RESUMO
PURPOSE: To compare whether health-related quality of life (HRQoL) is altered in patients undergoing a treatment strategy guided by changes in dietary vitamin K. METHODS: This study is a randomized clinical trial carried out with chronic oral anticoagulation outpatients randomized into a control group (conventional dose adjustment of oral anticoagulants) (n = 66) and an intervention group (strategy based on changes in dietary vitamin K intake) (n = 66). HRQoL was measured using the Duke Anticoagulation Satisfaction Scale (DASS) at baseline and 90 days of follow-up. RESULTS: Patients with worse HRQoL were younger (p = 0.005) and were using a higher dose of baseline oral anticoagulants (p = 0.008), while those with better HRQoL scores had a higher level of education (p = 0.01). Both groups had significant improvements in HRQoL from baseline to 90 days in the global DASS score (p < 0.001), as well as in the negative and positive psychological impact (p < 0.001) domains. We did not observe differences in the variations of HRQoL scores in any of the DASS domains (p values > 0.05) between groups of interventions. Patients who achieved oral anticoagulation stability (n = 23) had significantly better HRQoL scores than patients who did not achieve stability (p = 0.003). CONCLUSION: Patients receiving the treatment strategy based on changes in dietary vitamin K intake did not have better HRQoL scores; however, both treatment approaches to manage oral anticoagulation improved HRQoL. Patients with greater oral anticoagulation stability had better HRQoL scores.
Assuntos
Anticoagulantes/uso terapêutico , Dieta , Qualidade de Vida , Vitamina K/administração & dosagem , Adulto , Idoso , Brasil , Feminino , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Satisfação do PacienteRESUMO
BACKGROUND: Dietary vitamin K intake has been considered a major factor that influences stability of oral anticoagulation (OA) with coumarins. Few studies have evaluated the relationship between amounts of dietary vitamin K intake and stability of anticoagulation. OBJECTIVE: To assess whether high dietary vitamin K intake is associated to stability of International Normalized Ratio (INR) of the prothrombin time. METHODS: We performed a sub-analysis of a randomized clinical trial involving outpatients from the anticoagulation clinic of a university hospital. INR and vitamin K intake were prospectively collected at baseline, 15, 30, 60 and 90 days after randomization. Patients were considered with a stable anticoagulation when their INR coefficient of variation was less than 10%. Dietary vitamin K intake was assessed by a food frequency questionnair and a score of intake was derived. RESULTS: We studied 132 patients on chronic OA (57 ± 13 years; 55% males); 23 patients (17%) were achieved stable anticoagulation. Stable and unstable patients had no significant differences in baseline characteristics. The dietary vitamin K score over the entire follow-up for stable patients was significantly lower than that for unstable patients (p = 0.012). DISCUSSION: Our findings suggest that INR stability could be achieved with relatively low amounts of dietary vitamin K.
Assuntos
Anticoagulantes/farmacologia , Cumarínicos/farmacologia , Dieta , Interações Alimento-Droga , Vitamina K/administração & dosagem , Idoso , Doença Crônica , Feminino , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-IdadeRESUMO
The present study addressed the question whether ExoU, a Pseudomonas aeruginosa toxin with phospholipase A2 (PLA2) activity, may induce airway epithelial cells to overexpress tissue factor (TF) and exhibit a procoagulant phenotype. Cells from the human bronchial epithelial BEAS-2B line were infected with an ExoU-producing P. aeruginosa strain, pre-treated or not with the cytosolic PLA2 inhibitor methylarachidonyl fluorophosphate (MAFP), or with two ExoU-deficient mutants. Control noninfected and infected cells were assessed for the expression of: 1) TF mRNA by RT-PCR; 2) cell-associated TF by enzyme immunoassay and flow cytometry; 3) procoagulant activity by a colorimetric assay; and 4) microparticle-associated TF by flow cytometry. An enzyme immunoassay was also used to assess cell-associated TF in lung extracts from mice infected intratracheally with ExoU-producing and -deficient bacteria. Cells infected with the wild-type bacteria had higher levels of TF mRNA, cell-associated TF expression, procoagulant activity and released microparticle-associated TF than cells infected with the mutants. Bacterial treatment with MAFP significantly reduced the expression of TF by infected cells. Lung samples from mice infected with the wild-type bacteria exhibited higher levels of cell-associated TF and procoagulant activity. The present results demonstrate that ExoU may contribute to the pathogenesis of lung injury by inducing a tissue factor-dependent procoagulant activity in airway epithelial cells.
Assuntos
Proteínas de Bactérias/fisiologia , Brônquios/microbiologia , Coagulantes/metabolismo , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/metabolismo , Animais , Ácidos Araquidônicos/metabolismo , Proteínas de Bactérias/metabolismo , Brônquios/citologia , Citosol/metabolismo , Feminino , Humanos , Camundongos , Modelos Biológicos , Mutação , Organofosfonatos/metabolismo , Fosfolipases A2/metabolismo , Infecções por Pseudomonas/diagnóstico , Tromboplastina/metabolismoRESUMO
As Pseudomonas aeruginosa ExoU possesses two functional blocks of homology to calcium-independent (iPLA(2)) and cytosolic phospholipase A(2) (cPLA(2)), we addressed the question whether it would exhibit a proinflammatory activity by enhancing the synthesis of eicosanoids by host organisms. Endothelial cells from the HMEC-1 line infected with the ExoU-producing PA103 strain exhibited a potent release of arachidonic acid (AA) that could be significantly inhibited by methyl arachidonyl fluorophosphonate (MAFP), a specific PLA(2) inhibitor, as well as significant amounts of the cyclooxygenase (COX)-derived prostaglandins PGE(2) and PGI(2). Cells infected with an isogenic mutant defective in ExoU synthesis did not differ from non-infected cells in the AA release and produced prostanoids in significantly lower concentrations. Infection by PA103 induced a marked inflammatory response in two different in vivo experimental models. Inoculation of the parental bacteria into mice footpads led to an early increase in the infected limb volume that could be significantly reduced by inhibitors of both COX and lipoxygenase (ibuprofen and NDGA respectively). In an experimental respiratory infection model, bronchoalveolar lavage (BAL) from mice instilled with 10(4) cfu of PA103 exhibited a marked influx of inflammatory cells and PGE(2) release that could be significantly reduced by indomethacin, a non-selective COX inhibitor. Our results suggest that ExoU may contribute to P. aeruginosa pathogenesis by inducing an eicosanoid-mediated inflammatory response of host organisms.
Assuntos
Eicosanoides/biossíntese , Infecções por Pseudomonas/metabolismo , Pseudomonas aeruginosa/fisiologia , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Ácido Araquidônico/antagonistas & inibidores , Ácido Araquidônico/metabolismo , Ácidos Araquidônicos/farmacologia , Proteínas de Bactérias/metabolismo , Toxinas Bacterianas/metabolismo , Linhagem Celular , Dinoprostona/metabolismo , Células Endoteliais/metabolismo , Células Endoteliais/microbiologia , Epoprostenol/metabolismo , Feminino , Fosfolipases A2 do Grupo IV , Humanos , Ibuprofeno/uso terapêutico , Indometacina/uso terapêutico , Inflamação/patologia , Inibidores de Lipoxigenase/uso terapêutico , Masoprocol/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Organofosfonatos/farmacologia , Fosfolipases A/antagonistas & inibidores , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/patologia , Pseudomonas aeruginosa/patogenicidadeRESUMO
Intracranial hemorrhage ICH is one of the most common neurological events in pre-term newborn ICH is associated with low birth weight (< 1500 g) and gestational age (GA) at delivery (< 32 weeks). The most common site affected is the germinal matrix. Papile et al. classifies it at four grades. We analyzed, prospectively, 50 newborns (27 boys) with ultrasound diagnostic of ICH; all of them were pre-term (GA < 37 weeks). They were classified according to sex, gestational age, birth weight and degree of ICH. The children were divided into two groups: A--GA < or = 33 weeks and B--34-37 weeks. In group A there were 34 children (25 boys) with mean GA of 31 weeks and birth weights average of 1308 g. In group B there were 16 children (2 boys), mean GA 34 weeks and birth weight average of 1951 g. The grades of ICH were: Group A--I-14, II-14, III-4 and IV-2; Group B--I-12, II-3 and III-1. The complications were more common in group A with 12 than group B with 4 children. The lesions happen in greatest number and most severity in children with low birth weight and younger (low gestational age). Ultrasound has shown to be effective for diagnostic and follow up of those children.
A hemorragia intracraniana (HIC) é a manifestação mais comum no sistema nervoso central de recém-nascidos (RN) prematuros, especialmente os de peso menor que 1500 g, ou com idade gestacional (IG) menor que 32 semanas. O local mais acometido é a matriz germinal e é classificado em graus por Papile et al. Foram analisados prospectivamente 50 RN pré-termo (IG <37 semanas) com diagnóstico de HIC ao exame ultra-sonográfico (US) transfontanelar. Eles foram classificados quanto à idade, sexo, idade gestacional, peso ao nascer, gravidade e evolução ultra-sonográfica da lesão. As crianças foram divididas em dois grupos (A: IG < 33 semanas e B: 34> IG<37 semanas). No grupo A tivemos 34 RN (25 meninos) com IG média de 31 semanas e peso médio de 1308 g. No grupo B tivemos 16 RN (2 meninos) com IG média de 34 semanas e peso médio de 1951 g. A distribuição da HIC nos grupos foi: Grupo A-Grau I- 14, II-14, III-4 e IV-2 e Grupo B-I-12, II- 3, III-1. Não houve diferença estatística do grau da HIC entre meninos e meninas ou entre os grupos de RN. As complicações foram mais comuns no grupo A, com um total de 12, contra 4 no Grupo B. O US se mostrou método eficiente no diagnóstico e acompanhamento dos RN com HIC.
Assuntos
Feminino , Humanos , Recém-Nascido , Masculino , Hemorragias Intracranianas , Peso ao Nascer , Distribuição de Qui-Quadrado , Idade Gestacional , Hemorragias Intracranianas/classificação , Recém-Nascido Prematuro , Espectroscopia de Ressonância Magnética , Estudos ProspectivosRESUMO
Pseudomonas aeruginosa has been shown to enter into human endothelial cells in vitro. To ascertain the effects of bacterial intracellular (IC) infection, endothelial cells were exposed to PAK and PAO-1 strains for 1 h and treated with gentamicin in culture medium for different periods. P. aeruginosa induced a significant production of superoxide and hydrogen peroxide by endothelial cells. Concentrations of IC bacteria were reduced progressively with time and no viable PAO-1 was detected at 24 h after infection. However, IC infection led to killing of 32.2%+/-2.9 and 51.8%+/-3.5 of the cells infected with PAK and PAO-1, respectively, as determined by the MTT assay. By three criteria (transmission electron microscopy, DNA electrophoresis and reactivity with annexin V) infected cells exhibited features of apoptosis. Treatment of infected cells with anti-oxidants (catalase, tocopherol and N -acetyl-L-cysteine) significantly decreased the percentage of cell death. In contrast, treatment with aminoguanidine, an inhibitor of inducible NO synthase, increased significantly the killing of PAO-1 infected cells. Based on these results we speculate that in response to P. aeruginosa infection, endothelial cells increase the production of reactive oxygen intermediates to eliminate IC pathogens, but cells do not resist the oxidative stress and die by apoptosis.
Assuntos
Apoptose/fisiologia , Endotélio/microbiologia , Infecções por Pseudomonas/patologia , Pseudomonas aeruginosa/patogenicidade , Acetilcisteína/farmacologia , Antioxidantes/farmacologia , Catalase/farmacologia , Linhagem Celular , DNA Bacteriano/química , DNA Bacteriano/isolamento & purificação , Eletroforese em Gel de Ágar , Endotélio/citologia , Citometria de Fluxo , Corantes Fluorescentes/química , Formazans/química , Guanidinas/farmacologia , Humanos , Lipopolissacarídeos , Microscopia Eletrônica , Microscopia de Fluorescência , Fenantridinas/química , Pseudomonas aeruginosa/química , Pseudomonas aeruginosa/genética , Espécies Reativas de Oxigênio/fisiologia , Sais de Tetrazólio/química , Vitamina E/farmacologiaRESUMO
Proinflammatory cytokines have been shown to activate endothelial cells. To investigate the effect of cytokines on the interaction of human umbilical vein endothelial cells (HUVEC) with Pseudomonas aeruginosa, cells were treated with interferon-gamma (IFN-gamma) plus tumour necrosis factor-alpha (TNF-alpha) for 24 hr and exposed to P. aeruginosa suspension for 1 hr. Light microscopy showed that activated cells internalized significantly more bacteria than control cells. To ascertain the effect of cytokines on the microbicidal activity of HUVEC, the concentrations of viable intracellular (IC) bacteria in control and activated cells were determined, at 1 and 5 hr postinfection, by the gentamicin exclusion assay. In control cells, no significant decrease in the concentration of bacteria was detected 5 hr postinfection. In contrast, in activated cells the concentration of viable bacteria at 5 hr was significantly lower. Concentrations of superoxide and hydrogen peroxide detected in supernatants of activated cells were significantly higher than in control cell supernatants. HUVEC anti-P. aeruginosa activity was insensitive to the antioxidants superoxide dismutase, dimethylthiourea and allopurinol as well as to the L-arginine analogues aminoguanidine and NG-monomethyl-L-arginine (L-NMMA), but was significantly inhibited by catalase. Our results indicate that HUVEC can be activated by IFN-gamma plus TNF-alpha to kill IC P. aeruginosa and suggest a role for reactive oxygen radicals, notably hydrogen peroxide, in HUVEC antibacterial activity.
Assuntos
Endotélio Vascular/imunologia , Interferon gama/imunologia , Pseudomonas aeruginosa/imunologia , Fator de Necrose Tumoral alfa/imunologia , Técnicas de Cultura de Células , Sobrevivência Celular/imunologia , Endocitose/imunologia , Endotélio Vascular/microbiologia , Humanos , Óxido Nítrico/imunologia , Espécies Reativas de Oxigênio/imunologia , Veias Umbilicais/imunologia , Veias Umbilicais/microbiologiaRESUMO
Release of lactate dehydrogenase (LDH) from the cytoplasmic compartment, trypan blue exclusion and methylthiazole tetrazolium (MTT) colorimetric assays were compared with regard to their sensitivity in detecting damage of human cultured epithelial cells induced by sodium fluoride or puromycin. LDH assay did not detect any difference between controls and cells treated with either of the two drugs. Cell monolayers treated with 0.3 sodium fluoride or 10(-2) M puromycin presented higher percentages of cells that took up the trypan blue dye than controls but monolayers treated with lower drug concentrations did not differ from controls. Viability measured by MTT assay was the most sensitive assay, detecting a dose-dependent impairment of cell function after treatment with the two drugs. Moreover, MTT offered major advantages in speed, simplicity and precise quantitation over the other viability assays
Assuntos
Humanos , Animais , Estudo Comparativo , Técnicas de Cultura de Células/métodos , Fígado/citologia , Chlorocebus aethiops , Sobrevivência Celular , Corantes , L-Lactato Desidrogenase/metabolismo , Mamíferos , Sais de Tetrazólio , Tiazóis , Azul Tripano , Células VeroRESUMO
Release of lactate dehydrogenase (LDH) from the cytoplasmic compartment, trypan blue exclusion and methylthiazole tetrazolium (MTT) colorimetric assays were compared with regard to their sensitivity in detecting damage of human cultured epithelial cells induced by sodium fluoride or puromycin. LDH assay did not detect any difference between controls and cells treated with either of the two drugs. Cell monolayers treated with 0.3 sodium fluoride or 10(-2) M puromycin presented higher percentages of cells that took up the trypan blue dye than controls but monolayers treated with lower drug concentrations did not differ from controls. Viability measured by MTT assay was the most sensitive assay, detecting a dose-dependent impairment of cell function after treatment with the two drugs. Moreover, MTT offered major advantages in speed, simplicity and precise quantitation over the other viability assays
Assuntos
Humanos , Animais , Técnicas de Cultura de Células , Fígado/citologia , Sobrevivência Celular , Chlorocebus aethiops , Corantes , L-Lactato Desidrogenase , Mamíferos , Sais de Tetrazólio , Tiazóis , Azul Tripano , Células VeroRESUMO
Release of lactate dehydrogenase (LDH) from the cytoplasmic compartment, trypan blue exclusion and methylthiazole tetrazolium (MTT) colorimetric assays were compared with regard to their sensitivity in detecting damage of human cultured epithelial cells induced by sodium fluoride or puromycin. LDH assay did not detect any difference between controls and cells treated with either of the two drugs. Cell monolayers treated with 0.3% sodium fluoride or 10(-2) M puromycin presented higher percentages of cells that took up the trypan blue dye than controls but monolayers treated with lower drug concentrations did not differ from controls. Viability measured by MTT assay was the most sensitive assay, detecting a dose-dependent impairment of cell function after treatment with the two drugs. Moreover, MTT offered major advantages in speed, simplicity and precise quantitation over the other viability assays.
Assuntos
Técnicas de Cultura de Células/métodos , Sobrevivência Celular , Fígado/citologia , Animais , Chlorocebus aethiops , Corantes , Humanos , L-Lactato Desidrogenase/metabolismo , Mamíferos , Sais de Tetrazólio , Tiazóis , Azul Tripano , Células VeroRESUMO
Twenty-seven children with hydrocephalus of different etiologies diagnosed by clinical examination, neurosonography and computerized brain tomography were submitted to transfontanellar US-Doppler evaluation for measurement of blood flow velocity and for the calculation of resistance index (RI) in the anterior and middle cerebral arteries and internal carotids. All children were submitted to evaluation before surgery and on the 1st, 30th and 60th postoperative days. We conclude that neurosonography and US-Doppler technique is useful for determination of hydrocephalus, indication and control of cerebrospinal fluid shunts and monitoring of changes in RI, comparing data obtained immediately before and after surgery and during the late postoperative period. The results obtained when comparing the RI values for the various arteries during the different stages of the study also permitted us to conclude that the anterior cerebral arteries are representative of the maximal alterations that occur in cerebral vascular resistance in pediatric patients with hydrocephalus.
Assuntos
Artérias Cerebrais/fisiologia , Hidrocefalia/fisiopatologia , Ultrassonografia Doppler/métodos , Velocidade do Fluxo Sanguíneo , Artérias Cerebrais/diagnóstico por imagem , Circulação Cerebrovascular/fisiologia , Feminino , Humanos , Hidrocefalia/diagnóstico por imagem , Hidrocefalia/cirurgia , Lactente , Recém-Nascido , Masculino , Período Pós-Operatório , Resistência VascularRESUMO
Release of lactate dehydrogenase (LDH) from the cytoplasmic compartment, trypan blue exclusion and methylthiazole tetrazolium (MTT) colorimetric assays were compared with regard to their sensitivity in detecting damage of human cultured epithelial cells induced by sodium fluoride or puromycin. LDH assay did not detect any difference between controls and cells treated with either of the two drugs. Cell monolayers treated with 0.3
sodium fluoride or 10(-2) M puromycin presented higher percentages of cells that took up the trypan blue dye than controls but monolayers treated with lower drug concentrations did not differ from controls. Viability measured by MTT assay was the most sensitive assay, detecting a dose-dependent impairment of cell function after treatment with the two drugs. Moreover, MTT offered major advantages in speed, simplicity and precise quantitation over the other viability assays.