Single Oral Dose Pharmacokinetics of Decursin and Decursinol Angelate in Healthy Adult Men and Women

The ethanol extract of Angelica gigas Nakai (AGN) root has promising anti-cancer and other bioactivities in rodent models. It is currently believed that the pyranocoumarin isomers decursin (D) and decursinol angelate (DA) contribute to these activities. We and others have documented that D and DA were rapidly converted to decursinol (DOH) in rodents. However, our in vitro metabolism studies suggested that D and DA might be metabolized differently in humans. To test this hypothesis and address a key question for human translatability of animal model studies of D and DA or AGN extract, we conducted a single oral dose human pharmacokinetic study of D and DA delivered through an AGN-based dietary supplement Cogni.Q (purchased from Quality of Life Labs, Purchase, NY) in twenty healthy subjects, i.e., 10 men and 10 women, each consuming 119 mg D and 77 mg DA from 4 vegicaps. Analyses of plasma samples using UHPLC-MS/MS showed mean time to peak concentration (T_max) of 2.1, 2.4 and 3.3 h and mean peak concentration (C_max) of 5.3, 48.1 and 2,480 nmol/L for D, DA and DOH, respectively. The terminal elimination half-life (t_1/2) for D and DA was similar (17.4 and 19.3 h) and each was much longer than that of DOH (7.4 h). The mean area under the curve (AUC_0-48h) for D, DA and DOH was estimated as 37, 335 and 27,579 h∙nmol/L, respectively. Gender-wise, men absorbed the parent compounds faster and took shorter time to reach DOH peak concentration. The human data supported an extensive conversion of D and DA to DOH, even though they metabolized DA slightly slower than rodents. Therefore, the data generated in rodent models concerning anti-cancer efficacy, safety, tissue distribution and pharmacodynamic biomarkers will likely be relevant for human translation.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02114957","term_id":"NCT02114957"}}NCT02114957     

Urinary Excretion of Silicon in Men,Non-pregnant Women,and Pregnant Women: a Cross-sectional Study

Biological Trace Element Research - Silicon is a trace element found mainly in plant-based food and proposed to be beneficial for bone health. Urinary excretion of Si has been shown to be a...     

Circadian Variability of Cystatin C,Creatinine, and Glomerular Filtration Rate (GFR) in Healthy Men during Normal Sleep and after an Acute Shift of Sleep

The estimation of the glomerular filtration rate (GFR) is essential for the evaluation of patients with kidney disease and for the treatment of patients with medications that are eliminated by the kidneys. Plasma cystatin C has been shown in several studies to be superior to plasma creatinine for the estimation of GFR. However, there is limited information on the circadian variation of cystatin C and estimated GFR using cystatin C (eGFR_CystC) or “The Modification of Diet in Renal Disease Study” (MDRD) (eGFR_MDRD) equations. We studied the circadian variation of cystatin C and creatinine during night‐ and day‐sleep conditions in seven healthy volunteers. Serum samples were collected every hour (48 samples per individual) to evaluate the effect of different sampling times on the test results. The median intra‐individual coefficients of variations for the studied markers were 4.2% for creatinine, 4.7% for eGFR_MDRD, 5.5% for cystatin C, and 7.7% for eGFR_CystC. Neither cystatin C nor creatinine differed significantly between the night‐ and day‐sleep conditions. Cystatin C differed significantly with time of day (p=.0003), but this was not the case for creatinine (p=.11). The circadian variation of cystatin C was minor. Small but significant increases in creatinine values and a decrease of eGFR_MDRD were observed after food intake. Thus, cystatin C and creatinine sampling does not have to be restricted to specific times of the day.     

Comparison of Various Anthropometric and Body Fat Indices in Identifying Cardiometabolic Disturbances in Chinese Men and Women

Background

Although many adiposity indices may be used to predict obesity-related health risks, uncertainty remains over which of them performs best.

Objective

This study compared the predictive capability of direct and indirect adiposity measures in identifying people at higher risk of metabolic abnormalities.

Methods

This population-based cross-sectional study recruited 2780 women and 1160 men. Body weight and height, waist circumference (WC), and hip circumference (HC) were measured and body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) were calculated. Body fat (and percentage of fat) over the whole body and the trunk were determined by bioelectrical impedance analysis (BIA). Blood pressure, fasting lipid profiles, and glucose and urine acid levels were assessed.

Results

In women, the ROC and the multivariate logistic regression analyses both showed that WHtR consistently had the best performance in identifying hypertension, dyslipidemia, hyperuricemia, diabetes/IFG, and metabolic syndrome (MetS). In men, the ROC analysis showed that WHtR was the best predictor of hypertension, WHtR and WC were equally good predictors of dyslipidemia and MetS, and WHtR was the second-best predictor of hyperuricemia and diabetes/IFG. The multivariate logistic regression also found WHtR to be superior in discriminating between MetS, diabetes/IFG, and dyslipidemia while BMI performed better in predicting hypertension and hyperuricemia in men. The BIA-derived indices were the second-worst predictors for all of the endpoints, and HC was the worst.

Conclusion

WHtR was the best predictor of various metabolic abnormalities. BMI may be used as an alternative measure of obesity for identifying hypertension in both sexes.     

Comparison of Trace Elements in the Scalp Hair of Malignant and Benign Breast Lesions Versus Healthy Women

Trace elements including Al, Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, Pb, Sb, Sr, and Zn were analyzed in the scalp hair samples of women with malignant breast lesions, women with benign breast lesions, and healthy donors using atomic absorption spectrophotometric method. In the scalp hair of malignant-tumor patients, the highest average concentration was shown by Ca (1,187 μg/g), followed by Na (655 μg/g), Mg (478 μg/g), Zn (391 μg/g), Sr (152 μg/g), Fe (114 μg/g), and K (89.8), while in the case of benign-tumor patients, the average estimated element levels were 1,522, 1,093, 572, 457, 217, 80.4, and 74.7 μg/g, respectively. Most of the elements exhibited non-normal distribution evidenced by large spread, standard error, and skewness values. Mean concentrations of Ca (634 μg/g), Zn (206 μg/g), Mg (162 μg/g), Fe (129 μg/g), and Na (82.1 μg/g) were noteworthy in the scalp hair of healthy women. Average levels of Na, Sr, K, Cd, Co, Pb, Mg, Ca, Zn, Ni, Sb, and Mn were revealed to be significantly higher in the hair of malignant and benign patients compared to the healthy women; however, Fe, Cu, Al, and Cr were not significantly different in the scalp hair of the three groups. The quartile distributions of Ca, Cd, Co, Cr, K, Mg, Mn, Na, Ni, Pb, Sb, and Sr revealed maximum spread in the scalp hair of malignant and benign groups; nevertheless, Al, Cu, Fe, and Zn exhibited almost comparable quartile levels in the three groups. Strong correlation coefficients were found between Fe and Cd, Al and Na, Mn and Sr, Co and Cr, Cd and Cr, Pb and K, Pb and Mn, Cu and Na, and Al and Fe in the scalp hair of malignant-tumor patients, while Fe and K, Cd and Co, Na and Co, and Cr and Pb showed strong correlations in the scalp hair of benign-tumor patients, both of which were significantly different compared with the healthy subjects. Multivariate cluster analysis also revealed divergent clustering of the elements in the scalp hair of malignant and benign patients in comparison with the healthy women.     

The Elusive Embryo: How Men and Women Approach New Reproductive Technologies; Ideologies and Technologies of Motherhood: Race, Class, Sexuality, Nationalism

The Elusive Embryo: How Men and Women Approach New Reproductive Technologies. Gay Becker. Berkeley: University of California Press, 2000.x. 320 pp.
Ideologies and Technologies of Motherhood: Race, Class, Sexuality, Nationalism. Heléna Ragoné and France Winddance Twine. eds. New York: Routledge, 2000. xvii. 330 pp.     

Determinants of Free-Living Energy Expenditure in Normal Weight and Obese Women Measured by Doubly Labeled Water

Total free-living energy expenditure (TEE) was measured in 9 normal weight controls and 5 obese women using the doubly labeled water (DLW) method. Resting energy expenditure (REE) and the thermic effect of food (TEF) were measured by indirect calorimetry and the energy cost of physical activity (PA) calculated by deduction, in order to quantify the components and identify determinants of free-living TEE. Although REE was quantitatively the major component of TEE in both groups, PA best explained the variability, contributing 76% to the variance in free-living TEE. The obese women had elevated values for TEE (12397+/-2565 vs. 8339+/-1787 kJ/d, mean+/-SD; p<0.00S), compared with the control women. PA (5071+/-2385 vs. 2552+/-1452; p<0.0S) and REE (6393+/-678 vs. 5084+/-259; p<0.000S) were also raised in the obese, whereas TEF was not significantly different between the groups, accounting for 7.6% of energy expenditure for the obese and 8% for the control subjects. Body weight was the single best determinant of mean daily free-living TEE across both groups. We conclude that PA and body weight are the main determinants of free-living TEE .     

Soil Water Extraction, Measured by Computer-Assisted Tomography, in Seedling Lupinus angustifolius cv. Yandee when Healthy and Infected with Phytophthora cinnamomi

The water-mould fungus Phytophthora cinnamomi Rands causes drought-likesymptoms on many hosts, and yet the mechanisms by which infectionleads to wilting are not fully understood. This is the firststudy to describe in detail changes in soil water around theroot with infection. Computer-assisted tomography (CAT) wasused with Lupinus angustifolius L. cv. Yandee to examine drawdowns(removal of soil water) around a central root infected by P.cinnamomi in a white sand. No growth differences in roots or shoots were found betweenhealthy and diseased plants during the 8 d of the experiment.However,drawdowns failed at high levels of inoculum (8–16 /Pc-infectedmillet seeds/plant) by 8 d. Water contents in pots with uninfectedplants were in the range 0·09–0·12 cm³ watercm^–3 soil in the centre of the pot, while water contentsin pots with infected plants at 16 millet seeds applied werein the range of 0·16–0·19 cm³ water cm^–3soil in the centre of the pot. A higher transpirational demand produced lower soil water contentsnear the root but this effect was confounded with infection:disease was more pronounced with higher transpirational demand,and disease led to an increase in water content. Key words: Root disease, Phytophthora cinnamomi, water uptake, soil-root interface, computer-assisted tomography     

Iron,Hepcidin and Inflammatory Status of Young Healthy Overweight and Obese Women in Australia

Background and Aims

Evidence suggests obesity-related inflammation alters iron metabolism potentially increasing the risk of iron deficiency. This cross-sectional study aimed to investigate iron, hepcidin and inflammatory status in young, healthy overweight and obese women.

Methods

114 young (18–25 years), healthy comorbidity-free women with a body mass index (BMI) ≥27.5 kg/m² were recruited. Biochemical data were analysed using mean ± standard deviation or median (interquartile range) and multivariate modelling. Biochemical markers were also stratified according to varying degrees of overweight and obesity.

Results

Anaemia (haemoglobin <120 g/l) and iron deficiency (serum ferritin <15.0 µg/l) were prevalent in 10% and 17% of participants respectively. Mean/median soluble transferrin receptor was 1.61±0.44 mg/l; hepcidin 6.40 (7.85) ng/ml and C-reactive protein (CRP) 3.58 (5.81) mg/l. Multivariate modelling showed that BMI was a significant predictor of serum iron (coefficient = -0.379; standard error = 0.139; p = 0.008), transferrin saturation (coefficient = -0.588; standard error = 0.222; p = 0.009) and CRP (coefficient = 0.127; standard error = 0.024; p<0.001). Stratification of participants according to BMI showed those with ≥35.0 kg/m² had significantly higher CRP (p<0.001) than those in lower BMI categories.

Conclusions

Increasing obesity was associated with minor disturbances in iron metabolism. However, overall outcomes indicated simple iron deficiency (hypoferritinaemia) was the primary iron-related abnormality with no apparent contribution of inflammation or hepcidin, even in those with BMI >35.0 kg/m². This indicates that obesity alone may not be sufficient to induce clinically significant disturbances to iron metabolism as previously described. This may be attributed to the lack of comorbidity in this cohort.     

Olfactory Discrimination and Transient Mood Change in Young Men and Women: Variation by Season,Mood State,and Time of Day

Odor performance varies by clinical state and gender, though little is known about its variation by season or time of day. Many odors, including lavender, induce transient mood changes. This study explored discrimination differences between various lavender oil blends and their effects on transient mood in the morning and evening in depressed and nondepressed adults. We also determined seasonal influences on these measures. A total of 169 subjects, 98 women and 71 men (mean age ± SD, 19.3 ± 1.6 y) participated, with different subjects studied at different times of the year. The Beck Depression Inventory (BDI) classified subjects as depressed (score ≥10; N = 57) or nondepressed (score <10; N = 112). In the discrimination test, subjects compared pairs of two different lavender oil blends or a control. Transient change in mood was assessed by the Profile of Mood States (POMS) after each trial of five lavender blends interspersed by three control odors. Tests were conducted in the morning (08:00–10:00 h) and evening (18:00–20:00 h). In all subjects, discrimination was significantly better for some odor pairs than for others, thus demonstrating test specificity. Discrimination was better overall in the fall than winter/spring and better in depressed than nondepressed subjects for specific odor pairs. No significant gender or time-of-day differences in discriminability were detected. There were, however, significant group differences in transient mood profiles. Current depressed state affected mood response, with lavender increasing anger in depressed subjects only. In addition, depressed subjects and men, whether or not depressed, exhibited diurnal mood variation, with better mood in the evening; the former group also showed more evening energy. All subjects were more confused in the morning than evening. Season also affected transient mood; winter/spring-tested subjects reported more vigor than fall-tested subjects. In addition, summer-tested subjects showed more tension in the morning, whereas fall-tested subjects showed the opposite pattern in the evening. In all subjects, lavender increased fatigue, tension, confusion, and total mood disturbance, and it decreased vigor. The study showed that both chronobiological (seasonal and time-of-day) and clinical factors modify discrimination and mood response to odors. Brief lavender odor presentation may serve as a nonphotic method for altering mood in young depressed and nondepressed adults particularly during the fall, a time of heightened discriminability.     

Circulating Insulin Concentrations,Smoking, and Alcohol Intake Are Important Independent Predictors of Leptin in Young Healthy Men

Objective : Leptin, an adipocyte-secreted hormone, has been shown to signal the status of energy stores to the brain, regulate energy homeostasis, and mediate the neuroendocrine response to food deprivation. Obesity is associated with increased leptin levels, and several hormones, including insulin and glucocorticoids, have been associated with leptin levels and expression in rodents. Although obesity has been strongly associated with increased leptin in humans, a significant percentage of leptin's variability remains unexplained. The role of endogenous hormones, demographic factors, or certain life-style factors in explaining the residual variability of leptin levels has not yet been clarified. We performed this cross-sectional study to document the relative importance of obesity, lifestyle factor, and endogenous hormones in determining serum leptin levels. Research Methods and Procedures : We measured serum concentrations of insulin, Cortisol, testosterone, growth hormone, and dehydroepiandrosterone sulfate; ascertained anthropometric, demographic, and lifestyle characteristics; and studied these variables in relationship to serum leptin concentrations in a sample of young healthy men. Results : Obesity and alcohol intake were independently and positively associated with circulating leptin concentrations. Additionally, cigarette smoking was negatively and independently associated with leptin concentrations. Finally, serum insulin concentration was an independent hormonal determinant of circulating leptin concentrations, whereas serum testosterone was negatively associated with leptin only by bivariate analysis. Discussion : We conclude that, in addition to obesity, cigarette smoking, alcohol intake, and serum insulin levels are associated with leptin levels in a population of healthy young men.     

Spatial and Temporal Variability in the Diet of Anadromous Arctic Charr, Salvelinus Alpinus, In Northern Labrador

Spatial and temporal variation in the diet of anadromous Arctic charr, Salvelinus alpinus, was determined from over 2500 prey-containing stomachs collected from three stock complex areas in northern Labrador. Based on the percent wet mass, sand lance, Ammodytes spp., capelin, Mallotus villosus, and sculpins, Triglops spp. and Myoxocephalus spp., were the most important components of the diet in the Voisey stock complex, with capelin, sand lance, and hyperiid amphipods, Parathemisto spp., dominating in the Nain region. In contrast, hyperiid amphipods and sculpins were the main prey items in the more northern Hebron–Saglek complex indicating that diet differs among stocks, and at times over limited spatial scales. The relative importance of prey varied with size of predator. Mean weight of charr has declined over time (p < 0.01), and for one stock complex, is highly correlated with the average quantity of capelin found in the stomachs (r = 0.66, p < 0.001). Dietary shifts observed in anadromous charr in some areas of northern Labrador could be associated, in part, with changes in the distribution of capelin in the northwest Atlantic Ocean, possibly as a result of anomalous ocean climate conditions.     

Mealtime,Temporal, and Daily Variability of the Human Urinary and Plasma Metabolomes in a Tightly Controlled Environment

While metabolomics has tremendous potential for diagnostic biomarker and therapeutic target discovery, its utility may be diminished by the variability that occurs due to environmental exposures including diet and the influences of the human circadian rhythm. For successful translation of metabolomics findings into the clinical setting, it is necessary to exhaustively define the sources of metabolome variation. To address these issues and to measure the variability of urinary and plasma metabolomes throughout the day, we have undertaken a comprehensive inpatient study in which we have performed non-targeted metabolomics analysis of blood and urine in 26 volunteers (13 healthy subjects with no known disease and 13 healthy subjects with autosomal dominant polycystic kidney disease not taking medication). These individuals were evaluated in a clinical research facility on two separate occasions, over three days, while on a standardized, weight-based diet. Subjects provided pre- and post-prandial blood and urine samples at the same time of day, and all samples were analyzed by “fast lane” LC-MS-based global metabolomics. The largest source of variability in blood and urine metabolomes was attributable to technical issues such as sample preparation and analysis, and less variability was due to biological variables, meals, and time of day. Higher metabolome variability was observed after the morning as compared to the evening meal, yet day-to-day variability was minimal and urine metabolome variability was greater than that of blood. Thus we suggest that blood and urine are suitable biofluids for metabolomics studies, though nontargeted mass spectrometry alone may not offer sufficient precision to reveal subtle changes in the metabolome. Additional targeted analyses may be needed to support the data from nontargeted mass spectrometric analyses. In light of these findings, future metabolomics studies should consider these sources of variability to allow for appropriate metabolomics testing and reliable clinical translation of metabolomics data.     

Patterns in Temporal Variability of Temperature,Oxygen and pH along an Environmental Gradient in a Coral Reef

Spatial and temporal environmental variability are important drivers of ecological processes at all scales. As new tools allow the in situ exploration of individual responses to fluctuations, ecologically meaningful ways of characterizing environmental variability at organism scales are needed. We investigated the fine-scale spatial heterogeneity of high-frequency temporal variability in temperature, dissolved oxygen concentration, and pH experienced by benthic organisms in a shallow coastal coral reef. We used a spatio-temporal sampling design, consisting of 21 short-term time-series located along a reef flat-to-reef slope transect, coupled to a long-term station monitoring water column changes. Spectral analyses revealed sharp gradients in variance decomposed by frequency, as well as differences between physically-driven and biologically-reactive parameters. These results highlight the importance of environmental variance at organismal scales and present a new sampling scheme for exploring this variability in situ.     

Effect of Corn Fiber on Fecal Flora,Properties of Feces, β-Glucuronidase,and Levels of Serum Lipid in Healthy Men

The effects of corn fiber intake (6 and 12 g/day for 10 days) on the fecal weight, moisture, neutral detergent fiber (NDF), pH, microflora and β-glucuronidase activity, and on the serum lipids were investigated in five healthy men. Fecal weight and NDF increased depending on the fiber dose, whereas fecal moisture decreased. No remarkable change in fecal microflora was observed. Fecal β-glucuronidase activities (per gram of wet feces and daily output) were dose-dependently decreased by corn fiber intake. The levels of serum lipids did not change. These results show that corn fiber intake yielded an increase of fecal weight and a reduction of fecal β-glucuronidase activity.     

Hypnotizability,Hypnosis and Prepulse Inhibition of the Startle Reflex in Healthy Women: An ERP Analysis

A working model of the neurophysiology of hypnosis suggests that highly hypnotizable individuals (HHs) have more effective frontal attentional systems implementing control, monitoring performance, and inhibiting unwanted stimuli from conscious awareness, than low hypnotizable individuals (LHs). Recent studies, using prepulse inhibition (PPI) of the auditory startle reflex (ASR), suggest that HHs, in the waking condition, may show reduced sensory gating although they may selectively attend and disattend different stimuli. Using a within subject design and a strict subject selection procedure, in waking and hypnosis conditions we tested whether HHs compared to LHs showed a significantly lower inhibition of the ASR and startle-related brain activity in both time and intracerebral source localization domains. HHs, as compared to LH participants, exhibited (a) longer latency of the eyeblink startle reflex, (b) reduced N100 responses to startle stimuli, and (c) higher PPI of eyeblink startle and of the P200 and P300 waves. Hypnosis yielded smaller N100 waves to startle stimuli and greater PPI of this component than in the waking condition. sLORETA analysis revealed that, for the N100 (107 msec) elicited during startle trials, HHs had a smaller activation in the left parietal lobe (BA2/40) than LHs. Auditory pulses of pulse-with prepulse trials in HHs yielded less activity of the P300 (280 msec) wave than LHs, in the cingulate and posterior cingulate gyrus (BA23/31). The present results, on the whole, are in the opposite direction to PPI findings on hypnotizability previously reported in the literature. These results provide support to the neuropsychophysiological model that HHs have more effective sensory integration and gating (or filtering) of irrelevant stimuli than LHs.