scholarly journals Understanding the Metabolic Fate and Bioactivity of Dietary Anthocyanins

Proceedings ◽  
2020 ◽  
Vol 36 (1) ◽  
pp. 64
Author(s):  
Netzel ◽  
Wright ◽  
Sultanbawa ◽  
Netzel
Keyword(s):  
Human Subjects ◽  
Experimental Studies ◽  
Grape Juice ◽  
Grape Pomace ◽  
Metabolic Fate ◽  
Healthy Human ◽  
Potential Health ◽  
Beneficial Effects ◽  
Red Grape

Anthocyanins are plant pigments and dietary phytochemicals, and may have potential health benefits. There is emerging evidence from epidemiological and experimental studies that suggests a higher consumption of anthocyanin-rich foods is associated with a reduced risk of heart disease and diabetes. To better understand the observed beneficial effects of anthocyanins and their underlying mode of action, bioavailability and metabolic fate needs to be studied in more detail. Healthy human subjects (10–12 in two different studies) received red grape pomace (700 mg anthocyanins/mainly as malvidin-3-glucoside) or Queen Garnet plum (QGP) juice (426 mg anthocyanins/mainly as cyanidin-3-glucoside) and an anthocyanin-free control in a randomised crossover design. Malvidin- and cyanidin-glycosides are common in many fruits and beverages such as red grapes, red grape juice, red wine, blueberry, cherry, elderberry, (Japanese) plum and are therefore of dietary significance. 24-hr urine samples were collected and analysed for anthocyanins and metabolites by UHPLC-PDA-MS. Methylated, glucuronidated and sulphated anthocyanins could be identified as characteristic metabolites in both studies. Furthermore, the increase in urinary hippuric acid (microbial/hepatic metabolite) was considerable in both studies after the consumption of red grape pomace or QGP juice (1.8–4.5-fold vs. control; p < 0.05). These findings suggest that structurally different anthocyanins are exposed to a similar extensive metabolism by enzymes and the gut microbiome and that the generated metabolites are most likely the bioactive compounds in vivo. Therefore, more human studies are warranted to investigate the metabolic fate of dietary anthocyanins and the bioactivity of generated metabolites.

scholarly journals GH signaling in skeletal muscle and adipose tissue in healthy human subjects: impact of gender and age

2014 ◽  
Vol 171 (5) ◽  
pp. 623-631 ◽  
Author(s):  
Poul F Vestergaard ◽  
Mikkel H Vendelbo ◽  
Steen B Pedersen ◽  
Anders Juul ◽  
Steffen Ringgard ◽  
...  
Keyword(s):  
Human Subjects ◽  
Experimental Studies ◽  
Young Group ◽  
Healthy Human ◽  
Age And Gender ◽  
Healthy Human Subjects ◽  
Constitutive Overexpression ◽  
And Gender ◽  
The Impact

ObjectiveThe mechanisms underlying the impact of age and gender on the GH–IGF1 axis remain unclear. We tested the hypothesis that age and gender have impacts on GH signaling in human subjects in vivo.DesignA total of 20 healthy non-obese adults (‘young group’ <30 years (5F/5M) and ‘old group’ >60 years (5F/5M)) were studied after: i) an i.v. GH bolus (0.5 mg) and ii) saline.MethodsMuscle and fat biopsies were obtained after 30 and 120 min. Total and phosphorylated STAT5B proteins, gene expression of IGF1, SOCS1, SOCS2, SOCS3 and CISH, body composition, VO2max, and muscle strength were measured.ResultsIn the GH-unstimulated state, women displayed significantly elevated levels of CISH mRNA in muscle (P=0.002) and fat (P=0.05) and reduced levels of IGF1 mRNA in fat. Phosphorylated STAT5B (pSTAT5b) was maximally increased in all subjects 30 min after GH exposure and more pronounced in women when compared with men (P=0.01). IGF1, SOCS1, SOCS2, SOCS3, and CISH mRNA expression increased significantly in muscle after 120 min in all subjects with no impact of age and gender. GH-induced pSTAT5b correlated inversely with lean body mass (LBM; r=−0.56, P=0.01) and positively with the CISH mRNA response (r=0.533, P=0.05).Conclusioni) GH signaling in muscle and fat after a single GH bolus in healthy human subjects is age independent, ii) we hypothesize that constitutive overexpression of CISH may contribute to the relative GH resistance in women, and iii) experimental studies on the impact of sex steroid administration and physical training on GH signaling in human subjects in vivo are required.

scholarly journals Determination of receptor occupancy in the presence of mass dose: [11C]GSK189254 PET imaging of histamine H3 receptor occupancy by PF-03654746

2016 ◽  
Vol 37 (3) ◽  
pp. 1095-1107 ◽  
Author(s):  
Jean-Dominique Gallezot ◽  
Beata Planeta ◽  
Nabeel Nabulsi ◽  
Donna Palumbo ◽  
Xiaoxi Li ◽  
...  
Keyword(s):  
Binding Sites ◽  
Human Subjects ◽  
Receptor Occupancy ◽  
Healthy Human ◽  
Positron Emission ◽  
Relationship Of ◽  
The Relationship ◽  
Pet Scans

Measurements of drug occupancies using positron emission tomography (PET) can be biased if the radioligand concentration exceeds “tracer” levels. Negative bias would also arise in successive PET scans if clearance of the radioligand is slow, resulting in a carryover effect. We developed a method to (1) estimate the in vivo dissociation constant Kd of a radioligand from PET studies displaying a non-tracer carryover (NTCO) effect and (2) correct the NTCO bias in occupancy studies taking into account the plasma concentration of the radioligand and its in vivo Kd. This method was applied in a study of healthy human subjects with the histamine H3 receptor radioligand [11C]GSK189254 to measure the PK-occupancy relationship of the H3 antagonist PF-03654746. From three test/retest studies, [11C]GSK189254 Kd was estimated to be 9.5 ± 5.9 pM. Oral administration of 0.1 to 4 mg of PF-03654746 resulted in occupancy estimates of 71%–97% and 30%–93% at 3 and 24 h post-drug, respectively. NTCO correction adjusted the occupancy estimates by 0%–15%. Analysis of the relationship between corrected occupancies and PF-03654746 plasma levels indicated that PF-03654746 can fully occupy H3 binding sites ( ROmax = 100%), and its IC50 was estimated to be 0.144 ± 0.010 ng/mL. The uncorrected IC50 was 26% higher.

scholarly journals PHYSICOCHEMICAL COMPOSITION AND SENSORY ANALYSIS OF WHOLE JUICE EXTRACTED FROM GRAPES IRRADIATED WITH ULTRAVIOLET C

2017 ◽  
Vol 39 (3) ◽  
Author(s):  
TAÍSA CERATTI TREPTOW ◽  
FERNANDA WOUTERS FRANCO ◽  
LAURA GIZELE MASCARIN ◽  
LUISA HELENA RYCHECKI HECKTHEUER ◽  
CLÁUDIA KAEHLER SAUTTER
Keyword(s):  
Phenolic Compounds ◽  
Ultraviolet Irradiation ◽  
Storage Period ◽  
Grape Juice ◽  
Cabernet Sauvignon ◽  
Physicochemical Composition ◽  
Beneficial Effects ◽  
Red Grape Juice ◽  
Red Grape ◽  
Uv C

ABSTRACT Grape juice has been widely studied due to the presence of phenolic compounds and its beneficial effects on human health. Ultraviolet irradiation C (UV-C) can increase the content of phenolic compounds and anthocyanins and contribute to sensory acceptability. The aim of this study was to evaluate the effect of different doses of ultraviolet irradiation C (UV-C) on ‘Trebbiano’, ‘Niagara Branca’, ‘Isabel’ and ‘Cabernet Sauvignon’ grapes, as well as effect of the storage period. Juices were elaborated and evaluated for physicochemical analyses, and for the sensorial analysis in irradiated samples. In ‘Niagara Branca’ and ‘Trebbiano’ cultivars, storage and irradiation promoted few physicochemical alterations, and sensorially, irradiation reduced the intensity of flavor and color attributes. In juices from ‘Isabel’ and ‘Cabernet Sauvignon’ cultivars, the storage period led to the concentration of sugars and irradiation influenced physicochemical parameters and increased the intensity of aroma attribute at dose of 2 kJ m-2. Thus, UV-C irradiation contributes little for the improvement of white grape juices; however, it favors some sensory attributes in red grape juice, requiring further studies to elucidate the influence of UV-C irradiation on the phenolic and volatile composition of grape juice.

scholarly journals Morphometric changes in the human pulmonary acinus during inflation

2012 ◽  
Vol 112 (6) ◽  
pp. 937-943 ◽  
Author(s):  
A. J. Hajari ◽  
D. A. Yablonskiy ◽  
A. L. Sukstanskii ◽  
J. D. Quirk ◽  
M. S. Conradi ◽  
...  
Keyword(s):  
Human Subjects ◽  
Alveolar Volume ◽  
Healthy Human ◽  
Lung Inflation ◽  
Pulmonary Acinus ◽  
Anisotropic Expansion ◽  
Healthy Human Subjects ◽  
Alveolar Duct ◽  
Gas Volume

Despite decades of research into the mechanisms of lung inflation and deflation, there is little consensus about whether lung inflation occurs due to the recruitment of new alveoli or by changes in the size and/or shape of alveoli and alveolar ducts. In this study we use in vivo 3He lung morphometry via MRI to measure the average alveolar depth and alveolar duct radius at three levels of inspiration in five healthy human subjects and calculate the average alveolar volume, surface area, and the total number of alveoli at each level of inflation. Our results indicate that during a 143 ± 18% increase in lung gas volume, the average alveolar depth decreases 21 ±5%, the average alveolar duct radius increases 7 ± 3%, and the total number of alveoli increases by 96 ± 9% (results are means ± SD between subjects; P < 0.001, P < 0.01, and P < 0.00001, respectively, via paired t-tests). Thus our results indicate that in healthy human subjects the lung inflates primarily by alveolar recruitment and, to a lesser extent, by anisotropic expansion of alveolar ducts.

scholarly journals The in vivo use of the stable isotope-labelled biomarkers lactose-[15N]ureide and [2H4]tyrosine to assess the effects of pro- and prebiotics on the intestinal flora of healthy human volunteers

2004 ◽  
Vol 92 (3) ◽  
pp. 439-446 ◽  
Author(s):  
V. De Preter ◽  
K. Geboes ◽  
K. Verbrugghe ◽  
L. De Vuyst ◽  
T. Vanhoutte ◽  
...  
Keyword(s):  
Stable Isotope ◽  
Lactobacillus Casei ◽  
Functional Foods ◽  
Direct Evidence ◽  
Intestinal Flora ◽  
Healthy Human ◽  
Beneficial Effects ◽  
Potential Biomarker ◽  
Human Volunteers

Amongst the various claimed beneficial effects of pro- and prebiotics for the human host, it has been hypothesised that functional foods are able to suppress the generation and accumulation of toxic fermentation metabolites (NH3, p-cresol). Direct evidence supporting this hypothesis is lacking mainly because of the unavailability of reliable biomarkers. Preliminary data indicate that lactose-[15N]ureide and [2H4]tyrosine may be potential biomarker candidates. The aim of the present study was to evaluate the effect of pro- and prebiotics on the colonic fate of these biomarkers in a randomised, placebo-controlled, cross-over study with nineteen healthy volunteers. At the start of the study and at the end of each 2-week study period, during which they were administered either a probiotic (n 10; 6·5×109Lactobacillus casei Shirota cells twice daily) or a prebiotic (n 9; lactulose 10 g twice daily), the volunteers consumed a test meal containing the two biomarkers. Urine was collected during 48 h. Results were expressed as percentage of the administered dose. As compared with the placebo, the decrease in the percentage dose of p-[2H4]cresol in the 24–48 h urine fraction was significantly higher after probiotic intake (P=0·042). Similar changes were observed for the 15N tracer (P=0·016). After prebiotic intake, a significantly higher decrease in the percentage dose of p-[2H4]cresol (P=0·005) and 15N tracer (P=0·029) was found in the 0–24 h urine collection. The present results demonstrate that suppression of the generation and accumulation of potentially toxic fermentation metabolites by pro- and prebiotics can reliably be monitored in vivo by the use of stable isotope-labelled biomarkers.

scholarly journals Stable isotope-labelled vitamin C as a probe for vitamin C absorption by human subjects

2004 ◽  
Vol 91 (5) ◽  
pp. 699-705 ◽  
Author(s):  
Christopher J. Bates ◽  
Kerry S. Jones ◽  
Leslie J. C. Bluck
Keyword(s):  
Stable Isotope ◽  
Vitamin C ◽  
Peak Plasma ◽  
Human Subjects ◽  
Total Concentration ◽  
Grape Juice ◽  
Isotope Enrichment ◽  
Factors Affecting ◽  
Plasma Ascorbate ◽  
Red Grape

Factors affecting absorption of physiological doses of vitamin C in man have not been widely studied, partly because few suitable tools exist to distinguish recently absorbed vitamin C from endogenous vitamin. Stable isotope-labelled vitamin C provides such a tool. Fifteen healthy non-smoking subjects aged 26–59 years were studied. Each received 30 mg L-[1-13C]ascorbic acid orally on two occasions, 3–4 weeks apart. The ascorbate was given alone or with Fe (100 mg as ferrous fumarate) or with red grape juice, which is rich in polyphenols. Blood was collected at frequent intervals for 1 h, and then each hour for a further 3 h. Total concentration of vitamin C was measured fluorometrically and its 13C-isotope enrichment was measured by GC–MS after conversion to volatile trimethylsilyl esters. Peak plasma enrichment occurred within 25–50 min. No kinetic variables were significantly altered by the iron fumarate supplement. Grape juice attenuated vitamin C absorption, reaching significance at the 20 min time point. There were weak correlations between isotope enrichment and body weight or endogenous ascorbate concentration. The increment in total plasma ascorbate was smaller if calculated from isotope enrichment than from vitamin C concentration increase. The dilution pool was much larger than the plasma ascorbate pool. Further studies are needed to resolve these paradoxes. Stable isotope-labelled ascorbate is potentially useful for measurement of vitamin C absorption by human subjects.

scholarly journals The effect of marine oil-derived n-3 fatty acids on transepithelial calcium transport in Caco-2 cell models of healthy and inflamed intestines

2007 ◽  
Vol 97 (2) ◽  
pp. 281-288 ◽  
Author(s):  
Jennifer Gilman ◽  
Kevin D. Cashman
Keyword(s):  
Fatty Acids ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Human Subjects ◽  
Healthy Human ◽  
Marine Oil ◽  
Ca Transport ◽  
Tnf Α

Marine oil-derived n-3 fatty acids have been shown to stimulate intestinal Ca absorption in animal studies, but the effects of such fatty acids on Ca absorption in human subjects are relatively unknown. In particular, n-3 fatty acids may be of therapeutic value for some Crohn's disease patients who experience Ca malabsorption. Therefore, the aim of the present study was to investigate the effect of 20 : 5n-3 and 22 : 6n-3 on transepithelial Ca transport across monolayers of healthy Caco-2 cells as well as of TNF-α-treated Caco-2 cells (an in vitro model of Crohn's disease). Caco-2 cells were seeded onto permeable filter supports and allowed to differentiate into monolayers, which were treated with 80 μm-20 : 5n-3, 80 μm-22 : 6n-3, or 40 μm-20 : 5n-3+40 μm-22 : 6n-3 for 6 or 8 d, with or without co-treatment with TNF-α (10 ng/ml) (n 11–15 monolayers per treatment). On day 16, transepithelial and transcellular transport of 45Ca and fluorescein transport (a marker of paracellular diffusion) were measured. Treatment of healthy and inflamed Caco-2 cells with 20 : 5n-3, 22 : 6n-3 and both fatty acids combined for 8 d significantly (P < 0·005–0·01) increased total transepithelial Ca transport compared with that in control, effects which were mediated by an enhanced rate of transcellular Ca transport. The effects of n-3 fatty acids on Ca absorption after 6 d were less clear-cut. In conclusion, the present in vitro findings highlight the need to investigate the effect of marine oil-based n-3 fatty acids on Ca absorption in vivo in studies of healthy human subjects as well as of Crohn's disease patients.

scholarly journals Safety and Pharmacokinetics of Intranasally Administered Heparin

2021 ◽  
Author(s):  
Hannah M. Harris ◽  
Katherine L. Boyet ◽  
Hao Liu ◽  
Rohini Dwivedi ◽  
Nicole M. Ashpole ◽  
...  
Keyword(s):  
Platelet Count ◽  
Nasal Cavity ◽  
In Vivo Imaging ◽  
Human Subjects ◽  
International Normalized Ratio ◽  
Sulfated Polysaccharides ◽  
Two Phase ◽  
Healthy Human ◽  
Serious Adverse Events

Purpose Intranasally administered unfractionated heparin (UFH) and other sulfated polysaccharides are potential prophylactics for COVID-19. The purpose of this research was to measure the safety and pharmacokinetics of clearance of intranasally administered UFH solution from the nasal cavity. Methods Double-blinded daily intranasal dosing in C57Bl6 mice with four doses (60 ng to 60 ug) of UFH was carried out for fourteen consecutive days, with both blood coagulation measurements and subject adverse event monitoring. The pharmacokinetics of fluorescent-labeled UFH clearance from the nasal cavity were measured in mice by in vivo imaging. Intranasal UFH at 2000 U/day solution with nasal spray device was tested for safety in a small number of healthy human subjects. Results UFH showed no evidence of toxicity in mice at any dose measured. No significant changes were observed in activated partial thromboplastin time (aPTT), platelet count, or frequency of minor irritant events over vehicle-only control. Human subjects showed no significant changes in aPTT time, international normalized ratio (INR), or platelet count over baseline measurements. No serious adverse events were observed. In vivo imaging in a mouse model showed a two-phase clearance of UFH from the nasal cavity. After 12 hours, 2.1% of the initial administered UFH remained in the nasal cavity, decaying to background levels after 24 hours. Conclusions UFH showed no toxic effects for extended daily intranasal dosing in mice as well as humans. The clearance kinetics of intranasal heparin solution from the nasal cavity indicates potentially protective levels for up to 12 hours after dosing.

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