scholarly journals Integration Analysis of Pharmacokinetics and Metabolomics to Predict Metabolic Phenotype and Drug Exposure of Remdesivir

2022 ◽  
Vol 12 ◽  
Author(s):  
Ping Du ◽  
Guoyong Wang ◽  
Ting Hu ◽  
Han Li ◽  
Zhuoling An

Remdesivir has displayed pharmacological activity against SARS-CoV-2. However, no pharmacometabolomics (PM) or correlation analysis with pharmacokinetics (PK) was revealed. Rats were intravenously administered remdesivir, and a series of blood samples were collected before and after treatment. Comprehensive metabolomics profile and PK were investigated and quantitated simultaneously using our previous reliable HPLC-MS/MS method. Both longitudinal and transversal metabolic analyses were conducted, and the correlation between PM and PK parameters was evaluated using Pearson’s correlation analysis and the PLS model. Multivariate statistical analysis was employed for discovering candidate biomarkers which predicted drug exposure or toxicity of remdesivir. The prominent metabolic profile variation was observed between pre- and posttreatment, and significant changes were found in 65 metabolites. A total of 15 metabolites—12 carnitines, one N-acetyl-D-glucosamine, one allantoin, and one corticosterone—were significantly correlated with the concentration of Nuc (active metabolite of remdesivir). Adenosine, spermine, guanosine, sn-glycero-3-phosphocholine, and l-homoserine may be considered potential biomarkers for predicting drug exposure or toxicity. This study is the first attempt to apply PM and PK to study remdesivir response/toxicity, and the identified candidate biomarkers might be used to predict the AUC and Cmax, indicating capability of discriminating good or poor responders. Currently, this study originally offers considerable evidence to metabolite reprogramming of remdesivir and sheds light on precision therapy development in fighting COVID-19.

2017 ◽  
Vol 1 (21) ◽  
pp. 49-63
Author(s):  
Zdzisław Kaliniewicz ◽  
Piotr Markowski ◽  
Andrzej Anders ◽  
Paweł Tylek ◽  
Zbigniew Krzysiak ◽  
...  

The basic dimensions and the mass of common beech nuts and seeds from five nut batches, harvested from tree stands in northern Poland, were determined. Environmental conditions had a greater influence on seed plumpness than the age of tree stands. The results of measurements were analyzed statistically by analysis of variance, correlation analysis and linear regression analysis. Despite differences in their plumpness, nuts were characterized by nearly identical cross-sections which resembled an equilateral triangle. The thickness of nuts and seeds was highly correlated with their mass, and this information can facilitate seed husking and separation into mass categories. Before and after husking, seeds should be separated with the use of a mesh screen with longitudinal openings. Medium-sized (most numerous) seeds were separated into the following plumpness categories using a screen separator with ≠6 mm and ≠7 mm openings: 84% of moderately plump seeds, 3% of seeds with reduced plumpness, and 13% of plump seeds.


2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Ryan L. S. Sharpe ◽  
Mufti Mahmud ◽  
M. Shamim Kaiser ◽  
Jianhui Chen

AbstractHere we provide evidence with an exploratory pilot study that through the use of a Gamma 40 Hz entrainment frequency, mood, memory and cognition can be improved with respect to a 9-participant cohort. Participants constituted towards three binaural entrainment frequency groups: the 40 Hz, 25 Hz and 100 Hz. Participants attended a total of eight entrainment frequency sessions twice over the duration of a 4-week period. Additionally, participants were assessed based on their cognitive abilities, mood as well as memory, where the cognitive and memory assessments occurred before and after a 5-min binaural beat stimulation. The mood assessment scores were collected from sessions 1, 4 and 8, respectively. With respect to the Gamma 40 Hz entrainment frequency population, we observed a mean improvement in cognitive scores, elevating from 75% average to 85% average upon conclusion of the experimentation at weak statistical significance ($$\alpha$$ α = 0.10, p = 0.076). Similarly, memory score improvements at a greater significance ($$\alpha$$ α = 0.05, p = 0.0027) were noted, elevating from an average of 87% to 95%. In pertinence to the mood scores, a negative correlation across all populations were noted, inferring an overall increase in mood due to lower scores correlating with elevated mood. Finally, correlation analysis revealed a stronger R$$^2$$ 2 value (0.9838) within the 40 Hz group between sessions as well as mood score when compared across the entire frequency group cohort.


2019 ◽  
Author(s):  
Hyeon Jeong Yoon ◽  
Jonghwa Kim ◽  
Sang Woo Park ◽  
Hwan Heo

Abstract Background To investigate differences in refraction, accommodative factors, ocular parameters, and subjective symptoms after using two types of virtual reality (VR) content with different perception depths. Methods Twenty-three volunteers, who played VR games in two modes (immersive and non-immersive) for 30 min, were enrolled. Ocular parameters were examined before and after using VR. Accommodative factors were measured using static and dynamic methods, and subjective symptoms were assessed using a questionnaire. Differences according to VR content and correlations between each ocular parameter were analyzed. Results There were no changes in refraction and accommodative factors after use of the VR. However, there was a significant increase in near point accommodation (NPA), near point convergence (NPC), and subjective symptom scores after using the immersive mode. Correlation analysis revealed that NPA and accommodative lag were increased in subjects with exophoria, and that subjects with high NPA or NPC were more likely to exhibit an increase in mean accommodative lag. Conclusions The use of VR for 30 min reduced NPA and NPC especially after the immersive mode was used. In addition, using VR could further increase accommodation lag and reduce the amplitude of accommodation and convergence in subjects with exophoria.


2020 ◽  
Vol 10 (4) ◽  
pp. 94
Author(s):  
Suwakhon Phakeewai ◽  
Prayoon - Wongchantra

This research aims to develop the environmental recreation camp activity for youth in Roi-Et province of Thailand, to compare environmental knowledge, environmental attitudes before and after participating in the camp, as will as their participating in Environment Recreation camp activities during and after participating in the camp of youths with different gender and domicile, and to study the relationship between environmental knowledge, environmental attitudes and participation in environmental recreation camp activities. The data were collected though a survey with 40 youths from Phanom Phrai Wittayakarn School, Phanom Phrai District, Roi-Et Province. The research instruments was the manuals questionnaire measuring environmental knowledge, environmental attitudes and participation in environmental recreation camp activity. The data were analysed by using descriptive statistic and hypothesis testing by using t-test, One-way MANCOVA, One-way ANOVA and Correlation analysis. The results of this research indicated as below Environment Recreation Camp Activities for Youth in Roi-Et Province had effectively is 85.17/83.44 and an effectiveness index is 0.6117. After participating in environment recreation camp activities, youths had higher environmental knowledge and environmental attitudes than before participating in the camp. After participating in environment recreation camp activities, youth had higher participation in environment recreation camp activities than during participating in camp. The sample youths with different gender and domicile had no different environmental knowledge, environmental attitudes, and environmental participation. Environmental knowledge, environmental attitudes, and participation in environmental recreation camp activities were not correlated.


2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Haifeng Ma ◽  
Xia Liu ◽  
Ying Wu ◽  
Naixia Zhang

In this study, the antifatigue effects of acupuncture had been investigated at the metabolic level on the young male athletes with exhaustive physical exercises. After a series of exhaustive physical exercises and a short-term rest, the athletes either were treated with needling acupuncture on selected acupoints (TA group) or enjoyed an extended rest (TR group). NMR-based metabolomics analysis was then applied to depict the metabolic profiles of urine samples, which were collected from the athletes at three time points including the time before exercises, the time before and after the treatment of acupuncture, or taking the extended rest. The results from multivariate statistical analysis indicated that the recoveries of disturbed metabolites in the athletes treated with acupuncture were significantly faster than in those only taking rest. After the treatment with acupuncture, the levels of distinguished metabolites, 2-hydroxybutyrate, 3-hydroxyisovalerate, lactate, pyruvate, citrate, dimethylglycine, choline, glycine, hippurate, and hypoxanthine were recovered at an accelerated speed in the TA group in comparison with the TR group. The above-mentioned results indicated that the acupuncture treatment ameliorated fatigue by backregulating the perturbed energy metabolism, choline metabolism, and attenuating the ROS-induced stress at an accelerated speed, which demonstrated that acupuncture could serve as an alternative fatigue-relieving approach.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Yun-Long Guo ◽  
Yang Wang ◽  
Yi-Lin Zhao ◽  
Xiu-Ying Xu ◽  
Hao Zhang ◽  
...  

Ultrahigh-performance liquid chromatography Quadrupole-Orbitrap tandem mass spectrometry (UHPLC-Q-Orbitrap-MS/MS) was used to compare the composition of ginsenosides in white ginseng (WG) and extruded white ginseng (EWG). A total of 45 saponins, including original neutral ginsenosides, malonyl-ginsenosides, and chemical transformation of ginsenosides, were successfully identified in both WG and EWG. Multivariate statistical analyses including supervised orthogonal partial least squared discrimination analysis (OPLS-DA) and hierarchical clustering analysis (HCA) were used to analyze components of white ginseng before and after extrusion. As a result, three ginsenosides (malonyl (M)-Rb1, M-Rb2, and M-Rc) were found to be increased in WG, while three ginsenosides (Rb2, Rc, and Rg1) were elevated in EWG. In the OPLS-DA S-plot, the different compositions of ginsenoside that were distinguished between WG and EWG were screened out. Experimental results indicate that the UHPLC-Q-Orbitrap-MS/MS is a useful tool to characterize variations of ginsenosides in WG and EWG.


2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Franca Fruzzetti ◽  
Elena Benelli ◽  
Tiziana Fidecicchi ◽  
Massimo Tonacchera

The aim of this retrospective study was to evaluate the effects of a treatment with α-lipoic acid (ALA) associated with two different doses of myo-inositol (MI) on clinical and metabolic features of women with polycystic ovary syndrome (PCOS). Eighty-eight women received the treatment, and 71 among them had complete clinical charts and were considered eligible for this study. All women were treated with 800 mg of ALA per day: 43 patients received 2000 mg of MI and 28 received 1000 mg of MI per day. Menstrual cyclicity, BMI, FSH, LH, estradiol, testosterone, androstenedione, fasting insulin, HOMA-IR, and insulin response to a 2 h OGTT were evaluated before and after 6 months of treatment. The presence of diabetic relatives (DRs) was investigated. Cycle regularity was improved in 71.2% of women. The improvement of menstrual cyclicity occurred regardless of the state of IR and the presence of DRs of the patients. Women with IR mainly showed a significant improvement of metabolic parameters, while those without IR had significant changes of reproductive hormones. Patients with DRs did not show significant changes after the treatment. 85.7% of women taking 2000 mg of MI reported a higher improvement of menstrual regularity than those taking 1000 mg of MI (50%; p<0.01). In conclusion, ALA + MI positively affects the menstrual regularity of women with PCOS, regardless of their metabolic phenotype, with a more evident effect with a higher dose of MI. This effect seems to be insulin independent. The presence of IR seems to be a predictor of responsivity to the treatment in terms of an improvement of the metabolic profile.


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