Simultaneous estimation of ZY-19489 and its active metabolite ZY-20486 in human plasma using LC–MS/MS, a novel antimalarial compound

Aim: ZY-19489 is a new antimalarial drug candidate and selective LC–MS/MS method was established for estimation of ZY-19489 and its metabolite in human plasma. Materials & methods: LLE was employed for extraction, mass spectrometric quantification performed using positive ionization mode and DCP-IMP was used as an internal standard. The chromatographic separation was achieved using mobile phase 5 mM ammonium formate in water and 0.1% v/v ammonia solution in methanol: acetonitrile (90: 10%, v/v) and column Agilent Zorbex Extended C18, 3.5 μm, 100 × 4.6 mm with a 6-min run time. Results: The calibration curve of ZY-19489 was linear over range 1–500 ng/ml and 2–200 ng/ml for metabolite. Assay was reproducible, selective and devoid of matrix effect. Conclusion: The validated assay was implemented for clinical sample analysis derived from healthy human subjects and parasitemia-induced subjects.

Effect of timing delay between visual and vestibular stimuli on heading perception.

Heading direction is perceived based on visual and inertial cues. The current study examined the effect of their relative timing on the ability of offset visual headings to influence inertial perception. Seven healthy human subjects experienced 2 s of translation along a heading of 0°, ±35°, ±70°, ±105°, or ±140°. These inertial headings were paired with 2 s duration visual headings that were presented at relative offsets of 0°, ±30°, ±60°, ±90°, or ±120. The visual stimuli were also presented at 17 temporal delays ranging from -500 ms (visual lead) to 2,000 ms (visual delay) relative to the inertial stimulus. After each stimulus, subjects reported the direction of the inertial stimulus using a dial. The bias of the inertial heading towards the visual heading was robust at ±250 ms when examined across subjects during this period: 8.0 ± 0.5° with a 30° offset, 12.2 ± 0.5° with a 60° offset, 11.7 ± 0.6° with a 90° offset, and 9.8 ± 0.7° with a 120° offset (mean bias towards visual ± SE). The mean bias was much diminished with temporal misalignments of ±500 ms, and there was no longer any visual influence on the inertial heading when the visual stimulus was delayed by 1,000 ms or more. Although the amount of bias varied between subjects the effect of delay was similar.

Influence of Sound on Empirical Brain Networks

We analyze the influence of an external sound source in a network of FitzHugh–Nagumo oscillators with empirical structural connectivity measured in healthy human subjects. We report synchronization patterns, induced by the frequency of the sound source. We show that the level of synchrony can be enhanced by choosing the frequency of the sound source and its amplitude as control parameters for synchronization patterns. We discuss a minimum model elucidating the modalities of the influence of music on the human brain.

Correction to: Changes in Circulating Stem and Progenitor Cell Numbers Following Acute Exercise in Healthy Human Subjects: a Systematic Review and Meta-Analysis

A Correction to this paper has been published: 10.1007/s12015-021-10161-7

Aging steepens the slope of power spectrum density of 30-minute continuous blood pressure recording in healthy human subjects

Background The increase of blood pressure (BP) variability (BPV) is recognized as an important additional cardiovascular risk factor in both normotensive subjects and hypertensive patients. Aging-induced atherosclerosis and autonomic dysfunction impair the baroreflex and, in turn, augment 24-hour BPV. In small and large animal experiments, impaired baroreflex steepens the slope of the power spectrum density (PSD) of continuous BP in the frequency range of 0.01 to 0.1 Hz. Although the repeated oscillometric BP recording over 24 hours or longer is a prerequisite to quantify BPV in humans, how the very short-term continuous BP recording reflects BPV remains unknown. This study aimed to evaluate the impact of aging on the very short-term (30-min) BPV in healthy human subjects by frequency analysis. Methods We recorded continuous BP tonometrically for 30 min in 56 healthy subjects aged between 28 and 85 years. Considering the frequency-dependence of the baroreflex dynamic function, we estimated the PSD of BP in the frequency range of 0.01 to 0.1 Hz, and compared the characteristics of PSD among four age groups (26–40, 41–55, 56–70 and 71–85 years). Results Aging did not significantly alter mean and standard deviation (SD) of BP among four age groups. PSD was nearly flat around 0.01 Hz and decreased gradually as the frequency increased. The slope of PSD between 0.01 and 0.1 Hz was steeper in older subjects (71 years or older) than in younger subjects (55 years or younger) (p < 0.05). Conclusions Aging steepened the slope of PSD of BP between 0.01 and 0.1 Hz. This phenomenon may partly be related to the deterioration of the baroreflex in older subjects. Our proposed method to evaluate very short-term continuous BP recordings may contribute to the stratification of BPV.

Acacia Gum Is Well Tolerated While Increasing Satiety and Lowering Peak Blood Glucose Response in Healthy Human Subjects

Acacia gum (AG) is a non-viscous soluble fiber that is easily incorporated into beverages and foods. To determine its physiological effects in healthy human subjects, we fed 0, 20, and 40 g of acacia gum in orange juice along with a bagel and cream cheese after a 12 h fast and compared satiety, glycemic response, gastrointestinal tolerance, and food intake among treatments. Subjects (n = 48) reported less hunger and greater fullness at 15 min (p = 0.019 and 0.003, respectively) and 240 min (p = 0.036 and 0.05, respectively) after breakfast with the 40 g fiber treatment. They also reported being more satisfied at 15 min (p = 0.011) and less hungry with the 40 g fiber treatment at 30 min (p = 0.012). Subjects reported more bloating, flatulence, and GI rumbling on the 40 g fiber treatment compared to control, although values for GI tolerance were all low with AG treatment. No significant differences were found in area under the curve (AUC) or change from baseline for blood glucose response, although actual blood glucose with 20 g fiber at 30 min was significantly less than control. Individuals varied greatly in their postprandial glucose response to all treatments. AG improves satiety response and may lower peak glucose response at certain timepoints, and it is well tolerated in healthy human subjects. AG can be added to beverages and foods in doses that can help meet fiber recommendations.