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1.
Biomed Pharmacother ; 163: 114885, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37201262

RESUMO

BACKGROUND: Treatment with non-selective beta-blockers (NSBB) has been associated with anti-inflammatory and anti-cancer effects in patients with cirrhosis. This study aims to analyze the impact of chronic NSBB treatment on immune activation and disease progression in stable outpatients with cirrhosis. METHODS: In this prospective follow-up of 150 patients with cirrhosis, 39 received treatment with NSBB. Blood samples were taken every 6-9 months, and immune and adrenergic variables were measured. Mixed linear models were used to assess the effect of NSBB on these variables over time. Multivariate Cox regression was used to study associations with adverse clinical events (hepatocellular carcinoma, death, or liver transplant). RESULTS: Median follow-up was 1635 days. NSBB treatment was associated with significantly lower levels of IL-6 (ß - 4.7; 95% confidence interval [CI] -6.9, -2.6) throughout the study. During follow-up, 11 patients developed hepatocellular carcinoma, 32 died, and 4 underwent liver transplant. Patients with higher concentrations of IL-10, IL-6 and IFN-γ developed more clinical events. Event-free survival was significantly better in patients treated with NSBB (hazard ratio 0.36, 95% CI 0.18, 0.71) in a multivariate Cox regression adjusted for Child-Pugh-Score, esophageal varices, and platelets. CONCLUSION: Chronic treatment with NSBB in patients with stable cirrhosis gives rise to a different state of immune activation, characterized by lower concentrations of IL-6 over time, and it is associated with a reduced risk of adverse event (death, hepatocellular carcinoma, or transplant), after controlling for disease severity.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Estudos Prospectivos , Estudos Longitudinais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/induzido quimicamente , Interleucina-6 , Antagonistas Adrenérgicos beta/uso terapêutico , Cirrose Hepática/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/induzido quimicamente
2.
Rev. panam. salud pública ; 46: e116, 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1450225

RESUMO

ABSTRACT Objective. To report the risk from alcohol, cannabis, and their combined use for non-fatal road traffic injuries for drivers, passengers, and pedestrians. Methods. Risk was estimated using the case-crossover method. Participants (N= 306) were injured patients from an emergency department in Mar del Plata, Argentina. Results. Alcohol use (OR= 6.78, CI 95% 3.75-12.25) as well as combined alcohol and cannabis use (OR= 7.05, CI 95% 1.16-42.73) significantly increased the risk of a road traffic injuries. Alcohol use increased the risk in both, women (OR= 8.87, CI 95% 2.69-29.21) and men (OR= 6.16, CI 95% 3.10-12.23); in those >30 years old (OR= 6.01, CI 95% 2.09-17.24) and those <30 years old (OR= 7.15, CI 95% 3.49-14.65). This last group also had an increased risk after combined alcohol and cannabis use (OR= 7.05, CI 95% 1.16-42.75). Both drivers (OR= 6.40, CI 95% 3.23-12.69) and passengers (OR= 13.83, CI 95% 2.87-66.42) had an increased risk after alcohol consumption. Conclusions. To our knowledge, these are the first estimates of the risk of having a road traffic injury after alcohol and cannabis consumption in one of the countries of the Southern Cone (Argentina, Chile, and Uruguay). These results highlight the urgent need to implement and enforce comprehensive alcohol control measures. Furthermore, given the global trend towards legalizing cannabis for recreational use, our results could also inform policymakers to enact or amend impaired driving laws.


RESUMEN Objetivo. Informar sobre el riesgo lesiones por accidentes de tránsito debido al consumo de alcohol, cannabis o su combinación en conductores, pasajeros y peatones. Métodos. Se estimó el riesgo mediante el método de casos cruzados. Los participantes (N = 306) fueron pacientes que habían sufrido lesiones, provenientes de una sala de urgencias en Mar del Plata (Argentina). Resultados. El consumo de alcohol (OR = 6,78, IC95% 3,75-12,25), así como el consumo combinado de alcohol y cannabis (OR = 7,05, IC95% 1,16-42,73) aumentaron significativamente el riesgo de traumatismos por accidentes de tránsito. El consumo de alcohol aumentó el riesgo tanto en mujeres (OR = 8,87, IC95% 2,69-29,21) como en hombres (OR = 6,16, IC95% 3,10-12,23); así como en mayores de 30 años (OR = 6,01, IC95% 2,09-17,24) y en menores de 30 años (OR = 7,15, IC95% 3,49-14,65). Este último grupo también tuvo mayor riesgo tras un consumo combinado de alcohol y cannabis (OR = 7,05, IC95% 1,16-42,75). Tanto los conductores (OR = 6,40, IC95% 3,23-12,69) como los pasajeros (OR = 13,83, IC95% 2,87-66,42) presentaron mayor riesgo después del consumo de alcohol. Conclusiones. Hasta donde sabemos, estas son las primeras estimaciones del riesgo de sufrir lesiones por accidentes de tránsito tras el consumo de alcohol y cannabis en uno de los países del Cono Sur (Argentina, Chile y Uruguay). Estos resultados ponen de relieve la urgente necesidad de aplicar y hacer cumplir medidas integrales de control del alcohol. Además, dada la tendencia mundial hacia la legalización del cannabis para consumo recreativo, nuestros resultados también podrían orientar a los responsables de las políticas para que promulguen o enmienden las leyes sobre la conducción con capacidades alteradas debido al consumo de sustancias.


RESUMO Objetivo. Relatar o risco de lesões não fatais no trânsito atribuível ao álcool, à cannabis e a seu uso combinado para motoristas, passageiros e pedestres. Métodos. O risco foi estimado usando o método clínico cruzado (case-crossover). Os participantes (N=306) eram feridos atendidos em um pronto-socorro em Mar del Plata, Argentina. Resultados. O uso de álcool (OR = 6,78, IC95% 3,75; 12,25) e o uso combinado de álcool e cannabis (OR= 7,05, IC95% 1,16; 42,73) aumentaram significativamente o risco de lesões no trânsito. O uso de álcool aumentou o risco tanto em mulheres (OR = 8,87, IC95% 2,69; 29,21) quanto em homens (OR = 6,16, IC95% 3,10; 12,23); naqueles >30 anos de idade (OR = 6,01, IC95% 2,09; 17,24) e <30 anos de idade (OR = 7,15, IC95% 3,49; 14,65). Esse último grupo também apresentou um risco maior após o uso combinado de álcool e cannabis (OR = 7,05, IC95% 1,16; 42,75). Tanto motoristas (OR = 6,40, IC95% 3,23; 12,69) quanto passageiros (OR = 13,83, IC95% 2,87; 66,42) apresentaram risco maior após o consumo de álcool. Conclusões. Até onde sabemos, estas são as primeiras estimativas do risco de lesões de trânsito após o consumo de álcool e cannabis em um dos países do Cone Sul (Argentina, Chile e Uruguai). Os resultados destacam a necessidade urgente de implementar e aplicar medidas abrangentes de controle do álcool. Além disso, considerando a tendência global de legalização da cannabis para uso recreativo, nossos resultados também poderiam ajudar os formuladores de políticas a decretar ou alterar as leis sobre a condução sob efeito de substâncias psicoativas.

3.
Hepatol Int ; 14(5): 858-868, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32885366

RESUMO

BACKGROUND: In patients with cirrhosis, beta-adrenoceptors expressed on peripheral blood mononuclear cells have a reduced response to catecholamine stimulation. This study aimed to determine if chronic treatment with beta-blockers influences these changes. METHODS: Blood samples were collected from patients with cirrhosis treated in outpatient clinics. Differences in cyclic AMP production before and after stimulation of mononuclear cells with epinephrine and/or N-Formylmethionine-leucyl-phenylalanine (fMLP) was used as a marker of beta-adrenoceptors activity in patients treated (N = 19) versus not treated (N = 55) with beta-blockers. In addition, we studied the gene expression of different types of adrenoceptors and possible associations with the activity of beta-adrenoceptors, the serum concentrations of catecholamines and cytokines, and the presence of bacterial antigens such as DNA or gram-negative bacterial endotoxin in patients' blood. RESULTS: The increase in intracellular cAMP concentrations after stimulation of adrenergic receptors with epinephrine was significantly higher in samples from patients treated with beta-blockers. Older patients showed lower responses to epinephrine stimulus, while the response increased linearly with the duration of the beta-blocker treatment. mRNA expression levels of adrenoceptors ß1, ß2, ß3 and α1-A, B and D showed no significant differences according to treatment with beta-blockers. Neither serum cytokines nor catecholamines levels were significantly associated with the intracellular production of cAMP after adrenergic stimulation. CONCLUSION: Chronic treatment with beta-blockers in patients with cirrhosis enables beta-adrenoceptors to respond to catecholamine stimulation irrespective of the degree of systemic adrenergic or immune activations of the patient at the time of sampling.


Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Catecolaminas/metabolismo , AMP Cíclico , Leucócitos Mononucleares , Cirrose Hepática , Receptores Adrenérgicos beta/análise , Correlação de Dados , AMP Cíclico/análise , AMP Cíclico/metabolismo , Duração da Terapia , Feminino , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/imunologia , Cirrose Hepática/metabolismo , Masculino , Pessoa de Meia-Idade , Tempo de Reação , Estimulação Química
4.
Clin Transl Gastroenterol ; 11(3): e00143, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32352715

RESUMO

OBJECTIVES: Most patients with multiple colonic polyps do not have a known genetic or hereditary origin. Our aim was to analyze the presence of inflammatory cytokines and levels of glucose, insulin, and C-reactive protein (CRP) in patients with multiple colonic polyps. METHODS: Eighty-three patients with 10 or more adenomatous or serrated polyps and 53 control people with normal colonoscopy were included. Smoking habits were registered, and glucose, CRP, and basal insulin in the serum/blood were measured. Quantification of IL-2, IL-4, IL-6, IL-10, IL-11, IL-17A, and IL-23 cytokine levels in the serum was performed by a high-sensitivity enzyme-linked immunosorbent assay. RESULTS: Smoking and diabetes were more prevalent in those with colonic polyps than in the control people (67% vs 16%, P = 0.001; 11% vs 2%, P = 0.048). In addition, the cytokine serum levels were higher, i.e., IL-2 (P = 0.001), IL-4 (P = 0.001), IL-6 (P = 0.001), IL-17A (P = 0.001), IL-23 (P = 0.014), and CRP (P = 0.003). Adjusting for sex, smoking, and diabetes in a multivariate analysis, IL-2, IL-4, IL-6, IL-17A, and IL-23 remained independently elevated in cases with multiple polyps. DISCUSSION: These results indicate that immune responses mediated by Th17 cells may be involved in the pathogenesis of multiple colonic polyps.


Assuntos
Pólipos do Colo/imunologia , Citocinas/sangue , Células Th17/imunologia , Idoso , Estudos de Casos e Controles , Colo/diagnóstico por imagem , Colo/patologia , Pólipos do Colo/sangue , Pólipos do Colo/diagnóstico , Pólipos do Colo/patologia , Colonoscopia , Citocinas/metabolismo , Feminino , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Inflamação/imunologia , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Células Th17/metabolismo
5.
Sci Rep ; 9(1): 835, 2019 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-30696924

RESUMO

Bacterial (bact)DNA is an immunogenic product that frequently translocates into the blood in cirrhosis. We evaluated bactDNA clearance in patients undergoing liver transplantation (LT) and its association with inflammation and clinically relevant complications. We prospectively included patients consecutively admitted for LT in a one-year follow-up study. We evaluated bactDNA before and during the first month after LT, quantifying cytokine response at 30 days. One hundred patients were included. BactDNA was present in the blood of twenty-six patients undergoing LT. Twenty-four of these showed bactDNA in the portal vein, matching peripheral blood-identified bactDNA in 18 cases. Thirty-four patients showed bactDNA in blood during the first month after LT. Median TNF-α and IL-6 levels one month after LT were significantly increased in patients with versus without bactDNA. Serum TNF-α at baseline was an independent risk factor for bactDNA translocation during the first month after LT in the multivariate analysis (Odds ratio (OR) 1.14 [1.04 to 1.29], P = 0.015). One-year readmission was independently associated with the presence of bactDNA during the first month after LT (Hazard ratio (HR) 2.75 [1.39 to 5.45], P = 0.004). The presence of bactDNA in the blood of LT recipients was not shown to have any impact on complications such as death, graft rejection, bacterial or CMV infections. The rate of bactDNA translocation persists during the first month after LT and contributes to sustained inflammation. This is associated with an increased rate of readmissions in the one-year clinical outcome after LT.


Assuntos
Translocação Bacteriana/fisiologia , DNA Bacteriano/sangue , Interleucina-6/sangue , Transplante de Fígado , Fator de Necrose Tumoral alfa/sangue , Disbiose/microbiologia , Feminino , Microbioma Gastrointestinal/fisiologia , Trato Gastrointestinal/microbiologia , Humanos , Inflamação/microbiologia , Cirrose Hepática/patologia , Cirrose Hepática/cirurgia , Masculino , Pessoa de Meia-Idade , Veia Porta/microbiologia , Estudos Prospectivos , Fatores de Risco
6.
J Mol Med (Berl) ; 95(11): 1227-1236, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28879509

RESUMO

Interleukin IL26 supports killing of microbes and the innate sensing of bacterial-derived DNA (bactDNA). We evaluated the relationship between IL26 serum levels and bactDNA translocation in Crohn's disease (CD). We ran a prospective study on CD patients in remission. IL26 common polymorphisms, serum cytokines and complement protein, amplified-bactDNA, and anti-TNF-α were evaluated. In vitro PBMC analysis was performed. Three hundred and thirteen patients were included (mean CDAI: 83.6 ± 32.8; mean fecal calprotectin: 55.4 ± 35.3 µg/g). A total of 106 patients (33.8%) showed bactDNA and 223 patients (71%) had a varIL26 genotype. BactDNA significantly correlated with increased IL26 levels compared with bactDNA-negative patients. PBMCs from varIL26 patients significantly reduced E. coli killing capacity compared with wtIL26-genotyped patients. The stimulation with a recombinant IL26 protein reduced pro-inflammatory cytokines in response to E. coli in the varIL26 cell supernatants. Serum anti-TNF-α levels in varIL26 vs wtIL26-genotyped patients on biologics were significantly lower in the presence of bactDNA. Cells from varIL26 vs wtIL26-genotyped patients cultured with E. coli DNA and infliximab showed a significant decrease in free anti-TNF-α concentration. A varIL26 genotype was associated with the initiation of anti-TNF-α in CD patients during the 6-month follow-up. IL26 polymorphisms may prevent bactDNA clearance and identify CD patients with a worse inflammatory evolution and response to therapy. KEY MESSAGES: BactDNA translocation in CD is associated with an increased risk of relapse. IL26 is sensitive to bactDNA and modulates the inflammatory response in CD patients. The varIL26 genotype is associated with reduced PMN capacity to kill bacteria. A varIL26 genotype is associated with decreased levels of anti-TNF-α in CD patients. IL26 may help explain the role of bactDNA as a risk factor of flare in CD patients.


Assuntos
Doença de Crohn/genética , Doença de Crohn/imunologia , Citocinas/metabolismo , DNA Bacteriano/imunologia , Interleucinas/genética , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Feminino , Genótipo , Humanos , Interleucinas/sangue , Leucócitos/imunologia , Leucócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
7.
Basic Clin Pharmacol Toxicol ; 116(3): 257-63, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25154757

RESUMO

Use of non-steroidal anti-inflammatory drugs in cirrhosis has been associated with impairment of renal function based on its ability to inhibit the renal production of prostaglandins. Renal effects of dipyrone in patients with cirrhosis have not been evaluated. We aimed to assess the renal effect of therapeutic doses of dipyrone used for short periods of time in patients with cirrhosis. Twenty-nine patients with cirrhosis were included in an observer-blind clinical trial. Patients were randomized to receive three times a day oral acetaminophen (500 mg; N = 15) or dipyrone (575 mg; N = 14) for 72 hr. Serum and urine samples were obtained at baseline, 48 and 72 hr, and cystatin C, creatinine, aldosterone, 6-keto-Prostaglandin-F1 alpha and prostaglandin E2 were measured. Cystatin C and creatinine levels remained comparable in patients treated with acetaminophen and dipyrone. Urine and serum prostaglandins concentrations were significantly decreased at 72 hr in patients treated with dipyrone regardless of the status of ascites. One patient with ascites treated with dipyrone required a paracentesis and developed renal insufficiency. We conclude that dipyrone and acetaminophen did not reduce renal function when used for short periods of time (up to 72 hr) in patients with cirrhosis. However, considering that dipyrone lowered renal vasodilator prostaglandins synthesis, acetaminophen appears as the safest choice with respect to kidney function in cirrhosis.


Assuntos
Dipirona/efeitos adversos , Rim/efeitos dos fármacos , Cirrose Hepática/tratamento farmacológico , Prostaglandinas/metabolismo , Acetaminofen/administração & dosagem , Acetaminofen/efeitos adversos , Acetaminofen/uso terapêutico , Adulto , Idoso , Analgésicos não Narcóticos/administração & dosagem , Analgésicos não Narcóticos/efeitos adversos , Analgésicos não Narcóticos/uso terapêutico , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Ascite/tratamento farmacológico , Dipirona/administração & dosagem , Dipirona/uso terapêutico , Feminino , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Método Simples-Cego , Fatores de Tempo
8.
J Hepatol ; 62(1): 64-71, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25173967

RESUMO

BACKGROUND & AIMS: Inflammation is a common event in the pathogenesis of liver cirrhosis. The inflammasome pathway has acquired significant relevance in the pathogenesis of inflammation, but its role in the inflammatory response in patients with decompensated cirrhosis remains unexplored. METHODS: We performed a prospective study in which 44 patients with decompensated cirrhosis and 12 healthy volunteers were included. We isolated macrophages from blood and ascitic fluid and assessed the expression and activation of the inflammasome, its response to priming by bacterial products, and its association with the degree of liver disease. RESULTS: Macrophages from sterile ascitic fluids showed constitutive activation of caspase-1 and a marked increase in the expression of IL-1ß, IL-18, and absent in melanoma 2 (AIM2) when compared to blood macrophages. Pre-stimulation of blood-derived macrophages from cirrhotic patients with bacterial DNA increased the expression of AIM2 and induced a higher AIM2-mediated inflammasome response than priming with other bacterial products such as lipopolysaccharide. By contrast, activation of the AIM2 inflammasome did not require a priming signal in ascitic fluid-derived macrophages, demonstrating the preactivated state of the inflammasome in these cells. Last, higher IL-1ß and IL-18 production by ascitic fluid macrophages correlated with a more advanced Child-Pugh score. CONCLUSIONS: The inflammasome is highly activated in the ascitic fluid of cirrhotic patients, which may explain the exacerbated inflammatory response observed in these patients under non-infected conditions. Clinically, activation of the inflammasome is associated with a higher degree of liver disease.


Assuntos
Líquido Ascítico/citologia , Proteínas de Ligação a DNA/genética , DNA/genética , Regulação da Expressão Gênica , Inflamassomos/metabolismo , Cirrose Hepática/genética , Macrófagos/patologia , Adulto , Idoso , Western Blotting , Células Cultivadas , Citocinas/metabolismo , Proteínas de Ligação a DNA/biossíntese , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real
9.
J Gastroenterol ; 50(7): 758-68, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25500977

RESUMO

BACKGROUND: Anti-TNF-α therapies interact with the tolerogenic response in patients with Crohn's disease, modulating inflammation. However, drug levels and the genetic background may affect this interaction. METHODS: Patients with Crohn's disease in remission on biologic monotherapy were enrolled in this study. FoxP3+ lymphocytes, NOD2 genotype, serum cytokine, anti-TNF-α levels, and anti-drug antibodies were evaluated. Regulatory T cell response to infliximab was evaluated in vitro. RESULTS: Fifty-seven patients were included. Thirty-nine patients (68.4%) were receiving non-intensified biologic therapy whereas 18 patients (31.6%) were under an intensified biologic schedule due to loss of response. Eleven intensified patients (61.1%) showed a variant NOD2 genotype vs 9 on non-intensified biologics (23%, p < 0.01). Percentage of FoxP3+ T cells and serum free anti-TNF-α levels were significantly higher in patients with a wild-type vs variant NOD2 genotype, either under non-intensified or intensified schedule. Increasing amounts of infliximab significantly increased the expression of FoxP3+ T cells and anti-TNF-α levels in the supernatant from wild-type NOD2 patients cultured cells whereas the induction of FoxP3+ T cells and anti-TNF-α levels in the supernatant from variant NOD2 patients cultured cells were significantly lower. TNF-α and IL-10 showed a correlation with the FoxP3+ T cell population percentage and serum levels of anti-TNF-α, irrespective of NOD2 genotype. Eight variant NOD2 patients (66.6%) vs 4 wild-type NOD2 patients (8.8%) showed a perianal phenotype (p = 0.01). A significant reduction of the percentage of FoxP3+ T cells and serum levels of anti-TNF-α was observed in patients with the associated perianal disease. CONCLUSION: Anti-TNF-α loss of response is associated with a decreased percentage of FoxP3+ T cells and a variant NOD2 genotype in patients with CD.


Assuntos
Adalimumab/uso terapêutico , Doença de Crohn/tratamento farmacológico , Fatores de Transcrição Forkhead/metabolismo , Infliximab/uso terapêutico , Proteína Adaptadora de Sinalização NOD2/genética , Linfócitos T Reguladores/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Anti-Inflamatórios/uso terapêutico , Células Cultivadas , Doença de Crohn/sangue , Doença de Crohn/imunologia , Citocinas/sangue , DNA/genética , Feminino , Fármacos Gastrointestinais/uso terapêutico , Genótipo , Humanos , Masculino , Proteína Adaptadora de Sinalização NOD2/metabolismo , Fenótipo , Polimorfismo Genético , Linfócitos T Reguladores/imunologia
10.
PLoS One ; 7(8): e43371, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22916250

RESUMO

BACKGROUND: Bacterial translocation is a frequent event in cirrhosis leading to an increased inflammatory response. Splanchnic adrenergic system hyperactivation has been related with increased bacterial translocation. We aim at evaluating the interacting mechanism between hepatic norepinephrine and inflammation during liver damage in the presence of bacterial-DNA. ANIMALS AND METHODS: Forty-six mice were included in a 16-week protocol of CCl(4)-induced cirrhosis. Laparotomies were performed at weeks 6, 10, 13 and 16. A second set of forty mice injected with a single intraperitoneal dose of CCl(4) was treated with saline, 6-hydroxidopamine, Nebivolol or Butoxamine. After 5 days, mice received E. coli-DNA intraperitoneally. Laparotomies were performed 24 hours later. Liver bacterial-DNA, norepinephrine, TNF-alpha, IL-6 and beta-adrenergic receptor levels were measured. RESULTS: Bacterial-DNA translocation was more frequent in CCl(4)-treated animals compared with controls, and increased as fibrosis progressed. Liver norepinephrine and pro-inflammatory cytokines were significantly higher in mice with vs without bacterial-DNA (319.7 ± 120.6 vs 120.7 ± 68.6 pg/g for norepinephrine, 38.4 ± 6.1 vs 29.7 ± 4.2 pg/g for TNF-alpha, 41.8 ± 7.4 vs 28.7 ± 4.3 pg/g for IL-6). Only beta-adrenergic receptor-1 was significantly increased in treated vs control animals (34.6 ± 7.3 vs 12.5 ± 5.3, p=0.01) and correlated with TNF-alpha, IL-6 and norepinephrine hepatic levels in animals with bacterial-DNA. In the second set of mice, cytokine levels were increased in 6-hydroxidopamine and Nebivolol (beta-adrenergic receptor-1 antagonist) treated mice compared with saline. Butoxamine (beta-adrenergic receptor-2 antagonist) didn't inhibit liver norepinephrine modulation of pro-inflammatory cytokines. CONCLUSIONS: Beta-adrenergic receptor-1 mediates liver norepinephrine modulation of the pro-inflammatory response in CCl(4)-treated mice with bacterial-DNA.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Cirrose Hepática Experimental/tratamento farmacológico , Cirrose Hepática Experimental/metabolismo , Norepinefrina/metabolismo , Receptores Adrenérgicos beta/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Benzopiranos/uso terapêutico , Butoxamina/uso terapêutico , Tetracloreto de Carbono/toxicidade , DNA Bacteriano/metabolismo , Etanolaminas/uso terapêutico , Feminino , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/patologia , Camundongos , Camundongos Endogâmicos BALB C , Nebivolol
11.
Clinics ; 66(2): 255-260, 2011. tab
Artigo em Inglês | LILACS | ID: lil-581511

RESUMO

INTRODUCTION: Regular physical exercise has numerous benefits. However, there is a subset of the exercising population who may develop a compulsion to exercise excessively and who may, as a consequence, display physiological and psychological changes that have a direct influence on their quality of life. OBJECTIVE: Our objective was to determine if there are differences between male and female athletes' scores on measures of negative addiction symptoms, quality of life, mood and sleep. METHODS: 144 female and 156 male athletes participated in this study by answering the following questionnaires: Negative Addiction Scale, Beck Depression Inventory, Trait Anxiety Inventory, Profile of Mood States, SF-36 Quality of Life, Pittsburgh Sleep Quality and Epworth Sleepiness Scale. RESULTS: Higher dedication to training sessions in the male group, and members of the female group with symptoms of negative addiction to exercise showed a lower score on vigor observed by the Profile of Mood States compared to the males in both situations. We also observed depression symptoms in both members of groups who had negative addiction symptoms when compared with their peers without symptoms, and these figures were even higher in females compared with the male group in the same situation. CONCLUSION: No differences were seen in the development of negative addiction exercise symptoms in males and females and there were no changes in the quality of life and mood of these athletes. Further studies of eating disorders associated with changes in body image perception could contribute to a better understanding of negative addiction to exercise.


Assuntos
Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem , Afeto/fisiologia , Comportamento Aditivo/psicologia , Exercício Físico/psicologia , Qualidade de Vida , Análise de Variância , Comportamento Aditivo/epidemiologia , Depressão/epidemiologia , Testes Psicológicos , Distribuição por Sexo , Fatores Sexuais , Estatísticas não Paramétricas , Sono/fisiologia
12.
Rev. bras. med. esporte ; 15(5): 355-359, set.-out. 2009. tab
Artigo em Português | LILACS | ID: lil-530145

RESUMO

O objetivo do presente estudo foi verificar se existem diferenças nos escores de Dependência de Exercício (DE), escores de humor e qualidade de vida em atletas profissionais e amadores de modalidade esportivas coletivas e individuais. MÉTODOS: Participaram deste estudo 116 atletas praticantes de modalidades esportivas coletivas (n = 60, sendo 20 profissionais e 40 amadores) e individuais (n = 56, sendo 16 profissionais e 40 amadores) do gênero masculino. As médias (± desvio-padrão) da idade, estatura, massa corporal e índice de massa corpórea (IMC) foram: 22,13 ± 6,16 anos; 1,77 ± 0,10cm; 72,76 ± 10,04kg; e 23,10 ± 2,04kg/m², respectivamente. Os atletas responderam aos seguintes questionários: Escala de Dependência de Exercício (EDE), Inventário Beck de Depressão, Idate Traço e Estado de Ansiedade, Questionário POMS de perfil de humor, Questionário SF-36 de Qualidade de Vida, em um dia de folga dentro da periodização normal de treinamento, caracterizando o estudo como transversal. O trabalho foi aprovado pelo Comitê de Ética em Pesquisa da Unifesp (# 0616/06). RESULTADOS: Atletas amadores e profissionais apresentaram escores similares de DE, mas quando considerados os tipos de modalidade, os amadores praticantes de modalidades coletivas apresentam maiores escores, o que se inverte quando considerados atletas profissionais. Em relação aos resultados de humor, atletas profissionais apresentaram mais qualidade de vida e menores escores de humor. CONCLUSÃO: Atletas amadores e profissionais praticantes de modalidades esportivas coletivas e individuais respondem diferentemente à DE; o tipo de modalidade e seu envolvimento social e competitivo parecem ser o grande determinante. Além disso, pode-se concluir que atletas profissionais de modalidades coletivas apresentam melhor perfil de humor e qualidade de vida, tanto quando comparados com profissionais de modalidades individuais, quando com atletas amadores praticantes de modalidades coletivas...


The purpose of this study was to verify if there are differences between exercise dependence (ED), mood and quality of life scores in professional and amateur athletes of individual and collective sport modalities. METHODS: 116 male athletes of collective sport modalities (n=60, 20 professionals and 40 amateurs) and individual sport modalities (n=56, 16 professionals and 40 amateurs) participated in this study. Age, height, weight, BMI mean (± standard-deviation) were: 22.13 ± 6.16 years; 1.77 ± 0.10 cm; 72.76 ± 10.04 kg and 23.10 ± 2.04 kg/m², respectively. The athletes answered the following questionnaires: Exercise Dependence scale (EDE), Beck Depression Inventory, Trait and State of Anxiety - IDATE, POMS - profile of mood states, SF-36 Questionnaire of Quality of Life. The study was approved by the Ethics in Research Committee of UNIFESP (#0616/06). RESULTS: Amateur and professional athletes presented similar scores of ED, but when the kind of modality was considered, the amateurs of collective modalities presented higher scores than professional athletes. CONCLUSION: Amateur and professional athletes of collective and individual sport modalities answered differently to ED, and the sports modality and competitive and social involvement could be determinant. Moreover, it is possible to conclude that professional athletes of collective sports present better profile of mood and quality of life when compared with professional athletes of individual sports when compared with amateur athletes from collective or individual sport modalities.


Assuntos
Humanos , Masculino , Adolescente , Adulto Jovem , Ansiedade , Comportamento Compulsivo , Depressão , Esportes/psicologia , Qualidade de Vida
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