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1.
Eur J Clin Microbiol Infect Dis ; 34(3): 609-17, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25373530

RESUMO

In several studies on patients with bloodstream infection (BSI), prior use of statins has been associated with improved survival. Gram-positive and Gram-negative bacteria alert the innate immune system in different ways. We, therefore, studied whether the relation between prior statin use and 90-day total mortality differed between Gram-positive and Gram-negative BSI. We conducted a prospective observational cohort study of 1,408 adults with BSI admitted to Levanger Hospital between January 1, 2002, and December 31, 2011. Data on the use of statins and other medications at admission, comorbidities, functional status, treatment, and outcome were obtained from the patients' hospital records. The relation of statin use with 90-day mortality differed between Gram-negative and Gram-positive BSI (p-value for interaction 0.01). Among patients with Gram-negative BSI, statin users had significantly lower 90-day total mortality [odds ratio (OR) 0.42, 95 % confidence interval (CI) 0.23-0.75, p = 0.003]. The association remained essentially unchanged after adjusting for the effect of sex, age, functional status before the infection, and underlying diseases that were considered confounders (adjusted OR 0.38, 95 % CI 0.20-0.72, p = 0.003). A similar analysis of patients with Gram-positive BSI showed no association of statin use with mortality (adjusted OR 1.22, 95 % CI 0.69-2.17, p = 0.49). The present study suggests that prior statin use is associated with a lower 90-day total mortality in Gram-negative BSI, but not in Gram-positive BSI.


Assuntos
Anticolesterolemiantes/uso terapêutico , Infecções por Bactérias Gram-Negativas/mortalidade , Infecções por Bactérias Gram-Positivas/mortalidade , Sepse/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sepse/microbiologia , Análise de Sobrevida , Resultado do Tratamento
2.
Clin Exp Immunol ; 173(3): 502-11, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23668802

RESUMO

Anti-microbial peptides might influence the pathogenesis and course of inflammatory bowel disease (IBD). We sought to clarify the role of the anti-microbial glycoprotein lipocalin 2 (LCN2) in the colon by determining its localization and regulation in IBD. Following a microarray gene expression study of colonic biopsies from a large IBD population (n = 133), LCN2 was localized using immunohistochemistry and in-situ hybridization. Moreover, we examined the regulation of LCN2 in HT-29 cells with a panel of pattern recognition receptors (PRRs) and sought evidence by immunohistochemistry that the most relevant PRR, the Toll-like receptor (TLR)-3, was indeed expressed in colonic epithelium in IBD. LCN2 was among the 10 most up-regulated genes in both active ulcerative colitis (UCa) and active Crohn's disease (CDa) versus healthy controls. LCN2 protein was found in both epithelial cells and infiltrating neutrophils, while mRNA synthesis was located solely to epithelial cells, indicating that de-novo synthesis and thus regulation of LCN2 as measured in the gene expression analysis takes place in the mucosal epithelial cells. LCN2 is a putative biomarker in faeces for intestinal inflammation, different from calprotectin due to its epithelial site of synthesis. LCN2 release from the colonic epithelial cell line HT-29 was enhanced by both interleukin (IL)-1ß and the TLR-3 ligand poly(I:C), and TLR-3 was shown to be expressed constitutively in colonic epithelial cells and markedly increased during inflammation.


Assuntos
Proteínas de Fase Aguda/metabolismo , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/metabolismo , Lipocalinas/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Receptor 3 Toll-Like/genética , Adulto , Idoso , Biópsia , Colite Ulcerativa/genética , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Doença de Crohn/genética , Doença de Crohn/metabolismo , Doença de Crohn/patologia , Feminino , Regulação da Expressão Gênica , Inativação Gênica , Células HT29 , Humanos , Doenças Inflamatórias Intestinais/patologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Lipocalina-2 , Lipocalinas/sangue , Masculino , Pessoa de Meia-Idade , Poli I-C/farmacologia , Transporte Proteico , Proteínas Proto-Oncogênicas/sangue , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor 3 Toll-Like/metabolismo , Adulto Jovem
3.
Clin Exp Immunol ; 167(3): 492-8, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22288592

RESUMO

Based on the ability to recruit lymphocytes and dendritic cells to lymphoid tissue and to promote inflammation, we hypothesized a role for dysregulated CCL19 and CCL21 levels in human immunodeficiency virus (HIV)-infected patients with advanced immunodeficiency, and in particular in those with accompanying Mycobacterium avium complex (MAC) infection. The hypothesis was explored by studies in HIV-infected patients with and without MAC infection, as well as in vitro, examining the ability of proteins from MAC to promote CCL19 and CCL21 responses in peripheral blood mononuclear cells (PBMC) during highly active anti-retroviral therapy (HAART). Our main findings were: (i) raised serum levels of CCL19 in HIV-infected patients with CD4(+) T cell count <50 cells/µl compared with HIV-infected patients with CD4(+) T cell count >500 cells/µl and healthy controls, with particularly high levels in those with MAC infection; (ii) elevated plasma levels of CCL19 predicted a higher mortality in acquired immune deficiency syndrome (AIDS)-patients, independent of ongoing MAC infection; and (iii) marked production of CCL19 in MAC-stimulated peripheral blood mononuclear cells (PBMC) and pronounced disturbances in MAC-induced CCL19 production in PBMC from HIV patients that was partly reversed during HAART. Our findings suggest the involvement of CCL19 in AIDS patients with advanced immunodeficiency, potentially mediating both adaptive and maladaptive responses.


Assuntos
Síndrome da Imunodeficiência Adquirida/imunologia , Quimiocina CCL19/sangue , Infecções Oportunistas Relacionadas com a AIDS/sangue , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Síndrome da Imunodeficiência Adquirida/sangue , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Adulto , Terapia Antirretroviral de Alta Atividade , Proteínas de Bactérias/imunologia , Biomarcadores/sangue , Estudos de Casos e Controles , Quimiocina CCL21/sangue , Feminino , Humanos , Técnicas In Vitro , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/microbiologia , Masculino , Pessoa de Meia-Idade , Complexo Mycobacterium avium/imunologia , Infecção por Mycobacterium avium-intracellulare/sangue , Infecção por Mycobacterium avium-intracellulare/imunologia , Prognóstico
4.
Eur Respir J ; 36(5): 1027-33, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20413541

RESUMO

Previous studies suggest a relationship between systemic inflammation and body composition in chronic obstructive pulmonary disease (COPD). We examined the relationships between body composition (fat free mass index (FFMI) kg·m(-2) and fat mass index (FMI) kg·m(-2)) and three plasma inflammatory markers C-reactive Protein (CRP), soluble tumour necrosis factor receptor 1 (sTNF-R1) and osteoprotegerin (OPG) in 409 stable COPD patients (aged 40-75 yrs, Global Initiative for Obstructive Chronic Lung Disease (GOLD) categories II-IV, 249 male) from the Bergen COPD Cohort Study in Norway. FFMI and FMI were measured by bioelectrical impedance. Plasma CRP (µg·mL(-1)), sTNF-R1 (pg·mL(-1)) and OPG (ng·mL(-1)) were determined by enzyme immunoassays. Correlations and Kruskal-Wallis tests were used for bivariate analyses. Linear regression models were fitted for each of the three markers, CRP, sTNF-R1 and OPG, with FFMI and FMI as explanatory variables including sex, age, smoking habits, GOLD category, hypoxaemia, Charlson Comorbidity Index and inhaled steroid use as potential confounders. CRP and sTNF-R1 levels correlated positively with both FFMI and FMI. The adjusted regression coefficients for an increase in logCRP per unit increase in FFMI was 1.23 (1.14-1.33) kg·m(-2) and 24.9 (11.8-38.1) kg·m(-2) for sTNF-R1. Higher FMI was associated with a lower OPG, with adjusted regression coefficient -0.14 (-0.23- -0.04), whereas FFMI was unrelated to OPG. In conclusion, COPD patients with low FFMI had lower not higher plasma levels of CRP and sTNF-R1, whereas higher fat mass was associated with higher CRP and sTNF-R1 and lower OPG.


Assuntos
Biomarcadores/sangue , Composição Corporal/fisiologia , Caquexia/imunologia , Caquexia/metabolismo , Doença Pulmonar Obstrutiva Crônica/imunologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Adulto , Idoso , Proteína C-Reativa/metabolismo , Estudos Transversais , Feminino , Humanos , Inflamação/imunologia , Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Osteoprotegerina/sangue , Receptores Tipo I de Fatores de Necrose Tumoral/sangue
5.
Eur Respir J ; 35(3): 540-8, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19643942

RESUMO

Chronic obstructive pulmonary disease (COPD) is considered an inflammatory pulmonary disorder with systemic inflammatory manifestations. The aim of this study was to assess the systemic levels of six inflammatory mediators in a large cohort of COPD patients and controls. 409 COPD patients and 231 healthy subjects, aged 40-75 yrs, were included from the first phase of the Bergen COPD Cohort Study. All COPD patients were clinically diagnosed by a physician, and had a forced expiratory volume in 1 s/forced vital capacity ratio less than 0.7 and a smoking history of >10 pack-yrs. The plasma levels of C-reactive protein (CRP), soluble tumour necrosis factor receptor (sTNFR)-1, osteoprotegrin, neutrophil activating peptide-2, CXCL16 and monocyte chemoattractant protein-4 were determined by ELISA. After adjustment for all known confounders, COPD patients had significantly lower levels of osteoprotegrin than subjects without COPD (p<0.05), and higher levels of CRP (p<0.01). Among COPD patients, CRP was elevated in patients with frequent exacerbations (p<0.05). sTNFR-1 and osteoprotegrin were both related to Global Initiative for Chronic Obstructive Lung Disease stage and frequency of exacerbations in the last 12 months (p<0.05). In addition, sTNFR-1 was significantly associated with important comorbidities such as hypertension and depression (p<0.05). The present study confirms that certain circulating inflammatory mediators are an important phenotypic feature of COPD.


Assuntos
Proteína C-Reativa/análise , Osteoprotegerina/sangue , Doença Pulmonar Obstrutiva Crônica/sangue , Receptores Tipo I de Fatores de Necrose Tumoral/sangue , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Quimiocina CXCL16 , Quimiocinas CXC/sangue , Estudos de Coortes , Feminino , Humanos , Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Proteínas Quimioatraentes de Monócitos/sangue , Peptídeos/sangue , Doença Pulmonar Obstrutiva Crônica/imunologia , Receptores Depuradores/sangue
6.
Farm Hosp ; 34(5): 231-6, 2010.
Artigo em Espanhol | MEDLINE | ID: mdl-20630782

RESUMO

OBJECTIVES: To offer a rationale for assigning a minimum score for risk of malnutrition for total proteins lower than 5g/dl and a scoring scale for our filter (FILNUT-Scale); and to analyse results of the MUST screening test performed on positive scores in the FILNUT nutritional filter and assess usefulness of said test in this population. METHODS: We searched the laboratory database for laboratory test orders (dated between 2004 and 2007) for which total proteins and albumin or cholesterol levels were determined, and we identified those with results for the above three parameters plus lymphocyte count. A limit (less than 5g/dl) was placed on the total protein level and the results for other parameters were not limited. Distribution curves for albumin and cholesterol were analysed. The same protocol was followed after establishing the CONUT score for each sample with the necessary parameters. From September 2007 to January 2008, the MUST test was performed on all FILNUT positives and we analysed how the degrees of risk corresponded. RESULTS: In 95% of the cases in which total proteins are lower than 5g/dl (n=1,176), albumin values are between 0.98 and 2.94g/dl, resulting in CONUT scores of 4 or 6 for albumin. Regarding total cholesterol, (n=761) 89.1% of the samples are lower than 180mg/dl, which accounts for one or two points in the score. In 98.79 % of the cases (n=490) that presented all four parameters, CONUT score was >/=5, which could be classified as medium or high risk. During the study period, 100% of the patients identified as medium or high risk by the FILNUT-Scale (n=568) tested as at-risk by MUST: of these, 421 (74.1%) were at high risk and 147 (25.9%) were at medium risk. CONCLUSIONS: Total proteins lower than 5g/dl determine a medium or high risk of malnutrition where a complete nutritional screening profile is lacking. This is why it should be included in the FILNUT-Scale with a score of five points. Performing the MUST test on patients with five or more points is efficient and provides clinical data needed for a complete assessment.


Assuntos
Desnutrição/diagnóstico , Estado Nutricional , Humanos , Medição de Risco/métodos , Software
7.
Clin Exp Immunol ; 158(2): 237-45, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19747210

RESUMO

Common variable immunodeficiency (CVID) is a heterogeneous syndrome characterized by defective immunoglobulin production and high frequency of bacterial infections, autoimmunity and manifestations of chronic inflammation. The homeostatic chemokines CCL19 and CCL21 and their receptor CCR7 are associated with modulation of inflammatory responses. CVID patients have decreased proportions of CCR7(+) T cells in peripheral blood and we hypothesized a further dysregulation of CCL19/CCL21/CCR7 in CVID. Serum levels of CCL19 and CCL21 were compared in CVID patients and controls. T cell expression of CCR7 was related to clinical characteristics in CVID patients. Spleens extirpated from CVID patients were analysed for expression of CCL19, CCL21 and CCR7. Peripheral blood mononuclear cells (PBMC) from CVID patients and controls were analysed for cytokine response on stimulation with CCL19 and CCL21. The main findings were: (i) CVID patients have raised serum levels of CCL19 and CCL21 independently of features of chronic inflammation; (ii) CCL19 and CCR7 have similar expression in spleens from CVID patients and controls, while CCL21 is variably down-regulated in spleens from patients; (iii) T cell expression of CCR7 is particularly low in patients characterized by chronic inflammation in vivo; and (iv) PBMC from CVID patients had attenuated cytokine response to stimulation with CCL19 and CCL21. CVID patients have raised circulatory levels of CCL19 and CCL21, and an attenuated cytokine response to stimulation with these chemokines. Because CCR7, CCL19 and CCL21 are key mediators balancing immunity and tolerance in the immune system, the abnormalities of these mediators might contribute to the profound immune dysregulation seen in CVID.


Assuntos
Quimiocinas/metabolismo , Imunodeficiência de Variável Comum/imunologia , Adulto , Células Cultivadas , Quimiocina CCL19/genética , Quimiocina CCL19/imunologia , Quimiocina CCL19/metabolismo , Quimiocina CCL21/genética , Quimiocina CCL21/imunologia , Quimiocina CCL21/metabolismo , Quimiocinas/genética , Quimiocinas/imunologia , Citocinas/biossíntese , Feminino , Expressão Gênica/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , RNA Mensageiro/genética , Receptores CCR7/imunologia , Receptores CCR7/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Baço/imunologia , Subpopulações de Linfócitos T/imunologia
8.
Clin Exp Immunol ; 157(3): 400-7, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19664149

RESUMO

CCL19 and CCL21 and their receptor CCR7 are expressed constitutively within lymphoid organs, regulating lymphocyte homing. Recent studies suggest that these chemokines may have inflammatory properties. We hypothesized a role of CCL19/CCL21 in human immunodeficiency virus (HIV) infection by promoting inflammation. We examined the expression of CCL19 and CCL21 in mononuclear cells from peripheral blood mononuclear cells (PBMC) and bone marrow mononuclear cells (BMMC) in HIV-infected patients before and during highly active anti-retroviral therapy (HAART). We also examined the ability of CCL19/CCL21 to promote inflammatory responses in these patients. PBMC from untreated HIV-infected patients (n = 29) released enhanced levels of CCL19 spontaneously compared with cells from controls (n = 20), particularly in those with symptomatic disease (n = 15, P < 0.01 versus controls). During HAART (n = 9), there was a decrease in the spontaneous CCL19 release and an increase in the phytohaemagglutinin-stimulated CCL19 release in both PBMC (P < 0.01) and BMMC (P < 0.05). In patients with enhanced HIV replication there was an increased proportion of inflammatory CD8(+)CCR7(-)CD45RA(-) T cells in peripheral blood [P < 0.01 and P < 0.05 versus controls, untreated (n = 9) and treatment failure (n = 8), respectively]. In vitro, CCL19/CCL21 promoted an inflammatory response in PBMC when accompanied by high viral load, irrespective of HAART. The HIV-tat protein significantly boosted the inflammatory effect of CCL19/CCL21 in PBMC. These findings link a dysregulated CCL19/CCL21/CCR7 system in HIV-infected patients to persistent inflammation and HIV replication, not only in untreated HIV infection, but also in treatment failure during HAART.


Assuntos
Quimiocina CCL19/imunologia , Quimiocina CCL21/imunologia , Infecções por HIV/imunologia , Linfócitos T/imunologia , Adulto , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Células da Medula Óssea/química , Estudos de Casos e Controles , Quimiocina CCL19/análise , Quimiocina CCL21/análise , Estudos Transversais , Feminino , Infecções por HIV/tratamento farmacológico , Homeostase , Humanos , Memória Imunológica , Leucócitos Mononucleares/química , Masculino , Receptores CCR7/análise , Estatísticas não Paramétricas , Falha de Tratamento , Carga Viral , Replicação Viral , Adulto Jovem
9.
Eur J Clin Invest ; 39(11): 1017-24, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19674076

RESUMO

BACKGROUND: While some chemokines are thought to be protective in HIV-infected individuals by their ability to block HIV entry into T cells and macrophages, chemokines could also have harmful effects in HIV infection through their ability to promote inflammation. Here, we examined the regulation and the effects of CXCL16, a newly discovered chemokine of the CXC family, in HIV-infected patients. MATERIALS AND METHODS: We examined serum levels of CXCL16 in clinically well-defined subgroups of HIV-infected individuals both before (n = 62) and during HAART (n = 40) as well as in age- and sex-matched healthy controls (n = 30). We also examined the effects of CXCL16 on inflammatory and anti-inflammatory cytokines and HIV replication in peripheral blood mononuclear cells (PBMC). RESULTS: Our main and novel findings were: (i) HIV-infected patients had significant raised CXCL16 levels according to disease severity and progression. (ii) During HAART, the immunological improvement was accompanied by a modest increase in CXCL16 level. (iii) While soluble CXCL16 promoted an anti-inflammatory response in PBMC from those on successful HAART, it induced an inflammatory response and enhanced HIV replication in PBMC from those with high viral load irrespectively of ongoing HAART. (iv) Recombinant HIV-tat protein significantly increased CXCL16 release in THP-1 macrophages. CONCLUSIONS: Our findings suggest a complex interaction between CXCL16 and HIV, promoting both inflammatory and anti-inflammatory effects as well as HIV replication, partly dependent on accompanying HIV replication.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Quimiocinas CXC/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Receptores Depuradores/imunologia , Replicação Viral/imunologia , Adulto , Terapia Antirretroviral de Alta Atividade , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/efeitos dos fármacos , Células Cultivadas , Quimiocina CXCL16 , Estudos Transversais , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , RNA Viral/imunologia , Carga Viral , Replicação Viral/efeitos dos fármacos
10.
Clin Exp Immunol ; 152(1): 57-63, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18241231

RESUMO

Although neutrophil gelatinase-associated lipocalin (NGAL) may play a pivotal role in the innate immune response, there are currently no data on NGAL levels in human immunodeficiency virus (HIV)-infected patients. In this study we aimed to examine the regulation of NGAL in HIV infection. The regulation of NGAL in HIV infection was examined by different experimental approaches, including studies in peripheral blood and mononuclear cells (MNC) from bone marrow aspirates before and during highly active anti-retroviral therapy (HAART). We found that: before initiating HAART, HIV-infected patients (n = 37) had significantly decreased serum NGAL levels compared with healthy controls (n = 26); (ii) during HAART, there was a gradual and significant increase in NGAL concentrations reaching levels comparable to those in healthy controls after 12 months; (iii) this increase was seen primarily in virological responders to HAART (HIV RNA level <200 copies/ml after 24 months); (iv) phytohaemagglutinin-stimulated NGAL release in MNC cells from bone marrow aspirates was decreased in untreated HIV-infected patients compared with healthy controls, but increased after 26 weeks on HAART; and (v) there was a significant positive correlation between neutrophil counts and NGAL levels at all time-points during HAART. We have shown decreased NGAL levels in HIV-infected patients, potentially reflecting decreased number and function of neutrophils as well as impaired bone marrow myelopoiesis. These abnormalities were reversed by successful HAART. Our findings underscore further the involvement of neutrophils and innate immunity in HIV-related immunodeficiency.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/sangue , HIV-1/isolamento & purificação , Lipocalinas/sangue , Proteínas Proto-Oncogênicas/sangue , Proteínas de Fase Aguda , Adulto , Terapia Antirretroviral de Alta Atividade , Células da Medula Óssea/metabolismo , Contagem de Linfócito CD4 , Células Cultivadas , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Lipocalina-2 , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , RNA Viral/sangue , Carga Viral
11.
Rev. int. med. cienc. act. fis. deporte ; 22(88): 845-861, dic. 2022. tab
Artigo em Espanhol | IBECS (Espanha) | ID: ibc-213728

RESUMO

El objetivo del estudio fue investigar los efectos de proporcionar información probabilística, obtenida del análisis en vídeo de las tendencias de pase de las colocadoras oponentes, sobre el rendimiento en el bloqueo de una jugadora de alto nivel de voleibol. Se analizó su tiempo de reacción, toma de decisión y calidad de ejecución durante 1117 acciones de bloqueo realizadas en 18 partidos de competición, antes y después de recibir esa información contextual de los ataques rivales. Los resultados revelaron que la bloqueadora reaccionó antes (p < .001) en aquellos partidos que recibió información sobre las tendencias de pase de las colocadoras oponentes. En cambio, esta información contextual no tuvo influencia sobre sus decisiones, ni en la calidad de ejecución de sus movimientos. Estos resultados refuerzan el uso de información probabilística como una estrategia competitiva para iniciar antes una respuesta preparatoria a la acción de bloqueo en voleibol de alto nivel. (AU)


The aim of the study was to investigate the effects of providing probabilistic information, obtained from video-performance analytics on passing direction tendencies in opposing volleyball setters, on blocking performance in a high skilled female volleyballer. Data on reaction times, decision-making and quality of movement execution of the skilled blocker were analyzed during 1117 blocking actions in 18 competitive matches, before and after receiving information from the passing tendencies of opposition setters. Results revealed that the blocker reacted significantly earlier in those matches when she received information about opposition pass direction tendencies. No effects of contextual information were found for the blocker´s decisions and quality of movement execution. These results reinforced the use of probabilistic information as a competitive strategy for initiating an early preparatory response to the blocking action in high-skill levels of volleyball. (AU)


Assuntos
Humanos , Feminino , Adulto Jovem , Voleibol , Atletas , Destreza Motora , Espanha , Tempo de Reação
12.
J Thromb Haemost ; 4(10): 2140-7, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16856976

RESUMO

BACKGROUND: Chemokines and platelet activation are both important in atherogenesis. Platelet inhibitors are widely used in coronary artery disease (CAD), and we hypothesized that the platelet inhibitor clopidogrel could modify chemokines in CAD patients. OBJECTIVES: We sought to investigate the effect of clopidogrel on the expression of chemokines and chemokine receptors in peripheral blood mononuclear cells (PBMC) in CAD patients. PATIENTS/METHODS: Thirty-seven patients with stable angina were randomized to clopidogrel (n = 18) or placebo (n = 19). PBMC, blood platelets and plasma were collected at baseline and after 7-10 days in the patients, and in 10 healthy controls. mRNA levels of chemokines and chemokine receptors in PBMC were analyzed by ribonuclease protection assays and real-time reverse transcriptase polymerase chain reaction. Platelet activation was studied by flow cytometry. RESULTS: (i) At baseline, the gene expression of the regulated on activation normally T-cell expressed and secreted (RANTES) chemokines and macrophage inflammatory peptide (MIP)-1beta in PBMC, the expression of CD62P and CD63 on platelets and the levels of platelet-derived microparticles (PMP) were elevated in angina patients comparing healthy controls; (ii) markers of platelet activation were either reduced (CD63) or unchanged (CD62P, PMP, beta-thromboglobulin) during clopidogrel therapy; (iii) in contrast, clopidogrel significantly up-regulated the gene expression of RANTES and MIP-1beta in PBMC, while no changes were found in the placebo group; (iv) a stable adenosine 5'-diphosphate metabolite attenuated the release of MIP-1beta, but not of RANTES, from activated PBMC in vitro. CONCLUSIONS: Even if we do not argue against a beneficial role for clopidogrel in CAD, our findings may suggest potential inflammatory effects of clopidogrel in CAD.


Assuntos
Quimiocinas/biossíntese , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/tratamento farmacológico , Regulação da Expressão Gênica , Leucócitos Mononucleares/metabolismo , Inibidores da Agregação Plaquetária/uso terapêutico , Ticlopidina/análogos & derivados , Idoso , Células Cultivadas , Clopidogrel , Método Duplo-Cego , Endotélio Vascular/metabolismo , Feminino , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Placebos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ticlopidina/uso terapêutico
13.
J Ethnopharmacol ; 103(3): 433-8, 2006 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-16174557

RESUMO

Magnistipula butayei subsp. montana (Chrysobalanaceae) is known, in the Great Lakes Region, to possess toxicological properties. In this paper, we investigated the acute toxicity (dose levels 50-1600 mg/kg) of its aqueous extract, administered orally to adult Wistar rats. This study demonstrated that the freeze-dried aqueous extract (5%, w/w) possesses high toxicity. The extract caused hypothermia, neurological disorders, including extensor reflex of maximal convulsive induced-seizures at about 2 h after the administered dose, and death occurred (LD50=370 mg/kg) in a dose dependent manner. Blood parameter evaluation revealed slight variations, but these might not have clinical relevance. Histological examination of internal organs (lungs, liver, heart and kidneys) did not reveal any abnormality in the treated group compared to the control. Therefore, it can be concluded that Magnistipula butayei subsp. montana aqueous extract, given orally, is toxic and that its target is the central nervous system. General phytochemical screening revealed that the plant did not contain significant amounts of products known to be toxic, such as alkaloids or cardioactive glycosides, but only catechic tannins, amino acids, saponins and other aphrogen principles in the three parts of the species (fruit, leave and bark).


Assuntos
Sistema Nervoso Central/efeitos dos fármacos , Chrysobalanaceae/química , Extratos Vegetais/toxicidade , África Central , Animais , Antocianinas/isolamento & purificação , Temperatura Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Frutas , Dose Letal Mediana , Masculino , Casca de Planta , Extratos Vegetais/química , Folhas de Planta , Ratos , Ratos Wistar , Saponinas/isolamento & purificação , Convulsões/etiologia , Taninos/isolamento & purificação
14.
Nutr Hosp ; 21(4): 491-504, 2006.
Artigo em Espanhol | MEDLINE | ID: mdl-16913209

RESUMO

INTRODUCTION: According to several series, hospital hyponutrition involves 30-50% of hospitalized patients. The high prevalence justifies the need for early detection from admission. There several classical screening tools that show important limitations in their systematic application in daily clinical practice. OBJECTIVES: To analyze the relationship between hyponutrition, detected by our screening method, and mortality, hospital stay, or re-admissions. To analyze, as well, the relationship between hyponutrition and prescription of nutritional support. To compare different nutritional screening methods at admission on a random sample of hospitalized patients. Validation of the INFORNUT method for nutritional screening. MATERIAL AND METHODS: In a previous phase from the study design, a retrospective analysis with data from the year 2003 was carried out in order to know the situation of hyponutrition in Virgen de la Victoria Hospital, at Malaga, gathering data from the MBDS (Minimal Basic Data Set), laboratory analysis of nutritional risk (FILNUT filter), and prescription of nutritional support. In the experimental phase, a cross-sectional cohort study was done with a random sample of 255 patients, on May of 2004. Anthropometrical study, Subjective Global Assessment (SGA), Mini-Nutritional Assessment (MNA), Nutritional Risk Screening (NRS), Gassull's method, CONUT and INFORNUT were done. The settings of the INFORNUT filter were: albumin < 3.5 g/dL, and/or total proteins <5 g/dL, and/or prealbumin <18 mg/dL, with or without total lymphocyte count < 1.600 cells/mm3 and/or total cholesterol <180 mg/dL. In order to compare the different methods, a gold standard is created based on the recommendations of the SENPE on anthropometrical and laboratory data. The statistical association analysis was done by the chi-squared test (a: 0.05) and agreement by the k index. RESULTS: In the study performed in the previous phase, it is observed that the prevalence of hospital hyponutrition is 53.9%. One thousand six hundred and forty four patients received nutritional support, of which 66.9% suffered from hyponutrition. We also observed that hyponutrition is one of the factors favoring the increase in mortality (hyponourished patients 15.19% vs. non-hyponourished 2.58%), hospital stay (hyponourished patients 20.95 days vs. non-hyponourished 8.75 days), and re-admissions (hyponourished patients 14.30% vs. non-hyponourished 6%). The results from the experimental study are as follows: the prevalence of hyponutrition obtained by the gold standard was 61%, INFORNUT 60%. Agreement levels between INFORNUT, CONUT, and GASSULL are good or very good between them (k: 0.67 INFORNUT with CONUT, and k: 0.94 INFORNUT and GASSULL) and wit the gold standard (k: 0.83; k: 0.64 CONUT; k: 0.89 GASSULL). However, structured tests (SGA, MNA, NRS) show low agreement indexes with the gold standard and laboratory or mixed tests (Gassull), although they show a low to intermediate level of agreement when compared one to each other (k: 0.489 NRS with SGA). INFORNUT shows sensitivity of 92.3%, a positive predictive value of 94.1%, and specificity of 91.2%. After the filer phase, a preliminary report is sent, on which anthropometrical and intake data are added and a Nutritional Risk Report is done. CONCLUSIONS: Hyponutrition prevalence in our study (60%) is similar to that found by other authors. Hyponutrition is associated to increased mortality, hospital stay, and re-admission rate. There are no tools that have proven to be effective to show early hyponutrition at the hospital setting without important applicability limitations. FILNUT, as the first phase of the filter process of INFORNUT represents a valid tool: it has sensitivity and specificity for nutritional screening at admission. The main advantages of the process would be early detection of patients with risk for hyponutrition, having a teaching and sensitization function to health care staff implicating them in nutritional assessment of their patients, and doing a hyponutrition diagnosis and nutritional support need in the discharge report that would be registered by the Clinical Documentation Department. Therefore, INFORNUT would be a universal screening method with a good cost-effectiveness ratio.


Assuntos
Hospitalização , Desnutrição/diagnóstico , Desnutrição/epidemiologia , Avaliação Nutricional , Apoio Nutricional , Distribuição de Qui-Quadrado , Estudos de Coortes , Análise Custo-Benefício , Estudos Transversais , Mortalidade Hospitalar , Humanos , Programas de Rastreamento , Fenômenos Fisiológicos da Nutrição , Estado Nutricional , Readmissão do Paciente , Prevalência , Estudos Retrospectivos , Estudos de Amostragem , Sensibilidade e Especificidade , Espanha , Fatores de Tempo
15.
J Am Coll Cardiol ; 37(2): 485-91, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11216967

RESUMO

OBJECTIVES: We sought to study the relationships between chemokines and oxidative stress in acute coronary syndrome. BACKGROUND: In view of existing knowledge on the participation of leukocytes and oxidative stress in the pathogenesis of acute coronary syndrome, we hypothesized that chemokines may play a role in recruiting and activating leukocytes in this disorder. METHODS: The levels of chemokines and oxidative stress were studied in 38 patients with stable and 38 with unstable angina and in 20 controls. In separate in vitro experiments the effect of chemokines on reactive oxygen species in monocytes and the effect of antioxidants on chemokine levels in these cells were also studied. RESULTS: 1) Angina patients had raised serum levels of chemokines in both cross-sectional and longitudinal testing, with particularly high levels of interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory peptide (MIP)-1-alpha in unstable disease. 2) T cells, and particularly monocytes, seem to contribute to the raised IL-8, MCP-1 and MIP-1-alpha levels in unstable angina. 3) Concomitantly, and significantly correlated with MCP-1 and IL-8 levels, stable and particularly unstable angina patients had decreased plasma levels of antioxidants and increased lipid peroxidation, suggesting enhanced oxidative stress. 4) Monocyte chemoattractant protein-1 enhanced the generation of O2- in monocytes from unstable angina patients, and the antioxidant glutathione-monoethyl ester suppressed the production of IL-8 and MCP-1 in these cells. CONCLUSIONS: Our findings suggest an interaction between chemokines and oxidative stress in unstable angina. This interaction may represent a vicious circle involved in the pathogenesis of acute coronary syndromes.


Assuntos
Angina Pectoris/imunologia , Angina Instável/imunologia , Quimiocinas/sangue , Doença das Coronárias/imunologia , Estresse Oxidativo/imunologia , Adulto , Idoso , Antioxidantes/metabolismo , Feminino , Humanos , Leucócitos/imunologia , Peroxidação de Lipídeos/imunologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco
16.
J Am Coll Cardiol ; 38(1): 187-93, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11451272

RESUMO

OBJECTIVES: We sought to study the gene expression of chemokines and their corresponding receptors in mononuclear blood cells (MNCs) from patients with chronic heart failure (CHF), both of which were cross-sectional and longitudinal studies during therapy with intravenous immunoglobulin (IVIg). BACKGROUND: We have recently demonstrated that IVIg improves left ventricular ejection fraction (LVEF) in patients with CHF. Based on the potential pathogenic role of chemokines in CHF, we hypothesized that the beneficial effect of IVIg may be related to a modulatory, effect on the expression of chemokines and their receptors in MNCs. METHODS: We examined: 1) the gene expression of C, CC and CXC chemokines and their receptors in MNCs from 20 patients with CHF and 10 healthy blood donors; and 2) the expression of these genes in MNCs from 20 patients with CHF randomized in a double-blind fashion to therapy with IVIg or placebo for 26 weeks. RESULTS: Our main findings in CHF were: 1) markedly raised gene expression of macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and interleukin (IL)-8; 2) enhanced gene expression of their corresponding receptors; 3) modulation in a normal direction of this abnormal chemokine and chemokine receptor gene expression during IVIg, but not during placebo therapy; 4) down-regulation of MIP-1alpha, MIP-1beta and IL-8 during IVIg at the protein level in plasma; and 5) a correlation between down-regulation of MIP-1alpha gene expression and improved LVEF during IVIg therapy. CONCLUSIONS: Our results further support a pathogenic role for chemokines in CHF and suggest that IVIg may represent a novel therapeutic approach, with the potential to improve LVEF in patients with CHF, possibly by modulatory effects on the chemokine network.


Assuntos
Expressão Gênica , Insuficiência Cardíaca/fisiopatologia , Leucócitos Mononucleares/metabolismo , Receptores de Quimiocinas/metabolismo , Idoso , Quimiocinas C/metabolismo , Quimiocinas CC/metabolismo , Quimiocinas CXC/metabolismo , Feminino , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/imunologia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Interleucina-8/metabolismo , Proteínas Inflamatórias de Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia
17.
Cardiovasc Res ; 45(2): 428-36, 2000 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-10728363

RESUMO

OBJECTIVES: The purpose of the present study was to examine the circulating levels of CXC-chemokines in patients with various degree of congestive heart failure (CHF). BACKGROUND: CXC-chemokines may be important mediators in the persistent immune activation observed in CHF patients by activation of circulating neutrophils, T-cells and monocytes and possibly by the recruitment of these cells into the failing myocardium. METHODS: Levels of interleukin (IL)-8, growth-regulated oncogene (GRO) alpha and epithelial neutrophil activating peptide (ENA)-78 were measured both in serum and in platelet-free plasma by enzyme immunoassay in 47 patients with CHF and in 20 healthy controls. RESULTS: (i) CHF patients had significantly elevated levels of all the three CXC-chemokines with IL-8 and GRO alpha showing a gradual increase along with increasing NYHA class. (ii) There was an inverse correlation between IL-8 and left ventricular ejection fraction (EF) and cardiac index (CI). (iii) Both unstimulated and lipopolysaccharide (LPS)-stimulated monocytes from CHF patients released markedly elevated amounts of all three CXC-chemokines. (iv) Platelets from patients with severe CHF were characterised by decreased content of GRO alpha and ENA-78 as well as decreased release of these chemokines upon thrombin receptor stimulation. (v) Activated platelets stimulated peripheral blood mononuclear cells in vitro to enhanced release of IL-8, and neutralising antibodies against ENA-78 inhibited this interaction. CONCLUSIONS: This study demonstrates for the first time elevated levels of CXC-chemokines in CHF, which may be of importance for progression of heart failure. Our findings further suggest that activated monocytes and platelets may contribute to enhanced CXC-chemokine levels in CHF.


Assuntos
Quimiocinas CXC/sangue , Insuficiência Cardíaca/sangue , Peptídeos e Proteínas de Sinalização Intercelular , Análise de Variância , Estudos de Casos e Controles , Quimiocina CXCL1 , Quimiocina CXCL5 , Fatores Quimiotáticos/sangue , Feminino , Substâncias de Crescimento/sangue , Insuficiência Cardíaca/imunologia , Humanos , Interleucina-8/análogos & derivados , Interleucina-8/sangue , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Ativação Plaquetária , Estatísticas não Paramétricas
18.
Cardiovasc Res ; 47(4): 778-87, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10974226

RESUMO

OBJECTIVES: Chemokines regulate several biological processes, such as chemotaxis, collagen turnover, angiogenesis and apoptosis. Based on the persistent immune activation with elevated circulating levels of chemokines in patients with congestive heart failure (CHF), we have hypothesised a pathogenic role for chemokines in the development of CHF. The objective of this study was to examine mRNA levels and cellular localisation of chemokines and chemokine receptors in human CHF. METHODS: We examined explanted hearts from ten patients with end-stage heart failure (all chambers) and in ten organ donors using an RNase protection assays and immunohistochemical techniques. RESULTS: Our main findings were: (i) expression of eight chemokine and nine chemokine receptor genes in both failing and nonfailing myocardium, (ii) particularly high mRNA levels of monocyte chemoattractant protein (MCP)-1 and CXC-chemokine receptor 4 (CXCR4), in both chronic failing and nonfailing myocardium, (iii) decreased mRNA levels of MCP-1 and interleukin (IL)-8 in the failing left ventricles compared to failing left atria, (iv) decreased chemokine (e.g., MCP-1 and IL-8) and increased chemokine receptor (e.g., CCR2, CXCR1) mRNA levels in failing left ventricles and failing left atria compared to corresponding chambers in the nonfailing hearts and (v) immunolocalisation of MCP-1, IL-8 and CXCR4 to cardiomyocytes. CONCLUSION: The present study demonstrates for the first time chemokine and chemokine receptor gene expression and protein localisation in the human myocardium, introducing a new family of mediators with potentially important effects on the myocardium. The observation of chemokine dysregulation in human end-stage heart failure may represent a previously unknown mechanism involved in progression of chronic heart failure.


Assuntos
Quimiocinas CC/análise , Quimiocinas CXC/análise , Insuficiência Cardíaca/metabolismo , Miocárdio/química , Receptores de Quimiocinas/análise , Adulto , Análise de Variância , Cardiomiopatia Dilatada/metabolismo , Estudos de Casos e Controles , Quimiocinas CC/genética , Quimiocinas CXC/genética , Doença das Coronárias/metabolismo , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Hibridização In Situ , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/análise , Receptores CCR1 , Receptores CCR2 , Receptores CCR4 , Receptores CCR5/genética , Receptores CXCR4/genética , Receptores de Quimiocinas/genética , Receptores de Interleucina-8A/genética
19.
J Infect ; 70(4): 381-91, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25597826

RESUMO

OBJECTIVES: Biomarkers for diagnosis and therapy efficacy in tuberculosis (TB) are requested. We have studied biomarkers that may differentiate between active and latent TB infection (LTBI), the influence of HIV infection and changes during anti-TB chemotherapy. METHODS: Thirty-eight plasma cytokines, assessed by multiplex and enzyme immunoassays, were analyzed in patients with active TB before and during 24 weeks of anti-TB chemotherapy (n = 65), from individuals with LTBI (n = 34) and from QuantiFERON-TB (QFT) negative controls (n = 65). The study participants were grouped according to HIV status. RESULTS: Plasma levels of the CXC chemokine IP-10 and soluble TNF receptor type 2 (sTNFr2) significantly differentiated active TB from the LTBI group, irrespective of HIV status. In the HIV-infected group the sensitivity and specificity was 100% for IP-10 with a cut-off of 2547 pg/mL. Plasma IP-10 declined gradually during anti-TB chemotherapy (12-24 weeks, p = 0.002) to a level comparable to LTBI and QFT negative control groups. sTNFr2 fluctuated throughout therapy, but was decreased after 12-24 weeks (p = 0.006). CONCLUSIONS: IP-10 distinguished with high accuracy active TB from LTBI irrespective of HIV infection and declined during anti-TB chemotherapy. Plasma IP-10 may serve as a diagnostic biomarker to differentiate between the stages of TB infection and for monitoring therapy efficacy.


Assuntos
Quimiocina CXCL10/sangue , Infecções por HIV/complicações , Tuberculose Latente/diagnóstico , Tuberculose/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Coinfecção , Citocinas/sangue , Feminino , Humanos , Imunoensaio , Interferon gama/sangue , Tuberculose Latente/complicações , Tuberculose Latente/terapia , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Tuberculose/complicações , Tuberculose/terapia , Adulto Jovem
20.
Neurosci Biobehav Rev ; 19(4): 519-31, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-8684714

RESUMO

CI-943 is a new drug candidate with antipsychotic-like activity in a variety of behavioural tests in rodents and primates, but without any affinity for brain dopamine receptors. CI-943 does not cause dystonia in monkeys, a predictive symptom of extrapyramidal side effects (EPS). Its mechanism of action remains unclear. Neurotensin (NT) concentration in nucleus accumbens and caudate is increased by CI-943; this may be associated with its antipsychotic effect. Indeed various observations suggest that the clinical action of antipsychotic drugs may at least be partially mediated by some neuropeptides. Various actions of neurotensin are reviewed. The hypothesis on the role of neurotensin represents a new strategy in the development of pharmacological tools for the treatment of schizophrenia.


Assuntos
Antipsicóticos/farmacologia , Química Encefálica/efeitos dos fármacos , Imidazóis/farmacologia , Neuropeptídeos/metabolismo , Neurotensina/metabolismo , Pirimidinas/farmacologia , Animais , Humanos
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