904 research outputs found
Chylothorax in the neonate-A stepwise approach algorithm
Background: Chylothorax in neonates results from leakage of lymph from thoracic lymphatic ducts and is mainly congenital or posttraumatic. The clinical course of the effusion is heterogeneous, and consensus on treatment, timing, and modalities of measures has not yet been established. This review aims to present, along with levels of evidence and recommendation grades, all current therapeutic possibilities for the treatment of chylothorax in neonates.
Methods: An extensive search of publications between 1970 and 2020 was performed in the PubMed, Cochrane Database of Systematic Reviews, and UpToDate databases. A stepwise approach algorithm was proposed for both congenital and traumatic conditions to guide the clinician in a rational and systematic way for approaching the treatment of neonates with chylothorax.
Discussion and conclusion: The treatment strategy for neonatal chylothorax generally involves supportive care and includes drainage and procedures to reduce chyle flow. A stepwise approach starting with the least invasive method is advocated. Progression in the invasiveness of treatment options is determined by the response to previous treatments. A practical stepwise approach algorithm is proposed for both, congenital and traumatic chylothoraces
Pregnancy Outcomes in Women with Pre-Existing Diabetes
OBJETIVO: Avaliar as alterações epidemiológicas, de perfil clÃnico e de prognóstico obstétrico em pacientes portadoras de diabetes mellitus pré-gestacional. MÉTODOS: Estudo retrospetivo (coorte) de todas as gestações simples, com diagnóstico de diabetes prévio que foram seguidas num centro com apoio perinatal diferenciado entre 2004 e 2011 (n=194).
Analisaram-se tendências relacionadas com dados demográficos e variáveis clÃnicas maternas, dados de indicadores de
cuidados pre-concepcionais e durante a gravidez, e de controle metabólico. Dados do parto como a idade gestacional(IG) do parto, via do parto e peso do neonato foram variáveis também estudadas. RESULTADOS: A frequência global de diabetes prévia, durante o perÃodo estudado, foi de 4,4 por mil, não se verificando variações significativas durante o perÃodo de estudo. Os casos de diabetes tipo 2 permaneceram constantes. Em 67% dos casos o parto foi de termo(máximo de 80% em 2010–2011), registrou-se uma redução significativa dos partos por cesárea eletiva (p=0,03) e na incidência de neonatos considerados grandes para a IG (p=0,04) ao longo dos anos em estudo. Apesar dos bons resultados relacionados com o controle metabólico ao longo da vigilância da gravidez não foi registrada nenhuma
melhora ao longo do tempo. Da mesma forma a proporção de gestantes diabéticas com avaliação pre-concepcional permaneceu pouco animadora. CONCLUSÕES: O seguimento de gestantes portadoras de diabetes mellitus em unidades multidisciplinares parece permitir um ajuste metabólico tão precoce quanto possÃvel, de forma a conseguir melhorar o
prognóstico obstétrico. A melhora nos cuidados pré-concepcionais continua sendo um desafio
Sarcoidosis or Tuberculosis? Difficulties in Diagnosis
A sarcoidose é uma doença multissistémica rara, caracterizada por granulomas não caseosos. A clÃnica e os testes diagnósticos são pouco sensÃveis e especÃficos, dificultando o diagnóstico diferencial, particularmente com a tuberculose. Relata-se o caso clÃnico de um rapaz de 17 anos com nódulos cutâneos dolorosos, astenia, hipersudorese e uveÃte recorrente com dois anos de evolução. Apresentava prova tuberculÃnica e interferon gamma release assay positivos, anemia e velocidade de sedimentação elevada, hipergamaglobulinemia, lisozima e enzima de conversão de angiotensina elevadas. A tomografia computorizada torácica mostrava opacidades micronodulares centrilobulares, gânglios mediastinicos e hilares calcificados; a broncofibroscopia e o teste de difusão de monóxido de carbono foram normais. A biópsia de nódulo cutâneo revelou paniculite septolobular.
A cintigrafia das glândulas lacrimal e salivar sugeriu sarcoidose. Não se podendo excluir tuberculose concomitante, iniciou antibacilares. Dois meses depois, foram associados prednisolona e metotrexato. Seis meses depois verificou-se remissão dos sintomas e normalização dos exames laboratoriais.
Este caso mostra as dificuldades no diagnóstico de sarcoidose e tuberculose na ausência dos achados microbiológicos e histológicos tÃpicos e a possibilidade da coexistência destas entidades.info:eu-repo/semantics/publishedVersio
Oxidative Stress, DNA, Cell Cycle/Cell Cycle Associated Proteins and Multidrug Resistance Proteins: Targets of Human Amniotic Membrane in Hepatocellular Carcinoma
The anticancer effects of human amniotic membrane (hAM) have been studied over the last decade. However, the action mechanisms responsible for these effects are not fully understood until now. Previously results reported by our team proved that hAM is able to induce cytotoxicity and cell death in hepatocellular carcinoma (HCC), a worldwide high incident and mortal cancer. Therefore, this experimental study aimed to investigate the cellular targets of hAM protein extracts (hAMPE) in HCC through in vitro studies. Our results showed that hAMPE is able to modify oxidative stress environment in all HCC cell lines, as well as its cell cycle. hAMPE differently targets deoxyribonucleic acid (DNA), P21, P53, β-catenin and multidrug resistance (MDR) proteins in HCC cell lines. In conclusion, hAMPE has several targets in HCC, being clear that the success of this treatment depends of a personalized therapy based on the biological and genetic characteristics of the tumor
Global distribution of the sickle cell gene and geographical confirmation of the malaria hypothesis
It has been 100 years since the first report of sickle haemoglobin (HbS). More than 50 years ago, it was suggested that the gene responsible for this disorder could reach high frequencies because of resistance conferred against malaria by the heterozygous carrier state. This traditional example of balancing selection is known as the 'malaria hypothesis'. However, the geographical relationship between the transmission intensity of malaria and associated HbS burden has never been formally investigated on a global scale. Here, we use a comprehensive data assembly of HbS allele frequencies to generate the first evidence-based map of the worldwide distribution of the gene in a Bayesian geostatistical framework. We compare this map with the pre-intervention distribution of malaria endemicity, using a novel geostatistical area-mean comparison. We find geographical support for the malaria hypothesis globally; the relationship is relatively strong in Africa but cannot be resolved in the Americas or in Asia
Longer duration of obesity is associated with a reduction in urinary angiotensinogen in prepubertal children
Background: We aimed to study the impact of obesity on urinary excretion of angiotensinogen (U-AGT) in prepubertal children, focusing on the duration of obesity and gender. Also, we aimed to evaluate whether plasma angiotensinogen (P-AGT) and hydrogen peroxide (H2O2) play a role in the putative association.
Methods: Cross-sectional evaluation of 305 children aged 8–9 years (160 normal weight, 86 overweight, and 59 obese). Anthropometric measurements and 24-h ambulatory blood pressure monitoring were performed. Angiotensinogen (AGT) was determined by a commercial enzyme-linked immunosorbent assay (ELISA) kit and H2O2 by a microplate fluorometric assay.
Results: U-AGT and P-AGT levels were similar across body mass index (BMI) groups and between sexes. However, boys who were overweight/obese since the age of 4 years presented lower levels of U-AGT compared with those of normal weight at the same age. In children who were overweight/obese since the age of 4, urinary H2O2 decreased with P-AGT.
Conclusions: A higher duration of obesity was associated with decreased U-AGT in boys, thus reflecting decreased intrarenal activity of the renin–angiotensin system. Also, children with a longer duration of obesity showed an inverse association between urinary H2O2 and P-AGT. Future studies should address whether these results reflect an early compensatory mechanism to limit obesity-triggered renal dysfunction.This project was supported by funds from Fundo Europeu de Desenvolvimento Regional (FEDER) from Programa Operacional Factores de Competitividade – COMPETE (FCOMP-01-0124-FEDER-028751), by national funds from the Portuguese Foundation for Science and Technology (FCT) (PTDC/DTP-PIC/0239/2012) and by Calouste Gulbenkian Foundation, that granted the study design and data collection and analysis. Liane Correia-Costa was supported by FCT (grant SFRH/SINTD/95898/2013), Teresa Sousa was supported by FCT and POPH/FSE (EC) (Ciência 2008 and SFRH/BPD/112005) and Franz Schaefer was supported by the ERA-EDTA Research Programme and the KfH Foundation for Preventive Medicine. The Epidemiology Research Unit (EPIUnit) is funded by FCT (UID/DTP/04750/2013)
Independent association of the variant rs1333049 at the 9p21 locus and coronary heart disease.
Introdução: Estudos recentes de associação
genómica em larga escala (GWAS)
identificaram vários polimorfismos de um
único nucleótido (SNP), localizados no locus
9p21, associados com doença arterial
coronária (DAC). De entre eles o SNP
rs1333049 demonstrou uma associação
consistente com a DAC tendo sido
reproduzida, com sucesso,
em várias populações.
Objectivo: Investigar se a nova variante
rs1333049, no cromossoma 9p21,
é um factor de risco independente
para DAC, na população Portuguesa.
Material e métodos: Estudo caso-controlo,
que incluiu 1406 indivÃduos, 723 doentes
coronários internados consecutivamente
(idade média de 53,7±8,9 anos 79,9% do
sexo masculino) e 683 controlos
sem doença coronária (idade média
de 53,3±10,5 anos, 73,9 % do sexo
masculino) seleccionados para não serem
significativamente diferentes quanto ao sexo
e idade. Estudou-se o SNP rs1333049,
em todos os indivÃduos,
com recurso à técnica convencionada de
PCR combinada com a técnica TaqMan (Applied Biosystems). Determinou-se a
distribuição alélica e genotÃpica (C/G), odds
ratio e respectivo intervalo de confiança
para risco de DAC.
Foi construÃdo um modelo de regressão
logÃstica forward wald ajustado para a
idade, sexo, factores de risco convencionais,
marcadores bioquÃmicos e genótipos em
estudo, afim de avaliar quais as variáveis
associadas de forma significativa e
independente com DAC.
Resultados: 60% dos doentes coronários e
53% dos controlos apresentaram o alelo C
(OR=1,33; p=0,0002), 35,7% dos doentes e
29,3% dos controlos tinham o genótipo
homozigoto CC (OR=1,34;p=0,010).
O heterozigoto CG estava presente em
48,1% dos doentes e 47% nos controlos,
não atingindo significância estatÃstica, para
risco vascular (OR=1,05;p=0,670). Após
análise multivariada de regressão logÃstica o
genótipo CC do cromossoma 9p21 ficou na
equação com um OR=1,7, p=0,018 e o
genótipo heterozigoto
CG com um OR=1,5, p=0,048.
Conclusão: Com o presente trabalho
replicou-se, numa população portuguesa, o
risco coronário ligado à nova variante
rs1333049 do cromossoma 9p21.
A robustez deste genótipo,
tanto em homo como em heterozigotia,
tem sido consistente e relevante na
estratificação de risco para a DAC,
mesmo em contextos populacionais
muito diversos. Nestas circunstâncias,
a utilização do genótipo CC ou CG
poderá vir a revelar-se útil
para a previsão do risco de DAC
na nossa população.INTRODUCTION:
Recent genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) at the 9p21 locus as risk factors for coronary artery disease (CAD). Among them, the SNP rs1333049 has demonstrated a consistent association with CAD, which has been successfully replicated in several populations.
AIM:
To investigate whether the SNP rs1333049 located on the 9p21 chromosome is an independent risk factor for CAD in a Portuguese population.
METHODS:
We performed a case-control study which included 1406 individuals, 723 consecutive coronary patients (mean age 53.71 +/- 8.9 years, 79.9% male and 683 controls without coronary disease (mean age 53.3 +/- 10.5 years, 73.9% male). Cases and controls were selected so as not to be significantly different in terms of gender and age. We studied the SNP rs1333049 at the 9p21 locus in all individuals, using standard PCR combined with the TaqMan technique (Applied Biosystems). The allelic and genotype distribution (C/G), odds ratios and corresponding confidence intervals for CAD risk were determined. A forward Wald logistic regression analysis model was constructed, adjusted for age, gender, conventional risk factors, biochemical markers and the genotypes under study, in order to determine which variables were linked significantly and independently with CAD.
RESULTS:
The C allele was found in 60% of the CAD patients and 53% of the controls, with OR = 1.33; p = 0.0002. The CC genotype appeared in 35.7% of CAD patients, with OR = 1.34, p = 0.010. The heterozygous CG genotype was present in 48.1% of the CAD patients and 47% of the controls, and did not present vascular risk (OR = 1.05, p = 0.670). After logistic regression analysis, the CC genotype remained in the equation with OR = 1.7; p = 0.018 and CG with OR = 1.5, p = 0.048.
CONCLUSION:
In the present study we replicated the coronary risk linked to the recently discovered variant rs1333049 on the 9p21 chromosome in a Portuguese population. Although the mechanism underlying the risk is still unknown, the robustness of this risk allele in risk stratification for CAD has been consistent, even in very different populations. The presence of the CC or CG genotype may thus prove to be useful for predicting the risk of developing CAD in the Portuguese population.info:eu-repo/semantics/publishedVersio
Dasatinib inhibits CXCR4 signaling in chronic lymphocytic leukaemia cells and impairs migration towards CXCL12
Chemokines and their ligands play a critical role in enabling chronic lymphocytic leukaemia (CLL) cells access to protective microenvironmental niches within tissues, ultimately resulting in chemoresistance and relapse: disruption of these signaling pathways has become a novel therapeutic approach in CLL. The tyrosine kinase inhibitor dasatinib inhibits migration of several cell lines from solid-organ tumours, but effects on CLL cells have not been reported. We studied the effect of clinically achievable concentrations of dasatinib on signaling induced by the chemokine CXCL12 through its' receptor CXCR4, which is highly expressed on CLL cells. Dasatinib pre-treatment inhibited Akt and ERK phosphorylation in CLL cells upon stimulation with CXCL12. Dasatinib also significantly diminished the rapid increase in actin polymerisation observed in CLL cells following CXCL12 stimulation. Moreover, the drug significantly inhibited chemotaxis in a transwell assay, and reduced the percentage of cells able to migrate beneath a CXCL12-expressing murine stromal cell line. Dasatinib also abrogated the anti-apoptotic effect of prolonged CXCL12 stimulation on cultured CLL cells. These data suggest that dasatinib, akin to other small molecule kinase inhibitors targeting the B-cell receptor signaling pathway, may redistribute CLL cells from protective tissue niches to the peripheral blood, and support the investigation of dasatinib in combination strategies
Enhancing chemosensitivity to gemcitabine via RNA interference targeting the catalytic subunits of protein kinase CK2 in human pancreatic cancer cells
<p>Abstract</p> <p>Background</p> <p>Pancreatic cancer is a complex genetic disorder that is characterized by rapid progression, invasiveness, resistance to treatment and high molecular heterogeneity. Various agents have been used in clinical trials showing only modest improvements with respect to gemcitabine-based chemotherapy, which continues to be the standard first-line treatment for this disease. However, owing to the overwhelming molecular alterations that have been reported in pancreatic cancer, there is increasing focus on targeting molecular pathways and networks, rather than individual genes or gene-products with a combination of novel chemotherapeutic agents.</p> <p>Methods</p> <p>Cells were transfected with small interfering RNAs (siRNAs) targeting the individual CK2 subunits. The CK2 protein expression levels were determined and the effect of its down-regulation on chemosensitization of pancreatic cancer cells was investigated.</p> <p>Results</p> <p>The present study examined the impact on cell death following depletion of the individual protein kinase CK2 catalytic subunits alone or in combination with gemcitabine and the molecular mechanisms by which this effect is achieved. Depletion of the CK2α or -α' subunits in combination with gemcitabine resulted in marked apoptotic and necrotic cell death in PANC-1 cells. We show that the mechanism of cell death is associated with deregulation of distinct survival signaling pathways. Cellular depletion of CK2α leads to phosphorylation and activation of MKK4/JNK while down-regulation of CK2α' exerts major effects on the PI3K/AKT pathway.</p> <p>Conclusions</p> <p>Results reported here show that the two catalytic subunits of CK2 contribute differently to enhance gemcitabine-induced cell death, the reduced level of CK2α' being the most effective and that simultaneous reduction in the expression of CK2 and other survival factors might be an effective therapeutic strategy for enhancing the sensitivity of human pancreatic cancer towards chemotherapeutic agents.</p
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