Dietary polyphenols are thought to be beneficial for human health as antioxidants. Coffee beans contain a common polyphenol, chlorogenic acid. Chlorogenic acid is the ester of caffeic acid and quinic ...acid. Although these polyphenols have received much attention, there is little evidence indicating a relationship between the effect and the rate of absorption. In this study, we focused on the beneficial effects of chlorogenic acid and caffeic acid, a major metabolite of chlorogenic acid. We carried out in vitro and in vivo experiments. In the in vitro study, caffeic acid had stronger antioxidant activity than that of chlorogenic acid. The uptake of chlorogenic acid by Caco-2 cells was much less than that of caffeic acid. The physiological importance of an orally administered compound depends on its availability for intestinal absorption and subsequent interaction with target tissues. We then used an intestinal ischemia–reperfusion model to evaluate antioxidant activities in vivo. We found that both chlorogenic acid and caffeic acid had effects on intestinal ischemia–reperfusion injury. Since caffeic acid has a stronger antioxidant activity than that of chlorogenic acid and chlorogenic acid is hydrolyzed into caffeic acid in the intestine, it is possible that caffeic acid plays a major role in the protective effect of chlorogenic acid against ischemia–reperfusion injury.
Production of free radical species in cells and body tissues is known to cause many pathological disorders. Therefore, free radical scavengers play an important role in the prevention of various ...human diseases. Bamboo grass, Sasa senanensis, is a native Japanese plant. Sasa has been used for medicine in Japan for many centuries. In this study, we investigated the antioxidative activity of Absolutely Hemicellulose Senanensis (AHSS), a novel extract from Sasa. In the first part of this study, we found that AHSS has antioxidant activities by the assay using superoxide anion-2-methyl-6-methoxyphenylethynylimidazopyrazynone (MPEC) reaction kit. We then confirmed its antioxidative activity using a rat ischemia and subsequent reperfusion (I/R) injury model. Breakdown of the intestinal wall caused by intestinal I/R was attenuated by pretreatment with AHSS. Moreover, AHSS inhibited the production of lipid peroxide by intestinal I/R. AHSS could be an important source of ingredients for use in functional foods and other applications.
Coenzyme Q10 (CoQ10) is widely consumed as a food supplement because of its recognition as an important nutrient in supporting human health. Absorption of compounds from the gastrointestinal tract is ...one of the important determinants of oral bioavailability. However, the absorption of dietary CoQ10 is slow and limited due to its hydrophobicity and large molecular weight. The absorption of orally applied compounds can be enhanced by interactions with food or food components. Thus, we investigated the effect of food intake on the absorption of CoQ10 after oral supplementation. In this study, we demonstrated that food intake enhanced the intestinal absorption of CoQ10. In order to improve intestinal absorption of CoQ10 after oral supplementation, we developed an emulsion formulation. Intestinal absorption of CoQ10 after administration of the emulsion formulation was also enhanced by food intake. Moreover, the peak concentration and the extent of absorption after administration of the emulsion formulation were greater than those after administration of a suspension formulation. It is possible that administration of CoQ10 in an emulsion formulation enhances the pharmacological effects of CoQ10.
Lutein is a carotenoid and it has antioxidant effects. Lutein may have a protective effect on ischemia reperfusion (I/R) injury induced by free radical species. However, little is known about the ...protective effect of lutein on I/R injury in vivo. The present study was undertaken to clarify the protective effects of lutein on I/R injuries in the rat small intestine. Administration of lutein before intestinal I/R attenuated the damage to villi and deciduation of enterocytes and suppressed the increase in lipid peroxide.
Ferulic acid exhibits a wide range of therapeutic effects that are attributed to its potent antioxidant capacity. However,
in vitro antioxidant properties of ferulic acid have not been elucidated in ...detail. Evidence that polyphenols, including ferulic acid, act as antioxidants
in vivo is also limited. In order to elucidate in more detail the scientific background of antioxidant activities of ferulic acid, we carried out
in vitro and
in vivo experiments. We focused on superoxide anion scavenging activity, xanthine oxidase inhibition activity, and chain-breaking activity. The combined antioxidant activity from radical scavenging and xanthine oxidase inhibition of ferulic acid was much weaker than that of (−)-epigallocatechin gallate (EGCG) and ascorbic acid. On the other hand, EGCG, ascorbic acid and ferulic acid exhibited chain-breaking activity and prevented ischaemia-reperfusion-associated intestinal injury. Chain-breaking activity may play a contributory role in the protective effect of ferulic acid on oxidative injury in humans and in
in vivo studies.
O setor de transporte automotivo é um dos principais responsáveis pelas emissões de gases nocivos à saúde ou causadores do efeito estufa. Existem inúmeras propostas econômicas para a redução destas ...emissões, que se dividem basicamente entre regulamentação de emissões e impostos sobre combustível ou veículos. Apresentaremos neste trabalho um esquema de feebate, uma alternativa baseada num mercado de carbono em que um carro que tem emissões de poluentes abaixo de certo nível ganha um subsídio para sua compra, enquanto que outro que apresenta emissões acima paga um imposto. Este esquema é projetado para que no fim, contabilizados o imposto pago e o subsídio oferecido, faça com que o governo não tenha receita, nem despesas com este. Para mostrar sua eficácia, faremos simulações com base em estimações do mercado de automóveis brasileiro do período de 2008 a 2012 usando um modelo de escolhas discretas através de um logit multinomial aninhado, e faremos análises de bem estar.
The automotive transport sector is one of the main responsible for emissions of harmful gases and greenhouse gases. There are numerous economics proposals for reducing these emissions, which are basically divided between emission regulations and taxes on fuel or vehicles. We will present in this work a feebate scheme, an alternative based on a carbon market in which a car that has emissions of pollutants below a certain level gains a subsidy for its purchase, while another that presents emissions above a level pays a tax. This scheme is designed so that at the end, counting the tax paid and the subsidy offered, make the government have no revenue, nor expenses with it. To show its effectiveness, we will make simulations of this scheme based on estimates of the Brazilian auto market from 2008 to 2012 using a discrete choice model with a nested multinomial logit, and we will analise social welfare changes.
Coenzyme Q10 (CoQ10) is widely consumed as a food supplement because of its recognition as an important nutrient in supporting human health. Absorption of compounds from the gastrointestinal tract is ...one of the important determinants of oral bioavailability. However, the absorption of dietary CoQ10 is slow and limited due to its hydrophobicity and large molecular weight. The absorption of orally applied compounds can be enhanced by interactions with food or food components. Thus, we investigated the effect of food intake on the absorption of CoQ10 after oral supplementation. In this study, we demonstrated that food intake enhanced the intestinal absorption of CoQ10. In order to improve intestinal absorption of CoQ10 after oral supplementation, we developed an emulsion formulation. Intestinal absorption of CoQ10 after administration of the emulsion formulation was also enhanced by food intake. Moreover, the peak concentration and the extent of absorption after administration of the emulsion formulation were greater than those after administration of a suspension formulation. It is possible that administration of CoQ10 in an emulsion formulation enhances the pharmacological effects of CoQ10.
Background
Thrombocytopenia represents an obstacle for invasive procedures in chronic liver disease (CLD) patients. We aimed to estimate the appropriate dose and evaluate the efficacy and safety of ...lusutrombopag for the treatment of thrombocytopenia before percutaneous liver radiofrequency ablation (RFA) for primary hepatic cancer in patients with CLD.
Methods
In this multicenter, randomized, double-blind, placebo-controlled study conducted in Japan, 61 CLD patients with platelet count < 50 × 10
3
/µL at screening were randomized to placebo or lusutrombopag 2, 3, or 4 mg once daily for 7 days, followed by a 28-day post-treatment assessment period. The primary efficacy endpoint was the proportion of patients who did not require platelet transfusion before RFA. The pre-specified key secondary efficacy endpoint was the proportion of responders. Adverse events (AEs) and thrombosis-related AEs were evaluated.
Results
The proportion of patients who did not require platelet transfusion before RFA and that of responders were significantly higher (
p
< 0.01) in the 2-mg (80.0, 66.7%), 3-mg (81.3, 68.8%), and 4-mg groups (93.3, 80.0%) compared with the placebo group (20.0, 6.7%) and showed a dose-dependent effect. The incidence of AEs was 97.8 and 100% in the lusutrombopag (all groups) and placebo groups, respectively; no dose-related increase was observed. Four patients experienced thrombosis-related events (one each in the placebo and 2-mg groups, and two in the 4-mg group). A total of 16 (18%) adverse drug reactions occurred in the safety analysis set.
Conclusions
Lusutrombopag 3 mg once daily for 7 days was effective without raising concerns about excessive increases in platelet count.
Clinical trial registration
The study is registered at JapicCTI-121944.
Objectives The aim of this study was to investigate the antiatherogenic effects of the dipeptidyl peptidase-4 inhibitor, des-fluoro-sitagliptin (DFS). Background The new class of anti–type 2 diabetes ...drugs, dipeptidyl peptidase-4 inhibitors, improves glucose metabolism by increasing levels of active glucagon-like peptide (GLP)-1. Methods Endothelial function was examined by acetylcholine-induced endothelium-dependent vasorelaxation using aortic rings and atherosclerotic lesion development in the entire aorta in apolipoprotein E–deficient mice fed a high-fat diet with or without DFS, and the antiatherogenic effects of DFS were investigated in cultured human macrophages and endothelial cells. Plasma levels of active GLP-1 were measured in patients with or without coronary artery disease. Results DFS significantly improved endothelial dysfunction (89.9 ± 3.9% vs. 79.2 ± 4.3% relaxation at 10−4 mol/l acetylcholine, p < 0.05) associated with increased endothelial nitric oxide synthase phosphorylation and reduced atherosclerotic lesion area (17.7% 15.6% to 25.8% vs. 24.6% 19.3% to 34.6%, p < 0.01) compared with vehicle treatment. In cultured human macrophages, DFS significantly increased GLP-1-induced cytosolic levels of cyclic adenosine monophosphate compared with GLP-1 alone, resulted in inhibiting phosphorylation of c-jun N-terminal kinase and extracellular signal-regulated kinase 1/2 and nuclear factor-kappa B p65 nuclear translocation through the cyclic adenosine monophosphate/protein kinase A pathway, and suppressed proinflammatory cytokines (i.e., interleukin-1-beta, interleukin-6, and tumor necrosis factor-alpha) and monocyte chemoattractant protein-1 production in response to lipopolysaccharide. DFS-enhanced GLP-1 activity sustained endothelial nitric oxide synthase phosphorylation and decreased endothelial senescence and apoptosis compared with GLP-1 alone. In the human study, fasting levels of active GLP-1 were significantly lower in patients with coronary artery disease than those without (3.10 pmol/l 2.40 to 3.62 pmol/l vs. 4.00 pmol/l 3.10 to 5.90 pmol/l, p < 0.001). Conclusions A DPP-4 inhibitor, DFS, exhibited antiatherogenic effects through augmenting GLP-1 activity in macrophages and endothelium.
Platelet transfusion is used to prevent hemorrhagic events in patients with thrombocytopenia undergoing invasive procedures, but there are many disadvantages. We evaluated the efficacy and safety of ...lusutrombopag in patients with chronic liver disease and thrombocytopenia undergoing invasive procedures.
We performed a double-blind, parallel-group, phase 3 study of 96 patients with chronic liver disease and thrombocytopenia (platelet counts below 50,000/μL) undergoing invasive procedures from October 2013 to May 2014 at 81 centers in Japan. Patients were randomly assigned (1:1) to groups given once-daily lusutrombopag (3 mg) or placebo for up to 7 days. The primary efficacy endpoint was the proportion of patients not requiring platelet transfusion before the invasive procedure. The protocol-defined response (platelet count 50,000/μL or more with an increase of 20,000/μL or more from baseline) and the time course of the change in platelet count were also evaluated. Adverse events were recorded.
The proportions of patients who did not require preoperative platelet transfusion were 79.2% (38/48) in the lusutrombopag group and 12.5% (6/48) in the placebo group (P < .0001). A response was observed in 77.1% (37/48) of patients in the lusutrombopag group and 6.3% (3/48) of patients in the placebo group (P < .0001). In the lusutrombopag group without platelet transfusion, the median platelet count was 50,000/μL or more after 5 days; the mean time to reach the maximum platelet count was 13.4 days; and the number of days (adjusted mean) during which the platelet count was 50,000/μL or more was 21.09 days. Adverse drug reactions were reported in 8.3% of patients in the lusutrombopag group and 2.1% of patients in the placebo group. Two patients (1 per group) had a thrombotic event, but neither were associated with an excessive increase in platelet count (200,000/μL or more).
In a placebo-controlled trial, lusutrombopag was effective in achieving and maintaining the target platelet count in patients with chronic liver disease and thrombocytopenia undergoing invasive procedures. No significant safety concerns were raised. Japanese clinical trial registration no: JapicCTI-132323
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