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1.
Clin Microbiol Infect ; 21(7): 711.e1-8, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25882366

RESUMO

Very little information is available on the involvement of newly characterized adipokines in human immunodeficiency virus (HIV)/antiretroviral therapy (ART)-associated lipodystrophy syndrome (HALS). Our aim was to determine whether apelin, apelin receptor, omentin, RBP4, vaspin and visfatin genetic variants and plasma levels are associated with HALS. We performed a cross-sectional multicentre study that involved 558 HIV type 1-infected patients treated with a stable highly active ART regimen, 240 of which had overt HALS and 318 who did not have HALS. Epidemiologic and clinical variables were determined. Polymorphisms in the apelin, omentin, RBP4, vaspin and visfatin genes were assessed by genotyping. Plasma apelin, apelin receptor, omentin, RBP4, vaspin and visfatin levels were determined by enzyme-linked immunosorbent assay in 163 patients (81 with HALS and 82 without HALS) from whom stored plasma samples were available. Student's t test, one-way ANOVA, chi-square test, Pearson and Spearman correlations and linear regression analysis were used for statistical analyses. There were no associations between the different polymorphisms assessed and the HALS phenotype. Circulating RBP4 was significantly higher (p < 0.001) and plasma omentin was significantly lower (p 0.001) in patients with HALS compared to those without HALS; differences in plasma levels of the remaining adipokines were nonsignificant between groups. Circulating RBP4 concentration was predicted independently by the presence of HALS. Apelin and apelin receptor levels were independently predicted by body mass index. Visfatin concentration was predicted independently by the presence of acquired immunodeficiency syndrome. HALS is associated with higher RBP4 and lower omentin in plasma. These two adipokines, particularly RBP4, may be a link between HIV/ART and fat redistribution syndromes.


Assuntos
Antirretrovirais/administração & dosagem , Antirretrovirais/efeitos adversos , Citocinas/sangue , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Síndrome de Lipodistrofia Associada ao HIV/patologia , Lectinas/sangue , Proteínas Plasmáticas de Ligação ao Retinol/análise , Adulto , Idoso , Estudos de Casos e Controles , Estudos Transversais , Citocinas/genética , Ensaio de Imunoadsorção Enzimática , Feminino , Proteínas Ligadas por GPI/sangue , Proteínas Ligadas por GPI/genética , Genótipo , Humanos , Lectinas/genética , Masculino , Pessoa de Meia-Idade , Plasma/química , Polimorfismo Genético , Proteínas Plasmáticas de Ligação ao Retinol/genética , Adulto Jovem
2.
QJM ; 108(10): 795-801, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25660598

RESUMO

BACKGROUND: The factors related to ascending aorta dilation (AAD) in patients with bicuspid aortic valve (BAV) are not completely understood. In addition, the role of cholesterol metabolism in AAD has not been studied. METHODS: We analyzed the relationship between different lipid parameters and the ascending aorta diameter/presence of aortic dilatation in 91 consecutive patients with BAV. RESULTS: We observed a positive linear correlation between the total cholesterol, low-density lipoprotein (LDL) cholesterol and apolipoprotein B (ApoB) levels and the ascending aorta diameter. The patients with AAD had higher LDL cholesterol and ApoB levels. Whereas LDL cholesterol and ApoB were identified as independent factors predictors of the aortic root diameter, only ApoB predicted the diameter of the ascending aorta. On the other hand, the levels of ApoB were an independent factor related to the dilatation of the aortic root. CONCLUSIONS: We have observed that cholesterol is associated with ascending aorta diameter and dilation in BAV patients. Further experimental and clinical studies are needed to explain the pathobiology of this association.


Assuntos
Aorta/fisiopatologia , Valva Aórtica/anormalidades , Apolipoproteínas B/sangue , LDL-Colesterol/sangue , Doenças das Valvas Cardíacas/sangue , Adulto , Idoso , Doença da Válvula Aórtica Bicúspide , Dilatação Patológica , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos
3.
Int J Obes (Lond) ; 39(2): 279-87, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24675715

RESUMO

BACKGROUND: Obesity severely affects human health, and the accompanying non-alcoholic fatty liver disease (NAFLD) is associated with high morbidity and mortality. Rapid and non-invasive methods to detect this condition may substantially improve clinical care. METHODS: We used liquid and gas chromatography-quadruple time-of-flight-mass spectrometry (LC/GC-QTOF-MS) analysis in a non-targeted metabolomics approach on the plasma from morbidly obese patients undergoing bariatric surgery to gain a comprehensive measure of metabolite levels. On the basis of these findings, we developed a method (GC-QTOF-MS) for the accurate quantification of plasma α-ketoglutarate to explore its potential as a novel biomarker for the detection of NAFLD. RESULTS: Plasma biochemical differences were observed between patients with and without NAFLD indicating that the accumulation of lipids in hepatocytes decreased ß-oxidation energy production, reduced liver function and altered glucose metabolism. The results obtained from the plasma analysis suggest pathophysiological insights that link lipid and glucose disturbances with α-ketoglutarate. Plasma α-ketoglutarate levels are significantly increased in obese patients compared with lean controls. Among obese patients, the measurement of this metabolite differentiates between those with or without NAFLD. Data from the liver were consistent with data from plasma. Clinical utility was assessed, and the results revealed that plasma α-ketoglutarate is a fair-to-good biomarker in patients (n=230). Other common laboratory liver tests used in routine application did not favourably compare. CONCLUSION: Plasma α-ketoglutarate is superior to common liver function tests in obese patients as a surrogate biomarker of NAFLD. The measurement of this biomarker may potentiate the search for a therapeutic approach, may decrease the need for liver biopsy and may be useful in the assessment of disease progression.


Assuntos
Ácidos Cetoglutáricos/sangue , Metaboloma , Hepatopatia Gordurosa não Alcoólica/sangue , Obesidade Mórbida/sangue , Biomarcadores/sangue , Cromatografia Líquida , Progressão da Doença , Humanos , Metabolismo dos Lipídeos , Espectrometria de Massas , Metabolômica/métodos , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Obesidade Mórbida/complicações , Obesidade Mórbida/metabolismo , Obesidade Mórbida/fisiopatologia , Valor Preditivo dos Testes
4.
HIV Med ; 14(4): 233-40, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23171036

RESUMO

OBJECTIVES: Insulin resistance in viral infections is common. We have explored the effectiveness of metformin for alleviating insulin resistance in HIV-infected patients and assessed the relevance of the ataxia-telangiectasia mutated (ATM) rs11212617 variant in the clinical response with the rationale that metformin modulates cellular bioenergetics in an ATM-dependent process. METHODS: HIV-infected patients (n = 385) were compared with controls recruited from the general population (n = 300) with respect to the genotype distribution of the ATM rs11212617 variant and its influence on selected metabolic and inflammatory variables. We also followed up a subset of male patients with HIV and hepatitis C virus (HCV) coinfection (n = 47) who were not receiving antiviral treatment and for whom metformin was prescribed for insulin resistance, which tends to have a higher incidence and severity in coinfected patients. RESULTS: Among the HIV-infected patients, human cytomegalovirus (91.9%) and HCV (62.3%) coinfections were frequent. Selected metabolic and/or inflammatory variables were significantly altered in infected patients. Treatment with metformin in HIV and HCV coinfected patients was well tolerated and significantly increased the sensitivity of peripheral tissues to insulin. The minor allele (C) of the rs11212617 variant was associated with treatment success and may affect the course of insulin resistance in response to metformin (odds ratio 1.21; 95% confidence interval 1.07-1.39; P = 0.005). There were no differences between treated and untreated patients in viral loads or variables measuring immune defence, indicating that toxicity is unlikely. CONCLUSIONS: We provide novel data suggesting that identification of the ATM rs11212617 variant may be important in assessing the glycaemic response to metformin treatment for insulin resistance in HIV-infected patients.


Assuntos
Coinfecção/metabolismo , Infecções por Citomegalovirus/metabolismo , Infecções por HIV/metabolismo , Hipoglicemiantes/uso terapêutico , Resistência à Insulina , Metformina/uso terapêutico , Adulto , Proteínas Mutadas de Ataxia Telangiectasia , Proteínas de Ciclo Celular/genética , Citomegalovirus/isolamento & purificação , Proteínas de Ligação a DNA/genética , Feminino , Genótipo , Infecções por HIV/virologia , Humanos , Resistência à Insulina/genética , Masculino , Pessoa de Meia-Idade , Proteínas Serina-Treonina Quinases/genética , Proteínas Supressoras de Tumor/genética
5.
Curr Mol Med ; 11(6): 453-64, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21663591

RESUMO

Atherosclerosis in symptomatic peripheral arterial disease affects wide portions of numerous arteries in lower extremities. The resulting active inflammation in a considerable amount of arterial tissue facilitates systemic detection via measurement of inflammation-related variables. We reasoned that the combined assessment of defense against oxidative stress, in the form of paraoxonase-1 (PON1), and monocyte migration measured as circulating (C-C motif) ligand 2 (CCL2), may play a role in the evaluation of these patients. Plasma CCL2 and serum PON1-related variables, assessed by their interaction with functional genetic variants, were measured in a cross-sectional study in patients with symptomatic PAD. We found that PON1 activity and concentration were significantly lower and CCL2 concentration higher in PAD patients compared to controls, that the combination of plasma CCL2 and PON1- related values, especially PON1 concentration differentiated, almost perfectly, controls from patients and that the expression of CCL2 and PON1 generally co-localized in the atherosclerotic lesion. Since no association with genetic variants was found, such a relationship is probably the result of the disease. Our data suggest a coordinated role between CCL2 and PON1 that may be detected in blood with simple measurements and may represent an indicator of the extent of atherosclerosis.


Assuntos
Arildialquilfosfatase/sangue , Aterosclerose/metabolismo , Quimiocina CCL2/sangue , Doença Arterial Periférica/sangue , Idoso , Idoso de 80 Anos ou mais , Arildialquilfosfatase/genética , Aterosclerose/patologia , Quimiocina CCL2/genética , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Doença Arterial Periférica/tratamento farmacológico , Doença Arterial Periférica/genética , Doença Arterial Periférica/metabolismo
6.
Phytomedicine ; 18(5): 414-24, 2011 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-21211952

RESUMO

The incidence of obesity and related metabolic diseases is increasing globally. Current medical treatments often fail to halt the progress of such disturbances, and plant-derived polyphenols are increasingly being investigated as a possible way to provide safe and effective complementary therapy. Rooibos (Aspalathus linearis) is a rich source of polyphenols without caloric and/or stimulant components. We have tentatively characterized 25 phenolic compounds in rooibos extract and studied the effects of continuous aqueous rooibos extract consumption in mice. The effects of this extract, which contained 25% w/w of total polyphenol content, were negligible in animals with no metabolic disturbance but were significant in hyperlipemic mice, especially in those in which energy intake was increased via a Western-type diet that increased the risk of developing metabolic complications. In these mice, we found hypolipemiant activity when given rooibos extract, with significant reductions in serum cholesterol, triglyceride and free fatty acid concentrations. Additionally, we found changes in adipocyte size and number as well as complete prevention of dietary-induced hepatic steatosis. These effects were not related to changes in insulin resistance. Among other possible mechanisms, we present data indicating that the activation of AMP-activated protein kinase (AMPK) and the resulting regulation of cellular energy homeostasis may play a significant role in these effects of rooibos extract. Our findings suggest that adding polyphenols to the daily diet is likely to help in the overall management of metabolic diseases.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Aspalathus/química , Ingestão de Energia/efeitos dos fármacos , Fígado/metabolismo , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Células 3T3-L1 , Proteínas Quinases Ativadas por AMP/efeitos dos fármacos , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/enzimologia , Animais , Colesterol/sangue , Colesterol na Dieta/administração & dosagem , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Ingestão de Alimentos/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Fígado Gorduroso/etiologia , Fígado Gorduroso/prevenção & controle , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Polifenóis/administração & dosagem , Polifenóis/química , Triglicerídeos/sangue , Aumento de Peso/efeitos dos fármacos
7.
Phytomedicine ; 17(3-4): 186-91, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19765963

RESUMO

Diet supplementation and/or modulation is an important strategy to significantly improve human health. The search of plants as additional sources of bioactive phenolic compounds is relevant in this context. The aqueous extract of Hibiscus sabdariffa is rich in anthocyanins and other phenolic compounds including hydroxycitric and chlorogenic acids. Using this extract we have shown an effective protection of cultured peripheral blood mononuclear cells from the cellular death induced by H(2)O(2) and a significant role in the production of inflammatory cytokines. In vitro, the extract promotes the production of IL-6 and IL-8 and decreases the concentration of MCP-1 in supernatants in a dose-dependent manner. In humans, the ingestion of an acute dose of the extract (10g) was well tolerated and decreased plasma MCP-1 concentrations significantly without further effects on other cytokines. This effect was not due to a concomitant increase in the antioxidant capacity of plasma. Instead, its mechanisms probably involve a direct inhibition of inflammatory and/or metabolic pathways responsible for MCP-1 production, and may be relevant in inflammatory and chronic conditions in which the role of MCP-1 is well established. If beneficial effects are confirmed in patients, Hibiscus sabdariffa could be considered a valuable traditional herbal medicine for the treatment of chronic inflammatory diseases with the advantage of being devoid of caloric value or potential alcohol toxicity.


Assuntos
Anti-Inflamatórios/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Quimiocina CCL2/sangue , Hibiscus/química , Mediadores da Inflamação/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Extratos Vegetais/farmacologia , Adulto , Antioxidantes/farmacologia , Técnicas de Cultura de Células , Quimiocina CCL2/biossíntese , Feminino , Flores , Humanos , Peróxido de Hidrogênio , Interleucina-6/biossíntese , Interleucina-8/biossíntese , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Fenóis/farmacologia , Extratos Vegetais/química , Valores de Referência , Adulto Jovem
8.
J Chemother ; 14(4): 361-5, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12420853

RESUMO

The degree of penetration of an antibiotic into the infection site is an important factor in its therapeutic efficacy, particularly in bone and joint infections. In the present study, we examined the bone tissue penetration of isepamicin at a dose of 15 mg/Kg, and the results were correlated to microbiologic data to estimate the clinical efficacy of isepamicin in bone infections. In this open-label, single-arm, noncomparative study, subjects of similar age, body weight, height and creatinine clearance who were undergoing elective total hip replacement received a single, parenteral 15 mg/Kg dose of isepamicin. Plasma and bone tissue samples were collected a mean 1.3 hours later and analyzed by a high-pressure liquid chromatography method. Twelve patients (3 men and 9 women; mean age, 73.5 years; mean body weight, 53.5 Kg, mean creatinine clearance, 58.5 mL/min) were enrolled. The mean +/- SD plasma concentration of isepamicin at the time of bone removal was 43.0 +/- 10.4 microg/mL. The mean +/- SD isepamicin concentrations were 11.6 +/- 7.1 microg/mL in cancellous bone tissue and 12.0 +/- 7.3 microg/mL in cortical bone tissue. The mean +/- SD ratios of isepamicin concentration in bone and plasma (bone/plasma) were 0.28 +/- 0.14 for cancellous bone tissue and 0.31 +/- 0.20 for cortical bone tissue. The concentrations achieved in both cancellous and cortical bone tissue were greater than the minimum concentrations required to inhibit the growth of 90% of strains (MIC90) of most of the susceptible pathogens commonly involved in bone infections.


Assuntos
Antibacterianos/farmacocinética , Osso e Ossos/metabolismo , Gentamicinas/farmacocinética , Adulto , Idoso , Idoso de 80 Anos ou mais , Disponibilidade Biológica , Feminino , Quadril/cirurgia , Humanos , Infusões Intravenosas , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade
9.
Br J Anaesth ; 89(6): 925-7, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12453940

RESUMO

We describe a 25 mg intrathecal morphine overdose during a combined spinal-epidural block for a Caesarean delivery. Naloxone infusion (5.24 mg over 24 h) was started prior to the patient becoming symptomatic and almost immediately after the overdose. Invasive therapeutics such as mechanical ventilation were avoided.


Assuntos
Analgésicos Opioides/efeitos adversos , Anestesia Obstétrica/métodos , Cesárea , Erros de Medicação , Morfina/efeitos adversos , Adulto , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/sangue , Anestesia Epidural/métodos , Raquianestesia/métodos , Overdose de Drogas/terapia , Feminino , Humanos , Injeções Espinhais , Erros de Medicação/efeitos adversos , Morfina/administração & dosagem , Morfina/sangue , Gravidez
10.
Br J Anaesth ; 89(2): 231-6, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12378658

RESUMO

BACKGROUND: In several lung diseases, oxidative stress can be demonstrated. This has not been shown in patients with ventilator-associated pneumonia (VAP). METHODS: We studied plasma and bronchoalveolar lavage (BAL) samples for markers of oxidative stress, taken from patients with VAP. Seventy-eight patients likely to have VAP and 10 patients who were not suspected of having VAP were studied prospectively. A diagnosis of VAP was based on a positive quantitative mini-lavage culture of > or = 10(3) colony-forming units per ml. Blood and BAL samples were collected and analysed for thiobarbituric acid reactant substances (TBARS) and antioxidant activity. RESULTS: Plasma and alveolar TBARS increased significantly in patients who developed VAP compared with those who did not, by 43% and 259% respectively. Red cells and alveolar glutathione peroxidase concentrations (antioxidant activity) were lower in those with VAP compared with the non-VAP group, by 43% and 68% respectively. No significant differences were found for serum superoxide dismutase activity. Significant differences were found for alveolar glutathione peroxidase concentrations over time in the VAP group. No significant differences between survivors and non-survivors were found in the blood or BAL assays, in patients with VAP. CONCLUSIONS: VAP is associated with evidence of early oxidative stress in the alveolar fluid and blood.


Assuntos
Estresse Oxidativo/fisiologia , Pneumonia/fisiopatologia , Alvéolos Pulmonares/fisiopatologia , Respiração Artificial/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Lavagem Broncoalveolar , Feminino , Glutationa Peroxidase/análise , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia/sangue , Pneumonia/etiologia , Alvéolos Pulmonares/metabolismo , Superóxido Dismutase/análise , Substâncias Reativas com Ácido Tiobarbitúrico/análise
11.
Br J Anaesth ; 88(3): 369-73, 2002 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11990268

RESUMO

BACKGROUND: Although the postanaesthesia care unit (PACU) can be noisy, the effect of noise on patients recovering from anaesthesia is unknown. We studied the sources and intensity of noise in the PACU and assessed its effect on patients' comfort. METHODS: We measured noise in a five-bed PACU with a sound level meter. Noise levels were obtained using an A-weighted setting (dBA) and peak sound using a linear scale (dBL). Leq (average noise level at 5-s intervals), maximum Leq (LeqMax), minimum Leq (LeqMin) and noise peaks (Lpc) were calculated. During recording, an independent observer noted the origin of sounds from alarms and noise above 65 dB intensity (P65dB). Two hours after leaving the PACU, patients were asked about their experience and to rank their complaints on a visual analogue scale (VAS) using unstructured and structured questionnaires. RESULTS: We made 20,187 measurements over 1678 min. The mean Leq, LeqMax and LeqMin were 67.1 (SD 5.0), 75.7 (4.8) and 48.6 (4.1) dBA respectively. The mean Lpc was 126.2 (4.3) dBL. Five per cent of the noise was at a level above 65 dBA. Staff conversation caused 56% of sounds greater than 65 dB and other noise sources (alarm, telephone, nursing care) were each less than 10% of these sounds. Five patients reported disturbance from noise. There was no significant difference in Leq measured for patients who found the PACU noisy and those who did not [59.5 (3.1) and 59.4 (2.4) dBA respectively]. Stepwise multiple logistic regression indicated that only pain was associated with discomfort. CONCLUSIONS: Even though sound in the PACU exceeded the internationally recommended intensity (40 dBA), it did not cause discomfort. Conversation was the most common cause of excess noise.


Assuntos
Período de Recuperação da Anestesia , Ambiente de Instituições de Saúde , Ruído/efeitos adversos , Cuidados Pós-Operatórios , Sala de Recuperação , Adulto , Idoso , Anestesia Geral , Monitoramento Ambiental/métodos , Feminino , França , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Prospectivos , Fala
12.
J Chemother ; 14(2): 175-80, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12017373

RESUMO

The authors determined the pharmacokinetic parameters of a new immediate-release ciprofloxacin suspension in tube-fed intensive care patients with bacterial pneumonia, to compare two dosage regimens: 500 mg b.i.d and 750 mg b.i.d. in this prospective clinical trial. The 20 patients were critically ill and on mechanical ventilation and enteral feeding with bacterial pneumonia. They were randomized to receive two different ciprofloxacin dosages: 500 mg b.i.d (group 1) versus 750 mg b.i.d. (group 2). Blood samples were collected from these patients after reaching steady-state and the pharmacokinetic parameters were determined. The mean (range) serum steady-state concentration at 2 h after enteral administration was: C(max 500) = 2.6 (1.2-4.3) mg/L in group 1 and C(max 750) = 3.5 (1.5-5.9) mg/L in group 2. The mean (range) calculated 12-h area under the serum concentration was high in both groups: AUC(0-12 (500)) = 24.7 (12.9-36.2) mg.h/L in group 1 and AUC(0-12 (750)) = 28.9 (18.3-47.5) mg.h/L in group 2. In conclusion, ciprofloxacin oral suspension was well absorbed via nasogastric route in intensive care patients with severe pneumonia, achieving reliable pharmacokinetic parameters for most of the pathogens and important cost reduction compared to intravenous delivery. However, with less susceptible pathogens such as Staphylococcus aureus or Pseudomonas aeruginosa, higher dosages than 750 mg b.i.d. should be given.


Assuntos
Anti-Infecciosos/farmacocinética , Ciprofloxacina/farmacocinética , Pneumonia Bacteriana/metabolismo , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Infecciosos/administração & dosagem , Disponibilidade Biológica , Ciprofloxacina/administração & dosagem , Estado Terminal , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
13.
J Chemother ; 14(1): 54-8, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11892900

RESUMO

The degree of penetration of an antibiotic into the infected site is an important criterion for therapeutic success. This is particularly true for bone and joint infections. The association of piperacillin and tazobactam has been widely used in the treatment of serious infections including bone infections, but no study has been devoted to the subject of its diffusion into synovial tissue. Our objective was to quantify piperacillin/tazobactam synovial tissue penetration and to estimate the efficacy of the association against the microorganisms usually encountered in joint infections. In an open-label study, 6 subjects with similar age, weight, height and creatinine clearance, who were undergoing elective total hip replacement, received a single, parenteral, 4 g/500 mg dose of piperacillin/tazobactam. Plasma and synovial tissue samples were collected and analyzed by a validated HPLC method. The mean concentrations of piperacillin and tazobactam 1.5 h after the initiation of infusion were 69.9 +/- 4.9 microg/mL and 7.7 +/- 0.3 microg/mL, respectively, in plasma and 37.1 +/- 2.1 microg/g and 2.8 +/- 0.4 microg/g, respectively, in synovial tissue. The synovial tissue/plasma ratios were 0.5 +/- 0.0 for piperacillin and 0.4 +/- 0.0 for tazobactam. The piperacillin/tazobactam ratios were 9.1:1 in plasma and 13.5:1 in synovial tissue. The concentrations achieved in synovial tissue are above the MICs of most of the susceptible pathogens usually involved in joint infections, which suggests that the piperacillin/tazobactam combination should be effective in the treatment of most joint infections caused by susceptible microorganisms.


Assuntos
Quimioterapia Combinada/farmacocinética , Ácido Penicilânico/farmacocinética , Piperacilina/farmacocinética , Membrana Sinovial/metabolismo , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Quadril , Humanos , Pessoa de Meia-Idade , Ácido Penicilânico/análogos & derivados , Combinação Piperacilina e Tazobactam
14.
Br J Anaesth ; 86(6): 832-6, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11573592

RESUMO

Sevoflurane is widely used in anaesthetic protocols for patients undergoing surgical procedures. However, there are no reports on the influence of sepsis on minimum alveolar concentration of sevoflurane (MAC(SEV)) in animals or in humans. The aim of this study was to test the hypothesis that sepsis could alter the MAC(SEV) in a normotensive septic pig model. Twenty young, healthy pigs were used. After they had received 10 mg kg(-1) of ketamine i.m. for premedication, anaesthesia was established with propofol 3 mg kg(-1) and the trachea was intubated. Sevoflurane was used as the sole anaesthetic agent. Baseline haemodynamic recording included electrocardiography, carotid artery blood pressure and a pulmonary thermodilution catheter. Baseline MAC(SEV) in each pig was evaluated by pinching with a haemostat applied for 1 min to a rear dewclaw. MAC(SEV) was determined using incremental changes in sevoflurane concentration until purposeful movement appeared. Pigs were assigned randomly to two groups: the saline group (n = 10) received a 1-h i.v. infusion of sterile saline solution while the sepsis group (n = 10) received a 1-h i.v. infusion of live Pseudomonas aeruginosa. Epinephrine and hydroxyethylstarch were used to maintain normotensive and normovolemic haemodynamic status. In both groups, MAC(SEV) was evaluated 5 h after infusion. Significant increases in mean artery pulmonary pressure, filling, epinephrine and vascular pulmonary resistances occurred in the sepsis group. MAC(SEV) for the saline group was 2.4% [95% confidence interval (CI) 2.1-2.55%] and the MAC(SEV) for the sepsis group was 1.35% (95% CI 1.2-1.45%, P<0.05). These data indicate that MAC(SEV) is significantly decreased in this normotensive septic pig model.


Assuntos
Anestésicos Inalatórios/farmacocinética , Éteres Metílicos/farmacocinética , Alvéolos Pulmonares/metabolismo , Sepse/metabolismo , Suínos/metabolismo , Analgésicos , Anestésicos Intravenosos , Animais , Ketamina , Modelos Animais , Pré-Medicação , Propofol , Sevoflurano
15.
Anesth Analg ; 93(4): 981-5, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11574369

RESUMO

UNLABELLED: We evaluated the circulating and lung oxidative status during general anesthesia established with propofol, sevoflurane, or desflurane in mechanically ventilated swine. Blood samples and bronchoalveolar lavage fluid (BAL) specimens were respectively performed via an internal jugular vein catheter and a nonbronchoscopic BAL for baseline oxidative activity measurements: malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPX). A 4-h general anesthesia was then performed in the three groups of 10 swine: the Propofol group received 8 mg x kg(-1) x h(-1) of IV propofol as the sole anesthetic; the Desflurane group received 1.0 minimum alveolar concentration of desflurane; and the Sevoflurane group received 1.0 minimum alveolar concentration of sevoflurane. We observed significantly larger levels of MDA in plasma and BAL during desflurane exposure than with the other anesthetics. We also observed smaller concentrations of circulating GPX and alveolar GPX. We found a significant decrease for MDA measurements in the plasma and the pulmonary lavage during propofol anesthesia. We also found larger values of GPX measurements in the serum and the pulmonary lavage. No significant changes were observed when animals were exposed to sevoflurane. No significant changes were found for circulating concentrations of SOD during exposure to all anesthetics. In this mechanically ventilated swine model, desflurane seemed to induce a local and systemic oxidative stress, whereas propofol and sevoflurane were more likely to have antioxidant properties. IMPLICATIONS: Superoxide is an unavoidable byproduct of oxygen metabolism that occurs in various inflammatory reactions. Inhalation of volatile anesthetics under mechanical ventilation induces an inflammatory response. We evaluated the bronchoalveolar and systemic oxidative stress in swine during exposure to propofol and newer volatile anesthetics. Desflurane induces more lipid peroxidation than do the other anesthetics.


Assuntos
Anestésicos Inalatórios/farmacologia , Anestésicos Intravenosos/farmacologia , Líquido da Lavagem Broncoalveolar/química , Isoflurano/farmacologia , Éteres Metílicos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Propofol/farmacologia , Animais , Antioxidantes/metabolismo , Desflurano , Glutationa Peroxidase/metabolismo , Isoflurano/análogos & derivados , Peroxidação de Lipídeos/efeitos dos fármacos , Malondialdeído/sangue , Alvéolos Pulmonares/efeitos dos fármacos , Alvéolos Pulmonares/metabolismo , Sevoflurano , Superóxido Dismutase/sangue , Suínos
16.
Br J Anaesth ; 87(2): 280-3, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11493502

RESUMO

The effect of sepsis on the minimum alveolar concentration of desflurane (MAC(DES)) in humans and other animals has not been reported previously. The aim of this study was to test the hypothesis that sepsis might alter MAC(DES) in a normotensive septic porcine model. Twenty-four young healthy pigs were premedicated with ketamine 10 mg kg(-1 )i.m and then anaesthesia was established with propofol 3 mg kg(-1) and the trachea was intubated. Baseline MAC(DES) in each pig was evaluated by pinching with a haemostat applied for 1 min to a rear dewclaw. MAC(DES) was determined by changing desflurane concentrations stepwise until purposeful movement appeared. Pigs were randomly assigned to two groups of 12 animals: the saline group received a 1 h i.v. infusion of saline solution while the sepsis group received a 1 h i.v. infusion of live Pseudomonas aeruginosa. Epinephrine and hydroxyethylstarch were used to maintain normotensive and normovolaemic haemodynamic status. In both groups, MAC(DES) was evaluated 5 h after infusion. Significant increases in heart rate, cardiac output, mean pulmonary artery pressure and pulmonary vascular resistance occurred in the sepsis group. MAC(DES) was 9.2% (95% confidence interval (CI) 6.8-10.6%) for the saline group and 6.7% (95% CI: 4.7-10.4) for the sepsis group (P<0.05). These data indicate that MAC(DES) is significantly decreased in this normotensive hyperkinetic septic porcine model.


Assuntos
Anestésicos Inalatórios/farmacocinética , Bacteriemia/metabolismo , Isoflurano/farmacocinética , Alvéolos Pulmonares/metabolismo , Animais , Bacteriemia/fisiopatologia , Desflurano , Modelos Animais de Doenças , Hemodinâmica/efeitos dos fármacos , Isoflurano/análogos & derivados , Suínos
18.
Anesth Analg ; 92(2): 442-7, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11159248

RESUMO

We investigated the usefulness and reliability of the Gram stain value versus quantitative cultures in the early diagnosis of ventilator-associated pneumonia (VAP) using the protected bronchoalveolar lavage (PBAL). One hundred four mechanically ventilated patients (age = 52 +/- 19; SAPS II = 38 +/- 15) with a strong suspicion of VAP were consecutively included. One hundred sixteen PBAL were performed and mini-bronchoalveolar lavage were analyzed using the Gram stain standard method and the conventional quantitative culture technique. VAP diagnosis was based on a positive quantitative culture of mini-bronchoalveolar lavage fluid (cutoff > or = 10(3) CFU/mL). A final diagnosis of VAP was established in 67 patients and there was no infection in 49 cases. Regarding detection of bacteria using the Gram stain, we found a sensitivity of 76.2%, a specificity of 100%, a positive predictive value of 100% and a negative predictive value of 75.4%. There was a good agreement with the final diagnosis (kappa statistic 0.73; concordance 86.2%). The degree of qualitative agreement between Gram stain and quantitative cultures was analyzed in the VAP group: the correlation was complete in 39% (26 of 67 VAP), partial in 28% (19 of 67 VAP) and there was no correlation in 33% (22 of 67 VAP). We conclude that despite its overall "good agreement," the Gram stain is of limited use for the rapid diagnosis of VAP and unreliable for the early adaptation of empirical antimicrobial therapy when using the noninvasive PBAL procedure.


Assuntos
Bactérias/isolamento & purificação , Líquido da Lavagem Broncoalveolar/microbiologia , Pneumonia Bacteriana/diagnóstico , Respiração Artificial/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Corantes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
Anesth Analg ; 92(1): 180-3, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11133623

RESUMO

UNLABELLED: The combination of opioids with local anesthetics is commonly used for epidural labor analgesia. We examined whether increasing sufentanil in doses of 5, 10, and 15 microg prolonged the duration of labor analgesia produced by ropivacaine. One hundred healthy parturients in the first stage of labor who requested epidural analgesia were enrolled. Parturients were randomized to receive 12 mL ropivacaine 0.2% alone or with sufentanil 5 microg, sufentanil 10 microg, or sufentanil 15 microg. The duration of analgesia, pain score, degree of motor blockade (using a four-point Bromage scale), heart rate, blood pressure, respiratory rate, oxygen saturation, and incidence of nausea and pruritus were recorded. The mean duration of epidural analgesia was 96 +/- 32 min for patients without sufentanil, 134 +/- 27 min for Group 5 (p < 0.01 versus control), 135 +/- 33 min for Group 10 (p < 0.01 versus control), 130 +/- 33 min for Group 15 (p < 0.01 versus control) without differences among sufentanil groups. Between 30 and 90 min, the sufentanil groups (5 microg, 10 microg, and 15 microg) had lower pain scores than the control group (p < 0.01 versus control) but there were no differences among the sufentanil groups. No patient in any group had a Bromage score more than 1. No significant difference was found for opioid-related side effects. We conclude that 5-10 or 15 microg sufentanil induced a similar prolongation of analgesia when combined with ropivacaine 0.2% for initiation of labor analgesia. IMPLICATIONS: We studied the effect of adding one of three possible sufentanil doses to epidural ropivacaine 0.2% for labor analgesia. Adding sufentanil increased the duration of analgesia but there was no advantage in adding more than 5 microg of sufentanil.


Assuntos
Amidas/administração & dosagem , Analgesia Epidural/métodos , Analgesia Obstétrica/métodos , Analgésicos Opioides/administração & dosagem , Anestésicos Locais/administração & dosagem , Sufentanil/administração & dosagem , Adulto , Amidas/efeitos adversos , Analgesia Epidural/efeitos adversos , Analgesia Obstétrica/efeitos adversos , Analgésicos Opioides/efeitos adversos , Anestésicos Locais/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Náusea/induzido quimicamente , Gravidez , Estudos Prospectivos , Prurido/induzido quimicamente , Ropivacaina , Sufentanil/efeitos adversos
20.
FEBS Lett ; 460(1): 81-5, 1999 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-10571065

RESUMO

We undertook the characterization of an actin gene and its proximal promoter in the oyster Crassostrea gigas. A complete actin cDNA was identified, sequenced and its amino acid sequence deduced. Comparative analysis showed a high homology with actin of other species and that this gene is closer to the cytoplasmic form of actins than to the muscle type. A probe derived from the 5'-untranslated region of the cDNA was then used to isolate the actin gene from a genomic library. The gene was sequenced and shown to contain a single 643 bp intron. A 1670 bp fragment upstream from the open reading frame was isolated and sequenced. This upstream region displays typical features of actins such as a serum response element (CarG box). This fragment was cloned into the promoterless vector pGL3-basic and the resulting construct was transfected into cells of dissociated oyster heart primary cultures. Its capacity to express the luciferase in this in vitro homologous system was monitored and showed high expression levels. This is the first complete actin sequence reported so far for the oyster C. gigas and its promoter is the first available among bivalves.


Assuntos
Actinas/genética , Ostreidae/genética , Regiões Promotoras Genéticas , Actinas/química , Sequência de Aminoácidos , Animais , Sequência de Bases , Células Cultivadas , Clonagem Molecular , Proteínas de Ligação a DNA/genética , Regulação da Expressão Gênica , Genes Reporter , Dados de Sequência Molecular , Mutação , Proteínas Nucleares/genética , Fator de Resposta Sérica , Transfecção
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