RESUMO
BACKGROUND: Platelet (PLT) support is critical to the care of patients with thrombocytopenia, but allogeneic transfusions carry risk. Pathogen reduction mitigates some transfusion risks, but effects on PLT function remain a concern. This clinical pilot study assessed the effect of pathogen reduction technology with riboflavin plus ultraviolet light using thrombelastography (TEG). STUDY DESIGN AND METHODS: This prospective, randomized, crossover study compared Mirasol-treated (MIR) and standard reference (REF) PLT transfusions. PLT counts and TEG measurements were taken at pretransfusion and 1- and 24-hour-posttransfusion time points. The primary outcome measure was the pretransfusion to 1-hour-posttransfusion change in maximum amplitude (ΔMA(1 hr)). Secondary endpoints included ΔMA among other time points, relative MA, and the PLT count-MA correlation. RESULTS: Of 16 enrolled patients, one withdrew before study treatment and three did not require two transfusions, leaving 12 patients in the efficacy analyses (seven MIR-REF, five REF-MIR). ΔMA(1 hr) (mean ± SD) was 10.60 ± 6.47 mm for MIR and 14.33 ± 5.38 mm for REF (p = 0.20, n = 10). ΔMA(24hr) was 9.49 ± 7.94 for MIR and 7.13 ± 3.08 for REF (p = 0.38, n = 9); ΔMA(24hr-1 hr) was -1.11 ± 2.95 for MIR and -7.20 ± 4.81 for REF (p = 0.016, n = 8). MA values for MIR and REF correlated with the log of PLT count (rMIR = 0.6901, rREF = 0.7399). CONCLUSION: TEG is sensitive to changes in hemostatic function resulting from a single PLT transfusion. MIR and REF provided similar increments in hemostatic function in the immediate posttransfusion period and at 24 hours. A significant difference detected for ΔMA(24hr-1 hr) suggests different PLT clearance mechanisms. The relationship of these variables to clinically meaningful outcomes, for example, bleeding events or transfusion requirements, has yet to be determined.
Assuntos
Transfusão de Plaquetas/métodos , Trombocitopenia/terapia , Adulto , Idoso , Plaquetas , Estudos Cross-Over , Feminino , Hemostasia , Humanos , Masculino , Pessoa de Meia-Idade , Transfusão de Plaquetas/efeitos adversosRESUMO
AIMS: Anacetrapib is an orally active and potent inhibitor of CETP in development for the treatment of dyslipidaemia. These studies endeavoured to establish the safety, tolerability, pharmacokinetics and pharmacodynamics of rising single doses of anacetrapib, administered in fasted or fed conditions, and to preliminarily assess the effect of food, age, gender and obesity on the single-dose pharmacokinetics and pharmacodynamics of anacetrapib. METHODS: Safety, tolerability, anacetrapib concentrations and CETP activity were evaluated. RESULTS: Anacetrapib was rapidly absorbed, with peak concentrations occurring at approximately 4 h post-dose and an apparent terminal half-life ranging from approximately 9 to 62 h in the fasted state and from approximately 42 to approximately 83 h in the fed state. Plasma AUC and C(max) appeared to increase in a less than approximately dose-dependent manner in the fasted state, with an apparent plateau in absorption at higher doses. Single doses of anacetrapib markedly and dose-dependently inhibited serum CETP activity with peak effects of approximately 90% inhibition at t(max) and approximately 58% inhibition at 24 h post-dose. An E(max) model best described the plasma anacetrapib concentration vs CETP activity relationship with an EC(50) of approximately 22 nm. Food increased exposure to anacetrapib; up to approximately two-three-fold with a low-fat meal and by up to approximately six-eight fold with a high-fat meal. Anacetrapib pharmacokinetics and pharmacodynamics were similar in elderly vs young adults, women vs men, and obese vs non-obese young adults. Anacetrapib was well tolerated and was not associated with any meaningful increase in blood pressure. CONCLUSIONS: Whereas food increased exposure to anacetrapib significantly, age, gender and obese status did not meaningfully influence anacetrapib pharmacokinetics and pharmacodynamics.
Assuntos
Proteínas de Transferência de Ésteres de Colesterol/antagonistas & inibidores , Dislipidemias/tratamento farmacológico , Oxazolidinonas/farmacocinética , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos Cross-Over , Método Duplo-Cego , Jejum , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade , Oxazolidinonas/administração & dosagem , Oxazolidinonas/farmacologia , Fatores Sexuais , Resultado do Tratamento , Adulto JovemRESUMO
The potential effect of iron depletion by blood donation and its relevance to cardiovascular diseases are still under debate. Markers of vascular integrity are increasingly applied in investigations of atherothrombotic diseases. In this study, we investigated whether a lower iron status through blood donation was associated with markers of vascular integrity (circulating oxidised LDL, sICAM-1, sVCAM-1 and vWF-antigen) by comparing healthy male voluntary donors to non-donors, taking into account differences in baseline characteristics. Two fasting blood samples were collected within 1 week from 41 donors and 39 non-donors. The iron status was estimated by measuring the concentration of plasma iron, ferritin, haemoglobin and hematocrit. The markers of iron status were all significantly lower in donors compared to non-donors, especially for ferritin concentrations. However, the lower iron status by blood donation was not reflected in the concentrations of OxLDL, sICAM-1, sVCAM-1 and vWF-antigen in men after adjustment for BMI and ratio total/HDL cholesterol. In order to avoid possible selection-bias related to donorship, we have additionally investigated the difference in marker concentrations within the non-donors, comparing low- and high-ferritin concentrations. This analysis suggests that ferritin concentration is not associated with in vivo LDL oxidation.
Assuntos
Doadores de Sangue , Molécula 1 de Adesão Intercelular/sangue , Ferro/sangue , Lipoproteínas LDL/sangue , Molécula 1 de Adesão de Célula Vascular/sangue , Fator de von Willebrand/análise , Adulto , Idoso , Ferritinas/sangue , Hematócrito , Hemoglobinas/análise , Humanos , Masculino , Pessoa de Meia-Idade , OxirreduçãoRESUMO
OBJECTIVE: In this randomized double-blind placebo-controlled cross-over study the effects of spreads enriched with plant sterols were determined on serum lipids, lipoprotein and apolipoprotein concentrations in a Belgian population. METHODS: Fourty-two healthy adult volunteers (22 men and 20 women) with an average age of 55 (SD 9) years and with serum total cholesterol concentrations below 300 mg/dl, consumed during two consecutive periods of 4 weeks two different low-fat spreads. Both the plant sterol rich and control spreads contained 35% of fat and had an almost equal fat composition. The sterol content of the enriched spread was 8.3%. Intake of the spreads was 25 g/day. RESULTS: Serum total and LDL-cholesterol concentrations lowered by 7% (18 mg/dl) and 10% (16 mg/dl), respectively, with the plant sterol-enriched compared to the control spread. Serum HDL-cholesterol concentration did not significantly differ between the two spreads. Apolipoprotein B concentrations lowered by 8% (0.08 g/l) with the plant sterol-enriched spread, while concentrations of apolipoprotein A-I did not change. CONCLUSION: These findings indicate that a daily intake of 25 gram low-fat spread containing 2 gram plant sterol per day is effective in lowering blood total and LDL cholesterol, and apolipoprotein B concentrations. This lowering may help to reduce the risk of heart disease in the population.
Assuntos
Hipercolesterolemia/sangue , Hipercolesterolemia/tratamento farmacológico , Hipolipemiantes/farmacologia , Hipolipemiantes/uso terapêutico , Lipoproteínas/sangue , Lipoproteínas/efeitos dos fármacos , Fitosteróis/farmacologia , Fitosteróis/uso terapêutico , Adulto , Idoso , Apolipoproteína A-I/sangue , Apolipoproteína A-I/efeitos dos fármacos , Apolipoproteínas B/sangue , Apolipoproteínas B/efeitos dos fármacos , Bélgica , HDL-Colesterol/sangue , HDL-Colesterol/efeitos dos fármacos , LDL-Colesterol/sangue , LDL-Colesterol/efeitos dos fármacos , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Índice de Gravidade de Doença , Resultado do Tratamento , Triglicerídeos/sangueRESUMO
The purpose of this study was to investigate, in smokers, whether the oxidative balance of their dietary pattern affected mortality risk. To evaluate the oxidative balance of the dietary pattern, an oxidative balance score was constructed that summarized the combined intake of dietary antioxidants (vitamin C and beta-carotene) and a prooxidant (iron). The low oxidative balance score group included smokers with a diet high in vitamin C and beta-carotene and/or low in iron and the high oxidative balance score group included those with a diet low in vitamin C and beta-carotene and/or high in iron. Using the 10-y follow-up mortality data from the Belgian Interuniversity Research on Nutrition and Health (BIRNH) study, the association of this oxidative balance score with all-cause, cardiovascular disease (CVD) and total cancer mortality was investigated in 2814 male smokers. In multivariate-adjusted Cox models, men in the highest oxidative balance score group had a higher relative risk (RR) of all-cause [RR = 1.44, 95% confidence interval (CI): 1.13, 1.82] and of total cancer mortality (RR = 1.62, 95% CI: 1.07, 2.45) compared with men in the lowest score group. This association was less pronounced for CVD mortality risk and was not significant (RR = 1.31, 95% CI: 0.86, 2.00). The risk of all-cause and total cancer mortality was driven principally by the high score group, which suggested a threshold effect for risk rather than a linear trend. The findings are consistent with the hypothesis that the oxidative balance of the diet is associated with subsequent mortality. Smokers whose diet is unbalanced in terms of anti- and prooxidants may therefore benefit from a recommendation to consume more servings of fresh fruits and vegetables and less meat.