Bioavailability of orally administered water-dispersible hesperetin and its effect on peripheral vasodilatation in human subjects: implication of endothelial functions of plasma conjugated metabolites

2012 ◽  
Vol 3 (4) ◽  
pp. 389 ◽  
Author(s):  
Hiroko Takumi ◽  
Hiroyasu Nakamura ◽  
Terumi Simizu ◽  
Ryoko Harada ◽  
Takashi Kometani ◽  
...  
Keyword(s):  
Human Subjects ◽  
Water Dispersible ◽  
Peripheral Vasodilatation ◽  
Endothelial Functions ◽  
Conjugated Metabolites

scholarly journals Kruppel-Like Factors in Thrombosis and Hemostasis

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. SCI-45-SCI-45
Author(s):  
Mukesh Jain
Keyword(s):  
Cell Biology ◽  
Vascular System ◽  
Conflicts Of Interest ◽  
Human Subjects ◽  
Myeloid Cell ◽  
Nutrient Delivery ◽  
Inflammatory Processes ◽  
Endothelial Functions ◽  
And Function

Abstract Armed with the appreciation that the blood and vascular system share common origins and cooperate to ensure fundamental processes (e.g. blood flow/fluidity, oxygen/nutrient delivery, immunity) essential for organismal survival, we posited that shared molecular pathways may be operative in coordinating the function of both systems. Over the past 2 decades, studies from our group and others have identified a family of transcription factors termed Kruppel-like factors (KLFs) as essential for development, differentiation, and function of cellular constituents of both the hematopoietic and vascular systems. In this presentation, discussion will focus on the role KLFs in control of endothelium and myeloid cell biology in physiology and disease. Specifically, cellular and in vivo evidence will be discussed implicating KLFs as master regulators of all cardinal endothelial functions (permeability, vasoreactivity, blood fluidity, and inflammation). Further, studies demonstrating KLF-control of myeloid cell development, subset specification, and pro-inflammatory activation will be reviewed with particular emphasis on results of efforts altering myeloid KLFs in the context of acute (e.g. bacterial infection, sepsis) and chronic (e.g. atherosclerosis, arterial/venous thrombosis) inflammatory processes. Correlative studies in human subjects will be presented. And finally, insights into how targeting KLFs can be exploited for therapeutic gain will be discussed. Disclosures No relevant conflicts of interest to declare.

Isolation and identification of benzodiazepine drugs and their metabolites in urine by use of Amberlite XAD-2 resin and thin-layer chromatography.

1976 ◽  
Vol 22 (10) ◽  
pp. 1596-1603 ◽  
Author(s):  
H Sawada ◽  
A Hara ◽  
S Asano ◽  
Y Matsumoto
Keyword(s):  
Thin Layer ◽  
Ethyl Acetate ◽  
Human Subjects ◽  
Isolation And Identification ◽  
Urinary Ph ◽  
Analytical Recovery ◽  
Benzodiazepine Derivatives ◽  
Layer Chromatography ◽  
Conjugated Metabolites ◽  
Benzodiazepine Drugs

Abstract We used the method described here to detect and identify seven benzodiazepine derivatives--diazepam, chlorodiazepoxide, nitrazepam, cloxazolam, oxazolam, oxazepam, and medazepam--and their metabolites in the urine of rabbits given the seven drugs orally. We column-chromatographed 25-ml samples of urine on Amberlite XAD-2. The drugs and their metabolites in the urine were adsorbed by the resin, irrespective of urinary pH, and upon successive elution with methanol and ethyl acetate/methanol/acetic acid (90/10/0.1 by vol) they could be separated and extracted from the normal components of urine with satisfactory analytical recovery. The conjugated metabolites were then enzymatically hydrolyzed and the hydrolysate was extracted into ethyl acetate and the extract thin-layer chromatographed to detect and identify each drug and each of its metabolites. In an experiment in which the urine of human subjects given 5 mg of nitrazepam orally was analyzed by this method, the metabolites of nitrazepam in the 24-h urine could be identified satisfactorily.

scholarly journals Oral bioavailability of quercetin from different quercetin glycosides in dogs

2010 ◽  
Vol 104 (2) ◽  
pp. 198-203 ◽  
Author(s):  
Marianne Reinboth ◽  
Siegfried Wolffram ◽  
Getu Abraham ◽  
Fritz R. Ungemach ◽  
Rainer Cermak
Keyword(s):  
Oral Bioavailability ◽  
Human Subjects ◽  
Relative Bioavailability ◽  
Systemic Circulation ◽  
Absolute Bioavailability ◽  
Time Curve ◽  
Quercetin Glycosides ◽  
Maximal Plasma ◽  
Conjugated Metabolites

Although the flavonol quercetin is used as a supplement in commercial dog food, data on quercetin bioavailability in dogs are not available. Thus, we investigated quercetin bioavailability (measured as area under the concentration–time curve) in nine adult beagle dogs at an oral dose of 10 mg/kg body weight (b.w.). The major fraction (>80 %) of flavonols circulating in blood plasma were conjugated metabolites of quercetin. The absolute bioavailability of quercetin (i.e. the fraction that reaches the systemic circulation) was only about 4 %. We also compared the oral bioavailability between the aglycone quercetin and its more often used glucorhamnoside (rutin) and 3-O-glucoside (isoquercitrin) at an equimolar dose of 30 μmol/kg b.w. (corresponding to 10 mg quercetin/kg). Quercetin and isoquercitrin were mainly absorbed in the small intestine with isoquercitrin being one and a half times more bioavailable than quercetin. Maximal plasma concentration after isoquercitrin treatment was 0·89 (sem 0·07) μmol/l. Although quercetin absorption from rutin was delayed, relative bioavailability was not lower than from the aglycone itself. The latter observation is in clear contrast to findings in human subjects, pigs or rats and might indicate that rutin is a better source of quercetin in dogs than in other species. However, potential in vivo quercetin effects beyond the gastrointestinal tract are limited by the intensive metabolism as well as by the rather low bioavailability of this flavonol.

Elevated level of circulatory sTLT1 induces inflammation through SYK/MEK/ERK signalling in coronary artery disease

2019 ◽  
Vol 133 (22) ◽  
pp. 2283-2299
Author(s):  
Apabrita Ayan Das ◽  
Devasmita Chakravarty ◽  
Debmalya Bhunia ◽  
Surajit Ghosh ◽  
Prakash C. Mandal ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Chronic Inflammation ◽  
Ex Vivo ◽  
Human Subjects ◽  
Critical Role ◽  
Atherosclerotic Cardiovascular Disease ◽  
Tnf Α ◽  
Artery Disease

Abstract The role of inflammation in all phases of atherosclerotic process is well established and soluble TREM-like transcript 1 (sTLT1) is reported to be associated with chronic inflammation. Yet, no information is available about the involvement of sTLT1 in atherosclerotic cardiovascular disease. Present study was undertaken to determine the pathophysiological significance of sTLT1 in atherosclerosis by employing an observational study on human subjects (n=117) followed by experiments in human macrophages and atherosclerotic apolipoprotein E (apoE)−/− mice. Plasma level of sTLT1 was found to be significantly (P<0.05) higher in clinical (2342 ± 184 pg/ml) and subclinical cases (1773 ± 118 pg/ml) than healthy controls (461 ± 57 pg/ml). Moreover, statistical analyses further indicated that sTLT1 was not only associated with common risk factors for Coronary Artery Disease (CAD) in both clinical and subclinical groups but also strongly correlated with disease severity. Ex vivo studies on macrophages showed that sTLT1 interacts with Fcɣ receptor I (FcɣRI) to activate spleen tyrosine kinase (SYK)-mediated downstream MAP kinase signalling cascade to activate nuclear factor-κ B (NF-kB). Activation of NF-kB induces secretion of tumour necrosis factor-α (TNF-α) from macrophage cells that plays pivotal role in governing the persistence of chronic inflammation. Atherosclerotic apoE−/− mice also showed high levels of sTLT1 and TNF-α in nearly occluded aortic stage indicating the contribution of sTLT1 in inflammation. Our results clearly demonstrate that sTLT1 is clinically related to the risk factors of CAD. We also showed that binding of sTLT1 with macrophage membrane receptor, FcɣR1 initiates inflammatory signals in macrophages suggesting its critical role in thrombus development and atherosclerosis.

Intradermal challenge with interleukin-8 causes tissue oedema and neutrophil accumulation in atopic and non-atopic human subjects

1996 ◽  
Vol 26 (12) ◽  
pp. 1371-1379 ◽  
Author(s):  
J. Douglass ◽  
D. Dhami ◽  
M. Bulpitt ◽  
I. J. Lindley ◽  
J. Shute ◽  
...  
Keyword(s):  
Human Subjects ◽  
Interleukin 8 ◽  
Neutrophil Accumulation ◽  
Tissue Oedema

Research Recommendations for Applying Vitamin A-Labelled Isotope Dilution Techniques to Improve Human Vitamin A Nutrition

2014 ◽  
Vol 84 (Supplement 1) ◽  
pp. 52-59 ◽  
Author(s):  
Sherry A. Tanumihardjo ◽  
Anura V. Kurpad ◽  
Janet R. Hunt
Keyword(s):  
Public Health ◽  
Vitamin A ◽  
Vitamin A Deficiency ◽  
Human Subjects ◽  
The Body ◽  
Pool Size ◽  
Serum Retinol ◽  
Vitamin A Status ◽  
Status Assessment ◽  
Total Body

The current use of serum retinol concentrations as a measurement of subclinical vitamin A deficiency is unsatisfactory for many reasons. The best technique available for vitamin A status assessment in humans is the measurement of total body pool size. Pool size is measured by the administration of retinol labelled with stable isotopes of carbon or hydrogen that are safe for human subjects, with subsequent measurement of the dilution of the labelled retinol within the body pool. However, the isotope techniques are time-consuming, technically challenging, and relatively expensive. There is also a need to assess different types of tracers and doses, and to establish clear guidelines for the use and interpretation of this method in different populations. Field-friendly improvements are desirable to encourage the application of this technique in developing countries where the need is greatest for monitoring the risk of vitamin A deficiency, the effectiveness of public health interventions, and the potential of hypervitaminosis due to combined supplement and fortification programs. These techniques should be applied to validate other less technical methods of assessing vitamin A deficiency. Another area of public health relevance for this technique is to understand the bioconversion of β-carotene to vitamin A, and its relation to existing vitamin A status, for future dietary diversification programs.

Delay Discounting in Impulsive Behavior

2019 ◽  
Vol 24 (4) ◽  
pp. 312-321 ◽  
Author(s):  
Diana Moreira ◽  
Fernando Barbosa
Keyword(s):  
Delay Discounting ◽  
Human Subjects ◽  
Empirical Studies ◽  
Cochrane Collaboration ◽  
Initial Assessment ◽  
Impulsive Behavior ◽  
Manual Search ◽  
Study Results ◽  
Depth Analysis ◽  
The Future

Abstract. Delay discounting (DD) is the process of devaluing results that happen in the future. With this review, we intend to identify specificities in the processes of DD in impulsive behavior. Studies were retrieved from multiple literature databases, through rigorous criteria (we included systematic reviews and empirical studies with adult human subjects), following the procedures of the Cochrane Collaboration initiative. Of the 174 documents obtained, 19 were considered eligible for inclusion and were retained for in-depth analysis. In addition, 13 studies from the manual search were included. Thus, a total of 32 studies were selected for review. The objectives/hypotheses, results, and the main conclusion(s) were extracted from each study. Results show that people with pronounced traits of impulsivity discount rewards more markedly, that is, they prefer immediate rewards, though of less value, or postponed losses, even though they worsen in the future. Taken together, the existing data suggest the importance of inserting DD as a tool for initial assessment in conjunction with measures of addiction and stress level, as well as the consideration of new therapies.

Minimizing Carry-Over Effects After Treatment Failure and Maximizing Therapeutic Outcome

2014 ◽  
Vol 222 (3) ◽  
pp. 171-178 ◽  
Author(s):  
Mareile Hofmann ◽  
Nathalie Wrobel ◽  
Simon Kessner ◽  
Ulrike Bingel
Keyword(s):  
Treatment Failure ◽  
Human Subjects ◽  
Subsequent Treatment ◽  
Clinical Samples ◽  
Administration Route ◽  
Healthy Human ◽  
Negative Experiences ◽  
Analgesic Treatment ◽  
Balanced Design ◽  
Carry Over

According to experimental and clinical evidence, the experiences of previous treatments are carried over to different therapeutic approaches and impair the outcome of subsequent treatments. In this behavioral pilot study we used a change in administration route to investigate whether the effect of prior treatment experience on a subsequent treatment depends on the similarity of both treatments. We experimentally induced positive or negative experiences with a topical analgesic treatment in two groups of healthy human subjects. Subsequently, we compared responses to a second, unrelated and systemic analgesic treatment between both the positive and negative group. We found that there was no difference in the analgesic response to the second treatment between the two groups. Our data indicate that a change in administration route might reduce the influence of treatment history and therefore be a way to reduce negative carry-over effects after treatment failure. Future studies will have to validate these findings in a fully balanced design including larger, clinical samples.

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