RESUMO
This research presents an evaluation of a hybrid material based on gold nanoparticles (AuNPs), stabilized with the thiol 3-mercapto-propanesulfonate (3MPS) and loaded with the methotrexate drug (MTX). The AuNPs-3MPS-MTX nanosystem was tested for the treatment of cervical cancer and melanoma, using the B16-F10 melanoma and HeLa cell lines. The tests performed on cell cultures assessed the efficiency of the studied nanosystem on tumor cells, as well as its toxicology.
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Gluten-free pasta production with a low glycaemic index and improved nutritional profile is still a challenge for the food industry. In this study, pasta was produced from fenugreek (FF), chickpea (CPF) and tiger nut (TNF) flours. CPF and FF are interesting for a balanced contribution of soluble and insoluble fibre by combining the health benefits of each type of fibre that promotes health. TNF, also rich in insoluble fibre, can provide additional healthy properties. The partial substitution of TNF for FF (0, 2.5, 5, 7.5 and 10% w/w solids) was assessed, and the relation linking chemical composition, structure, cooking and rheological properties and predictive in-vitro starch digestion (eGI, expected glycaemic index) was analysed. The results revealed that FF, rich in galactomannans, not only improves the nutritional profile and lowers the eGI but also helps to naturally enhance the structure of the pasta product and, thus, cooking behaviour (higher swelling index and fewer cooking losses).
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The feasibility of replacing wheat semolina by tiger nut flour (20 and 40%) and xanthan gum (1%) in order to obtain high fibre dry pappardelle with fair techno-functional, structural and sensory attributes, was assessed. The cooking properties, texture, colour and sensory acceptance of uncooked and cooked pasta were evaluated. The proximate chemical composition of the raw materials, and the microstructure of the dry pasta were also assessed. The results in this manuscript address the improved nutritional value in terms of its dietary fibre, mineral content, oleic and linoleic acids, and the positive effects on the textural characteristics and cooking behaviour achieved on dry tiger nut based pappardelle using 1% of xanthan gum as a structural agent. Micrographs revealed in fact that the gluten network was better formed when xanthan gum was used. Furthermore, the obtained results seem to support that consumers would prefer pappardelle with 40% tiger nut flour.
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The aim of the work was to produce fibre-enriched fresh pasta based on micronised wheat bran and durum wheat semolina with appropriate techno-functional properties. Wheat semolina was replaced with fine particle size (50% below 75 µm) wheat bran - up to 11.54% (w/w). A Box-Behnken design with randomised response surface methodology was used to determine a suitable combination of carboxymethylcellulose, xanthan gum and locust bean gum to improve pasta attributes: minimum cooking loss, maximum values for water gain and swelling index, as well as better colour and texture characteristics before and after cooking. The proximate chemical composition of wheat semolina and bran was determined and the microstructure of uncooked pasta was observed as well. From the response surface methodology analysis, it is recommended to use: (i) xanthan gum over 0.6% w/w as it led to bran-enriched pasta with a better developed structure and superior cooking behaviour, (ii) a combination of xanthan gum (0.8% w/w) and carboxymethylcellulose (over 0.6% w/w) to enhance uncooked pasta yellowness.
Assuntos
Fibras na Dieta/análise , Aditivos Alimentares/química , Alimentos Fortificados , Cor , Manipulação de Alimentos , Galactanos/química , Mananas/química , Tamanho da Partícula , Gomas Vegetais/química , Polissacarídeos Bacterianos/química , Triticum/químicaRESUMO
Lactobacillus reuteri 6475 (Lr) of the human microbiome synthesizes histamine and can suppress inflammation via type 2 histamine receptor (H2R) activation in the mammalian intestine. Gut microbes such as Lr promote H2R signaling and may suppress H1R proinflammatory signaling pathways in parallel by unknown mechanisms. In this study, we identified a soluble bacterial enzyme known as diacylglycerol kinase (Dgk) from Lr that is secreted into the extracellular milieu and presumably into the intestinal lumen. DgK diminishes diacylglycerol (DAG) quantities in mammalian cells by promoting its metabolic conversion and causing reduced protein kinase C phosphorylation (pPKC) as a net effect in mammalian cells. We demonstrated that histamine synthesized by gut microbes (Lr) activates both mammalian H1R and H2R, but Lr-derived Dgk suppresses the H1R signaling pathway. Phospho-PKC and IκBα were diminished within the intestinal epithelium of mice and humans treated by wild-type (WT) Lr, but pPKC and IκBα were not decreased in treatment with ΔdgkA Lr. Mucosal IL-6 and systemic interleukin (IL)-1α, eotaxin, and granulocyte colony-stimulating factor (G-CSF) were suppressed in WT Lr, but not in ΔdgkA Lr colonized mice. Collectively, the commensal microbe Lr may act as a "microbial antihistamine" by suppressing intestinal H1R-mediated proinflammatory responses via diminished pPKC-mediated mammalian cell signaling.
Assuntos
Proteínas de Bactérias/metabolismo , Diacilglicerol Quinase/metabolismo , Mucosa Intestinal/imunologia , Limosilactobacillus reuteri/metabolismo , Proteína Quinase C/metabolismo , Receptores Histamínicos H2/metabolismo , Animais , Proteínas de Bactérias/genética , Citocinas/metabolismo , Diacilglicerol Quinase/genética , Histamina/imunologia , Humanos , Mediadores da Inflamação/metabolismo , Mucosa Intestinal/microbiologia , Limosilactobacillus reuteri/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Microbiota , Mutação/genética , Fosforilação , Receptores Histamínicos H1/metabolismo , Transdução de SinaisRESUMO
Low cardiac output syndrome (LCOS) after surgical aortic valve replacement (SAVR) is related to increased mortality and treatment related costs. We aimed to evaluate whether echocardiography-derived left ventricular global longitudinal strain (LV-GLS) relates to the occurrence of postoperative LCOS in patients undergoing SAVR. We prospectively enrolled 75 patients with symptomatic severe aortic stenosis, left ventricular ejection fraction (LVEF) >40%, NYHA Class Assuntos
Estenose da Valva Aórtica/cirurgia
, Valva Aórtica/cirurgia
, Baixo Débito Cardíaco/diagnóstico por imagem
, Ecocardiografia
, Implante de Prótese de Valva Cardíaca/efeitos adversos
, Função Ventricular Esquerda
, Função Ventricular Direita
, Idoso
, Valva Aórtica/diagnóstico por imagem
, Valva Aórtica/fisiopatologia
, Estenose da Valva Aórtica/diagnóstico por imagem
, Estenose da Valva Aórtica/mortalidade
, Estenose da Valva Aórtica/fisiopatologia
, Área Sob a Curva
, Fenômenos Biomecânicos
, Baixo Débito Cardíaco/etiologia
, Baixo Débito Cardíaco/mortalidade
, Baixo Débito Cardíaco/fisiopatologia
, Distribuição de Qui-Quadrado
, Feminino
, Implante de Prótese de Valva Cardíaca/mortalidade
, Humanos
, Modelos Logísticos
, Masculino
, Pessoa de Meia-Idade
, Análise Multivariada
, Variações Dependentes do Observador
, Razão de Chances
, Valor Preditivo dos Testes
, Estudos Prospectivos
, Curva ROC
, Reprodutibilidade dos Testes
, Medição de Risco
, Fatores de Risco
, Estresse Mecânico
, Fatores de Tempo
, Resultado do Tratamento
RESUMO
We studied 298 patients with severe aplastic anaemia (SAA) allografted in four Latin American countries. The source of cells was bone marrow (BM) in 94 patients and PBSCs in 204 patients. Engraftment failed in 8.1% of recipients with no difference between BM and PBSCs (P=0.08). Incidence of acute GvHD (aGvHD) for BM and PBSCs was 30% vs 32% (P=0.18), and for grades III-IV was 2.6% vs 11.6% (P=0.01). Chronic GvHD (cGvHD) between BM and PBSCs was 37% vs 59% (P=0.002) and extensive 5% vs 23.6% (P=0.01). OS was 74% vs 76% for BM vs PBSCs (P=0.95). Event-free survival was superior in patients conditioned with anti-thymocyte globulin (ATG)-based regimens compared with other regimens (79% vs 61%, P=0.001) as excessive secondary graft failure was seen with other regimens (10% vs 26%, P=0.005) respectively. In multivariate analysis, aGvHD II-IV (hazard ratio (HR) 2.50, confidence interval (CI) 1.1-5.6, P=0.02) and aGvHD III-IV (HR 8.3 CI 3.4-20.2, P<0.001) proved to be independent negative predictors of survival. In conclusion, BM as a source of cells and ATG-based regimens should be standard because of higher GvHD incidence with PBSCs, although the latter combining with ATG in the conditioning regimen could be an option in selected high-risk patients.
Assuntos
Anemia Aplástica/terapia , Soro Antilinfocitário/administração & dosagem , Antígenos HLA , Irmãos , Transplante de Células-Tronco , Doença Aguda , Adolescente , Adulto , Idoso , Aloenxertos , Anemia Aplástica/mortalidade , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , América Latina , Masculino , Pessoa de Meia-Idade , Taxa de SobrevidaRESUMO
BACKGROUND: A paucity of data exists about left atrium (LA) function in aortic valve stenosis (AS) or regurgitation (AR). Two-dimensional speckle tracking echocardiography allows the noninvasive study of LA functional disturbances in aortic valve disease and their impact in the development of pulmonary hypertension (PH). METHODS: Consecutive patients with moderate or severe AS or AR were included. Left ventricle (LV) and LA speckle tracking strain quantification was performed. We included 42 patients with AS and 30 with AR. Differences were not found in LA volumes and strain in AS or AR. The LA volumetric derangements parallel the decrease in LA longitudinal strain. Maximum LA volume, minimum LA volume, and indexed LA volume were higher in severe valvular disease (SVD) than in moderate [23 cc (P=.018, IC95% : 4-41), 16 cc (P=.035, IC95% : 2-31), and 14 cc (P=.022, IC95% : 2-25), respectively], occurred in the same way with LA strain in the conduit (6.3%, P=.034, IC95% : 1-12) and reservoir (7.1%, P=.04, IC95% : 2-14) phases. In multivariable model, strain of reservoir phase was the variable mainly associated with PH; each decrease in one unit of strain of reservoir phase increased 6% the PH probability (OR: 1.06, P=.01). CONCLUSIONS: This study demonstrates that in patients with AS and AR, the LA has a similar behavior and that exist a close correlation between LA volumetric and functional parameters. The variable mainly associated with PH was LA strain of reservoir phase.
Assuntos
Valva Aórtica/diagnóstico por imagem , Função do Átrio Esquerdo/fisiologia , Ecocardiografia/métodos , Átrios do Coração/fisiopatologia , Doenças das Valvas Cardíacas/fisiopatologia , Interpretação de Imagem Assistida por Computador/métodos , Valva Aórtica/fisiopatologia , Feminino , Seguimentos , Átrios do Coração/diagnóstico por imagem , Doenças das Valvas Cardíacas/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
PRIMARY OBJECTIVE: The aim of this study was to investigate the reparative potential of a polymeric scaffold designed for brain tissue repair in combination with lipoic acid. RESEARCH DESIGN: Histological, cytological and structural analysis of a combined treatment after a brain cryo-injury model in rats. METHODS AND PROCEDURES: Adult Wistar rats were subjected to cryogenic brain injury. A channelled-porous scaffold of ethyl acrylate and hydroxyethylacrylate, p(EA-co-HEA) was grafted into cerebral penumbra alone or combined with intraperitoneal LA administration. Histological and cytological evaluation was performed after 15 and 60 days and structural magnetic resonance (MRI) assessment was performed at 2 and 6 months after the surgery. MAIN OUTCOMES AND RESULTS: The scaffold was suitable for the establishment of different cellular types. The results obtained suggest that this strategy promotes blood vessels formation, decreased microglial response and neuron migration, particularly when LA was administrated. CONCLUSIONS: These evidences demonstrated that the combination of a channelled polymer scaffold with LA administration may represent a potential treatment for neural tissue repair after brain injury.
Assuntos
Acrilatos/uso terapêutico , Amilopectina/análogos & derivados , Lesões Encefálicas Traumáticas/terapia , Ácido Tióctico/uso terapêutico , Amilopectina/uso terapêutico , Animais , Encéfalo/patologia , Lesões Encefálicas/reabilitação , Lesões Encefálicas/terapia , Masculino , Plásticos , Ratos , Ratos Wistar , Alicerces TeciduaisRESUMO
There is substantial comorbidity between stress disorders and substance use disorders (SUDs), and acute stress augments the locomotor stimulant effect of cocaine in animal models. Here we endeavor to understand the neural underpinnings of comorbid stress disorders and drug use by determining whether the glutamatergic neuroadaptations that characterize cocaine self-administration are induced by acute stress. Rats were exposed to acute (2 h) immobilization stress, and 3 weeks later the nucleus accumbens core was examined for changes in glutamate transport, glutamate-mediated synaptic currents and dendritic spine morphology. We also determined whether acute stress potentiated the acquisition of cocaine self-administration. Acute stress produced an enduring reduction in glutamate transport and potentiated excitatory synapses on medium spiny neurons. Acute stress also augmented the acquisition of cocaine self-administration. Importantly, by restoring glutamate transport in the accumbens core with ceftriaxone the capacity of acute stress to augment the acquisition of cocaine self-administration was abolished. Similarly, ceftriaxone treatment prevented stress-induced potentiation of cocaine-induced locomotor activity. However, ceftriaxone did not reverse stress-induced synaptic potentiation, indicating that this effect of stress exposure did not underpin the increased acquisition of cocaine self-administration. Reversing acute stress-induced vulnerability to self-administer cocaine by normalizing glutamate transport poses a novel treatment possibility for reducing comorbid SUDs in stress disorders.
Assuntos
Transtornos Relacionados ao Uso de Cocaína/psicologia , Fármacos Atuantes sobre Aminoácidos Excitatórios/metabolismo , Fármacos Atuantes sobre Aminoácidos Excitatórios/uso terapêutico , Animais , Ceftriaxona/uso terapêutico , Estimulantes do Sistema Nervoso Central/farmacologia , Cocaína/metabolismo , Cocaína/farmacologia , Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Comorbidade , Espinhas Dendríticas/efeitos dos fármacos , Fármacos Atuantes sobre Aminoácidos Excitatórios/farmacocinética , Extinção Psicológica/efeitos dos fármacos , Ácido Glutâmico/metabolismo , Masculino , Núcleo Accumbens/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Autoadministração/métodos , Autoadministração/psicologia , Estresse Psicológico/metabolismo , Sinapses/efeitos dos fármacosRESUMO
The analysis of fertility in colonizing populations is of great interest, since its individuals experience a major environmental change, and fertility rates can reflect the level of adaptation of the population to its new conditions. Using Northrop's genealogical compilations, this paper examines the fertility pattern of California's early Spanish-Mexican colonists between 1742 and 1876, their fitness levels and their trend across time throughout the colonizing period. A total of 197 women from 599 compiled families who had completed their reproductive period and had at least one child were analysed. The correlations among variables were also analysed in order to infer the relationship between longevity and fertility, and the influence of fertility determinants. The results show a natural fertility pattern, with a very young age at marriage and birth of first child (17.2 and 19.1 years respectively), and also a young age at last childbirth (38.8 years). The population's fitness showed greater values than for contemporary European populations, with 8 of 9.2 children surviving to adulthood, in comparison with 55% of newborns in Finland for the same period, suggesting a good adaptation of the population to their new environmental conditions. No relationship between fertility and lifespan was observed, as has been reported by other authors and in opposition to classical theories. A temporal trend in the number of children, consisting of three different phases, was observed, in accordance with the stability of living conditions in the region.
Assuntos
Coeficiente de Natalidade , Colonialismo , Emigração e Imigração/história , Fertilidade , Adolescente , Adulto , Fatores Etários , Intervalo entre Nascimentos , Coeficiente de Natalidade/etnologia , California , Criança , Colonialismo/história , Feminino , Finlândia , História do Século XVIII , História do Século XIX , Humanos , Idade Materna , México/etnologia , Espanha/etnologia , Adulto JovemRESUMO
Highly aggressive cancer types such as pancreatic cancer possess a mortality rate of up to 80% within the first 6months after diagnosis. To reduce this high mortality rate, more sensitive diagnostic tools allowing an early stage medical imaging of even very small tumours are needed. For this purpose, magnetic, biodegradable nanoparticles prepared using recombinant human serum albumin (rHSA) and incorporated iron oxide (maghemite, γ-Fe2O3) nanoparticles were developed. Galectin-1 has been chosen as target receptor as this protein is upregulated in pancreatic cancer and its precursor lesions but not in healthy pancreatic tissue nor in pancreatitis. Tissue plasminogen activator derived peptides (t-PA-ligands), that have a high affinity to galectin-1 have been chosen as target moieties and were covalently attached onto the nanoparticle surface. Improved targeting and imaging properties were shown in mice using single photon emission computed tomography-computer tomography (SPECT-CT), a handheld gamma camera, and magnetic resonance imaging (MRI).
Assuntos
Magnetismo , Nanopartículas de Magnetita , Neoplasias Pancreáticas/diagnóstico , Animais , Linhagem Celular Tumoral , Compostos Férricos/química , Galectina 1/química , Galectina 1/metabolismo , Humanos , Imageamento por Ressonância Magnética , Camundongos , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Cintilografia , Compostos Radiofarmacêuticos , Proteínas Recombinantes/química , Albumina Sérica/química , Ativador de Plasminogênio Tecidual/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Multiple myeloma (MM) is a monoclonal gammopathy characterized by abnormal proliferation of malignant plasma cells. The median overall survival rate has changed from 2-3 to 5-6 or more years with the introduction of novel agents. Recently CD200 protein has been described as an immunosuppressive protein that confers a poor prognostic factor in several neoplastic diseases, including MM. The purpose of our study was to determine CD200 protein in plasma cells of newly diagnosed patients with MM and in CD3+ lymphocytes of healthy donors. METHODS: 35 newly diagnosed MM patients and 25 healthy donors were studied. For flow cytometry tests, a FacsCalibur device and CellQuestPro software were used. Monoclonal antibodies for CD38 (PeCyC5), CD138 (APC), and CD200 (PE) were used. The statistical analysis was performed with SPSS 19v. Mann-Whitney U test, Kaplan-Meier survival curves with Log-Rank tests were done when indicated. RESULTS: The frequencies of anemia, hypercalcemia, increased in LDH, serum creatinine and b2-microglobulin were 68%, 34%, 20%, 22% and 45% respectively. The treatment consisted in MPT 20 (57%), Thal-Dex 8 (23%), and VAD 7 (20%). Five patients (14%) achieved complete response, 17 (49%) partial response, and 13 (37%) minor response or failure to treatment. CONCLUSION: CD200 is a poor prognostic factor for overall survival in multiple myeloma patients. Bone marrow CD3 lymphocytes from MM patients express CD200 protein in higher proportion than healthy donors.
Introducción: el mieloma múltiple (MM) es una gammopatía monoclonal caracterizada por la proliferación anormal de células plasmáticas malignas. La proteína CD200 se ha descrito como una proteína con funciones inmunosupresoras y que es un factor de mal pronóstico en algunas enfermedades malignas, incluyendo al MM. El objetivo de este artículo es determinar la cantidad de proteína CD200 en células plasmáticas de pacientes con MM de reciente diagnóstico y en linfocitos CD3+ de donadores sanos. Métodos: se estudiaron 35 pacientes con diagnóstico reciente de MM y 25 individuos sanos. Se usaron los anticuerpos monoclonales para CD38 (PeCyC5), CD138 (APC), y CD200 (PE). El análisis estadístico fue realizado con el programa SPSS 19v. Se utilizaron las pruebas estadísticas U de Mann Whitney, curvas de supervivencia de Kaplan y Meier y la prueba de log-rank. Resultados: las frecuencias de anemia, hipercalcemia, elevación de DHL, creatinina sérica y beta-2 microglobulina fueron de 68%, 34%, 20%, 22% y 45% respectivamente. El tratamiento administrado fue MPT 20, Tal-Dex 8, y VAD 7. Cinco pacientes lograron respuesta completa, 17 respuesta parcial, y 13 respuesta menor o falla al tratamiento. Conclusiones: el CD200 es un factor de mal pronóstico para supervivencia global en pacientes con mieloma múltiple. Los linfocitos CD3+ de medula ósea de pacientes con MM expresan en mayor proporción CD200 en comparación con sujetos sanos.
Assuntos
Antígenos CD/metabolismo , Biomarcadores Tumorais/metabolismo , Mieloma Múltiplo/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Células da Medula Óssea/metabolismo , Estudos de Casos e Controles , Feminino , Citometria de Fluxo , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/mortalidade , Plasmócitos/metabolismo , Prognóstico , Estudos ProspectivosRESUMO
Poisoning is the fifth leading cause of death from unintentional injury in the WHO European region, while Spain is in the group with a lower rate. Most involuntary poisonings occur in young children while they are at the home, due to unintentional ingestion of therapeutic drugs or household products. Of these, a large percentage is stored in non-original containers and/or within reach of children. In this article, the Committee on Safety and Non-Intentional Injury Prevention in Childhood of the Spanish Association of Pediatrics provides a series of recommendations, educational as well as legal, to prevent such cases.
Assuntos
Intoxicação/prevenção & controle , Criança , Produtos Domésticos , Humanos , Preparações Farmacêuticas , Intoxicação/etiologia , EspanhaRESUMO
Mycobacterium tuberculosis, the primary causative agent of tuberculosis, infects macrophages and transforms the hostile intracellular environment into a permissive niche. M. tuberculosis infects macrophages using a variety of microbial ligand/cell receptor systems. In this study, binding assays with biotin-labelled mycobacterial cell wall proteins revealed five Concanavalin A-reactive proteins that bind macrophages. Among these proteins, we identified PstS-1, a 38-kDa M. tuberculosis mannosylated glycolipoprotein, and characterized it as an adhesin. Inhibition assays with mannan and immunoprecipitation demonstrated that PstS-1 binds the mannose receptor. We purified PstS-1 to 95.9% purity using ion exchange chromatography. The presence of mannose in purified PstS-1 was demonstrated by Concanavalin A interaction, which was abolished in the presence of sodium m-periodate and α-D-mannosidase. Gas chromatography revealed that purified PstS-1 contained 1% of carbohydrates by weight, which was mainly mannose. Finally, we used fluorescent microbeads coated with purified PstS-1 in phagocytosis assays and discovered that microbead uptake was inhibited by the pre-incubation of cells with GlcNAc, mannan and α-methyl mannoside. The interaction of PstS-1 coated beads with the mannose receptor was confirmed by confocal colocalization studies that showed high Pearson and Manders's colocalization coefficients. Our findings contribute to a better understanding of the strategies M. tuberculosis uses to infect host cells, the critical first step in the pathogenesis of tuberculosis.
Assuntos
Transportadores de Cassetes de Ligação de ATP/imunologia , Adesinas Bacterianas/imunologia , Proteínas de Bactérias/imunologia , Lectinas Tipo C/imunologia , Macrófagos/imunologia , Lectinas de Ligação a Manose/imunologia , Mycobacterium tuberculosis/imunologia , Receptores de Superfície Celular/imunologia , Acetilglucosamina/farmacologia , Aciltransferases/imunologia , Animais , Antígenos de Bactérias/imunologia , Aderência Bacteriana/imunologia , Linhagem Celular Tumoral , Parede Celular/imunologia , Concanavalina A/química , Imunoprecipitação , Mananas/farmacologia , Manose/metabolismo , Receptor de Manose , Proteínas de Membrana/imunologia , Metilmanosídeos/farmacologia , Camundongos , Mycobacterium tuberculosis/patogenicidade , Ácido Periódico/metabolismo , Fagocitose/imunologia , Ligação Proteica , Tuberculose Pulmonar/patologia , alfa-Manosidase/metabolismoRESUMO
Drowning is the second leading cause of non-intentional death in children under the age of 19 in Europe. Weather conditions in Spain allow an extended period of contact with water, therefore increasing the risk of drowning (due to the increased exposure), and constitutes the second leading cause of accidental death in children less than 14 years of age. In children younger than 5 years, drowning occurs mostly in pools belonging to private homes or communities, while in older children, drowning is often linked to aquatic recreational activities in lakes, sea, rivers and canals, and at times associated with alcohol consumption. In this article, the Committee on Safety and Non-Intentional Injury Prevention in Childhood of the Spanish Association of Pediatrics provides a series of architectonic, educational and legislative recommendations to prevent such incidents.
Assuntos
Afogamento/prevenção & controle , Criança , HumanosRESUMO
Great effort has been paid to identify novel targets for pharmaceutical intervention to control inflammation associated with different diseases. We have studied the effect of signalling inhibitors in the secretion of the proinflammatory and profibrogenic cytokine interleukin (IL)-1ß in monocyte-derived macrophages (M-DM) obtained from the ascites of cirrhotic patients and compared with those obtained from the blood of healthy donors. Peritoneal M-DM were isolated from non-infected ascites of cirrhotic patients and stimulated in vitro with lipopolysaccharide (LPS) and heat-killed Candida albicans in the presence or absence of inhibitors for c-Jun N-terminal kinase (JNK), mitogen-activated protein kinase kinase 1 (MEK1), p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K). The IL1B and CASP1 gene expression were evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The expression of IL-1ß and caspase-1 were determined by Western blot. IL-1ß was also assayed by enzyme-linked immunosorbent assay (ELISA) in cell culture supernatants. Results revealed that MEK1 and JNK inhibition significantly reduced the basal and stimulated IL-1ß secretion, while the p38 MAPK inhibitor had no effect on IL-1ß levels. On the contrary, inhibition of PI3K increased the secretion of IL-1ß from stimulated M-DM. The activating effect of PI3K inhibitor on IL-1ß release was mediated mainly by the enhancement of the intracellular IL-1ß and caspase-1 content release to the extracellular medium and not by increasing the corresponding mRNA and protein expression levels. These data point towards the role of MEK1 and JNK inhibitors, in contrast to the PI3K-protein kinase B inhibitors, as potential therapeutic tools for pharmaceutical intervention to diminish hepatic damage by reducing the inflammatory response mediated by IL-1ß associated with liver failure.
Assuntos
Ascite/imunologia , Interleucina-1beta/metabolismo , Cirrose Hepática/imunologia , Macrófagos Peritoneais/imunologia , Fosfatidilinositol 3-Quinases/fisiologia , Proteínas Proto-Oncogênicas c-akt/fisiologia , Adulto , Idoso , Caspase 1/fisiologia , Cromonas/farmacologia , Feminino , Humanos , Interleucina-1beta/genética , Sistema de Sinalização das MAP Quinases/fisiologia , Macrófagos Peritoneais/metabolismo , Masculino , Pessoa de Meia-Idade , Morfolinas/farmacologia , Inibidores de Fosfoinositídeo-3 QuinaseRESUMO
AIM: To describe the morbimortality associated to the development of acute kidney injury (AKI) defined by the pediatric adaptation of the RIFLE criteria in a Pediatric Intensive Care Unit (PICU). DESIGN: A retrospective cohort study was carried out. SETTING: Children admitted to a PICU in a tertiary care hospital. Patients or participants A total of 320 children admitted to a tertiary care hospital PICU during the year 2011. Neonates and renal transplant patients were excluded. Primary endpoints AKI was defined and classified according to the pediatric adaptation to the RIFLE criteria. PICU and hospital stays, use of mechanical ventilation and mortality were used to evaluate morbimortality. RESULTS: A total of 315 children met the inclusion criteria, with a median age of 19 months (range 6-72). Of these patients, 128 presented AKI (73 reached the Risk category and 55 reached the Injury and Failure categories). Children with AKI presented a longer PICU stay (6.0 [4.0-12.5] vs. 3.5 [2.0-7.0] days) and hospital stay (17 [10-32] vs. 10 [7-15] days), and a greater need for mechanical ventilation (61.7 vs. 36.9%). The development of AKI was an independent factor of morbidity, associated with a longer PICU and hospital stay, and with a need for longer mechanical ventilation, with a proportional relationship between increasing morbidity and the severity of AKI. CONCLUSION: The development of AKI in critically ill children is associated with increased morbimortality, which is proportional to the severity of renal injury.
Assuntos
Injúria Renal Aguda/complicações , Injúria Renal Aguda/mortalidade , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Unidades de Terapia Intensiva Pediátrica , Masculino , Admissão do Paciente , Estudos RetrospectivosRESUMO
BACKGROUND: The use of low-molecular-weight heparin (LMWH) for the chemoprophylaxis of venous thromboembolism (VTE) in trauma patients is supported by Level-1 evidence. Because Enoxaparin was the agent used in the majority of studies for establishing the efficacy of LMWH in VTE, it remains unclear if Dalteparin provides an equivalent effect. OBJECTIVE: To compare Dalteparin to Enoxaparin and investigate their equivalence as VTE prophylaxis in trauma. PATIENTS/SETTING: Trauma patients receiving VTE chemoprophylaxis in the Surgical Intensive Care Unit of a Level-1 Trauma Center from 2009 (Enoxaparin) to 2010 (Dalteparin) were included. MEASUREMENTS: The primary outcome was the incidence of clinically significant VTE. Secondary outcomes included heparin-induced thrombocytopenia (HIT), major bleeding, and drug acquisition cost savings. Equivalence margins were set between -5 and 5 %. MAIN RESULTS: A total of 610 patient records (277 Enoxaparin, 333 Dalteparin) were reviewed. The two study groups did not differ significantly: blunt trauma 67 vs. 62 %, p = 0.27; mean Injury Severity Score (ISS) 17 ± 10 vs. 16 ± 10, p = 0.34; Acute Physiology and Chronic Health Evaluation (APACHE) II score 17 ± 9 vs. 17 ± 10, p = 0.76; time to first dose of LMWH 69 ± 98 vs. 65 ± 67 h, p = 0.57). The rates of deep venous thrombosis (DVT) (3.2 vs. 3.3 %, p = 1.00), pulmonary emboli (PE) (1.8 vs. 1.2 %, p = 0.74), and overall VTE (5.1 vs. 4.5 %, p = 0.85) did not differ. The absolute difference in the incidence of overall VTE was 0.5 % [95 % confidence interval (CI): -2.9, 4.0 %, p = 0.85]. The 95 % CI was within the predefined equivalence margins. There were no significant differences in the frequency of HIT or major bleeding. The total year-on-year cost savings, achieved with 277 patients during the switch to Dalteparin, was estimated to be $107,778. CONCLUSIONS: Dalteparin is equivalent to Enoxaparin in terms of VTE in trauma patients and can be safely used in this population, with no increase in complications and significant cost savings.