through ACE activation, an event that could be inhibited either by ACE inhibitor (Lisinopril) or by the silencing of ACE. In addition, we found that stimulation of ACE by Ang-II caused the melanoma cells to migrate, at least in part due to decreased vinculin expression, a focal adhesion structural protein. CONCLUSION: ACE activation regulates melanoma cell proliferation and migration.
Assuntos
Angiotensina II/metabolismo , Núcleo Celular/metabolismo , Melanoma/enzimologia , Peptidil Dipeptidase A/metabolismo , Fosfolipase C beta/metabolismo , Vinculina/metabolismo , Animais , Células CHO , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Simulação por Computador , Cricetulus , Humanos , Lisinopril/farmacologia , Melanoma/genética , Melanoma/metabolismo , Peptidil Dipeptidase A/genética , Transporte ProteicoRESUMO
Abstract This report describes a case of multisystem inflammatory syndrome in a child that evolved with a pattern of toxic shock syndrome with coronary artery ectasia and neurological involvement, documented by magnetic resonance imaging, with changes in the corpus callosum and myopathy in the pelvic girdle and paravertebral musculature.
Assuntos
Humanos , Criança , Infecções por Coronavirus , Doenças Musculares/diagnóstico , Síndrome , Imageamento por Ressonância Magnética , Síndrome de Resposta Inflamatória Sistêmica , BetacoronavirusRESUMO
Cancer remains one of the world's most devastating diseases with millions of fatalities and new cases every year. In this work, we attempted to develop a facile "enzyme-free" fluoroimmunoassay based on the novel nanoconjugates composed of CdS quantum dots (QDs) as the fluorescent inorganic core and an antibody-modified polysaccharide as the organic shell, modeling their possible application for the in vitro diagnosis of non-Hodgkin lymphoma (NHL) cancer. Chitosan was conjugated with an anti-CD20 polyclonal antibody (pAbCD20) by the formation of covalent amide bonds. In the sequence, these chitosan-antibody conjugates were utilized as direct ligands for the surface biofunctionalization of CdS QDs (CdS/chitosan-pAbCD20) using a single-step colloidal process in aqueous medium at room temperature. The most relevant physico-chemical properties of these nanoconjugates were assessed by morphological and spectroscopic techniques. The results indicated that CdS nanocrystals were produced with an average diameter of 2.5 nm and with cubic zinc blende crystalline nanostructure. The CdS-immunoconjugates (CdS/chitosan-pAbCD20) presented colloidal hydrodynamic diameter (HD) of 15.0 ± 1.2n m. In addition, the results evidenced that the "enzyme-free" QD-linked immunosorbent assay (QLISA) was effective for the in vitro detection against the antigen CD20 (aCD20) based on fluorescent behavior of the CdS nanoconjugates. Moreover, the CdS-immunoconjugates were successfully used for fluorescence bioimaging of NHL cancer cells. Finally, the cell viability results using different cell cultures based on LDH, MTT and Resazurin bio-assays have demonstrated no cytotoxicity of the new CdS-chitosan bioconjugates relative to the standard controls. Thus, CdS conjugates may offer a promising platform for the future development of in vitro and in vivo applications for the detection and diagnosis of NHL cancer cells.
Assuntos
Quitosana/química , Nanoconjugados/química , Pontos Quânticos , Animais , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Fluorimunoensaio , Nanoconjugados/efeitos adversos , Nanopartículas/química , Nanotecnologia , Difração de Raios XRESUMO
In this study, our aims were to investigate transient receptor potential melastatin-8 channels (TRPM8) involvement in rotundifolone induced relaxation in the mesenteric artery and to increase the understanding of the role of these thermosensitive TRP channels in vascular tissue. Thus, message and protein levels of TRPM8 were measured by semi-quantitative PCR and western blotting in superior mesenteric arteries from 12 week-old Spague-Dawley (SD) rats. Isometric tension recordings evaluated the relaxant response in mesenteric rings were also performed. Additionally, the intracellular Ca2+ changes in mesenteric artery myocytes were measured using confocal microscopy. Using PCR and western blotting, both TRPM8 channel mRNA and protein expression was measured in SD rat mesenteric artery. Rotundifolone and menthol induced relaxation in the isolated superior mesenteric artery from SD rats and improved the relaxant response induced by cool temperatures. Also, this monoterpene induced an increase in transient intracellular Ca2+. These responses were significantly attenuated by pretreatment with capsazepine or BCTC, both TRPM8 channels blockers. The response induced by rotundifolone was not significantly attenuated by ruthenium red, a non-selective TRP channels blocker, or following capsaicin-mediated desensitization of TRPV1. Our findings suggest that rotundifolone induces relaxation by activating TRPM8 channels in rat superior mesenteric artery, more selectively than menthol, the classic TRPM8 agonist, and TRPM8 channels participates in vasodilatory pathways in isolated rat mesenteric arteries.
Assuntos
Ativação do Canal Iônico/efeitos dos fármacos , Artérias Mesentéricas/fisiologia , Monoterpenos/farmacologia , Canais de Cátion TRPM/metabolismo , Vasodilatação/fisiologia , Animais , Western Blotting , Cálcio/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Capsaicina/farmacologia , Temperatura Baixa , Citosol/metabolismo , Técnicas In Vitro , Masculino , Mentol/farmacologia , Artérias Mesentéricas/efeitos dos fármacos , Pirazinas/metabolismo , Piridinas/metabolismo , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Rutênio Vermelho/metabolismo , Canais de Cátion TRPV/metabolismo , Vasodilatação/efeitos dos fármacosRESUMO
Ebstein's anomaly, although the most common malformation of the tricuspid valve, is a rare disease. Its association with other syndromes and extracardiac anomalies is very rare and has been reported in only a few cases. A case of prenatal diagnosis of Ebstein's anomaly in a patient with Down's syndrome is reported.
Assuntos
Síndrome de Down/diagnóstico , Anomalia de Ebstein/diagnóstico , Diagnóstico Pré-Natal , Adulto , Síndrome de Down/complicações , Anomalia de Ebstein/complicações , Ecocardiografia , Eletrocardiografia , Feminino , Humanos , GravidezRESUMO
Marfan's syndrome is an inherited disorder of the connective tissue. Cardiologic manifestations, especially aortic dilation, are important causes of morbidity and mortality in the clinical course of the disease in adults and teenagers. In children, the presence of aortic aneurysm and its dissection or rupture is rare, occurring in patients with genetic mutation of the fibrillin gene but not in those who have the familial form of the disease. We describe here 2 patients, from the same family (siblings), diagnosed with gigantic aortic aneurysm early in infancy, one of them successfully undergoing surgery.
Assuntos
Aneurisma Aórtico/diagnóstico , Síndrome de Marfan/diagnóstico , Irmãos , Aneurisma Aórtico/tratamento farmacológico , Aneurisma Aórtico/cirurgia , Criança , Evolução Fatal , Feminino , Humanos , Masculino , Síndrome de Marfan/tratamento farmacológico , Síndrome de Marfan/cirurgiaRESUMO
OBJECTIVE: Noninvasive cardiac assessment of newborns and infants of women with systemic lupus erythematosus. The children had no congenital total atrioventricular block and were compared with the children of healthy women. METHODS: We prospectively assessed 13 newborns and infants aged 1 to 60 days, children of women with systemic lupus erythematosus and without congenital total atrioventricular block. These children were compared with 30 children of women who had no lupus or anti-Ro/SSA antibodies, and no risk factors for congenital heart disease either. Their age groups matched. The following examinations were performed: cardiological physical examination, electrocardiography, echocardiography, and signal-averaged electrocardiography. RESULTS: The statistical analysis showed no significant difference in ventricular function or in the cardiac conduction system between the groups. CONCLUSION: In regard to the conduction system and ventricular function in the absence of total atrioventricular block, no statistically significant difference was observed between the children of women with systemic lupus erythematosus and children of healthy women.
Assuntos
Filho de Pais com Deficiência , Bloqueio Cardíaco/diagnóstico , Lúpus Eritematoso Sistêmico , Anticorpos Antinucleares/sangue , Ecocardiografia Doppler em Cores , Eletrocardiografia , Feminino , Bloqueio Cardíaco/diagnóstico por imagem , Bloqueio Cardíaco/imunologia , Frequência Cardíaca , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Prospectivos , Estatísticas não ParamétricasRESUMO
O objetivo foi investigar a associação de curto prazo entre a poluição do ar e atendimentos em emergências por doenças respiratórias, em crianças de 0 a 6 anos. Estudo ecológico, espacial e temporal realizado na Região Metropolitana da Grande Vitoria, Espírito Santo, Brasil. Utilizou-se o modelo aditivo generalizado (MAG) de regressão de Poisson, com a variável dependente o número diário de atendimentos por doenças respiratórias, e as variáveis independentes, concentrações diárias dos poluentes atmosféricos (MP10, SO2, NO2, O3 e CO), temperatura, umidade e precipitação pluviométrica. Por meio das médias diárias das concentrações, foram feitas estimativas para toda a região e análises in loco com a consideração de crianças residentes no entorno de 2km de oito estações de monitoramento da qualidade do ar. O incremento de 10μg/m3 nos níveis de concentração dos poluentes atmosféricos aumentou o risco de atendimento em emergência por doença respiratória. Na região geral, para o MP10, o aumento foi de 2,43%, 2,73% e 3,29% nos acumulados de 5, 6 e 7 dias, respectivamente. Para o SO2, o acréscimo foi de 4,47% no dia da exposição, 5,26% dois dias após, 6,47%, 8,8%, 8,76% e 7,09% nos acumulados de 2, 3, 4 e 5 dias, respectivamente. O CO apresentou associação significativa para residentes no entorno de duas estações, e o O3 somente em uma. Mesmo dentro dos limites estabelecidos pela Organização Mundial da Saúde, os poluentes MP10, SO2, NO2 e O3 estão associados ao maior risco para atendimento por doenças respiratórias em crianças de 0 a 6 anos, e alguns efeitos só foram identificados nas localidades desagregadas por região, isto é, in loco, o que possibilita captar maior variabilidade dos dados.
El objetivo fue investigar la asociación de corto plazo entre la contaminación del aire y la atención en urgencias por enfermedades respiratorias, en niños de 0 a 6 años. Estudio ecológico, espacial y temporal realizado en la Región Metropolitana de la Grande Vitória, Espírito Santo, Brasil. Se utilizó el modelo aditivo generalizado (MAG) de regresión de Poisson, con la variable dependiente que es el número diario de consultas por enfermedades respiratorias, y las variables independientes: concentraciones diarias de los contaminantes atmosféricos (MP10, SO2, NO2, O3 y CO), temperatura, humedad y precipitación pluviométrica. Mediante las medias diarias de las concentraciones, se realizaron estimativas para toda la región y análisis in loco, considerando a niños residentes en un entorno de 2km con 8 estaciones de monitoreo de la calidad del aire. El incremento de 10μg/m3 en los niveles de concentración de los contaminantes atmosféricos aumentó el riesgo de atención en urgencias por enfermedad respiratoria. En la región como un todo, en el caso del MP10, el aumento fue de 2,43%, 2,73% y 3,29% en los acumulados de 5, 6 y 7 días, respectivamente. En el SO2, el incremento fue de 4,47% durante el día de la exposición, 5,26% dos días después, 6,47%, 8,8%, 8,76% y 7,09% en los acumulados de 2, 3, 4 y 5 días, respectivamente. El CO presentó asociación significativa para residentes alrededor de dos estaciones, y el O3 solamente en una. Incluso dentro de los límites establecidos por la Organización Mundial de la Salud, los contaminantes MP10, SO2, NO2 y O3 están asociados a un mayor riesgo en relación con la atención por enfermedades respiratorias en niños de 0 a 6 años, y algunos efectos sólo se identificaron en las localidades desagregadas por región, esto es, in loco, lo que posibilita captar una mayor variabilidad de los datos.
The study aimed to investigate the short-term association between air pollution and emergency treatments for respiratory diseases in children 0 to 6 years of age. This was an ecological space-time study in Greater Metropolitan Vitória, Espírito Santo State, Brazil. A Poisson regression general additive model (GAM) used the number of daily treatments for respiratory diseases as the dependent variable, and the independent variables were daily concentrations of air pollutants (PM10, SO2, NO2, O3, and CO), temperature, humidity, and precipitation. Average daily concentrations were used to make estimates for the entire metropolitan area and in loco analyses considering children residing in a 2km radius around 8 air quality monitoring stations. An increase of 10μg/m3 in the concentration of air pollutants increased the risk of emergency treatment for respiratory disease. In the overall area, for PM10, the increase was 2.43%, 2.73%, and 3.29% in the cumulative values at 5, 6, and 7 days, respectively. For SO2, the increase was 4.47% on the day of exposure, 5.26% two days later, and 6.47%, 8.8%, 8.76%, and 7.09% for the cumulative values at days 2, 3, 4, and 5 days, respectively. CO showed a significant association for residents around two stations, and O3 for only one. Even within the limits set by the World Health Organization, the pollutants PM10, SO2, NO2, and O3 are associated with increased risk of treatment for respiratory diseases in children 0 to 6 years of age, and some effects were only identified when disaggregating by neighborhood, i.e., in loco, which allows capturing greater variation in the data.